Conformational changes in cytochrome c directed by ethylene glycol accompanying complex formation: Protein-solvent preferential interaction or/and kosmotropic effect.
When proteins interact with solvent or co-solutes with a high specificity and affinity, protein-ligand complexes may be formed. Such phenomenon may involve the processes like intra- and intermolecular interactions, which result in interaction based protein folding. In this study, cytochrome c (cyt c) was treated with different concentrations of ethylene glycol (EG) in crowded and confined media to check its structural stability using various spectroscopic techniques at pH 7.0 and 25 °C. The various spectroscopic techniques including circular dichroism (Soret, far- and near-UV regions), Fourier transform infrared (FTIR), absorption (UV and visible) and Trp fluorescence shows both secondary and tertiary structure of cyt c increases when treated with EG. The investigations using dynamic light scattering (DLS), time resolved fluorescence and isothermal titration calorimetry (ITC) for binding studies shows weak interaction between EG and cyt c. Small increase in the structure of the protein and insignificant decrease in hydrodynamic radii of the protein was observed from the studies. Molecular docking studies showed that EG has binding site on the protein and interact with few amino acid residues by weak interactions such as van der Waals and hydrogen bonding. This study helps in understanding the protein-ligand interactions, provides facts and the mechanisms that mediates the recognition of binding site for specific ligand to the receptor protein, which make possible of the discovery, design, and development of drugs at molecular level without affecting proteins within an organism.


Cholesterol transfer from rat, human and sheep erythrocytes.
1. The spontaneous transfer of cholesterol out of sheep, rat and human erythrocyte membranes was measured. 2. The rates of cholesterol transfer did not correlate with the very different levels of sphingomyelin in the membranes. 3. Cholesterol transferred at similar rates out of vesicles made of lipids extracted from the three types of erythrocyte. 4. The results are discussed in relation to the proposal that cholesterol and sphingomyelin are closely associated in cell surface membranes.


Avoidance of calcineurin inhibitors with use of proliferation signal inhibitors in de novo heart transplantation with renal failure.
This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period. Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m(2)), and 4 patients required dialysis. Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m(2) at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events. Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.


[A comparative analysis of learning and exploratory behavior in rats with different resistances to stress exposures and to the brain monoamine level].
Wistar rats stable (S) to sound stimulus differed from the unstable (NS) ones by a heightened investigatory activity in condition of moderate stress in the open field test, by heightened reactivity to sensory stimuli of various modalities (somatosensory, visual and olfactory), lowered level of investigatory behaviour in the test of burrow chamber. S-rats differed from NS-animals by a higher ability to learning of goal-directed reaction and a lower ability to discrimination of different emotional influences. The results of biochemical analysis of the content of biogenic amines in various brain structures revealed in stable rats an increase of noradrenaline level and in non-stable ones--a higher level of dopamine and serotonin.


AMPA, kainic acid, and N-methyl-D-aspartic acid stimulate locomotor activity after injection into the substantia innominata/lateral preoptic area.
The substantia innominata/lateral preoptic area (SI/LPO) is a subpallidal region which has been shown to regulate the hypermotility produced by drugs acting in the nucleus accumbens. Evidence has been presented that the SI/LPO contains glutamatergic nerve terminals and receptors for excitatory amino acids. The purpose of this study was to determine the effects of the activation of excitatory amino acid receptors in the SI/LPO on locomotor activity following the direct injection of excitatory amino acids into this brain site. It was found that the bilateral injection of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainic acid, and N-methyl-D-aspartic acid into the SI/LPO produced marked dose-dependent stimulations of locomotor activity which resembled the effects of these agents after their injection into the nucleus accumbens. The effect, however, was bell-shaped in that at high doses, the locomotor activity values decreased from their peak values. The coinjection of gamma-glutamylaminomethylsulfonate (GAMS) with AMPA into the SI/LPO was found to inhibit the hypermotility response to AMPA at doses that were unable to produce a significant inhibition of the hypermotility responses to kainic acid or N-methyl-D-aspartic acid. The injection of 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the SI/LPO inhibited the hypermotility responses to AMPA or kainic acid while having no significant inhibitory effect on N-methyl-D-aspartic acid stimulated locomotor activity. The injection of D-alpha-aminoadipic acid into the SI/LPO produced a significant inhibition of the hypermotility response produced by N-methyl-D-aspartic acid at a dose that did not produce a significant inhibition of the hypermotility response produced by AMPA.(ABSTRACT TRUNCATED AT 250 WORDS)


Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid.
Insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) are trophic factors for cartilage and have been shown to be chondroprotective in animal models of osteoarthritis (OA). IGFBP-5 is degraded in joint fluid and inhibition of IGFBP-5 degradation has been shown to enhance the trophic effects of IGF-I. To determine the identity of IGFBP-5 protease activity in human OA joint fluid. OA joint fluid was purified and the purified material was analyzed by IGFBP-5 zymography. Both crude joint fluid and purified material contained a single band of proteolytic activity that cleaved IGFBP-5. Immunoblotting of joint fluid for complement 1s (C1s) showed a band that had the same Mr estimate, e.g., 88 kDa. In gel tryptic digestion and subsequent peptide analysis by LC-MS/MS showed that the band contained human C1s. A panel of protease inhibitors was tested for their ability to inhibit IGFBP-5 cleavage by the purified protease. Three serine protease inhibitors, FUT175 and CP-143217 and CB-349547 had IC50's between 1 and 6 microM. Two other serine protease inhibitors had intermediate activity (e.g., IC50's 20-40 microM) and MMP inhibitors had no detectible activity at concentrations up to 300 microM. Human OA fluid contains a serine protease that cleaves IGFBP-5. Zymography, immunoblotting and LC-MS/MS analysis indicate that C1s is the protease that accounts for this activity.


Alternative soilless media for growing Petunia x hybrida and Impatiens wallerana: physical behavior, effect of fertilization and nitrate losses.
The use of alternative soilless media for the production of potted plants requires knowledge of their physical and chemical characteristics to result in the best conditions for plant growth. We investigated the use of alternative soilless media based on river waste and Sphagnun sp. and Carex sp. from Argentinean peatlands on Petuniaxhybrida and Impatiens wallerana production at two fertilization levels (200 and 400mgl(-1)N). River waste or 'temperate peat' is the name given to a material, resulting from the accumulation of aquatic plant residues under an anaerobic subtropical environment, which is dredged from river banks. Our results showed that alternative substrates based on river waste can be used to grow high quality plants. This result was not fully explained on the basis of established methods to evaluate substrate quality. Highly concentrated fertigation solution decreased the substrate quality parameters and plant growth. Nitrate leaching from the alternative substrates containing river waste was lower than the standard peat-based materials, which makes river waste desirable from a sustainable pot production system perspective. River waste and Carex peat are suitable alternatives to Sphagnum peat from the Northern Hemisphere.


Growth, structural, optical, thermal and mechanical properties of ammonium pentaborate single crystal.
Nonlinear optical single crystals of ammonium pentaborate (APB) were grown by the slow cooling method from aqueous solution. Grown crystal was characterized by powder X-ray diffraction (PXRD) and FT-IR spectral analysis. Perfection of the grown crystal was evaluated by high-resolution X-ray diffractometry (HRXRD). The effect of nylon threading on the perfection of the grown bigger crystal was also studied by HRXRD. The range and percentage of optical transmission was ascertained by recording UV-vis-NIR spectrum. Thermal properties were investigated by TG-DTA and DSC analyses. Its mechanical hardness was estimated by Vickers microhardness tester.


Intraspecific variation in muscle growth of two distinct populations of Port Jackson sharks under projected end-of-century temperatures.
Although pervasive, the effects of climate change vary regionally, possibly resulting in differential behavioral, physiological, and/or phenotypic responses among populations within broadly distributed species. Juvenile Port Jackson sharks (Heterodontus portusjacksoni) from eastern and southern Australia were reared at their current (17.6 °C Adelaide, South Australia [SA]; 20.6 °C Jervis Bay, New South Wales [NSW]) or projected end-of-century (EOC) temperatures (20.6 °C Adelaide, SA; 23.6 °C Jervis Bay, NSW) and assessed for morphological features of skeletal muscle tissue. Nearly all skeletal muscle properties including cellularity, fiber size, myonuclear domain, and satellite cell density did not differ between locations and thermal regimes. However, capillary density was significantly influenced by thermal treatment, where Adelaide sharks raised at current temperatures had a lower capillarity than Jervis Bay sharks raised at ambient or projected EOC temperatures. This may indicate higher metabolic costs at elevated temperatures. However, our results suggest that regardless of the population, juvenile Port Jackson sharks may have limited acclimatory potential to alter muscle metabolic features under a temperature increase, which may make this species vulnerable to climate change.


