Comparative Analysis of the Most Used Versus the Recently Developed Vitiligo Activity and Extent Scores and Their Change with Treatment.
There are diverse assessment tools for vitiligo, with no standardized approach that helps unify treatment outcome measures. Thus, comparing different treatment modalities and developing evidence-based recommendations for vitiligo management has been quite challenging. We compared the most commonly used tools assessing both vitiligo activity and extent, namely, Vitiligo Disease Activity Score (VIDA) and Vitiligo Area and Severity Index (VASI) score to their newly developed counterparts, namely, Vitiligo Extent Score Plus (VES plus) and Vitiligo Signs of Activity score (VSAS), to provide insights that would help set recommendations for a unified outcome assessment protocol for vitiligo patients. Thirty-six active non-segmental vitiligo cases were recruited, 30 of whom completed 48 sessions of narrow band ultraviolet B (NB-UVB). Patients were assessed for both extent and activity both before and after treatment with NB-UVB. Scores were correlated. Additionally, VES plus was assessed for its reliability in comparison to VASI score. Both extent (VASI and VES plus) and activity scores (VIDA and VSAS) showed significant improvement following treatment. Additionally, VES plus and VASI were positively correlating both before and after treatment as well as their percent change. Furthermore, VES plus proved as reliable as VASI. Regarding activity scores, total, hypochromic and Koebner VSAS only correlated with VIDA following treatment. Confetti VSAS neither correlated with VIDA before nor after treatment. VES plus and VASI scores have proven of comparable reliability. While examination-based VSAS score comes as an additive tool to the history-based VIDA score.


Region-specific depression of striatal activity in Wistar rat by modest ethanol consumption over a ten-month period.
The nucleus accumbens (nAc) is the primary target for the mesolimbic dopamine system and a key brain region for the reinforcing effects displayed by drugs of abuse, including ethanol. During the transition from recreational to compulsive consumption of reinforcing drugs, however, the dorsal striatum seems to be recruited. Understanding how synaptic activity is altered in a sub-region specific manner in the striatum during the course of long-term drug consumption thus could be essential for understanding the long-lasting changes produced by addictive substances, including ethanol. Here we evaluated synaptic activity in the dorsolateral striatum (DLS) and ventral striatum (nucleus accumbens, nAc) of single-housed Wistar rats consuming water, or water and ethanol, for up to 10 months. Even though ethanol intake was moderate, it was sufficient to decrease input/output function in response to stimulation intensity in the DLS, while recorded population spike (PS) amplitudes in the nAc were unaffected. Striatal disinhibition induced by the GABAA receptor antagonist bicuculline had a slower onset in rats that had consumed ethanol for 2 months, and was significantly depressed in slices from rats that had consumed ethanol for 4 months. Bicuculline-induced disinhibition in the nAc, on the other hand, was not significantly altered by long-term ethanol intake. Changes in PS amplitude induced by taurine or the glycine receptor antagonist strychnine were not significantly altered by ethanol in any brain region. Even though input/output function was not significantly affected by age, there was a significant decline in antagonist-induced disinhibition in brain slices from aged rats. The data presented here suggest that even modest consumption of ethanol is sufficient to alter neurotransmission in the striatum, while synaptic activity appears to be relatively well-preserved in the nAc during the course of long-term ethanol consumption.


Facile synthesis of a free-standing Ag@AgCl film for a high performance photocatalyst and photodetector.
A novel and facile method is developed to prepare an Ag@AgCl film which exhibits high photocatalytic activity under visible light irradiation. In addition, it can also be used to fabricate a photodetector that possesses a fast response time and good photocurrent reproducibility.


Biochemical events in nitrosamine-induced hepatocarcinogenesis: relevance of animal data to human carcinogenesis.
Administration of carcinogens to experimental animals results in the early formation of phenotypically altered cell foci. Evidence suggesting their intermediary role in hepatocarcinogenesis, and some of their biological properties are reviewed. Two concepts relating to the mechanism of tumour promotion are described briefly, i.e., the 'resistant cell' hypothesis and that of 'overexpression of adaptive growth'. It is concluded that studies on liver foci may be helpful in elucidating the nature of the events involved in the initiation of carcinogenesis. Some aspects relating to human hepatocarcinogenesis are also considered briefly.


Segmentation of fat in MRI using a preparatory pair of rectangular RF pulses of opposite direction.
A radiofrequency (RF) pulse-based MRI method is introduced as a novel fat (or water) segmentation method that, unlike the mostly used Dixon's method, does not depend on the echo times. A pair of rectangular RF pulses of opposite direction, when the duration of its rectangular pulse and the off-resonance of its carrier frequency are set to specific values, is proposed as a preparatory RF pulse to be used for the quantitative fat segmentation. The optimal duration of its rectangular pulse and its specific off-resonance were first determined theoretically. Then, such pair of rectangular pulses of opposite direction (PROD pulse) was applied in imaging a few phantoms and volunteers. During the imaging experiments, MRI images were dynamically acquired with the PROD pulse while its carrier frequency was varied in a predefined off-resonance range. By analyzing the dynamically acquired signal changes, the theoretical properties of the PROD pulse were confirmed and the utility of the PROD pulse for the fat segmentation was verified. All MRI scans were performed in a clinical 3T system. The PROD pulse, if the duration of each rectangular pulse was set to 1.66ms and its carrier frequency was set to a specific off-resonance (e.g. ±223.5Hz, or -670.5Hz) in 3T, was effective in optimally modulating MRI signals to be used for the fat-water segmentation. Therefore, the PROD pulse can successfully be used as a preparatory RF pulse in MRI to achieve effective fat (or water) segmentation in MRI.


Hand, foot, and spine deformities in parkinsonian disorders.
Hand and foot deformities, known as "striatal deformities", and other musculoskeletal abnormalities such as dropped head, bent spine, camptocormia, scoliosis and Pisa syndrome, are poorly understood and often misdiagnosed features of Parkinson's disease and other parkinsonian syndromes. These deformities share some similarities with known rheumatologic conditions and can be wrongly diagnosed as rheumatoid arthritis, osteoarthritis, psoriatic arthritis, Dupuytren's contracture, trigger finger, or other rheumatologic or orthopedic conditions. Neurologists, rheumatologists, and other physicians must be familiar with these deformities to prevent misdiagnosis and unnecessary diagnostic tests, and to recommend appropriate treatment options.


Management of cytogenetic data in multi-center leukemia trials.
This paper provides methods for storing and retrieving cytogenetics data, which must reside jointly in a reference laboratory and in a data co-ordinating center. The major piece of data is the character string that uses the International System for Human Cytogenetic Nomenclature. Simple and complex data retrieval, using Statistical Analysis System (SAS) functions INDEX and SUBSTR, are illustrated. Use of the methods of this paper can save considerable costs in setting up cytogenetic data systems compared with other proposed systems which have come to the authors' attention.


Comparative pharmacokinetics of coumarin anticoagulants XXXV: Examination of possible pharmacokinetic interaction between (R)-(+)- and (S)-(--)-warfarin in humans.
The elimination kinetics and anticoagulant effect produced by single 1.5-mg/kg doses of (R)-(+(-, (S)-(--)-, and racemic warfarin were determined in 10 healthy men. The results obtained in experiments with the individual enantiomers were used to predict the elimination kinetics and anticoagulant effect of racemic warfarin, assuming that there is no interaction between the two enantiomers. These predictions were compared to experimental results, and no significant differences were observed. This finding suggests that there are no pronounced pharmacokinetic or pharmacodynamic interactions between single large doses of (R)-(+)- and (S)-(--)-warfarin in humans.


Convolutional neural network (CNN) with metaheuristic optimization algorithms for landslide susceptibility mapping in Icheon, South Korea.
Landslides are a geological hazard that can pose a serious threat to human health and the environment of highlands or mountain slopes. Landslide susceptibility mapping is an essential tool for predicting and mitigating landslides. This study aimed to investigate the application of deep learning algorithms based on convolutional neural networks (CNNs) with metaheuristic optimization algorithms, namely the grey wolf optimizer (GWO) and imperialist competitive algorithm (ICA), to landslide susceptibility mapping. The study area was Icheon City, South Korea, for which an accurate landslide inventory dataset was available. The landslide inventory map was prepared and randomly divided into datasets of 70% for training and 30% for validation. Additionally, 18 landslide-related factors, including geo-environmental and topo-hydrological factors, were considered as predictive variables. The models were compared using area under the curve (AUC) values in receiver operating characteristic (ROC) curve analysis. The validation results showed that optimized models based on CNN-GWO (AUC = 0.876, RMSE = 0.08) and CNN-ICA (AUC = 0.852, RMSE = 0.09) outperformed the standalone CNN model (AUC = 0.847, RMSE = 0.12). Nevertheless, the CNN model outperformed previous research that used a machine learning algorithm alone. Thus, the deep learning algorithm with optimization algorithms proposed in this study can generate more suitable models for landslide susceptibility mapping in the study area due to its improved accuracy.


Therapeutic application of 6-Hz-primed low-frequency rTMS combined with intensive speech therapy for post-stroke aphasia.
To clarify the safety, feasibility and efficacy of 6-Hz-primed low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive speech therapy (ST) for post-stroke aphasic patients. Four adult patients with history of left hemispheric stroke and with motor-dominant aphasia were studied. During 11-day hospitalization, each patient received 18 treatment sessions consisting of 10-min 6-Hz priming stimulation followed by 20-min 1-Hz low-frequency rTMS and intensive ST for 60 min daily. Both the priming stimulation and low-frequency rTMS were applied to the right frontal lobe. The intensive ST was provided on one-to-one basis. Language function was assessed by Standard Language Test of Aphasia (SLTA), Supplementary Test of SLTA (SLTA-ST), and the Japanese version of Western Aphasia Battery (WAB) within 2 weeks prior to the admission and on the day of discharge. The in-patient protocol was successfully completed by all patients without any adverse effects. Each patient showed an increase in the correct answer rate after the intervention. Improvement was found in both expressive and recessive language modalities in all patients. The protocol of 6-Hz-primed low-frequency rTMS and intensive ST for post-stroke aphasia was safe and feasible, suggesting its potential usefulness in the treatment of this population.


