Quantitation of craniofacial anomalies in utero: fetal alcohol and Crouzon syndromes and thanatophoric dysplasia.
The study of fetal growth and development by ultrasound has been greatly facilitated in the past few years by the availability of anthropometric standards for the fetal body. Thus, the obstetrician is able to discern between normal and grossly abnormal, and even to quantitate certain fine fetal structures such as the face. This paper presents results obtained from a group of 5 patients referred to the Medical Center from private practices in Indianapolis, Indiana. Prenatal cephalometric analyses by ultrasound suggested the presence of craniofacial anomalies in all 5 cases. However, such defects were not detectable by routine ultrasonographic examination. A clinical examination after birth of each of these 5 patients suggested the following diagnoses: Fetal Alcohol Syndrome (FAS) in 2 individuals, Fetal Alcohol Effects (FAE) in one individual, Crouzon Syndrome (CS) in one patient, and Thanatophoric Dysplasia (TD) in one patient. In order to compare the craniofacial measurement values for each patient to normal standards, we developed Z-Score profiles and Pattern Variability Indexes (PVI) as described by Garn et al. [1984, 1985]. The values presented here support the idea that even mildly abnormal fetal craniofacial patterns are detectable by this relatively new application of ultrasound. At the present time, no conclusions can be made regarding the diagnostic accuracy of these patterns and profiles. However, the potential value of fetal cephalometry for documenting craniofacial dysmorphology is clearly indicated.


Occupational exposure to airborne solvents during nail sculpturing.
This study describes occupational exposure to acrylates and other solvents during nail sculpturing, including comparative measurements of the exposure using four different sculpturing methods: The acrylic method, the UV-gel method, the acrylic powder method and the resin method. Thirty-two nail technicians working in 22 different salons participated in the study. In total, 92 measurements were performed, comprising 70 solvent measurements and 22 measurements of ethyl 2-cyanoacrylate. The solvents most frequently present in all samples were acetone, ethyl acetate, toluene and n-butyl acetate, measured in 96%, 94%, 91% and 81% of the samples, respectively. The study shows that the overall solvent exposure was low, with all measurements calculated as the additive effect (n = 70) below 20% of the OEL (arithmetic mean 0.06 and range 0.01-0.19). No statistically significant difference between sculpturing methods were observed (p = 0.05).


Consumer product in vitro digestion model: Bioaccessibility of contaminants and its application in risk assessment.
This paper describes the applicability of in vitro digestion models as a tool for consumer products in (ad hoc) risk assessment. In current risk assessment, oral bioavailability from a specific product is considered to be equal to bioavailability found in toxicity studies in which contaminants are usually ingested via liquids or food matrices. To become bioavailable, contaminants must first be released from the product during the digestion process (i.e. become bioaccessible). Contaminants in consumer products may be less bioaccessible than contaminants in liquid or food. Therefore, the actual risk after oral exposure could be overestimated. This paper describes the applicability of a simple, reliable, fast and relatively inexpensive in vitro method for determining the bioaccessibility of a contaminant from a consumer product. Different models, representing sucking and/or swallowing were developed. The experimental design of each model can be adjusted to the appropriate exposure scenarios as determined by the risk assessor. Several contaminated consumer products were tested in the various models. Although relevant in vivo data are scare, we succeeded to preliminary validate the model for one case. This case showed good correlation and never underestimated the bioavailability. However, validation check needs to be continued.


Acute respiratory distress syndrome secondary to inhalation of chlorine gas in sheep.
Toxic industrial chemicals (TICs) are potential terrorist weapons. Several TICs, such as chlorine, act primarily on the respiratory tract, but knowledge of the pathophysiology and treatment of these injuries is inadequate. This study aims to characterize the acute respiratory distress syndrome (ARDS) caused by chlorine gas (Cl2) inhalation in a large-animal model. Anesthetized female sheep were ventilated with 300 L of a Cl2/air/oxygen mixture for 30 minutes. In phase 1 (n = 35), doses were 0 ppm (Group 1, n = 6); 120 ppm (Group 2, n = 6); 240 to 350 ppm (Group 3, n = 11); and 400 to 500 ppm (Group 4, n = 12). In phase 2 (n = 17), doses were 0 ppm (Group 5, n = 5); 60 ppm (Group 6, n = 5); and 90 ppm (Group 7, n = 7), and the multiple inert gas elimination technique (MIGET) was used to characterize the etiology of hypoxemia. Computed tomography (CT) scans were performed daily for all animals. In Phase 1, lung function was well maintained in Group 1; Cl2 caused immediate and sustained acute lung injury (PaO2-to-FiO2 ratio, PFR<3.0) in Group 2 and ARDS (PFR<2.0) in Groups 3 and 4. All animals in Groups 1 and 2 survived 96 hours. Kaplan-Meier analysis showed dose-related differences in survival (log-rank test, p < 0.0001). Logistic regression identified 280 ppm as the lethal dose 50%. CT and histopathology demonstrated lesions of both small airways and alveoli. In Phase 2, MIGET showed diversion of blood flow from normal to true-shunt lung compartments and, transiently, to poorly ventilated compartments. Cl2 causes severe, dose-related lung injury, with features seen in both smoke inhalation and in ARDS secondary to systemic disease. This model will be used to test new therapeutic modalities.


Electrochemistry/Photoelectrochemistry-Based Immunosensing and Aptasensing of Carcinoembryonic Antigen.
Recently, electrochemistry- and photoelectrochemistry-based biosensors have been regarded as powerful tools for trace monitoring of carcinoembryonic antigen (CEA) due to the fact of their intrinsic advantages (e.g., high sensitivity, excellent selectivity, small background, and low cost), which play an important role in early cancer screening and diagnosis and benefit people's increasing demands for medical and health services. Thus, this mini-review will introduce the current trends in electrochemical and photoelectrochemical biosensors for CEA assay and classify them into two main categories according to the interactions between target and biorecognition elements: immunosensors and aptasensors. Some recent illustrative examples are summarized for interested readers, accompanied by simple descriptions of the related signaling strategies, advanced materials, and detection modes. Finally, the development prospects and challenges of future electrochemical and photoelectrochemical biosensors are considered.


[Role of sonography in post-therapeutic control of tumors of the head and neck area].
During a 3 year period 572 high-resolution sonograms were carried out in the follow-up examinations of 348 patients who had been treated for ENT malignancy. Our experiences in routine application of this diagnostic method are described and illustrated by typical sonograms. Ultrasound findings of complications (chylous cysts, seromas, granulomas, fistulae) are demonstrated and the value and limitations of sonography in detecting lymph node metastases and primary recurrences are pointed out. In spite of the high accuracy of this method, it is not possible to differentiate between lymph nodes which are invaded by tumour and those with non-specific lymph adenopathy by echographic criteria only. We used ultrasound for follow-up studies on patients treated by irradiation or chemotherapy. Finally, sonography provided additional information on the exact site and size of the tumor. Real-time sonography is not time-consuming and can be applied without any special preparation of the patient. It has therefore become a satisfactory diagnostic method in the follow-up of patients who have undergone treatment of malignant tumors.


Assessment of response bias in mild head injury: beyond malingering tests.
The evaluation of response bias and malingering in the cases of mild head injury should not rely on a single test. Initial injury severity, typical neuropsychological test performance patterns, preexisting emotional stress or chronic social difficulties, history of previous neurological or psychiatric disorder, other system injuries sustained in the accident, preinjury alcohol abuse, and a propensity to attribute benign cognitive and somatic symptoms to a brain injury must be considered along with performances on specific measures of response bias. This article reviews empirically-supported tests and indices. Use of the likelihood ratio and other statistical indicators of diagnostic efficiency are demonstrated. Bayesian model averaging as a statistical technique to derive optimal prediction models is performed with a clinical data set.


Novel TGF-β inhibitors ready for prime time in onco-immunology.
Transforming Growth Factor (TGF)-β inhibitors have been in development for decades with the outmost results of being promising candidates. From the latest clinical results at the 2016 ASCO meeting converging evidences suggest that we have moved from promising to effective drug nominees.


[Hepatology. New research results in its significance for the understanding of liver diseases].
By two exemplary clinical situations--acute viral hepatitis, acute-phase reaction of the liver--the significance of basic research for the understanding of clinical phenomena and for the development of new diagnostic and therapeutic procedures is demonstrated. The very different phenomena following infection with the hepatitis-B-virus can be explained by the variation in the interactions of virus and liver cell, by the immune reaction of the host, and by mutants of the virus. The reaction of the liver to an extrahepatic infection is mediated by interleukin-6, and characterized by an alteration in protein metabolism. The synthesis of acute-phase proteins is increased. The proteins confine the local injury and establish the homeostasis of the organism.


[Different congenital forms of Steinert's myopathy: contribution of EMG].
The study of two families with myotonic dystrophy enables us to recall the existence of two congenital forms: one severe form with important neonatal hypotonia and one mild form with talipes equinovarus and intellectual deficiency. In both forms EMG detection is very often of the myogenic type. It confirms the diagnosis of myopathic disorder.


Hypertension and cardiovascular diseases in an epidemiological study in Hokkaido, Japan.
The present study describes the results from the 10-year follow-up data of a prospective epidemiological study for hypertension and cardiovascular diseases in two communities of rural agricultural districts in Hokkaido, Japan. The number of incidences of cerebrovascular accidents (CVAs) in persons who were normotensive, borderline hypertensive (BHT), untreated hypertensive (HT), well-controlled HT [blood pressure (BP) less than 150/90 mm Hg], and poorly controlled HT (BP greater than or equal to 150/90 mm Hg) were 0.46, 3.24, 4.17, 3.49, and 12.76 per 1,000 person-years. respectively: CVAs were markedly high in poorly controlled HT persons. The winter-summer mean BP differences in the first year were significantly and positively correlated with the differences in mean BP between the tenth and the first year, and were significantly higher in the progression to hypertension group than in the nonprogression group in both towns. Multivariate analysis indicated that the winter-summer mean BP difference was a significant variable for indication of progression to hypertension. From these results, we concluded that (a) good control of hypertension could considerably prevent CVA, (b) cold environment may contribute to the progression to hypertension, and (c) winter-summer variation in BP may predict the future course of BP.


