Shared decision making for elective abdominal aortic aneurysm surgery.
Decisions on how and when to treat an abdominal aortic aneurysm involve a number of clinicians; interventional radiologists and vascular surgeons assess the technical ability to repair the aneurysm. Patients' fitness and past medical history is assessed to estimate their short- and long-term survival with or without surgery. Most importantly the patients' personal preference for treatment must be identified. Getting a patient to share what matters most to them requires shared decision making.


Diagnostic accuracy of endoscopic ultrasonography-guided tissue acquisition prior to resection of pancreatic carcinoma: a nationwide analysis.
Endoscopic ultrasonography guided tissue acquisition (EUS + TA) is used to provide a tissue diagnosis in patients with suspected pancreatic cancer. Key performance indicators (KPI) for these procedures are rate of adequate sample (RAS) and sensitivity for malignancy (SFM). assess practice variation regarding KPI of EUS + TA prior to resection of pancreatic carcinoma in the Netherlands. Results of all EUS + TA prior to resection of pancreatic carcinoma from 2014-2018, were extracted from the national Dutch Pathology Registry (PALGA). Pathology reports were classified as: insufficient for analysis (b1), benign (b2), atypia (b3), neoplastic other (b4), suspected malignant (b5), and malignant (b6). RAS was defined as the proportion of EUS procedures yielding specimen sufficient for analysis. SFM was calculated using a strict definition (malignant only, SFM-b6), and a broader definition (SFM-b5+6). 691 out of 1638 resected patients (42%) underwent preoperative EUS + TA. RAS was 95% (range 89-100%), SFM-b6 was 44% (20-77%), and SFM-b5+6 was 65% (53-90%). All centers met the performance target RAS>85%. Only 9 out of 17 met the performance target SFM-b5+6 > 85%. This nationwide study detected significant practice variation regarding KPI of EUS + TA procedures prior to surgical resection of pancreatic carcinoma. Therefore, quality improvement of EUS + TA is indicated.


Total intracardiac repair for tetralogy of Fallot in adults.
The anatomic and clinical features of 47 patients who were 18 years of age or older at the time of total intracardiac repair for tetralogy of Fallot are reviewed. Twenty (43%) patients had had previous palliative surgery. Of 14 pulmonary-systemic shunts, 9 (64%) remained patent. The location of the ventricular septal defect was infracristal in 90% of patients. The predominant right ventricular outflow tract obstruction was at the infundibulum in 30%; another 64% of patients had combined valvular and infundibular obstruction. Total intracardiac repair was achieved; hospital mortality was 8.5%. Morbidity was minor, and hemorrhage was a significant problem in only 2 patients. Thirty-five patients have been followed from 11 months to 15 years after surgery. There were 4 late deaths; the actuarial 10-year survival rate was 82%.


An in vitro assessment of fluoride uptake by tooth enamel from four different fluoride dentifrices.
The aim of this study was to evaluate fluoride uptake by tooth enamel with four different fluoride dentifrices. Sixty human premolars extracted for orthodontic purpose were selected for the study. The teeth were covered with nail varnish leaving a window of 4 × 4 mm on the enamel surface of the buccal and lingual sides. The teeth were demineralised and were divided into four groups with 15 teeth in each group. The buccal window served as experimental and the lingual as control. The teeth were immersed in toothpaste slurry containing: sodium fluoride (Group A); sodium monofluorophosphate (Group B); stannous fluoride (Group C) and amine fluoride (Group D). The fluoride content in the etched superficial enamel layer in the windows was analysed using a fluoride ion-specific electrode. Within the parameters of this study, the uptake of fluoride was statistically significant in Group D (p < 0.05). The uptake of fluoride by tooth enamel in an increasing order was Group A < Group B < Group C < Group D. The study showed that enamel treated with amine fluoride had the highest fluoride uptake.


Association of homocysteine level with risk of stroke: A dose-response meta-analysis of prospective cohort studies.
Homocysteine (Hcy) level has been increasingly linked with stroke and ischemic stroke (IS). However, a dose-response meta-analysis of prospective cohort studies of the association is lacking. We aimed to explore the quantitative dose-response association of Hcy level with stroke and IS in a meta-analysis of prospective cohort studies. We performed a systematic search of PubMed, Embase and Web of Science databases up to April 25, 2019 for prospective cohort studies assessing the association of Hcy level with stroke and IS. We used random-effect models to estimate the pooled relative risk (RRs) (with 95% confidence intervals [CIs]) for the association of Hcy with risk of stroke and IS. Restricted cubic splines were used to evaluate possible linear or nonlinear association of Hcy level with stroke and IS. We included 10 prospective cohort studies (7 articles) with 11,061 participants in the meta-analysis. Hcy level was associated with increased risk of stroke (RR = 1.58, 95% CI 1.25-2.00, I2 = 39.5%) and IS (RR = 1.54, 95% CI 1.21-1.97, I2 = 36.4%) for the highest versus the lowest categories. We found a linear association between Hcy level and stroke (Pnonlinearity = 0.660) and IS (Pnonlinearity = 0.981). For each 1-μmol/L increase in Hcy, the pooled RR was 1.06 (95% CI 1.01-1.12, I2 = 59.0%) for stroke and 1.05 (95% CI 1.00-1.11, I2 = 58.6%) for IS. This meta-analysis indicated that elevated Hcy level was associated with increased risk of stroke and IS.


Effects of recurrent major depressive disorder on behavior and cognitive function in female depressed patients.
Little is known about the effects of recurring depressive episodes on cognition and behavior. The objective of the study was to compare cognitive function and depression-related behavior between healthy female subjects and female outpatients with early-onset DSM-IV recurrent major depressive disorder and to investigate the effect of cumulative depressive duration. Neuropsychological tests and scales for apathy, anhedonia and psychomotor retardation were assessed in 23 female patients and 60 healthy age-matched female controls. Significantly higher levels of apathy, anhedonia and psychomotor retardation, and worse performance on tests of executive function were found in the patient group compared with the healthy controls. In the patient group, cumulative depression duration was not significantly correlated with cognitive function, apathy, anhedonia or psychomotor retardation. The deficits in executive function were not related to the actual level of depression. Mild executive dysfunction may be the effect of the illness process underlying recurrent depressive disorder. Repeated or extensive depressive episodes do not seem to additionally affect cognitive deficits or behavior in depressed patients.


Three layer functional model and energy exchange concept of aging process.
Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of 'energy flow' between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called 'death.' This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.


Palliative rehabilitation interventions in palliative care: a scoping review protocol.
The objective of this scoping review is to examine and map interventions of palliative rehabilitation that are implemented and evaluated in palliative care. Palliative rehabilitation is defined as the process of helping individuals with a progressive, often advanced or incurable disease reach their physical, psychological, and social potential consistent with physiological and environmental limitations and life preferences. Rehabilitation may prolong functional independence and improve quality of life. Information on palliative rehabilitation interventions, their characteristics, contexts, and population is dispersed throughout the literature, hence the need for a scoping review. This scoping review will consider all studies that focus on qualified health care professionals working in palliative care who are caring for patients 18 years of age or older, and studies that focus on the concepts of palliative rehabilitation interventions. This scoping review will consider all palliative rehabilitation interventions implemented and evaluated in the context of palliative care. The search strategy aims to find published and unpublished studies. The databases to be searched will include CINAHL Complete, PubMed, Scopus, SciELO, Cochrane Central Register of Controlled Trials, and PEDro. The search for unpublished studies will include DART-Europe, OpenGrey, and RCAAP. Studies published in English, Spanish, and Portuguese carried out from 2009 onward will be considered for inclusion. Retrieved papers will be screened for inclusion by two reviewers. Data will be extracted and presented in tabular form and a narrative summary that aligns with the review's objective. Any disagreements that arise between the reviewers will be resolved through discussion or with a third reviewer.


Pseudo-dynamic contact surface areas: estimation of apolar bonding.
A new Monte Carlo based algorithm has been written for the computation of pseudo-dynamic contact surface areas. The linear correlation of this contact area with solute transfer free energies (water leads to organic liquid) is established for apolar amino acid side chains. The slope of these linear plots, deltaGosp, is a unitary free energy which has potential use in the estimation of apolar bond free energies in proteins. The magnitude of deltaGosp is dependent upon the nature of the organic solvent involved in the transfer process, varying from 86 to 130 cal/A2. Analogues linear correlations with the same range of deltaGosp values are observed for inhibitors of protein-catalyzed reactions.


[Effect of enteral feeding on exercise tolerance and clinical picture in patients with NYHA class III-IV chronic heart failure].
To elucidate efficacy of enteral feeding and the role of small intestine in pathogenesis of cardiac cachexia in patients with heart failure and reduced body mass. Patients with NYHA class III-IV chronic heart failure and deficient body mass (n=34). Control group comprised 32 patients. In intervention group standard therapy was supplemented for 24 weeks with balanced nutritional mixture constituting 25% of daily energy requirements. Efficacy of treatment was assessed by 6 minute walk test, evaluation of lean body mass. Studies of intestinal functional activity and biopsies of small intestinal mucosa with morphometrical analysis of bioptates were also performed. Results of 6-minute walk test improved in intervention and control groups by 46.8 and 10.3%, respectively. Average lean body mass increased in intervention group (by 6.7%) and decreased in controls (by 4.9%, p=0.03). Morphometrical study of bioptates revealed augmentation of relative collagen area up to 35-37% (normal value - 10-15%) and pronounced villus atrophy.


