Treatment of Mentally Ill Offenders in Nine Developing Latin American Countries.
The prevalence of psychiatric conditions among prisoners in Latin America is greatly underestimated, and because of the lack of awareness about mental illness among service providers in Latin American prisons, oftentimes these conditions go unrecognized or are not treated properly. In the worst-case scenarios, human rights violations occur. Despite the high levels of need, many prisoners have not received adequate or timely treatment. The sparse existing literature documents prison conditions throughout Latin American countries, ranging from poor to extremely harsh, overcrowded, and life threatening. Most prison systems do not meet international prison standards. The information on forensic mental health services and the treatment of offenders with mental illness have been less extensively studied and compared with forensic practices in developed American nations. This study analyzes the existing literature on forensic psychiatry, focusing on nine socioeconomically developing nations in Latin America, to improve understanding of treatment approaches for offenders with mental illness and identify emerging themes. A review was conducted and data were included in regression analyses to investigate information relative to the treatment of offenders with mental illness and its interaction with the mental health system.


Binding specificity of guinea pig anti-alpha-keratin polypeptide sera on human keratinocytes: comparison of their receptors with those of human epidermal cytoplasmic antibodies.
Experimental anti-keratin polypeptide sera (KPS) which were prepared by immunizing guinea pigs with the P1 polypeptide (molecular weight: 67 0000 dalton) of alpha-keratin of normal human stratum corneum, were shown to react in immunofluorescence only to cell cytoplasmic antigen of the upper layers of the epidermis. No staining was detected in the basal layer. An immunolabeling performed on free epidermal cells obtained after trypsinization demonstrated by electron microscopy that receptors for KPS were tonofilaments. Minor proportions of negative cells containing tonofilaments and numerous melanosomes detected might correspond to the basal cells. An IF pattern similar to that seen with KPS was observed with some human epidermal cytoplasmic sera (ECS). However, reciprocal blocking tests performed on both rabbit lip and normal human skin with the different sera showed no inhibition. No cross-reaction was detected by immunodiffusion test between whole purified alpha-keratin and human ECS. In electron microscopy, the receptors for ECS appeared not to be keratin-like, but were located on a granular part of the peripheral keratinocyte cytoplasm. These findings confirmed two steps (basal and malphighian layers) in epidermal differentiation defined by antigenic markers and especially by the alpha-keratin component of MW 67 000 d present in normal stratum corneum.


Longitudinal machine learning model for predicting systolic blood pressure in patients with heart failure.
Systolic blood pressure (SBP) strongly indicates the prognosis of heart failure (HF) patients, as it is closely linked to the risk of death and readmission. Hence, maintaining control over blood pressure is a vital factor in the management of these patients. In order to determine significant variables associated with changes in SBP over time and assess the effectiveness of classical and machine learning models in predicting SBP, this study aimed to conduct a comparative analysis between the two. This retrospective cohort study involved the analysis of data from 483 patients with HF who were admitted to Farshchian Heart Center located in Hamadan in the west of Iran, and hospitalized at least two times between October 2015 and July 2019. To predict SBP, we utilized a linear mixed-effects model (LMM) and mixed-effects least-square support vector regression (MLS-SVR). The effectiveness of both models was evaluated based on the mean absolute error and root mean squared error. The LMM analysis revealed that changes in SBP over time were significantly associated with sex, body mass index (BMI), sodium, time, and history of hypertension (P-value < 0.05). Furthermore, according to the MLS-SVR analysis, the four most important variables in predicting SBP were identified as history of hypertension, sodium, BMI, and triglyceride. In both the training and testing datasets, MLS-SVR outperformed LMM in terms of performance. Based on our results, it appears that MLS-SVR has the potential to serve as a viable alternative to classical longitudinal models for predicting SBP in patients with HF.


[11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells].
Recent years, the incidence and mortality of prostate cancer have increased dramatically in China. At earlier stages, most diagnosed prostate cancers are responsive to androgen depletion treatment, yet, nearly all patients will eventually progress to metastatic androgen-independent prostate cancer (AIPC), which still has no effective therapeutic method or drug to deal with. 11'-Deoxyverticillin A (C42) belongs to the family of epipolythiodioxopiperazines (ETPs), an interesting class of fungal toxins that inhibit farnesyl transferase. Compounds holding such a property have been explored as putative anticancer agents. In this study, using PC3M cells, an AIPC cell line, we investigated the effect of the compound on apoptosis and explored the underlying mechanism. It revealed that C42 markedly enhanced the activity of caspase-3/7 and increased the accumulation of the cleaved PARP, all of which are the markers of apoptosis. It also revealed that C42 either decreased cell viability or inhibited the growth of PC3M cells. Moreover, we observed that the loss of cell viability and cell growth inhibition induced by C42 were both time- and dosage dependent. Taken together, we indicated that C42 can induce caspase-dependent apoptosis in AIPC cells, and the results presented here will broaden our knowledge about the molecular mechanisms by which C42 exerts its anticancer activity, and future work in this direction may provide valuable information in the development of these compounds into effective cancer therapeutic strategies against androgen-independent prostate cancer.


Infantile hemangiopericytoma of the tongue-Efficacy of ex utero intrapartum treatment procedure and combined-modality therapy.
Here we present an extremely rare case of giant infantile hemangiopericytoma (HPC) of the tongue diagnosed prenatally by fetal ultrasonography and MR imaging. Due to airway stenosis, the patient was delivered by the ex utero intrapartum treatment (EXIT) procedure at 36 weeks of pregnancy. Initial diagnosis was infantile hemangioma based on physical examination, diagnostic imaging and the high incidence of hemangioma. The tumor was resistant to conservative treatments. Due to severe tumor hemorrhage, the nutrient vessel was embolized by endovascular treatment on the 73th day after birth. Two days after embolization, a hemiglossectomy was performed. Histological analysis after surgery diagnosed infantile HPC with microscopically positive stumps. After receiving adjuvant chemotherapy, the patient has had no recurrence after 53 months with normal speech and swallowing function resulting in normal growth. Our findings support that infantile HPC is one of the differential diagnosis of infantile hemangioma. The EXIT procedure could be effective for infants with upper respiratory stenosis by head and neck tumor diagnosed prenatally. Though complete resection is required for infantile HPC, our report suggests that a conservative surgical approach followed by adjuvant chemotherapy should be used for giant head and neck infantile HPC.


Chelatococcus thermostellatus sp. nov., a new thermophile for bioplastic synthesis: comparative phylogenetic and physiological study.
The poly(3-hydroxybutyrate), PHB, accumulating thermophilic strain MW9(T), isolated from an aerobic organic waste treatment plant, was characterized by detailed physiological and phylogenetic studies. The strain is a Gram-stain-negative, rod shaped, non-spore forming member of Alphaproteobacteria. It shows optimum growth at 50 °C. Based on 16S rRNA gene sequence similarity, the strain together with five very similar isolates, was affiliated to the genus Chelatococcus (Ibrahim et al. in J Appl Microbiol 109:1579-1590, 2010). Rep-PCR genomic fingerprints and partial dnaK gene sequence also revealed that these isolates are very similar, but differ from other Chelatococcus type strains. The major fatty acids were similar to those of other strains of the genus Chelatococcus. DNA-DNA hybridization of strain MW9(T) with Chelatococcus species type strains revealed 11.0-47.7 % relatedness. G+C content of DNA was 67.1 mol%, which is comparable with the other strains of Chelatococcus species. The physiological and phenotypic characteristics of the new strain MW9(T) are sufficient to differentiate it from previously described species in the genus Chelatococcus. Strain MW9(T) is considered to represent a novel species of the genus Chelatococcus, for which the name Chelatococcus thermostellatus is proposed. The type strain is MW9(T) (=LMG 27009(T) = DSM 28244(T)). Compared to known Chelatococcus strains, strain MW9(T) could be a potent candidate for bioplastic production at elevated temperature.


Combining Perfluorobutylpentane (F4H5) with Glaucoma Drainage Device Implantation for Silicone Oil-Induced Glaucoma: A Pilot Study.
Our aim was to perform a perfluorobutylpentane (F4H5) washout in conjunction with glaucoma drainage device (GDD) placement in patients with silicone oil (SO)-induced glaucoma. In this report we present our preliminary results concerning the effectiveness in clearing the SO and the safety of the procedure. Eight patients who previously underwent pars plana vitrectomy with SO tamponade due to retinal detachment were selected. Removal of SO was performed on average 10 months after initial surgery. All patients developed glaucoma with evidence of SO remnants in the anterior chamber (AC) and angle. Removal of the remaining SO with F4H5 washout was performed in all cases with concomitant insertion of a GDD to treat the refractory glaucoma. Intraocular pressure (IOP), SO remnants, endothelial cell count, and need for glaucoma medications were evaluated up to 12 months after the surgical procedure. All patients had uneventful surgery with no major complications 12 months postoperatively. A marked reduction of SO remnants in the AC and angle was observed in all cases after surgery. There was a 60.9% decrease in mean IOP 12 months postoperatively (p<0.05) and the need for glaucoma medication was lower in all patients (mean topical medicines: 4 preoperatively vs. 0.75±0.89 postoperatively; p<0.05). Endothelial cell density showed no significant change (mean 2012±129 cells/mm2 preoperatively vs. 1985±134 cells/mm2 postoperatively; p>0.05), and there were no signs of corneal edema. F4H5 is an effective emulsifier for removing SO remnants and may be safely used in conjunction with GDD placement in order to control IOP in eyes with silicone oil-induced glaucoma.