Pharmacological Treatment in Presbyopia.
Pharmacological treatment of presbyopia may be an alternative for those who want a spectacle-free scenario and an easy-to-use method with lower risk of irreversible ocular adverse events. There are two main agents, miotics and lens softeners, investigated as agents for the pharmacological treatment. Miotic agents treat presbyopia by creating a pinhole effect which may increase the depth of focus at all working distances. The miotic agents have been studied for application to only one eye for monovision or both eyes. Their effect is temporary with common adverse events, such as headache and dim vision at nighttime, with no known long-term safety and efficacy. There have been studies on the miotic agents in combination with other agents for additive treatment effects or lessening adverse events, however, these combination effects are not clear. Lens softeners increase the elasticity of the lens, which is targeted at one of the etiologic mechanisms of presbyopia. There is only one lens softener being investigated in only a few trials. The results were inconclusive. The recent approval of 1.25% pilocarpine for treatment of presbyopia by the US FDA may be an important milestone for investigation of real-world data of pharmacological treatment of presbyopia.


Choosing the choice: Reflections on modelling decisions and behaviour in demographic agent-based models.
This paper investigates the issues associated with choosing appropriate models of choice for demographic agent-based models. In particular, we discuss the importance of context, time preference, and dealing with uncertainty in decision modelling, as well as the heterogeneity between agents in their decision-making strategies. The paper concludes by advocating empirically driven, modular, and multi-model approaches to designing simulations of human decision-making, given the lack of an agreed strategy for dealing with any of these issues. Furthermore, we suggest that an iterative process of data collection and simulation experiments, with the latter informing future empirical data collection, should form the basis of such an endeavour. The discussion is illustrated with reference to selected demographic agent-based models, with a focus on migration.


Matrin3: Disorder and ALS Pathogenesis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons in the brain and spinal cord. ALS is associated with protein misfolding and inclusion formation involving RNA-binding proteins, including TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS). The 125-kDa Matrin3 is a highly conserved nuclear DNA/RNA-binding protein that is implicated in many cellular processes, including binding and stabilizing mRNA, regulating mRNA nuclear export, modulating alternative splicing, and managing chromosomal distribution. Mutations in MATR3, the gene encoding Matrin3, have been identified as causal in familial ALS (fALS). Matrin3 lacks a prion-like domain that characterizes many other ALS-associated RNA-binding proteins, including TDP-43 and FUS, however, our bioinformatics analyses and preliminary studies document that Matrin3 contains long intrinsically disordered regions that may facilitate promiscuous interactions with many proteins and may contribute to its misfolding. In addition, these disordered regions in Matrin3 undergo numerous post-translational modifications, including phosphorylation, ubiquitination and acetylation that modulate the function and misfolding of the protein. Here we discuss the disordered nature of Matrin3 and review the factors that may promote its misfolding and aggregation, two elements that might explain its role in ALS pathogenesis.


Single-Particle Interferometric Reflectance Imaging Characterization of Individual Extracellular Vesicles and Population Dynamics.
Extracellular vesicles (EVs) are nanometer-sized vesicles with a lipid bilayer that are secreted by most cells. EVs carry a multitude of different biological molecules, including protein, lipid, DNA, and RNA, and are postulated to facilitate cell-to-cell communication in diverse tissues and organs. Recently, EVs have attracted significant attention as biomarkers for diagnostics and therapeutic agents for various diseases. Many methods have been developed for EV characterization. However, current methods for EV analysis all have different limitations. Thus, developing efficient and effective methods for EV isolation and characterization remains one of the crucial steps for this cutting-edge research field as it matures. Here, we provide a detailed protocol outlining a single-particle interferometric reflectance imaging sensor (SP-IRIS), as a method that is capable of detecting and characterizing EVs from unpurified biological sources and purified EVs by other methodologies. This advanced technique can be used for multi-level and comprehensive measurements for the analysis of EV size, EV count, EV phenotype, and biomarker colocalization.


PpASCL, a moss ortholog of anther-specific chalcone synthase-like enzymes, is a hydroxyalkylpyrone synthase involved in an evolutionarily conserved sporopollenin biosynthesis pathway.
Sporopollenin is the main constituent of the exine layer of spore and pollen walls. Recently, several Arabidopsis genes, including polyketide synthase A (PKSA), which encodes an anther-specific chalcone synthase-like enzyme (ASCL), have been shown to be involved in sporopollenin biosynthesis. The genome of the moss Physcomitrella patens contains putative orthologs of the Arabidopsis sporopollenin biosynthesis genes. We analyzed available P.patens expressed sequence tag (EST) data for putative moss orthologs of the Arabidopsis genes of sporopollenin biosynthesis and studied the enzymatic properties and reaction mechanism of recombinant PpASCL, the P.patens ortholog of Arabidopsis PKSA. We also generated structure models of PpASCL and Arabidopsis PKSA to study their substrate specificity. Physcomitrella patens orthologs of Arabidopsis genes for sporopollenin biosynthesis were found to be expressed in the sporophyte generation. Similarly to Arabidopsis PKSA, PpASCL condenses hydroxy fatty acyl-CoA esters with malonyl-CoA and produces hydroxyalkyl α-pyrones that probably serve as building blocks of sporopollenin. The ASCL-specific set of Gly-Gly-Ala residues predicted by the models to be located at the floor of the putative active site is proposed to serve as the opening of an acyl-binding tunnel in ASCL. These results suggest that ASCL functions together with other sporophyte-specific enzymes to provide polyhydroxylated precursors of sporopollenin in a pathway common to land plants.


Gross motor coordination in relation to weight status and age in 5- to 12-year-old boys and girls: a cross-sectional study.
The purpose of this study was to investigate differences in gross motor coordination in healthy-weight, overweight, and obese children of different ages. Using a cross-sectional design, data were collected in 954 Flemish primary school children (500 girls, 454 boys) stratified in consecutive age groups (5-7 years, 8-9 years, 10-12 years). Weight status (healthy-weight, overweight, obese) was defined according to the International Obesity Task Force body mass index (BMI) cut-off points for children. Gross motor coordination was assessed by means of the Körperkoordinationstest für Kinder (KTK). Childhood overweight and particularly obesity were found to result in poorer KTK performances (p < 0.001), with the most apparent effect of BMI on items requiring physical properties next to dynamic body coordination. Expressed as an age-related Motor Quotient (MQ), overall KTK performance was featured by a BMI × AGE interaction (p < 0.01). Healthy-weight children displayed similar MQs across age groups (p = 0.999). Overweight and obese children in the 10-12-year-old group showed significantly poorer motor coordination performance compared with the corresponding 5-7-year-old group (p < 0.01). Less than 20% of the healthy-weight participants was identified as being motor impaired, while that proportion increased to 43.3% and up to 70.8% in children with overweight and obesity, respectively. Results indicate that BMI-related differences in gross motor coordination were more pronounced as children belonged to an older age group. Although this outcome needs to be confirmed in future longitudinal research, it emphasizes the need of an early focus on motor skill improvement to encourage overweight and obese children to be physically active.


Eicosapentaenoic acid improves insulin sensitivity and blood sugar in overweight type 2 diabetes mellitus patients: a double-blind randomised clinical trial.
Diabetes mellitus is the most common metabolic disorder in humans, and its incidence is increasing rapidly worldwide. Although polyunsaturated fatty acids have beneficial effects on diabetes mellitus, previous data regarding the possible positive effects of n-3 fatty acids on glycaemic indices were inconclusive. We conducted a double-blind randomised clinical trial to determine the effects of eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, on overweight patients with type 2 diabetes mellitus (T2DM). This double-blind, placebo-controlled randomised clinical trial was conducted on a total of 67 overweight patients with T2DM for a duration of three months. Of these 67 patients, 32 received 2 g purified EPA daily, while 35 received a placebo of 2 g corn oil daily. The patients' fasting plasma glucose (FPG), serum insulin, glycated haemoglobin (HbA1c) and insulin sensitivity indices were assessed. After three months of EPA supplementation, the group that received EPA showed significant decreases in FPG (p < 0.001), HbA1c (p = 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR) (p = 0.032), when compared to the placebo group. EPA supplementation resulted in decreased serum insulin levels, with the levels between the EPA and placebo groups showing a significant difference (p = 0.004). The results of our study indicate that EPA supplementation could improve insulin sensitivity. It was able to decrease serum insulin, FPG, HbA1c and HOMA-IR. EPA could have beneficial effects on glycaemic indices in patients with T2DM.


Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation.
As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.