Neurophysiological correlates of perception-action binding in the somatosensory system.
Action control requires precisely and flexibly linking sensory input and motor output. This is true for both, visuo-motor and somatosensory-motor integration. However, while perception-action integration has been extensively investigated for the visual modality, data on how somatosensory and action-related information is associated are scarce. We use the Theory of Event Coding (TEC) as a framework to investigate perception-action integration in the somatosensory-motor domain. Based on studies examining the neural mechanisms underlying stimulus-response binding in the visuo-motor domain, the current study investigates binding mechanisms in the somatosensory-motor domain using EEG signal decomposition and source localization analyses. The present study clearly demonstrates binding between somatosensory stimulus and response features. Importantly, repetition benefits but no repetition costs are evident in the somatosensory modality, which differs from findings in the visual domain. EEG signal decomposition indicates that response selection mechanisms, rather than stimulus-related processes, account for the behavioral binding effects. This modulation is associated with activation differences in the left superior parietal cortex (BA 7), an important relay of sensorimotor integration.


Synthesis of pyrrothiamine, a novel thiamine analogue, and evaluation of derivatives as potent and selective inhibitors of pyruvate dehydrogenase.
Inhibition of thiamine pyrophosphate (TPP)-dependent enzymes with thiamine/TPP analogues that have the central thiazolium ring replaced with other rings is well established, but a limited number of central rings have been reported. We report a novel analogue, pyrrothiamine, with a central pyrrole ring. We further develop pyrrothiamine derivatives as potent and selective inhibitors of pyruvate dehydrogenase, which might have anti-cancer potential.


Rapid separation and measurement of rat urinary kallikrein by high-performance liquid chromatography with a continuous flow enzyme detector.
Rat urinary kallikrein was separated by high-performance liquid chromatography (HPLC) using an ion-exchange or gel-permeation column. Kallikrein activity was monitored continuously with peptidase or esterase activity using a post-reactor system directly adapted to HPLC. A PTFE helically coiled tube served as the enzyme reactor vessel. Four and three peaks with peptidase and esterase activity, respectively, were detected on application of normal rat urine.


MRI Evaluation of Gene Therapy in the Canine Model of Duchenne Muscular Dystrophy.
Magnetic resonance imaging (MRI) is a well-established and widely used technique to characterize and quantify skeletal and cardiac muscle changes in Duchenne muscular dystrophy (DMD). Recently, MRI has been explored to study disease progression and response to gene therapy in the canine DMD model. Using traditional sequences, delayed gadolinium enhancement, novel sequences, and spectroscopy, investigators have begun to (i) establish the baseline MRI characteristics of the muscles in normal and affected dogs and (ii) evaluate gene therapy outcomes in treated dogs. As a noninvasive assay, MRI offers an excellent opportunity to study longitudinal muscle changes in long-term gene therapy studies in the canine model. In this chapter, we outline the MRI method used to study DMD in the canine model.


The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.
Protective ileostomy is always applied to avoid clinically significant anastomotic leakage and other postoperative complications for patients receiving laparoscopic rectal cancer surgery. However, whether it is necessary to perform the ileostomy is still controversial. This meta-analysis aims to analyze the efficacy of ileostomy on laparoscopic rectal cancer surgery. Cochrane Library, EMBASE, Web of Science, and PubMed were applied for systematic search of all relevant literature, updated to May 07, 2021. Studies compared patients with and without ileostomy for laparoscopic rectal cancer surgery. We applied Review Manager software to perform this meta-analysis. The quality of the non-randomized controlled trials was assessed using the Newcastle-Ottawa scale (NOS), and the randomized studies were assessed using the Jadad scale. We collected a total of 1203 references, and seven studies were included using the research methods. The clinically significant anastomotic leakage rate was significantly lower in ileostomy group (27/567, 4.76%) than that in non-ileostomy group (54/525, 10.29%) (RR = 0.47, 95% CI 0.30-0.73, P for overall effect = 0.0009, P for heterogeneity = 0.18, I2 = 32%). However, the postoperative hospital stay, reoperation, wound infection, and operation time showed no significant difference between the ileostomy and non-ileostomy groups. The results demonstrated that protective ileostomy could decrease the clinically significant anastomotic leakage rate for patients undergoing laparoscopic rectal cancer surgery. However, ileostomy has no effect on postoperative hospital stay, reoperation, wound infection, and operation time. The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.


Cognitive decline associated with pathological burden in primary age-related tauopathy.
Primary age-related tauopathy (PART) is a neuropathological diagnosis characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. Although most individuals over 50 years of age have evidence of NFTs, the clinical and cognitive consequences of PART are not known. We evaluated 226 neuropathologically confirmed PART cases from the National Alzheimer's Coordinating Center database who participated in a total of 846 longitudinal neuropsychological assessments from the Alzheimer's Disease Center program's Uniform Data Set. Mixed-effects statistical models tested whether cognitive decline was associated with Braak stage NFT burden. Higher stages of NFT burden in PART, with no evidence or minimal evidence of amyloid pathology, were associated with more rapid decline on tasks involving episodic and semantic memory along with tests of processing speed and attention. We conclude that PART has cognitive consequences that should be considered in the context of emerging tau-targeted therapies in age-associated neurodegenerative diseases.


Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.
The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fast (half life less than 1 min) and was slowed by the cardioselective muscarine antagonists, gallamine, methoctramine and AF-DX 116, concentration dependently. [3H]Dexetimide dissociation from tracheal muscarine receptors was biphasic, with a fast phase (half-life less than 1 min) followed after 4-5 min by a slow phase (half-life = 38.5 min). The fast component, but not the slow component, was slowed by the muscarine antagonists with concentration dependencies very similar to those found in the heart. We conclude from these data that the major population of tracheal smooth muscle muscarine receptors resembles the cardiac M2 type not only with respect to equilibrium binding affinities but also with respect to the secondary, allosteric binding site on the muscarine receptor. The results also imply that the cardiac receptor subtype is much more sensitive to allosteric modulation than the glandular/smooth muscle receptor subtype.


Electrical activity in endocrine pituitary cells in situ: a support for a multiple-function coding.
The anterior pituitary is an endocrine gland that controls basic body functions. Pituitary cell functioning depends on membrane excitability, which induces cytosolic calcium rises. Here, we reported the first identification of small-amplitude voltage fluctuations that controlled spike firing in endocrine cells recorded in situ. Three patterns of voltage fluctuations were distinguishable by their durations (1-100 s). These patterns could be ordered on top of each other, namely in response to secretagogues. Thus, pituitary endocrine cells express in situ a cell code in which small-amplitude voltage fluctuations lead to a multimodal arrangement of spike firing, which may finely tune calcium-dependent functions.


Hair analysis for ketamine and its metabolites.
A rapid and sensitive method was developed for the simultaneous identification and quantitation of ketamine (K) and its major metabolite, norketamine (NK) in hair. After decontamination, the hair sample was incubated and extracted, and analyzed by gas chromatography-mass spectrometry (GC-MS). Limits of quantitation were found to be 0.05 ng/mg. Hair segments in black color were collected from 15 K abusers. Based on an experiment with 15 cavies with black, white, and brown hair, the mechanism of incorporation of K into hair was investigated. After shaving hair on the back of the cavies (8 cm x 4 cm), they were separated into three groups and administered intraperitoneally once a day for 7 successive days with high, medium, and low doses of K, respectively. Two days after this, hair segments with different colors were shaved. There was a direct correlation between the concentration of K in cavy hair and the dose and DHNK was detected only in high dosage group. The concentration of K increased in the order of white, brown, and black hair. The possible factors responsible for the incorporation of K and its metabolites in hair were discussed.


Understanding Spatially Complex Segmental and Branch Anatomy Using 3D Printing: Liver, Lung, Prostate, Coronary Arteries, and Circle of Willis.
Three-dimensional (3D) manufacturing is shaping personalized medicine, in which radiologists can play a significant role, be it as consultants to surgeons for surgical planning or by creating powerful visual aids for communicating with patients, physicians, and trainees. This report illustrates the steps in development of custom 3D models that enhance the understanding of complex anatomy. We graphically designed 3D meshes or modified imported data from cross-sectional imaging to develop physical models targeted specifically for teaching complex segmental and branch anatomy. The 3D printing itself is easily accessible through online commercial services, and the models are made of polyamide or gypsum. Anatomic models of the liver, lungs, prostate, coronary arteries, and the Circle of Willis were created. These models have advantages that include customizable detail, relative low cost, full control of design focusing on subsegments, color-coding potential, and the utilization of cross-sectional imaging combined with graphic design. Radiologists have an opportunity to serve as leaders in medical education and clinical care with 3D printed models that provide beneficial interaction with patients, clinicians, and trainees across all specialties by proactively taking on the educator's role. Complex models can be developed to show normal anatomy or common pathology for medical educational purposes. There is a need for randomized trials, which radiologists can design, to demonstrate the utility and effectiveness of 3D printed models for teaching simple and complex anatomy, simulating interventions, measuring patient satisfaction, and improving clinical care.


Effect of dimensions on function: A 2-dimensional sonographic assessment to correlate facial muscle and smile type.
The aim of this study was to measure the dimensions of the select facial muscles and correlate them with different types of smiles. The study group included 30 South Asian adults (17 men and 13 women) aged between 24 and 30 years divided into 3 groups of 10 subjects each according to Rubin's classification of smile. The zygomaticus major, levator labii superioris, depressor anguli oris, and mentalis muscles were ultrasonographically evaluated. The length and thickness of the muscles were measured bilaterally. The data obtained were analyzed statistically. The maximum mean value thickness of the zygomaticus major was found in the canine smile group. The maximum mean value thickness of the depressor anguli oris and mentalis was seen in the full denture smile group. However, the thickness of the levator labii superioris muscle was similar between the different smile groups. There was no significant difference in the measurements of the length of the muscles between the right and the left sides. This study did not find any statistically significant correlation between the type of smiles described in Rubin's classification and the dimensions of the associated facial muscle.