Daily Vibrotactile Stimulation Exhibits Equal or Greater Spasticity Relief Than Botulinum Toxin in Stroke.
To test the feasibility and efficacy of the VibroTactile Stimulation (VTS) Glove, a wearable device that provides VTS to the impaired limb to reduce spastic hypertonia. Prospective 2-arm intervention study-including 1 group of patients who use Botulinum toxin (BTX-A) for spasticity and 1 group of patients who do not use BTX-A. Participants were recruited through rehabilitation and neurology clinics. Patients with chronic stroke (N=20; mean age=54 years, mean time since stroke=6.9 years). Patients who were previously receiving the standard of care (BTX-A injection) were eligible to participate and started the intervention 12 weeks after their last injection. Participants were instructed to use the VTS Glove for 3 hours daily, at home or during everyday activities, for 8 weeks. Spasticity was assessed with the Modified Ashworth Scale and the Modified Tardieu Scale at baseline and then at 2-week intervals for 12 weeks. Primary outcomes were the difference from baseline and at week 8 (end of VTS Glove use) and week 12 (4 weeks after stopping VTS Glove use). Patients who were receiving BTX-A were also assessed during the 12 weeks preceding the start of VTS Glove use to monitor the effect of BTX-A on spastic hypertonia. Range of motion and participant feedback were also studied. A clinically meaningful difference in spastic hypertonia was found during and after daily VTS Glove use. Modified Ashworth and Modified Tardieu scores were reduced by an average of 0.9 (P=.0014) and 0.7 (P=.0003), respectively, at week 8 of daily VTS Glove use, and by 1.1 (P=.00025) and 0.9 (P=.0001), respectively, 1 month after stopping VTS Glove use. For participants who used BTX-A, 6 out of 11 showed greater change in Modified Ashworth ratings during VTS Glove use (mean=-1.8 vs mean=-1.6 with BTX-A) and 8 out of 11 showed their lowest level of symptoms during VTS Glove use (vs BTX-A). Daily stimulation from the VTS Glove provides relief of spasticity and hypertonia. For more than half of the participants who had regularly used BTX-A, the VTS Glove provided equal or greater symptom relief.


Deconvoluting the context-dependent role for autophagy in cancer.
Autophagy (also known as macroautophagy) captures intracellular components in autophagosomes and delivers them to lysosomes, where they are degraded and recycled. Autophagy can have two functions in cancer. It can be tumour suppressive through the elimination of oncogenic protein substrates, toxic unfolded proteins and damaged organelles. Alternatively, it can be tumour promoting in established cancers through autophagy-mediated intracellular recycling that provides substrates for metabolism and that maintains the functional pool of mitochondria. Therefore, defining the context-specific role for autophagy in cancer and the mechanisms involved will be important to guide autophagy-based therapeutic intervention.


Projection patterns of lateral-line afferents in anurans: a comparative HRP study.
Primary projections of the anterior and posterior lateral-line nerves were traced by means of transganglionic transport of horseradish peroxidase in species belonging to five of the six anuran superfamilies. Both anterior and posterior lateral-line nerve afferents each enter the brain via a single root which divides into two or more bundles. These bundles carry fibers from neuromasts only. No separate dorsal fascicle and no ampullary organs as in urodeles and gymnophions have been found. All bundles join in the neuropil of the nucleus intermedius to form ascending and descending fascicles. Two distinct fascicles are found in species showing little collateralization. No fasciculation is found in species with an elaborate telodendritic arborization. Afferents of the anterior lateral-line nerve run ventromedially and those of the posterior lateral-line nerve dorsolaterally within the ipsilateral nucleus intermedius neuropil. Rostrally they terminate in the vicinity of the eminentia granularis and caudally in the vicinity of the calamus scriptorius. The metamorphic changes in the alar plate do not support the hypothesis of Larsell ('34) as to a change in function of second-order lateral-line neurons into second-order auditory neurons. The rostral part of the nucleus intermedius shows numerous degenerating neurons at metamorphic climax whereas the caudal part becomes part of the nucleus caudalis of adult anurans. Besides the members of the Pipoidea, there is at least the genus Bombina which retains parts of the lateral-line system. The term "dorsal island," its relevance for any part of the anuran brain, and the possible relation between absence of electroreception and the development of the nucleus dorsolateralis are discussed.


Controversies in Oral and Maxillofacial Oncology.
Imaging studies are essential components of tumor diagnosis, staging, assessing tumor response to neoadjuvant and adjuvant therapies, and postoperative surveillance on completion of definitive treatment. Treatment of early stage clinically node negative oral cavity squamous cell carcinoma is controversial. Approximately 3% of all head and neck tumors arise within the parotid gland and most often within the superficial lobe, lateral to the facial nerve; about 80% are benign and most are pleomorphic adenoma. In patients with dry eyes failing multiple other treatment modalities and facing ongoing pain and loss of vision, microvascular transplant of the submandibular gland is a viable option.


Shape differences of the brain ventricles in Alzheimer's disease.
The brain ventricles are surrounded by gray and white matter structures that are often affected in dementia in general and Alzheimer's disease (AD) in particular. Any change of volume or shape occurring in these structures must affect the volume and shape of the ventricles. It is well known that ventricular volume is significantly higher in AD patients compared to age-matched healthy subjects. However, the large overlap between the two volume distributions makes the measurement unsuitable as a biomarker of the disease. The purpose of this work was to assess whether local shape differences of the ventricles can be detected when comparing AD patients and controls. In this work, we captured the ventricle's shape and shape variations of 29 AD subjects and 25 age-matched controls, using a fully automatic shape modeling technique. By applying permutation tests on every single node of a mesh representation of the shapes, we identified local areas with significant differences. About 22% of an average surface of the ventricles presented significant difference (P < 0.05) ( approximately 14% of the left against approximately 7% of the right side). We found out that in patients with Alzheimer disease, not only the lateral horns were significantly affected, but also the areas adjacent to the anterior corpus callosum, the splenium of the corpus callosum, the amygdala, the thalamus, the tale of the caudate nuclei (especially the left one), and the head of the left caudate nucleus.


Anesthetics produce differential actions on membrane responses of the crayfish stretch receptor neuron.
The actions of ethanol, halothane and pentobarbital on the membrane electrical properties and synaptic transmission of isolated crayfish stretch receptor neurons were studied to determine possible sites of action contributing to differential effects previously described on physiological discharge activity. The three agents depressed GABA-mediated transmission and altered postsynaptic membrane electrical properties. Both pre- and postsynaptic sites of action appeared to contribute to the anesthetic-induced alteration of neuronal function. The agents studied produced different, concentration-dependent, membrane effects which included biphasic actions on membrane resistance and spike threshold. The results suggest that multiple-sites of action are involved and different anesthetics may not act via the same mechanism(s) at these sites.


Multi-region radiomics for artificially intelligent diagnosis of breast cancer using multimodal ultrasound.
The ultrasound (US) diagnosis of breast cancer is usually based on a single-region of a whole breast tumor from a single ultrasonic modality, which limits the diagnostic performance. Multiple regions on multimodal US images of breast tumors may all have useful information for diagnosis. This study aimed to propose a multi-region radiomics approach with multimodal US for artificially intelligent diagnosis of malignant and benign breast tumors. Firstly, radiomics features were extracted from five regions of interest (ROIs) on B-mode US and contrast-enhanced ultrasound (CEUS) images, including intensity statistics, gray-level co-occurrence matrix texture features and binary texture features. The multiple ROIs included the whole tumor region, strongest perfusion region, marginal region and surrounding region. Secondly, a deep neural network, composed of the point-wise gated Boltzmann machine and the restricted Boltzmann machine, was adopted to comprehensively learn and select features. Thirdly, the support vector machine was used for classification between benign and malignant breast tumors. Finally, five single-region classification models were generated from five ROIs, and they were fused to form an integrated classification model. Experimental evaluation was conducted on multimodal US images of breast from 187 patients with breast tumors (68 malignant and 119 benign). Under five-fold cross-validation, the classification accuracy, sensitivity, specificity, Youden's index and area under the receiver operating characteristic curve (AUC) with our model were 87.1% ± 3.3%, 77.4% ± 11.8%, 92.4% ± 7.2%, 69.8% ± 8.6% and 0.849 ± 0.043, respectively. Our model was significantly better than single-region single-modal methods in terms of the AUC and accuracy (p < 0.05). In addition to the whole tumor region, the other regions including the strongest perfusion region, marginal region and surrounding region on US images can assist breast cancer diagnosis. The multi-region multimodal radiomics model achieved the best classification results. Our artificially intelligent model would be potentially useful for clinical diagnosis of breast cancer.


Critical appraisal of routine supraclavicular lymph node biopsy in staging of testicular tumors.
Supraclavicular lymph node biopsy was performed as a staging procedure in 36 patients with germ cell tumors of the testis and nonpalpable supraclavicular nodes. Of 28 patients with clinical Stage A or B disease, 1 patient (4 per cent) was found to have supraclavicular metastases. Of 8 patients with clinical Stage C disease, 2 (25 per cent) had supraclavicular metastases. The apparent infrequency with which subclinical supradiaphragmatic disease is documented with this procedure and the current use of adjuvant systemic therapy in patients with pathologic Stage B nonseminomatous tumors suggest that supraclavicular lymph node biopsy should be abandoned as a routine staging procedure.


Effect of pilocarpine and substance P on ganglionic transmission.
The effect of pilocarpine and substance P on the amplitudes of the postganglionic compound action potentials (unconditioned response, UR and post-train conditioned response, PTR) were studied in the isolated rabbit superior cervical ganglion (SCG). Pilocarpine (50 microM) and substance P (1 microM) produced an increase in the amplitudes of both UR & PTR responses in the rabbit SCG. Facilitation and subliminal fringe values decreased. It was concluded that both pilocarpine and substance P increase the amplitudes of the transmitted postganglionic compound action potentials and they may facilitate ganglionic transmission in the rabbit SCG.


Pirfenidone regulates LPS mediated activation of neutrophils.
Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils.


