Chemical mixture toxicity testing with Vibrio fischeri: combined effects of binary mixtures for ten soft electrophiles.
The toxicity of 30 binary combinations of 10 soft electrophiles was examined in Microtox using dose-response curve (DRC) analysis. Chemicals from three groups of soft electrophiles-vinyl Michael acceptors (I--react with a thiol group), dicarbonyl reactive agents (II--react with a primary amine), and alpha-haloactivation compounds (III--react with a thiol group)--were selected for testing to evaluate the relationship between molecular site of chemical action and combined toxic effect. For each combination tested, each single agent was tested alone at six duplicated concentrations and three 1:1 mixtures of the agents were also tested, each at six duplicated concentrations. Exposure duration was 15 min for each single agent and mixture test. Sigmoid DRCs for each single chemical and mixture were constructed and the single chemical curves were used to develop a theoretical dose-addition DRC for the combination. Additivity quotient (AQ) values for slope and EC50 were calculated by dividing the actual mixture slope or EC50 for a given combination by the predicted slope or EC50, respectively, from the theoretical dose-addition DRC. Three criteria were selected for value in determining the combined effect obtained for each combination: (1) slope AQ 95% confidence interval (CI) overlap with 1.0 (1.0=dose addition), (2) EC50 AQ 95% CI overlap with 1.0, and (3) mean mixture data point 95% and 99% CI overlap with the theoretical dose-addition DRC. Each of three sham combinations showed combined effects consistent with dose addition for each criterion. Dose addition was expected for 15 nonsham combinations (nine within-group combinations and six group I:III combinations) and a nondose-additive effect was expected for 12 combinations (all I:II and II:III combinations). Actual combined effects obtained by incorporating all three criteria (noted above) showed only six instances of dose addition. Therefore, time-dependent toxicity (TDT) tests of each soft electrophile alone and for three nonpolar narcotic chemicals alone were conducted, using 15-, 30-, and 45-min exposure durations, to assess the time-dependent nature of the toxicity. Results of the TDT tests suggested that five had fully (or nearly fully) TDT (interpreted as an irreversible effect representing one molecular site of action), five of the soft electrophiles had partially TDT (i.e., representing two or more molecular sites of action for the agents, one irreversible and one reversible), and the three nonpolar narcotics had no TDT (i.e., a fully reversible toxic effect). With this TDT information, the combined effects for 25 of the 27 mixtures, although rather complex, could be explained. It is noteworthy that all combined effects obtained, whether concluded to be dose-additive or not, were close to dose-additive for hazard assessment purposes.


Identification of TMCO2 as an acrosome-associated protein during rat spermiogenesis.
We isolated the transmembrane and coiled-coil domains 2 (Tmco2) gene using a polymerase chain reaction-based subtraction technique. Tmco2 is predominantly expressed in rat testes starting from 4 weeks of age. Rat TMCO2 consists of 187 amino acids with a predicted molecular mass of 20.6 kDa. When expressed in COS7 cells, TMCO2 was found as vesicle-like structures in the cytoplasm, whereas TMCO2ΔTM lacking the transmembrane (TM) region was found diffused in the cytoplasm. These results suggest that the TM region in TMCO2 is essential for its specificity of localization. Immunocytochemical analyzes indicated that rat TMCO2 was localized as small semiluminate bodies or cap-like structures in the vicinity of round spermatid nuclei and as curved lines associated with nuclei of elongated spermatids and caput epididymal spermatozoa. However, it was detected in only a small part of cauda epididymal spermatozoa. Double immunolabeling of the spermatids and spermatozoa with the anti-TMCO2 antibody and the monoclonal anti-MN7 antibody showed that TMCO2 was predominantly associated with the inner acrosomal membrane in spermatids and caput epididymal spermatozoa. Our findings suggest that TMCO2 might be involved in the process of acrosome biogenesis, especially binding of acrosome to a nucleus, during spermiogenesis.


Properties and substrate specificity of the leucyl-, the threonyl- and the valyl-transfer-ribonucleic acid synthetases from Aesculus species.
1. Leucyl- and threonyl-tRNA synthetases were partially purified up to 100-fold and 30-fold respectively from cotyledons of Aesculus hippocastanum and were largely separated from the other aminoacyl-tRNA synthetases. Valyl-tRNA synthetase was purified 25-fold from cotyledons of Aesculus californica. 2. Some properties are reported for the three enzymes when assayed by the [(32)P]pyrophosphate-ATP exchange technique. 3. beta-(Methylenecyclopropyl)alanine, isoleucine, azaleucine, norleucine and gamma-hydroxynorvaline acted as alternative substrates for the leucyl-tRNA synthetase; the enzyme's affinity for beta-(methylenecyclopropyl)-alanine and for isoleucine was about 80-fold less than that exhibited for leucine. 4. alpha-Cyclopropylglycine and alpha-cyclobutylglycine acted as alternative substrates for the valyl-tRNA synthetase.


Preliminary report: a pregnancy from frozen centrifuged dog semen.
Semen obtained from a pure-bred Beagle was diluted 1:3 with a Tris (hydroxymethyl) - aminomethane buffered egg yolk diluent, centrifuged at 450 g for 10 minutes and the spermatozoa thus concentrated stored in 8 Cassou mini straws (0,25 ml) in liquid nitrogen. One month after collection, a single semen straw was thawed, rediluted with 4 ml of diluent containing no glycerol and inseminated into a Beagle in oestrus. This was repeated daily for 4 days. The vagina of the bitch was flushed with 4 ml of the diluent immediately prior to insemination on each occasion. The bitch whelped 7 pups 60 days after the first insemination.


The validity of self-reported diabetes quality of care measures.
First, to test the validity of self-reported quality of care and treatment measures compared with medical records and administrative data for: eye examinations, hemoglobin A1C tests, and use of insulin and oral agents for adult patients with diabetes; and secondly to assess the consistency between medical record information and administrative data for the same measures plus microalbumin testing. Cross-sectional study using data from telephone survey, primary care medical and eye records, and administrative claims. Statewide health maintenance organization in Minnesota, USA, 1995. Four hundred and forty adults with diabetes, aged 31-64 years. Validity++ of self-reported diabetes quality of care measures compared with a criterion standard combining information from primary care and eye records with information from administrative data; and reliability of medical record information compared with administrative data. Although the sensitivity of self-reported eye examination was high (89%), the specificity was low (65%). Self-report of hemoglobin A1C also had high sensitivity (99%) and a lower specificity than that of eye examination (28%). The two information sources (medical records and claims) used in the criterion standard each contained complementary and non-overlapping information. Reliability was highest for microalbumin testing (kappa, 0.75) and lowest for eye examination (kappa, 0.37). Quality of care measures for diabetes are often drawn from a variety of sources. To the extent that data sources are biased, the measures can be misleading. Self-report is likely to lead to an overestimate of eye screening and the measurement of hemoglobin A1C. Reported rates of quality of care should be inspected carefully. The 'same' rate taken from different sources may vary.


Relationship between male age, accessory gland, sperm transferred, and fitness traits in Drosophila bipectinata.
The number of cells and the size of the cells in the male accessory gland, the quantity of accessory gland proteins, and their effects on fitness in males of different ages were studied in Drosophila bipectinata Duda (Diptera: Drosophilidae). Male age was significantly positively correlated with the size of accessory gland, the number of main cells of the accessory gland, the quantity of protein in unmated males, the duration of copulation, the transferred quantity of protein and sperm to the mated female, fecundity, and fertility, while male age was significantly negatively correlated with the size of main cell in the accessory gland and the quantity of protein in mated males. The size of the main cells was significantly positively correlated with the quantity of protein in unmated males but significantly negatively correlated with the size of the accessory gland and the number of main cells in the accessory gland. These results suggest that D. bipectinata young males, with their smaller size of their accessory glands and having fewer and larger main cells in their accessory glands, produced the least quantity of protein and transferred significantly less protein and sperm to the mated female than did middle and old age males. Thus, this study suggests that in D. bipectinata, male age affects the number of accessory gland cells and the quantity of protein in the accessory gland. The size and number of main cells in the accessory gland and the size of the accessory gland were related to the production of protein. Females who mated with old males obtained a fitness benefit.


Theoretical pi-pi absorption and circular dichroic spectra of beta-turn model peptides.
The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate pi-pi absorption and circular dichroic spectra of beta-turn model peptides in certain conformations. These include Ac-Gly-Gly-NHMe, Ac-L-Ala-L-Ala-NHMe, and Ac-L-Ala-Gly-NHMe in the standard beta-turn conformations I, II, and III of Venkatachalam and cyclo(L-Ala-Gly-epsilon-aminocaproyl), cyclo(L-Ala-L-Ala-epsilon-aminocaproyl), and cyclo(L-Ala-D-Ala-epsilon-aminocaproyl) in the minimum-energy conformations of Nemethy et al. Boltzmann average circular dichroic spectra of the cyclic compounds agree with experimental spectra in most respects. The results are compared with previous theoretical CD spectra for these molecules and with conformational assignments based on other evidence. Absorption spectra in the pi-pi band are predicted to be moderately sensitive to conformation.


[The Starr-Edwards heart valve: one of the oldest mechanical heart valves still functioning today].
In the 1960s, the Starr-Edwards valve was the first artificial heart valve to be successfully implanted in humans. This valve has now been in use for decades with outstanding results: patients whose life expectancy had previously been short acquired a good prognosis with this development. Nowadays the Starr-Edwards valve is not used anymore, but patients are being described today in whom these valves are still functioning well after more than 40 years.


[Cognitive Function and Calcium. Cognitive improvement through T type calcium channel stimulation].
Low-threshold Ca2+ spikes are mediated by T-type Ca2+ channels, which have fast inactivation and slow deactivation kinetics (transient) , and single channel conductance. The activation are triggered by -60 to -65 mV. T-type Ca2+ channels are predominantly expressed in the brain and heart pacemaker cells. Three subtypes of T-type Ca2+ channels Cav3.1 (α1G), Cav3.2 (α1H), Cav3.3 (α1I) encoding by CACNA1G, CACNA1H, CACNA1I genes have been cloned. Although high-threshold voltage-gated Ca2+ channels have auxiliary α2δ, β, γ subunits, T-type Ca2+ channels are composed only by α1 subunit. Although T-type Ca2+ channels are involved in the pace making in heart and a robust low-threshold Ca2+ spike in neurons, the physiological functions in the memory and synaptic plasticity remain unclear. In this paper, I would like to focus on the pathophysiological relevance of T-type Ca2+ channels in the brain functions including cognition.