Genetic and non-genetic parameter estimates for growth traits and Kleiber ratios in Dorper × indigenous sheep.
Genetic improvement programme will only be successful when accompanied by a good understanding of the influence of different environmental factors, knowledge of the genetic parameters and the genetic relationships between the traits of interest. This study aimed to evaluate the influence of non-genetic factors on growth traits and Kleiber ratios and to estimate genetic parameters for early growth traits in Dorper × indigenous crossbred sheep. The effects of fixed factors were analysed by the general linear model procedure of statistical analysis system, while the genetic parameters were estimated using a WOMBAT computer program fitted animal model. The overall least-square mean for birth weight (BRW), weaning weight (3MW), six-month weight, nine-month weight, and yearling weight were 3.03 ± 0.02, 14.5 ± 0.18, 20.4 ± 0.26, 24.8 ± 0.31, and 28.3 ± 0.40 kg, respectively. The overall least-square mean for Kleiber ratio from birth to weaning (KR1), weaning to six months, six to nine months and nine months to yearling age were 16.8 ± 0.10, 6.41 ± 0.17, 4.55 ± 0.21 and 3.38 ± 0.20 g/kg of metabolic weight, respectively. The inclusion of maternal genetic effect had a significant influence on BRW, and it explains 20% of the phenotypic variation. The total heritability estimates for BRW, 3MW, birth to weaning average daily weight gain and KR1 were 0.10, 0.14, 0.16 and 0.12, respectively. The phenotypic correlation varied from -0.11 ± 0.05 to 0.98 ± 0.02, whereas the direct genetic correlation ranged from -0.32 ± 0.40 to 0.98 ± 0.17. The mean inbreeding coefficient was 0.105% with an annual rate of 0.02%. The heritability estimates for growth traits and Kleiber ratio suggest that slow genetic progress would be expected from the selection. However, the integration of selection with crossbreeding programme can enhance genetic gain. Therefore, selection should be conducted based on breeding values estimated from multiple information sources to increase the selection response.


Rare primary hepatic malignancies: A case-based review.
The two most common primary liver malignancies that radiologists encounter in clinical practice are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, there are other less common primary hepatic malignancies that radiologists should be aware of. The correct radiographic and pathologic diagnosis of these entities have important treatment and prognostic implications. In this paper, we review a series of five cases that we have encountered in clinical practice at our institution that were initially thought to be HCC or ICC, but turned out to be a rarer primary hepatic malignancy. We will review the radiographic and pathologic characteristics of each of these rare primary hepatic malignancies as well as discuss the prognosis and treatment for each.


Evaluation of transabdominal ultrasound after oral administration of an echoic cellulose-based gastric ultrasound contrast agent for gastric cancer.
With the remarkable improvements in ultrasound equipment, transabdominal ultrasound after oral administration of an echoic cellulose-based gastric ultrasound contrast agent (TUS-OCCA) has recently been suggested to be effective in initial screening of gastric cancer. The aim of this study was to evaluate the diagnostic value of TUS-OCCA for gastric cancer. Consecutive patients with gastric cancers who underwent resection in our hospital were enrolled. Before the lesion was resected, TUS-OCCA examination was performed by a skilled examiner who was blinded to the site, size, and endoscopy diagnosis of the lesion. TUS-OCCA findings were compared with those of endoscopy and pathological diagnoses as the gold standard. There were a total of 288 consecutive patients enrolled in the study, including 228 with advanced gastric cancers (T2-T4 stage), 50 with early gastric cancer (26 with stage T1b and 24 with stage T1a), and 10 with high-grade intraepithelial neoplasia. TUS-OCCA had a detection rate of 100% (228/228) for advanced gastric cancers, 77% (20/26) for stage T1b, 67% (16/24) for stage T1a, and 60% (6/10) for high-grade intraepithelial neoplasia. The majority of patients with undetectable neoplasms using TUS-OCCA were obese (body mass index, 28.7-31.8 kg/m(2)). The overall accuracy of TUS-OCCA in determining the T stage of gastric cancer was 77.3% (62.5% for T1a, 70% for T1b, 71.1% for T2, 85.2% for T3, and 73.3% for T4). These findings indicate that TUS-OCCA achieved a high detection rate for gastric cancers and was useful in assessing the degree of gastric cancer invasion.


Conditioned response to apomorphine in nigro-striatal system-lesioned rats: the origin of undrugged rotational response.
Development and time-course characteristics of Early rotational response (ER) to apomorphine in 6-hydroxydopamine-lesioned rats is explored. We show here how this ER can be considered a conditioned response that arises when the drug is repeatedly administered, according to a classical conditioning paradigm. In this way, the ER to apomorphine can be considered a non-pharmacological, conditioned, placebo response, the drug action being the unconditioned stimulus (UCS). In our model, the undrugged rotational response elicited by saline injections two weeks after drug treatment can be considered as the conditioned response (CR) to the conditioned stimulus, the CS being the environment associated with the drug treatment. This CR had not previously been identified during the drug treatment. Thus, we studied the acquisition of the ER, nonexistent after the first injection of apomorphine. Furthermore, we distinguish between this ER and the later, strictly pharmacological rotational response (LR) to apomorphine. Finally, we related this ER to the undrugged, paradoxical response to saline. In conclusion, we demonstrate the paradigm of pharmacological conditioning using this animal model of Parkinson's disease, supported by our own results and those of Silverman and Ho (1981).


Inactivation of cathepsin B by active site-directed disulfide exchange. Application in covalent affinity chromatography.
The ability of cystamine, bis-N-aminoethyl disulfide, to inactivate cathepsin B by disulfide exchange is considerably enhanced by the addition of hydrophobic residues which apparently occupy secondary binding sites in the extended active center of the protease. For example, a peptidyl cystamine derivative such as symmetrical Gly-Phe-cystamine is substrate-like and promotes the disulfide exchange by affinity labeling. The effectiveness of this type of reagent is dependent on the peptidyl sequence. The inactivation is more rapid with increasing pH in the narrow range studied, pH 5-7, and is completely reversed by added thiols. Immobilization of the peptidyl cystamine derivatives provided an effective and rapid procedure for the covalent chromatography of cathepsin B following ammonium sulfate fractionation of beef spleen or pork liver homogenates, replacing the need for ion exchange chromatography. Pork liver cathepsin B thus obtained was a mixture of single chain and double chain forms as found by other methods.


Aortic arch impingement with Salter Harris II epiphyseal fracture of the medial clavicle: A novel use of video assisted thoracoscopy.
Posterior dislocation of the sternoclavicular joint (SCJ), although uncommon, can be life-threatening. Displacement of the clavicular head poses a threat to the vital structures of the mediastinum. We describe the case of a 15-year-old boy with traumatic Salter Harris II medial clavicular fracture with posterior dislocation of the metaphysis resulting in impingement of the aortic arch, left subclavian and common carotid artery, as well as partial obstruction of the brachiocephalic vein. We describe the novel use of video-assisted thoracoscopy to assist with a safe open reduction and fixation of the fracture dislocation. The case highlights the importance of computer tomography imaging for diagnosis of posterior SCJ fracture/dislocations and the early recognition of potential life-threatening complications in the mediastinum.


Long-Term Follow-Up of Endovascular Repair in the Management of Arterial Stenosis Caused by Takayasu's Arteritis.
This retrospective study evaluated the long-term results of endovascular repair in the management of arterial stenosis caused by Takayasu's arteritis (TA). Sixty-seven endovascular procedures (percutaneous transluminal balloon angioplasty or stenting) were performed for 49 arterial lesions in 35 patients. Endovascular treatment was performed when the disease was inactive. The patients were pretreated with immunosuppressive drugs and were followed every 3-6 months to monitor disease activity and medical treatment. Doppler ultrasonography and magnetic resonance angiography were performed every 6 months. Kaplan-Meier method with the log-rank test was used to analyze the survival of renal artery procedures because the number of lesions in other territories was not sufficient for statistical analysis. The mean follow-up duration after the endovascular procedure was 83 months (range: 12-144 months). Twenty-two (33%) endovascular interventions resulted in restenosis or occlusion. Reinterventions resulted in primary assisted patency in 45 (92%) lesions with restenosis. Only 4 (8%) of the 49 arterial lesions were occluded at the time of the final evaluation. The overall patency rate for the renal artery stents was 93.7% (15/16) after 8 years of follow-up. In the Kaplan-Meier survival analyses of the renal artery lesions, the 1- and 8-year restenosis-free survival rates of renal arterial interventions were 74% and 57%, respectively, (P = 0.281). In this study, endovascular treatment with adequate immunosuppressive medication resulted in long-term patency with one- or multi-stage reinterventions in 92% of stenotic arterial lesions caused by TA.


Large prostatic hematomas associated with carcinoma of the prostate.
Two cases are presented of large prostatic hematomas secondary to adenocarcinoma of the prostate. The similarity of these cases at examination to prostatic abscesses complicated diagnosis and delayed treatment. To avoid diagnostic error it is important to remain alert to this atypical presentation and to remember the necessity to obtain adequate biopsies.


Beyond partnering: creating the healthcare community.
Growing stress on the healthcare system has encouraged policy makers and care providers to reconsider the current system. While universal access must be maintained, the authors argue that greater recognition of the differences in the health needs of Canada's diverse communities should shape service delivery. The creation of "healthcare communities" based on targeted research and stakeholder advice is more efficient and cost-effective than a standardized model based on population aggregates.