Development of human lymphohematopoietic stem and progenitor cells defined by expression of CD34 and CD81.
In this study, cord blood CD34(+) cells expressed CD81, a member of the transmembrane 4 superfamily, and were classified into 3 subpopulations on the basis of their expression levels: CD34(+)CD81(+), CD34(low)CD81(+), and CD34(+)CD81(high). The lymphohematopoietic activity of each subpopulation was then examined by using suspension and clonogenic cultures for hematopoietic potential, coculture with MS-5 cells for B-cell potential, organ cultures of thymus lobes from nonobese diabetic/severe combined immunodeficiency disease (NOD/SCID) fetal mice, coculture with stromal cells derived from NOD/SCID fetal-mouse liver tissue for natural killer (NK) cell and mast cell potentials, and xenotransplantation into NOD/SCID mice for long-term repopulating (LTR) ability. CD34(+)CD81(+) cells represented a heterogeneous population that had all the lymphohematopoietic activities, including NOD/SCID mouse-repopulating ability. CD34(low)CD81(+) cells were enriched in erythroid, megakaryocytic, and NK lineage potentials but had lost T-cell and B-cell potentials and LTR ability. The CD34(+)CD81(high) fraction was depleted of most lymphohematopoietic potentials except NK cell and mast cell potentials. Thus, along the differentiation cascade from CD34(+)CD81(+) lymphohematopoietic stem cells, an up-regulation of CD81 or a down-regulation of CD34 results in a change in lymphohematopoietic properties. CD81 may serve as a marker for defining developmental stages of lymphohematopoietic stem cells. (Blood. 2001;97:3755-3762)


[Abrikossoff's tumor--a rare differential diagnosis in neoplastic lesions of the esophagus].
We report the case of a 49-year-old male patient who was referred to our department in February 1998. Due to his complaints of dysphagia and retrosternal pain an upper gastrointestinal endoscopy was performed showing a polypoid lesion of the lower esophagus. This lesion presenting with a wide base and indurated surface was removed by endoscopic snare and forceps biopsies. Histologic and immunohistochemical analyses revealed this lesion to be a benign granular-cell tumor (Abrikossoff's tumor) which is considered to be of neuroectodermal origin. Abrikossoff's tumor is a rare differential diagnosis of polypoid lesions of the esophagus.


EEG Microstates in Early Phase Psychosis: The Effects of Acute Caffeine Consumption.
Individuals with schizophrenia use on average twice as much caffeine than the healthy population, but the underlying cortical effects of caffeine in this population are still not well understood. Using resting electroencephalography (EEG) data, we can determine recurrent configurations of the electric field potential over the cortex. These configurations, referred to as microstates, are reported to be altered in schizophrenia and can give us insight into the functional dynamics of large-scale brain networks. In the current study, we use a placebo-controlled, randomized, double-blind, repeated-measures design to examine the effects of a moderate dose of caffeine (200mg) on microstate classes A, B, C, and D in a sample of individuals within the first five years of psychosis onset compared to healthy controls. The results support the reduction of microstate class C and D, as well as the increase of microstate class A and B in schizophrenia. Further, acute caffeine administration appears to exacerbate these group differences by reducing class D, and increasing occurrences of class A and B states in the patient group only. The current results support the hypothesis of a microstate class D reduction as an endophenotypic marker for psychosis and provide the first descriptive account of how caffeine is affecting these microstate classes in an early phase psychosis sample.


Point Cloud Resampling by Simulating Electric Charges on Metallic Surfaces.
3D point cloud resampling based on computational geometry is still a challenging problem. In this paper, we propose a point cloud resampling algorithm inspired by the physical characteristics of the repulsion forces between point electrons. The points in the point cloud are considered as electrons that reside on a virtual metallic surface. We iteratively update the positions of the points by simulating the electromagnetic forces between them. Intuitively, the input point cloud becomes evenly distributed by the repulsive forces. We further adopt an acceleration and damping terms in our simulation. This system can be viewed as a momentum method in mathematical optimization and thus increases the convergence stability and uniformity performance. The net force of the repulsion forces may contain a normal directional force with respect to the local surface, which can make the point diverge from the surface. To prevent this, we introduce a simple restriction method that limits the repulsion forces between the points to an approximated local plane. This approach mimics the natural phenomenon in which positive electrons cannot escape from the metallic surface. However, this is still an approximation because the surfaces are often curved rather than being strict planes. Therefore, we project the points to the nearest local surface after the movement. In addition, we approximate the net repulsion force using the K-nearest neighbor to accelerate our algorithm. Furthermore, we propose a new measurement criterion that evaluates the uniformity of the resampled point cloud to compare the proposed algorithm with baselines. In experiments, our algorithm demonstrates superior performance in terms of uniformization, convergence, and run-time.


There Is Nothing So Theoretical as a Good Method.
This article documents two facts that are provocative in juxtaposition. First: There is multidecade durability of theory controversies in psychology, demonstrated here in the subdisciplines of cognitive and social psychology. Second: There is a much greater frequency of Nobel science awards for contributions to method than for contributions to theory, shown here in an analysis of the last two decades of Nobel awards in physics, chemistry, and medicine. The available documentation of Nobel awards reveals two forms of method-theory synergy: (a) existing theories were often essential in enabling development of awarded methods, and (b) award-receiving methods often generated previously inconceivable data, which in turn inspired previously inconceivable theories. It is easy to find illustrations of these same synergies also in psychology. Perhaps greater recognition of the value of method in advancing theory can help to achieve resolutions of psychology's persistent theory controversies.


Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.
Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.


Rhinolith in the concha bullosa as a rare location: a case report.
The presence of a rhinolith is a rare condition, which can cause long-standing symptoms, such as rhinorrhea, foul-smelling discharge, nasal obstruction, and headache. A rhinolith is usually easily diagnosed by a clinical examination and a paranasal computed tomographic scan. Rhinoliths are usually found in nasal cavities, but rare locations are also possible. We report a patient who was evaluated in our clinic for nasal obstruction, headache, and snoring symptoms. A clinical examination showed no major findings, but a paranasal computed tomographic scan of coronal sections showed a hyperdense mass within the right concha bullosa. A rhinolith in the concha bullosa is a rare condition. Our case is the third case of a rhinolith in the concha bullosa to be reported in the literature.


Identification of extended-spectrum β-lactamase and quinolone resistance genes in Escherichia coli isolated from hospital wastewater from central India.
To investigate the presence of antibiotic resistance genes (ARGs), related to commonly used β-lactams and quinolones, in Escherichia coli present in hospital wastewater in central India. Cefotaxime- and ciprofloxacin-resistant E. coli isolates from hospital-associated wastewater samples were collected from two tertiary care hospitals in the Ujjain district of India during 2008-09. The presence of bla(CTX-M), bla(TEM,) bla(SHV), qnrA, qnrB, qnrS, aac(6')-Ib-cr and qepA genes was detected by PCR and sequencing. Twenty-five E. coli isolates were extended-spectrum β-lactamase (ESBL) positive. bla(CTX-M-15) and bla(TEM-1) genes were identified in 21 and 16 ESBL-positive isolates by PCR, respectively. Amongst 30 fluoroquinolone-resistant E. coli isolates, aac(6')-Ib-cr was detected in 27 isolates, qnrA in 1 isolate, qnrB in 2 isolates and qepA in 3 isolates. bla(CTX-M-15,) bla(TEM-1), aac(6')-Ib-cr, qnrA, qnrB and qepA genes are present in E. coli occurring in hospital wastewater in central India.


Development and validation of a selective and rapid LC-MS-MS method for the quantification of abacavir in human plasma.
A simple, precise, and rapid liquid chromatography-tandem mass spectrometry method is developed and validated for the quantification of abacavir, a nucleoside reverse transcriptase inhibitor. Abacavir and granisetron (internal standard) were isolated from 100 muL human plasma by liquid-liquid extraction in ethyl acetate and dichloromethane (90:10, v/v). The chromatographic separation is achieved on Gemini C(18) analytical column (150 mm x 4.6mm, 5-mum particle size) under isocratic conditions at a flow rate of 1.0 mL/min. The parent --> product ion transitions for abacavir (m/z 287.2-->191.2) and internal standard (m/z 313.1-->138.2) were monitored on a triple quadrupole mass spectrometer operating in the multiple reaction monitoring (MRM) and positive ion mode. The linearity of the method for abacavir is established in the range of 29.8-9318 ng/mL with an analysis time of 2.0 min. Acceptable precision and accuracy were obtained for concentrations over the standard curves studied. The mean recovery and process efficiency of analyte obtained at three quality control levels was 86.8% and 87.9%, respectively. The application of this method for routine measurement of plasma abacavir concentration is demonstrated by a pharmacokinetic and/or bioequivalence study conducted in 28 healthy volunteers for a 300 mg tablet formulation under fasting condition.


[Treatment of dislocated lenses in patients with Marfan's syndrome using vitrectomy and intraocular lenses].
To evaluate results of surgical complex treatment of lens dislocation in Marfan syndrome cases. Nineteen eyes of 13 patients were operatively treated for lens dislocation. Pars plana vitrectomy was done in all eyes. Dislocated lenses were removed by lensectomy in 5 eyes and with an intracapsular method in 14 eyes. The scleral fixation technique was used for primary posterior chamber intraocular lens implantation in 18 eyes, and one eye remained aphakic. Time of observation ranged between 6 and 71 months (mean 3.5 years). All eyes achieved improvement in visual acuity or good preoperative visual acuity was maintained. The vision between 6/6 and 6/8 was achieved in 14 patients. There were no serious intraoperative or early postoperative complications. Retinal detachment appeared in two eyes in a long observation time and it was successfully operatively treated. The not good visual results were due to amblyopia (n = 2), complications of retinal detachment surgery (n = 2) and glaucomatous optic disc atrophy coexisting with macular degeneration (n = 1). Pars plana vitrectomy and primary scleral-fixated IOL implantation gives quick and good visual rehabilitation in adult patients with Marfan's syndrome. The described surgical method is complex and need a prolonged operative time, but gives very good functional results and very few complications.


Analysis of the expression of murine glutaryl-CoA dehydrogenase: in vitro and in vivo studies.
Glutaric acidemia type I (GAI) is an autosomal recessive organic acidemia caused by a mutation in the gene encoding glutaryl-CoA dehydrogenase (GCD). Clinically, GAI is characterized by progressive dystonia, resulting from degeneration of neurons in the caudate and putamen nuclei of the striatum. In an attempt to understand the basis for the specific neuropathology in GAI, we have analyzed the expression of the murine GCD gene using both in vitro and in vivo approaches. Transfection studies mapped the mouse GCD promoter to a 500-bp region of DNA 5' of the translation start site. The promoter lacks a TATA consensus sequence, but includes possible binding sites for several transcription factors with roles in the regulation of nuclear genes encoding mitochondrial proteins. Western blot and RT/PCR analyses of mouse tissues demonstrated that GCD is ubiquitously expressed, with the highest levels of expression in liver and kidney, consistent with its role in amino acid oxidation. Expression in multiple regions of the brain was also detected by Western blotting. Based on these results we conclude that the specific neuropathology associated with GCD deficiency in GAI cannot be accounted for by its expression pattern.