Central action of C-type natriuretic peptide on vasopressin secretion in conscious rats.
The effect of intracerebroventricular injection of C-type natriuretic peptide (CNP) on arginine vasopressin (AVP) secretion was studied in conscious rats, and was compared to that of atrial natriuretic peptide (ANP). The AVP secretion induced by central injection of 0.1 nmol angiotensin II was significantly suppressed by the pretreatment with 1 nmol CNP. ANP at a dose of 0.1 nmol elicited almost equivalent suppressive action to 1 nmol CNP. Considering that CNP is a specific ligand for ANP-B receptor, while ANP is that for ANP-A receptor, the result demonstrates that CNP possesses the similar central action to ANP, and suggests that the distribution of ANP-A and ANP-B receptors and/or their affinity towards each natriuretic peptide are different in the central nervous system.


Contiguous invasion per se does not affect prognosis in colon cancer.
Locally advanced colon cancer can result in serious clinical conditions unless treated appropriately. The aim of this study was to examine the feasibility of en bloc resection and the significance of depth of invasion by analyzing the outcomes of the procedure in colon cancer invading adjacent organs. Outcomes of 65 locally advanced colon cancer patients who underwent en bloc resections for contiguous invasion were compared with 285 pT3 colon cancer patients. En bloc combined resection was performed in 75 patients and 10 (13.3%) of them showed no true malignant infiltration into adjacent organs. In both pT3 and pT4 groups, there was no significant difference in major postoperative complications or mortality. The survival rate of pT4 group was similar to that of pT3 group (5-year rate, 64.0% vs. 72.7%; P = 0.287). In multivariate analysis, lymph node metastasis, lymphovascular infiltration, and perineural invasion were independently associated with patient survival. The prognosis of colon cancer, even in locally advanced cases, is mainly correlated with nodal status rather than depth of invasion. Therefore, en bloc combined resection in locally advanced colon cancer invading adjacent organs can improve survival as well as local control with acceptable morbidity and mortality.


Letter to the editor: Comment on "multiannual monitoring (1974-2019) of rare earth elements in wild growing edible mushroom species in Polish forests" by Siwulski et al. https://doi.org/10.1016/j.chemosphere.2020.127173. A recurring question - What are the real concentrations and patterns of REE in mushrooms?
Siwulski et al. (2020) investigated the occurrence of the lanthanides (La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu), scandium (Sc) and yttrium (Y) in 4 species of wild mushrooms, which were sampled over a 45 years period in Poland. The reported mean lanthanide concentrations for mushrooms were in the range from 539 to 1601 μg kg-1 dry weight. These values are considered as highly elevated in the light of data published earlier for the same species, where the analytical results were assessed as not being biased by errors (these could arise from contamination of the samples with soil dust or unsuitable choice of analytical methodology including the use of unsuitable analytical instrumentation for measurement). It has long been established that the lanthanides are naturally distributed in ores, soil bedrock, soils, natural waters and plants in a pattern that reflects the Oddo-Harkins rule. This pattern is correspondingly reflected in fungi, including the same species and have been published earlier by other authors. However, when the individual lanthanide concentration data of B. edulis, I. badia, L. scabrum and M. procera from the study by Siwulski et al. are plotted, they do not display the expected sawtooth (zigzag) concentration pattern - in other words, the concentration data do not follow the Oddo-Harkins rule. Lanthanides are naturally found in very low concentration in foods including wild mushrooms. There is a striking lack of convergence in the results obtained for ICP-MS techniques, and the results obtained from ICP-OES measurement (as used by Siwulski et al.). If the reasons discussed here for anomalies in the reported lanthanides data hold true, how does this affect the data for other elements in mushrooms reported in the commented article?


Hematopoietic colony-forming cells from mice after wound trauma.
The changes produced in the pluripotential and progenitor cell compartments of the hind leg bone marrow and spleen of skin-wounded mice were examined over a 2-week post-trauma period. Pluripotent cells (colony-forming unit-spleen, CFU-s) were significantly increased in the spleen and slightly reduced in the leg marrow the first week after trauma. Granulocyte macrophage colony-forming cells (GM-CFC) were significantly increased in the spleen throughout the 2-week period and were increased in the leg marrow during the first post-trauma week. Macrophage colony-forming cells (M-CFC) were significantly decreased in the spleen during the 2-week period and were slightly elevated in the leg marrow during that time. The peripheral blood contained significantly increased concentrations of CFU-s and GM-CFC but not M-CFC. Serum of wounded mice supported growth of GM-CFC but not M-CFC. The growth-promoting factor was extractable by CHCl3 treatment. Serum C-reactive protein concentrations were significantly increased for a 5-day period after wound trauma.


Enhancement of the antitumor effect of illudin S by including it into liposomes.
Entrapping illudin S in liposome markedly enhanced life prolonging effect in ddN mice bearing Ehrlich ascites tumors, presumably by decreasing the side effects.


Associations between physical activity and the built environment in patients with schizophrenia: a multi-centre study.
This study investigated the variance in walking, moderate and vigorous physical activity (PA), explained by neighbourhood design and other environmental variables above and beyond the variance accounted for by demographical variables. A total of 138 patients (46♀) with schizophrenia (mean age = 41.2 ± 12.5 years) from 13 different centres in Belgium were included in this 4-month cross-sectional study. The built environment was rated using the Instruments for Assessing Levels of Physical Activity and Fitness (ALPHA) environmental questionnaire, which was validated first. PA levels were assessed with the International Physical Activity Questionnaire. Validity coefficients for the ALPHA ranged between 0.44 and 0.86 and test-retest reliability intraclass correlation coefficients ranged between 0.64 and 0.84. Regression analyses showed that environmental variables were related to all types of PA. The variance explained by the models including demographic and environmental variables ranged from 20% for vigorous PA up to 68% for walking. Minutes of walking (r=0.63, P<.001) and of moderate-intensity PA (r = 0.43, P<.001) were related to emotional satisfaction with the environment. Moderate-intensity PA was also related to the presence of PA supplies at home (r=0.49, P<.001). Neighbourhood design and other environmental variables show significant associations with multiple types of PA in patients with schizophrenia.


Variability across subjects in free recall versus cued recall.
Memory scientists usually compare mean performance on some measure(s) (accuracy, confidence, latency) as a function of experimental condition. Some researchers have made within-subject variability in task performance a focal outcome measure (e.g., Yao et al., Journal of Clinical and Experimental Neuropsychology, 38, 227-237, 2016). Here, we explored between-subject variability in accuracy as a function of experimental conditions. This work was inspired by an incidental finding in a previous study, in which we observed greater variability in accuracy of memory performance on cued recall (CR) versus free recall (FR) of English animal/object nouns (Mah et al., Frontiers in Psychology, 14, 1146200, 2023). Here we report experiments designed to assess the reliability of that pattern and to explore its causes (e.g., differential interpretation of instructions, [un]relatedness of CR word pairs, encoding time). In Experiment 1 (N = 120 undergraduates), we replicated the CR:FR variability difference with a more representative set of English nouns. In Experiments 2A (N = 117 Prolific participants) and 2B (N = 127 undergraduates), we found that the CR:FR variability difference persisted in a forced-recall procedure. In Experiment 3 (N = 260 Prolific participants), we used meaningfully related word pairs and still found greater variability in CR than in FR performance. In Experiment 4 (N = 360 Prolific participants), we equated CR and FR study phases by having all participants study pairs and, again, observed greater variability in CR than FR. The same was true in Experiment 5 (N = 120 undergraduates), in which study time was self-paced. Comparisons of variability across subjects can yield insights into the mechanisms underlying task performance.


Phase II clinical trial of advanced and metastatic gastric cancer based on continuous infusion of 5-fluorouracil combined with epirubicin and oxaliplatin.
To evaluate the efficacy and tolerability of systematic treatment of unresectable advanced or metastatic gastric cancer (A/MGC) based on EOF5 regimen (the combination of epirubicin, oxaliplatin and 5-day continuous infusion of 5-fluorouracil). Twenty-six patients (18 males, 8 females; age range, 35-72 years) with histologically confirmed metastatic (n = 23) or unresectable advanced (n = 3) gastric adenocarcinoma with (n = 6) or without previous chemotherapy (n = 20) were consented to receive EOF5 (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1, followed by continuous infusion of 5-fluorouracil 375-425 mg/m(2) day(-1) on day 1-5), and the treatment cycle was repeated every 3 weeks. Responses to treatment and toxicity were evaluated every 2 cycles. In the first-line treatment group of 20 patients, complete (CR) and partial (PR) remission were observed in two (10%) and six (30%) patients, respectively with an overall response rate of 40%). Eleven (55%) patients showed stable (SD) and one (5%) progressive disease (PD). One-year survival rate, time to progression (TTP) and median overall survival (OS) were 45%, 9.7 and 12.5 months, respectively. In the second-line treatment group of six patients, the numbers of CR, PR, SD and PD were 0, 1, 4 and 1, respectively. Symptomatic response rates were 88.2, 76.9, 89.5, and 88.9% for abdominal pain, distention, anorexia and weight loss. The mean Karnofsky performance status score was increased (P < 0.001) and maintained after two and four cycles treatment. The major adverse events were nausea/vomiting, oral mucositis, peripheral neuropathy, phlebitis, constipation and myelosuppression. CTC grade 3 or 4 hematologic toxicities included leucopenia (7.7%), neutropenia (15.4%), thrombocytopenia (19.2%), and anemia (3.8%). No treatment-related deaths were recorded. EOF5 regimen shows good efficacy and an acceptable safety profile in A/MGC patients, and would be a suitable alternative regimen for this indication.