Severe dyshidrosis in two patients with HIV infection shortly after starting highly active antiretroviral treatment.
The use of highly active antiretroviral therapy (HAART) is the gold-standard treatment for HIV infected patients. We here describe two HIV positive patients whose histories are suggestive for dyshidrosis as an immune reconstitution inflammatory syndrome (IRIS). Several factors have been associated with the exacerbation of dyshidrosis lesions but no direct relationship with HAART has been reported until now.


Isocratic high-performance liquid chromatographic method with ultraviolet detection for simultaneous determination of levels of voriconazole and itraconazole and its hydroxy metabolite in human serum.
A simple, specific method is presented for simultaneous determination of voriconazole and itraconazole and its metabolite, hydroxyitraconazole, in human serum using one-step liquid-liquid extraction and high-performance liquid chromatography. Linearity tests ranged from 0.1 to 8.0 microg/ml; the minimum detectable concentration was 0.03 microg/ml.


Sonocatalytic degradation of acid red B and rhodamine B catalyzed by nano-sized ZnO powder under ultrasonic irradiation.
Nano-sized ZnO powder was introduced to act as the sonocatalyst after the treatment of high-temperature activation, and the ultrasound of low power was used as an irradiation source to induce nano-sized ZnO powder performing sonocatalytic degradation of acid red B and rhodamine B. At the same time, the effects of operational parameters such as solution pH value, initial concentration of dyestuff and addition amount of nano-sized ZnO powder have been examined in this paper. We found that the degradation ratios of acid red B and rhodamine B in the presence of nano-sized ZnO powder were much higher than that with only ultrasonic irradiation. However, the degradation ratio of acid red B was about two times higher than that of rhodamine B for the initial concentration of 10.0mg/L, addition amount of 1.0 g/L nano-sized ZnO powder, solution acidity of pH 7.0 and 60 min irradiation experimental condition. The difference of the degradation ratios can be illustrated by the difference of chemical forms of acid red B and rhodamine B in aqueous solution and the surface properties of nano-sized ZnO particles. In addition, the researches on the kinetics of sonocatalytic reactions of acid red B and rhodamine B have also been performed and found to the follow pseudo first-order kinetics. All the experiments indicated that the sonocatalytic method in the presence of nano-sized ZnO powder was an advisable choice for the treatments of non- or low-transparent organic wastewaters in future.


PD 115,199: an antagonist ligand for adenosine A2 receptors.
PD 115,199, N-[2-(dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- dipropyl-1H-purin-8-yl)benzenesulfonamide, was found to have high affinity for the A2 adenosine receptor labeled by 3H-NECA in rat striatal membranes (Ki 15.5 nM). Unlike other potent adenosine antagonists, which always showed some degree of selectivity for the A1 receptor, PD 115,199 had equal affinity at A1 and A2 receptors (Ki in 3H-CHA binding to A1 receptors 13.9 nM). 3H-PD 115,199 (126 Ci/mmol) was prepared by reduction of the diallyl analog, and binding experiments were performed with 0.5 nM 3H-PD 115,199 at 25 degrees C in rat striatal membranes. By nonlinear least-squares analysis of the concentration-inhibition curve for the highly A1-selective adenosine antagonist PD 116,948 (8-cyclopentyl-1,3-dipropylxanthine), it could be demonstrated that about 11% of specific 3H-PD 115,199 binding was to A1 receptors, and the remainder to A2 receptors. A 20 nM concentration of PD 116,948 was included in subsequent experiments to eliminate the A1 component of binding. The remaining binding had a Kd of 2.6 nM and Bmax of 56 pmol/g wet weight. Specific binding was about 79% of total binding. Affinities of compounds in the 3H-PD 115,199 assay were consistent with binding to a high-affinity A2 receptor: antagonists were consistently about three times more potent in 3H-PD 115,199 binding than in 3H-NECA binding, whereas agonists were consistently about fivefold less potent.(ABSTRACT TRUNCATED AT 250 WORDS)


Spatial organization of human perioral reflexes.
Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.


Effects of ammonium nitrate exposure and water acidification on the dwarf newt: the protective effect of oviposition behaviour on embryonic survival.
Embryonic mortality in many aquatic animals, including most amphibian species, is usually very high. In addition to mechanical and chemical defences, some species have developed behavioural patterns that can increase egg survival. For example, females of some newt species protect their eggs by wrapping them in leaves of aquatic plants. We have studied the effects of ammonium nitrate (nominal concentration of 90.3 mg N-NO(3)NH(4)/L) and water acidification (pH 4-5) on egg wrapping behaviour of the dwarf newt, Triturus pygmaeus, and on whether this specific behaviour may protect embryos from contamination. Although either ammonium nitrate or low pH did not inhibit oviposition, the mean percentage of eggs that were wrapped by the females was significantly lower at low pH than in controls. In order to assess the potential effects of oviposition behaviour on embryonic survival, we exposed simultaneously wrapped and unwrapped eggs to ammonium nitrate and acid pH during their development. After 25 days of exposure, ammonium nitrate reduced length and developmental stage at eclosion of the exposed individuals, regardless of whether they were wrapped or unwrapped. The fertilizer caused a significantly higher mortality in unwrapped than wrapped eggs. The potential impact of water pollution on amphibians in the field may include not only direct effects on embryonic and larval survival but also alteration of breeding behaviours, which may reduce reproductive success and ultimately affect population's condition.


Evaluation of the effect of sickle cell disease on the mandibular bone of children and adolescents by image texture and radiomorphometric analysis.
Sickle cell disease (SCD) can cause osteoporotic changes in the jaw bones. In this study, it was aimed to evaluate possible bone changes using fractal analysis (FA) and morphometric analyses in dental panoramic radiographs of children and adolescents diagnosed with both homozygous and heterozygous forms of SCD. Sixty-five individuals (33 SCD, 32 controls) aged 6-17 years were included in the study. Four separate areas of interest (ROI) were selected for the right and left sides of all panoramic radiographs, and the FA value of the ROIs was calculated. Mandibular cortical width (MCW), panoramic mandibular index (PMI) and mandibular cortical index (MCI) and were evaluated. Data were statistically analyzed and p < 0.05 was accepted for statistical significance. Fractal values of right and left ROI1 (the center of the mandibular angle.) and ROI4 (the cortical bone), and right ROI2 (the middle of the mandibular ramus) were statistically lower in the case group (p < 0.05). Right ROI2 and ROI4 fractal values of individuals in the case group were lower than those on the left side (p < 0.05). While MCI categories did not differ from the case-control group (p > 0.05), PMI and MCW values were lower in the case group (p < 0.05). All evaluated parameters did not differ according to age and gender (p > 0.05). The results of this study showed that SCD affects the mandible. FA, MCW and PMI parameters can be used to detect early osteoporotic changes in the disease.


Acquired immunity to the trematode Fasciola hepatica in rats.
Following a primary infection of 5 metacercariae (mc) of Fasciola hepatica, rats became immune to challenge with 30 mc. Immunity was less consistently demonstrated following challenge infection with 5 mc. The levels of precipitating and miracidial immobilizing antibodies, and antibodies detected by an indirect fluorescent antibody test, were monitored during the course of a primary infection of 5 mc and challenge infection of 30 mc. Following primary infection, peaks in the antibody response were associated with the invasion and migration of juvenile flukes in the liver parenchyma. Antibody titres fell when flukes entered the bile duct. There was a slight elevation in the titre of all antibodies following challenge, but, apart from those detected by the fluorescent antibody test, this elevation was not as marked as in control animals. It is suggested that flukes become isolated from, or have diminished contact with, the immune system once they enter the bile duct. This might explain why adult flukes survive in immune hosts whereas challenge metacercariae are destroyed.


Clinical usefulness of transpapillary removal of common bile duct stones by frequency doubled double pulse Nd:YAG laser.
To study the efficacy and the safety of laser lithotripsy without direct visual control by using a balloon catheter in patients with bile duct stones that could not be extracted by standard technique. The seventeen patients (7 male and 10 female; mean age 67.8 years) with difficult common bile duct (CBD) stones were not amenable for conventional endoscopic maneuvers such as sphincterotomy and mechanical lithotripsy were included in this study. Laser wavelengths of 532 nm and 1064 nm as a double pulse were applied with pulse energy of 120 mJ. The laser fiber was advanced under fluoroscopic control through the ERCP balloon catheter. Laser lithotripsy was continued until the fragment size seemed to be less than 10 mm. Endoscopic extraction of the stones and fragments was performed with the use of the Dormia basket and balloon catheter. Bile duct clearance was achieved in 15 of 17 patients (88%). The mean number of treatment sessions was 1.7 +/- 0.6. Endoscopic stone removal could not be achieved in 2 patients (7%). Adverse effects were noted in three patients (hemobilia, pancreatitis, and cholangitis). The Frequency Doubled Double Pulse Nd:YAG (FREDDY) laser may be an effective and safe technique in treatment of difficult bile duct stones.