A biologically plausible embodied model of action discovery.
During development, animals can spontaneously discover action-outcome pairings enabling subsequent achievement of their goals. We present a biologically plausible embodied model addressing key aspects of this process. The biomimetic model core comprises the basal ganglia and its loops through cortex and thalamus. We incorporate reinforcement learning (RL) with phasic dopamine supplying a sensory prediction error, signalling "surprising" outcomes. Phasic dopamine is used in a cortico-striatal learning rule which is consistent with recent data. We also hypothesized that objects associated with surprising outcomes acquire "novelty salience" contingent on the predicability of the outcome. To test this idea we used a simple model of prediction governing the dynamics of novelty salience and phasic dopamine. The task of the virtual robotic agent mimicked an in vivo counterpart (Gancarz et al., 2011) and involved interaction with a target object which caused a light flash, or a control object which did not. Learning took place according to two schedules. In one, the phasic outcome was delivered after interaction with the target in an unpredictable way which emulated the in vivo protocol. Without novelty salience, the model was unable to account for the experimental data. In the other schedule, the phasic outcome was reliably delivered and the agent showed a rapid increase in the number of interactions with the target which then decreased over subsequent sessions. We argue this is precisely the kind of change in behavior required to repeatedly present representations of context, action and outcome, to neural networks responsible for learning action-outcome contingency. The model also showed cortico-striatal plasticity consistent with learning a new action in basal ganglia. We conclude that action learning is underpinned by a complex interplay of plasticity and stimulus salience, and that our model contains many of the elements for biological action discovery to take place.


Regulation of adipokine secretion by n-3 fatty acids.
Obesity leads to several chronic morbidities including type 2 diabetes, dyslipidaemia, atherosclerosis and hypertension, which are major components of the metabolic syndrome. White adipose tissue (WAT) metabolism and WAT-derived factors (fatty acids and adipokines) play an important role in the development of these metabolic disturbances. In fact, dysregulated adipokine secretion from the expanded WAT of obese individuals contributes to the development of systemic low-grade inflammation, insulin resistance and metabolic syndrome. The n-3 PUFA EPA and DHA have been widely reported to have protective effects in a range of chronic inflammatory conditions including obesity. In fact, n-3 PUFA have been shown to ameliorate low-grade inflammation in adipose tissue associated with obesity and up-regulate mitochondrial biogenesis and induce beta-oxidation in WAT in mice. Moreover, the ability of n-3 PUFA to regulate adipokine gene expression and secretion has been observed both in vitro and in vivo in rodents and human subjects. The present article reviews: (1) the physiological role of adiponectin, leptin and pre-B cell colony-enhancer factor/visfatin, three adipokines with immune-modulatory properties involved in the regulation of metabolism and insulin sensitivity and (2) the actions of n-3 PUFA on these adipokines focusing on the underlying mechanisms and the potential relationship with the beneficial effects of these fatty acids on obesity-associated metabolic disorders. It can be concluded that the ability of n-3 PUFA to improve obesity and insulin resistance conditions partially results from the modulation of WAT metabolism and the secretion of bioactive adipokines including leptin, adiponectin and visfatin.


Celiac disease causing severe osteomalacia: an association still present in Morocco!
Celiac disease (CD), a malabsorption syndrome caused by hypersensitivity to gliadin fraction of gluten. CD can manifest with classic symptoms; however, significant myopathy and multiple fractures are rarely the predominant presentation of untreated celiac disease. Osteomalacia complicating celiac disease had become more and more rare. We describe here a case of osteomalacia secondary to a longstanding untreated celiac disease. This patient complained about progressive bone and muscular pain, weakness, fractures and skeletal deformities. Radiological and laboratory findings were all in favor of severe osteomalacia. Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron. This case affirms that chronic untreated celiac disease, can lead to an important bone loss and irreversible complications like skeletal deformities.


Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer.
Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).


Temporal, spatial and spatiotemporal analysis of the occurrence of visceral leishmaniasis in humans in the City of Birigui, State of São Paulo, from 1999 to 2012.
In 1999, Birigui and Araçatuba were the first municipalities in the State of São Paulo to present autochthonous cases of visceral leishmaniasis in humans (VLH). The aim of this study was to describe the temporal, spatial and spatiotemporal behaviors of VLH in Birigui. Secondary data were obtained from the Notifiable Diseases Information System from 1999 to 2012. The incidence, mortality and case fatality rates by sex and age were calculated. The cases of VLH were geocoded and grouped according to census tracts. Local empirical Bayesian incidence rates were calculated. The existence of spatial and spatiotemporal clusters was investigated using SaTScan software. There were 156 confirmed cases of autochthonous VLH. The incidence rate was higher in the 0-4-year-old children, and the mortality and case fatality rates were higher in people aged 60 years and older. The peaks of incidence occurred in 2006 and 2011. The Bayesian rates identified the presence of VLH in all of the census tracts in the municipality; however, spatial and spatiotemporal clusters were found in the central area of the municipality. Birigui, located in the Araçatuba region, has recently experienced increasing numbers of VLH cases; this increase is contrary to the behavior observed over the entire region, which has shown a decreasing trend in the number of VLH cases. The observations that the highest incidence is in children 0-4 years old and the highest mortality is in people 60 years and older are in agreement with the expected patterns of VLH.


SynCLay: Interactive synthesis of histology images from bespoke cellular layouts.
Automated synthesis of histology images has several potential applications in computational pathology. However, no existing method can generate realistic tissue images with a bespoke cellular layout or user-defined histology parameters. In this work, we propose a novel framework called SynCLay (Synthesis from Cellular Layouts) that can construct realistic and high-quality histology images from user-defined cellular layouts along with annotated cellular boundaries. Tissue image generation based on bespoke cellular layouts through the proposed framework allows users to generate different histological patterns from arbitrary topological arrangement of different types of cells (e.g., neutrophils, lymphocytes, epithelial cells and others). SynCLay generated synthetic images can be helpful in studying the role of different types of cells present in the tumor microenvironment. Additionally, they can assist in balancing the distribution of cellular counts in tissue images for designing accurate cellular composition predictors by minimizing the effects of data imbalance. We train SynCLay in an adversarial manner and integrate a nuclear segmentation and classification model in its training to refine nuclear structures and generate nuclear masks in conjunction with synthetic images. During inference, we combine the model with another parametric model for generating colon images and associated cellular counts as annotations given the grade of differentiation and cellularities (cell densities) of different cells. We assess the generated images quantitatively using the Frechet Inception Distance and report on feedback from trained pathologists who assigned realism scores to a set of images generated by the framework. The average realism score across all pathologists for synthetic images was as high as that for the real images. Moreover, with the assistance from pathologists, we showcase the ability of the generated images to accurately differentiate between benign and malignant tumors, thus reinforcing their reliability. We demonstrate that the proposed framework can be used to add new cells to a tissue images and alter cellular positions. We also show that augmenting limited real data with the synthetic data generated by our framework can significantly boost prediction performance of the cellular composition prediction task. The implementation of the proposed SynCLay framework is available at https://github.com/Srijay/SynCLay-Framework.


Recurrence of instability after Latarjet procedure: causes, results and treatment algorithm.
Latarjet modifies the anatomy of the shoulder, and subsequent revision surgery is challenging. It is mandatory to determine the cause of recurrence in order to select the best treatment option. A CT scan is needed to measure glenoid track and evaluate coracoid graft status: position, degree of consolidation, and osteolysis. Conservative management can be advocated in selected patients in whom the instability level does not interfere with the activities they wish to perform. Surgical treatment is based on the glenoid track measurement and coracoid graft suitability. The coracoid graft is considered suitable if it preserves the conjoint tendon insertion, does not show osteolysis, and is large enough to reconstruct the glenoid surface. Adding a remplissage is recommended for those cases with a coracoid graft insufficient to convert large off-track Hill-Sachs lesions into on-track. If the coracoid graft is suitable to reconstruct bone defects in terms of size and viability but is poorly positioned or avulsed, graft repositioning can be a valid option. In patients with unsuitable coracoid bone graft, free bone graft is the revision technique of choice. The size of the graft should be large enough to restore the glenoid surface and to convert any off-track Hill-Sachs lesion into on-track. There is a small group of patients in whom bone defects were properly addressed but Latarjet failed due to hyperlaxity or poor soft tissue quality. Extraarticular capsular reinforcement is suggested in this population.


Mitochondrial but not plasmalemmal BK channels are hypoxia-sensitive in human glioma.
Tumor cells are resistant to hypoxia but the underlying mechanism(s) of this tolerance remain poorly understood. In healthy brain cells, plasmalemmal Ca(2+)-activated K(+) channels ((plasma)BK) function as oxygen sensors and close under hypoxic conditions. Similarly, BK channels in the mitochondrial inner membrane ((mito)BK) are also hypoxia sensitive and regulate reactive oxygen species production and also permeability transition pore formation. Both channel populations are therefore well situated to mediate cellular responses to hypoxia. In tumors, BK channel expression increases with malignancy, suggesting these channels contribute to tumor growth; therefore, we hypothesized that the sensitivity of (plasma)BK and/or (mito)BK to hypoxia differs between glioma and healthy brain cells. To test this, we examined the electrophysiological properties of (plasma)BK and (mito)BK from a human glioma cell line during normoxia and hypoxia. We observed single channel activities in whole cells and isolated mitoplasts with slope conductance of 199 ± 8 and 278 ± 10 pA, respectively. These currents were Ca(2+)- and voltage-dependent, and were inhibited by the BK channel antagonist charybdotoxin (0.1 μM). (plasma)BK could only be activated at membrane potentials >+40 mV and had a low open probability (NPo) that was unchanged by hypoxia. Conversely, (mito)BK were active across a range of membrane potentials (-40 to +40 mV) and their NPo increased during hypoxia. Activating (plasma)BK, but not (mito)BK induced cell death and this effect was enhanced during hypoxia. We conclude that unlike in healthy brain cells, glioma (mito)BK channels, but not (plasma)BK channels are oxygen sensitive.