Antidepressant-like and antinociceptive-like actions of 4-(4'-chlorophenyl)-6-(4''-methylphenyl)-2-hydrazinepyrimidine Mannich base in mice.
This study investigated the possible antidepressant and antinociceptive action of CPMPH Mannich base, as well as the involvement of serotonergic, dopaminergic, noradrenergic and opioid systems and the L-arginine-nitric oxide pathway in the antidepressant-like effect of CPMPH in the forced swimming test (FST) in mice. The immobility time in the FST was significantly reduced by CPMPH (0.1-10 mg/kg, i.p.), without accompanying changes in the ambulation in an open-field. CPMPH at high doses (i.p. or s.c. routes) produced a significant inhibition of acetic acid-induced writhing. The antidepressant-like effect of CPMPH (1 mg/kg, i.p.) in the FST was prevented by pre-treatment of mice with methysergide (2 mg/kg, i.p., a non-selective serotonin receptor antagonist), sulpiride (32 mg/kg, i.p., a D2 receptor antagonist) or yohimbine (1 mg/kg, i.p., an alpha2-adrenoceptor antagonist). In contrast, the antidepressant-like effect of CPMPH was not affected by pre-treatment (i.p.) with naloxone (1 mg/kg, a non-selective opioid receptor antagonist) or L-arginine (750 mg/kg, a nitric oxide precursor). The results demonstrate that CPMPH had an antidepressant-like action that appears to be mediated through its interaction with serotonergic, dopaminergic and noradrenergic systems.


Assessing HIV/AIDS stigma in south India: validation and abridgement of the Berger HIV Stigma scale.
HIV-related stigma has been associated with depression, poor adherence, and nondisclosure of HIV-positive status, all of which can lead to increased transmission of HIV and poorer health outcomes for HIV-infected individuals. The Berger HIV Stigma scale has been used in multiple settings but never adapted and validated in India, home to the world's second largest HIV-infected population. We assessed the reliability and validity of a Tamil translation of the original 40-item scale, and conducted confirmatory and exploratory factor analyses to assess cultural appropriateness and abbreviate the scale. Reliability and validity were high (alpha = 0.91; test-retest reliability ICC = 0.89). Exploratory and confirmatory factor analysis resulted in an abridged 25-item version of the scale that possessed better psychometric properties than the 40-item version. This culturally validated, abridged HIV-Stigma scale can be used in busy clinical settings to identify individuals in need of psychosocial support and assess post-intervention changes in stigma in Southern India.


Latitudinal diversity gradient and cetaceans from the perspective of MHC genes.
Pathogen diversity is a key source of selective pressure on immune system genes, shaping molecular evolution mainly on widely distributed or migratory organisms such as cetaceans. Here, we investigated the effects of latitudinal span migration, different biomes occupation, and pathogen-mediated selection on MHC DQB locus divergence on cetaceans. We applied some evolutionary genetics methods using a dataset of 15 species and 121 sequences, and we found a trend on greater MHC divergence on tropical species when compared with either temperate or migratory species. In addition, oceanic cetaceans exhibit greater MHC divergence. Here, we show that, despite there was a correlation between the diversity of MHC DQB alleles with the distribution of organisms, the pattern of diversity found is not completely explained by pathogenic pressure, suggesting that other factors must be investigated for a better understanding of the processes related to the diversity of MHC in cetaceans.


Central Nervous System Cryptococcosis due to Cryptococcus gattii in the Tropics.
Cryptococcosis of the central nervous system due to Cryptococcus gattii species complex is a serious mycosis with worldwide distribution but of great importance in the tropics. This article aims to review the progress made in these regions in the knowledge of this disease and its etiological agent. They can be summarized in the presence in apparently immunocompetent patients of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which is a hidden risk factor for acquiring C. gattii infection; this finding strengthens the concept that C. gattii is an opportunistic pathogen. A greater knowledge of the clinical and molecular epidemiology of C. gattii infection and of the different environmental niches of this fungus in the tropics. The discovery of a new lineage of C. gattii, VGV, in environmental samples from Africa. Until now, the COVID-19 pandemic has not meant an increase in cryptococcosis cases. Advances have been made in the identification of risk factors for cryptococcosis due to C. gattii as well as in the knowledge of its etiological agent and its relationship with the environment. Remarkably, there have been no significant achievements in diagnosis and treatment notwithstanding the documented importance.


Process evaluation of in-person, news and social media engagement of a community-based programme Brown Buttabean Motivation (BBM): a research protocol.
The community group Brown Buttabean Motivation (BBM) initially began to assist Auckland Pasifika and Māori to manage weight problems, predominantly through community-based exercise sessions and social support. BBM's activities expanded over time to include many other components of healthy living in response to community need. With advent of the COVID-19 pandemic, BBM outreach grew to include a foodbank distributing an increasing amount of donated healthy food to families in need, a community kitchen and influenza and COVID-19 vaccine drives. A strong social media presence has served as the main means of communication with the BBM community as well as use of traditional news media (written, radio, television) to further engage with vulnerable members of the community. The study aims to conduct mixed method process evaluation of BBM's community engagement through in-person, social and news media outreach activities with respect to the health and well-being of Pasifika and Māori over time. The project is informed by theoretical constructs including Pacific Fa'afaletui and Fonofale and Māori Te Whare Tapa Whā Māori research frameworks and principles of Kaupapa Māori. It is further framed using the concept of community-driven diffusion of knowledge and engagement through social networks. Data sources include in-person community engagement databases, social and news media outreach data from archived documents and online resources. Empirical data will undergo longitudinal and time series statistical analyses. Qualitative text thematic analyses will be conducted using the software NVivo, Leximancer and AntConc. Image and video visual data will be randomly sampled from two social media platforms. The social media dataset contains almost 8000 visual artefacts. Ethics approval obtained from University of Auckland Human Participants Ethics Committee UAHPEC 23456. Findings will be published in peer-reviewed publications, disseminated through community meetings and conferences and via BBM social network platforms. ACTRN 12621 00093 1875.


[Sociodemographic, clinical and ultrasound characterization of thyroid nodule pathology and its association with malignancy in a Colombian high-complexity center].
Thyroid nodules are among the most frequent conditions, with a 10% risk of malignancy. The objective is to describe the frequency of demographic, clinical, and ultrasonographic characteristics of thyroid nodule pathology in adults and to explore the relationship with tumor malignancy. An analytical, retrospective cross-sectional study in adults with thyroid nodules and nodular fine-needle aspiration performed in adult patients from a Colombian reference center between 2009-2019. Data were obtained from the clinical history, descriptive measures of the patient's demographic, clinical, and ultrasound variables were estimated, and their relationship with the malignancy of the tumor was explored. A total of 445 patients and 515 nodules were included. The median age was 55 years (IQR 44-64), 86.8% of women, and 54.8% had a single lesion. Percentages of 80.2 and 19.8 were benign and malignant nodules, with a median of 15.7mm (IQR 11-25) and 12.7mm (IQR 8.5-18.3), respectively (p<0.001). Hypothyroidism and levothyroxine consumption were higher in those with malignant nodules (p<0.001). The echographic characteristics were statistically different between the nodules. In the malignant ones, there was a higher frequency of solid composition, hypoechogenicity, and irregular margins. In contrast, in the benign ones, the absence of echogenic focus stood out (p<0.001). The ultrasound characteristics are essential to define the risk of malignancy of a thyroid nodule. Therefore, considering the most frequent ones can help in the most appropriate approach to primary care.


Paradoxical effect of antibodies against chorionic gonadotropin on BeWo choriocarcinoma cells in vitro and in vivo: evidence for heterogeneity of cell types.
Antisera raised in monkey or baboon against purified beta-subunit of human chorionic gonadotropin (beta-hCG) coupled to tetanus toxoid exert complement-dependent cytotoxic effects on BeWo choriocarcinoma cells maintained in tissue culture. The cytotoxic effect is manifested morphologically as well as by incorporation of radioactive thymidine and leucine. However, in the presence of saturating amounts of anti-beta-hCG antibodies and complement, antibodies failed to kill all of the BeWo choriocarcinoma cells. Evidence is presented to suggest that the partial and not complete cytotoxic effect of antibodies may be due to the heterogeneity of cell types, one sensitive to immune attack by anti-beta-hCG antibodies, the other resistant. Immunoenzymatic localization of hCG revealed its presence on the cell surface of only a fraction of BeWo cells. The antibody-resistant BeWo cell population had no demonstrable hCG on the cell surface. Resistant cells did not secrete hCG into the medium when cultured for up to 4 days. However, the resistant cell population, upon transplantation to the hamster cheek pouch, regained the ability to secrete hCG. Heterogeneity of cell types may explain the refractoriness of the BeWo cells transplanted to the hamster cheek pouch to an inhibitory effect of antibodies at later stages of tumor growth.


Proliferative and migratory activity of glial cells in the partially deafferented hippocampus.
The proliferative response of the glial cell population of the adult rat hippocampus deafferented by unilateral lesion of the entorhinal cortex was studied using 3H-thymidine autoradiography. Two experimental paradigms were used, involving: (1) intraventricular 3H-thymidine injection at a number of post-lesion intervals with sacrifice six hours later and (2) intraventricular injection at 30 hours post-lesion with sacrifice at 6, 96, or 192 hours later. The first increase in the number of labeled glial cells was obtained at 20 hours post-lesion and was confined to areas of degenerating axons. By 30 hours a large and uniformly dense proliferative response was observed throughout the ipsilateral, and medial aspects of the contralateral, hippocampus encompassing both deafferented and intact regions. Cell division continued through 50 and 65 hours post-lesion particularly in directly deafferented regions, but diminished to control levels by 80 hours. Although oligodendroglia and astrocyte-like cells were sometimes found to have incorporated the label the most common proliferative element within the hippocampus corresponded to previous light microscopic descriptions of "microglial" cells. The experiments using thymidine injection given at the peak proliferative period followed by survival periods of varying lengths indicated that a progressive redistribution of labeled nuclei occurred resulting in an accumulation of labeled cells in the zones of deafferentation. Multiple division of cells within these areas as well as the migration of nuclei from non-deafferented regions was found to contribute to this effect. The possible involvement of glial proliferation with other morphological effects of deafferentation, including the sprouting response of intact afferents, is discussed.