COVID-19 in the Healthy Patient Population: Demographic and Clinical Phenotypic Characterization and Predictors of In-Hospital Outcomes.
Coronavirus disease 2019 (COVID-19) can infect patients in any age group including those with no comorbid conditions. Understanding the demographic, clinical, and laboratory characteristics of these patients is important toward developing successful treatment strategies. Approach and Results: In a retrospective study design, consecutive patients without baseline comorbidities hospitalized with confirmed COVID-19 were included. Patients were subdivided into ≤55 and >55 years of age. Predictors of in-hospital mortality or mechanical ventilation were analyzed in this patient population, as well as subgroups. Stable parameters in overall and subgroup models were used to construct a cluster model for phenotyping of patients. Of 1207 COVID-19-positive patients, 157 met the study criteria (80≤55 and 77>55 years of age). Most reliable predictors of outcomes overall and in subgroups were age, initial and follow-up d-dimer, and LDH (lactate dehydrogenase) levels. Their predictive cutoff values were used to construct a cluster model that produced 3 main clusters. Cluster 1 was a low-risk cluster and was characterized by younger patients who had low thrombotic and inflammatory features. Cluster 2 was intermediate risk that also consisted of younger population that had moderate level of thrombosis, higher inflammatory cells, and inflammatory markers. Cluster 3 was a high-risk cluster that had the most aggressive thrombotic and inflammatory feature. In healthy patient population, COVID-19 remains significantly associated with morbidity and mortality. While age remains the most important predictor of in-hospital outcomes, thromboinflammatory interactions are also associated with worse clinical outcomes regardless of age in healthy patients.


Does additional extracorporeal shock wave therapy improve the effect of isolated percutaneous radiofrequency coblation in patients with insertional Achilles tendinopathy? Study protocol for a randomized controlled clinical trial.
No conclusive evidence recommends a prior treatment for insertional Achilles tendinopathy (IAT). It is theorized that both percutaneous radiofrequency coblation and extracorporeal shockwave therapy (ESWT) relieve pain within the insertion. However, no clinical evidence shows that either treatment promotes the regeneration of the tendon or if the combination of these 2 interventions offers better function and less pain than one therapy. The study is a randomized, controlled trial with patients allocated in a 1:1 ratio to one of two parallel groups. Patients with insertional Achilles tendinopathy who are not satisfied with the effect of conservative treatment will be screened. A minimum of 38 patients will be enrolled after deciding to participate in the trial on an informed basis. Then the intervention group and the control group perform radial ESWT and sham-ESWT respectively at 6 months after percutaneous radiofrequency coblation. The primary outcome will be the Victorian Institute of Sports Assessment Achilles (VISA-A) Score. Secondary outcome measures will be Foot and Ankle Outcome Score (FAOS) scale, visual analog scale (VAS), Tegner Score, and MRI ultra-short echo time (UTE) T2* value. The assessments will occur in 6 months, 1 year, and 2 years, post-operatively. The differences between the 2 groups will be conducted as intention-to-treat basis. We aim to investigate if radiofrequency coblation associated with ESWT can provide more encouraging imaging findings as well as functional and clinical outcomes regarding the treatment of the IAT comparing to the single radiofrequency coblation treatment. ChiCTR1800017898; pre-results. Registered on 20 August 2018.


Estramustine phosphate therapy in carcinoma of the prostate.
Estramustine phosphate, a nor nitrogen mustard derivative of estradiol 17-beta-phosphate, was introduced in the treatment of prostatic carcinoma in 1966. Until March 1975, 466 patients have been reported on this treatment in open clinical trials: 82% of the patients were in stage IV. In 402 patients, nonresponsive to previous estrogen therapy, signigicant improvement occurred in 55%. In 64 previously untreated patients there was a favourable response in 83%. Side-effects were mainly bone marrow suppression. liver disturbance, thrombophlebitis following intravenous injection, and gastrointestinal troubles, mainly following oral administration. A prospective, randomized study comparing oral estramustine phosphate and conventional estrogen therapy in carcinoma of the prostate is in progress.


Construction of a lncRNA-miRNA-mRNA network to determine the key regulators of the Th1/Th2 imbalance in multiple sclerosis.
Aim: The exact epigenetic mechanisms that determine the balance of T helper (Th)1 and Th2 cells and autoimmune responses in multiple sclerosis (MS) remain unclear. We aim to clarify these. Methods: A combination of bioinformatics analysis and molecular evaluations was utilized to identify master hub genes. Results: A competitive endogenous RNA network containing six long noncoding RNAs (lncRNAs), 21 miRNAs and 86 mRNAs was provided through enrichment analysis and a protein-protein interaction network. NEAT1 and MALAT1 were found as differentially expressed lncRNAs using Gene Expression Omnibus (GSE21942). Quantitative real-time PCR results demonstrate dysregulation in the RUNX3 (a regulator of Th1/Th2 balance), GATA3 and TBX21, as well as miR-544a and miR-210-3p (which directly target RUNX3). ELISA also confirmed an imbalance in IFN-γ (Th1)/IL-4 (Th2) in MS patients. Conclusion: Our findings introduce novel biomarkers leading to Th1/Th2 imbalance in MS.


Early orchiopexy and testis tumors.
A testicular tumor developed in a twenty-year-old man who had undergone orchiopexy at age six. The case illustrates that early orchiopexy affords no protection against subsequent malignant degeneration. The importance of an inguinal approach and a high orchiectomy are stressed.


Effect of PANDER in βTC6-cell lipoapoptosis and the protective role of exendin-4.
Chronic exposure to high concentrations of saturated fatty acids, such as palmitic acid (PA), leads to apoptosis of pancreatic β-cells through the activation of the c-Jun N-terminal kinase (JNK) signaling pathway. This study of β-cell lipoapoptosis was designed to investigate the roles of pancreatic-derived factor (PANDER), a pro-apoptosis cytokine-like peptide, and exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor and anti-apoptosis factor. The glucose-sensitive mouse β-pancreatic cell line, βTC6, was used to investigate the mechanisms of PA-induced apoptosis. Twenty-four hours of PA exposure led to increased PANDER expression in a dose- and time-dependent manner, and significantly increased phosphorylation of JNK. Treatment with the JNK-specific inhibitor SP600125 reduced the PA-induced PANDER expression. After the 24h of PA exposure, cells also underwent marked apoptosis and showed increased activation of the apoptosis protease, caspase-3. The small interfering (si)RNA-mediated silencing of PANDER gene expression significantly reduced both of these effects. When PA-treated βTC6 cells were exposed to exogenous exendin-4, JNK activation was inhibited, PANDER expression was decreased, and the numbers of apoptotic cells were reduced. Collectively, these results demonstrated that the JNK-mediated signaling mechanism of PA-induced β-cell apoptosis involves up-regulated expression of PANDER and activation of caspase-3. Exendin-4 may protect against lipoapoptosis by interfering with the JNK-PANDER pathway.


A new insight into the role of plasma fibrinogen in the development of metabolic syndrome from a prospective cohort study in urban Han Chinese population.
Elevated levels of fibrinogen may contribute to a prothrombotic state. Cross-sectional studies suggest fibrinogen possibly linked with MetS/its components, while results of cohort studies remain controversial. Thus, this study was designed to identify the association of plasma fibrinogen with metabolic syndrome (MetS) and further to clarify the role of fibrinogen in the development of MetS. A large-scale prospective cohort study was conducted in routine health check-up population. 6209 participants free of MetS at baseline were included in the original cohort, with annually routine health check-up for incident MetS from 2005 to 2011. Then, 4 pre-MetS sub-cohorts, with overweight, hypertension, hyperglycemia and dyslipidemia at baseline respectively, were also created from the original cohort. Various strategies of Cox model analysis were performed for attempting to confirm the role of fibrinogen in the development of MetS. Total MetS incidence density was 75.58 per 1000 person-years. Cox regression analysis by adjusting for potential confounders as well as four MetS components showed a significant effect of fibrinogen on MetS just in female, with risk ratio (RR) (95 % CI) of 1.48 (1.02, 2.13) for Q4 vs. Q1. Further analysis in the 4 pre-MetS female sub-cohorts revealed this significant effect only in overweight sub-cohort, with RR (95 % CI) of 1.97 (1.20, 3.23), but no significant interaction of overweight with fibrinogen on MetS was revealed in original female cohort. Then, stratification analysis among the 4 sub-groups of fibrinogen quartiles showed that effects of overweight on MetS were different among the 4 sub-groups of fibrinogen quartiles, with RR of 2.98 for Q1, 4.40 for Q2, 3.93 for Q3, and 4.82 for Q4 respectively. Fibrinogen was associated with MetS just in overweight sub-cohort of female individuals, and fibrinogen might be a potential modifier in the pathway from overweight to MetS.


Networks of worry-towards a connectivity-based signature of late-life worry using higher criticism.
Severe worry is a complex transdiagnostic phenotype independently associated with increased morbidity, including cognitive impairment and cardiovascular diseases. We investigated the neurobiological basis of worry in older adults by analyzing resting state fMRI using a large-scale network-based approach. We collected resting fMRI on 77 participants (>50 years old) with varying worry severity. We computed region-wise connectivity across the default mode network (DMN), anterior salience network, and left executive control network. All 22,366 correlations were regressed on worry severity and adjusted for age, sex, race, education, disease burden, depression, anxiety, rumination, and neuroticism. We employed higher criticism, a second-level method of significance testing for rare and weak features, to reveal the functional connectivity patterns associated with worry. The analysis suggests that worry has a complex, yet distinct signature associated with resting state functional connectivity. Intra-connectivities and inter-connectivities of the DMN comprise the dominant contribution. The anterior cingulate, temporal lobe, and thalamus are heavily represented with overwhelmingly negative association with worry. The prefrontal regions are also strongly represented with a mix of positive and negative associations with worry. Identifying the most salient connections may be useful for targeted interventions for reducing morbidity associated with severe worry in older adults.


Linking Heterochromatin Protein 1 (HP1) to cancer progression.
All cells of a given organism contain nearly identical genetic information, yet tissues display unique gene expression profiles. This specificity is in part due to transcriptional control by epigenetic mechanisms that involve post-translational modifications of histones. These modifications affect the folding of the chromatin fiber and serve as binding sites for non-histone chromosomal proteins. Here we discuss functions of the Heterochromatin Protein 1 (HP1) family of proteins that recognize H3K9me, an epigenetic mark generated by the histone methyltransferases SU(VAR)3-9 and orthologues. Loss of HP1 proteins causes chromosome segregation defects and lethality in some organisms; a reduction in levels of HP1 family members is associated with cancer progression in humans. These consequences are likely due to the role of HP1 in centromere stability, telomere capping and the regulation of euchromatic and heterochromatic gene expression.


Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool.
Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.


Preparation of anti-idiotypic antibodies specific for anti-HEL and analysis of their functional mimicry.
This study is to investigate the functional mimicry by using anti-idiotypic antibodies of enzymes. Monoclonal anti-idiotypic antibodies against anti-HEL (hen egg-white lysozyme, HEL) antibodies were obtained by fusion of Sp2/0 myeloma cells with spleen cells of syngeneic mice immunized with monoclonal anti-HEL antibodies against HEL's different antigenic epitopes. Then bacteriolysis of the anti-idiotypic antibodies were observed. Eight hybridomas strains secreting anti-idiotypic antibodies were selected and characterized. It was shown that two of eight anti-idiotypic antibodies secreted by two hybridomas (1A10C9 and 2A11C1B3) could mimic HEL catalytic activity to lyse Micrococcus lysodeikticus and that the catalytic effect of mixed anti-idiotypic antibodies of 1A10C9 and 2A11C1B3 was stronger than that of one of them, but less than HEL. The results demonstrated that the anti-idiotypic antibodies that could mimic enzyme activity existed in the idiotype network during anti-enzymatic immune response.


Physiological and molecular response of colored wheat seedlings against phosphate deficiency is linked to accumulation of distinct anthocyanins.
Anthocyanin rich colored wheat with additional health benefits has created interest among breeders, consumers and policy makers to address the prevailing malnutrition in the vulnerable population. Researchers are exploring how colored wheat could perform under different nutrient conditions for the maintenance of growth and development. The present study was aimed to investigate the differential response of phosphorous (Pi) deficiency at the seedling stage using hydroponics. Our results showed that Pi-deficiency triggered typical response in the wheat along with the changes in the plant root morphology, total biomass, micronutrient concentration and distinct anthocyanin accumulation. Our physiological and biochemical data revealed that these parameters were positively altered under stress in the colored wheat and the adaptation followed the trend of white < blue <purple < black. Our results also confirmed that stress induced accumulation of distinct anthocyanins including derivatives of cyanidin, delphinidin and peonidin in a genotype dependent manner. Differential expression pattern visualized for the transcripts encoding phosphate transporters, anthocyanin biosynthesis, putative transporters and regulators may be one of the underlying factors. Altogether, our data showed that the black wheat genotype with highest anthocyanin content could able to adapt better with the P stress. This study will help in identifying suitable colored wheat adapting the stress condition and have potential for influence on the future agricultural cultivation practices.


Spontaneous uroflowmetry in prostatism.
Uroflowmetry is a valuable urodynamic screening procedure in selecting patients with prostatism for surgery. A prospective study was undertaken in which patients were selected for transurethral resection of the prostate by means of nonurodynamic data only. All patients underwent extensive urodynamic testing. Fifty-three patients were studied preoperatively, while 38 were examined at three months and 22 at twelve months postoperatively. A weak correlation was noted between maximum flow rate and symptom scores, pressure variables, and minimum urethral resistance. However, classification of patients by groups of high, medium, and low maximum flow rates did not identify groups of patients with less favorable outcome of surgery, i.e., patients with higher flow rates did as well as those with lower flow rates. A clear role for spontaneous uroflowmetry could not be identified in the preoperative evaluation of patients with prostatism.


Altered expression of angiogenesis and lymphangiogenesis markers in the uninvolved skin of plaque-type psoriasis.
Vascular alterations are significant events in the pathomechanism of psoriasis. A disorder in the mechanisms regulating skin angiogenesis and lymphangiogenesis could participate in the pathogenesis of the disease. To quantify differences in the expression of angiogenesis and lymphangiogenesis growth factors, receptors, coreceptors as well as their antagonists in the uninvolved skin of patients with psoriasis compared with the skin of nonpsoriatic volunteers. Skin biopsies were collected from the involved skin of 13 patients with untreated plaque-type psoriasis, from their nonlesional skin at distance from the lesions and from the skin of 16 healthy volunteers. The mRNA steady-state level of keratins 10, 14 and 16, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), vimentin, collagen I and IV, proliferating cell nuclear antigen, the various splice variants of vascular endothelial growth factor, VEGF-A, VEGF-C and VEGF-D, their receptors VEGFR1, VEGFR2 and VEGFR3, neuropilin (NRP)-1 and its soluble forms, NRP-2, semaphorin 3A and prox-1, was measured by reverse transcription-polymerase chain reaction. Immunohistochemistry was performed for Ki-67, von Willebrand factor and D2-40. Blood and lymphatic vessel density, area and distance from epidermis were estimated by morphological analysis coupled to an original computer-assisted method of quantification. Skin from healthy volunteers and nonlesional skin from patients with psoriasis displayed similar histological, morphometric and proliferative features. However, a significant overexpression of VEGFR3, the VEGF-A isoform VEGF121, soluble 12 NRP-1 and GAPDH was observed in the nonlesional psoriatic skin as compared with that of normal volunteers. These data point to significant differences in the blood and lymphatic vascular transcriptome between the clinically normal-appearing skin of patients with psoriasis and the skin of volunteers without psoriasis.


Adrenal cortex, tumor, and peripheral production of deoxycorticosterone.
A method is reported for the measurement of the urine excretion rates of tetrahydro-11-deoxycorticosterone (3 alpha,5 beta-THDOC), an important metabolite of 11-deoxycorticosterone (DOC). Quantification using gas chromatography/mass spectrometry (GC/MS) was achieved by comparing the ion fragment response for the molecular ion (m/z 507) of the analyte (as methyloxime trimethylsilyl ether derivative) to that of a fixed amount of an isomer of THDOC added to urine as internal standard. To improve the specificity of measuring THDOC in clinical samples, an additional Sephadex LH-20 chromatography step was introduced to separate 11-deoxycortisol and some progesterone metabolites. In the luteal phase of the menstrual cycle, THDOC excretion was higher than in the follicular phase; it was also higher than in women taking oral contraceptives. The correlation of THDOC with progesterone production, independent of a constant cortisol output, supports an ovarian or peripheral conversion of progesterone to DOC. The assay proved useful (1) in monitoring for the recurrence of a mineralocorticoid-secreting tumor and (2) when adrenal production of DOC was not fully suppressed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Under the latter circumstances, the renin-angiotensin system seemed to be an important regulator of DOC production.


Effects of local anaesthetics on retinal spreading depression.
This study examines the effect of two local anaesthetics, benzocaine and lidocaine, on propagation, amplitude and duration of the slow potential change of spreading depression. The experiments were performed in isolated chick retina superfused with Ringer's solution. We observed, for both drugs, a dose-related decrease in all parameters analysed. The maximal effect on propagation was blockade of the reaction.


Resolution-matched reflection mode photoacoustic microscopy and optical coherence tomography dual modality system.
Photoacoustic microscopy (PAM) and optical coherence tomography (OCT) are sensitive to optical absorption and scattering characteristics, respectively. As such, the integration of these two modalities in order to combine important complementary information has garnered much attention. Due to the relatively low axial resolution of PAM, PAM and OCT dual modality systems generally have a large resolution gap, especially for reflection mode systems. In this study, based on a wide-band transparent pure-optical ultrasonic detector, we developed a dual modality system (PAM-OCT system) in which PAM has a similar spatial resolution (i.e. several micrometers in both the lateral and axial directions) to OCT. In addition, due to the optical transparency advantage, the integrated system works in reflection mode, which is ideal for in vivo biomedical imaging. We successfully imaged the skin of a mouse hindlimb, which cannot be done by a transmission mode dual modality system. Our work demonstrates this dual modality system has potential in biomedical studies with complementary imaging contrasts.


Reduction of cadmium accumulation in the grains of male sterile rice Chuang-5S carrying Pi48 or Pi49 through marker-assisted selection.
To reduce cadmium (Cd) accumulation in the grains of rice Chuang-5S (C5S), a gene OsHMA3 and a QTL qlGCd3 related to low-Cd accumulation were separately introgressed into the recipient parent C5S (male sterile line) by molecular marker-assisted breeding. The recurrent parent C5S was then replaced by NIL (near-isogenic line)-C5S with the blast resistance gene Pi48 or Pi49 to construct the BC2F1 generation. Finally, two groups of improved materials of C5S, which pyramided the gene/QTL associated with low-Cd accumulation and blast resistance gene, were developed. The Cd accumulation, agronomic traits, genetic background and blast resistance of these improved C5S materials were evaluated. The results showed that the average Cd content of improved C5S material carrying OsHMA3 and qlGCd3 was, respectively, reduced by 52.8% and 50.8% compared with that of C5S, indicating that the gene related to low-Cd accumulation was, successfully, transferred to C5S with stable expression. The main agronomic traits of the improved materials were consistent with those of C5S. Besides, the improved C5S lines showed stronger blast resistance than C5S and more than 88% similarity to the genetic background of C5S. These two groups of improved materials may be further utilized for the breeding of advanced male sterile lines or superior hybrid rice.