Sitting movement in elderly subjects with and without Parkinson's disease: a biomechanical study.
The aim of the present study was to compare kinetic, kinematic, and electromyographic variables during the sitting movement between healthy elderly and in those with Parkinson's disease (PD) with moderate involvement. We hypothesized that subjects with PD would show difficulty in selecting the muscles for the task and that this could be related to the co-activation pattern and would be reflected in the behavior of some biomechanical variables. Fifteen subjects participated in this study, seven healthy subjects (NN group) and eight with Parkinson's disease. Electromyography (EMG) activity of the tibialis anterior (TA), soleus (SO), vastus medialis oblique (VMO), biceps femoris (BF), and erector spinae (ES) were recorded, and biomechanical variables were calculated, during four phases of the sitting movement. Compared to healthy subjects, the subjects with PD showed more flexion at the ankle, knee, and hip joints in the initial position and lower joint velocity. However, the EMG activity and hip, knee, and ankle joint torques were not different during all phases of movement. The sitting movement in PD subjects with moderate involvement generates EMG activity and joint torques similar to healthy elderly subjects. Only a reduced movement velocity was found in PD patients during the sitting task.


Ecological robustness of the gut microbiota in response to ingestion of transient food-borne microbes.
Resident gut microbes co-exist with transient bacteria to form the gut microbiota. Despite increasing evidence suggesting a role for transient microbes on gut microbiota function, the interplay between resident and transient members of this microbial community is poorly defined. We aimed to determine the extent to which a host's autochthonous gut microbiota influences niche permissivity to transient bacteria using a fermented milk product (FMP) as a vehicle for five food-borne bacterial strains. Using conventional and gnotobiotic rats and gut microbiome analyses (16S rRNA genes pyrosequencing and reverse transcription qPCR), we demonstrated that the clearance kinetics of one FMP bacterium, Lactococcus lactis CNCM I-1631, were dependent on the structure of the resident gut microbiota. Susceptibility of the resident gut microbiota to modulation by FMP intervention correlated with increased persistence of L. lactis. We also observed gut microbiome configurations that were associated with altered stability upon exposure to transient bacteria. Our study supports the concept that allochthonous bacteria have transient and subject-specific effects on the gut microbiome that can be leveraged to re-engineer the gut microbiome and improve dysbiosis-related diseases.


Single and multiple dose pharmacokinetics of nelfinavir and CYP2C19 activity in human immunodeficiency virus-infected patients with chronic liver disease.
To evaluate the single-dose and multiple-dose pharmacokinetics of nelfinavir and its active M8 metabolite in eight HIV-seropositive patients with liver disease, and to examine the relationship between CYP2C19 activity (genotype and plasma M8/nelfinavir metabolic ratio) and the severity of liver disease in these patients. Nelfinavir was given as a single dose (500 or 750 mg) to patients beginning therapy and twice (500, 750 or 1000 mg) or three times (250 or 750 mg) daily during chronic therapy. Single-dose pharmacokinetic values were used to predict multiple-dose regimens. Peak and total plasma exposures between 2-4 microg ml-1 and 45-75 microg ml-1 h, respectively, and predose levels > 0.7 microg ml-1 were targeted for multidose nelfinavir. Genotype was determined by analysis for CYP2C19*1, CYP2C19*2, and CYP2C19*3. Individuals were grouped according to their genotype, molar M8/nelfinavir AUC ratio (low: < 0.1, intermediate: 0.1-0.3, high > 0.3), and Child-Pugh classification for severity of liver disease. Nelfinavir pharmacokinetics were characterized by wide interindividual variability, low clearance (181-496 ml min-1 70 kg-1, n = 7), and prolonged half-life (5-20 h, n = 7). M8/nelfinavir AUC ratio increased 58% (n = 4) and alpha 1-acid glycoprotein levels decreased up to 39% (n = 5) from single to multiple dosing. CYP2C19 activity was low (metabolic AUC ratio < 0.1) in four patients with moderate to severe liver disease even though they were genetically extensive CYP2C19 metabolizers (*1/*1 or *1/*2). Three patients required lower daily doses than the standard regimen of 750 mg every 8 h to achieve target concentrations and maintain virologic suppression at < 50 RNA copies ml-1 (up to 20 months). Acquired CYP2C19 deficiency from moderate or severe liver disease resulted in decreased M8 formation. Long-term HIV suppression is possible using low nelfinavir doses in patients with liver disease.


Dietary supplements used by otolaryngology patients in Turkey during the COVID-19 pandemic: A cross-sectional survey.
This study investigated the characteristics of dietary supplement (DS) use of patients who attended the otolaryngology clinic at a university training and research hospital in Turkey during the pandemic, including patients who had experienced Coronavirus disease 2019 (COVID-19). This cross-sectional study was conducted between March and September 2021. 277 literate patients aged ≥ 18 years who attended the otolaryngology clinic were enrolled. A questionnaire was used to collect sociodemographic data, as well as data on DS use during the pandemic. The questionnaire was administered in a face-to-face setting by a single researcher. Approximately half of the participants (50.18%) took DSs during the pandemic and 67.18% of those who experienced COVID-19 infection used DSs during their illness. The most commonly used supplements were vitamin C (43.16%) and D (33.09%), along with herbal supplements such as lemon (54.68%), garlic (46.76%), ginger (46.04%), and thyme (43.88%). In total, 85.23% of the patients primarily used DSs to enhance their immunity, while 32.95% used them to prevent cough, and 26.14% to improve breathing. The majority of the patients (85.23%) felt benefit from DSs. Typically, the patients obtained information about DSs from doctors (32.37%) or friends and relatives (29.49%), and most of them used the supplements without first consulting a doctor (63.64%). DSs were commonly used by otolaryngology patients during the COVID-19 pandemic, particularly to enhance immunity. Although the majority of patients reportedly benefited from these products, most of them did not inform their physicians that they were using them and often obtained information from unofficial sources.


A qualitative study of how people with severe mental illness experience living in sheltered housing with a private fully equipped apartment.
There are a number of supported housing options for people with severe mental illness (SMI), but limited knowledge about residents' experiences. The aim of this study was to explore how people with SMI experienced sheltered housing consisting of both a private fully equipped apartment and a shared accommodation room for socializing. Fourteen people with SMI living in sheltered housing apartments participated in a qualitative study with semi-structured face to face individual or group interviews. Residents' access to the service providers in the sheltered housing, who were seen as both "ordinary people" and skilled to observe symptom changes at an early stage, were major factors for the perception of security. In addition, residents highlighted the possibility of living in a fully equipped apartment, and having access to a shared accommodation room to connect with other residents. Having a fully equipped apartment including their own equipment such as a washing machine was said to help reduce conflicts. Short tenancy agreements made some informants feel insecure. It was also essential to have meaningful daily activities outside the residence to avoid re-hospitalization. The positive experience was connected to having a fully private equipped apartment including shared accommodation room. The service providers should be aware of the dilemma with in-house support, to make residents feel secure versus increased dependency on service providers.


"Phase capture" in the perception of interpolated shape: cue combination and the influence function.
This study was concerned with what stimulus information observers use to judge the shape of simple objects. We used a string of four Gabor patches to define a contour. A fifth, center patch served as a test pattern. The observers' task was to judge the location of the test pattern relative to the contour. The contour was either a straight line, or an arc with positive or negative curvature (the radius of curvature was either 2 or 6 deg). We asked whether phase shifts in the inner or outer pairs of patches distributed along the contour influence the perceived shape. That is, we measured the phase shift influence function. We found that shifting the inner patches of the string by 0.25 cycle results in almost complete phase capture (attraction) at the smallest separation (2 lambda), and the capture effect falls off rapidly with separation. A 0.25 cycle shift of the outer pair of patches has a much smaller effect, in the opposite direction (repulsion). In our experiments, the contour is defined by two cues--the cue provided by the Gabor carrier (the 'feature' cue) and that defined by the Gaussian envelope (the 'envelope' cue). Our phase shift influence function can be thought of as a cue combination task. An ideal observer would weight the cues by the inverse variance of the two cues. The variance in each of these cues predicts the main features of our results quite accurately.


Mental Health in the Specialized Athlete.
The aim of this review is to interpret the existing evidence regarding the psychological aspects of sport specialization within the context of a developmental framework. The growing trend toward early sport specialization is associated with increased risk for injury and burnout, both of which have significant implications for mental health. Mental health literacy programs designed to promote awareness, decrease stigma, and encourage help-seeking behaviors can be an effective way to increase resilience and early recognition of those in need. The trend toward early sport specialization is likely motivated in large part by the expectation that it will increase the likelihood of long-term athletic success. However, recent studies suggest that the majority of elite athletes delay specialization at least until mid to late adolescence. It is essential to consider the developmental psychology of children and adolescents and to avoid imposing expectations that are beyond their neurocognitive capabilities. In addition to depression, anxiety, and burnout, young athletes who are pressured to perform to excessively high standards are likely to internalize athletic failures as feelings of shame. This can lead to maladaptive perfectionistic traits and potentially overtraining, clinical eating disorders, or other harmful behaviors that will result in declines in performance, physical health, and overall wellbeing. Further work is needed to better inform sport-specific recommendations regarding sport specialization and to optimize the beneficial effects of sport participation while limiting the risks of harm.


Importance of urinary tract investigation in metastatic malignant melanoma.
Metastatic melanoma, although rarely recognized clinically, may involve the urinary tract in a high percentage of cases. Routine excretory urography and cystoscopy may establish the diagnosis of recurrent metastatic melanoma and prevent further surgical exploration.