LncRNA-uc.167 influences cell proliferation, apoptosis and differentiation of P19 cells by regulating Mef2c.
In our previous study we screened thousands of lncRNAs for their relationship with ventricular septal defect. Among these lncRNAs, uc.167 attracted our attention for its high level of conservation and that it was antisense to the Mef2c gene, which encodes myocyte enhancer factor 2C. This study aims to investigate the role of uc.167 during cardiomyocyte maturation in P19 cells induction and possible mechanism. The uc.167 expression level in human heart tissue of ventricular septum defect (VSD) was evaluated by qRT-PCR. The UCSC database was searched to investigate the bioinformatics of uc.167. We constructed overexpression vector of uc.167 and Mef2c. To detect proliferation and apoptosis, we combined cell cycle analysis and CCK8, Hoechst staining, flow cytometry and caspase-3 assays, respectively. The cardiomyogenesis related RNAs (cTnT, GATA4, and Mef2c) and proteins were detected by qRT-PCR and Western blotting. In this study, we found that uc.167 expression was significantly increased in VSD heart tissues. uc.167 is on the opposite strand to the coding gene Mef2c. The expression model of Mef2c and uc.167 showed an opposite correlation in the embryonic development and process of differentiation of P19 cells into cardiomyocytes. Overexpression of uc.167 inhibited proliferation but promoted apoptosis in P19 cells compared with the vector group, and those relative mRNAs and proteins decreased during the differentiation process. Whereas, co-expression of Mef2c and uc.167 can partially reverse the negative effects of uc.167 on proliferation, apoptosis and differentiation. Taken together, our findings suggest that uc.167 contributes to the development potential of VSD and may constitute a potential therapeutic target in this disease. uc.167 influences cell proliferation, apoptosis and differentiation of P19 cell by regulating Mef2c.


Influence of scene-based expectation on facial expression perception: The moderating effect of cognitive load.
Prior expectations play an important role in the process of perception. In real life, facial expressions always appear within a scene, which enables individuals to generate predictions that affect facial expression judgments. In the present study, using event-related potentials, we investigated the influence of scene-based expectation on facial expression processing. In addition, we used a cognitive task to manipulate cognitive load to interfere with scene-based expectation. Results showed that under the condition of sufficient cognitive resources, faces elicited more negative N170 amplitudes and more positive N400 amplitudes when the emotional valence of the scenes and faces was congruent. However, in the condition of cognitive load, no such difference was observed. The findings suggested that the effect of expectation on facial expression recognition emerges during both the early and late stages of facial expression processing, and the effect is weakened when cognitive resources are occupied by unrelated tasks.


Inflammasomes.
Ketelut-Carneiro and Fitzgerald discuss the basic concepts about inflammasome composition, assembly and activation, effector functions and role in infection and inflammatory disease.


Author Correction: An assay for the identification of Plasmodium simium infection for diagnosis of zoonotic malaria in the Brazilian Atlantic Forest.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Anti-inflammatory therapy in Alzheimer's disease: is hope still alive?
Based on observations from neuropathology, epidemiology, and in vitro and animal experiments, the inflammatory component of Alzheimer's disease (AD) has been considered a compelling target for therapeutic intervention. However, a summary of all published trial reports to date suggests that AD patients do not benefit from treatment with anti-inflammatory drugs. In this brief review, we try to reconcile these sobering trial results with recent observations from basic research and epidemiology that continue to strengthen the idea that inflammatory mechanisms play an important role in the pathogenesis of AD. We review the possibilities that (1) not all components of the inflammatory response in AD are detrimental, (2) beneficial effects of anti-inflammatory drugs may not be mediated by inflammatory pathways, and (3) the timing of the intervention should be in the earliest stages of the pathogenesis of AD, perhaps even before the first symptoms emerge. We conclude that studies on primary prevention of AD are the logical next step in testing the inflammatory hypothesis of AD.


Pneumococcal sepsis due to functional hyposplenism in a bone marrow transplant patient.
Encapsulated bacteria can cause severe infections following bone marrow transplantation, usually in patients with chronic graft-versus-host disease (GVHD). Presented here is the case of an allogenic bone marrow transplantation recipient with chronic GVHD who developed overwhelming pneumococcal sepsis 3 years following transplantation. One year earlier the male patient had developed non-meningococcal, non-gonococcal neisseria infection. The infection recurred repeatedly despite monthly replacement immunoglobulin prophylaxis. These infections were attributed to functional hyposplenism after a prominent number of Howell-Jolly bodies was noticed in a peripheral blood smear during the patient's most recent admission. The case report is followed by a discussion of the policy of administering antibiotic prophylaxis to patients with chronic GVHD.


HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment.
Several human HLA alleles have been found associated with type 1 diabetes (T1D), but their precise role is not clearly defined. Herein, we report that a human MHC class II (HLA-DR*0401) allele transgene that has been expressed into NOD (H-2(g7)I-E(null)) mice prone to T1D rendered the mice resistant to the disease. T1D resistance occurred in the context of multi-point T-cell alterations such as: (i) skewed CD4/CD8 T-cell ratio, (ii) decreased size of CD4(+)CD44(high) T memory pool, (iii) aberrant TCR Vβ repertoire, (iv) increased neonatal number of Foxp3(+) and TR-1(+) regulatory cells, and (v) reduced IFN-γ inflammatory response vs. enhanced IL-10 suppressogenic response of T-cells upon polyclonal and antigen-specific stimulation. The T-cells from NOD/DR4 Tg mice were unable to induce or suppress diabetes in NOD/RAG deficient mice. This study describes a multifaceted regulatory function of the HLA-DR*0401 allele strongly associated with the lack of T1D development in NOD mice.


Role of exercise for type 2 diabetic patient management.
Exercise is integral to the management of type 2 diabetes. Unfortunately, the majority of adults with type 2 diabetes do not engage in regular exercise. Three hundred patients with type 2 diabetes were randomly selected from a patient pool of diabetic patients encountered in 1996 at the Department of Veterans Affairs Medical Center in New Orleans, Louisiana. Medical records from October 1996 to June 1999 were reviewed. Information about exercise, alcohol intake, smoking, medications, laboratory results, and other variables was extracted from medical records. Patients with mean glycosylated hemoglobin (HbA1c) < 8.0 (good diabetic control) were compared with those who had poor diabetic control (mean (HbA1c) > or = 8.0). The effect of exercise in the management of type 2 diabetes was assessed. After adjustment for other variables, patients without exercise had an odds ratio of 2.71 (95% CI, 1.38-5.32) for poor diabetic control compared with patients with exercise. These findings suggest that exercise by itself is important for type 2 diabetes management.


Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo.
Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A-independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell-cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer.


The association between rheumatoid arthritis and periodontitis.
The relationship between rheumatoid arthritis and poor oral health has been recognised for many decades. The association between periodontal infection and the risk of developing RA has been the subject of epidemiological, clinical and basic science research in recent times. Converging and reproducible evidence now makes a clear case for the role of specific periodontal infective pathogens in initiating, amplifying and perpetuating rheumatoid arthritis. The unique enzymatic properties of the periodontal pathogen Porphyromonas gingivalis and its contribution to the burden of citrullinated peptides is now well established. The impact of localized infection such as periodontitis in shaping specific anti-citrullinated peptide immune responses highlights a key area for treatment, prevention and risk assessment in rheumatoid arthritis.


Smallness for gestational age is associated with persistent change in insulin-like growth factor I (IGF-I) and the ratio of IGF-I/IGF-binding protein-3 in adulthood.
Implication of the IGF-IGF-binding protein (IGFBP) axis in the development of metabolic and cardiovascular diseases has been well documented. It has also been shown that an adverse intrauterine environment alters the IGF-IGFBP axis during childhood. The objective of this study was to investigate whether these alterations persist into adulthood. Fasting serum IGF-I, IGFBP-3, and insulin concentrations were measured, and their determinants were analyzed in a cohort of young adult subjects (22 yr of age) born either small (SGA; n = 461) or appropriate (AGA; n = 568) for gestational age. In adulthood, subjects born SGA had significantly lower mean serum IGF-I (320 +/- 137 vs. 348 +/- 143 microg/liter; P = 0.0015), IGFBP-3 (4700 +/- 700 vs. 4800 +/- 800 microg/liter; P = 0.04), and IGF-I/IGFBP-3 ratio (0.067 +/- 0.026 vs. 0.072 +/- 0.025; P = 0.01) than those born AGA. The fasting IGF-I concentration and the IGF-I/IGFBP-3 ratio were significantly inversely associated with age, body mass index, smoking, and oral contraception and were positively related to birth weight and fasting insulin levels. The IGFBP-3 concentration was significantly negatively correlated to age and smoking and was positively related to insulin concentration and oral contraception. After adjustment for age, height, body mass index, gender, smoking, and oral contraception, the mean IGF-I concentration and the mean IGF-I/IGFBP-3 ratio remained significantly lower in the SGA compared with the AGA group (P = 0.003 and P = 0.01, respectively). Serum IGF-I concentrations and the IGF-I/IGFBP-3 ratio are lower in adult subjects born SGA. Although the origin of this persisting alteration of the IGF-IGFBP axis in adulthood needs to be elucidated, its potential contribution to the long-term metabolic and cardiovascular complications associated with fetal growth restriction is important to consider in the future.