Ablation of atrial fibrillation in an ambulatory outpatient setting.
The safety of atrial fibrillation (AF) ablation in an ambulatory outpatient center has not previously been reported. The aim of this study is to report the feasibility and safety of AF ablation in an ambulatory setting. We identified all AF ablations performed at the Alaska Heart and Vascular Institute's ambulatory center since program initiation to current day using billing records. Procedural complications, postoperative utilization of hospital services, and emergency room (ER) utilization were captured by chart review. A total of 476 patients underwent pulmonary vein isolation in the ambulatory setting over a 6.3-year period. Patients' average age was 58 ± 9.3 years, body mass index was 32.9 kg/m2, and the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) score was 1.7. For 85%, this was the first AF ablation, and 55% had paroxysmal AF. Cryoablation was used in 85%. A combined primary safety outcome capturing potentially unstable perioperative safety events occurred in 1.5% of patients, all of whom were stabilized prior to hospital transfer. A total of 1.5% of patients required same-day hospital services, with another 1.5% returning to the ER within 24 hours. A total of 96% of patients did not require hospital services within 24 hours of ablation. The 30-day ER utilization was 13.7%, similar to published data of same-day discharge of AF ablation done in the hospital setting. There were no emergent cardiac surgical interventions and no mortality events. Catheter ablation for AF in the ambulatory setting is both feasible and safe in this large single-center experience. More studies are needed to confirm this next frontier in catheter ablation for AF.


Post-myomectomy omental infarction: a case report.
Omental Infarction (OI) is uncommon and mimics common causes of acute abdomen. It is important to differentiate it from other abdominal conditions that require emergency management. It was first reported in literature in 1896 and about 400 cases have been reported till date. We reported on a 41 year-old Para 0+0 Ibo house wife who presented with 10 years history of supra-pubic mass and five months history of excessive menstrual flow. After physical examination, a diagnosis of symptomatic uterine fibroid was made. She had myomectomy and the raw surface created after the excision of the myomas was covered with omentum. Wound infection developed on the 8th post-operative day leading to a wound breakdown and later partial extrusion of infarcted omental tissue through the dehisced wound. During re-exploration, the infarcted omental tissue was extracted and the residual abdominal abscess was drained. Surgical site wound infection occurred on the 3rd day after re-operation and a sub-acute intestinal obstruction developed on the 4th day thereafter which responded to conservative management. Careful surgical technique is imperative when utilizing the omentum for reconstructive abdominal surgery. Torsion of the omentum and creation of excess tension while using the omentum for reconstructive procedures should be avoided and increase awareness of this uncommon disease condition by the surgeon is also important. This case is to report a rare finding of omental infarction following myomectomy.


Assessment of missile hazards: evaluation of the fragment number and drag factors.
An approach was proposed for the assessment of the expected number and drag factor of fragments generated in the collapse of a vessel due to internal pressure. The analysis of a database reporting data on more than 140 vessel fragmentation events allowed the identification of a limited number of fragment reference shapes. The correlation of fragment reference shapes to the vessel credible fragmentation patterns allowed the assessment of the expected number and reference shape of fragments generated. Starting from the fragment reference shapes identified, simplified functions for drag factor calculation were developed, based on few geometrical parameters of the vessel undergoing the fragmentation event. The probabilistic models for the expected shape and number of fragments generated and the simplified drag factor functions developed may constitute an important input for the analysis of the possible fragment trajectories in the framework of missile hazard assessment.


rBAT is an amino acid exchanger with variable stoichiometry.
The rBAT protein, when expressed in Xenopus oocytes, was previously shown to reproduce the selectivity of the Na(+)-independent neutral and basic amino acid transport system called bo,+. More recently, the capacity of rBAT to generate a transmembrane current was demonstrated when addition of neutral amino acids stimulated the efflux of cations (presumably basic amino acids) in rBAT-injected oocytes. In the present paper, aminoisobutyric acid (AIB), a neutral amino acid analogue, was shown to induce outward currents (efflux of basic amino acids) through rBAT similar to those caused by alanine in terms of affinity, maximal currents and I-V curves. Despite generating similar currents, the AIB transport rate was more than 30 times lower than that of alanine, thus challenging the assumption that rBAT functions as a classical exchanger. Experiments using a cut-open oocyte voltage clamp demonstrated that AIB was capable of stimulating rBAT-mediated currents from either side of the membrane. AIB, like alanine, was able to stimulate the efflux of radiolabeled alanine and arginine while no rBAT-mediated efflux was measurable in the absence of external rBAT substrates. These results demonstrate that (i) the presence of amino acids is required on both sides of the membrane for rBAT to mediate amino acid flux and thus rBAT must be some type of exchanger but (ii) rBAT-mediated amino acid influx is not stoichiometrically related to the efflux. A model of a "double gated pore" is proposed to account for these properties of rBAT, which contravene standard models of exchangers and other transporters.


Gastrointestinal adaptation in response to soluble non-available polysaccharides in the rat.
1. Rats were fed on a control semi-synthetic diet containing insoluble cellulose (Solkafloc; 100 g/kg; control group) as the only source of dietary fibre, or on one of two test diets containing the same quantity of either guar gum or carboxymethylcellulose (CMC). Animals in the test groups showed similar growth rates and food intakes, which were significantly lower than those of the control group. The CMC group produced frequent poorly formed faeces throughout the 21 d feeding period. 2. The small intestines of animals in both test groups were significantly longer than those of the control group at the end of the study. The caeca were also enlarged and heavier, particularly in the CMC-fed group. 3. The rate of production of mucosal cells was increased in the small and large intestines of both test groups. The CMC-fed group exhibited a particularly high rate in the distal ileum, where the rate of cell divisions per crypt was over three times greater than at the same site in the control group. The increased proliferation was associated with a significant lengthening of the crypts and an approximately 25% increase in the basal width of the villi. 4. Mucosal alkaline phosphatase (EC 184.108.40.206) and lactase (EC 220.127.116.11) levels were lower than those of the control group at proximal and distal sites in the small intestines of both CMC- and guar-gum-fed groups. Altered spatial distributions of maltase (EC 22.214.171.124) and sucrase (EC 126.96.36.199) activities were also observed in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Yeasts as adjunct starters in matured Cheddar cheese.
Debaryomyces hansenii and Yarrowia lipolytica are typical foodborne yeast species frequently associated with dairy products and capable of predominating the yeast composition in such systems. The two species fulfil a number of criteria to be regarded as co-starters for cheesemaking. They are known for their proteolytic and lipolytic activity as well as their compatibility and stimulating action with the lactic acid starter cultures when co-inoculated. Recent studies indicated that yeasts could be included as part of starter cultures for the manufacturing of cheese, enhancing flavour development during the maturation. The potential of D. hansenii and Y. lipolytica as agents for accelerated ripening of matured Cheddar cheese has been evaluated during four cheese treatments. The interaction between the two yeast species and the lactic acid bacteria was surveyed incorporating (i) D. hansenii, (ii) Y. lipolytica, (iii) both species as adjuncts to the starter culture and (iv) a control cheese without any additions for the production of matured Cheddar cheese. The physical and chemical properties of the cheeses were monitored in order to evaluate the contribution of the yeasts to cheese maturation. The yeasts grew in association with the lactic acid bacteria without any inhibition. The yeasts species when individually added contributed to the development of bitter flavours despite accelerated development of strong Cheddar flavours. When both species were incorporated as part of the starter culture, the cheese, however, had a good strong flavour after a reduced ripening period. The cheese retained this good flavour and aroma after 9 months of production. The simultaneous application of D. hansenii and Y. lipolytica as part of the starter culture for the production of matured Cheddar cheese is proposed.


Neuropathic pain symptoms on the modified painDETECT correlate with signs of central sensitization in knee osteoarthritis.
Clinical tools are needed to identify and target a neuropathic-like phenotype, which may be associated with central sensitization (CS), in osteoarthritis (OA). The modified painDETECT questionnaire (mPD-Q) has face and content validity for identifying neuropathic-like symptoms in knee OA. To further validate the mPD-Q, this study assessed the unknown relationship between mPD-Q scores and signs of CS on quantitative sensory testing (QST) in knee OA. 36 Individuals were recruited with chronic, symptomatic, knee OA without other pain/neurological conditions. Reference QST data were obtained from 18 controls/32 eligible knees, enabling identification of sensory abnormalities/CS among case knees. A standardized questionnaire assessed psychological factors (depressive symptoms and pain catastrophizing), and for individual knees, mPD-Q and pain intensity scores. A standardized/comprehensive QST protocol was conducted for each knee. QST signs of CS were defined as: mechanical hyperalgesia and/or enhanced temporal summation and/or allodynia. The relationship between the presence of CS (yes/no) and a pre-selected mPD-Q score (≤12 or >12), by knees, was assessed using generalized estimating equations. Among 57 eligible case knees, 45.6% had ≥1 sign of CS. Controlling for age, knees with higher mPD-Q scores (>12.0) had higher odds of having QST signs of CS (adjusted odds ratio (OR) = 5.6; 95% confidence interval (CI), 1.3-22.9). This relationship was unaffected by controlling for depression and pain intensity, but was attenuated by pain catastrophizing. Among painful OA knees, higher mPD-Q scores were associated with greater odds of having signs of CS. Thus, the mPD-Q may aid the identification of CS in people with chronic knee OA.


Efficient gene transfer into normal human skeletal cells using recombinant adenovirus and conjugated adenovirus-DNA complexes.
In order to assess efficient DNA gene transfer into human primary cell cultures derived from the skeleton we tested two viral-based procedures. First, replication-deficient recombinant adenoviruses (ADV) were used to infect post-confluent human marrow stromal fibroblasts (HMSF) and human trabecular bone (HTB) cells. Both cell types were readily infected by modified adenoviral vectors carrying a reporter gene making this virus an attractive candidate to facilitate DNA gene transfer. In a second approach we coincubated DNA with ADV that had polylysine (PLL) covalently attached. With this ADV/PLL/DNA complex, very efficient gene transfer into multilayered HMSF and HTB cell cultures was observed, and DNA coincubated with unmodified ADV failed to be effectively transferred. These data imply that the covalently bound PLL more effectively binds exogenous DNA, resulting in a highly efficient internalization event in both cell types. Thus, this latter method has many advantages over conventional ADV gene transfer procedures. It is simple, rapid, and it does not require engineering of DNA into the viral genome, thereby allowing transfer of large fragments of DNA.