[Human papillomavirus infections and carcinoembryonic antigen expression in cervix intra-epithelial neoplasia of intermediate grade].
The objective was to investigate a possible correlation between expression of carcino-embryonic antigen (CEA) and human papilloma virus (HPV) infection in moderate cervical intraepithelial neoplasia (CIN II). We examined the correlation of the incidence in different cases and the topographical correspondence. CEA was detected by immunohistochemistry and HPV infection was diagnosed by in situ hybridization (including typing of 6/11, 16/18, 31/33) and well-established histologic criteria. Samples from 32 women were examined. In 29 cases (91%) CEA was expressed, mainly in the superficial layer of the epithelium. Twenty-three tissue samples (72%) showed HPV infection. There was topographical correspondence of the two markers (mainly in superficial cell layers) but no correlation concerning the incidence of HPV infection or particular HPV subtypes. The highest prevalence of HPV was found in dysplasias of the large-cell reserve cell type.


Executive functioning in chronic alcoholism and Korsakoff syndrome.
Korsakoff syndrome (KS) is characterized by dense anterograde and retrograde amnesia. There is often a temporal gradient to the retrograde amnesia, with earlier memories more readily recalled than recent memories. Executive functioning has also been found to be impaired in KS. However, research comparing executive functioning between chronic alcoholics (AL) and patients with KS has been relatively sparse to date. In a group comparison design, executive functioning in 15 KS patients and 16 chronic alcoholic patients was assessed using the Behavioural Assessment of the Dysexecutive Syndrome test (BADS) and other secondary measures. The KS group was found to be significantly more impaired than the AL group on overall performance on the BADS (p < .05). Korsakoff patients are significantly more impaired in executive functioning than non-Korsakoff chronic alcoholics. We thank the participants of the study and also acknowledge the support of the University of Nottingham, particularly Nadina Lincoln, and the North East London NHS Foundation Trust. We are also very grateful to the anonymous reviewers of earlier drafts of this manuscript for their invaluable comments.


Cerebral dysfunction revealed by EEG mapping in the schizoform epileptic psychosis.
Twenty schizophrenia-like psychotic patients suspected of epilepsy were explored using EEG techniques (recordings in the 10-20 International System, source derivation, EEG mapping and EEG spectral reaction mapping by photic and somesthetic stimulation). In 16 of them, latent epileptic disorders were found. EEG spiking foci could be located either: (a) in temporal, (b) fronto-basal, or (3) in the sagittal-line leads. A corresponding associated dysrhythmia was clearly revealed by EEG mapping. On EEG spectral reaction mapping a suggestive aberrant displacement of the area of maximal sensory response was found. These EEG disorders were in significant relation with the psychotic syndrome observed in the respective group of patients: (a) patients with fronto-basal (temporal anterior) foci were prevalently paranoid; (b) patients with temporal lobe foci were prevalently depressive; (c) patients with sagittal line (singular) foci presented a predominantly expansive, hypomanic behaviour. The study shows the importance of normal fronto-limbic circuits for the preservation of mental health.


Late open conversion after endovascular repair of abdominal aneurysm failure: Better and easier option than complex endovascular treatment.
Conversion to open repair becomes the last option in case of endovascular repair of abdominal aneurysm failure, when radiological interventional procedures are unfeasible. While early conversion to open repair generally derives from technical errors, aetiopathogenesis and results of late conversion to open repair often remain unclear. We report data from our Institute's experience on late conversion to open repair. Twenty-two late conversion to open repairs out of 435 consecutive patients treated during a 18 years period, plus two endovascular repair of abdominal aneurysms performed in other centres, are analysed. The indication for conversion to open repair was aneurysm enlargement because of type I, type III, type II endoleak and endotension. Even if seven cases (23%) had shown an initial aneurysmal shrinkage, in a later phase, the sac began to enlarge again. In 12 patients, conversion to open repair was the last chance after unsuccessful secondary endovascular procedures. Three cases (12.5%) were treated in emergency. Aortic cross-clamping was only infrarenal in 10 cases, only or temporarily suprarenal in 14 and temporarily supraceliac in 9 cases, for 19 total and 5 partial endograft excisions. Two patients died for Multiple Organ Failure (MOF), on 42nd (endovascular repair of abdominal aneurysm infection) and 66th postoperative day. No other conversion to open repair-related deaths or major complications were revealed by follow-up post-conversion to open repair (mean: 68 months ranging from 24 to 180 months). Late conversion to open repair is often an unpredictable event. It represents a technical challenge: specifically, the most critical point is the proximal aortic clamping that often temporarily excludes the renal circulation. In our series, conversion to open repair can be performed with a low rate of complications. In response to an endovascular repair of abdominal aneurysm failure, before applying complex procedures of endovascular treatment, conversion to open repair should be taken into account.


Inverse Association Between Variety of Proteins With Appropriate Quantity From Different Food Sources and New-Onset Hypertension.
The relationships of the variety and quantity of different sources of dietary proteins with hypertension remain uncertain. We aimed to investigate associations between the variety and quantity of proteins intake from 8 major food sources and new-onset hypertension among 12 177 participants from the China Health and Nutrition Survey. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for types and quantity of proteins. New-onset hypertension was defined as systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥90 mm Hg, or physician-diagnosed hypertension or receiving antihypertensive treatment, during the follow-up. During a median follow-up of 6.1 years, there were U-shaped associations of percentages energy from total, unprocessed or processed red meat-derived, whole grain-derived, and poultry-derived proteins with new-onset hypertension; an reverse J-shaped association of fish-derived protein with new-onset hypertension; L-shaped associations of eggs-derived and legumes-derived proteins with new-onset hypertension; and an reverse L-shaped association of refined grain-derived protein with new-onset hypertension (all P values for nonlinearity <0.001). That is, for each protein, there is a window of consumption (appropriate level) where the risk of hypertension is lower. Moreover, a significantly lower risk of new-onset hypertension was found in those with higher variety score of protein sources (per score increment, hazard ratio, 0.74 [95% CI, 0.72-0.76]). In summary, there was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset hypertension.


Identification and validation of protein targets of bioactive small molecules.
Identification and validation of protein targets of bioactive small molecules is an important problem in chemical biology and drug discovery. Currently, no single method is satisfactory for this task. Here, we provide an overview of common methods for target identification and validation that historically were most successful. We have classified for the first time the existing methods into two distinct and complementary types, the 'top-down' and 'bottom-up' approaches. In a typical top-down approach, the cellular phenotype is used as a starting point and the molecular target is approached through systematic narrowing down of possibilities by taking advantage of the detailed existing knowledge of cellular pathways and processes. In contrast, the bottom-up approach entails the direct detection and identification of the molecular targets using affinity-based or genetic methods. A special emphasis is placed on target validation, including correlation analysis and genetic methods, as this area is often ignored despite its importance.


[Physical Activity Guidelines for Chinese (2021)].
The Physical Activity Guidelines for Chinese(2021) consists of seven parts, including general guidelines, children aged 2 years and below, children aged 3-5 years, children and adolescents aged 6-17 years, adults aged 18-64 years, the elderly aged 65 years and above, and patients with chronic diseases. The development of this guideline is initiated by the Bureau for Diseases Prevention and Control of the National Health Commission, led by the Chinese Center for Disease Control and Prevention as well as China Institute of Sport Science, and finalized by the Composing and Editorial Board of Physical Activity Guidelines for Chinese.


Use of folate-conjugated imaging agents to target alternatively activated macrophages in a murine model of asthma.
Pro-inflammatory macrophages play a prominent role in such autoimmune diseases as rheumatoid arthritis, Crohn's disease, psoriasis, sarcoidosis, and atherosclerosis. Because pro-inflammatory macrophages have also been shown to overexpress a receptor for the vitamin folic acid (i.e., folate receptor beta; FR-β), folate-linked drugs have been explored for use in imaging and treatment of these same diseases. To determine whether allergic inflammatory disorders might be similarly targeted with folate-linked drugs, we have examined the characteristics of macrophages that are prominent in the pathogenesis of asthma. We report here that macrophages from the lungs of mice with experimental allergic asthma express FR-β. We further document that these FR-β(+) macrophages coexpress markers of alternatively activated (M2-type) macrophages, including the mannose receptor and arginase-1. Finally, we demonstrate that folate-conjugated fluorescent dyes and radioimaging agents can be specifically targeted to these asthmatic lung macrophages, with little uptake by macrophages present in healthy lung tissue. These data suggest strategies for the development of novel diagnostic agents for the imaging of asthma and other diseases involving alternatively activated macrophages.


The effect of electrolyzed strong acid aqueous solution on hemodialysis equipment.
We reported the high effectiveness of electrolyzed strong acid aqueous solution (ESAAS) in cleaning hemodialysis lines. Although ESAAS has a strong bactericidal action, one concern is its strong acidity. It has a pH of 2.3-2.7, more than 1,000 mV in oxidation-reduction potential (ORP), and 10-50 ppm of available chlorine. The possibility of metal corrosion, degradation of synthetic resins, chorine gas emission, or dissolving calcium carbonate (CaCO3) deposits due to ESAAS's acidity was tested using in vitro experiments. The bactericidal and antiviral effects of various ESAAS's were also tested. Metal corrosion and synthetic resin degradation, although they occurred, were not serious. There were no problems with chlorine gas emission and dissolving of CaCO3 deposits. Each type of ESAAS showed almost the same bactericidal and antiviral effect, but in some cases differences were observed.


Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis.
Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for several diseases in consideration of both anti-inflammatory and immunosuppressive activity but, if used at high doses for prolonged periods, it can determine the systemic effects characteristic of Cushing's syndrome. In addition to signs and symptoms of hypercortisolism, patients on chronic GC therapy are at risk to develop tertiary adrenal insufficiency after the reduction or the withdrawal of corticosteroids or during acute stress. This effect is mediated by the negative feedback loop on the hypothalamus-pituitary-adrenal (HPA) axis, which mainly involves corticotropin-release hormone (CRH), which represents the most important driver of adrenocorticotropic hormone (ACTH) release. In fact, after withdrawal of chronic GC treatment, reactivation of CRH secretion is a necessary prerequisite for the recovery of the HPA axis. In addition to the well-known factors which regulate the degree of inhibition of the HPA during synthetic GC therapy (type of compound, method of administration, cumulative dose, duration of the treatment, concomitant drugs which can increase the bioavailability of GCs), there is a considerable variation in individual physiology, probably related to different genetic profiles which regulate GC receptor activity. This may represent an interesting basis for possible future research fields.


Acute stroke management in the local general hospital.
The majority of stroke patients are treated in local general hospitals. Despite this fact, little is known about stroke care in these institutions. We sought to investigate the status quo of acute stroke management in nonspecialized facilities with limited equipment and resources. Four general hospitals located in smaller cities of a rural area in Germany participated in this study. The 4 hospitals were similar in structure and technical equipment; none had a CT scanner in-house. We reviewed the medical records of every stroke patient hospitalized in 1 of the 4 hospitals within a period of 8 weeks within 1 year. We collected data of a total of 95 patients at all 4 hospitals. The frequency of diagnostic tests was low: at least 1 CT scan was obtained in only 36.8% of all cases, whereas diagnostic methods available in-house were used more frequently, such as Doppler ultrasound (49.0%), echocardiography (42.3%), and 24-hour ECG registration (48.4%). Each hospital had a different therapeutic approach. Main therapeutic options were the use of pentoxyfilline (0% to 90.5%), osmodiuretics (0% to 90%), piracetam (0% to 93.3%), and hydroxyethylstarch (4.8% to 30%). Medication for long-term secondary prevention was given to 69.8% of all patients. This study provides one of the few data samples reflecting stroke care in smaller general hospitals. The findings demonstrate a partially suboptimal level of care in these institutions. To achieve future improvements, extended human and technical resources as well as research for stroke care should not be restricted to academic stroke centers.


Mycobiota of the air in hospital rooms and the fungal colonisation of tracheostomy tubes used by patients diagnosed with larynx cancer--preliminary research.
A tracheotomy tube, as well as the stoma through which it is inserted into the patient's throat, may represent a potential risk of fungal infections for patients suffering from larynx cancer. The study was aimed at evaluating the influence of the hospital room environment on the fungal colonisation of tracheotomy tubes in the case of patients diagnosed with larynx cancer and operated on in the Laryngology ward. The mycological research was carried out in the rooms of the Laryngology ward, from which 105 air samples were collected. Twenty-two Portex and metal tracheostomy tubes collected from 13 patients diagnosed with larynx cancer. Fungi were cultured on 15 tracheostomy tubes: moulds were isolated from 3 of these tubes, and fungi belonging to the genus Candida from the remaining 12. The simultaneous occurrence of the same moulds in the air and on the tracheotomy tubes was observed only in one case (Aspergillus flavus). In conclusion, the same moulds observed in the air can sometimes also be found on the tracheotomy tubes used by patients diagnosed with larynx cancer. Yeast-like fungi are isolated from tracheotomy tubes much more frequently than moulds, and this requires further mycological research.


Viral growth factor- and STAT3 signaling-dependent elevation of the TCA cycle intermediate levels during vaccinia virus infection.
Metabolism is a crucial frontier of host-virus interaction as viruses rely on their host cells to provide nutrients and energy for propagation. Vaccinia virus (VACV) is the prototype poxvirus. It makes intensive demands for energy and macromolecules in order to build hundreds and thousands of viral particles in a single cell within hours of infection. Our comprehensive metabolic profiling reveals profound reprogramming of cellular metabolism by VACV infection, including increased levels of the intermediates of the tri-carboxylic acid (TCA) cycle independent of glutaminolysis. By investigating the level of citrate, the first metabolite of the TCA cycle, we demonstrate that the elevation of citrate depends on VACV-encoded viral growth factor (VGF), a viral homolog of cellular epidermal growth factor. Further, the upregulation of citrate is dependent on STAT3 signaling, which is activated non-canonically at the serine727 upon VACV infection. The STAT3 activation is dependent on VGF, and VGF-dependent EGFR and MAPK signaling. Together, our study reveals a novel mechanism by which VACV manipulates cellular metabolism through a specific viral factor and by selectively activating a series of cellular signaling pathways.


Escalating systemic exposure of continuous infusion topotecan in children with recurrent acute leukemia.
To determine the maximum-tolerated systemic exposure (MTSE) and exposure-limiting toxicity of continuous infusion topotecan in children with recurrent acute leukemia. Patients received escalating levels of topotecan systemic exposure as measured by steady-state topotecan lactone concentration (Css). Samples obtained within the first 24 hours were measured by high-pressure liquid chromatography (HPLC) for topotecan. A two-compartment model was fit to the data using a Bayesian algorithm. Css was calculated for each patient; if it differed by more than 20% of target, a new dosage was begun within 6 hours. Follow-up concentrations were obtained as well as serial plasma samples postinfusion. Toxicity and evidence of activity were assessed after each course. Thirteen boys and five girls received 23 courses of topotecan. Target Css ranged from 1.0 to 5.3 ng/mL (topotecan doses, 0.5 to 3.3 mg/m2/d). Nineteen of 23 courses were within +/- 20% of target after adjustment (range, 77% to 139%). The MTSE was 4.0 ng/mL, and mucositis was exposure-limiting at 5.3 ng/mL. A significant relation between topotecan lactone Css and the severity of mucositis was observed. Myelosuppression was experienced but was not considered exposure-limiting. One complete response and one partial response were noted. The MTSE for continuous infusion topotecan was 4.0 ng/mL. Responses were noted at Css comparable to those producing responses in a severe combined immunodeficiency (SCID) mouse model. Further studies of topotecan are warranted.


Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination.
Activation of phosphatidylinositol-3-kinase (PI3K)-AKT and Kirsten rat sarcoma viral oncogene homologue (KRAS) can induce cellular immortalization, proliferation, and resistance to anticancer therapeutics such as epidermal growth factor receptor inhibitors or chemotherapy. This study assessed the consequences of inhibiting these two pathways in tumor cells with activation of KRAS, PI3K-AKT, or both. We investigated whether the combination of a novel RAF/vascular endothelial growth factor receptor inhibitor, RAF265, with a mammalian target of rapamycin (mTOR) inhibitor, RAD001 (everolimus), could lead to enhanced antitumoral effects in vitro and in vivo. To address this question, we used cell lines with different status regarding KRAS, PIK3CA, and BRAF mutations, using immunoblotting to evaluate the inhibitors, and MTT and clonogenic assays for effects on cell viability and proliferation. Subcutaneous xenografts were used to assess the activity of the combination in vivo. RAD001 inhibited mTOR downstream signaling in all cell lines, whereas RAF265 inhibited RAF downstream signaling only in BRAF mutant cells. In vitro, addition of RAF265 to RAD001 led to decreased AKT, S6, and Eukaryotic translation initiation factor 4E binding protein 1 phosphorylation in HCT116 cells. In vitro and in vivo, RAD001 addition enhanced the antitumoral effect of RAF265 in HCT116 and H460 cells (both KRAS mut, PIK3CA mut); in contrast, the combination of RAF265 and RAD001 yielded no additional activity in A549 and MDAMB231 cells. The combination of RAF and mTOR inhibitors is effective for enhancing antitumoral effects in cells with deregulation of both RAS-RAF and PI3K, possibly through the cross-inhibition of 4E binding protein 1 and S6 protein.


Response to chilling of tomato seedlings and cells in suspension cultures.
Tomato cell suspensions and seedlings (Lycopersicon esculentum) responded comparably when exposed to chilling temperatures (10 C or below). Seedling growth and cellular activities related to cell viability and culture growth (triphenyltetrazolium chloride reduction, fluoroscein diacetate uptake, and hydrolysis) were sharply diminished below 10 C. Arrhenius plots of the respiratory O(2) consumption by both seedlings and cell suspensions had a break at 10 C, as is characteristic for chilling-sensitive species. The acyl chains that were found in the phospholipids of both cell cultures and seedlings were similar. These results indicate the potential usefulness of plant suspension cultures for studies of chilling injury.


Uncoupling Proteins: Do They Have a Role in Body Weight Regulation?
Several members of the mitochondrial carrier protein family are classified as uncoupling proteins. In contrast to the uncoupling protein specific to brown adipose tissue (UCP1), the physiological role of skeletal muscle uncoupling proteins (UCP2 and UCP3) in weight regulation seems more closely associated with the regulation of lipids as fuel substrate than as mediators of adaptive thermogenesis.