Alternative pathway fof bovine complement Immunochemical studies on factor B-like serum protein and its conversion product B gamma 2.
Rabbits produced antibodies to a factor B-like serum protein (factor Bbov), its conversion product B gamma 2 and some other bovine serum proteins after repeated immunization with zymosan which previously had been incubated with fresh bovine serum. Such antisera were used to monitor purification of B gamma 2 from fresh bovine sera incubated with zxymosan. Subsequently, antisera specific for factor Bbov and B gamma 2 were produced. Antiserum produced against B gamma 2 cross-reacted with factor Bbov. Functional assays for factor Bbov were carried out in a hemolytic system with guinea pig erythrocytes in EGTA buffer. Heat inactivation (56 degrees C/5 min) of bovine serum destroyed the antigenicity of factor Bbov but not that of B gamma 2. Factor Bbov had an apparent molecular weight of 95,000 and B gamma 2 a molecular weight of 40,000 daltons. Conversion of factor Bbov to B gamma 2 was determined qualitatively by immunoelectrophoresis and quantitatively by radial immunodiffusion. Conversion of factor Bbov to B gamma 2 in bovine serum, in the presence of zymosan or cobra venom factor (CoVF) required Mg++ but not Ca++, did not occur in heat inactivated (56 degrees C/5 min) serum and was maximal, but not complete, when fresh bovine serum was incubated with zymosan (20 mg/mL) at 37 for two hours.


[Study of depressive and anxiety disorder in menopausal gynecologic outpatients in three Chinese cities].
To describe the prevalence of depressive and/or anxiety symptom and disorder in menopausal outpatients at gynecologic departments of main China cities. A hospital-based cross-sectional study was conducted in the four general hospitals from three main cities in China in 2004. Face-to-face interview were used to collect data, and the self-completed HAD scale was used to evaluate depressive and/or anxiety symptom. Subjects getting a HADS score > or = 9 were further assessed for depressive and/or anxiety disorders with HAMA and HAMD scales by licensed psychologists or psychiatrists. During the study, 306 eligible subjects were recruited from the outpatient of gynecologic departments continually within three months. The prevalence of depressive and anxiety symptoms was evaluated by HADS as 11.1% and 12.4% respectively. The prevalence of depressive and anxiety symptoms was evaluated by HADS as 11.1% and 12.4% respectively. And further HAMD/HAMA evaluation indicated that the proportion of depressive (HAMD > or = 17) and anxiety (HAMA > or = 14) symptoms were 6.2% and 9.8%, respectively. Insurance status were significantly associated with the proportion of depression and/or anxiety symptoms. The prevalence of menopausal depressive and/or anxiety symptoms of this study was higher than those of other similar studies in Urban China. Special attention should be given to the menopausal women with lower education level and lack of medical insurance.


Chemical reactivity of matched cytosine and thymine bases near mismatched and unmatched bases in a heteroduplex between DNA strands with multiple differences.
The chemical reactivity of matched T and C bases to osmium tetroxide and hydroxylamine near mismatched and unmatched bases in a heteroduplex between two strands of DNA with multiple differences was examined. Data was available for matched bases one or two positions away from 24 mismatches. Reactive bases were found near 16 of the mismatches and were usually one or two bases away. This reactivity is consistent with structural studies indicating perturbation of the duplex around mismatches and will allow another mode of study of the effect of mismatches. The reactivity of these bases was found not to be strongly correlated with mismatch type or GC basepair content of the basepairs around the mismatches. Extra reactivity may have been promoted by the presence of either T or C in the mismatch allowing increased reactivity of nearby T or C. The utility of the phenomenon for the detection of mutations is discussed. Unmatched bases in the heteroduplex also gives rise to reactive matched bases nearby.


Covalent functionalization of N-doped graphene by N-alkylation.
Nitrogen doped graphene was modified by N-alkylation using a combination of phase transfer catalysis and microwave irradiation. The resulting derivatives of N-doped graphene were analysed showing that the bandgap of the material varied depending on the alkylation agent used.


IL-13 receptor α2 is a negative prognostic factor in human lung cancer and stimulates lung cancer growth in mice.
IL-13 receptor subunit alpha-2 (IL13Rα2) is associated with poor prognosis in some cancers. However, the role of IL13Rα2 in lung cancer remains unknown. We showed that IL13Rα2 overexpression was associated with late stages of disease progression and shorter disease-free survival (DFS) as well as overall survival (OS) in resected lung cancer patients. IL13Rα2 promoted the migration, invasion and anoikis resistance of lung cancer cells in vitro. Silencing of IL13Rα2 in lung cancer cells decreased invasion in vitro and lung metastasis in vivo. IL13Rα2 activated phosphatidylinositol 3 kinase (PI3K), Akt, and transcriptional coactivator with PDZ-binding motif (TAZ). Inhibition of PI3K attenuated activation of TAZ and its downstream target genes by IL13Rα2. We suggest that inhibition of IL13Rα2 is a potential therapeutic approach in lung cancer.


Enhancing effect of malachite green on the development of hepatic pre-neoplastic lesions induced by N-nitrosodiethylamine in rats.
The effects of malachite green (MG) and phenobarbitone (PB) were compared on the development of pre-neoplastic lesions during N-nitrosodiethylamine(DEN)-induced hepatocarcinogenesis in male Wistar rats. Rats were administered 200 p.p.m. DEN in drinking water for a period of 1 month. After an interval of 2 weeks the animals were given either MG (25 p.p.m.) or PB (500 p.p.m.) in drinking water for 2.5 months. The effects were monitored on the basis of the morphological appearance of the liver, histological pattern, gamma-glutamyltranspeptidase (GGT)-positive foci, total GGT activity and the induction of glycogen-deficient islands. Both MG and PB were found to enhance liver carcinogenesis to a significant extent when compared with either their corresponding controls or animals given DEN alone. The enhancing effect of MG at 25 p.p.m. is comparable with PB at 500 p.p.m. An enhancing effect of MG on DEN-induced hepatocarcinogenesis in the rats was demonstrated.


Detection of the G-->T polymorphism at the Sp1 binding site of the collagen type I alpha 1 gene by a novel ARMS-PCR method.
The G-->T mutation at base 1 of intron 1 at the binding site of the Sp1 transcription factor of the collagen type I alpha 1 gene (COLIA1, GenBank accession no. AF017178) is a putative marker for low bone mineral density and osteoporotic fractures. A new method for the detection of this mutation is presented, based on the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), which utilizes two separate and simultaneous PCRs to detect the normal and mutated alleles. The forward primer (positions 1307-1336 of the gene) is common to both amplifications. Two reverse primers (positions 1566-1546) are used, differing in the 3' base (3'-C for the normal S allele and 3'-A for the mutated s allele). The former amplification uses the reverse primer specific for the S allele; the latter uses the reverse primer with the 3'-base complementary to the mutated base of the s allele. In the SS condition, amplification occurs only in the former reaction and in the ss condition only in the latter. Both reactions give a product in the Ss condition. Direct DNA sequencing of a COLIA1 region containing the G-->T polymorphism demonstrates the validity of this ARMS-PCR method. The new method is more reliable than a previously published detection method, which utilizes a mismatched reverse primer, introducing a restriction site in the T-substituted (s) allele. However, the restriction enzyme is costly, its digestion time long, and incomplete digestion can lead to an underestimation of the frequency of ss homozygosity. The latter can result in incorrect conclusions about a linkage between osteoporosis and the COLIA1 polymorphism. In a survey of the COLIA1 polymorphism in 133 osteoporotic subjects with femur fractures, 7 cases of ss homozygosity were consistently detected both by direct DNA sequencing and by the ARMS-PCR method. This, in contradistinction to the mismatched-primer method by which 3 of these 7 cases were inaccurately diagnosed as Ss heterozygosities.


Dental Anxiety Scales Used in Pediatric Dentistry: A Systematic Review and Meta-analysis.
To assess various dental anxiety scales used in children and to know the effectiveness of different projective dental anxiety scales used in pediatric dentistry. Dental anxiety poses a significant problem in child patient management and is considered to be the main barrier for successful completion of the dental treatment. This systematic review and meta-analysis has been registered at the International prospective register of systematic reviews-PROSPERO-CRD42021247586. The systematic review was conducted in accordance with the Preferred Reporting Items in Systematic Review and Meta-Analysis (PRISMA) guidelines. Electronic databases [PubMed (MEDLINE), COCHRANE Library, EMBASE, EBSCO host, and Google Scholar database] were searched for corresponding references up to 2021. Observational cross-sectional studies comparing two different dental anxiety scales were selected for this systematic review. Search strategy generated 500 articles out of which 13 studies included in qualitative synthesis and only 7 studies were taken for quantitative synthesis. Among these seven studies, five studies compared FIS and VPT scales, two studies compared RMS, FIS, and VPT scales. Results of meta-analysis showed that an overall mean difference of dental anxiety between VPT and FIS scales was 0.11 (95% CI: 0.26-0.48), RMS and FIS scales was 0.05 (95% CI: 0.40-0.50), RMS and VPT was 0.27 (95% CI: 0.80-0.27) in the investigated population. No statistically significant difference was noted in all comparisons suggesting that all these scales are at par in assessing anxiety levels in pediatric population. The projective scales Raghavendra, madhuriu, sujata pictorial scale (RMS), Facial image scale (FIS), and Venham's picture test (VPT) can be a pragmatic tool in assessing children's dental anxiety.


Circadian and ultradian rhythms in blood glucose and plasma insulin of healthy adults.
The circadian and ultradian variations of blood glucose and plasma insulin have been characterized individually and as a group phenomenon in five healthy young adults studied while adhering as closely as possible to their usual routine of sleep, activity, meal content and timing. Three complementary methods were used to analyze the data: displaying raw data as a function of time; cosinor method according to Nelson and Halberg; and time series analyses as proposed by De Prins and Malbecq. The subjects were studied in the laboratory and their life routine were controlled, but very close to that of their habitual routine. They had mainly ultradian rhythms of blood glucose (mainly about 6 hr) and circadian rhythms of immunoreactive insulin (I.R.I.). Blood glucose ultradian rhythms seem to be mainly but not exclusively mealtime dependent, while I.R.I. circadian rhythms appear to be primarily endogenous in origin. Therefore, the role played by insulin in the control of blood glucose levels seems to be programmed on a circadian basis rather than by a time independent feedback phenomenon as postulated by the conventional homeostatic hypothesis. The advantage of this chronophysiologic approach is to consider circadian rhythms of both I.R.I. and insulin effectiveness as an adaptive phenomenon able to maintain blood sugar changes in the ultradian domain of rhythms.