Expression of adipokines in preimplantation rabbit and mice embryos.
Recent studies point to a role for adipokines in reproduction. Leptin is involved in embryo metabolism and may participate in embryo-maternal crosstalk. Little is known about potential roles of other adipokines in reproduction. We therefore studied the expression of adiponectin and pathway members during the pre- and periimplantation period in rabbits and mice. Adiponectin protein is localized in glandular epithelium of the rabbit endometrium on day 6 and 8 p.c. and in mouse endometrium on day 3.5 and 5 p.c. Rabbit, but not mice blastocysts express adiponectin mRNA. Adiponectin receptors one and two, adiponectin paralogues and PPARs were found in both species. Both, trophoblast and embryoblast were adiponectin positive. Real time PCR for adipoR1 and adipoR2 in rabbit blastocysts of different gastrulation stages at day 6 p.c. revealed a specific switch in expression: Expression was high in the trophoblast in early stages and in the embryoblast shortly prior to implantation. In conclusion, during the pre- and periimplantation period, members of the adiponectin pathway are expressed in endometrium and blastocysts, with a specific expression pattern in the embryonic disk of the gastrulating rabbit blastocyst, giving support to a role of the adipokine network in blastocyst differentiation and embryo-maternal interactions.


Downstream projection of Barrington's nucleus to the spinal cord in mice.
Barrington's nucleus (Bar), which controls micturition behavior through downstream projections to the spinal cord, contains two types of projection neurons, BarCRH and BarESR1, that have different functions and target different spinal circuitry. Both types of neurons project to the L6-S1 spinal intermediolateral (IML) nucleus, whereas BarESR1 neurons also project to the dorsal commissural nucleus (DCN). To obtain more information about the spinal circuits targeted by Bar, we used patch-clamp recording in spinal slices from adult mice in combination with optogenetic stimulation of Bar terminals. Recording of opto-evoked excitatory postsynaptic currents (oEPSCs) in 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfonate (DiI)-labeled lumbosacral preganglionic neurons (LS-PGNs) revealed that both Bar neuronal populations make strong glutamatergic monosynaptic connections with LS-PGNs, whereas BarESR1 neurons also elicited smaller-amplitude glutamatergic polysynaptic oEPSCs or polysynaptic opto-evoked inhibitory postsynaptic currents (oIPSCs) in some LS-PGNs. Optical stimulation of BarCRH and BarESR1 terminals also elicited monosynaptic oEPSCs and polysynaptic oIPSCs in sacral DCN neurons, some of which must include interneurons projecting to either the IML or ventral horn. Application of capsaicin increased opto-evoked firing during repetitive stimulation of Bar terminals through the modulation of spontaneous postsynaptic currents in LS-PGNs. In conclusion, our experiments have provided insights into the synaptic mechanisms underlying the integration of inputs from Bar to autonomic circuitry in the lumbosacral spinal cord that may control micturition.NEW & NOTEWORTHY Photostimulation of BarCRH or BarESR1 axons in the adult mouse spinal cord elicits excitatory or inhibitory postsynaptic responses in multiple cell types related to the autonomic nervous system including preganglionic neurons (PGNs) in the lumbosacral intermediolateral nucleus and interneurons in the lumbosacral dorsal commissure nucleus. Integration of excitatory inputs from Bar and from visceral primary afferents in PGNs may be important in the regulation of micturition behavior.


Use of ultrasound imaging for the diagnosis of abnormal uterine bleeding in the bonnet macaque ( Macaca radiata).
Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P < 0.0002). 3D ultrasound also showed a homogeneous mass in the uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.


A presynaptic site of action within the mesencephalic reticular formation for (+)-amphetamine-induced electrocortical desynchronization.
1. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of (-)-noradrenaline (NA) or (-)-alpha-methylnoradrenaline (AMNA) into the same sites. 3. Perfusion of 6-hydroxydopamine (6-OHDA) also induced desynchronization but, over the 1 h perfusion period, slow wave activity gradually returned to the electrical record. 4. Following the application of 6-OHDA the effect of (+)-amphetamine was abolished or significantly attenuated, whereas the effect of NA or AMNA was not affected. 5. The electrocortical desynchronization induced by (+)-amphetamine could be restored if its application was preceded by perfusion with NA or AMNA. 6. Fluorescence studies using AMNA indicated that 6-OHDA depleted noradrenergic nerve terminals near the cannulae tips. However, the terminals were still capable of taking up exogenously applied AMNA. 7. These results suggest that (+)-amphetamine has a presynaptic action on noradrenergic nerve terminals within the MRF.


The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study.
Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects. We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P<0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (P<0.0001 for trend), but not in the obese/overweight group (P=0.88 for trend). Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.


Design, Synthesis and Evaluation of Triazole-Pyrimidine Analogues as SecA Inhibitors.
SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. Through a combination of virtual screening and experimental exploration of the surrounding chemical space, we identified a hit bistriazole SecA inhibitor, SCA-21, and studied a series of analogues by systematic dissections of the core scaffold. Evaluation of these analogues allowed us to establish an initial structure-activity relationship in SecA inhibition. The best compounds in this group are potent inhibitors of SecA-dependent protein-conducting channel activity and protein translocation activity at low- to sub-micromolar concentrations. They also have minimal inhibitory concentration (MIC) values against various strains of bacteria that correlate well with the SecA and protein translocation inhibition data. These compounds are effective against methicillin-resistant Staphylococcus aureus strains with various levels of efflux pump activity, indicating the capacity of SecA inhibitors to null the effect of multidrug resistance. Results from studies of drug-affinity-responsive target stability and protein pull-down assays are consistent with SecA as a target for these compounds.


Successful resolution of symmetrical peripheral gangrene after severe acute pancreatitis: a case report.
Symmetrical peripheral gangrene is an uncommon but devastating complication in critically ill patients, and it has a high mortality. It is seen in a wide variety of medical conditions, presenting as symmetrical gangrene of two or more extremities without large blood vessel obstruction. We report a case of a 44-year-old Chinese man who was diagnosed with alcohol-related severe acute pancreatitis and presented with systemic inflammatory response syndrome and intractable vomiting. On the fourth day of admission, the patient developed cyanosis and gangrene of the fingers bilaterally. His cyanosis and gangrene did not resolve despite tapering of the vasopressor treatment. Gradually, his digital gangrene improved after administration of anti-platelet medication and pentoxifylline. To the best of our knowledge, this is the first case report of symmetrical peripheral gangrene occurring after acute pancreatitis with successful resolution. We highlight the importance of prompt and aggressive fluid resuscitation and consideration of multiple treatment options to prevent a hypovolemic state caused by acute pancreatitis.


Factors associated with motorcycle-related road traffic crashes in Africa, a Scoping review from 2016 to 2022.
The toll associated with road traffic crashes (RTC) is high, and the burden of injury is disproportionately borne by pedestrians and motor riders, particularly in developing countries. This study synthesized the factors associated with motorcycle-related RTC in Africa. The PICO framework and the PRISMA guidelines for conducting reviews were incorporated in searching, screening, and reporting the findings. Advanced search in five electronic databases (Google Scholar, PubMed Central, Scopus, CINAHL, and Embase) yielded 2552 titles and 22 from manual search, filtered for 2016 to 2022 (to generate 1699) and then further for primary studies (854). Through the title, abstract and full-text screening, 22 were appropriate for this review. Data extraction was done by the two researchers independently, and the results were compared. Convergent synthesis was adopted to integrate results, transformed into a narrative, and analyzed using thematic synthesis. The four main themes identified were the rider-related, non-rider-related factors, prevalence and severity of injuries from RTC, and the measures to reduce RTC. The behavioral factors associated with RTC were alcohol use, smoking, use of illicit drugs, tiredness of rider, poor knowledge on traffic regulations, more than one pillow rider, lack of rider license, non-observance of traffic regulations, and non-use of personal protective equipment. Road traffic crashes were common among younger age and male gender. Other factors identified included poor road network, unplanned stoppage by police, unlawful vehicular packing, increased urbanization, and slippery floors. There is the need to institute multi-sectoral measures that target riders' behavior change. Coordinated efforts should target governments, enforcement authorities, and regulatory bodies to enforce enactment that ensures safe use of roads.


IASP taxonomy of chronic pain syndromes: preliminary assessment of reliability.
Communication and consequently advancement of knowledge in understanding and treatment of chronic pain has been hindered by the absence of a taxonomy of chronic pain syndromes. Recently the IASP Subcommittee on Taxonomy proposed a classification method based on a multiaxial system. In the present study the interjudge reliability of 2 of the 5 axes, body location and presumed etiology are evaluated. Overall, axis I demonstrated good reliability, however, the reliability of several categories contained within this axis were low enough to suggest minor changes to this axis may increase its clinical utility. Axis V was found to have only fair reliability and many of the categories comprising this axis were demonstrated to have reliabilities that are not clinically acceptable. The implications of these results for future development and refinement of the IASP taxonomy are discussed.


[Small suggestive lesions of the prostate. Histological and immunohistochemical analyses -- report of the uropathology consultation service].
Punch biopsies have been taken from the prostate with increasing frequency in recent years, with a resulting increase in the number of diagnoses made. To check the diagnosis of "small two- or three-gland carcinoma" we prepared new H and E sections and, when the atypical glands were no longer available, also performed immunohistochemical analyses in 1,041 cases referred to our uropathology consultation service, comparing the diagnoses supplied by the referring doctors with the final diagnoses. In 61.6 of these cases histology confirmed the diagnosis of adenocarcinoma of the prostate; the diagnosis recorded when the basal cell marker was absent and the tumour marker P504S was strongly expressed was atypical microglandular proliferation or suspected carcinoma. Previous diagnoses of prostatic carcinoma were confirmed in 99% of cases. In this way we also confirmed a further 27.9% of cases of prostate carcinoma in the grey area of diagnoses endorsed "suggestive" or "suspected". The patients concerned were thus spared multiple screening biopsies and were assigned for definitive treatment.