Ski acts as a co-repressor with Smad2 and Smad3 to regulate the response to type beta transforming growth factor.
The c-ski protooncogene encodes a transcription factor that binds DNA only in association with other proteins. To identify co-binding proteins, we performed a yeast two-hybrid screen. The results of the screen and subsequent co-immunoprecipitation studies identified Smad2 and Smad3, two transcriptional activators that mediate the type beta transforming growth factor (TGF-beta) response, as Ski-interacting proteins. In Ski-transformed cells, all of the Ski protein was found in Smad3-containing complexes that accumulated in the nucleus in the absence of added TGF-beta. DNA binding assays showed that Ski, Smad2, Smad3, and Smad4 form a complex with the Smad/Ski binding element GTCTAGAC (SBE). Ski repressed TGF-beta-induced expression of 3TP-Lux, the natural plasminogen activator inhibitor 1 promoter and of reporter genes driven by the SBE and the related CAGA element. In addition, Ski repressed a TGF-beta-inducible promoter containing AP-1 (TRE) elements activated by a combination of Smads, Fos, and/or Jun proteins. Ski also repressed synergistic activation of promoters by combinations of Smad proteins but failed to repress in the absence of Smad4. Thus, Ski acts in opposition to TGF-beta-induced transcriptional activation by functioning as a Smad-dependent co-repressor. The biological relevance of this transcriptional repression was established by showing that overexpression of Ski abolished TGF-beta-mediated growth inhibition in a prostate-derived epithelial cell line.


The structural basis of DNA flexibility.
Although the average physico-chemical properties of a long DNA molecule may approximate to those of a thin isotropic homogeneous rod, DNA behaves more locally as an anisotropic heterogeneous rod. This bending anisotropy is sequence dependent and to a first approximation reflects both the geometry and stability of individual base steps. The biological manipulation and packaging of the molecule often depend crucially on local variations in both bending and torsional flexibility. However, whereas the probability of DNA untwisting can be strongly correlated with a high bending flexibility, DNA bending, especially when the molecule is tightly wrapped on a protein surface, may be energetically favoured by a less flexible sequence whose preferred configuration conforms more closely to that of the complementary protein surface. In the latter situation the lower bending flexibility may be more than compensated for on binding by a reduced required deformation energy relative to a fully isotropic DNA molecule.


Oral Factors as Predictors of Frailty in Community-Dwelling Older People: A Prospective Cohort Study.
The purpose of this prospective cohort study was to identify predictors for frailty among possible oral factors in community-dwelling older people. Ninety-seven participants (≥60 years old) without frailty at baseline were included and assigned to either the robust or the frailty group after 2-year follow-up. The frailty was defined using the Japan Cardiovascular Health Study index. The numbers of present and functional teeth and periodontal disease severity were recorded. Bacterial counts on the dorsum of the tongue, oral moisture, tongue pressure, occlusal force, masticatory ability, and the oral diadochokinesis (ODK) rate were measured. Swallowing function, along with psychosocial status, relationships with communities and people, nutritional status, medical history, and comorbidities were evaluated using a questionnaire. The newly identified frailty group at follow-up showed significantly lower values in the number of teeth present, ODK/ta/sound and ODK/ka/sound rates, and clinical attachment level at baseline compared to the robust group. A logistic regression model showed a significantly negative association between the ODK/ta/sound rate at baseline and the incidence of frailty. Articulatory oral motor skill was found to be a predictor of frailty after two years.


Role of infectious secretions in the transmission of rhinovirus.
In a series of studies aimed at investigating the role of environmental surfaces in the transmission of certain respiratory virus infections, it was shown that small amounts of nasal mucus containing rhinovirus (infectious mucus) can spread from fingertips to door knobs, faucet handles, or other environmental surfaces and remain infectious for many hours. These surfaces can serve as a reservoir of virus and may provide sufficient infectious material to contaminate hands. Recent studies have shown that once virus is on the fingers, it may be transferred to the nasal and conjunctival mucosa by means of autoinoculation. It has been estimated that as little as 1.0 plaque-forming unit can produce an infection in a susceptible human. In the present experiments, the amount of rhinovirus transmitted from fingers contaminated with infectious mucus to environmental surfaces and from there onto the fingers of a volunteer who touched the contaminated objects was quantitated, and the efficiency of transfer was studied. From 3 to 1,800 plaque-forming units of rhinovirus were recovered from the fingertips of volunteers (recipients) who handled either a door knob or a faucet that had previously been manipulated by another volunteer (donor) whose fingers were contaminated with infectious mucus. The average amount of rhinovirus recovered from the fingers of the recipients was approximately 13.5% of the amount recoverable from the fingers of the donor. In experiments in which there was direct hand-to-hand contact between donor and recipient, about 6.7% of the virus present on the fingertips of donors was recoverable from the recipients.


Construction and application of highly efficient waste cooking oil degrading bacteria consortium in oily wastewater.
The treatment of cooking oil wastewater is an urgent issue need to be solved. We aimed to screen for efficient oil-degrading bacteria and develop a new microbial agent for degrading waste cooking oil in oily wastewater. Three extremely effective oil-degrading bacteria, known as YZQ-1, YZQ-3, and YZQ-4, were found by the enrichment and acclimation of samples from various sources and separation using oil degradation plates. The 16S rRNA sequencing analysis and phylogenetic tree construction showed that the three strains were Bacillus tropicus, Pseudomonas multiresinivorans, and Raoultella terrigena. Under optimal degradation conditions, the maximal degradation rates were 67.30 ± 3.69%, 89.65 ± 1.08%, and 79.60 ± 5.30%, respectively, for YZQ-1, YZQ-3, and YZQ-4. Lipase activity was highest for YZQ-3, reaching 94.82 ± 12.89 U/L. The best bacterial alliance was obtained by adding equal numbers of microbial cells from the three strains. Moreover, when this bacterial alliance was applied to oily wastewater, the degradation rate of waste cooking oil was 61.13 ± 7.30% (3.67% ± 2.13% in the control group), and COD removal was 62.4% ± 5.65% (55.60% ± 0.71% in the control group) in 72 h. Microbial community analysis results showed YZQ-1 and YZQ-3 were adaptable to wastewater and could coexist with local bacteria, whereas YZQ-4 could not survive in wastewater. Therefore, the combination of YZQ-1 and YZQ-3 can efficiently degrade oil and shows great potential for oily wastewater treatment.


MR imaging in solvent-induced chronic toxic encephalopathy.
To use MR to examine patients with CNS symptoms indicating +chronic intoxication. Thirty-two subjects exposed to industrial solvents for 5 to 28 years and 40 age-matched, healthy controls were examined. All patients showed decreased signal in the basal ganglia on T2-weighted images. In 11 of the patients the white matter showed diffuse hyperintensity with loss of the grey-white matter discrimination and with distinct periventricular hyperintensities in 5 of the patients. The controls had no pathological changes in the brain. Although the relatively small number of patients may obscure the significance, findings observed on T2-weighted images were patchy periventricular hyperintensities and hypointensities in the basal ganglia. Fast spin-echo is a good technique with fast acquisition of images with true spin-echo contrast features.


Characterization of Pseudomonas aeruginosa exoenzyme S as a bifunctional enzyme in J774A.1 macrophages.
Pseudomonas aeruginosa exoenzyme S (ExoS) is a type III secretion (TTS) effector, which includes both a GTPase-activating protein (GAP) activity toward the Rho family of low-molecular-weight G (LMWG) proteins and an ADP-ribosyltransferase (ADPRT) activity that targets LMWG proteins in the Ras, Rab, and Rho families. The coordinate function of both activities of ExoS in J774A.1 macrophages was assessed by using P. aeruginosa strains expressing and translocating wild-type ExoS or ExoS defective in GAP and/or ADPRT activity. Distinct and coordinated functions were identified for both domains. The GAP activity was required for the antiphagocytic effect of ExoS and was linked to interference of lamellopodium and membrane ruffle formation. Alternatively, the ADPRT activity of ExoS altered cellular adherence and morphology and was linked to effects on filopodium formation. The cellular mechanism of ExoS GAP activity included an inactivation of Rac1 function, as determined in p21-activated kinase 1-glutathione S-transferase (GST) pull-down assays. The ADPRT activity of ExoS targeted Ras and RalA but not Rab or Rho proteins, and Ral binding protein 1-GST pull-down assays identified an effect of ExoS ADPRT activity on RalA activation. The results from these studies confirm the bifunctional nature of ExoS activity within macrophages when translocated by TTS.


Defining gastrointestinal failure.
Gastrointestinal failure (GIF) has been postulated as the motor of multiple organ dysfunction syndrome (MODS) but is not commonly included among other organ failures in scoring systems identifying MODS. Relevant articles and published reviews were identified and analyzed through a PubMed search of English language literature on gastrointestinal problems. Wide variability in terms and definitions was observed. Data on the incidence of GIF and its impact on mortality in critically ill patients are controversial. Very few objectively measurable variables of GI function are available. Most of the definitions of GIF are diagnosis-, but not function-based. Diagnosis-based approach to GIF differs significantly from the function-based assessment of other organ failures and has not justified itself over time. There is no consensus on definition of GIF and different medical specialties have different approaches. Development of a proper definition of GIF is warranted.


From mesohepatectomy to mini-mesohepatectomy: evolving the concept of resectability of hepatic tumors at the hepatocaval confluence.
In the case of tumors in contact with or invading the middle hepatic vein (MHV) at the hepatocaval confluence, extended right hepatectomy or mesohepatectomy is usually recommended. Major or extended hepatectomy is associated with significant rates of morbidity and mortality, and a more conservative approach would be desirable. Thus, we developed a new conservative operation, the so-called mini-mesohepatectomy that, in some specific circumstances, allowed the en-bloc resection of segment 8, segment 4-sup and the MHV at the hepatocaval confluence and at the same time preservation of the remaining parenchyma of the right anterior section and left median section drained by the MHV. The present work describes the rationale, indications, as well as the surgical technique of this new operation which we believe should be part of the armamentarium of the modern hepatic surgeon, and will probably limit the need for a formal mesohepatectomy.