Urban biodiversity: Cuterebriasis in free-ranging Robinson's mouse opossum (Marmosa robinsoni) in the suburbs of Barranquilla, Colombia.
The tropical dry forest is one of the world's most threatened ecosystems and is the habitat of the Robinson's Mouse Opossum (Marmosa robinsoni), a small marsupial within the Didelphidae family. This study aimed to describe cases of cuterebriases in free-ranging M. robinsoni by examining individuals caught in live animal traps. Sherman traps were deployed in four different sites over three different periods in five days. All animals passed through biometry, weighing, sampling parasites, and sampling feces. Only animals captured in the study site located close to the city were anesthetized and examined. The evaluation included blood samples and a clinical examination. Animals received anesthesia under physical restraint by intramuscular injections of ketamine and xylazine. For anesthetic reversion, the protocol was Yohimbine administered before release. In total, 8% (5/60) of all captured animals had fly larvae extracted from wounds. The molecular Barcode of the mitochondrial Cytochrome Oxidase I gene showed no match with any recognized species of Cuterebra. The animals weighed from 35 to 80 g and had lesions in the scapular region with parasites under their skin in sizes ranging from 1.3 to 2.2 cm. The animals with parasites were in good physical condition without evidence of disturbances in health conditions. This is compatible with literature, reporting little effect on population dynamics of other host species infected with Cuterebra larvae. The study included 24 animals captured in three areas far from any city, which showed no evidence of cuterebrid infection, suggesting that proximity to the city could increase exposure to cuterebriasis. There are reports of cuterebrids in M. robinsoni in Brazil; however, this is the first report of cuterebriasis in M. robinsoni in Colombia.


Production of bacteriocin-like agents of Budvicia aquatica and "Pragia fontium".
In cultures of 9 budvicia aquatica and 5 "Pragia fontium" strains production of distinct bacteriocin-like agents was proved. It is suggested to call them aquaticins and fonticins. They display strain specific antibacterial activities towards both genera; however, they are not active towards Escherichia coli or Shigella sonnei indicators. Their inhibition zones are conspicuously narrow (turbid or clear). Their spontaneous production may be enhanced by UV-induction of producing bacteria. They are readily set free into the medium; no intracellular accumulation occurs. With only one exception, they are trypsin-resistant and remarkably heat-sensitive, being damaged at 45 degrees C to 55 degrees C. All these results suggest that aquaticins and fonticins are of corpuscular character. This assumption was proved true by electron microscopic observation of one of the fonticins: this resembles contracted tails of bacteriophage T4.


Hydroxychloroquine and dexamethasone in COVID-19: who won and who lost?
On June 30, 2020, the WHO reported over 10 millions of COVID-19 cases worldwide with over half a million deaths. In severe cases the disease progresses into an Acute Respiratory Distress Syndrome (ARDS), which in turn depends on an overproduction of cytokines (IL-6, TNFα, IL-12, IL-8, CCL-2 and IL1) that causes alveolar and vascular lung damage. Clearly, it is essential to find an immunological treatment that controls the "cytokine storm". In the meantime, however, it is essential to have effective antiviral and anti-inflammatory drugs available immediately. Hydroxychloroquine or chloroquine have been widely adopted worldwide for the treatment of SARS-CoV-2 pneumonia. However, the choice of this treatment was based on low quality of evidence, i.e. retrospective, non-randomized controlled studies. Recently, four large Randomized Controlled Trials (RCTs) have been performed in record time delivering reliable data: (1) the National Institutes of Health (NIH) RCT included 60 hospitals participating all over the world and showed the efficacy of remdesivir in reducing the recovery time in hospitalized adults with COVID-19 pneumonia; (2) three large RCTs already completed, for hydroxychloroquine, dexamethasone and Lopinavir and Ritonavir respectively. These trials were done under the umbrella of the 'Recovery' project, headed by the University of Oxford. The project includes 176 participating hospitals in the UK and was set up to verify the efficacy of some of the treatments used for COVID-19. These three 'Recovery' RCTs concluded definitely: (a) that treatment with hydroxychloroquine provides no benefits in patients hospitalized with COVID-19; (b) that treatment with dexamethasone reduced deaths by one-third in COVID-19 patients that were mechanically ventilated, and by one-fifth in patients receiving oxygen only; (c) that the combination of Lopinavir and Ritonavir is not effective in reducing mortality in COVID-19 hospitalized patients. The results of these four large RCTs have provided sound indications to doctors for the treatment of patients with COVID-19 and prompted the correction of many institutional provisions and guidelines on COVID-19 treatments (i.e. FDA, NIH, UK Health Service, etc.). Even though a definitive treatment for COVID-19 has not yet been found, large RCTs stand as the Gold Standards for COVID-19 therapy and offer a solid scientific base on which to base treatment decisions.


Flow Diverter Apposition in Patients with Large or Giant Intracranial Aneurysms Evaluated on Three-Dimensional Fusion Images Acquired by High-Resolution Cone-Beam Computed Tomography and Digital Subtraction Angiography.
To investigate flow diverter (FD) apposition on fused images acquired by high-resolution cone-beam computed tomography (CBCT) and 3-dimensional (3D) digital subtraction angiography. Patients with large or giant internal carotid artery aneurysms treated with Pipeline FDs who underwent CBCT imaging at our institution between October 2016 and May 2019 were included. Two neurosurgeons measured the maximum malapposition between FDs and vessel walls on 3D fusion images of high-resolution CBCT images displaying the FD and 3D digital subtraction angiography images displaying the vessels. Associations between the relative malapposition, FD diameter, vessel diameter, proximal and distal vessel diameter discrepancy, and siphon angle were evaluated by linear regression analysis. Inter-rater and intermethod (3D and 2D image) agreements of the malapposition measurements were assessed by Bland-Altman analysis and by interclass correlation coefficients. Images of 2 patients were excluded because of image artifacts or fusion errors, and 3D fusion images were acquired in the remaining 26 patients. Our results did not suggest that relative malapposition was associated with vessel diameter (P = 0.12), vessel diameter discrepancy (P = 0.60), or syphon angle (P = 0.34), but relative malapposition increased by an estimated 13% (95% confidence interval: 4%-23%, P = 0.006) for each 1 mm increase in FD diameter. Inter-rater and intermethod agreements for apposition measurements were excellent and good, respectively. Three-dimensional fusion images provided clear visualization of structures of both the stent and parent artery with excellent diagnostic reliability. Careful deployment may be needed for FDs with larger diameters, as they tended to have larger relative malapposition.


PPARs as Key Mediators in the Regulation of Metabolism and Inflammation.
Nuclear receptors (NRs) form a large family of ligand-dependent transcription factors that control the expression of a multitude of genes involved in diverse, vital biological processes [...].


Markers of older widows' trust of nonprofessional home-care helpers.
There is little literature about the relationships of older women who live alone and the paid nonprofessional helpers who assist them. Studies of interpersonal trust have focused on the vulnerability of the trusting person and actions of the trusted person. The actions of the trusting person, or empirical indicators of trust, have had little attention. Our purpose was to describe the actions of older women that were indicative of their trust in nonprofessional home-care helpers. In a descriptive phenomenological study of 25 older widows, a subsample of 11 women who had hired nonprofessional helpers reported actions toward the helpers that we deemed markers of trust. The overarching marker of trust was keeping my eyes off of the helper, with five subsidiary markers, including allowing the helper to enter my house at will. Findings extend empirical knowledge about trust, raise new questions about interpersonal theories of trust, and suggest further areas of study.


PCT Kinetics in the First Week Postburn for Sepsis Diagnosis and Death Prognosis-An Accuracy Study.
Despite continuous advances in burn care, sepsis is still the main cause of death in burn patients. Procalcitonin (PCT) has been reported as an accurate sepsis biomarker and also as a fair predictor of death. The aim of this study was to assess PCT kinetics in the first week postburn regarding sepsis diagnosis and death prognosis. Sample included 142 patients with ≥15% TBSA, admitted from January 2011 to December 2014 at Coimbra Burns Unit, Portugal. Sepsis diagnosis was done according to American Burn Association criteria. PCT range and median values in the first 7 days after burns were statistically analyzed for its potential for sepsis diagnosis and death prognosis. A subanalysis was done regarding TBSA, sex, age, and inhalation injury. First week PCT range and median were significant for sepsis diagnosis and death prognosis, but the median area under the curve was greater in the last case. TBSA influenced PCT accuracy, which was greater for TBSA less than 40% either for diagnosis or prognosis. Age was inversely related to the accuracy, being better in younger than 40 years in both cases. PCT diagnostic accuracy was not affected by sex, opposing to the prognostic one which is better in women. Inhalation injury had no effect on diagnostic accuracy, but it happens with prognostic accuracy. PCT levels' variation is related to sepsis evolution and outcome. Its median performs better than its range. Always coupled with clinical examination, monitoring PCT levels kinetics may help early sepsis detection, potentially reducing morbidity and mortality, being also useful for death prognosis.


Association of bacteriuria and pyuria during intermittent catheterization after spinal cord injury.
Because patients on intermittent catheterization often suffer asymptomatic bacteriuria it is important to know how serious such a colonization may be. We followed 156 hospitalized spinal cord injury subjects on intermittent catheterization. Daily bacterial cultures were performed. When bacteriuria was detected bacterial cultures and uncentrifuged urinary leukocytes were quantified. Gram-positive bacteria, such as Staphylococcus epidermidis and Streptococcus faecalis, produced minimal white cell response, even in high colony counts. However, gram-negative and fungal organisms elicited significant pyuria. Analysis of pyuria in conjunction with urine cultures may serve as a clinical guide to treatment of significant bacteriuria.