Dose finding study for on-demand HIV pre-exposure prophylaxis for insertive sex in sub-Saharan Africa: results from the CHAPS open label randomised controlled trial.
The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown. HIV-negative males 13-24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge. 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24day15 geometric mean ratio 1.06, 95% confidence interval: 0.65-1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin. A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted. EDCTP2, Gilead Sciences, Vetenskapsrådet.


Exploring the upper particle size limit for field flow fractionation online with ICP-MS to address the challenges of water samples from the Taihu Lake.
Regular algal blooms are occurring in Taihu lake, which may be triggered by resuspension of sediments containing relevant amounts of phosphorus. Therefore, our study aims at quantification of phosphorus concentrations bound to suspended particulate matter in Taihu water samples to investigate this hypothesis. A field flow fractionation (FFF) method online with ICP-MS detection was developed to achieve an overview on particulate fractions of phosphorus and related elements including Fe, Al and C from the low nanometer to the low micrometer size range. Mass balance of dissolved and particulate elemental contents was established for quality control purpose and indicated low recovery of Fe, Al and P. Complementary determination of volume based particle size distribution by dynamic imaging analysis showed a majority of particle volume and thus mass in particles with size >5 μm. In order to address this challenge, the upper particle size limit of FFF online with ICP-MS was for the first time investigated in detail using well characterised monodisperse latex particles as model for organic matter in the low micrometer size range including microalgae. The effect of pre-filtration of the sample as well as the contribution of sample introduction via three different interfaces including micromist nebuliser/spray chamber, direct injection nebulisation and APEX with heated spray chamber and solvent removal by condensation on the particulate carbon recovery was studied by ICP-MS detection. The same instrumental setup was also applied for the characterisation of particulate elemental contents in the Taihu water samples as far as possible. Significant improvement of the detected particulate fraction in Taihu water samples was achieved by increasing the membrane pore size for pre-filtration and by using the APEX for introduction of the eluate from FFF into ICP-MS.


Effect of the ethyl acetate extract of Sophora flavescens Aiton on diabetic retinopathy based on untargeted retinal metabolomics.
Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a leading cause of vision impairment and blindness, which lacks effective diagnostic measures and therapeutic options. Sophora flavescens Aiton or "Kushen" is a traditional Chinese medicine used since ancient times, either alone or in combination, to clear heat, dampness, and tearing, and to treat ocular diseases and improve eyesight. Additionally, the flavonoids of Sophora flavescens Aiton extracted using ethyl acetate (EtOAc) (SFE) is effective in managing diabetes and diabetic vascular complications. In this study, we explored the pharmacodynamic effects and material basis of action of SFE on DR for the first time and elucidated the mechanism based on untargeted retinal metabolomics. Results from the pharmacodynamic studies showed that SFE could reduce blood glucose levels in rats, regulate serum lipopolysaccharide, tauroursodeoxycholic acid, and trimethylamine oxide levels, and significantly improve the structure of retina in rats with DR. Moreover, SFE could protect the blood-retinal barrier, reduce angiogenesis and capillary formation, and inhibit retinal nerve cell apoptosis. A total of 13 compounds were identified in the aqueous humor and retina, which were dihydroflavonoid, isoflavonoid, pterostane flavonoid, chalcone, and dihydroflavonol derivatives. In addition, 39 differential metabolites were screened based on retinal metabolomics data and 23 were found to be affected by SFE, indicating its anti-DR effect by regulating the synthetic metabolic pathways, including lactose, bile acid, glycerophospholipid, arginine, purine, and pyrimidine metabolism pathways. Collectively, our findings elucidated the effects, material basis, and treatment mechanism of SFE on DR systematically and could lay the foundation for promoting the clinical application of Sophora flavescens Aiton.


Fungal annexins: a mini review.
The large family of annexins is composed of more than a thousand members which are typically phospholipid-binding proteins. Annexins act in a number of signalling networks and membrane trafficking events which are fundamental to cell physiology. Annexins exert their functions mainly through their calcium-dependent membrane binding abilities; however, some calcium-independent interactions have been documented in the literature. Although mammalian and plant annexins have been well characterized, little is known about this family in fungi. This mini review summarizes the available data on fungal annexins.


Transformation of LRP gene into Brassica napus mediated by Agrobacterium tumefaciens to enhance lysine content in seeds.
Lysine rich protein (LRP) gene derived from the seed of Psophocarpus tetragonolobus was transformed into Brassica napus, employing cotyledon petiole as explants and by using the Agrobacterium tumefaciens strain LBA4404. Transformation efficiency was found to be closely related with phytohormone concentration, infection incubation, and co-cultured time. A medium containing 4 mg/l 6-benzyladenine (6-BA) and 0.3 mg/l naphthalene acetic acid (NAA) was used for plant regeneration. With infection incubation of A. tumefaciens (OD600 = 0.4) for 20 min and co-culture of infected cotyledon petiole for 3 days, the highest transformation efficiency of 8.5% was obtained. To confirm LRP gene expression, PCR and Southern blot analysis were performed on leaf-isolated DNA from regenerated plants resistant to kanamycin. All transgenic plants of the generation T0 formed fertile seeds, which were sowed for the inheritance study of generational T1 and amino acid analysis. It was found that the lysine content of seeds from T1 generation increased by 16.7% compared with non-transgenic lines.


Linum mucronatum: organ to organ lignan variations.
The percentage of podophyllotoxin (PTOX) and its congener lignans were measured by HPLC in Linum mucronatum ssp. mucronatum (Linaceae) fresh plant organs. The highest amounts of PTOX (0.595 +/- 0.060% g/g dry wt) and 6-methoxypodophyllotoxin (MPTOX) (1.491 +/- 0.125% g/g dry wt) were found in the plant sexual organs. Whereas, the highest levels of beta-peltatin, 5'-demethoxy-MPTOX and yatein were found in not developed buds, petals and sepals, respectively.


Genome sequence of Aspergillus flavus A7, a marine-derived fungus with antibacterial activity.
Due to the specific properties of the marine environment, marine microorganisms have exclusive physicochemical characteristics that are different from those of terrestrial microorganisms, which can produce various secondary metabolites (SMs) with considerable structural diversity and biological activity. In this study, three strains of coepiphytic Aspergillus with potential antibacterial activities, A7 (Aspergillus flavus), B27 (Aspergillus flavipes), and R12 (Aspergillus sydowii), were isolated from the South China Sea. Via the Illumina MiSeq sequencing platform, the genomes of the three strains were sequenced, and genome comparison showed the highest diversity of the biosynthetic gene clusters (BGCs) in A7. In addition, a comparison of physiological and genomic characteristics between A7 and other A. flavus strains demonstrated the superior environmental adaptability of A7, which is apparently consistent with the genetic richness of BGCs. By assigning reads to known BGCs, putative BGCs were allocated in A7 that corresponded to various SMs, including naphthopyrone, pyranonigrin E, and cyclopiazonic acids. Based on gene homology analysis, we surmise that a region is involved in the biosynthesis of ustiloxin-like RiPPs, a less thoroughly studied SM in fungi. Our results provide genetic information for the investigation of marine Aspergillus spp., which may help to elucidate their chemical diversity and adaptive strategies.


Calcium supplementation modulates arsenic-induced alterations and augments arsenic accumulation in callus cultures of Indian mustard (Brassica juncea (L.) Czern.).
In the present study, the effect of arsenate (AsV) exposure either alone or in combination with calcium (Ca) was investigated in callus cultures of Brassica juncea (L.) Czern. cv. Pusa Bold grown for a period up to 24 h. The AsV (250 μM) + Ca (10 mM) treatment resulted in a significantly higher level of As (464 μg g(-1) dry weight (DW)) than AsV without Ca (167 μg g(-1) DW) treatment at 24 h. Furthermore, AsV + Ca-treated calli had a higher percent of AsIII (24-47%) than calli subjected to AsV treatment (12-14%). Despite this, AsV + Ca-treated calli did not show any signs of hydrogen peroxide (H(2)O(2)) accumulation or cell death upon in vivo staining, while AsV-exposed calli had increased H(2)O(2), shrinkage of cytoplasmic contents, and cell death. Thus, AsV treatment induced oxidative stress, which in turn elicited a response of antioxidant enzymes and metabolites as compared with control and AsV + Ca treatment. The positive effects of Ca supplementation were also correlated to an increase in thiolic constituents', viz., cysteine, reduced glutathione, and glutathione reductase in AsV + Ca than in AsV treatment. An analysis of selected signaling related genes, e.g., mitogen-activated protein kinases (MAPK3 and MAPK6) and jasmonate ZIM-domain (JAZ3) suggested that AsV and AsV + Ca followed variable pathways to sense and signal the As stress. In AsV-alone treatment, jasmonate signaling was seemingly activated, while MAPK3 was not involved. In contrast, AsV + Ca treatment appeared to specifically inhibit jasmonate signaling and activate MAPK3. In conclusion, Ca supplementation may hold promise for achieving increased As accumulation in plants without compromising their tolerance.


