Systematic Review of Cost-Effectiveness of Injury Prevention Interventions in Soccer-Evidence Why Health Agencies Should Address It.
Soccer injuries are a recognized problem worldwide. Several injury prevention programs have been confirmed to reduce the number of injuries in female and male players. Unfortunately, there is a lack of data about their cost, burden, and benefit for the health care system. In this paper we aim to systematically review the literature and critically evaluate the economic quality of injury prevention interventions implemented across different populations of soccer players. Web of Science, Medline, SPORTDiscus, Ovid, and other databases were searched from January 2011 through July 2021. Research articles were only selected for analysis if they focused on the cost-effectiveness of injury prevention, were experimental papers written in English, and were published following the peer-review process. Three cluster RCT and one retrospective study met the criteria. Cost data on incremental cost-effectiveness ratios (ICERs) were extracted. The included studies had a good/average quality of economic evaluation. Based on ICERs, injury prevention interventions were cost-effective in three out of the three comparisons. One study did not report the ICER value. However, since economic analyses were reported with varying methodological approaches and results, more data are required to recognize the cost-effectiveness of soccer-specific injury prevention interventions and their benefit for the health care system.


[Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial].
To compare the clinical results of surgical resection (SR) and percutaneous thermal ablation (PTA) for early-stage hepatocellular carcinoma (HCC) (single tumor nodule <or= 5 cm in diameter, or <or= 3 nodules with <or= 3 cm in diameter). One hundred and five patients with 114 HCC nodules were randomly allocated to SR (n = 54) and ultrasound-guided PTA with microwave or radiofrequency energy (n = 51). The complete tumor elimination rates in SR and PTA groups were similar (100% vs 94.7%) and the local recurrence rates were both 0. There were no significant differences in distance recurrence rate (16.7% vs 27.5%, P = 0.182) and time to the first recurrence (4.9 month vs 9.6 month, P = 0.130) between the SR and PTA groups. One, 2-, and 3-year disease-free survival rates were 82.4%, 82.4% and 82.4%, respectively, in SR group, whereas they were 78.5%, 61.5% and 51.3% in PTA group, respectively. The difference between these two groups was statistically not significant (P = 0.128). The overall survival rates in SR group were 91.3%, 86.4% and 86.4% at 1, 2, and 3 years, respectively, and those in PTA group were 93.5%, 87.1% and 87.1%, respectively. There was no significant difference between these two groups (P = 0.808). Compared with SR, PTA required less treatment time (27 min vs 145 min, P < 0.005), less necessity for blood transfusion (0 patient vs 7 patients, P = 0.013) and less hospital-stay (5.2 d vs 19.1, P < 0.005). There was no significant difference in the rate of treatment-related complication between the two groups (11.1% for SR vs 7.8% for PTA, P = 0.742). At day 7 and day 30 after treatment, the numbers of patient with physical status (WHO Performance Status grades) of grade 0 - 1 were 32 and 44 in PTA group, respectively, significantly more than 16 and 33 in SR group (P = 0.001 and P = 0.004, respectively). Besides minimal invasiveness, easy to access and cost saving, PTA achieved equivalent local therapeutical effectiveness and 3-year survival outcomes as SR did, and may be considered as a one of the first-choice treatment modality for treatment of early-stage HCC.


Modeling of the naked facet sign in the lumbar spine.
The study design is a computer visualization model that simulated flexion deformities about the lumbar spine for evaluation of the naked facet sign (NFS). The objectives were to ascertain the angles of rotation required for NFS to occur in the lumbar spine with various centers of rotation about the vertebral body and to assess whether NFS correlates with unstable flexion-distraction injuries in the lumbar spine. The presence of the NFS on axial computed tomography (CT) images occurs when the inferior articulating facet of the cephalad vertebra is not paired with an adjacent superior articulating facet of the caudal vertebra. This sign, when evidenced in the lumbar spine, is suggestive of significant injury secondary to a flexion-distraction force. A previous study using a computer-generated spine model challenged the utility of the NFS in the thoracolumbar spine. The NFS may prove to be more diagnostic of an unstable injury in the lumbar spine because of its normal lordotic resting position. A commercial spine computer visualization model was used to simulate various degrees of flexion injury in the lumbar spine. Lumbar functional spinal units (FSU) L2-L5 were each examined separately. The model simulated two CT scan slices (each 2 mm thick), which were created parallel to the inferior endplate of the cephalad vertebra of each FSU. The cephalad vertebra was rotated in 0.5 degrees increments until NFS was produced. The appearance of NFS required >/=11 degrees kyphotic angulation in more than two thirds of simulated centers of rotation about the lumbar vertebral bodies. The NFS was produced between a range of 8-24.5 degrees. For rotations about a point located 3 cm anterior to the vertebral body (to simulate seat-belt-type flexion-distraction injuries), the minimum angle required for NFS was 7.5 degrees. Our data correlate well with previously published results from in vitro and cadaveric studies. As opposed to the thoracolumbar spine, which normally rests in a neutral position, the lumbar spine normally rests in a lordotic position. Therefore, NFS in the lumbar spine may be more suggestive of an unstable injury and would warrant closer examination of the patient and additional radiographic studies.