[Endoscopically assisted removal of posterior fossa meningioma combined with microvascular decompression of trigeminal nerve root (early experience)].
The article presents an example of endoscopically assisted neurosurgical removal of petrous apex meningioma associated with trigeminal neuralgia. Endoscopy was used during the operation for control of completeness of tumor removal and for identification of offending vessel and control of position of protector. Total resection of the tumor was achieved, complete regression of trigeminal pain was observed in early postoperative period.


The migraine-dopamine link: do migraine and Parkinson's disease coexist?
The role of the dopaminergic system in the pathogenesis of migraine was studied by evaluating the course of migraine after the onset of Parkinson's disease (PD) in 5 migraineurs. The course of migraine in patients with a family history of migraine was not changed after the onset of PD. On the other hand, in migraineurs without a family history, the migraine attacks either subsided or became shorter and less severe after the onset of PD. These findings may suggest a different role of the dopaminergic system in migraineurs with and without a family history of migraine, and call for a larger survey.


Hemodynamic performance of carotid artery shunts.
Although the use of shunts for carotid artery surgery remains controversial, the hemodynamics of the shunts currently available have not been carefully evaluated in vivo. We developed an animal model using contralateral carotid artery ligation, which produced ipsilateral carotid blood flows (640 +/- 44 ml/min) and internal carotid stump pressures (52 +/- 4 mm Hg) over a range commonly seen in carotid artery surgery. Seven shunts were tested and included Javid; 10F and 8F Brener; and 14F, 12F, 10F, and 8F Argyle shunts. The hemodynamic features evaluated for each shunt included maximum shunt flow, the pressure gradients occurring across each shunt, the increase in cerebral perfusion pressure over occlusion pressure associated with shunt placement, and the distal pressure pulse waveform. The larger diameter shunts were consistently better than the smaller diameter shunts. The correlation between shunt flow and the increase in distal pressure produced by shunt placement was high (r = 0.98, p less than 0.05), confirming that high flow rates maintained high perfusion pressure. By relating maximum shunt flow and the pressure gradient to the change in the pressure pulse contour for each shunt, it could be demonstrated that at the larger diameters, straight shunts displayed superior hemodynamic characteristics compared with tapered shunts, whereas at smaller diameters, tapered shunts were superior.


Perceptions of the Jackson-Timberlake Super Bowl incident: role of sexism and erotophobia.
201 college women's and 179 men's impressions of the Jackson-Timberlake Super Bowl incident were related to measures of benevolent sexism, hostile sexism, and erotophobia. For both women and men high benevolent sexism was correlated (.17-.24) to perceptions that the incident was degrading and that agents (e.g., MTV, NFL, Hollywood) other than the actors were responsible for the incident, whereas high erotophobia was correlated (.29-.39) to perceptions that the incident was degrading, attributable to others, and personally upsetting.


Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis.
Large clostridial toxin-negative, binary toxin-positive (A(-) B(-) CDT(+)) strains of Clostridium difficile are almost never associated with clinically significant C. difficile infection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A(-) B(-) CDT(+) ribotype 033 (RT033) strain of C. difficile from a young patient with ulcerative colitis and severe diarrhea.


Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.
Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant NSCLC cells. Accordingly, inhibition of Skp2 partially restores MLKL and sensitizes NSCLC cells to cisplatin in vitro and in vivo. Mechanistically, Skp2 interacts and promotes ubiquitination-mediated degradation of MLKL in cisplatin-resistant NSCLC cells. Our results provide evidence of an Skp2-dependent mechanism regulating MLKL degradation and cisplatin resistance, suggesting that targeting Skp2-ubiquitinated MLKL degradation may overcome NSCLC chemoresistance.


Practice patterns and the adequacy of residency training in consultation medicine.
To describe consultation practice patterns of graduates of an internal medicine residency program and to determine whether they consider themselves to be adequately trained to practice in the area of internal medicine consultations. The authors surveyed graduates of the internal medicine residency program at the University of California, San Diego, School of Medicine from 1980 to 1989. Respondents described their practice types and the mechanics of consultations they currently perform, as well as the adequacy of their training in and frequency of encountering 74 clinical problems in the area of internal medicine consultation. Topics were categorized as Group I: excessive training; Group II: adequate training, frequently encountered; Group III: adequate training, infrequently encountered; Group IV: inadequate training, frequently encountered; and Group V: inadequate training, infrequently encountered. University teaching hospital. Of 214 graduates, 91 returned surveys adequate for analysis. Internists prefer verbal communication with their colleagues and seeing surgical patients in the office prior to admission. Residents perceive that they have been excessively trained in preoperative evaluations of the asymptomatic and chronically ill adult and in several postoperative complications. Topics seen frequently in clinical practice but inadequately taught include: issues in convalescence and rehabilitation from surgical procedures, use of psychotropic medications, and management of eating disorders. To prepare residents for practice, program directors in consultation medicine might consider incorporating outpatient preoperative evaluation assessments, encouraging a liaison between surgeons and internists, and modeling verbal communication among colleagues. Consideration should be given for more didactic training for Group IV topics.


Partially hearing and hearing children's speaking, writing and comprehension of sentences.
Partially hearing, deaf, and hearing children's ability to say, write, and comprehend the same sentences, from the Sentence Comprehension Test (1979), were compared. It was hypothesized that writing sentences would be more difficult than saying the same sentences in all of the three groups. It was further hypothesized that the partially hearing would form an intermediate group between the hearing and deaf. The partially hearing made more errors in both the spoken and written conditions than the hearing who were 2 years younger. The number of phonetic and visual spelling errors made by the three groups were compared.


Refractory myeloid sarcoma with a FIP1L1-PDGFRA rearrangement detected by clinical high throughput somatic sequencing.
Next generation sequencing (NGS) is increasingly being used clinically to characterize the molecular alterations found in patients' tumors. These testing results have the potential to affect clinical care by guiding therapeutic approaches based upon genotype. NGS based testing approaches have a distinct advantage over provider-ordered single gene testing in that they can detect unexpected, yet clinically important genetic changes. Here, we illustrate this principle with the case of a 33-year-old man with myeloid sarcoma that was refractory to six different chemotherapeutic regimens. Our clinical NGS assay detected an unanticipated FIP1L1-PDGFRA rearrangement in his tumor. The patient was immediately placed on Imatinib therapy to which he responded, and remains in remission 10 months after the rearrangement was initially detected.


Angiopoietin 2 levels decrease after HCV-cure and reflect the evolution of portal hypertension.
Portal hypertension (PH) does not resolve in a considerable proportion of patients who achieved HCV-cure. To investigate (i)whether HCV-cure impacts cytokines that orchestrate angiogenesis (i.e.,Ang1/Ang2/VEGF) and fibrogenesis (i.e.,PDGF/TGF-β) and (ii)whether their changes reflect PH-evolution and its complications. We measured plasma levels of cytokines and von Willebrand factor (VWF) and assessed hepatic venous pressure gradient (HVPG) before/after HCV-cure in 66 patients with pre-treatment PH and 23 patients without advanced disease, who served as controls. Following HCV-cure, we observed a decrease in Ang2/TGF-β, but no changes in the other cytokines. The differences in circulating cytokine profiles in PH patients persisted after removing the primary etiological factor. Patients with pre-treatment HVPG≥10 mmHg with HVPG-reduction≥10% had a more pronounced relative decrease in Ang2. Finally, post-treatment Ang2 predicted FU-HVPG≥16 mmHg/decompensation with AUROC-values of 0.804/0.835. HCV-cure decreases circulating Ang2 - a mediator/indicator of dysangiogenesis/endothelial dysfunction, as well as TGF-β - a profibrogenic cytokine. The dynamics of Ang2 mirrored those of PH, rendering FU-Ang2 a non-invasive test for pronounced PH at FU that also predicts hepatic decompensation. The pathophysiological significance of the persistently altered cytokine levels for mechanisms that hinder the PH-regression warrants further study.


A computational framework for ultra-high resolution cortical segmentation at 7Tesla.
This paper presents a computational framework for whole brain segmentation of 7Tesla magnetic resonance images able to handle ultra-high resolution data. The approach combines multi-object topology-preserving deformable models with shape and intensity atlases to encode prior anatomical knowledge in a computationally efficient algorithm. Experimental validation on simulated and real brain images shows accuracy and robustness of the method and demonstrates the benefits of an increased processing resolution.


[Status Quo and Prospects of Research on Precision Nursing of Life-Cycle Health and Disease].
With the changing lifestyle and spectrum of diseases among Chinese people, the life-cycle approach to health has been given national strategic importance. Over the past decade, global nursing researchers have gradually started to pay more attention to the research related to precision nursing at different stages of the life cycle. Researchers have applied multi-omics to explore the pathogenesis and novel biomarkers of relevant symptoms in tumor patients or patients with chronic diseases in order to manage symptoms with better precision. However, systematic theories of precision nursing of life-cycle health and disease have not yet been developed, and the research field and its implications still need to be continuously expanded and innovated. In the nursing discipline, the advantages of interdisciplinary integration should be given full play and the precise and effective resolution of life-cycle health problems should be taken as its goal. Through accurately defining key quantitative objective indicators of nursing care, the nursing discipline will be able to achieve early identification of life-cycle health problems, clarify the occurrence and patterns of change in life-cycle health problems, and gain a better understanding of the regulatory mechanisms. Precise and effective nursing-related technologies and products of non-medication and non-surgery nature should be developed to achieve better precision in nursing interventions, thereby effectively promoting recovery from diseases and improving the overall health of the people.