Mutation spectrum of CYP1B1 in Chinese patients with primary open-angle glaucoma.
The CYP1B1 gene has been shown to be related to primary open-angle glaucoma (POAG). This study aimed to identify the mutation profile of CYP1B1 in Chinese individuals with POAG. The study included 416 unrelated cases diagnosed as POAG by standard ophthalmological examinations, and 657 unrelated healthy controls in a Chinese population. Genomic DNA was collected from peripheral blood of all the participants. The coding sequence of CYP1B1 was amplified by PCR from genomic DNA, followed by direct DNA sequencing. Among 416 patients with POAG, 13 missense mutations, including nine reported mutations and four novel mutations (p.P93S, p.R259C, p.A295T, p.L475P), were detected in 25 patients. All these mutations were found as heterozygotes and the reported mutations have been previously found in primary congenital glaucoma and/or POAG patients. Three of them (p.L107V, p.E229K, p.V320L) were also found in healthy controls. In addition, six previously reported single nucleotide polymorphisms (p.R48G, p.A119S, p.V243V, p.V432L, p.D449D, p.N453S) were also observed in POAG patients and controls, and they showed no obvious frequency difference between patients and controls. This study provides a mutation spectrum of CYP1B1 resulting in POAG development in a Chinese population, which may demonstrate an involvement of the gene in a proportion of subjects with POAG and help to improve our understanding of the pathogenesis of CYP1B1-associated POAG.


[Effects of low-frequency pulsed wave ultrasound on the shear properties of the interface of vancomycin-loaded acrylic bone cement-stem].
Objective: To investigate the effects of low-frequency pulsed wave ultrasound on the shear properties of interface of the vancomycin -loaded acrylic bone cement-stem. Methods: The interfaces of 1% vancomycin-loaded acrylic bone cement-stem specimences were successfully manufactured and randomly divided into three groups: the control group, 450 mW/cm(2) ultrasound group and 1 200 mW/cm(2) ultrasound group, each group consisted of eight samples.Two ultrasound groups were exposed to a local ultrasonic field for 7 d, then immersed in PBS for 23 d, and the control groups were immersed in PBS for 30 d. After curing in air for 24 h, the shear strength of the stem-cement interface was determined by push-out test.The specimens were then photographed using SEM and analysed using Image-Pro Plus 6.0 to determine the porosity at the stem-cement interface. Results: The mean shear strength of stem-cement interface additionally decreased by 9% (P>0.05) and 17% (P<0.05) in 450 mW/cm(2) ultrasound group and 1 200 mW/cm(2) group respectively comparing with the control group, but no significant difference was found between the two ultrasound groups.The porosity at the stem-cement interface additionally increased by 44% (P>0.05) and 110% (P<0.05) in 450 mW/cm(2) ultrasound group and 1 200 mW/cm(2) group respectively comparing with the control group, furthermore.The porosity in 1 200 mW/cm(2) ultrasound group increased by 46% (P<0.05) comparing with the 450 mW/cm(2) group. There are much more fluid penetration along the stem-cement interface in ultrasound group . Conclusion: Low-frequency pulsed wave ultrasound signifiantly enhanced porosity and fluid penetration interface, and reduced the interface shear strength and initial stability.


Silver staining of protoplasmic astrocytes by physical development.
The protoplasmic astrocytes adsorb complex Ag(SCN)2- ions from a 40% sodium rhodanide solution containing 1% silver nitrate. The complex is decomposed during a subsequent washing with 5% sodium carbonate, by the excess of rhodanide ions being removed from the sections. Thus, colloid AgSCN grains are made to deposit in the protoplasmic astrocytes. These grains will be reduced first to metallic silver, then enlarged to microscopic dimensions by means of a special physical developer, rendering the protoplasmic astrocytes visible. A pretreatment with 0.01% iodine dissolved in 5% potassium iodide is used to suppress the simultaneous staining of some unwanted tissue elements.


[Pharmacokinetics of ceftriaxone in intensive care].
Pharmacokinetic parameters of ceftriaxone were studied on day 1 and 5 in 21 patients admitted in an ICU for severe infections. All patients received a single daily infusion of 2 g of ceftriaxone during 15 minutes. We have determined the ratio to the daily dose of serum ceftriaxone concentrations (peak level and trough level) and of areas under the curve. According to renal function and the existence of cholestasis, the results of our study showed: 1) In patients with creatinine clearance greater than 10 ml/mn and without cholestasis, a single daily infusion of 2 g ceftriaxone achieves therapeutic blood levels without any accumulation phenomenon. 2) In patients requiring hemodialysis without cholestasis, the period between two 2 g doses should be prolonged to 48 h. 3) Marked cholestasis and creatinine clearance greater than 10 ml/mn prolong the elimination half-life of ceftriaxone leading to an interval extension of the single dose of 2 g. Further investigations are needed in the latter situation.


Neural correlates of absolute pitch differ between blind and sighted musicians.
Several reports have indicated a higher incidence of absolute pitch in blind than in sighted musicians. Employing a pitch memory task, we examined whether a blind absolute pitch musician would rely on different neural correlates than a group of sighted absolute pitch musicians. The blind musician showed significantly more activation of bihemispheric visual association areas, lingual gyrus, parietal and frontal areas than the sighted musicians. Sighted musicians showed more activation of the right primary auditory cortex and the cerebellum when compared with the blind musician. These differences in the activation pattern suggest the use of a different neural network including visual association areas while performing pitch categorization and identification in this blind musician in comparison with sighted musicians.


Regional and cellular expression of the dentatorubral-pallidoluysian atrophy gene in brains of normal and affected individuals.
Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative disorder characterized by dementia and spinocerebellar degeneration. Recently, part of the gene responsible for this disorder was cloned containing a CAG repeat, and predominant neuronal expression of the gene was proved only through Northern blot analysis in rats. In this study, we investigated the regional and cellular expression of the dentatorubral-pallidoluysian atrophy gene in the central nervous system of normal and affected humans, as well as in rat brains. In normal control human subjects, the gene messenger RNA was present in all brain regions examined, with the highest levels seen in the cerebellum, hippocampus, substantia nigra, and pontine nuclei. Its expression in the striatum, globus pallidus, and cerebral cortex was intermediate. The gene was expressed predominantly in neurons; a low but significant level of expression was also seen in glial cells. Neurons susceptible to degeneration in dentatorubral-pallidoluysian atrophy did not selectively express high or low levels of its gene messenger RNA. In brains affected by the disorder, the distribution and levels of gene messenger RNA were comparable to those of the normal controls in all the areas. In the rat brains, gene messenger RNA expression was very similar to that in human brain. It was also expressed predominantly in neurons, while low-level expression was observed in glial cells. It is apparent from these results that the presence of expanded trinucleotide repeats in dentatorubral-pallidoluysian atrophy does not result in the absence of its gene messenger RNA expression or in altered patterns or levels of expression.


Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study.
Aim: Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC. Methods: The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria. Results: In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria. Conclusion: Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.


Understanding the Emergence of Multidrug-Resistant Candida: Using Whole-Genome Sequencing to Describe the Population Structure of Candida haemulonii Species Complex.
The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of C. haemulonii and C. duobushaemulonii in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection.


[Expression of hypoxia-inducible factor 1α in gastric cancer and its clinical signficance].
To explore the expression level and location of hypoxia-inducible factor 1α (HIF-1α) in gastric cancer (GC) tissues and their relationship with clinicopathological features and clinical outcomes. From July to September 2015, 27 pairs of fresh paired GC tissues and adjacent normal tissues were gathered from the Eighth Department of General Surgery of the First Affiliated Hospital of Anhui Medical University. Quantitative real-time PCR (qRT-PCR) and Western blot were performed to detect the expression of HIF-1α mRNA and protein in these tissues. A total of 191 GC tissues and 46 randomly selected adjacent normal gastric tissues were consecutively collected between December 2006 and September 2008 from Department of General Surgery of the same hospital. Immunohistochemistry were performed on them to detect the expression of HIF-1α and CD34[described in terms of microvessel density (MVD)], and correlation of different locations of HIF-1α (in cytoplasm or nucleus) with MVD, clinicopathological features, and clinical prognosis was analyzed. The average relative expression level of HIF-1α mRNA in GC tissues (0.625±0.170) was significantly higher than in normal adjacent tissues (0.218±0.036, t=2.336, P=0.023) by qRT-PCR. From the results of Western blot, the expression level of HIF-1α protein increased in GC tissues compared with its corresponding normal tissues. Immunohistochemistry results revealed that positive HIF-1α staining was observed in 67.54% GC tissues and 45.65% normal tissues, with significant difference (P=0.006). And 35.08% in GC and 45.65% in normal tissues were cytoplasmic positive (P=0.138); while 37.17% in GC and only 2.17% in normal tissues were nuclear positive, with significant difference (P<0.001). High differentiation group and TNM clinical early stage (Ⅰ+ Ⅱ) group had significantly higher cytoplasmic HIF-1α expression positive rate compared with low differentiation group (P=0.008) and TNM clinical intermediate-advanced stage (Ⅲ+ Ⅳ) group (P=0.019); whereas low differentiation group had significantly higher nuclear HIF-1α expression positive rate compared with high differentiation group (P=0.043). The mean MVD in the nuclear HIF-1α positive GC group (115.6 ± 7.8) was higher than that in the cytoplasmic HIF-1α positive GC group (93.1±7.5, t=2.077, P=0.040). The median follow-up time was 56(3-81)months. Kaplan-Meier survival analysis and Log-Rank test results showed that nuclear HIF-1α positive patients had a shorter survival time (median 45 months) than cytoplasmic HIF-1α positive patients (median 64 months, P<0.001). Multivariate Cox regression analysis revealed that differentiation (HR=1.713; 95% CI: 1.019-2.882), depth of invasion (tumor stage, HR=6.137; 95% CI: 1.832-20.556) and lymph node metastasis (HR=2.788; 95% CI: 1.313-5.920) were independent prognostic factors for GC (all P<0.05). Different location of HIF-1α protein may be realted to the tumorigenesis and progression of GC, and may become a potential prognostic indicator of GC.