Advances in skin cancer early detection and diagnosis.
To provide an overview of 1) traditional methods of skin cancer early detection, 2) current technologies for skin cancer detection, and 3) evolving practice models of early detection. Peer-reviewed databased articles and reviews, scholarly texts, and Web-based resources. Early detection of skin cancer through established methods or newer technologies is critical for reducing both skin cancer mortality and the overall skin cancer burden. A basic knowledge of recommended skin examination guidelines and risk factors for skin cancer, traditional methods to further examine lesions that are suspicious for skin cancer and evolving detection technologies can guide patient education and skin inspection decisions.


The efficacy of paracervical injections of lignocaine before laser ablation of the cervical transformation zone. A randomized placebo-controlled double-blind clinical trial.
In a prospective double-blind randomized placebo-controlled clinical trial the efficacy of paracervical lignocaine was compared with saline in reducing pain in 70 women undergoing laser ablation of the cervical transformation zone. Paracervical lignocaine had no significant measurable effect on reducing the pain experience during the laser procedure. The mean subjective visual linear analogue pain score in the lignocaine and saline groups was 27% (95% CI 17 to 38) and 30% (95% CI 24 to 41) respectively (t = 1.0; P = 0.35). The median (quartiles) objective pain scores for the same groups were 0 (0-2) and 0 (0-1) respectively (P = 0.58).


The section-Golgi impregnation procedure. 1. Description of the method and its combination with histochemistry after intracellular iontophoresis or retrograde transport of horseradish peroxidase.
A method is described for impregnating neurons by the Golgi procedure in sections of brain tissue that are of a thickness 80-100 microns, so allowing a variety of histochemical procedures to be carried out prior to Golgi-impregnation. The method has been applied to the retina of the adult primate and to brain sections incubated to reveal horseradish peroxidase activity with substrates that give electron-dense reaction products. Sections containing neurons that have been filled with horseradish peroxidase by intracellular iontophoresis following electrophysiological characterization, or containing neurons retrogradely labelled by horseradish peroxidase, can be impregnated by this Golgi procedure. Subsequent gold-toning of the Golgi-impregnated neurons makes it possible to study, in the electron-microscope, both Golgi-impregnated and peroxidase-containing neurons and their afferent and efferent synaptic contacts within the same section. The procedure also makes it possible to repeat Golgi impregnation on sections already Golgi-impregnated and gold-toned, or to repeat the Golgi impregnation if the first impregnation is not satisfactory. The procedure is illustrated by examples from the monkey retina, cat visual cortex and rat neostriatum.


Analysis of adherent cell culture lysates with low metabolite concentrations using the Biocrates AbsoluteIDQ p400 HR kit.
The AbsoluteIDQ p400 HR kit is a commercial product for targeted metabolomics. While the kit has been validated for human plasma and serum, adherent cell lysates have not yet been evaluated. We have optimized the detection of polar and lipid metabolites in cell lysates using the kit to enable robust and repeatable analysis of the detected metabolites. Parameters optimized include total cell mass, loading volume and extraction solvent. We present a cell preparation and analytical method and report on the performance of the kit with regard to detectability of the targeted metabolites and their repeatability. The kit can be successfully used for a relative quantification analysis of cell lysates from adherent cells although validated only for human plasma and serum. Most metabolites are below the limit of the Biocrates' set quantification limits and we confirmed that this relative quantification can be used for further statistical analysis. Using this approach, up to 45% of the total metabolites in the kit can be detected with a reasonable analytical performance (lowest median RSD 9% and 13% for LC and FIA, respectively) dependent on the method used. We recommend using ethanol as the extraction solvent for cell lysates of osteosarcoma cell lines for the broadest metabolite coverage and 25 mg of cell mass with a loading volume of 20 µL per sample.


Jieduquyuziyin prescription enhances CD11a and CD70 DNA methylation of CD4+ T cells via miR-29b-sp1/DNMT1 pathway in MRL/lpr mice.
Jieduquyuziyin prescription (JP) is a traditional Chinese medicine utilized to treat systemic lupus erythematosus (SLE). Its efficacy has been confirmed through clinical trials and empirical evidence, leading to its authorized use in Chinese hospitals. The development of JP exemplifies the integration of traditional wisdom and scientific approaches, demonstrating the interdisciplinary essence of ethnopharmacology. These results emphasize the potential value of traditional medicine in addressing autoimmune disorders. This study aims to address the effect of JP in MRL/lpr mice and elucidate the pharmacological mechanism by which JP targets CD11a and CD70 DNA methylation via the miR-29b-sp1/DNMT1 pathway. MRL/lpr mice were divided into three groups: the model group (received distilled water), the positive group (administered AAV/miR-29b-3p inhibitor), and the JP group (treated with JP decoction). C57BL/6 mice were constituted as a control group. Through ELISA assay, serum and urine samples were assessed for anti-dsDNA, TNF-α, TGF-β, IL-2, and UP. HE and Masson staining were conducted to reveal renal pathology. Genome DNA was extracted from CD4+ T cells of mice spleens to evaluate methylation level. The methylation of CD11a, CD70, and CD40L promoter regions was analyzed by targeted bisulfate sequencing. Their expression at the mRNA and protein levels was examined using quantitative real-time PCR, western blot analysis, immunohistochemistry, and immunofluorescence staining of kidney tissues. Furthermore, the molecular mechanisms underlying the regulation of the miR-29b-sp1/DNMT1 pathway by JP were explored with Jurkat cells transfected with miR-inhibitors or miR-mimics. Mice treated with JP exhibited a significant decrease in anti-dsDNA, TNF-α, TGF-β, and UP, accompanied by a significant increase in IL-2. HE staining revealed JP effectively mitigated renal inflammatory response, while Masson staining indicated a reduction in collagen fiber content. In addition, JP exhibited a significant impact on the global hypomethylation of SLE, as evidenced by the induction of high methylation levels of CD11a and CD70 promoter regions, mediated through the miR-29b-sp1/DNMT1 pathway. Our findings demonstrate JP exerts a protective effect against spontaneous SLE development, attenuates renal pathological changes, and functions as a miRNA inhibitor to enhance CD11a and CD70 DNA methylation through the modulation of the miR-29b-sp1/DNMT1 pathway.


[The prognostic significance of tissue-specific antibodies in the extraction of cataracts of different etiologies].
The authors demonstrate a high informative value of preoperative lacrimal fluid examinations to predict postoperative uveitis in patients with complicated cataracts. Detection of antituberculin antibodies in titers 1:128 or higher is a factor of risk of development of a postoperative inflammatory reaction. The risk of postoperative uveitis is increased to 100% if antibodies to tuberculin, tissue-specific retinal S antigen, and lenticular proteins are simultaneously detected in the lacrimal fluid.


[X-rayfilm analysis of the sinus paranasales from cleft patients (in comparison with a healthy group) (author's transl)].
A report on 301 x-rayfilms from cleft patients and 120 x-rayfilms of a control group to show the behaviour of the pneumatisation of the maxillar sinus is being given. The sinus maxillares of the left side by the male and female patients are greater than of the right side. The sinus maxillares are greater by female patients than by male patients. Patients with cleft formation: The sinus maxillares by female patients are significant smaller than the sinus maxillares by the control group. No different are the sinus maxillares by the control group and male with cleft formation patients with the right-sided clefts and female patients with right-sided clefts and on bilateral clefts. The sinus maxillares are of the side of localisation smaller than of the opposite side. By clefts of the primary and secondary palate (L-A-P-clefts) are the sinuses maxillares statistically larger than by clefts of the primary palate (L-A-clefts) and by subtotally and totally clefts of the secondary palate (P-clefts).


Gene therapy for inborn errors of liver metabolism.
In humans, treatment for inborn errors of liver metabolism has focused on dietary, drug, and cell therapies. However, significant morbidity and mortality still remain and alternative and/or adjunctive strategies are needed. It has been 15 years since human gene therapy trials were initiated for genetic diseases. While significant progress has been made in the preclinical arena in a variety of disease models, sustained effect in humans has still eluded the field of inborn errors of liver metabolism. At this time, achievement of clinical efficacy in different animal models has been reported with multiple gene transfer technologies. Current efforts are aimed at fully understanding host-vector interactions, and how manipulation of these interactions can help us to increase the therapeutic index of any specific therapy. As with any therapy, it will be the balance of this index and the disease natural history which will determine the future of clinical studies and their outcomes.


Contributions of adhesive proteins to the cellular and bacterial response to surfaces treated with bioactive polymers: case of poly(sodium styrene sulfonate) grafted titanium surfaces.
The research developed on functionalized model or prosthetic surfaces with bioactive polymers has raised the possibility to modulate and/or control the biological in vitro and in vivo responses to synthetic biomaterials. The mechanisms underlying the bioactivity exhibited by sulfonated groups on surfaces involves both selective adsorption and conformational changes of adsorbed proteins. Indeed, surfaces functionalized by grafting poly(sodium styrene sulfonate) [poly(NaSS)] modulate the cellular and bacterial response by inducing specific interactions with fibronectin (Fn). Once implanted, a biomaterial surface is exposed to a milieu of many proteins that compete for the surface which dictates the subsequent biological response. Once understood, this can be controlled by dictating exposure of active binding sites. In this in vitro study, we report the influence of binary mixtures of proteins [albumin (BSA), Fn and collagen type I (Col I)] adsorbed on poly(NaSS) grafted Ti6Al4V on the adhesion and differentiation of MC3T3-E1 osteoblast-like cells and the adhesion and proliferation of Staphylococcus aureus (S. aureus). Outcomes showed that poly(NaSS) stimulated cell spreading, attachment strength, differentiation and mineralization, whatever the nature of protein provided at the interface compared with ungrafted Ti6Al4V (control). While in competition, Fn and Col I were capable of prevailing over BSA. Fn played an important role in the early interactions of the cells with the surface, while Col I was responsible for increased alkaline phosphatase, calcium and phosphate productions associated with differentiation. Poly(NaSS) grafted surfaces decreased the adhesion of S. aureus and the presence of Fn on these chemically altered surfaces increased bacterial resistance ≈70% compared to the ungrafted Ti6Al4V. Overall, our study showed that poly(NaSS) grafted Ti6Al4V selectively adsorbed proteins (particularly Fn) promoting the adhesion and differentiation of osteoblast-like cells while reducing bacterial adhesion to create a bioactive surface with potential for orthopaedic applications.