Physician follow-up and observation of guidelines in the post treatment surveillance of colorectal cancer.
Guidelines for post resection surveillance of colorectal cancer recommend a collection of the patient's history and physical examination, testing for carcinoembryonic antigen (CEA), and colonoscopy. No consistent guidelines exist for the use of abdominal computed tomography (CT) and position emission tomography (PET)/PET-CT. The goal of our study was to describe current trends, the impact of oncologic follow-up on guideline adherence, and the patterns of use of nonrecommended tests. We used Texas Cancer Registry-Medicare-linked data (2000-2009) to identify physician visits, CEA testing, colonoscopy, abdominal CT, and PET/PET-CT scans in patients ≥ 66 years old with stage I-III colorectal cancer who underwent curative resection. Compliance with guidelines was assessed with a composite measure of physician visits, CEA tests, and colonoscopy use from start of surveillance. In patients who survived 3 years, the overall compliance with guidelines was 25.1%. In patients seen regularly by a medical oncologist, compliance with guidelines increased to 61.5% compared with 8.8% for those not seen by a medical oncologist regularly (P < .0001). The use of abdominal CT and PET/PET-CT increased from 57.5% and 9.5%, respectively, in 2001 to 65.8% and 24.6% (P < .0001) in 2006. Patients who saw a medical oncologist were more likely to get cross-sectional imaging than those who did not (P < .0001). Compliance with current minimum guidelines for post treatment surveillance of colorectal cancer is low and the use of nonrecommended testing has increased over time. Both compliance and use of nonrecommended tests are markedly increased in patients seen by a medical oncologist. The comparative effectiveness of CT and PET/PET-CT in the surveillance of colorectal cancer patients needs further examination.


Interplay between microRNAs and the epigenetic machinery: an intricate network.
microRNAs take their place into the epigenetic world revealing a complicated network of reciprocal interconnections: not only they are able to control gene expression at a post-transcriptional level, thus representing a new important class of regulatory molecules, but they are also directly connected to the epigenetic machinery through a regulatory loop. Indeed, if epigenetic modifications, such as DNA methylation or histone acetylation, have been demonstrated to affect microRNA expression, and to be potentially responsible for the aberrant miRNA regulation observed in cancer, the other side of the coin is represented by the capacity of microRNAs to control the epigenetic machinery directly targeting its enzymatic components. This review will analyze and describe the regulatory loop interconnecting microRNAs and epigenetics, describing either how epigenetics can affect the miRNome, as well as how epi-miRNAs can control the epigenome, particularly focusing on the alterations observed in human cancer.


[Differential expression of exosomal miRNAs in osteoblasts in osteoarthritis].
To analyze the differentially expressed exosomal miRNAs in subchondral osteoblasts in patients with osteoarthritis (OA) and to investigate the key miRNAs potentially involved in the occurrence and progression of OA. Methods: Subchondral bones were harvested from 6 patients with OA. All subjects were divided into two groups which was based on the severity of joint wear: An OA group, severely worn side of subchondral bone, and a control group, less worn side of subchondral bone. The exosomes were extracted from osteoblast cells and their characteristics were identified. Then exosomal miRNAs were extracted and sequencing analysis was conducted to compare the expression in the two groups. The most differentially expressed ones (log2Ratio≥2) were subject to miRNA target prediction and quantitative reverse transcription PCR (RT-qPCR) to further quantify the difference. Results: Osteoblast extractions were confirmed to be exosomes, which were small double-membranous vesicles with 30-200 nm in diameter and 50-150 nm in peak value of particle size under the scanning microscope. High-throughput sequencing revealed 124 miRNAs whose expression significantly increased in the OA group. The most differentially expressed one with maximum fold change was hsa-miR-4717-5p and its target gene was RGS2. RT-qPCR demonstrated hsa-miR-4717-5p expression in the OA group was relatively higher than that in the control group (2.243 vs 0.480, P<0.01). Conclusion: There is distinct difference in expression profiles of exosomal miRNAs in subchondral osteoblasts between patients with OA and normal subjects. Up-regulated expression of miRANs might participate in OA occurrance and progression.


Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1: A Placebo-Controlled Randomized Clinical Trial.
In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this first-in-human, randomized, placebo-controlled trial was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of lumasiran in healthy participants and patients with primary hyperoxaluria type 1. This phase 1/2 study was conducted in two parts. In part A, healthy adults randomized 3:1 received a single subcutaneous dose of lumasiran or placebo in ascending dose groups (0.3-6 mg/kg). In part B, patients with primary hyperoxaluria type 1 randomized 3:1 received up to three doses of lumasiran or placebo in cohorts of 1 or 3 mg/kg monthly or 3 mg/kg quarterly. Patients initially assigned to placebo crossed over to lumasiran on day 85. The primary outcome was incidence of adverse events. Secondary outcomes included pharmacokinetic and pharmacodynamic parameters, including measures of oxalate in patients with primary hyperoxaluria type 1. Data were analyzed using descriptive statistics. Thirty-two healthy participants and 20 adult and pediatric patients with primary hyperoxaluria type 1 were enrolled. Lumasiran had an acceptable safety profile, with no serious adverse events or study discontinuations attributed to treatment. In part A, increases in mean plasma glycolate concentration, a measure of target engagement, were observed in healthy participants. In part B, patients with primary hyperoxaluria type 1 had a mean maximal reduction from baseline of 75% across dosing cohorts in 24-hour urinary oxalate excretion. All patients achieved urinary oxalate levels ≤1.5 times the upper limit of normal. Lumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels. Study of Lumasiran in Healthy Adults and Patients with Primary Hyperoxaluria Type 1, NCT02706886.


Modeling Genetic and Environmental Factors in Biological Systems Using Structural Equation Modeling: An Application to Energy Balance.
To improve our understanding of the role(s) that genes and environmental factors play in a complex disease, we need statistical approaches that model multiple factors simultaneously in a hierarchical manner that aims to reflect the underlying biological system(s). We present an approach that models genes as latent constructs, defined by multiple variants (single nucleotide polymorphisms, SNPs) within each gene, using the multivariate statistical framework of structural equation modeling (SEM) to model multiple, putative genetic and environmental factors involved in energy imbalance ('obesity') using subjects from a colon polyp case-control study. We found that modeling constructs for the leptin receptor (LEPR) gene (defined by SNPs rs1137100, rs1137101, rs1805096, rs6588147) and the fat mass-and-obesity-associated (FTO) gene (defined by SNPs rs9939609, rs1421085, rs8044769) together with demographic (age, race, gender), physical activity, diet and sleep variables increased the strength of the association (β(std)=-0.13 ± 0.06; p=0.03) between the FTO and obesity constructs compared to that observed in a reduced model with only the FTO and LEPR constructs and demographic variables (β(std)=-0.05 ± 0.03; p=0.08). Several indirect paths, including an association between the LEPR and physical activity constructs (β(std)=-0.15 ± 0.04; p=0.01), were found. Interestingly, removing FTO revealed a marginal association between the LEPR and obesity constructs (β(std)=0.24 ± 0.14; p=0.09), which was not present when FTO was in the model. These results illustrate the importance of modeling multiple relevant genes and other factors in the same model, which is a major strength of this approach. Moreover, our latent gene construct approach exploits the correlation structure between SNPs while capturing overall effects of variation in that gene, which will enable better utilization of candidate gene and genome-wide SNP array data.


The effect of femoral component head size on posterior dislocation of the artificial hip joint.
Posterior dislocation continues to be a relatively common complication following total hip arthroplasty. In addition to technical and patient-associated factors, prosthetic features have also been shown to influence stability of the artificial hip joint. In this study, a dynamic model of the artificial hip joint was used to examine the influence of the size of the head of the femoral component on the range of motion prior to impingement and posterior dislocation following total hip replacement. Six fresh cadaveric specimens were dissected, and an uncemented total hip prosthesis was implanted in each. Each specimen was mounted in a mechanical testing machine and loaded with use of a system of seven cables attached to the femur and pelvis that simulated the action of the major muscle groups crossing the hip joint. The hip was taken through a range of motion similar to that experienced when rising from a seated position. The three-dimensional position of the femur at the points of impingement and dislocation was recorded electronically. The range of joint motion was tested with prosthetic femoral heads of four different diameters (twenty-two, twenty-six, twenty-eight, and thirty-two millimeters). Significant associations were noted between the femoral head size and the degree of flexion at dislocation in ten (p = 0.001), twenty (p < 0.001), and thirty (p = 0.003) degrees of adduction. Increasing the femoral head size from twenty-two to twenty-eight millimeters increased the range of flexion by an average of 5.6 degrees prior to impingement and by an average of 7.6 degrees prior to posterior dislocation; however, increasing the head size from twenty-eight to thirty-two millimeters did not lead to more significant improvement in the range of joint motion. The site of impingement prior to dislocation varied with the size of the femoral head. With a twenty-two-millimeter head, impingement occurred between the neck of the femoral prosthesis and the acetabular liner, whereas with a thirty-two-millimeter head, impingement most frequently occurred between the osseous femur and the pelvis. With the particular prosthesis that was tested, increasing the diameter of the femoral head component increased the range of motion prior to impingement and dislocation, decreased the prevalence of prosthetic impingement, and increased the prevalence of osseous impingement. These results suggest that femoral heads with a twenty-eight-millimeter diameter increase the range of motion after total hip replacement. This may be beneficial when additional factors compromising joint stability are encountered.