Outcomes in urinary incontinence: reconciling clinical relevance with scientific rigour.
To aid clinicians in selecting an outcome measure for the assessment of urinary incontinence (UI), from the perspective of both scientific rigour and clinical utility. We conducted a comprehensive review of the literature on outcome measures for the assessment of UI in adults. Tools were classified by instrument type (ie, subjective measures, objective measures, clinical observations, quality of life, and combined instruments) and assessed for scientific rigour based on their psychometric properties (reliability, validity, responsiveness). The clinical relevance of each tool was considered in terms of current usage and practicality. The most rigorous validation processes were identified for quality-of-life questionnaires, including the Incontinence Impact Questionnaire, King's Health Questionnaire, Incontinence Quality of Life questionnaire, and Urogenital Distress Inventory. Bladder diaries, goal-attainment scales, and combined measures such as the International Consultation on Incontinence Questionnaire appear to be more practical for use in clinics. The Clinical Global Impression of Improvement is the outcome most widely used clinically, but least well validated. To elevate the level of outcome assessment for UI to meet that of other urology specialties, it is necessary to reconcile the realities of clinical practice with the scientific rigour of UI research, and to mainstream outcome measures that are reciprocally translatable between the two settings.


Corticosteroids in Lupus.
Corticosteroids are the mainstay of treatment of systemic lupus erythematosus, with most patients receiving them at some point in the course of their disease. Corticosteroid use is associated with significant side effects, including infections, hypertension, hyperglycemia, osteoporosis, avascular necrosis, myopathy, cataracts, and glaucoma. Dosing regimens are based on limited data, with the goal of adequately controlling inflammatory symptoms while minimizing steroid exposure in order to reduce adverse effects.


Late sodium current blocker GS967 inhibits persistent currents induced by familial hemiplegic migraine type 3 mutations of the SCN1A gene.
Familial hemiplegic migraine (FHM) is a group of genetic migraine, associated with hemiparesis and aura. Three causative different genes have been identified, all of which are involved in membrane ion transport. Among these, SCN1A encodes the voltage-gated Na+ channel Nav1.1, and FHM caused by mutations of SCN1A is named FHM3. For 7 of the 12 known FHM3-causing SCNA1 mutations functional consequences have been investigated, and even if gain of function effect seems to be a predominant phenotype, for several mutations conflicting results have been obtained and the available data do not reveal a univocal FHM3 pathomechanism. To obtain a more complete picture, here, we characterized by patch clamp approach the remaining 5 mutations (Q1489H, I1498M, F1499 L, M1500 V, F1661 L) in heterologous expression systems. With the exception of I1498M, all mutants exhibited the same current density as WT and exhibited a shift of the steady state inactivation to more positive voltages, an accelerated recovery from inactivation, and an increase of the persistent current, revealing that most FHM3 mutations induce a gain of function. We also determined the effect of GS967, a late Na+ current blocker, on the above mentioned mutants as well as on previously characterized ones (L1649Q, L1670 W, F1774S). GS967 inhibited persistent currents of all SCNA1 FMH3-related mutants and dramatically slowed the recovery from fast inactivation of WT and mutants, consistent with the hypothesis that GS967 specifically binds to and thereby stabilizes the fast inactivated state. Simulation of neuronal firing showed that enhanced persistent currents cause an increase of ionic fluxes during action potential repolarization and consequent accumulation of K+ and/or exhaustion of neuronal energy resources. In silico application of GS967 largely reduced net ionic currents in neurons without impairing excitability. In conclusion, late Na+ current blockers appear a promising specific pharmacological treatment of FHM3.


A 2-phase labeling and choice architecture intervention to improve healthy food and beverage choices.
We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. At baseline (977,793 items, including 199,513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P < .001), and green items increased in phase 1 (P < .001). The largest changes occurred among beverages. Red beverages decreased 16.5% during phase 1 (P < .001) and further decreased 11.4% in phase 2 (P < .001). Green beverages increased 9.6% in phase 1 (P < .001) and further increased 4.0% in phase 2 (P < .001). Bottled water increased 25.8% during phase 2 (P < .001) but did not increase at 2 on-site comparison cafeterias (P < .001). A color-coded labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention.


Cometabolic biodegradation of antibiotics by ammonia oxidizing microorganisms during wastewater treatment processes.
Studies on antibiotic removal during wastewater treatment processes are crucial since their release into the environment could bring potential threats to human health and ecosystem. Cometabolic biodegradation of antibiotics by ammonia oxidizing microorganisms (AOMs) has received special attentions due to the enhanced removal of antibiotics during nitrification processes. However, the interactions between antibiotics and AOMs are less well-elucidated. In this review, the recent research proceedings on cometabolic biodegradation of antibiotics by AOMs were summarized. Ammonia oxidizing bacteria (AOB), ammonia oxidizing archaea (AOA) and complete ammonia oxidizers (comammox) played significant roles in both nitrification and cometabolic biodegradation of antibiotics. Antibiotics at varying concentrations might pose inhibiting or stimulating effect on AOMs, influencing the microbial activity, community abundance and ammonia monooxygenase subunit A gene expression level. AOMs-induced cometabolic biodegradation products were analyzed as well as the corresponding pathways for each type of antibiotics. The effects of ammonium availability, initial antibiotic concentration, sludge retention time and temperature were assessed on the cometabolic biodegradation efficiencies of antibiotics. This work might provide further insights into the fate and removal of antibiotics during nitrification processes.


Modification of primary afferent depolarization in cat group Ia afferents following high frequency intra-axonal tetanization of individual afferents.
Intra-axonal tetanization of a single, functionally-identified group Ia afferent from the triceps surae muscle in the anesthetized cat produces marked enhancement and slowing of the primary afferent depolarization (PAD) generated in the Ia afferent by volleys in flexor muscle group Ia afferents, plus a pronounced transmembrane hyperpolarizing undershoot (HPU) which disappears more rapidly than the enhanced PAD. These alterations are qualitatively and quantitatively similar to those found after conditioning tetani are applied to the whole muscle nerve. The occurrence of these PAD changes after intra-axonal tetanization of a single group Ia afferent appears to rule out the participation of non-specific alterations in extracellular ionic concentrations or activation of polysynaptic pathways in their genesis.


Generalization of visual regularities in newly hatched chicks (Gallus gallus).
Evidence of learning and generalization of visual regularities in a newborn organism is provided in the present research. Domestic chicks have been trained to discriminate visual triplets of simultaneously presented shapes, implementing AAB versus ABA (Experiment 1), AAB versus ABB and AAB versus BAA (Experiment 2). Chicks distinguished pattern-following and pattern-violating novel test triplets in all comparisons, showing no preference for repetition-based patterns. The animals generalized to novel instances even when the patterns compared were not discriminable by the presence or absence of reduplicated elements or by symmetry (e.g., AAB vs. ABB). These findings represent the first evidence of learning and generalization of regularities at the onset of life in an animal model, revealing intriguing differences with respect to human newborns and infants. Extensive prior experience seems to be unnecessary to drive the process, suggesting that chicks are predisposed to detect patterns characterizing the visual world.


The biological activity and signaling profile of EGF/EGFR were affected under heat stress conditions in IEC6 cells.
Epidermal growth factor (EGF) is an effective cytoprotective peptide. It is the main nutritional factor involved in the development of the intestinal tract. It has many important biological effects on the intestinal mucosa. After binding to epidermal growth factor receptor (EGFR), it initiates a signal transduction cascade to jointly promote the migration, proliferation, and differentiation of various cell types. Heat stress severely affects the intestinal health of livestock and is becoming increasingly prevalent due to the yearly increase in ambient temperature and intestinal diseases. However, the effect of heat stress on the activity and signaling of EGF/EGFR in intestinal cells is still unclear. Therefore, rat intestinal crypt epithelial cell line (IEC6) was used as a model to explore this issue, and the results showed that EGF/EGFR is internalized into IEC6 cells in a time-dependent manner under physiological conditions. However, the activity of EGF/EGFR was altered under heat stress. Furthermore, we explored the effect of heat stress on EGF/EGFR-activated signaling transduction in IEC6 cells, and the results showed that levels of factors involved in EGFR-mediated intracellular signaling (such as EGFR, signal transducers and activators of transcription 3/protein kinase B, and extracellular regulatory kinase 1/2) were downregulated under heat stress. In summary, this study shows that heat stress could damage the biological activity and intracellular signaling of EGF/EGFR. These findings have scientific importance in the field of animal husbandry; and lay the foundation for the further study of the biological activities of EGF/EGFR in the intestine.


Spirituality and religiosity contribute to ongoing COVID-19 vaccination rates: Comparing 195 regions around the world.
Vaccine hesitancy has taken global prominence with the rapid spread of COVID-19, but what factors are related to this considerable variation in vaccination rates globally? Three studies that encompass 195 unique regions from around the world found that the relative spirituality and religiosity of a region predict ongoing COVID-19 vaccination rates, such that those regions higher in spirituality and/or religiosity are regions with lower COVID-19 vaccination rates. In Study 1, data from 23 regions globally were obtained, and both spirituality and religiosity were negatively associated with vaccination rates. These effects held when applying two methods to account for vaccine supply issues. In Study 2, data from 144 regions globally were obtained, and once again religiosity negatively predicted COVID-19 vaccination rates. It remained a significant predictor of vaccination rates when controlling for GDP, population age, collectivism, general skepticism towards vaccinations, and previous inoculation history. In Study 3, data from all USA states and the District of Columbia were obtained, and religiosity and spirituality once again were negatively associated with COVID-19 vaccination rates. Effects held controlling for other factors. Across studies, spirituality and religiosity account for a large amount of the variance in vaccination rates. These results suggest that real-world behavior can be predicted by the relative spirituality and religiosity of a region.