The immunologic profile of adoptively transferred lymphocytes influences stroke outcome of recipients.
Animals that have myelin basic protein (MBP) specific lymphocytes with a Th1(+) phenotype have worse stroke outcome than those that do not. Whether these MBP specific cells contribute to worsened outcome or are merely a consequence of worse outcome is unclear. In these experiments, lymphocytes were obtained from donor animals one month after stroke and transferred to naïve recipient animals at the time of cerebral ischemia. The MBP specific phenotype of donor cells was determined prior to transfer. Animals that received either MBP specific Th1(+) or Th17(+) cells experienced worse neurological outcome, and the degree of impairment correlated with the robustness of MBP specific Th1(+) and Th17(+) responses. These data demonstrate that the immunologic phenotype of antigen specific lymphocytes influences stroke outcome.


Distance metrics for heme protein electron tunneling.
There is no doubt that distance is the principal parameter that sets the order of magnitude for electron-tunneling rates in proteins. However, there continue to be varying ways to measure electron-tunneling distances in proteins. This distance uncertainty blurs the issue of whether the intervening protein medium has been naturally selected to speed or slow any particular electron-tunneling reaction. For redox cofactors lacking metals, an edge of the cofactor can be defined that approximates the extent in space that includes most of the wavefunction associated with its tunneling electron. Beyond this edge, the wavefunction tails off much more dramatically in space. The conjugated porphyrin ring seems a reasonable edge for the metal-free pheophytins and bacteriopheophytins of photosynthesis. For a metal containing redox cofactor such as heme, an appropriate cofactor edge is more ambiguous. Electron-tunneling distance may be measured from the conjugated heme macrocycle edge or from the metal, which can be up to 4.8 A longer. In a typical protein medium, such a distance difference normally corresponds to a approximately 1000 fold decrease in tunneling rate. To address this ambiguity, we consider both natural heme protein electron transfer and light-activated electron transfer in ruthenated heme proteins. We find that the edge of the conjugated heme macrocycle provides a reliable and useful tunneling distance definition consistent with other biological electron-tunneling reactions. Furthermore, with this distance metric, heme axially- and edge-oriented electron transfers appear similar and equally well described by a simple square barrier tunneling model. This is in contrast to recent reports for metal-to-metal metrics that require exceptionally poor donor/acceptor couplings to explain heme axially-oriented electron transfers.


Effect of Jianpi therapy in treatment of chronic obstructive pulmonary disease: a systematic review.
To evaluate the efficacy of Jianpi therapy in Traditional Chinese Medicine (TCM) for treatment of chronic obstructive pulmonary disease (COPD) in stable phase by performing a systematic review and meta-analysis. The literatures concerning randomized controlled trials (RCTs) and quasi-RCTs comparing TCM treatment plus Western Medicine (WM) treatment with TCM alone, or TCM treatment vs no treatment, placebo for stable phase of COPD were searched in PubMed (1990-December 2010), in English and using Chinese National Knowledge Infrastructure (CNKI, 1990-December 2010), Chinese Biomedical Database (1990-December 2010), Wangfang Database (1990-December 2010), and Weipu (VIP) Database in Chinese. The quality assessment and data extraction for RCTs were conducted by two reviewers independently. Jadad scale and allocation concealment were used to assess the quality of the included studies, and meta-analyses were conducted with the Collaboration's Revman 5.0 software. Seventeen RCTs or quasi-RCTs involving 1269 patients were included. The methodological quality was poor in all trials except one trial (Jadad score = 4). In the meta-analysis, TCM-WM treatment was significantly superior to WM treatment in cure rate [OR = 3.82, 95% CI (2.45, 5.95)], and the effective rate between TCM treatment and placebo also had significant difference [OR = 4.31, 95% CI (2.35, 7.91)]. Moreover, pulmonary function of the patients in TCM-WM group and TCM group was significantly improved [forced vital capacity (FVC), P = 0.01, quality of life, P < 0.001]. The experience in TCM-WM treatment of COPD in stable phase was encouraging. The current evidence shows that TCM-WM treatment might be more efficient in effective rate, quality of life, and FVC than WM treatment alone. But for forced expiratory volume in one second (FEV1) and FEV1/FVC, no matter TCM-WM treatment compared with WM treatment alone or TCM treatment compared with placebo, there was no significant difference, with no obvious adverse reactions. Due to the low methodological quality of trials included, more RCTs of high quality in large scale are required.


Endocrine resistance and breast cancer plasticity are controlled by CoREST.
Resistance to cancer treatment remains a major clinical hurdle. Here, we demonstrate that the CoREST complex is a key determinant of endocrine resistance and ER+ breast cancer plasticity. In endocrine-sensitive cells, CoREST is recruited to regulatory regions co-bound to ERα and FOXA1 to regulate the estrogen pathway. In contrast, during temporal reprogramming towards a resistant state, CoREST is recruited to AP-1 sites. In reprogrammed cells, CoREST favors chromatin opening, cJUN binding to chromatin, and gene activation by controlling SWI/SNF recruitment independently of the demethylase activity of the CoREST subunit LSD1. Genetic and pharmacological CoREST inhibition reduces tumorigenesis and metastasis of endocrine-sensitive and endocrine-resistant xenograft models. Consistently, CoREST controls a gene signature involved in invasiveness in clinical breast tumors resistant to endocrine therapies. Our studies reveal CoREST functions that are co-opted to drive cellular plasticity and resistance to endocrine therapies and tumorigenesis, thus establishing CoREST as a potential therapeutic target for the treatment of advanced breast cancer.


Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease.
The diabetic state confers an increased propensity to accelerated atherogenesis. In addition to the established risk factors, there is evidence for increased oxidative stress in diabetes. Increased oxidative stress is manifested by increased lipid peroxidation, increased F2-isoprostanes, increased nitrotyrosine, and increased DNA damage. Also, in diabetics, there is increased superoxide release. With regard to diabetes, antioxidants such as alpha-tocopherol, alpha-lipoate, and ascorbic acid supplementation have been shown to be beneficial. Most importantly, alpha-tocopherol therapy, especially at high doses, clearly shows a benefit with regard to low-density lipoprotein oxidation, isoprostanes, and monocyte superoxide release. Thus, it appears that, in diabetes, antioxidant therapy could alleviate the increased attendant oxidative stress and emerge as an additional therapeutic modality.


CRISPR-Act3.0-Based Highly Efficient Multiplexed Gene Activation in Plants.
CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)-mediated genome editing has revolutionized fundamental research and plant breeding. Beyond gene editing, CRISPR/Cas systems have been repurposed as a platform for programmable transcriptional regulation. Catalytically inactive Cas variants (dCas), when fused with transcriptional activation domains, allow for specific activation of any target gene in the genome without inducing DNA double-strand breaks. CRISPR activation enables simultaneous activation of multiple genes, holding great promise in the identification of gene regulatory networks and rewiring of metabolic pathways. Here, we describe a simple protocol for constructing a dCas9-mediated multiplexed gene activation system based on the CRISPR-Act3.0 system. The resulting vectors are tested in rice protoplasts. © 2022 Wiley Periodicals LLC. Basic Protocol 1: sgRNA design and construction of CRISPR-Act3.0 vectors for multiplexed gene activation Basic Protocol 2: Determining the activation efficiency of CRISPR-Act3.0 vectors using rice protoplasts.


Control of outbreaks of viral diarrhoea in hospitals--a practical approach.
Outbreaks of viral diarrhoea are common in hospitals, particularly in the geriatric and children's wards. Person-to-person spread is the most frequent mode of transmission of infection. Establishment of alerting mechanisms, liaison with laboratories with electron microscopy facilities for making the diagnosis, isolation of patients, use of appropriate disinfectants and maintaining good lines of communication are all important for successful control of these outbreaks.


Isolation of a non-thionein copper-binding protein from liver of copper-injected rats.
1. The characterization of a low molecular weight, non-thionein, Cu-binding protein isolated from rat liver is reported. The protein was isolated following chronic administration of Cu(NO3)2 using a combination of Sephadex G75 and Sephadex DEAE A-25 chromatography. The protein did not bind to fully equilibrated Sephadex DEAE which formed the basis of the isolation procedure. 2. The final protein pereparation was found to be homogenous by a variety of electrophoretic techniques and was distinguished from metallothionein on the basis of its behaviour on ion exhcange and electrophoretic systems, spectral properties, and amino acid composition and metal content. It contains 6.8% cysteine and was found to bind Cu in a ration of 1.5:1 based on a molecular weight of 11 000. 3. These results confirm the necessity to use techniques other than gel filtration alone to obtain adequate separation of low molecular weight metal-binding protein fractions.