Recent advances in understanding the clinical relevance of antiplatelet alloantibodies.
Alloimmunization to human platelet antigens (HPAs) may occur either during pregnancy, when a HPA‑negative mother gives birth to a newborn who inherits HPAs from the father, or following blood transfusion or stem cell transplantation. Antiplatelet alloantibodies do not cause thrombocytopenia in a patient, but their detection must always be recorded in medical records because they may induce fetal and neonatal alloimmune thrombocytopenia in present and all subsequent pregnancies, platelet refractoriness, posttransfusion purpura, or prolonged thrombocytopenia with engraftment failure after stem cell transplantation. Passive transfer of platelet alloantibodies through transfused blood components may trigger thrombocytopenia and severe posttransfusion reactions in the recipient. In a Caucasian population, such clinical outcome of platelet alloimmunization is mostly due to anti‑HPA‑1a antibodies, less frequently to anti‑HPA‑5b, anti‑HPA‑1b, and others. Information on anti‑HPA alloantibodies is crucial for the prevention and treatment of their consequences.


A rare case of paediatric meningioma masquerading as intra-axial lesion.
Meningiomas are neoplasm arising from meningoepithelial cells, most commonly in the fifth to sixth decade of life. Meningiomas are rare in paediatric population, accounting for 0.4-4.1% of all paediatric tumours and less than 3% of paediatric brain tumours. However, meningiomas represent the most common dural based tumours in children. We describe a rare case of paediatric fibroblastic meningioma within the left middle cranial fossa masquerading as an intra-axial mass lesion. Our discussion will be centred on atypical features of paediatric meningiomas and differential diagnosis of extra-axial mass lesion in the paediatric population.


[Arthroscopic double-bundle posterior cruciate ligament reconstruction using achilles tendon allograft].
To study the method and clinical results of arthroscopic double-bundle posterior cruciate ligament (PCL) reconstruction using achilles tendon allograft. From September 2005 to September 2006, 17 patients with PCL injuries of grade III received arthroscopic double-bundle PCL reconstruction using achilles tendon allograft. There were 12 males and 5 females with an average age of 31.7 years (range, 19-48 years), including 10 cases of left PCL injuries and 7 cases of right PCL injuries. Injury was caused by sports in 6 cases and traffic accident in 11 cases. The average time from injury to surgery was 16 days (range, 7-30 days). The preoperative knee flexion was (121.8 +/- 4.1) degrees. The posterior drawer test was positive and the varus angulation test was negative in all 17 patients. Lysholm score was 50.8 +/- 6.1 and Tegner score was 1.3 +/- 0.7. The side-to-side difference was (10.5 +/- 1.6) mm by KT-1000 arthrometer. The hospitalization were (13.6 +/- 2.4) days. The operation time was (67.8 +/- 9.4) minutes. The time was (5.4 +/- 1.2) days when the body temperature was higher than 37.4 degrees C after operation. All incisions healed by first intention. No complication occurred. All 17 patients were followed up 25 months on average (range, 18-30 months). The knee flexion was (116.9 +/- 3.1) degrees at the final follow-up, showing no significant difference when compared with that of preoperation (P > 0.05). The posterior drawer test and the varus angulation test were negative in all 17 patients. Lysholm score and Tegner score were 91.6 +/- 3.2 and 6.0 +/- 0.7, respectively, and the side-to-side difference was (2.7 +/- 1.7) mm, showing significant differences when compared with those of preoperation (P < 0.05). Achilles tendon allograft is fit for PCL reconstruction. Arthroscopic double-bundle posterior cruciate ligament reconstruction using achilles tendon allograft can reconstruct both anterolateral and posteromedial bundles of the PCL. The knee joint function can be restored effectively. The short-term outcome has been proved, but the long-term outcome needs more observations.


Cutaneous nerve-conscious surgical repair of vascular access-related aneurysm assisted by anatomical ultrasonography in hemodialysis patients.
The superficial runoff veins anatomically run alongside the cutaneous nerves in the volar forearm. Consequently, the surgical repair of vascular access (VA)-associated venous aneurysms attached to the cutaneous nerves could cause intraoperative nerve injury. Therefore, we proposed a cutaneous nerve-conscious VA-related aneurysmal repair assisted by nerve ultrasonography. This ultrasonography aids in the preoperative examination of the courses of the nerves neighboring the aneurysm. Sixteen consecutive patients who underwent surgical revisions of VA-related aneurysms (14 venous aneurysms and two arterial pseudoaneurysms) were enrolled. The locations of aneurysms derived from preexisting arteriovenous fistulas included 11 radiocephalic arteriovenous fistulas in the wrist or distally, three radiocephalic arteriovenous fistulas at the antecubital fossa, and two brachiocephalic arteriovenous fistulas at the antecubital fossa or in the distal upper arm. A preoperative ultrasonographic scan of the cutaneous nerve trunks that ran peripherally toward and along the aneurysms was attempted to avoid nerve injuries during operations. Basically, the aneurysms were resected from the proximal to the distal ends after being separated from the preserved adjacent nerves. The cutaneous nerve trunks that coursed toward and along the aneurysm could be identified by preoperative ultrasonography and could be preserved intraoperatively based on ultrasonographic findings in all patients. In four patients, the cutaneous nerve branch was unexpectedly or intentionally severed for a seamless surgical process because the nerve branch that divided from the cutaneous nerve trunk was strongly attached to the aneurysm. They subsequently suffered from hypoesthesia, but did not experience neuropathic pain. Preoperative ultrasonographic examination of the cutaneous nerve facilitated the intraoperative prevention of cutaneous nerve injury in VA-related aneurysmectomy. Nerve-sparing VA surgery assisted by preoperative nerve ultrasonography based on the understanding of topological anatomy might contribute to the reduction in postoperative neuropathy and enhance comfort in the daily life of hemodialysis patients.


[Epidemiologic study on peripheral vascular diseases in Shanghai].
Epidemiologic investigation and study were made on peripheral vascular diseases in Shanghai area during 1988 and 1989. The total number of examined subjects was 30,712, including peasants and workers from heavy and light industries. The number of the subjects suffered from peripheral vascular diseases was 2,679, with an incidence of 8.72%. Among them, varicosity of the superficial veins in the lower extremities was found in 2,577, and other peripheral vascular diseases were found in 102. Risk factors for varicose veins include hard labour, body mass, standing, pregnancy and sitting. New concepts about the varicose veins were advanced by the authors.


[Remodeling of heart and neutrophil intracellular metabolism in obese men].
To study remodeling of heart and its influence on intracellular metabolism of neutrophils in obese men. 85 men aged 30-63 years free from coronary heart disease underwent ECG examination with the evaluation of diastolic properties and diagnostics of left ventricle remodeling with special reference to oxygen-dependent metabolism and antioxidant protection of neutrophils. Increased degree of obesity in men leads to enhanced frequency of diastolic dysfunction and left ventricular myocardium remodeling accompanied by a rise in myeloperoxidase activity in neutrophils. The latter was especially high in patients with concentric hypertrophy of left ventricular myocardium. Increased degree of heart remodeling with enhanced severity of obesity in men is accompanied by activation of oxygen-dependent metabolism in neutrophils.


Stage 1 hybrid palliation for hypoplastic left heart syndrome--assessment of contemporary patterns of use: an analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.
Hybrid palliation is an alternative to Norwood stage 1 for the initial management of hypoplastic left heart syndrome. Contemporary multicenter hybrid use and institutional/patient factors associated with hybrid use relative to the Norwood have not been evaluated. We describe hybrid use in relation to institutional volume, patient factors, and short-term outcomes. Infants aged 60 days or less listed in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2012) undergoing initial palliation of hypoplastic left heart syndrome were included. Annual institutional hybrid use rates were calculated: [hybrid procedures/(Norwood + hybrid + transplant procedures)]. In-hospital outcomes for primary hybrid and primary Norwood were compared and stratified by high (defined as ≥50%) versus low (defined as ≤10%) institutional hybrid use. Of 1728 patients (100 centers), most (n = 1496, 87%) underwent an index Norwood; 232 patients (13%) underwent an index hybrid procedure. Preoperative patient risk factors were more prevalent in patients undergoing the hybrid procedure. Only 13 of 100 institutions were high hybrid users, and these tended to have lower annual hypoplastic left heart syndrome index case volume. Unadjusted in-hospital mortality was higher for the hybrid compared with the Norwood procedure (30% vs 16%; P < .001). In-hospital mortality for the hybrid procedure was not associated with hybrid use (26% among institutions with low use vs 28% among institutions with high use). However, centers with high hybrid use had higher mortality after the Norwood (43%) compared with centers with low hybrid use (16%). Few centers currently select the hybrid procedure for most infants with hypoplastic left heart syndrome. Although unadjusted in-hospital hybrid mortality is higher than Norwood mortality, potential risk factors are more prevalent among hybrid cases. Institutions with higher hybrid use have lower hypoplastic left heart syndrome case volume and higher Norwood mortality.


Influence of linear equality constraints on object restoration in incoherent light.
We investigate how prior knowledge of the object in the form of linear equality constraints influences the inverse problem of incoherently illuminated object reconstruction by using an elimination method in the context of least squares by regularized singular-value decomposition. Some representative numerical calculations that use noisy images were carried out to illustrate the analysis. When compared with the corresponding unconstrained inversion it appears that the linear constrained inverse does not seem to be any better when viewed in the global sense.


[Diagnosis of a sudden loss of vision (without redness nor eye pain)].
Sudden loss of vision without redness nor eye pain may come from numerous causes of varying severity. It presents a major source of anxiety for the patient who will seek for urgent consultation. The diagnostic approach is based on history and eye examination, eventually completed by a neurological examination. The purpose of this article is to provide general practitioners simple clues allowing them to quickly orientate the diagnosis. Following simple guidelines, they will be able to treat the condition correctly or refer to an adequate specialist when needed. True emergencies are retinal detachment, central retinal artery occlusion, intracranial hypertension, Horton giant cells arteritis, transient ischemic attack, stroke, pituitary apoplexy and cortical visual loss.