Punicic acid production in Brassica napus.
Punicic acid (PuA; 18:3Δ9cis,11trans,13cis), a conjugated linolenic acid isomer bearing three conjugated double bonds, is associated with various health benefits and has potential for industrial use. The major nature source of this unusual fatty acid is pomegranate (Punica granatum) seed oil, which contains up to 80% (w/w) of its fatty acids as PuA. Pomegranate seed oil, however, is low yielding with unstable production and thus limits the supply of PuA. Metabolic engineering of established temperate oil crops for PuA production, therefore, has the potential to be a feasible strategy to overcome the limitations associated with sourcing PuA from pomegranate. In this study, the cDNAs encoding a pomegranate fatty acid conjugase and a pomegranate oleate desaturase were co-expressed in canola-type Brassica napus. Transgenic B. napus lines accumulated up to 11% (w/w) of the total fatty acids as PuA in the seed oil, which is the highest level of PuA reported in metabolically engineered oilseed crops so far. Levels of seed oil PuA were stable over two generations and had no negative effects on seed germination. The transgenic B. napus lines with the highest PuA levels contained multiple transgene insertions and the PuA content of B. napus seed oil was correlated with efficiency of oleic acid desaturation and linoleic acid conjugation. In addition, PuA accumulated at lower levels in polar lipids (5.0-6.9%) than triacylglycerol (7.5-10.6%), and more than 60% of triacylglycerol-associated PuA was present at the sn-2 position. This study provides the basis for the commercial production of PuA in transgenic oilseed crops and thus would open new prospects for the application of this unusual fatty acid in health and industry.


Using Molecular Initiating Events To Generate 2D Structure-Activity Relationships for Toxicity Screening.
Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to exhibit this behavior, be these properties stereochemical, electronic, or otherwise. In an attempt to discover some of these chemical characteristics, we have constructed structural alert-style structure-activity relationships (SARs) to computationally predict MIEs. This work utilizes chemical informatics approaches, searching the ChEMBL database for molecules that bind to a number of pharmacologically important human toxicology targets, including G-protein coupled receptors, enzymes, ion channels, nuclear receptors, and transporters. By screening these compounds to find common 2D fragments and combining this approach with a good understanding of the literature, bespoke 2D structural alerts have been written. These SARs form the beginning of a tool for screening novel chemicals to establish the kind of interactions that they may be able to make in humans. These SARs have been run through an internal validation to test their quality, and the results of this are also discussed. MIEs have proven to be difficult to find and characterize, but we believe we have taken a key first step with this work.


Chronic Trichuris trichiura Infection Presenting as Ileocecal Valve Swelling Mimicking Malignancy.
A 46-year-old man presented with a history of passing bright red blood per rectum over the last one month. He also had on and off diarrhea with visible mucus in the stool for two months' duration. Further history was unremarkable, and physical examination revealed hemorrhoids which were subsequently banded. A colonoscopy was arranged in view of the prolonged diarrhea whereby an edematous and swollen ileocecal valve was seen. This was shown to be due to Trichuris trichiura infection, confirmed on histopathological examination of biopsies taken from the site. The patient was started on oral albendazole treatment and has been asymptomatic on latest followup. This case illustrates an accidental finding of T. trichuria infection on colonoscopic examination, which was done to investigate the patient's prolonged diarrhea.