Cerebrospinal fluid drainage and dynamics in the diagnosis of normal pressure hydrocephalus.
Because of the difficulty in distinguishing idiopathic normal pressure hydrocephalus (INPH) from other neurodegenerative conditions unrelated to cerebrospinal fluid (CSF) dynamics, response to CSF shunting remains highly variable. We examined the utility of CSF drainage and CSF pressure (Pcsf) dynamics in predicting response to CSF shunting for patients with INPH. Fifty-one consecutive INPH patients underwent continuous lumbar Pcsf monitoring for 48 hours followed by 72 hours of slow CSF drainage before ventriculoperitoneal shunting. Response to CSF drainage and B-wave characteristics were assessed via multivariate proportional-hazards regression analysis. Improvement in 1, 2, or all 3 INPH symptoms was observed in 35 (69%), 28 (55%), and 11 (22%) patients, respectively, after CSF shunt implantation by 12 months after surgery. A positive response to CSF drainage was found to be an independent predictor of shunt responsiveness (relative risk, 0.30; 95% confidence interval, 0.09-0.98; P = 0.05). There was no difference in Pcsf wave characteristics between the shunt-responsive and -nonresponsive groups, regardless of whether 1-, 2-, or 3-symptom improvement was used to define response to CSF shunting. In this study of 51 INPH patients who underwent Pcsf monitoring with waveform analysis and CSF drainage followed by shunt surgery, there was no correlation between specific Pcsf wave characteristics and objective symptomatic improvement after shunt placement. Pcsf monitoring with B-wave analysis contributes little to the diagnostic dilemma with INPH patients. Clinical response to continuous CSF drainage over a 72-hour period suggests a high likelihood of shunt responsiveness.


Gender Differences in Attending Physicians' Feedback to Residents: A Qualitative Analysis.
Prior research has shown a gender gap in the evaluations of emergency medicine (EM) residents' competency on the Accreditation Council for Graduate Medical Education (ACGME) milestones, yet the practical implications of this are not fully understood. To better understand the gender gap in evaluations, we examined qualitative differences in the feedback that male and female residents received from attending physicians. This study used a longitudinal qualitative content analysis of narrative comments by attending physicians during real-time direct observation milestone evaluations of residents. Comments were collected over 2 years from 1 ACGME-accredited EM training program. In total, 1317 direct observation evaluations with comments from 67 faculty members were collected for 47 postgraduate year 3 EM residents. Analysis of the comments revealed that the ideal EM resident possesses many stereotypically masculine traits. Additionally, examination of a subset of the residents (those with 15 or more comments, n = 35) showed that when male residents struggled, they received consistent feedback from different attending physicians regarding aspects of their performance that needed work. In contrast, when female residents struggled, they received discordant feedback from different attending physicians, particularly regarding issues of autonomy and assertiveness. Our study revealed qualitative differences in the kind of feedback that male and female EM residents received from attending physicians. The findings suggest that attending physicians should endeavor to provide male and female residents with consistent feedback and guard against gender bias in their perceptions of residents' capabilities.


Structural and genetic diversity in antibody repertoires from diverse species.
The antibody repertoire is the fundamental unit that enables development of antigen specific adaptive immune responses against pathogens. Different species have developed diverse genetic and structural strategies to create their respective antibody repertoires. Here we review the shark, chicken, camel, and cow repertoires as unique examples of structural and genetic diversity. Given the enormous importance of antibodies in medicine and biological research, the novel properties of these antibody repertoires may enable discovery or engineering of antibodies from these non-human species against difficult or important epitopes.


Quality Evaluation and Mathematical Modelling Approach to Estimate the Growth Parameters of Total Viable Count in Sausages with Different Casings.
The growth kinetics for the total viable count (TVC) in sausages with modified hog casings (treated by surfactant solutions and slush salt with lactic acid), natural hog casings and sheep casings as a function of the storage time (up to 50 days) were studied for the first time. The growth of TVC was fitted by the Baranyi model, and the maximum specific growth rate, lag time and initial and final cell populations were estimated via DMFit. The coefficient of determination of the Baranyi model reached 0.94, 0.77 and 0.86 for sausages stuffed in modified hog casings (MHC), control hog casings (CHC) and natural sheep casings (NSC), respectively. The experimental data for the initial populations were 4.69 ± 0.10 log cfu/g for MHC, 4.79 ± 0.10 log cfu/g for CHC and 3.74 ± 0.14 log cfu/g for NSC, whilst the predicted initial cell populations for MHC, CHC and NSC were 4.81 ± 0.20 log cfu/g, 5.19 ± 0.53 log cfu/g and 3.74 ± 0.54 log cfu/g, respectively. Their shelf lives can also be predicted. The results show that the average pH value of MHC samples (6.96 ± 0.01) was significantly lower than that of CHC (7.09 ± 0.01) and NSC (7.05 ± 0.02) samples at day 50 (p < 0.05). Sausages with CHC possessed a significant higher water holding capacity (99.48 ± 0.14%) at d 29 than those with MHC (97.40 ± 0.46%) and NSC (98.55 ± 0.17%) (p < 0.05). On the last day, the average moisture content for samples with NSC (38.30 ± 3.23%) was significantly higher than that for those with MHC (29.38 ± 2.52%) and CHC (29.15 ± 1.16%) (p < 0.05).


A 3D fibrous scaffold inducing tumoroids: a platform for anticancer drug development.
The development of a suitable three dimensional (3D) culture system for anticancer drug development remains an unmet need. Despite progress, a simple, rapid, scalable and inexpensive 3D-tumor model that recapitulates in vivo tumorigenesis is lacking. Herein, we report on the development and characterization of a 3D nanofibrous scaffold produced by electrospinning a mixture of poly(lactic-co-glycolic acid) (PLGA) and a block copolymer of polylactic acid (PLA) and mono-methoxypolyethylene glycol (mPEG) designated as 3P. Cancer cells cultured on the 3P scaffold formed tight irregular aggregates similar to in vivo tumors, referred to as tumoroids that depended on the topography and net charge of the scaffold. 3P scaffolds induced tumor cells to undergo the epithelial-to-mesenchymal transition (EMT) as demonstrated by up-regulation of vimentin and loss of E-cadherin expression. 3P tumoroids showed higher resistance to anticancer drugs than the same tumor cells grown as monolayers. Inhibition of ERK and PI3K signal pathways prevented EMT and reduced tumoroid formation, diameter and number. Fine needle aspirates, collected from tumor cells implanted in mice when cultured on 3P scaffolds formed tumoroids, but showed decreased sensitivity to anticancer drugs, compared to tumoroids formed by direct seeding. These results show that 3P scaffolds provide an excellent platform for producing tumoroids from tumor cell lines and from biopsies and that the platform can be used to culture patient biopsies, test for anticancer compounds and tailor a personalized cancer treatment.


Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.
We report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment in which the critical linkage interval spans a genetic distance of 5.41 cM and a physical distance of 15.1 Mb that overlaps the DFN2 locus. Mutation screening of the PRPS1 gene in this family and in the three previously reported DFN2 families identified four different missense mutations in PRPS1. These mutations result in a loss of phosphoribosyl pyrophosphate (PRPP) synthetase 1 activity, as was shown in silico by structural analysis and was shown in vitro by enzymatic activity assays in erythrocytes and fibroblasts from patients. By in situ hybridization, we demonstrate expression of Prps1 in murine vestibular and cochlea hair cells, with continuous expression in hair cells and postnatal expression in the spiral ganglion. Being the second identified gene associated with X-linked nonsyndromic deafness, PRPS1 will be a good candidate gene for genetic testing for X-linked nonsyndromic hearing loss.


Generation of visual representations.
The visual confusability of uppercase letters was manipulated in a successive same-different task to study the conditions under which visual generation from auditory inputs would occur and to investigate the figural specificity of the generated representations. Prior experiments have shown that visual confusions do occur when the initial stimulus is auditory and the second one is visual, which indicates that auditory stimuli can be encoded into visual forms. There has been some suggestion, however, that the generated visual code may have been too abstract to differentiate between the two cases in which letters can appear. In the present experiment, although the confusion effect was not eliminated when the subjects had no advance knowledge regarding the case in which the visual stimulus would appear, the marked confusion effect obtained when the visual stimulus was an uppercase letter was substantially attenuated when the letter appeared in lowercase. This was taken to indicate that the visual characteristics of a generated visual representation may be relatively specific. The results also suggested that subjects may wait until after the second stimulus is presented before they generate the visual representation of the initial auditory stimulus.


Diagnosis experiences from 50 hepatitis B patients in Chongqing, China: a qualitative study.
The aim of this study was to provide recommendations for reducing the impact of hepatitis B infection on patients with chronic hepatitis B by describing their experiences during the diagnosis process. We conducted face-to-face interviews with 50 hepatitis B patients recruited by convenient sampling from an infectious diseases department of a teaching hospital in Chongqing, China from July to August 2019. Thematic analysis framework included interviewees' social demographic characteristics, diagnosis approach, signs and symptoms before diagnosis, feelings after diagnosis, and doctor's instructions. Most patients first detected hepatitis B through various types of physical examinations when the patients were asymptomatic or had only mild symptoms. Most patients were shocked, scared, or overwhelmed when they were diagnosed with hepatitis B. They were able to remember the doctor's instructions about maintaining a healthy lifestyle, but not impressed by the doctor's advice about regular follow-up liver function tests. The lack of regular follow-up has caused irreversible damage to some patients. Most patients are passively diagnosed with hepatitis B due to their lack of awareness on active hepatitis B prevention. Patients need professional mental health care to overcome the negative emotions that following the diagnosis. Physicians' instruction should emphasize the importance of regular follow-up liver function tests in addition to a healthy lifestyle.


Evaluation of KGF, EGF, VEGF, bcl-2, IL-6 and ki67 expression in oral epithelium adjacent to bisphosphonate-related osteonecrosis and florid osseous dysplasia: a comparative immunohistochemical study.
The aim of this study was to compare the expression of proliferative markers and apoptosis-associated proteins in the oral mucosa adjacent to bone sequestrum associated with osteonecrosis (ON) of the jaws and florid osseous dysplasia (OD). Oral mucosal samples derived from surgical procedures performed for treatment of ON and OD (10 cases each) were retrieved. Histologic analysis was done on hematoxylin and eosin-stained slides; immunohistochemical reactions against epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), Bcl-2 protein, interleukin-6 (IL-6), and Ki-67 antigen were performed with the immunoperoxidase technique. The epithelium was hyperplastic in 60% and 22% of ON and OD samples, respectively. Cytoplasmic EGF and KGF expression; Bcl-2, VEGF, and IL-6 expressions; and the mean epithelial proliferative index were not statistically different between the 2 groups. Membranous EGF expression was more evident in samples showing hyperplastic epithelium. Exposure to bisphosphonates did not alter the expression of KGF, EGF, VEGF, Bcl-2, IL-6, and the epithelial proliferating index in comparison with inflamed oral mucosa not exposed to bisphosphonates.