Sequential outbreaks of infection due to Klebsiella pneumoniae in a neonatal intensive care unit: implication of a conjugative R plasmid.
Sequential outbreaks of infection in a neonatal intensive care unit were due to multiple antibiotic-resistant strains of Klebsiella pneumoniae of different serotypes. In investigations of these outbreaks, the transfer of resistance to gentamicin, ampicillin, cephalothin, carbenicillin, and kanamycin from gentamicin-resistant organisms to standard laboratory recipients and between recipients was observed. Purified plasmid DNA, isolated from all multiple antibiotic-resistant strains, was analyzed by agarose gel electrophoresis, which revealed a common, large plasmid component with a molecular size of 71 megadaltons. Analysis of drug-resistant progeny suggested this plasmid encoded resistance to antibiotics and the information needed for its transmission. The identity of the plasmid from three different sources was established by the use of restriction-enzyme fingerprinting. The dissemination and persistence of this plasmid in environmental and fecal organisms, despite the disappearance of multiple antibiotic-resistant K. pneumoniae, provided a potential source for spread to other bacteria.


Characterization of dielectric and electro-optic properties of PLZT 9/65/35 films on sapphire for electro-optic applications.
Lead lanthanum zirconate titanate (PLZT) thin films were deposited on r-plane sapphire at low temperatures by RF triode magnetron sputtering using lead compensated hot-pressed targets. To obtain fully perovskite phase in the films, two types of post-deposition processing were investigated: rapid thermal annealing (RTA) and furnace annealing (FA). Dielectric and electro-optic properties of PLZT films were found to be strongly dependent on annealing conditions. The peak dielectric constant of the films were 1200 and 2800 with Curie temperatures of 110 degrees C and 190 degrees C after RTA and FA processing, respectively. The dielectric losses in the films were fairly low; tan deltas were less than 0.02 after RTA and less than 0.04 after FA processing. The films showed good optical transmission characteristics after annealing and an anomalously large effective quadratic electro-optic effect was observed in one furnace annealed film.


Ferritin heavy chain is the host factor responsible for HCV-induced inhibition of apoB-100 production and is required for efficient viral infection.
Hepatic fat export occurs by apolipoprotein B-100-containing lipoprotein production, whereas impaired production leads to liver steatosis. Hepatitis C virus (HCV) infection is associated to dysregulation of apoB-100 secretion and steatosis; however, the molecular mechanism by which HCV affects the apoB-100 secretion is not understood. Here, combining quantitative proteomics and computational biology, we propose ferritin heavy chain (Fth) as being the cellular determinant of apoB-100 production inhibition. By means of molecular analyses, we found that HCV nonstructural proteins and NS5A appear to be sufficient for inducing Fth up-regulation. Fth in turn was found to inhibit apoB-100 secretion leading to increased intracellular degradation via proteasome. Notably, intracellular Fth down-regulation by siRNA restores apoB-100 secretion. The inverse correlation between ferritin and plasma apoB-100 concentrations was also found in JFH-1 HCV cell culture systems (HCVcc) and HCV-infected patients. Finally, Fth expression was found to be required for robust HCV infection. These observations provide a further molecular explanation for the onset of liver steatosis and allow for hypothesizing on new therapeutic and antiviral strategies.


Characterization of BpGH16A of Bacteroides plebeius, a key enzyme initiating the depolymerization of agarose in the human gut.
Seaweeds have received considerable attention as sources of dietary fiber and biomass for manufacturing valuable products. The major polysaccharides of red seaweeds include agar and porphyran. In a marine environment, marine bacteria utilize agar and porphyran through the agarase and porphyranase genes encoded in their genomes. Most of these enzymes identified and characterized so far originate from marine bacteria. Recently, Bacteroides plebeius, a human gut bacterium isolated from seaweed-eating Japanese individuals, was revealed to contain a polysaccharide utilization locus (PUL) targeting the porphyran and agarose of red seaweeds. For example, B. plebeius contains an endo-type β-agarase, BpGH16A, belonging to glycoside hydrolase family 16. BpGH16A cleaves the β-1,4-glycosidic linkages of agarose and produces neoagarooligosccharides from agarose. Since it is crucial to study the characteristics of BpGH16A to understand the depolymerization pathway of red seaweed polysaccharides by B. plebeius in the human gut and to industrially apply the enzyme for the depolymerization of agar, we characterized BpGH16A for the first time. According to our results, BpGH16A is an extracellular endo-type β-agarase with an optimal temperature of 40 °C and an optimal pH of 7.0, which correspond to the temperature and pH of the human colon. BpGH16A depolymerizes agarose into neoagarotetraose (as the main product) and neoagarobiose (as the minor product). Thus, BpGH16A is suggested to be an important enzyme that initiates the depolymerization of red seaweed agarose or agar in the human gut by B. plebeius. KEY POINTS: • Bacteroides plebeius is a human gut bacterium isolated from seaweed-eating humans. • BpGH16A is an extracellular endo-type β-agarase with optimal conditions of 40 °C and pH 7.0. • BpGH16A depolymerizes agarose into neoagarotetraose and neoagarobiose.


Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation.
Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14(+)DR(int) MQs characterized inflamed intestinal mucosa while total CD141(+) or CD1c(+) DCs numbers were unchanged. However, CD103(+) DCs, including CD141(+)CD103(+) and CD1c(+)CD103(+) DCs, were reduced in inflamed intestine. In MLNs, two CD14(-) DC populations were identified: CD11c(int)HLADR(hi) and CD11c(hi)HLADR(int) cells. A marked increase of CD11c(hi)HLADR(int) DC, particularly DR(int)CD1c(+) DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH(+) cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.


Examining and reexamining the structure of Chinese-English bilingual memory.
The asymmetry model of bilingual memory proposed by Kroll and Stewart assumes that translation from a first language (L1) into a second language (L2), or forward translation, is mediated by an underlying conceptual memory, whereas L2-to-L1, or backward, translation is lexical and direct. Lexical links from L2 to L1 are hypothesized to be stronger than those from L1 to L2, but conceptual links are stronger for L1 than L2. These assumptions were evaluated in this study, which used stimulus items with similar recognition thresholds. Proficient Chinese-English bilinguals were tested on picture naming, word naming, word translation and category matching. The translation asymmetry effect predicted by the model (i.e., backward being faster than forward translation) was demonstrated; matching an L1 item to a category name was also faster than matching an L2 item. This pattern of results, nevertheless, did not completely hold after an adjustment procedure which sought to control for variations in response production and concept retrieval times due to stimulus types. The present findings are consistent with previous ones which show increased L2 conceptual processing for the proficient bilingual. They also suggest that an extended version of the asymmetry model should take into account possible biasing effects associated with some conventionally used bilingual tasks.


CD31 density is a novel risk factor for patients with B-cell chronic lymphocytic leukaemia.
CD31 is the physiological ligand for CD38. CD38 expression in a high percentage of malignant cells is a risk factor for patients with B-cell chronic lymphocytic leukaemia (B-CLL). A previous investigation demonstrated that quantification of CD38 improves upon the prognostic value of the percentage expression. A recent study states that the percentage of CD31 expression is not predictive in B-CLL. We reassessed the predictive power of CD31 in a cohort of 120 patients with B-CLL. Peripheral blood cells were stained with PCP-labelled anti (alpha)-CD19, FITC-alpha-CD5 and PE-alpha-CD31 antibodies. CD31 expression was quantified using beads of specific antibody binding capacity and the density was correlated with clinical outcome. End points were disease-specific survival and time to treatment (TTT). We report that CD31 density was significantly lower in the group of patients with Binet stage B and C of disease progression (P=0.0003). There was an inverse, significant correlation between CD31 and CD38 densities (R= -0.281, P=0.002). All CLL-related deaths occurred in patients with low CD31 density. Low CD31 predicted for poor disease outcome (survival, P=0.0087; TTT, P=0.0064) and identified Binet stage A patients (survival, P=0.0350; TTT, P=0.0716) and those with low CD38 (survival: all patients, P<0.0001; stage A, P=0.003) who followed a more aggressive clinical course. Disease-specific survival of patients with low CD31 and high CD38 densities was significantly shorter than all other groups. In addition, low CD31 density was a poor risk factor irrespective of patient age (survival: all patients, P=0.045; stage A, P=0.021) and identified patients with Binet stage B/C as the highest risk group (P<0.0001). In conclusion, low CD31 density is an adverse prognostic indicator in B-CLL. Also, low CD31 density enhances the prognostic power of CD38 density. The interaction between CD31 and CD38 and its clinical significance in B-CLL requires further investigation.


Calcium oscillations triggered by cardiotonic steroids.
Na(+), K(+)-ATPase (NKA) is well known for its function as an ion pump. Studies during the last decade have revealed an additional role for NKA as a signal transducer. In this brief review, we describe how cardiotonic steroids, which are highly specific NKA ligands, trigger slow Ca(2+) oscillations by promoting the interaction between NKA and the inositol trisphosphate receptor, and how this Ca(2+) signal activates the NF-κB subunit p65 and increases the expression of the antiapoptotic factor Bcl-xL. The potential tissue-protective effects of this signal are discussed.


Analysis of genetic elements controlling Staphylococcus aureus lrgAB expression: potential role of DNA topology in SarA regulation.
Penicillin-induced killing and murein hydrolase activity in Staphylococcus aureus are dependent on a variety of regulatory elements, including the LytSR two-component regulatory system and the virulence factor regulators Agr and Sar. The LytSR effects on these processes can be explained, in part, by the recent finding that a LytSR-regulated operon, designated lrgAB, affects murein hydrolase activity and penicillin tolerance. To examine the regulation of lrgAB expression in greater detail, we performed Northern blot and promoter fusion analyses. Both methods revealed that Agr and Sar, like LytSR, positively regulate lrgAB expression. A mutation in the agr locus reduced lrgAB expression approximately sixfold, while the sar mutation reduced lrgAB expression to undetectable levels. cis-acting regulatory elements involved in lrgAB expression were identified by fusing various fragments of the lrgAB promoter region to the xylE reporter gene and integrating these constructs into the chromosome. Catechol 2,3-dioxygenase assays identified DNA sequences, including an inverted repeat and intrinsic bend sites, that contribute to maximal lrgAB expression. Confirmation of the importance of the inverted repeat was achieved by demonstrating that multiple copies of the inverted repeat reduced lrgAB promoter activity, presumably by titrating out a positive regulatory factor. The results of this study demonstrate that lrgAB expression responds to a variety of positive regulatory factors and suggest that specific DNA topology requirements are important for optimal expression.