Fetal alcohol effects: evidence of developmental impairment in the absence of immunotoxicity.
Pregnant CD-1 mice were intubated from Days 5-17 of gestation with an isocaloric solution of ethanol and/or maltose dextrins in 10% Bio-Serv liquid diet, at doses of 0, 6, and 9 g/kg/day. The control females were food-restricted so that their food consumption matched that of the high-dose females. At delivery, the pups were assigned surrogate mothers and litters were culled to a uniform litter size, when possible. Immediately following birth some pups were examined using a battery of behavioral/developmental tests to monitor postnatal development. At 6-8 weeks of age, other pups were evaluated for changes in immune function. Another group of pups was terminated at 12 weeks of age for hematology and clinical chemistry determinations and histological examination of selected organs. Postnatal developmental delays were seen in pinna detachment, surface righting reflex, eye opening, and incisor eruption. There was no characteristic pattern to immune alterations of the plaque forming cell response to a T-dependent antigen sheep red blood cells, delayed hypersensitivity, and T- and B-lymphocyte blastogenesis. Possible kidney pathology was indicated by a reduction in blood urea nitrogen in the offspring of females treated with 9 g/kg/day. No treatment-related effects were noted in those tissues which were examined histologically.


Titanium alloy pins versus stainless steel pins in external fixation at the wrist: a randomized prospective study.
Pin-track complications remain the most troublesome disadvantages of external fixation. The purpose of this study was to compare pin-related complications and pain levels after the use of external fixation for the stabilization of distal radial fractures with pins composed of two different materials. In a prospective trail 80 patients (320 pins) with unstable distal radial fracture were randomized for standard small AO-external fixator treatment with the use of identical pin geometry either composed of stainless-steel (Ss) (n = 40) or titanium alloy (Ti6Al4V) (n = 40). The patients were followed at biweekly intervals until the external fixators were removed (44 days after surgery). The patients were evaluated with regard to erythema, drainage, cellulitis, occurrence of pain at each pin-site, clinical or radiographic evidence of pin-loosening, the need for antibiotics, and the need for pin removal before fracture-healing due to infection. The complication rate was 21%, and age was found to be significantly associated with an increased risk of pin-loosening (p = 0.003). There were no significant differences among the two groups with regard to the prevalence of pin-site complications. However, the rate of premature removal of fixator because of severe pin-track infection (5% vs. 0%) and the rate of pin-loosening (10% vs. 5%) was higher in the Ss-pin group. Furthermore, pain values were significantly reduced in the Ti6Al4V-pin group. The use of Ti6Al4V-pin external fixator in distal radial fractures yields a trend of reduced pin-related complications and significantly reduced pain levels than does the Ss-pin fixator.


Aspiration cytodiagnosis of the breast with abundant acellular calcific material indicative of soft tissue calcinosis (a study of 3 cases).
Calcific deposits in soft tissue are rare and may clinically resemble a tumour. It seems feasible, therefore, to investigate them by the non-invasive technique of fine needle aspiration cytology (FNAC). In this study three cases with extensive accumulation of acellular calcific material in the breast are described in which FNAC was indicative of soft tissue calcinosis. In all cases routine mammogram had shown a partially cystic opacity. All other investigations were normal and no significant family or medical history was present. Cytopreparations in all cases showed only abundant acellular calcium. The patients had no further treatment and on follow up were clinically well with no changes. The cases are interesting, since the cytohistological findings in the aspirate sample appeared to be strongly indicative of soft tissue calcinosis.


A powerful partnership: researchers and patients working together to develop a patient-facing summary of clinical trial outcome data.
Availability of easy-to-understand patient-reported outcome (PRO) trial data may help individuals make more informed healthcare decisions. Easily interpretable, patient-centric PRO data summaries and visualizations are therefore needed. This three-stage study explored graphical format preferences, understanding, and interpretability of clinical trial PRO data presented to people with prostate cancer (PC). A 7-day online survey exploring people with PC's preferences for different PRO data presentations (stage 1; n = 30) informed development of a draft plain-language resource sheet containing PRO data. After refining for clarity during cognitive debriefing interviews (stage 2; n = 18), the final resource sheet was circulated to people with PC for broader feedback (stage 3; n = 45). Although participants expressed preferences for certain graphical formats (pie charts and bar charts), preference did not always associate with interpretability and overall message clarity. Iterative development (stages 1 and 2) led to a final resource sheet, which 91.1% of participants in stage 3 considered useful and informative, and 88.9% expressed interest in receiving similar resources in the future. Findings demonstrate PRO data are relevant to people with PC and highlights that targeted resource sheets can support patient-clinician discussions. Appropriate graphical formatting and use of plain-language text is essential for conveying interpretable PRO data. Data visualization preferences are context dependent. Resource sheets summarizing clinical trial PRO data can be helpful for decision-making in PC. Researchers and patients can work together to develop clear, relevant, sensitive, and understandable resource sheets, which equally consider patient priorities as well as those of scientists.


Multifaceted roles of TAK1 signaling in cancer.
Context-specific signaling is a prevalent theme in cancer biology wherein individual molecules and pathways can have multiple or even opposite effects depending on the tumor type. TAK1 represents a particularly notable example of such signaling diversity in cancer progression. Originally discovered as a TGF-β-activated kinase, over the years it has been shown to respond to numerous other stimuli to phosphorylate a wide range of downstream targets and elicit distinct cellular responses across cell and tissue types. Here we present a comprehensive review of TAK1 signaling and provide important therapeutic perspectives related to its function in different cancers.


Synthesis of optically active alpha-aminoalkyl alpha'-halomethyl ketone: a cross-Claisen condensation approach.
A simple and versatile method was developed for the synthesis of alpha-aminoalkyl alpha'-halomethyl ketone derivatives, which are useful intermediates of protease inhibitors. It involves selective halogenation of the alpha-position on a beta-ketoester, which is prepared by cross-Claisen condensation using N-protected amino acid ester. The title compound is obtained in high yield after decarboxylation of the alpha-halo-beta-ketoester.


How do providers discuss the results of pediatric exome sequencing with families?
This study provides preliminary data on the process and content of returning results from exome sequencing offered to children through one of the Clinical Sequencing Exploratory Research (CSER) projects. We recorded 25 sessions where providers returned diagnostic and secondary sequencing results to families. Data interpretation utilized inductive thematic analysis. Typically, providers followed a results report and discussed diagnostic findings using technical genomic and sequencing concepts. We identified four provider processes for returning results: teaching genetic concepts; assessing family response; personalizing findings; and strengthening patient-provider relationships. Sessions should reflect family interest in medical management and next steps, and minimize detailed genomic concepts. As the scope and complexity of sequencing increase, the traditional information-laden counseling model requires revision.


A Biomimetic Smart Nanoplatform as "Inflammation Scavenger" for Regenerative Therapy of Periodontal Tissue.
The functional reconstruction of periodontal tissue defects remains a clinical challenge due to excessive and prolonged host response to various endogenous and exogenous pro-inflammatory stimuli. Thus, a biomimetic nanoplatform with the capability of modulating inflammatory response in a microenvironment-responsive manner is attractive for regenerative therapy of periodontal tissue. Herein, a facile and green design of engineered bone graft materials was developed by integrating a biomimetic apatite nanocomposite with a smart-release coating, which could realize inflammatory modulation by "on-demand" delivery of the anti-inflammatory agent through a pH-sensing mechanism. In vitro and in vivo experiments demonstrated that this biocompatible nanoplatform could facilitate the clearance of reactive oxygen species in human periodontal ligament stem cells under inflammatory conditions via inhibiting the production of endogenous proinflammatory mediators, in turn contributing to the enhanced healing efficacy of periodontal tissue. Moreover, this system exhibited effective antimicrobial activity against common pathogenic bacteria in the oral cavity, which is beneficial for the elimination of exogenous pro-inflammatory factors from bacterial infection during healing of periodontal tissue. The proposed strategy provides a versatile apatite nanocomposite as a promising "inflammation scavenger" and propels the development of intelligent bone graft materials for periodontal and orthopedic applications.


Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection.
Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown. We carried out 16S rRNA microbiota profiling of infants in the first year of life from (1) a cross-sectional cohort of 89 RSV-infected infants sampled during illness and 102 matched healthy controls, and (2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection. We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs infected than of disease severity. Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition.


Prognostic significance of positive peritoneal cytology in endometrial carcinoma.
A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence.


7,8-Dimethyl-11H-indeno-[1,2-b]quinoxalin-11-one.
In the title compound, C17H12N2O, the mean planes of the indene ring and quinoxaline system (r.m.s. deviations = 0.0131 and 0.0082 Å) are approximately parallel to one another, making a dihedral angle of 1.2 (5)°. This means that the indeno-[1,2-b]quinoxaline ring is almost in the same plane (r.m.s. deviation = 0.0181 Å).


Mutational spectrum of TP53 gene correlates with nivolumab treatment efficacy in advanced gastric cancer (TP53MUT study).
Although nivolumab has a high efficacy, reliable biomarkers are needed to predict the efficacy. We evaluated the nivolumab efficacy according to the TP53 mutation in advanced gastric cancer patients enrolled in the GI-SCREEN project. Sequence data of tumour specimens and clinicopathological information of 913 patients with advanced gastric cancer who were enrolled between April 2015 and March 2017 were obtained from the GI-SCREEN database. The follow-up information of 266 patients treated with nivolumab was also provided. Among 266 patients treated with nivolumab, the objective response rate (ORR) of TP53 wild type (wt) patients (24.6%) was higher than that of TP53 mutant patients (14.8%). Among TP53 mutant patients, the ORR of the frameshift type tended to be higher than the transition and transversion type (23.1%, 13.6%, and 13.0%, respectively). The median progression-free survival (PFS) was statistically longer in TP53 wt patients than in mutant patients (3.3 vs 2.1 months, HR 1.4, 95% CI 1.1-1.9). Among TP53 mutant patients, PFS was statistically longer in the frameshift type than in the transversion type. Nivolumab showed better efficacy in TP53 wt patients than in mutant patients. Among TP53 mutant patients, the frameshift type may have efficacy from nivolumab treatment.