The Colour Violet: Chemistry or Physics?
Violet iridescence in purple emperor butterflies arises from structural order in the wing-scales in contrast to the chemical pigments responsible for some violet colours in Nature.


Understanding the Female African American Facial Aesthetic Patient
BACKGROUND: The patient populations seeking facial aesthetic treatments is expanding in terms of racial, ethnic, and cultural diversity. While treatment of facial aging patterns among white women is well-documented, far less information describes the aesthetic needs of the African American patient. OBJECTIVE: An online study was conducted to survey facial aesthetic concerns and treatment priorities among US-based population of African American women. MATERIALS AND METHODS: A total of 401 female African American participants ages 30 to 65 years reported their attitudes toward facial aging, current facial conditions, most bothersome facial areas and areas most/least likely to be treated first, awareness of treatment options and their consideration rates, and motives and barriers factoring into consideration of injectable treatments. RESULTS: Uneven skin tone/color (57%) and dark circles under the eyes (48%) were the most frequently-reported facial concerns. Other common bothersome facial areas affected by signs of aging were the submental area, periorbital area, forehead lines, and chin. Similarly, areas given greater priority with respect to future treatment included the periorbital area, submental area, and forehead lines. With advancing age, priorities heightened for the mid and lower facial areas, which included the nasolabial folds, chin, and oral commissures. Although the majority of participants would consider injectables, cost, and safety/side effects were cited as frequent concerns. CONCLUSION: For African American women, concerns about facial aging may be less about fine lines and wrinkles caused by increasing skin laxity, and more about pigmentary concerns and shifts in underlying soft tissue volume. J Drugs Dermatol. 2019;18(9):858-866.


[Diagnostic approach for acquired and isolated third cranial nerve palsy: 18 case reports].
The aim of this work was to establish a clinical diagnostic flow chart for third nerve palsy. [corrected] We report a series of 18 patients with third nerve palsy seen at the department of ophthalmology in the Marseille North Hospital between 1997 and 1999. All patients had a complete clinical examination and were classified into four clinic types. An etiological diagnosis was given in all cases after a systematic approach, including first intention MRI. Three patients presented abnormal pupil reflex secondary to an aneurysm diagnosed by carotid angiography; the MRI was pathological in two cases. The 15 other patients had pupil sparing. Among them, eight patients had a total external involvement secondary to diabetes mellitus; the MRI suggested an ischelic origin in four cases (50%) showing nuclear infarctus. In seven cases the external involvement was incomplete secondary to multiple etiologies: demyelinating illness, traumatic lesions, orbital tumor, metastasis or myasthenia gravis. The MRI contributed to diagnosing four cases. The MRI must be systematically used in all the patients with isolated third nerve palsy, except for patients with pupil sparing associated with total external involvement. Ischemic etiology was the rule: simple clinical surveillance is proposed, total spontaneous regression being the norm.


Steatosis of indeterminate cause in a pediatric group: is it a primary mitochondrial hepatopathy?
In children, hepatic steatosis may be related to inborn errors of metabolism (IEMs) or to non-alcoholic fatty liver disease (NAFLD). The aim of this study was to assess and characterize steatosis of indeterminate cause through morphological and morphometric analysis of liver tissue. Cross-sectional study at the Departments of Pathology of Faculdade de Ciências Médicas, Universidade Estadual de Campinas (FCM-Unicamp) and Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (FMB-Unesp). Eighteen consecutive liver biopsies obtained from 16 patients of ages ranging from 3 months to 12 years and nine months that were inserted in a database in the study period were analyzed using optical microscopy and transmission electron microscopy. Through electron microscopy, the mitochondrial density and mean mitochondrial surface area were determined in hepatocytes. Ten patients ranging in age from 1 to 14 years were used as a control group. "Pure" steatosis was detected, unaccompanied by fibrosis or any other histological alteration. Microvesicular steatosis predominated, with a significant increase in mean mitochondrial surface area. Microvesicular steatosis may be related to primary mitochondrial hepatopathy, especially due to reduction of β-oxidation or partial stagnation of oxidative phosphorylation. For these reasons, this form of steatosis (which should not be called "pure") is likely to represent an initial stage in the broad spectrum of NAFLD. We have drawn attention to cases of steatosis in the pediatric group, in which the microvesicular form predominates, since this may be associated with mitochondrial disorders.


Comparison of the inoue and single balloon techniques during long term percutaneous balloon mitral valvoplasty follow-up. Analysis of risk factors for death and major events.
To analyze the long term evolution of patients undergoing percutaneous balloon mitral valvoplasty comparing the Inoue and Balt single balloon methods, and to identify predictors of death and major events (death, repeat balloon mitral valvoplasty or mitral valve surgery). The follow-up for the single and Inoue balloon groups were 54 +/- 31 (1 to 126) months and 34 +/- 26 (2 to 105) months, respectively (p < 0.0001). The Balt single balloon was used in 254 (84.1%) patients and the Inoue balloon in 48 (15.9%). The following data were found for the Inoue and single balloon groups, respectively: age, 36.9 +/- 10.4 (19 to 63) years and 38.0 +/- 12.6 (13 to 83) years (p = 0.5769); echocardiographic score, 7.5 +/- 1.3 points and 7.2 +/- 1.5 points (p = 0.1307); female gender, 72.9% and 87.4% (p = 0.0097); atrial fibrillation, 10.4% and 16.1% (p = 0.4275); mortality during follow-up, 2.1% and 4.3% (0.6984); and major events, 8.3% and 17.7% (p = 0.1642). Univariate and Kaplan-Meier curve analyses revealed no differences between the Inoue and Balt single balloon techniques in relation to survival and major event free survival. In the multivariate analysis, age > 50 years and an echocardiographic score > 8 were independent predictors of death; and an echocardiographic score > 8 and post operative mitral valve area < 1.50 cm(2) were predictors for major events. No differences were found in the long term evolution of patients undergoing the Inoue versus the single balloon technique. Predictors of death and/or major events were: age > 50 years, echocardiographic score > 8 and mitral valve area < 1.50 cm(2) after the procedure.


In-migration and diphtheria mortality among children in the Sundsvall region during the epidemics of the 1880s.
While many works have examined urban mortality rates in nineteenth-century Europe, much less attention has been placed on disease patterns in the peripheral areas surrounding these population centers. This study demonstrates that during the Swedish diphtheria epidemic of the early 1880s, mortality rates among children living in the industrial parishes on the outskirts of the town of Sundsvall exceeded those found in the town itself. The epidemic was fueled by the mass in-migration of laborers and their families from distant provinces who sought work in the region's sawmills. Thus, in contrast to the common pattern of disease entering through a port city and spreading into the interior, in this case diphtheria followed the paths of migrants through the rural parishes of the Sundsvall region to the sawmills and then finally into the town itself. This spatial pattern was reversed in the late fall when migrants returned home. Conflicts within the medical profession regarding how best to prevent or contain diphtheria, popular suspicion and distrust of local physicians, and the introduction of the disease into a population with no prior contact with it, all helped increase the number of young corpses.


[Effectiveness of endovideosurgical technology in diagnosis and treatment of patient with hemoblastoses].
Results of using endovideosurgical technology for diagnosis and treatment of hematological diseases in 123 patients are described. It was shown that laparoscopy is highly effective parallel with ultrasound examination and tomography in a complex diagnostic program. Using the developed diagnostic algorithm was shown to be very expedient for making primary diagnosis, recurrent diseases and control of the effectiveness of chemotherapy. Endovideosurgical interventions were shown to be less invasive and safe in hematological patients. Laparoscopy is an alternative to diagnostic laparotomy which is often used in this group of patients.


[Expression of the gene coding for a thermostable alpha-amylase from Pyrococcus furious in Chiamydomonas reinhardtii chloroplast ].
Thermostable alpha-amylase from Pyrococcus furious is an important industrial enzyme in brewing and alcohol production. Eexpression of the thermostable a-amylase in plants can reduce greatly costs in the production of alcohol using crop plants. A chloroplast expression vector, p64A, containing the thermostable alpha-amylase gene from Pyrococcus furious, was constructed with clpP-trnL-petB-chlL-rp123-rpl2 as Chlamydomonas reinhardtii plastid homologous recombinant fragments and spetinomycin-resistant aadA gene as select marker. The plasmid p64A was transferred into the chloroplast genome of C. reinhardtii by the biolistic method. Nine independently transformed lines were obtained by 100 mg/L spectinomycin selection. PCR amplification, Southern blot analysis of the transgene and cultivation in the dark all showed that the a-amylase gene had been integrated into chloroplast genome of C. reinhardtii. The activity of amylase expressed in the chloroplast of C. reinhardtii was detected by amylase activity assay and found to be as high as 77.5 u/g fresh weight of cells. These experimental results demonstrated the possibility of using transgenic chloroplasts of plant as bioreactors for production of industrial enzymes.


Sound analysis in an in vitro endotracheal tube model.
Complete endotracheal tube obstruction is a medical emergency, and partial occlusion causes increased breathing rates and failure to wean off mechanical ventilation. Partial occlusion may be underestimated due to the lack of proper detection methods. We tested whether the sound of an endotracheal tube could be used to detect an endotracheal tube obstruction using an in vitro model. An endotracheal tube was connected to a ventilator on one end and a test lung on the other. Sounds were recorded with a microphone located inside the endotracheal tube via a connector. During mechanical ventilation, we changed the endotracheal tube internal diameter from 5.0 to 8.0 mm and different grades of obstruction at different sites were used along the tube. Sound energy was compared among the different conditions. The energy of endotracheal tube sounds was positively correlated with the internal diameter and negatively correlated with the degree of obstruction. The rate of decline in energy differed with obstruction location. When the obstruction was more distal, the rate of decline in endotracheal sound energy was more rapid. Changes in the sound of an endotracheal tube can be used to detect an obstruction. Further studies are needed for clinical application.