Superinfection of chronic multifocal osteomyelitis with Enterobacter cloacae.
A case is presented of a 6-year-old boy from Nigeria who developed chronic multifocal osteomyelitis with bilateral and symmetrical proximal humeral involvement. Superimposed changes of acute osteomyelitis were noted on the histopathological evaluation of the lesions. Cultures from both sides were positive for Enterobacter cloacae, which was presumably contracted during intravenous therapy for typhoid fever in Nigeria 1 month prior to his presentation.


Redox signalling in cardiovascular disease.
Oxidative stress has almost universally and unequivocally been implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress in cells and cardiovascular biology was once considered only in terms of injury, disease and dysfunction. However, it is now appreciated that oxidants are also produced in healthy tissues, and they function as signalling molecules transmitting information throughout the cell. Conversely, when cells move to a more reduced state, as can occur when oxygen is limiting, this can also result in alterations in the function of biomolecules and subsequently cells. At the centre of this 'redox signalling' are oxidoreductive chemical reactions involving oxidants or reductants post translationally modifying proteins. These structural alterations allow changes in cellular redox state to be coupled to alterations in cell function. In this review, we consider aspects of redox signalling in the cardiovascular system, focusing on the molecular basis of redox sensing by proteins and the array of post-translational oxidative modifications that can occur. In addition, we discuss studies utilising proteomic methods to identify redox-sensitive cardiac proteins, as well as those using this technology more broadly to assess redox signalling in cardiovascular disease.


Distributions of beta sheets in proteins with application to structure prediction.
We recently developed the Rosetta algorithm for ab initio protein structure prediction, which generates protein structures from fragment libraries using simulated annealing. The scoring function in this algorithm favors the assembly of strands into sheets. However, it does not discriminate between different sheet motifs. After generating many structures using Rosetta, we found that the folding algorithm predominantly generates very local structures. We surveyed the distribution of beta-sheet motifs with two edge strands (open sheets) in a large set of non-homologous proteins. We investigated how much of that distribution can be accounted for by rules previously published in the literature, and developed a filter and a scoring method that enables us to improve protein structure prediction for beta-sheet proteins. Proteins 2002;48:85-97.


Phenobarbital-induced expression of cytochrome P450 genes.
In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.


Idiopathic pulmonary hemosiderosis. Electron microscopic, immunofluorescent, and iron kinetic studies.
The clinical course of a 37-year-old white man with idiopathic pulmonary hemosiderosis is presented. This patient is unusual in that he has had repeated exacerbations and remissions over a period of seven years and remains currently in spontaneous remission with no therapy. Routine sections of the lung biopsy revealed characteristec findings. Immunofluorescence staining of the lung was negative, and electron microscopic studies showed only nonspecific findings. While in remission, 51chromium-labelled red-blood-cell survival studies and 59iron kinetic studies were performed; the results were normal.


When children seek asylum from their parents: a Canadian case study.
When children seek asylum from alleged abuse by a custodial parent, the notion that family reunification is always in the best interests of independent child migrants is undermined. In this chapter, the authors discuss the legal tensions between the Refugee Convention, the Convention on the Civil Aspects of International Child Abduction (the "Hague Convention"), and the Convention on the Rights of the Child that arise in such cases. They recommend that the principle of expediency underlying the Hague Convention should not override the time and due process requirements necessary to adequately assess the best interests of the child involved.


Neurological observations in infants, children and young people: part two.
Neurological observations are a vital part of the assessment of infants, children and young people with a suspected or confirmed acquired brain injury (ABI). They are designed to identify neurological deterioration and inform the management of ABIs. Children's nurses may perform many of these neurological observations, including by using tools such as the AVPU scale, the Glasgow Coma Scale, pupillary response and limb assessment. This is the second of two articles that aim to encourage accuracy and consistency when performing neurological observations in infants, children and young people with a suspected or confirmed ABI to optimise their care. The article explains how to undertake various elements of a neurological assessment, how often to perform neurological observations, when to escalate concerns and why it is important to use family-centred care.


The role of lens implantation in cataract surgery.
Cataract surgery results in a substantial loss of the refractive power of the eye, which may be corrected by wearing cataract glasses, by using contact lenses, or by replacing the cataractous lens with an intraocular lens implant. This chapter discusses the advantages and disadvantages of each of these methods, and emphasizes the role of lens implants. The three kinds of intraocular lens implants currently available include the iris-supported lens, the anterior chamber lens, and the posterior chamber lens. Intraocular lens implants are rapidly becoming the method of choice in many patients who require cataract operations.


[MINIMALLY INVASIVE GLAUCOMA SURGERIES].
The goal of all glaucoma surgery is to lower eye pressure to prevent or reduce damage to the optic nerve. Standard glaucoma surgeries - trabeculectomy, ExPRESS shunts and external tube-shunts like the Ahmed and Baerveldt valves - are major surgeries. While they are very often effective at lowering eye pressure and preventing progression of glaucoma, they have a long list of potential complications. Minimal invasive glaucoma surgery (MIGS) is a group of operations that have been developed in recent years to reduce some of the complications of most standard glaucoma surgeries. MIGS procedures work by using microscopic-sized equipment and tiny incisions. The purpose of this study is to review the available MIGS currently in use, their benefits and limitations.


Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated Cl(-) channel expressed in the apical plasma membrane in fluid-transporting epithelia. Although CFTR is rapidly endocytosed from the apical membrane of polarized epithelial cells and efficiently recycled back to the plasma membrane, little is known about the molecular mechanisms regulating CFTR endocytosis and endocytic recycling. Myosin VI, an actin-dependent, minus-end directed mechanoenzyme, has been implicated in clathrin-mediated endocytosis in epithelial cells. The goal of this study was to determine whether myosin VI regulates CFTR endocytosis. Endogenous, apical membrane CFTR in polarized human airway epithelial cells (Calu-3) formed a complex with myosin VI, the myosin VI adaptor protein Disabled 2 (Dab2), and clathrin. The tail domain of myosin VI, a dominant-negative recombinant fragment, displaced endogenous myosin VI from interacting with Dab2 and CFTR and increased the expression of CFTR in the plasma membrane by reducing CFTR endocytosis. However, the myosin VI tail fragment had no effect on the recycling of endocytosed CFTR or on fluid-phase endocytosis. CFTR endocytosis was decreased by cytochalasin D, an actin-filament depolymerizing agent. Taken together, these data indicate that myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments.


Synthesis of pyranopyrazolo N-glycoside and pyrazolopyranopyrimidine C-glycoside derivatives as promising antitumor and antimicrobial agents.
As a part of systematic investigation of the synthesis and biological activities of pyrazole analogues linked to various heterocyclic systems, a new series of pyrazolo-N-glycoside derivatives, pyrazolopyranopyrimidine and C-glycoside of pyrazolopyranotriazolo-pyrimidine derivatives was synthesized through the reaction of the key intermediate 6-amino-3-methyl-4-(substituted-phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (3a,b) with different reagents. Structures of the newly synthesized compounds were elucidated by elemental microanalysis and spectroscopic methods. The compounds were subjected to in vitro antitumor evaluation using the MTT assay. N-(β-D-ribofuranosyl)- and N-(β-D-xylofuranosyl)-6{[(1E)-4-chlorophenyl)-methylene] amino}4-(4-florophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile (6a,b) were the most active compounds against three human cancer cell lines. Also, most of the newly synthesized compounds exhibited high activity towards Gram-negative and Gram-positive bacteria. Compound 6a exhibited excellent activity towards bacteria compared to ofloxacine as the reference drug.


A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types.
The study of induced pluripotency is complicated by the need for infection with high-titer retroviral vectors, which results in genetically heterogeneous cell populations. We generated genetically homogeneous 'secondary' somatic cells that carry the reprogramming factors as defined doxycycline (dox)-inducible transgenes. These cells were produced by infecting fibroblasts with dox-inducible lentiviruses, reprogramming by dox addition, selecting induced pluripotent stem cells and producing chimeric mice. Cells derived from these chimeras reprogram upon dox exposure without the need for viral infection with efficiencies 25- to 50-fold greater than those observed using direct infection and drug selection for pluripotency marker reactivation. We demonstrate that (i) various induction levels of the reprogramming factors can induce pluripotency, (ii) the duration of transgene activity directly correlates with reprogramming efficiency, (iii) cells from many somatic tissues can be reprogrammed and (iv) different cell types require different induction levels. This system facilitates the characterization of reprogramming and provides a tool for genetic or chemical screens to enhance reprogramming.


Social Media Usage and Its Effects on the Psychological Health of Adolescents.
Social media usage is ubiquitous among adolescents. Although social media may appeal to adolescents due to the ability to connect with peers and develop relationships, many teens also report feelings of exclusion or victimization associated with their social media use. High usage of social media may act as a forum for negative behaviors and psychological detriments. Awareness and understanding of how social media affects adolescents' psychological well-being will help parents and school staff better support teenagers and develop programs to improve coping skills and self-regulation of social media for adolescents.


Mycophenolate mofetil: selective T cell inhibition.
Mycphenolate mofetil is a suppressor of T cell proliferation and adhesion. Its primary mode of action is inhibition of inosine monophosphate dehydrogenase, a purine salvage pathway required by T lymphocytes. Although the role of T cells in rheumatoid arthritis (RA) has been controversial, a preliminary report of mycophenolate mofetil's successful use in RA patients clearly suggests that its efficacious properties need further investigation. Its favorable risk/benefit ratio, a broad clinical experience in kidney transplantation, and its recent extension to other rheumatic diseases suggests that this new antirheumatic agent has significant therapeutic potential for suppression of synovial inflammation.


Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant.
Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, to lipid bodies (LBs). The physiological relevance and dynamics of LB association remain unclear. We now show that endogenous caveolin-1 and caveolin-2 redistribute to LBs in lipid loaded A431 and FRT cells. Association with LBs is regulated and reversible; removal of fatty acids causes caveolin to rapidly leave the lipid body. We also show by subcellular fractionation, light and electron microscopy that during the first hours of liver regeneration, caveolins show a dramatic redistribution from the cell surface to the newly formed LBs. At later stages of the regeneration process (when LBs are still abundant), the levels of caveolins in LBs decrease dramatically. As a model system to study association of caveolins with LBs we have used brefeldin A (BFA). BFA causes rapid redistribution of endogenous caveolins to LBs and this association was reversed upon BFA washout. Finally, we have used a dominant negative LB-associated caveolin mutant (cavDGV) to study LB formation and to examine its effect on LB function. We now show that the cavDGV mutant inhibits microtubule-dependent LB motility and blocks the reversal of lipid accumulation in LBs.


Polarized targeting of neurexins to synapses is regulated by their C-terminal sequences.
Two families of cell-adhesion molecules, predominantly presynaptic neurexins and postsynaptic neuroligins, are important for the formation and functioning of synapses in the brain, and mutations in several genes encoding these transmembrane proteins have been found in autism patients. However, very little is known about how neurexins are targeted to synapses and which mechanisms regulate this process. Using various epitope-tagged neurexins in primary hippocampal neurons of wild-type and knock-out mice in vitro and in transgenic animals in vivo, we show that neurexins are trafficked throughout neurons via transport vesicles and the plasma membrane insertion of neurexins occurs preferentially in the axonal/synaptic compartment. We also observed that exit of neurexins from the ER/Golgi and correct targeting require their PDZ-binding motif at the C terminus, whereas two presumptive ER retention signals are inactive. The ubiquitous presence of neurexin-positive transport vesicles and absence of bassoon colabeling demonstrate that these carriers are not active zone precursor vesicles, but colocalization with CASK, RIM1alpha, and calcium channels suggests that they may carry additional components of the exocytotic machinery. Our data indicate that neurexins are delivered to synapses by a polarized and regulated targeting process that involves PDZ-domain mediated interactions, suggesting a novel pathway for the distribution of neurexins and other synaptic proteins.


Osmoregulatory role of alanine during salt stress in the nitrogen fixing cyanobacterium Anabaena sp. 287.
The freshwater cyanobacterium, Anabaena sp. 287 exhibited enhanced tolerance to NaCl in the presence of ammonium, nitrate, and the amino acids, alanine, valine, proline, lysine, histidine, methionine and aspartic acid. Apart from providing permanent protection to the growth during stress, like NO3- and NH4+, alanine also relieved the initial salt mediated inhibition on enzymes involved in nitrogen fixation, photosynthesis and respiration. The accumulation of sugars was observed only during molecular nitrogen growth in the presence of salt. The cellular total nitrogen content was inversely proportional to the total sugar concentration. All nitrogenous substances which supported growth in the presence of salt curtailed the Na+ influx. Sodium chloride concentration-dependent [3H]D-alanine uptake in this cyanobacterium favours the conclusion that alanine acts as an osmoregulator along with sugars.


[Solid-pseudopapillary tumor of the pancreas: report of four cases].
Solid-pseudopapillary tumor of the pancreas is a rare neoplasia of pancreas, with a rate varying from 0.17%-2.7% of non-endocrine tumors of the pancreas. Recently there has been a steady increase in the number of solid-pseudopapillary tumors of the pancreas, with more than two thirds of the total cases described in the last 10 years. To evaluate four patients with Frantz's tumor in a Brazilian institution. Four patients with diagnosis of solid-pseudopapillary tumor were analysed in a retrospective analysis from December 2000 to February 2003, clinically and histopathologically. Therapeutical approach and prognosis were also studied. There were three females and one male with a median age of 27 years (range, 17-42). Dyspeptic symptoms and abdominal palpable mass represented the initial clinical findings. The main localization of the tumor was the pancreatic head (three of four cases). Enucleation was performed in one case, Whipple's surgery in two cases, and distal pancreatectomy in one case. Curative resection was possible in all cases confirmed by free margins. Two cases showed venous invasion histopathologically. Immunohistochemical analysis was done in three cases to confirm the diagnosis. In an average of 15-month follow-up, no recurrence has been observed. Our casuistic showed the preference of the tumor to the head of the pancreas, controversial to literature. However, other characteristics were similar to literature reports (clinical, histopathological, immunohistochemical and therapeutics). In addition, a longer postoperative follow-up will be necessary to affirm about prognosis.


[Diazepam-induced disinhibition].
Benzodiazepines are among the most often prescribed drugs worldwide, and are mostly prescribed by general practitioners and family physicians. Their side-effects include tolerance, dependence, intoxication, withdrawal syndrome, retrograde amnesia, paradoxical agitation (frequent in the elderly) and disinhibition. A 32-year-old woman is presented. She was brought to the emergency room because of psychotic-like behavior. It was caused by severe disinhibition due to a single 5 mg dose of diazepam prescribed during uncomplicated bereavement. 14 hours later all symptoms had subsided and she was discharged.


Expectancies and memory retrieval in three-month-old infants.
The ability of 3-month-olds to acquire generalized expectancies of reward and the role of these expectancies in memory retrieval was assessed in 2 experiments. In both, infants learned to activate the components of a crib mobile by kicking and were trained with mobiles containing either the same (invariant) or different (variable) components in successive daily sessions. In Experiment 1, infants exhibited positive transfer over both the invariant and variable stimulus series. However, there was a trend toward disruption of retrieval when infants were tested with a familiar set of components following training on a variable stimulus series. In Experiment 2, infants were trained for 2 sessions with mobile components that either did or did not change between sessions. In a 24-hour retention test, mobile components that either continued or violated the serial order established during the preceding sessions were presented as retrieval cues. Infants again exhibited positive transfer over both variable and invariant series when the test stimulus was predicted by the serial order of training stimuli, but violations of either expected order produced a retention deficit. These results were interpreted as suggesting that very young infants develop generalized expectancies of reward that are based on the serial pattern in which events occur.


Microwave-Induced Behavior and Digestive Properties of the Lotus Seed Starch-Chlorogenic Acid Complex.
The effect of chlorogenic acid (CA) on the dielectric response of lotus seed starch (LS) after microwave treatment, the behavior and digestive characteristics of the resulting starch/chlorogenic acid complex (LS-CA) at different degrees of gelatinization and the inhibition of α-amylase by chlorogenic acid were investigated. The variation in dielectric loss factor, ε″, and dielectric loss tangent, tanδε, of the microwave thermal conversion indicated that LS-CA had a more efficient microwave-energy-to-thermal-energy conversion efficiency than LS. This gelatinized LS-CA to a greater extent at any given temperature between 65 and 85 °C than LS, and it accelerated the degradation of the starch crystalline structure. The greater disruption of the crystal structure decreased the bound water content and increased the thermal stability of LS-CA compared to LS. The simulated in vitro digestion found that the presence of the LS-CA complex improved the slow-digestion property of lotus seed starch by increasing its content of resistant and slowly digested starch. In addition, the release of chlorogenic acid during α-amylase hydrolysis further slowed starch digestion by inhibiting α-amylase activity. These findings provide a foundation for understanding the correlation between the complex behavior and digestive properties of naturally polyphenol-rich, starch-based foods, such as LS, under microwave treatment, which will facilitate the development of starch-based foods with tailored digestion rates, lower final degrees of hydrolysis and glycemic indices.


JCAHO: meeting the standards for pain management.
Chronic, unrelieved pain costs approximately $100 billion per year. The impact of unrelieved pain has yet to be determined. Postoperatively, an individual has a 50-80% chance of having unrelieved moderately severe to severe pain sometime during the surgical period. In spite of knowing how to manage pain, we still have a long way to go. New and updated guidelines will assist in providing a basis for standardization in the future. This article focuses on the newly adopted JCAHO guidelines on pain management and their impact on the management of pain in the operative period.


Validity of patient self-reports and clinical signs in the assessment of sleep bruxism based on home-recorded electromyographic/electrocardiographic data.
Reliable and suitable bruxism assessment would be desirable, but available studies presented heterogeneous results. To determine the agreement of patient self-reports and clinical signs of sleep bruxism (SB) with electromyographic/electrocardiographic data. Two hundred individuals from a German dental clinic population (120 women and 80 men) participated in the study. Participants completed different SB questionnaires, had a clinical examination to evaluate bruxism signs and used the Bruxoff® device to record electromyographic/electrocardiographic data for five nights. To investigate interrater reliability for clinical diagnosis of bruxism, 126 of the 200 participants were assessed for clinical signs of bruxism by two independent uncalibrated examiners. Statistical evaluation included calculation of sensitivity, specificity and accuracy and of Cohen's kappa. Based on the Bruxoff® data, 106 participants were identified as bruxers and 94 as non-bruxers. The 106 bruxers were further classified into 47 moderate and 59 intense bruxers. The highest accuracy and sensitivity values were recorded for the overall score for clinical bruxism signs (accuracy: 72.0% and sensitivity: 70.8%). The best specificity (96.8%) was seen for the question regarding tooth grinding in the last two weeks reported by others, but concurrent sensitivity was very low (3.8%). Analysis of interrater reliability revealed a substantial agreement (Cohen's kappa of 0.6). The study results indicate that self-report questionnaires and clinical signs have moderate sensitivity, specificity and accuracy for diagnosing bruxism comparing with an ambulatory device for current SB (Bruxoff®). Regarding interrater reliability for clinical signs of SB, substantial agreement was found between the two examiners. NCT03039985.