Role of Ca2+ ions in the regulation of intramitochondrial metabolism in rat epididymal adipose tissue. Evidence against a role for Ca2+ in the activation of pyruvate dehydrogenase by insulin.
The sensitivity of rat epididymal-adipose-tissue pyruvate dehydrogenase phosphate phosphatase, NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase to Ca2+ ions was studied both in mitochondrial extracts and within intact coupled mitochondria. It is concluded that all three enzymes may be activated by increases in the intramitochondrial concentration of Ca2+ and that the distribution of Ca2+ across the mitochondrial inner membrane is determined, as in rat heart mitochondria, by the relative activities of a uniporter (which transports Ca2+ into mitochondria and is inhibited by Mg2+ and Ruthenium Red) and an antiporter (which allows Ca2+ to leave mitochondria in exchange for Na+ and is inhibited by diltiazem). Previous studies with incubated fat-cell mitochondria have indicated that the increases in the amount of active non-phosphorylated pyruvate dehydrogenase in rat epididymal tissue exposed to insulin are the result of activation of pyruvate dehydrogenase phosphate phosphatase. In the present studies, no changes in the activity of the phosphatase were found in extracts of mitochondria, and thus it seemed likely that insulin altered the intramitochondrial concentration of some effector of the phosphatase. Incubation of rat epididymal adipose tissue with medium containing a high concentration of CaCl2 (5mM) was found to increase the active form of pyruvate dehydrogenase to much the same extent as insulin. However, the increases caused by high [Ca2+] in the medium were blocked by Ruthenium Red, whereas those caused by insulin were not. Moreover, whereas the increases resulting from both treatments persisted during the preparation of mitochondria and their subsequent incubation in the absence of Na+, only the increases caused by treatment of the tissue with insulin persisted when the mitochondria were incubated in the presence of Na+ under conditions where the mitochondria are largely depleted of Ca2+. It is concluded that insulin does not act by increasing the intramitochondrial concentration of Ca2+. This conclusion was supported by finding no increases in the activities of the other two Ca2+-responsive intramitochondrial enzymes (NAD+-isocitrate dehydrogenase and 2-oxoglutarate dehydrogenase) in mitochondria prepared from insulin-treated tissue compared with controls.


Custom-Made Cleft Palate Models to Teach V-Y Pushback Palatoplasty.
We developed custom-made cleft palate (CP) models to teach V-Y pushback palatoplasty, with a focus on design and mucoperiosteal elevation.A model (23 cm wide, 30 cm long, and 13 cm high) was made using silicone (model 1; M1). On the palate of a skull model, 2 layers of colored rubber clay were applied to represent the superficial oral mucoperiosteum and deep nasal mucosa (model 2; M2). From the greater palatine foramen, threads of dental floss were inserted inside the clay, representing the greater palatine artery. In a workshop, a mouth gag was applied on M1, and participants designed 2-flap palatoplasty and 4-flap palatoplasty. On the palate of M2, incisions were made with a #15 blade. On M2, a mucoperiosteal flap (rubber clay over the hard palate) was elevated using a periosteal elevator, avoiding injury to the dental floss mimicking the greater palatine artery. Six participants were recruited for the workshop and were asked to rate their satisfaction with the outcome on a Likert scale.For CP design, participants answered that they had learned useful knowledge from this workshop, reflecting a significant improvement (4.0 ± 1.1 for incomplete CP, 4.2 ± 1.2 for complete CP). They became confident in this skill after the workshop (4.2 ± 0.8 for incomplete CP, 3.8 ± 0.8 for complete CP). For cleft mucoperiosteal flap elevation, they likewise learned useful knowledge (4.7 ± 0.5 for incomplete CP, 4.5 ± 0.5 for complete CP) and became confident in this skill (3.8 ± 0.8 for incomplete CP, 4.0 ± 0.6 for complete CP.)These models can be useful for V-Y pushback palatoplasty training for medical personnel.


Gastrointestinal complications after renal transplantation: predictive factors and morbidity.
In a ten-year study involving 109 renal transplant patients, 37 (34%) developed gastrointestinal complications. The immediate mortality from these complications was 27%. Three of four patients with erosive gastritis died. Five deaths occurred among 17 patients who developed ulcers after transplantation. Emergency surgery for ulcers resulted in two deaths. Patients with peptic ulcer disease, esophagitis, or bleeding before transplantation were much more likely to develop recurrences that patients not so affected. Peptic ulcer occurred notably more often in recipients whose kidneys came from cadavers than from related donors. Experience with gastrointestinal bleeding or its absence during a first transplant is a useful predictor of the results after a second transplant. The high recurrence rate and high mortality suggest that patients with ulcer disease demonstrated before kidney transplantation should either undergo elective surgery for ulcer disease or not be accepted for transplantation. Patients in whom ulcer disease develops after a kidney transplant shoud undergo early elective surgery.


Transgenic apple plants overexpressing the chalcone 3-hydroxylase gene of Cosmos sulphureus show increased levels of 3-hydroxyphloridzin and reduced susceptibility to apple scab and fire blight.
Overexpression of chalcone-3-hydroxylase provokes increased accumulation of 3-hydroxyphloridzin in Malus . Decreased flavonoid concentrations but unchanged flavonoid class composition were observed. The increased 3-hydroxyphlorizin contents correlate well with reduced susceptibility to fire blight and scab. The involvement of dihydrochalcones in the apple defence mechanism against pathogens is discussed but unknown biosynthetic steps in their formation hamper studies on their physiological relevance. The formation of 3-hydroxyphloretin is one of the gaps in the pathway. Polyphenol oxidases and cytochrome P450 dependent enzymes could be involved. Hydroxylation of phloretin in position 3 has high similarity to the B-ring hydroxylation of flavonoids catalysed by the well-known flavonoid 3'-hydroxylase (F3'H). Using recombinant F3'H and chalcone 3-hydroxylase (CH3H) from Cosmos sulphureus we show that F3'H and CH3H accept phloretin to some extent but higher conversion rates are obtained with CH3H. To test whether CH3H catalyzes the hydroxylation of dihydrochalcones in planta and if this could be of physiological relevance, we created transgenic apple trees harbouring CH3H from C. sulphureus. The three transgenic lines obtained showed lower polyphenol concentrations but no shift between the main polyphenol classes dihydrochalcones, flavonols, hydroxycinnamic acids and flavan 3-ols. Increase of 3-hydroxyphloridzin within the dihydrochalcones and of epicatechin/catechin within soluble flavan 3-ols were observed. Decreased activity of dihydroflavonol 4-reductase and chalcone synthase/chalcone isomerase could partially explain the lower polyphenol concentrations. In comparison to the parent line, the transgenic CH3H-lines showed a lower disease susceptibility to fire blight and apple scab that correlated with the increased 3-hydroxyphlorizin contents.


High-frequency oscillatory ventilation in adults: the Toronto experience.
To review the clinical experience with high-frequency oscillatory ventilation (HFOV) in three medical-surgical ICUs in Toronto, ON, Canada, and to describe patient characteristics, HFOV strategies, and outcomes. Retrospective chart review of all patients treated with HFOV at three academic university-affiliated ICUs since 1998. The data extracted included patient demographics, etiology of respiratory failure, ventilator settings, and gas exchange and cardiovascular data from baseline to 72 h of treatment, as well as at the transition from HFOV to conventional ventilation (CV). Heart rate and BP were recorded at regular intervals in all patients, and hemodynamic data were recorded in 32 patients who had pulmonary artery catheters in place. Cointerventions and ICU mortality were also recorded. A total of 156 adults (67 women and 89 men; mean [+/- SD] age, 48 +/- 18 years; mean acute physiology and chronic health evaluation [APACHE] II score, 23.8 +/- 7.5) with severe ARDS (ie, mean Pao(2)/fraction of inspired oxygen [Fio(2)] ratio, 91 +/- 48 mm Hg; mean oxygenation index [OI], 31 +/- 14) who had received CV for a duration of 5.6 +/- 7.6 days underwent 171 trials of HFOV. HFOV was discontinued within 4 h in 19 patients (12%) because of difficulties with oxygenation, ventilation, or hemodynamics. Pao(2)/Fio(2) ratios and OI ([Fio(2) x mean airway pressure x 100]/Pao(2)) improved significantly with the application of HFOV, and this benefit persisted for the 72-h study duration. Significant changes in hemodynamics following HFOV initiation included an increase in central venous pressure and a reduction in cardiac output (throughout the 72 h), and an increase in pulmonary artery occlusion pressure (at 3 and 6 h). Patients were treated with HFOV for 5.1 +/- 6.3 days. The 30-day mortality rate was 61.7%. Pneumothorax occurred in 21.8% of patients, 43.6% of patients were treated with inhaled nitric oxide, and 37.2% of patients were treated with steroids. Independent predictors of mortality on multivariate analysis were older age, higher APACHE II score, lower pH at the initiation of HFOV, and a greater number of days receiving CV prior to HFOV. HFOV has beneficial effects on Pao(2)/Fio(2) ratios and OI, and may be an effective rescue therapy for adults with severe oxygenation failure. The early institution of HFOV may be advantageous.


Attachment and cancer: a conceptual integration.
Cancer traditionally has been explained by the biomedical model; however, it is limited in comprehensively accounting for all factors in this disease. Recently, it has been suggested that a broader theoretical framework that includes psychosocial components in cancer is needed to complement the traditional approach. The purpose of this article, therefore, is to explore the utility of attachment theory as a biopsychosocial model of both development and health. Attachment, a developmental theory, explains how repeated interactions between caregiver and child in the early years establish lifelong psychosocial, physiological, affective, and cognitive patterns as well as enduring patterns of stress response to threat or illness. Despite attachment theory's biopsychosocial foundation, the application of attachment security as a factor in physical health and psychosomatic medicine is relatively recent. The current work reviews attachment theory and psychosocial literature with regard to cancer and follows with a novel attempt to conceptually integrate both bodies of literature. A concluding integrative model of attachment theory and the type C behavior pattern is provided to illustrate potential links and integrative processes that may lead to disease resilience or vulnerability.