Psychosocial implications of pregnancy after infertility.
Couples who become pregnant after being infertile experience profound psychosocial changes related to the "identity shift" that they must make from infertility to pregnancy. They often straddle the two worlds of infertility and fertility, not feeling completely a part of either world. Nurses play a key role in counseling, educating, and supporting these individuals and couples during the antepartum, intrapartum, and postpartum periods. This article discusses current knowledge about pregnancy after infertility and the implications for nursing practice.


Encapsulation response of Ciona intestinalis (Ascidiacea) to intratunical erythrocyte injection. I. The inner capsular architecture.
Previous studies on the ascidian Ciona intestinalis have shown that an encapsulation response is experimentally induced by inserting vertebrate erythrocytes into the tunic, which initiates a massive inflammatory cell infiltration to isolate the injured area. Several hemocytes contribute to capsule formation, destruction of the foreign cells, tunic regeneration, and wound healing. The fine features of some inflammatory cell types are described although the complete capsular structure is not yet reported. Accordingly, the present investigation further examines various aspects of this cellular reaction against erythrocytes and, for the first time, presents the involvement of extratunical circulating hemocytes and mantle epithelium in capsule formation.


[Cultivation and nitrogen removal characteristics of deammonifition granules].
An SBR reactor seeded with anaerobic granular sludge was started up to enrich deammonifition bacteria and investigate its nitrogen removal characteristics. Research results showed that deammonification granular sludge could be cultivated successfully with firstly enriched ANAMMOX microorganisms in anaerobic condition and then controlled the dissolved oxygen in the SBR reactor between 0.3 and 0.5 mg/L, in which the maximum total nitrogen removal rate reach 75.3%. When the Ca and P concentrations of the medium exceeded the necessary quantity, salt precipitation was observed and interfered with microbial activity and caused a decrease of the nitrogen removal rate of the reactor system. Salt precipitation was avoided by diminishing adequately the Ca and P concentrations of the medium during the following operation period, and the total nitrogen removal rate restored.


Isolation of a bacterial strain from the gut of the fish, Systomus sarana, identification of the isolated strain, optimized production of its protease, the enzyme purification, and partial structural characterization.
The present study focuses on the isolation of Bacillus thuringiensis bacterium from the gut of fresh water fish, Systomus sarana, the innovative optimization of culture parameters to produce maximum protease enzyme, by the isolated bacterium, and the elucidation of peptide profile of the protease. And the experimental data and results were authenticated through the response surface method (RSM) and Box-Behnken design (BBD) model. During the RSM optimization, the interaction of the highest concentrations (%) of 2.2 maltose, 2.2 beef extract, and 7.0 pH, at 37 °C incubation, yielded a maximum protease enzyme of 245 U/ml by the fish gut-isolated, B. thuringiensis. The spectral analysis of the obtained enzyme revealed the presence of major functional groups at the range of 610-3852 cm-1 viz., alkynes (-C≡C-H: C-H stretch), misc (P-H phosphine sharp), α, β-unsaturated aldehydes, and through PAGE analysis, its molecular weight was determined as 27 kDa. The enzyme's MALDI-TOF/MS analysis revealed the presence of 15 peptides from which the R.YHTVCDPR.L peptide has been found to be a major one. The fish gut-isolated bacterium, B. thuringiensis, SS4 exhibited the potential for high protease production under the innovatively optimized culture conditions, and the obtained result provides scope for applications in food and pharmaceutical industries.


Finding common ground: patient-centeredness and evidence-based chronic illness care.
Health outcomes for patients with major chronic illnesses depend on the appropriate use of proven pharmaceuticals and other therapeutic technologies, and effective self-management by patients. Effective chronic illness care then bases clinical decisions on the best, rigorous scientific evidence, or evidence-based medicine. Effective support for patient self-management includes efforts to increase patient participation in care and collaborative goal-setting and planning of treatment. These interventions appear somewhat consistent with recent conceptualizations of patient-centered care. The consistent delivery of proven therapies and information and support for self-management requires practice systems organized for that purpose. The Chronic Care Model is a compilation of those practice system changes shown to improve chronic care. This paper explores the concept of patient-centeredness and its relationship to the Chronic Care Model. We conclude that the Model is both evidence-based and patient-centered and that these can be properties of health systems, and not just of individual practitioners.


Synthesis of Citrate-Coated Penta-twinned Palladium Nanorods and Ultrathin Nanowires with a Tunable Aspect Ratio.
Green and scalable methodologies for the preparation of metal nanoparticles with fine control of shape and size are of high interest in many areas including catalysis, nanomedicine, and nanodiagnostics. In this contribution, we describe a new synthetic method for the production of palladium (Pd) penta-twinned nanowires and nanorods utilizing sodium citrate, formic acid, ascorbic acid, and potassium bromide (KBr) in water, without the use of surfactants or polymers. The synthesis is green, fast, and without the need of complex setups. Interestingly, a microwave-assisted scale-up process has been developed. The combination of a synthetic protocol for seeds and the seed-mediated growth process allows us to synthesize nanorods and nanowires by modulating the concentration of KBr. The synthesized nanomaterials have been physicochemically characterized. High-resolution transmission electron microscopy shows that the nanorods and nanowires have a penta-twinned structure enclosed by {100} lateral facets. Moreover, the absence of sticky molecules or toxic byproducts guarantees the biocompatibility of the nanomaterials, while leaving the surface clean to perform enzymatic activities.


[Resonance-scattering spectral determination of H2O2 using rhodamine 6G association particles].
Under the conditions of 0.02 mol x L(-1) HCl-4.0 x 10(-4) mol x L(-1) KI-1.6 x 10(-5) mol x L(-1) Mo(VI), there is a fluorescence peak at 540 nm and a synchronous fluorescence peak at 540 nm for Rhodamine 6G (RhG). When there exists H2O2, it reacts with I- to form I3-. RhG and I3- combine to form an ion association particle. The particles exhibit three resonance scattering peaks at 320 nm, 400 and 595 nm respectively. And there is fluorescence quenching at 540 nm. H2O2 concentration in the range of 0.068-34 microg x mL(-1) is proportional to the resonance scattering peak at 400 nm. And a new resonance scattering spectral method has been described for the determination of H2O2 in water samples. The spectral results have verified that the formation of (RhG-I3)n association particles and the interface are the main factor that causes the fluorescence quenching and resonance scattering effects.


Spinal Muscular Atrophy: Autopsy Based Neuropathological Demonstration.
Spinal muscular atrophy (SMA) encompasses a group of disorders with loss of spinal motor neurons.The report describes the neuropathological findings including brain and spinal cord at autopsy in a five-and-half-month-old boy with suspected type 1 SMA. The anterior motor neurons, Clarke's column at all the levels of spinal cord showed neuronal loss and degeneration while neurons at all the deep grey nuclei were preserved apart from variable degree anoxic changes. Skeletal muscle biopsy revealed features of neurogenic atrophy consistent with SMA. A differential diagnosis like storage disorders was excluded using electron microscopy. No extra-neural manifestations were seen. Neuropathological features at autopsy have seldom been reported in the literature.


Corticosteroid suppression of trauma-induced hyaluronan in rabbit cornea and aqueous.
Corneal and aqueous hyaluronan have recently been shown to react in response to several different types of trauma, including cataract surgery. In order to find ways to influence the reaction, we have evaluated the effect of topical dexamethasone (Isopto-Maxidex, Alcon Universal Ltd, Fort Worth, Tex) or indomethacin (Confortid, Dumex Ltd, Copenhagen, Denmark) on the postoperative hyaluronan concentration in rabbit cornea and aqueous after extracapsular lens extraction. The drugs were administered as topical eye drops three times daily. The hyaluronan concentration in rabbit cornea and aqueous after extracapsular lens extraction was measured with a radioligand assay. Dexamethasone treatment (1 mg/mL) significantly suppressed the increase in corneal hyaluronan seen after extracapsular lens extraction, 2 (p < or = 0.0022) and 3 weeks (p < or = 0.0002) after surgery, while indomethacin did not induce any significant difference at 2 weeks. When the dexamethasone concentration was lowered to 0.1 and 0.2 mg/mL, there was still a significant decrease (p < or = 0.009) in hyaluronan concentration, but at lower concentrations of dexamethasone (0.01 and 0.02 mg/mL), no significant decrease was seen. The increase in aqueous hyaluronan concentration seen 2 days after surgery in untreated eyes was significantly lowered by both dexamethasone (p < or = 0.0076) and indomethacin (p < 0.036). Dexamethasone lowers reactive corneal and aqueous hyaluronan concentration in vivo after extracapsular lens extraction.


Copper-Catalyzed Cross-Nucleophile Coupling of β-Allenyl Silanes with Tertiary C-H Bonds: A Radical Approach to Branched 1,3-Dienes.
Described herein is a distinctive approach to branched 1,3-dienes through oxidative coupling of two nucleophilic substrates, β-allenyl silanes, and hydrocarbons appending latent functionality by copper catalysis. Notably, C(sp3)-H dienylation proceeded in a regiospecific manner, even in the presence of competitive C-H bonds that are capable of occurring hydrogen atom transfer process, such as those located at benzylic and other tertiary sites, or adjacent to an oxygen atom. Control experiments support the intermediacy of functionalized alkyl radicals.


Clinical approach to re-irradiation for recurrent diffuse intrinsic pontine glioma.
We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes. Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015-September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan-Meier method and log-rank test were used for survival analysis. Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6-41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage. Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.