Distinct spatial and temporal distribution of ZAP70 and Lck following stimulation of interferon and T-cell receptors.
T-cell receptor (TCR) stimulation results in the recruitment and activation of the proteins ZAP70 and Lck. These two proteins have been implicated in signalling derived from interferon receptors, although their precise role in this independent pathway has not been determined fully. These observations raise a fundamental question of how a given protein in a cell can be involved in more than one signalling pathway, yet each pathway is able to produce a highly specific downstream response to its own stimulant. To maintain exclusivity of response, each pathway must isolate its component molecules chemically, spatially or dynamically from other prevailing pathways. To address this question, the proteins ZAP70 and Lck were investigated following stimulation of the interferon-alpha receptor and the TCR in T cells by two different extracellular stimulants: interferon-alpha and the anti-CD3 antibody, OKT3, respectively. We first demonstrate that ZAP70 plays a pivotal role in interferon-stimulated MAPK activation, and that the tyrosine residue at position 319 of ZAP70 is important for interferon-stimulated ERK activation. Translocation of both ZAP70 and Lck to the nucleus following interferon receptor stimulation is demonstrated for the first time. Fluorescence resonance energy transfer microscopy revealed a high degree of spatial localization of the ZAP70/Lck complex within the cell following IFNalpha stimulation, in contrast to a diffuse presence following the application of OKT3. The difference in the spatio-temporal localization of these proteins following stimulation may eliminate signal crosstalk, and could explain the differentiation of the specific downstream responses of these pathways.


Radio frequency hearing: electrostrictive detection and bone conduction.
A hearing aid patented by C. R. Schafer and supposedly based on detection of an amplitude-modulated carrier wave in the auditory cortex was re-examined. It is shown here that the hearing aid actually works by bone conduction of sound. It is concluded that detection of the modulation signal occurs by electrical nonlinearities and electrostriction in the bones of the face and skull.


Evaluation of Usability, Perception of Usefulness, and Efficiency of an Application in Interpreting Imaging Examinations and Supporting Decision-Making in Orthopedics.
Background: Medical smartphone applications have rendered positive results in daily practice and also serve as potentially valuable educational tools. In orthopedics, radiograph analysis and angle measurements comprise an essential mechanism in the diagnosis, treatment, planning, and evaluation of the results in orthopedic surgery. Purpose: Thus, the present study aimed to evaluate an application for mobile devices for orthopedic doctors and orthopedic residents. The application proposes the analysis and interpretation of radiographic imaging examinations through assessments and angle measurements. In this survey, we analyzed the parameter usability and usefulness of a mobile application for the iOS system, in addition to conducting its validation. Patients and Methods: The application was tested by 26 volunteers: 13 orthopedists and 13 orthopedic residents. Results: After applying the System Utility Score (SUS) questionnaire, which assesses the usability of an application, a score of 84.5 was obtained, a value that represents an A+ rating on the Sauro and Lewis scale. There was no statistically significant difference when comparing the SUS between the orthopedic residents and orthopedists. According to the usefulness perception analysis, 90% of the residents responded positively to the questions, while among orthopedists, the percentage was 75%, denoting a statistically significant difference (p = 0.002). Subsequently, the application underwent validation to assess whether the calculated angle measurements were reliable when compared with those obtained using the goniometer. No significant differences were observed when comparing the angles measured by the two evaluated methods. Conclusion/Clinical Relevance: In conclusion, the developed application can reliably contribute to the measurement of angles in radiographs, assisting in therapeutic decision-making, and may be used as an instrument to promote the teaching and learning processes in orthopedics.


Epidemiology of candidemia in neonatal intensive care units: a persistent public health problem.
Candidemia has become an increasingly important problem in infants hospitalized in the Neonatal Intensive Care Units (NICUs). Candida species are the third most common agents of late-onset infections in critically ill neonates and they are associated with high morbidity and mortality rates. In this study we evaluated the epidemiology of Candida bloodstream infections in the NICU of an Italian university hospital during a 15-year period. Our specific aims were to analyze the change in species distribution and the vitro susceptibility of these yeasts to fluconazole (FCZ) and amphotericin B (AmB). A retrospective study of candidemia in the NICU of a university hospital in southern Italy, covering the years 2000-2014 was carried out. The isolates were identified using the VITEK2 yeast identification system and antifungal susceptibility was determined using the E-test method. Among the 57 patients with confirmed candidemia, 60% were males (n = 34 cases) and 82% (n = 47) had a gestational age of 24-32 weeks. Twenty-seven neonates (47%) had a very low birth weight (<1500 g), 20 (35%) an extremely low birth weight (<1000 g), and 10 (18%) a low birth weight (<2500 g). The most important potential risk factors were the placement of a central venous catheter, total parenteral nutrition, and endotracheal intubation (100%, each). Candida albicans was the most frequent yeast (47%), followed by Candida parapsilosis (44%). The proportion of Candida non-albicans increased slightly, from 46% in 2000-2004 to 71% in 2010-2014 (χ2 test for trend, p = 0.030). All isolates were susceptible to FCZ and AmB. The detection in this epidemiologic study of an increase in Candida non-albicans highlights the importance of correct species-level identification in the rapid diagnosis for an efficient treatment of candidemia. Knowledge of the local epidemiological trends in Candida species isolated in blood cultures will facilitate therapeutic decision-making.


Clinical Significance and Potential Mechanisms of ATP Binding Cassette Subfamily C Genes in Hepatocellular Carcinoma.
The purpose of this investigation was to assess the diagnostic and prognostic significance of ATP binding cassette subfamily C (ABCC) genes in hepatocellular carcinoma (HCC). The Student t-test was used to compare the expression level of ABCCs between HCC and paraneoplastic tissues. Receiver operating characteristic curve (ROC) analysis was applied for diagnostic efficiency assessment. The Kaplan-Meier method and Cox proportional hazards model were respectively applied for survival analysis. Genes with prognostic significance were subsequently used to construct prognostic models. From the perspective of genome-wide enrichment analysis, the mechanisms of prognosis-related ABCC genes were attempted to be elaborated by gene set enrichment analysis (GSEA). It was observed in the TCGA database that ABCC1, ABCC4, ABCC5, and ABCC10 were significantly upregulated in tumor tissues, while ABCC6 and ABCC7 were downregulated in HCC tissues. Receiver operating characteristic analysis revealed that ABCC7 might be a potential diagnostic biomarker in HCC. ABCC1, ABCC4, ABCC5, and ABCC6 were significantly related to the prognosis of HCC in the TCGA database. The prognostic significance of ABCC1, ABCC4, ABCC5, and ABCC6 was also observed in the Guangxi cohort. In the Guangxi cohort, both polymerase chain reaction and IHC (immunohistochemical) assays demonstrated higher expression of ABCC1, ABCC4, and ABCC5 in HCC compared to liver tissues, while the opposite was true for ABCC6. GSEA analysis indicated that ABCC1 was associated with tumor differentiation, nod-like receptor signal pathway, and so forth. It also revealed that ABCC4 might play a role in HCC by regulating epithelial-mesenchymal transition, cytidine analog pathway, met pathway, and so forth. ABCC5 might be associated with the fatty acid metabolism and KRT19 in HCC. ABCC6 might impact the cell cycle in HCC by regulating E2F1 and myc. The relationship between ABCC genes and immune infiltration was explored, and ABCC1,4,5 were found to be positively associated with infiltration of multiple immune cells, while ABCC6 was found to be the opposite. In conclusion, ABCC1, ABCC4, ABCC5, and ABCC6 might be prognostic biomarkers in HCC. The prognostic models constructed with ABCC1, ABCC4, ABCC5, and ABCC6 had satisfactory efficacy.


Ultra-Low Loading of Ultra-Small Fe3 O4 Nanoparticles on Nonmodified CNTs to Improve Green EMI Shielding Capability of Rubber Composites.
From a material design perspective, the incorporation of Fe3 O4 @carbon nanotube (Fe3 O4 @CNT) hybrids is an effective approach for reconciling the contradictions of high shielding and low reflection coefficients, enabling the fabrication of green shielding materials and reducing the secondary electromagnetic wave pollution. However, the installation of Fe3 O4 nanoparticles on nonmodified and nondestructive CNT walls remains a formidable challenge. Herein, a novel strategy for fabricating the above-mentioned Fe3 O4 @CNTs and subsequently assembling segregated Fe3 O4 @CNT networks in natural rubber (NR) matrices is proposed. The advanced and unique structure, magnetism, and lossless conductivity endow the as-obtained Fe3 O4 @CNT/NR with a shielding effectiveness (SE) of 63.8 dB and a low reflection coefficient of 0.24, which indicates a prominent green-shielding capability that surpasses those of previously reported green-shielding materials. Moreover, the specific SE reaches 531 dB cm-1 , exceeding that of those of previously reported carbon/polymer composites. Meanwhile, the outstanding conductivity enables the composite to reach a saturation temperature of ≈95 °C at a driving voltage of 1.5 V with long-term stability. Therefore, the as-fabricated Fe3 O4 @CNT/rubber composites represent an important development in green-shielding materials that are applied in cold environment.


COVID-19: Immunology and treatment options.
The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.


Review: monoclonal antibodies to the vascular endothelial growth factor receptor-2 in cancer therapy.
Angiogenesis is a fundamental mechanism of cancer growth and invasion. Current translational approaches are using both small-molecule inhibitors and antibodies that modulate various steps of these processes, and several such compounds have already received regulatory approval for the therapy of specific indications in cancer. Among the many molecular targets involved in the control of angiogenesis, the vascular endothelial growth factor receptor-2 (VEGFR-2; or kinase insert domain-containing receptor) is attractive as shown in part by the efficacy of small-molecule inhibitors directed to this receptor. Two small-molecule inhibitors that target VEGFR-2 have recently been granted approval for the treatment of renal cell cancer and gastrointestinal stromal tumors. The development of antibodies that can selectively block VEGFR-2 could potentially result in improved potency or tolerability. Here, we discuss the role of VEGFR-2 in cancer and ongoing efforts to develop highly specific monoclonal antibodies for cancer therapy.