[Effectiveness of the cryoprotective effect of glycerol and polyethylene glycol on plasma membranes].
The barrier properties of erythrocyte membranes were studied under freezing-thawing in cryopreservatives based on glycerol or polyethylene glycol Mm 1500 Da (PEG-1500) (at cryoprotectant concentrations from 0.5 to 30%). The state of the membrane barrier function in reconstituted and native erythrocytes subjected to rapid (200-400 degrees C per min) freezing has been registered by spectrophotometry, flame photometry, and radiolabel analysis as judged by labeled compound release (hemoglobin, K+, [14C]sucrose, 86Rb+). It is demonstrated that the effective cryoprotection of erythrocyte membranes in reconstituted erythrocytes is attained at cryoprotectant concentrations in the medium of 0.5-1% or in erythrocytes of 8-30%.


Evaluating cluster analysis techniques in ChatGPT versus R-language with visualizations of author collaborations and keyword cooccurrences on articles in the Journal of Medicine (Baltimore) 2023: Bibliometric analysis.
Analyses of author collaborations and keyword co-occurrences are frequently used in bibliographic research. However, no studies have introduced a straightforward yet effective approach, such as utilizing ChatGPT with Code Interpreter (ChatGPT_CI) or the R language, for creating cluster-oriented networks. This research aims to compare cluster analysis methods in ChatGPT_CI and R, visualize country-specific author collaborations, and then demonstrate the most effective approach. The research focused on articles and review pieces from Medicine (Baltimore) published in 2023. By August 20, 2023, we had gathered metadata for 1976 articles using the Web of Science core collections. The efficiency and effectiveness of cluster displays between ChatGPT_CI and R were compared by evaluating their time consumption. The best method was then employed to present a series of visualizations of country-specific author collaborations, rooted in social network and cluster analyses. Visualization techniques incorporating network charts, chord diagrams, circle bar plots, circle packing plots, heat dendrograms, dendrograms, and word clouds were demonstrated. We further highlighted the research profiles of 2 prolific authors using timeline visuals. The research findings include that (1) the most active contributors were China, Nanjing Medical University (China), the Medical School Department, and Dr Chou from Taiwan when considering countries, institutions, departments, and individual authors, respectively; (2) the highest cited articles originated from Medicine (Baltimore) accounting for 4.53%: New England Journal of Medicine, PLOS ONE, LANCET, and The Journal of the American Medical Association, with respective contributions of 3.25%, 2.7%, 2.52%, and 1.54%; (3) visual cluster analysis in R proved to be more efficient and effective than ChatGPT_CI, reducing the time taken from 1 hour to just 3 minutes; (4) 7 cluster-focused networks were crafted using R on a custom platform; and (5) the research trajectories of 2 prominent authors (Dr Brin from the United States and Dr Chow from Taiwan) and articles themes in Medicine 2023 were depicted using timeline visuals. This research highlighted the efficient and effective methods for conducting cluster analyses of author collaborations using R. For future related studies, such as keyword co-occurrence analysis, R is recommended as a viable alternative for bibliographic research.


Impact of Surgeon Gender on Online Physician Reviews.
The increasing use of review websites by consumers has become a crucial first step in choosing a physician with more than half of Americans consulting review sites before physician selection. We sought to identify whether differences exist in the quality and content of online reviews for men versus women surgeons. Using a deliberate sampling algorithm of the two most populated physician review websites, RateMDs.com and Yelp.com, we purposefully sampled reviews for the top 20 surgeons per tercile from the four most populated urban areas in the United States: New York, Houston, Los Angeles, and Chicago. A grounded theory qualitative assessment was performed of major and minor thematic elements including global rating, communication, technical skills, and comments on ancillary elements. Four-hundred and thirty-one online patient reviews of 238 surgeons were identified from RateMDs.com (51%) and Yelp.com (49%) with available information on gender for analysis. Seventy-six percent of reviews were of male surgeons. Reviewers were more likely to mention a global rating and technical skill for men compared with women surgeons. Most reviews were positive with no difference in global rating by gender (83.7% positive for men and 74.3% positive for women, P = 0.08). Women surgeons were more likely to have positive comments on social interactions as compared with men (94.7% versus 88.0%, P = 0.03); whereas men surgeons were more likely to have a positive rating on technical skill compared with women (88.2% versus 76.2%, P = 0.04). The content and quality of online surgeon reviews differ by gender. There is no difference in global rating between men and women. Women are rated higher for social interaction domains and men are rated higher on technical skill domains.


Germline PTEN mutations are associated with a skewed peripheral immune repertoire in humans and mice.
Individuals with germline mutations in the gene encoding phosphatase and tensin homolog on chromosome ten (PTEN) are diagnosed with PTEN hamartoma tumor syndrome (PHTS) and are at high risk for developing breast, thyroid and other cancers and/or autoimmunity or neurodevelopmental issues including autism spectrum disorders. Although well recognized as a tumor suppressor, involvement of PTEN mutations in mediating such a diverse range of phenotypes indicates a more central involvement for PTEN in immunity than previously recognized. To address this, sequencing of the T-cell receptor variable-region β-chain was performed on peripheral blood from PHTS patients. Based on patient findings, we performed mechanistic studies in two Pten knock-in murine models, distinct from each other in cell compartment-specific predominance of Pten. We found that PTEN mutations in humans and mice are associated with a skewed T- and B-cell gene repertoire, characterized by increased prevalence of high-frequency clones. Immunological characterization showed that Pten mutants have increased B-cell proliferation and a proclivity towards increased T-cell reactivity upon Toll-like-receptor stimulation. Furthermore, decreases in nuclear but not cytoplasmic Pten levels associated with a reduction in expression of the autoimmune regulator (Aire), a critical mediator of central immune tolerance. Mechanistically, we show that nuclear PTEN most likely regulates Aire expression via its emerging role in splicing regulation. We conclude that germline disruption of PTEN, both in human and mouse, results in compromised central immune tolerance processes that may significantly impact individual stress responses and therefore predisposition to autoimmunity and cancer.


Cytotoxicity of submicron emulsions and solid lipid nanoparticles for dermal application.
The cytotoxicity and physical properties of various submicron O/W emulsions and solid lipid nanoparticles for dermal applications were investigated. Droplet size and zetapotential of submicron emulsions depended on the composition of the cosurfactant blend used. The viability of J774 macrophages, mouse 3T3 fibroblasts and HaCaT keratinocytes was significantly reduced in the presence of stearylamine. Nanoparticles consisting of stearic acid or different kinds of adeps solidus could be manufactured when formulated with lecithin, sodium taurocholate, polysorbate 80 and stearylamine. Survival of macrophages was highly affected by stearic acid and stearylamine. In general a viability of more than 90% was observed when semi-synthetic glycerides or hard fat was employed to formulate nanoparticles.


Mutational studies on conserved histidine residues in the chlorophyll-binding protein CP43 of photosystem II.
Two chlorophyll-binding antenna proteins in the photosystem II core, CP43 and CP47, are structurally similar and are thought to have evolved from a common ancestor. Several conserved histidine residues in hydrophobic regions of CP47 have been shown to be important for photosystem II structure, function, and energy transfer. The purpose of this study was to determine whether similarly located histidine residues in CP43 function in a similar way. Three conserved histidine residues in presumed membrane-spanning regions of CP43, His40, His105, and His119, were mutated to glutamine (Q) and tyrosine (Y). The strains H105Q, H119Q, and H119Y were photoautotrophs whereas H40Q, H40Y, and H105Y were obligate photoheterotrophs. The H40Y and H105Y strains lacked detectable amounts of photosystem II reaction centers and hence could not evolve oxygen whereas H40Q retained a significant amount of photosystem II and oxygen evolution capacity. The observation that mutation of histidine residues to tyrosine has more drastic effects than mutation of these residues to glutamine is in agreement with results obtained for CP47 and suggests the involvement of these residues in chlorophyll binding. The drastic functional changes observed upon mutating His40 and His105 of CP43 are similar to those observed when mutating the corresponding histidine residues in CP47, thus suggesting that the similarity between CP43 and CP47 extends to the relative importance of functionally relevant residues. Interestingly, the His40-->Gln mutation in CP43 had significant effects on photosystem II electron transfer in that it affected the thermodynamics of Q(A)- oxidation by Q(B) and increased the charge recombination rate between Q(A)- and donor side components. This indicates that relatively minor changes in CP43 can significantly impact the properties of the photosystem II reaction center. The implications of this finding are discussed.


Effects of degradable magnesium on paracrine signaling between human umbilical cord perivascular cells and peripheral blood mononuclear cells.
Human mesenchymal stem cells (MSC) interact with numerous immune cells that can promote regenerative processes and inhibit inflammatory responses. We hypothesised that the cross-talk between human umbilical cord perivascular cells (HUCPV; an alternative source of MSC) and peripheral blood mononuclear cells (PBMC) could be influenced by degradable transwell magnesium (Mg). To study the correlations between paracrine signaling and specific cellular behaviour during the host response to Mg, we used a transwell coculture system for up to 7 days. The proliferation and viability of both cell types were not significantly influenced by Mg. When HUCPV were cultured with degradable Mg, a moderate inflammation (e.g., lower secretions of pro-inflammatory interleukin 1 beta and IL2, and tumour necrosis factor alpha, interferon gamma, anti-inflammatory interleukins 4, 5, 10, 13, and 1 receptor antagonists and granulocyte colony stimulating factor), and an increased pro-healing M2 macrophage phenotype were observed. Moreover, when PBMC were cultured with degradable Mg, the expression of migration/wound healing related cytokines (interleukin 8, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α/β) was upregulated, accompanied by an increase in the migration ability of HUCPV (cell scratch assay). In addition, an increased pro-osteogenic potential was demonstrated via an increase of osteoblastic markers (e.g., alkaline phosphatase activity, specific gene expression and cytokine release). These results collectively imply that Mg possesses osteo-immunomodulatory properties. They also help to design Mg-based bone substitute biomaterials capable of exhibiting desired immune reactions and good clinical performance.