Cryopreservation of Drosophila melanogaster embryos.
There is an urgent need to preserve the ever-increasing number (greater than 30,000) of different genetic strains of D. melanogaster that are maintained in national and international stock centres and in the laboratories of individual investigators. In all cases, the stocks are maintained as adult populations and require transfer to fresh medium every two to four weeks. This is not only costly in terms of materials, labour and space, but unique strains are vulnerable to accidental loss, contamination, and changes in genotype that can occur during continuous culture through mutation, genetic drift or selection. Although cryopreservation of Drosophila germ-plasm would be an enormous advantage, many attempts using conventional procedures have been unsuccessful. D. melanogaster embryos are refractory to conventional cryopreservation procedures because of the contravening conditions required to minimize mortality resulting from both intracellular ice formation and chilling injury at subzero temperatures. To overcome these obstacles, we have developed a vitrification procedure that precludes intracellular ice formation so that the embryos can be cooled and warmed at ultra-rapid rates to minimize chilling injury, and have recovered viable embryos following storage in liquid nitrogen. In a series of 53 experiments, a total of 3,711 larvae emerged from 17,280 eggs that were cooled in liquid nitrogen (18.4 +/- 8.8%). Further, using a subset from this population, approximately 3% of the surviving larvae (24/800) developed into adults. These adults were fertile and produced an F1 generation.


Response of the coronary vasculature to myocardial hypertrophy.
Cardiac hypertrophy is often characterized by abnormalities in myocardial perfusion, including decreased coronary reserve, increased minimal coronary vascular resistance, underperfusion of the subendomyocardium during conditions of high oxygen demand and increased risk of infarction in the presence of coronary occlusion. Two major anatomic variables may cause these perfusion deficits. First, the coronary resistance vessels may not grow in proportion to the magnitude of the cardiac enlargement. Second, the luminal diameter of resistance vessels may become reduced as a consequence of medial hypertrophy, hyperplasia or fibrosis. A luminal narrowing coupled with a lack or inadequate numeric proliferation of resistance vessels can markedly limit maximal myocardial perfusion. However, not all models of cardiac hypertrophy are characterized by perfusion abnormalities. A substantial growth of arterioles and capillaries has been documented in exercise- and thyroxine-induced left ventricular hypertrophy. Moreover, at least in some models, angiogenesis occurs when the duration of the ventricular hypertrophy is sufficient. The hypothesis that coronary angiogenesis is stimulated by increased blood flow or prolongation of diastole appears to have support from a number of experimental studies. However, the cascade of events underlying angiogenesis and the numerous variables that characterize the various models of hypertrophy are complex and require elucidation.


Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).
Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.


The effect of translatory and rotatory movements upon the eye. Their significance in the development of retinal detachment.
It was shown in experimental models that translational movements of a closed chamber do not induce liquid flow in the chamber, but rotational movements do induce a current. It was also demonstrated in the experiments that rotational currents are able to elevate a rubber membrane if there is a hole and that a liquid flow is then passing through the opening. These observations initiated the idea of fixation of the eye in cases of retinal detachment in order to promote a reattachment.


Treatment of myopic macular hole and detachment. Intravitreal gas exchange.
Exchanging liquid vitreous with an intravitreal gas bubble was used to treat 19 eyes with retinal detachment caused by myopic macular holes. Twelve retinas were successfully reattached with one exchange, one with a repeated exchange, and three with subsequent conventional pars plana vitrectomy techniques. The procedure was unsuccessful in three patients: two refused additional exchanges or surgery and proliferative vitreoretinopathy developed in one and the retina could not be successfully reattached despite pars plana vitrectomy. Visual improvement 6 months after exchange was limited due to myopic macular degeneration, but a visual acuity of 20/400 was obtained in nine patients and finger counting vision in nine. The eye with proliferative vitreoretinopathy deteriorated to light perception.


Multiple phase equilibria in binary mixtures of phospholipids.
Approximate phse diagrams describing lateral phase separations are given for binary mixtures of dimyristoyl phosphatidylcholine with dipalmitoyl phosphatidylcholine, distearoyl phosphatidycholine, and dipalmitoyl phosphatidylethanolamine. These diagrams are based in part on freeze-fracture electron microscopic data. These phase diagrams represent an improvement over previous studies in that both solid phses (Pbeta' and Lbeta') of the phosphatidylcholines are included. Further consideration is given to the problem of binary mixtures in which there are two Pbeta' phases that do not form a continuous range of solid solutions.


[Effect of apressin, obsidan, diprazine and their combination on the concentration of NAD and NADH2 in the liver and brain of hypoxic rats].
Apressin (2.5 mg/kg), obsidan (10 mg/kg), and diprazine (10mg/kg) caused an increase in the content of NAD + NAD.H2, without affecting their ratio, in the liver and brain of intact animals. These drugs, taken in the same doses, especially when used together, caused an increase in the NAD + NAD.H2 level; as to NAD/NAD.H2 ratio--it decreased in the state of hypoxia. The authors believe the antihypoxic action of apressin, obsidan, and diprazine to be connected with the rise in the total nicotinamide adenine denucleotide content and with increase of its oxidized form.


[Dental receptor projections to the sensomotor zone of the rabbit cerebral cortex].
Topic organization of the dental representation was studied in experiments on rabbits by the method of induced potentials. Every tooth proved to be locally represented in the sensory-motor zone of the brain cortex. These zones do not overlap in the case of stimulation of the threshold strength. Topic dental projection region occupies a territory including fields Par I, Praecag, Preacgr, and PC.


Efficacy and safety of the tranexamic acid in reducing blood loss and transfusion requirements during percutaneous nephrolithotomy: a systematic review and meta-analysis of randomized controlled trials.
Percutaneous nephrolithotomy (PCNL) is a minimally invasive approach used for large kidney stones. Although tranexamic acid (TA) has the property of reducing perioperative bleeding, the effect of this drug on PCNL is equivocal. This meta-analysis was conducted to determine the efficacy and safety of TA in preventing hemorrhagic complications, transfusion requirements and other perioperative outcomes during PCNL with available randomized-controlled trials (RCTs). We performed a systematic review of the literature according to Cochrane guidelines for studies comparing TA and normal saline. All studies reporting the outcomes of interest were included. The data analysis was completed using the Cochrane Collaboration's software RevMan 5.3. Data from three RCTs on 570 patients were included in the final meta-analysis. Patients receiving TA experienced less blood loss (MD: -0.82; 95% CI: -1.24 to -0.40; P=0.0001), fewer transfusion requirements (OR: 0.40; 95% CI: 0.01-0.76; P=0.005), lower minor complication rate (OR:0.51, 95% CI: 0.32-0.80, P=0.003), fewer major complication rate (OR:0.31, 95% CI: 0.11-0.88, p=0.03), shorter operative time (SMD: -0.39; 95% CI: -0.75 to -0.02; P=0.04) and less length of stay (LOS) (SMD: -0.68; 95% CI: -1.01 to -0.35; P<0.0001) than their counterparts during PCNL with statistically significant P value and no significant between-study heterogeneity except for LOS and operative time. Our work assessing the use of TA in the clinical management of patients undergoing PCNL indicated promising results. Further well-designed trials are warranted to determine the optimal dose and indications of this drug in practice.


Reactions of pyrzdoxal 5'-phosphate, 6-aminocaproic acid, cysteine, and penicilamine. Models for reactions of Schiff base linkages in pyridoxal 5'-phosphate-requiring enymes.
Schiff base formation, transaldimination, and reaction with aminothiols are important reactions which occur on the surface of pyridoxal-P-requiring enzymes. As a first step in assessing the role of the protein in these reactions, models for these reactions were studied in the absence of enzyme at 25 degrees, gamma/2 0.28. The reaction of 6-aminocaproic acid with pyridoxal-P to form the Schiff base N6-(P-pyridoxylidene)-aminocaproic acid was studied as a model for formation of Schiff base on the holoenzyme...


Change score or follow-up score? Choice of mean difference estimates could impact meta-analysis conclusions.
In randomized controlled clinical trials, continuous outcomes are typically measured at both baseline and follow-up, and mean difference could be estimated using the change scores from baseline or the follow-up scores. This study assesses the impact of using change score vs. follow-up score on the conclusions of meta-analyses. A total of 63 meta-analyses from six comparative effectiveness reviews were included. The combined mean difference was estimated using a random-effects model, and we also evaluated whether the impact qualitatively varied by alternative random-effects estimates. Based on the Dersimonian-Laird (DL) method, using the change vs. the follow-up score led to five meta-analyses (7.9%) showing discrepancy in conclusions. Based on the profile likelihood (PL) method, nine (14.3%) showed discrepancy in conclusions. Using change score was more likely to show a significant difference in effects between interventions (DL method: 4 of 5; PL method: 7 of 9). A significant difference in baseline scores did not necessarily lead to discrepancies in conclusions. Using the change vs. the follow-up score could lead to important discrepancies in conclusions. Sensitivity analyses should be conducted to check the robustness of results to the choice of mean difference estimates.


AC instrumentation amplifier for bioimpedance measurements.
We analyze the input impedance and CMRR requirements for an amplifier for bioimpedance measurements when considering the capacitive components of the electrode-skin contact impedance. We describe an ac-coupled instrumentation amplifier (IA) that, in addition to fulfilling those requirements, both provides interference and noise reduction, and yields a zero phase shift over a wide frequency band without using broadband op amps.


Maternal behaviors in toddlerhood as predictors of children's private speech in preschool.
Private speech is an important strategy reflecting children's self-regulation, and thus understanding how parenting may support private speech can inform intervention work on improving self-regulation. The current study longitudinally investigated how sensitive parenting and directive parenting in toddlerhood interacted to predict preschoolers' private speech in an emotion-eliciting task. In toddlerhood, maternal parenting behaviors were observed during two freeplay sessions. Preschoolers' social and private speech were transcribed and coded during a frustration task. Whereas parenting did not relate to other forms of private speech, preschoolers' facilitative task-relevant private speech was predicted by the interaction of mothers' sensitive and directive behaviors. When sensitivity was high, parents who were less directive had children who used more facilitative task-relevant private speech. These findings highlight that children's regulation may be supported through the combination of high sensitivity and low directiveness when parents and children are engaged in unstructured play together.