The HMG-CoA reductase inhibitor fluvastatin inhibits insect juvenile hormone biosynthesis.
Fluvastatin (Sandoz Compound XU 62-320), a synthetic HMG-CoA reductase inhibitor, was assayed in vitro and in vivo for its ability to suppress juvenile hormone (JH) biosynthesis by corpora allata of Locusta migratoria migratorioides. Fluvastatin inhibited JH biosynthesis by corpora allata in vitro. Exogenous mevalonic acid lactone restored JH biosynthesis in corpora allata inhibited by fluvastatin. Fluvastatin injected into locusts in vivo inhibited JH biosynthesis, but maximal inhibition lasted for only 6 hr. There were no discernible effects on either JH-regulated metamorphosis or oocyte maturation. Lengthening of the fourth larval stadium was observed and increased doses (single or repeated injections) were fatal.


Lack of the SOX9 gene polymorphism in sex reversal dogs (78,XX; SRY negative).
The molecular background of the most frequent intersexuality syndrome in dogs (female-to-male sex reversal with the female karyotype and a lack of the SRY gene) is unknown. In this article, new cases of this syndrome are described in two unrelated American Staffordshire terrier dogs and one miniature pinscher dog subjected to cytogenetic and molecular analysis due to the presence of an enlarged clitoris. One dog was operated on and histological studies of the gonads revealed a testicular structure without signs of spermatogenesis, but the uterus wall appeared to be normal. All three dogs had female chromosome complements and lacked the Y-linked genes SRY and ZFY. Eight fragments, representing the vast majority of the coding sequence of the SOX9 gene, and two fragments of the 5' flanking region of this gene were analyzed. The studied fragments had identical DNA sequences when comparing the intersexual dogs with GenBank sequences (AY237827; NW139883). Thus a mutation in the coding sequence as well as the promoter region of the SOX9 gene might be excluded as a cause of this type of intersexuality. The importance of further studies of the 5' flanking region of this gene is discussed.


Alterations of Caspr2 and Nav1.6 on myelinated axon damage in a rat model of chronic cerebral hypoperfusion.
Myelinated axons require the correct localization of key proteins that are essential for nerve conduction and cognitive function. Little is known regarding the altered expression of contactin-associated protein 2 (Caspr2) at the juxtaparanodal regions and Nav1.6 at the node of Ranvier in response to chronic cerebral hypoperfusion (CCH). The aim of the present study was to examine the alterations in the key protein of myelinated axons and the potential mechanisms that may follow CCH. We established a rat model of CCH by controllable partial narrowing of bilateral common carotid arteries. Then, we detected cerebral blood flow (CBF) after surgery. We also evaluated motor-evoked potentials (MEPs), assessed the Morris water maze test, analyzed Caspr2 expression through immunohistochemistry and Nav1.6 protein expression through western blot analysis at 2, 4 and 12 weeks. The results revealed that the mean CBF value was significantly decreased to 33.90±5.48%. The MEP latencies and the escaping latencies were significantly prolonged. There was also an elongation of the first time passing of the hidden platform with a reduction of crossing platform times in spatial probing. Furthermore, the Caspr2 immunoreactivity demonstrated that the Caspr2 level was significantly downregulated with abnormal locations in the corpus callosum. The western blot analysis of Nav1.6 protein revealed that the level was reduced significantly over time. The results demonstrate that CCH leads to central conductive function loss, cognitive function damage and alterations in the key protein of myelinated axons, which may provide a molecular basis and key link for white matter damage.


Cassette mutagenesis and photoaffinity labeling of adenine binding domain of ADP regulatory site within human glutamate dehydrogenase.
The adenine binding domain of the ADP site within human glutamate dehydrogenase (GDH) was identified by cassette mutagenesis at the Tyr187 position. The wild type GDH was activated 3-fold by ADP at a concentration of 1 mM at pH 8.0, whereas no significant activation by ADP was observed with the Tyr187 mutant GDH regardless of the size, hydrophobicity, and ionization of the side chains. Studies of the steady-state velocity of the mutant enzymes revealed essentially unchanged apparent K(m) values for 2-oxoglutarate and NADH, but an approximately 4-fold decrease in the respective apparent V(max) values. The binding of ADP to the wild type or mutant GDH was further examined by photoaffinity labeling with [alpha-(32)P]8-azidoadenosine 5'-diphosphate (8N(3)ADP). 8N(3)ADP, without photolysis, mimicked the stimulatory properties of ADP on GDH activity. Saturation of photoinsertion with 8N(3)ADP occurred with apparent K(d) values near 25 microM for the wild type GDH, and the photoinsertion of [alpha-(32)P]8N(3)ADP was decreased best by ADP in comparison to other nucleotides. Unlike the wild type GDH, essentially no photoinsertion was detected for the Tyr187 mutant GDH in the presence or absence of 1 mM ADP. For the wild type GDH, photolabel-containing peptide generated by tryptic digestion was identified in the region containing the sequence EMSWIADTYASTIG, and the photolabeling of this peptide was prevented >95% by the presence of 1 mM ADP during photolysis, whereas no such a peptide was detected for the Tyr187 mutant GDH in the presence or absence of ADP. These results with cassette mutagenesis and photoaffinity labeling demonstrate selectivity of the photoprobe for the ADP binding site and suggest that the photolabeled peptide is within the ADP binding domain of the human GDH and that Tyr187 is responsible for the efficient base binding of ADP to human GDH.


Coagulation aggravates blood-induced joint damage in dogs.
Joint bleeding due to trauma, major joint surgery, or hemophilia leads to joint damage. It is unclear if there are differences between coagulating blood and anticoagulated blood with respect to joint degeneration, especially in vivo. Therefore, we undertook this study to evaluate in a canine in vivo model whether intraarticular exposure to coagulating blood is more destructive than exposure to anticoagulated blood, and whether inflammation plays a role in the cartilage- damaging process. In 7 dogs the left knees were injected with coagulating blood 4 times a week during weeks 1 and 4, and the right knees were injected with saline. In 7 other dogs, anticoagulated heparinized blood was injected, and heparinized saline was used as control. Ten weeks after the last injection, cartilage matrix turnover and synovial inflammation were analyzed. To study inflammation-independent cartilage damage, explants of cartilage from at least 6 human donors per group were exposed in vitro to coagulating and anticoagulated blood, plasma, and serum for 4 days. Cartilage matrix turnover was determined after a recovery period of 12 days. Canine knees injected with coagulating blood showed more disturbed proteoglycan turnover than knees injected with anticoagulated blood. Synovial inflammation was present only after intraarticular injections with coagulating blood. In in vitro experiments, exposure of human cartilage explants to coagulating blood resulted in more damage than did exposure to anticoagulated blood, while exposure to plasma and serum did not alter cartilage matrix turnover. This study shows that coagulating blood causes more long-lasting in vivo joint damage than anticoagulated blood, thereby suggesting that along with joint bleeding in hemophilia, exposure to intraarticular blood should also be avoided during surgery and trauma to prevent joint damage.


Cyclic AMP and tumor necrosis factor-alpha regulate CXCR4 gene expression in Schwann cells.
Rat peripheral nerve Schwann cells have been shown to express the alpha-chemokine receptor CXCR4 as well as the corresponding ligand stromal cell-derived factor-1 (SDF-1). We have investigated gene regulatory mechanisms acting on the expression of CXCR4 in cultured rat Schwann cells and found that receptor expression at transcript- and protein levels is directly dependent on intracellular cyclic AMP. Such increased levels of CXCR4 expression were found to be efficiently reversed by the action of tumor necrosis factor-alpha (TNFalpha). We also provide evidence that the POU box transcription factor Oct-6/SCIP is involved in the control of CXCR4 transcription. Finally, we could demonstrate that CXCR4 activation by SDF-1alpha increases the number of dying Schwann cells, indicating that this receptor/ligand interaction is modulating cell survival. Our data, therefore, suggest that in the Schwann cell lineage signal transduction cascades controlled by the activation of TNF- and CXCR4 receptors are functionally coupled.


RecA binding to bulge- and mismatch-containing DNAs. Certain single base mismatches provide strong signals for RecA binding equal to multiple base bulges.
Studies from several laboratories have demonstrated that RecA protein can recognize a variety of perturbations in the DNA helix. Here, using a nitrocellulose filter binding assay, it was observed that RecA bound to bulge-containing DNAs more effectively than non-bulged DNA. The degree of binding of RecA protein to bulged DNA was dependent on the conformation of the bulged bases and the kinking angles produced by the bulges as determined by the type and number of bases in the bulge. Although a single base mismatch does not kink DNA, RecA protein showed preferential binding to DNAs containing certain single base mismatches. An A.C mismatch flanked by A.T base pairs in a 28-base pair (bp) DNA facilitated the binding of RecA protein to the same high level as when the 28-bp DNA contained a 4-base cytosine bulge. Chemical probing techniques were used to examine the structure of DNA within the RecA filament. It was found that upon binding of RecA protein, the DNA helix becomes accessible over at least 14 bp, and the degree of sensitivity agrees with the binding efficiency of RecA protein.


Characterization and validation of a bioluminescent bioreporter for the direct detection of Escherichia coli.
A two-component bacteriophage-based bioluminescent reporter system was developed for the detection of Escherichia coli in environmental samples. The bioreporter system consists of a luxI integrated lambda bacteriophage and a lux-based bioluminescent reporter cell that responds to the infection event through acyl-homoserine lactone (AHL) mediated quorum sensing and bioluminescent signal stimulation. This work addresses the ability of the bioreporter system to detect and quantify the target pathogen in response to two analytical challenges: (1) detection of target cells in the presence of lactonase-producing non-target organisms that could interrupt AHL signal transduction, and (2) detection of sub-lethally injured or physiologically stressed target cells. The bioreporter system was able to autonomously respond to lambda phage infection events with a target host E. coli at 1x10(8) cfu/mL against a background of lactonase-producing Arthrobacter globiformis at cell densities ranging from 1 to 1x10(8) cfu/mL. E. coli target cells stressed by carbon-limitation for 2 weeks (i.e., starvation) or exposure to iodine for 1 week at 2 and 20 ppm (i.e., disinfection) yield a reduced, but detectable, biosensor response. Conversely, short-term iodine exposure produces a significant increase in bioreporter response within the first 24 h. The signal response and limit of detection for the two-component bioreporter system were affected by the physiology and environment of the target, but the bioreporter maintained target specificity demonstrating its potential application for remote sensing of pathogens.