[Postoperative analgesia with continuous intra-articular infusion of ropivacaine following trapeziectomy].
A pilot study was implemented to evaluate the efficacy of patient controlled analgesia (PCA) with continuous intra-articular infusion of ropivacaine following trapeziectomy with ligament reconstruction and tendon interposition. Twelve patients were prospectively included. A catheter was placed into the trapezium void and connected to a PCA pump set on a continuous intra-articular infusion rate of ropivacaine: 2mg/ml. Patients were allowed to deliver additional boluses when analgesia was incomplete. Pain was evaluated less than 3/10 (Numeric Scale Evaluation) by 92% of the patients during the first 48 h. No toxicity of the local anaesthetic nor catheter-related complication were reported. This preliminary study showed continuous basal and bolus infusion of ropivacaine through a single catheter placed into the trapezium void to provide an excellent postoperative pain control and to be related to a high patient's satisfaction level.


Efficacy, safety, and parental anxiety in a randomized trial of two dietary instruction methods for children with suspected hen's egg allergy.
Little has been reported on how to introduce hen's egg into the diet of children with suspected egg allergy. We compared the efficacy, safety, and parental anxiety of two different dietary instruction methods to introduce egg. Eligible participants were children aged 1-4 years who were positive for egg white IgE, and ovomucoid IgE <3.5 kUA/L. Participants were either naïve in egg consumption or had a history of an immediate, but non-anaphylactic, allergic reaction to egg. After a negative result of baseline 2 g boiled egg white oral food challenge (OFC), participants were randomly assigned to the step-up OFC testing (SOFT) or home incrementing group. The primary outcome was the proportion of participants who were able to ingest 20 g of boiled egg white 6 months after initiation. This study is registered with the University Hospital Medical Information Network clinical trial registry (UMIN000024192). Between September 2016 and August 2018, we randomly allocated 55 participants to the SOFT (n = 33 [60%]) and home incrementing (n = 22 [40%]) groups and analyzed 51 patients. Four patients were excluded because they were lost to follow-up. Thirty-one (96.9%) of 32 participants in the SOFT and 12 (63.2%) of 19 in the home incrementing group achieved the primary outcome (p = 0.003). No serious adverse reactions were observed in either group. Parental anxiety significantly improved during treatment in both groups. The SOFT method was more effective than home incrementing as dietary instruction to introduce egg in children with suspected egg allergy.


Irritable bowel syndrome: assessment of psychological disturbance and its influence on the response to fibre supplementation.
This study describes the effect of fibre supplementation on the gastrointestinal symptoms and general wellbeing of patients with constipated irritable bowel syndrome. In a single centre, double blind, placebo controlled trial of 3 months duration, a daily supplement of 4.1 g fibre produced no greater change in gastrointestinal symptoms than placebo. Pretreatment constipation was related to baseline fibre intake. Overall outcome was the same in treated and control groups; a considerable placebo response was evident. This level of fibre supplementation is not a useful treatment; improving neither constipation nor other symptoms. At the outset pain severity correlated with depression score on psychometric testing. Those who felt better at the end of the study scored significantly lower for depression at outset than those who felt no better. In irritable bowel syndrome a depressive emotional state profile is a powerful determinant of outcome, shaping the response to treatment, which includes a considerable placebo element.


Considerations in the design of vaccines that induce CD8 T cell mediated immunity.
The protective capacity of many currently used vaccines is based on induction of neutralizing antibodies. Many pathogens, however, have adapted themselves in different ways to escape antibody-based immune protection. In particular, for those infections against which conventional neutralizing antibody-based vaccinations appear challenging, CD8 T-cells are considered to be promising candidates for vaccine targeting. The design of vaccines that induce robust and long-lasting protective CD8 T-cell responses however imposes new challenges, as many factors such as kinetics and efficiency of antigen-processing and presentation by antigen presenting cells, T-cell repertoire and cytokine environment during T cell priming contribute to the specificity and functionality of CD8 T-cell responses. In the following, we review the most prominent aspects that underlie CD8 T-cell induction and discuss how this knowledge may help to improve the design of efficient CD8 T-cell inducing vaccines.


Elevated hepatic and depressed renal cytochrome P450 activity in the Tg2576 transgenic mouse model of Alzheimer's disease.
Recent studies indicate that the Tg2576 transgenic mouse model of Alzheimer's disease [tg(hAPP)] demonstrates disturbances in plasma glucose and neuroendocrine function reminiscent of Alzheimer's disease (AD). Alterations in any one of these systems can have a profound effect on hepatic cytochrome P450 (CYP) expression. Additionally, the recent discovery that amyloid beta 1-42 can induce the expression of CYP reductase in neuronal cultures further suggests that hepatic CYP-related metabolism may be affected by the expression of mutant human amyloid precursor protein in these tg(hAPP) mice. Therefore, the current study was conducted to investigate the activity and protein content of several CYP isoforms in the livers and kidneys of aged (20-month-old) tg(hAPP) mice. tg(hAPP) mice exhibit significant elevations in hepatic CYP2B, CYP2E1-, CYP3A- and CYP4A-associated activities and CYP4A immunoreactive protein compared with wild-type. In contrast to the liver, a significant depression in renal CYP2E1- and CYP4A-associated activities were demonstrated in tg(hAPP) mice. The presence of the mutant hAPP protein was detected in the brain, kidney and livers of tg(hAPP) mice.


Association of HLA-DRw8 and DQw3 with minimal change nephrotic syndrome in Japanese adults.
The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.


Palliative and end-of-life care: where are we now?
Despite regional and national efforts to improve access, many eligible patients aren't getting the care they need.


Association between age, breed and sex in relation to urinary disorders in insured cats in Japan during fiscal year 2012.
Data from 48,187 cats insured between April 2012 and March 2013 were analyzed using logistic regression analysis to determine the association of age, breed and sex with the occurrence of urinary disorders. The overall annual prevalence of urinary disorders was 12.2%. Using crossbreeds as the reference breed, Abyssinian cats had the highest odds of having urinary disorders with a ratio of 1.40 (95% confidence interval: 1.20-1.63), followed by Norwegian Forest Cats and Somalis. Male cats had higher odds of having urinary disorders with a ratio of 1.27 (1.20-1.35) over female cats. Older cats had higher odds of having urinary disorders than young cats.


Nutrition is a powerful independent risk factor for coronary heart disease in women--The CORA study: a population-based case-control study.
It is still common practice to rely mostly on drug treatment for preventing cardiovascular disease, although a healthy nutrition has been defined that may prevent most premature cardiovascular events. This research raises the question of the magnitude of the effect of nutrition on cardiovascular disease independent of that of clinical risk factors, which are the targets of drug therapy. The study of coronary risk factors for atherosclerosis in women compares clinical, biochemical, and lifestyle factors in 200 consecutive pre- and postmenopausal women with incident coronary heart disease (CHD) to those in 255 age-matched population-based controls. Cases reported a higher intake of energy, predominantly through animal fat and protein reflected by a higher consumption of meat and sausage, while controls ate more fruit and vegetables. Multivariate analysis adjusted for clinical risk factors depicted a high intake of meat and sausage and a low consumption of fruit and vegetables as independent risk factors with an odds ratio of 2.5 (95% confidence interval 1.1-5.7) and 0.7 (95% confidence interval 0.5-1.0) for each 100 g per day, respectively. These dietary factors were found to be significantly more pronounced in cases with any clinical risk factor identified in this population as compared to controls with the same risk factors. The CORA-study clearly indicates a major impact of dietary habits on CHD in women independent of, and additive to, that of conventional risk factors. Thus, in clinical practice, the potential of nutrition as part of a healthy lifestyle is commonly greatly underestimated in favour of drug treatment.


Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T cell-derived cytokine production in ovalbumin (OVA)-immunized C57Bl/6 mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress both cellular and humoral immunity. Effector T cell-derived type-2 cytokines, including IL-4 and IL-5, play pivotal roles in humoral immunity. Herein, we studied whether TCDD affects type-2 cytokine productions during the immune response. C57Bl/6 mice were intraperitoneally immunized with ovalbumin (OVA) and orally administered 5 or 20 microg TCDD/kg on Day 0, and then challenged with OVA on Day 21. Seven days later (Day 28), antigen-specific antibodies in plasma, and T cell-derived cytokines produced by splenocytes and proliferation of splenocytes upon ex vivo re-stimulation with OVA were investigated. The quantities of IgM class and IgG1 class OVA-specific antibodies in plasma were reduced by 5 or 20 microg TCDD/kg and by 20 microg TCDD/kg, respectively. While thymus weight and cellularity were reduced by 20 microg TCDD/kg, spleen weight and cellularity were not changed by either 5 or 20 microg TCDD/kg. The proportions of B and T cells in the spleen were not affected by TCDD exposure. On the other hand, splenocytes from mice treated with 5 or 20 microg TCDD/kg were shown to produce less IL-4 or IL-5 upon ex vivo re-stimulation with OVA. Production of the T cell growth factor IL-2 was also decreased in splenocytes from TCDD-treated mice. In contrast, the type-1 cytokine IFN-gamma was increased by TCDD. Twenty micrograms of TCDD/kg suppressed OVA- or T cell mitogen (Con A)-stimulated proliferation of splenocytes, but did not affect B cell mitogen (LPS)-stimulated proliferation. These results suggested compromised T cell activation and suppressed type-2 cytokine production by T cells to be involved in the impaired humoral immunity associated with TCDD exposure.