Influence of patient, visit, and oral health factors on dental service provision.
Service provision should reflect the oral health of the patient. However, patient and visit factors may influence service patterns and the appropriateness of care delivered. The aim of this study was to examine factors associated with variation in dental services and to assess whether variation by patient and visit characteristics persisted after controlling for oral health status. A random sample of Australian dentists was surveyed during 1997-98 (response rate = 60.3%). Private general practitioners (n = 345) provided data on service provision, as well as patient, visit and oral health variables from a log of a typical clinical day (n = 4,115 patients). Multivariate Poisson regression models were run for eight service areas (e.g., diagnostic, preventive, and restorative). Significant effects (P < .05) were observed for oral health factors in all eight models, visit factors in all eight models, patient demographics in four models, dental knowledge/behavior in one model, and area-based socioeconomic status in one model. After controlling for oral health, visit characteristics persisted as significant predictors of services, with nonemergency visits, insurance, and capital city location associated with more favorable service mix patterns. Higher socioeconomic status areas and payment scale ratings also were associated with a better service pattern in particular service areas. These findings show that a wide range of factors, in addition to oral health, contribute to variation in service provision.


[Prognostic value of e-cadherin in papillary thyroid carcinoma].
The prognostic significance of e-cadherin in papillary thyroid carcinoma was evaluated in a retrospective study. From September 1985 to December 1996, 113 patients underwent surgery for papillary thyroid carcinoma. Seventy-eight formalin-fixed, paraffin-embedded tissue samples were available for immunohistochemical analysis of e-cadherin expression. In 74 of these 78 patients the postoperative course is known for 2 months to 35.2 years (median 3.6 years, mean: 4.9 +/- 4.8 years). Reduced or negative e-cadherin expression (< or = 20%) was associated with advanced T categories of the primary tumours and higher rates of synchronous lymph node involvement and distant metastasis. During follow-up in this group of patients locoregional tumour recurrence occurred more frequently and survival was shorter than in patients with tumours which exhibited e-cadherin expression of > 20%. Statistical analysis revealed e-cadherin expression (< or = 20%/ > 20%), synchronous distant metastasis (M0/pM1, cM1) and radicality of resection (R0/R1, 2) as significant risk factors for survival. Our findings provide evidence that e-cadherin is a prognostic factor in papillary thyroid carcinoma.


Evaluation of safety and efficacy of transjugular liver biopsy in allogeneic hematopoietic stem cell transplant recipients.
We retrospectively evaluated the safety and utility of transjugular liver biopsy (TJLB) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Ten patients underwent HSCT between 1991 and 2013. Eight patients with thrombocytopenia received platelet transfusions before and/or during TJLB. No complications associated with TJLB were observed. Samples adequate for a pathological diagnosis were obtained in 9 of the 10 patients, and the diagnoses made by TJLB were graft-versus-host-disease in eight patients and non-specific hepatitis in one. These results suggest that TJLB is a safe and effective procedure for the evaluation of liver injury in HSCT recipients.


Effect of polystyrene microplastics on tetracycline photoconversion under simulated sunlight: Vital role of aged polystyrene.
Photoconversion of tetracycline (TC) has been widely reported. However, the effect of microplastics (MPs) on TC conversion kinetics and mechanism has rarely been discussed. In this study, we investigated the effect of (aged) MPs on TC degradation under simulated sunlight and elucidated the underlying mechanism. Our findings demonstrated that the physical and chemical properties of polystyrene (PS), such as particle size, surface groups, and morphology, were significantly altered after aging. Moreover, photoconversion efficiency of TC was suppressed with the spiking of aged PS, while virgin PS showed an opposite tendency. The photodegradation reaction for photosensitization of PS involved 1O2 and HO·. The light-screening effect of aged PS occupied predominance, weakening the direct UV-light absorption of TC and resulting in lower TC degradation efficiency. Additionally, triplet-excited state PS was generated after photon acceptance by aged PS, which could transfer energy to O2, leading to the production of 1O2. The toxicity test manifested that the direct impact of TC products on fathead minnow was ignorable, but long-term negative effects on growth deserved observation. This study enhances our understanding of the environmental fate of PS and TC under sunlight, and provides crucial reference information for better evaluating the potential risk of MPs and chemicals.


A systematic review of the distribution of take-home naloxone in low- and middle-income countries and barriers to the implementation of take-home naloxone programs.
Opioid overdose epidemic is hitting record highs worldwide, accounting for 76% of mortality related to substance use. Take-home naloxone (THN) strategies are being implemented in many developed countries that suffer from high opioid overdose death rates. They aim to provide overdose identification and naloxone administration training, along with THN delivery to opioid users and others likely to witness an overdose incident such as family members and peers. However, little is known about such measures in low- and middle-income countries (LMIC), where opioid use and opioid-related deaths are reportedly high. This systematic literature review aims to examine the distribution of THN in LMIC, review studies identifying barriers to the implementation of THN programs worldwide, and assess their applicability to LMIC. The literature was searched and analyzed for eligible studies with quality assessment. Two studies were found from LMIC on THN programs with promising results, and 13 studies were found on the barriers identified in implementing THN programs worldwide. The main barriers to THN strategies were the lack of training of healthcare providers, lack of privileges, time constraints, cost, legislative/policy restrictions, stigma, fear of litigation, and some misperceptions around THN. The barriers outlined in this paper are probably applicable to LMIC, but more difficult to overcome considering the differences in their response to opioid overdose, their cultural attitudes and norms, the high cost, the waivers required, the legislative differences and the severe penalties for drug-related offenses in some of these countries. The solutions suggested to counter-act these obstacles can also be more difficult to achieve in LMIC. Further research is required in this area with larger sample sizes to provide a better understanding of the obstacles to the implementation, feasibility, accessibility, and utilization of THN programs in LMIC.


An implantable vascularized protein gel construct that supports human fetal hepatoblast survival and infection by hepatitis C virus in mice.
Widely accessible small animal models suitable for the study of hepatitis C virus (HCV) in vivo are lacking, primarily because rodent hepatocytes cannot be productively infected and because human hepatocytes are not easily engrafted in immunodeficient mice. We report here on a novel approach for human hepatocyte engraftment that involves subcutaneous implantation of primary human fetal hepatoblasts (HFH) within a vascularized rat collagen type I/human fibronectin (rCI/hFN) gel containing Bcl-2-transduced human umbilical vein endothelial cells (Bcl-2-HUVEC) in severe combined immunodeficient X beige (SCID/bg) mice. Maturing hepatic epithelial cells in HFH/Bcl-2-HUVEC co-implants displayed endocytotic activity at the basolateral surface, canalicular microvilli and apical tight junctions between adjacent cells assessed by transmission electron microscopy. Some primary HFH, but not Huh-7.5 hepatoma cells, appeared to differentiate towards a cholangiocyte lineage within the gels, based on histological appearance and cytokeratin 7 (CK7) mRNA and protein expression. Levels of human albumin and hepatic nuclear factor 4alpha (HNF4alpha) mRNA expression in gel implants and plasma human albumin levels in mice engrafted with HFH and Bcl-2-HUVEC were somewhat enhanced by including murine liver-like basement membrane (mLBM) components and/or hepatocyte growth factor (HGF)-HUVEC within the gel matrix. Following ex vivo viral adsorption, both HFH/Bcl-2-HUVEC and Huh-7.5/Bcl-2-HUVEC co-implants sustained HCV Jc1 infection for at least 2 weeks in vivo, based on qRT-PCR and immunoelectron microscopic (IEM) analyses of gel tissue. The system described here thus provides the basis for a simple and robust small animal model of HFH engraftment that is applicable to the study of HCV infections in vivo.


Role of indenter material and size in veneer failure of brittle layer structures.
The roles of indenter material and size in the failure of brittle veneer layers in all-ceramic crown-like structures are studied. Glass veneer layers 1 mm thick bonded to alumina layers 0.5 mm thick on polycarbonate bases (representative of porcelain/ceramic-core/dentin) are subject to cyclic contact loading with spherical indenters in water (representative of occlusal biting environment). Two indenter materials-glass and tungsten carbide-and three indenter radii-1.6, 5.0, and 12.5 mm-are investigated in the tests. A video camera is used to follow the near-contact initiation and subsequent downward propagation of cone cracks through the veneer layer to the core interface, at which point the specimen is considered to have failed. Both indenter material and indenter radius have some effect on the critical loads to initiate cracks within the local Hertzian contact field, but the influence of modulus is weaker. The critical loads to take the veneer to failure are relatively insensitive to either of these indenter variables, since the bulk of the cone crack propagation takes place in the contact far field. Clinical implications of the results are considered, including the issue of single-cycle overload versus low-load cyclic fatigue and changes in fracture mode with loading conditions.


microRNAs and the regulation of glucose and lipid metabolism.
Over recent years, metabolic disorders such as type 2 diabetes have finally become recognized as a major challenge to global health. The attention of scientists therefore has to focus on improving our understanding of the molecular mechanisms behind these diseases and towards the design of new drug therapy strategies. The pathophysiology of diabetes is undoubtedly complex, oftentimes characterized by varying states of insulin resistance and impaired beta-cell function; however, the identification of new pathways is constantly improving our understanding of the disease. We and others have recently shown that microRNAs (miRNAs) can play a role in insulin secretion and glucose homostasis. Thus, in this review, we will discuss the potential role of miRNAs in type 2 diabetes and related metabolic diseases.