Relationship between cerebral palsy severity and cognition, aids and education.
Cerebral palsy (CP) refers to a non-progressive permanent lesion of the developing brain, which can manifest with motor function disability and various comorbidities and complications. However, there is little data on the correlation between motor and mental function in CP, as cognitive assessments are rarely the main focus of studies on children with CP. We studied a large cohort of 381 children and adolescents with CP. We analyzed the relationship between severity of CP and the presence of developmental disturbances (motor, motor-linguistic, global) including cognition, the number of aids and education. We found a strong correlation between the severity of CP according to the Gross Motor Function Classification System (GMFCS) and developmental disturbances. In line with this finding, the number of aids per individual also correlated significantly with CP severity and the extent of developmental disturbance. Going beyond the number of aids most patients already received special education in kindergarten. Later, the type of schooling correlated significantly with severity of CP and developmental disturbance. While developmental disturbance and cognition correlated, this was not the case for CP severity and cognition. The latter indicates a wide range in individual manifestation and resources. Our data underline that cognition does not necessarily correlate with CP severity. Thus, in addition to the evaluation and treatment of motor deficits, cognitive assessment should be offered early-on to improve patient-centered counselling and support with respect to appropriate education.


[Possible mechanism of production of the musical second heart sound and its clinical significance].
To investigate the predisposing factors and the clinical significance of the musical aortic component of the second heart sound (musical S2), 18 patients with musical S2 (musical group) among the consecutive 2,000 patients with phonocardiographic examination were noninvasively studied by analyzing underlying diseases, phonocardiographic findings, organic changes of the aortic valve, severity of aortic regurgitation and left ventricular dysfunction. Organic changes of the aortic valve were assessed by two-dimensional echocardiography, and aortic regurgitation was assessed by color Doppler flow imaging. Twenty-two normal subjects (normal group) and 17 patients with essential hypertension (hypertensive group) served as controls. Mean ages were matched among the three groups. 1. Left ventricular dilatation (seven patients) and hypertension (six patients) were the dominant part of underlying disease in the musical group. 2. Musical S2 was classified in the following two types based on the phonocardiographic characteristics; musical vibrations followed immediately after the accentuated S2, and the S2 which was replaced by regular vibratory waves. 3. Frequency of the musical vibrations ranged from 120 to 200 Hz, and its duration ranged from 60 to 120 msec. Amplitude of the musical vibrations decreased by inhalation of amyl nitrite, but increased by infusion of methoxamine. In a case with mild rheumatic valve disease, methoxamine induced marked intensification of the amplitude and prolongation of the duration of the musical vibrations, finally giving a typical cooing murmur. 4. Echo intensity of the aortic valve tended to be higher in the musical group than in the other two groups. 5. Echocardiographically, aortic regurgitation appeared more frequently in the musical group (88%) than in the normal (36%) and hypertensive (41%) groups. Area of the aortic regurgitant signal was significantly larger in the musical group (4.1 +/- 1.4 cm2) than in the normal (1.2 +/- 0.8 cm2) and hypertensive (2.3 +/- 1.2 cm2) groups. 6. Left ventricular end-diastolic dimension was significantly larger in the musical group (5.8 +/- 0.6 cm) than in the normal (4.7 +/- 0.5 cm) and hypertensive (4.8 +/- 0.7 cm) groups. Fractional shortening of the left ventricle was significantly smaller in the musical group (26 +/- 10%) than in the normal (37 +/- 5%) and hypertensive (37 +/- 8%) groups. In a case of the musical group, musical vibrations following the S2, which was large in amplitude at the state of heart failure, decreased markedly after the recovery from heart failure.(ABSTRACT TRUNCATED AT 400 WORDS)


How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch.
Systems and Synthetic Biology use computational models of biological pathways in order to study in silico the behaviour of biological pathways. Mathematical models allow to verify biological hypotheses and to predict new possible dynamical behaviours. Here we use the tools of non-linear analysis to understand how to change the dynamics of the genes composing a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-engineering and Modelling Assessment (IRMA). Guided by previous theoretical results that make the dynamics of a biological network depend on its topological properties, through the use of simulation and continuation techniques, we found that the network can be easily turned into a robust and tunable synthetic oscillator or a bistable switch. Our results provide guidelines to properly re-engineering in vivo the network in order to tune its dynamics.


Analysis of cannabis in oral fluid specimens by GC-MS with automatic SPE.
Methamphetamine (MA) is the most commonly abused drug in Korea, followed by cannabis. Traditionally, MA analysis is carried out on both urine and hair samples and cannabis analysis in urine samples only. Despite the fact that oral fluid has become increasingly popular as an alternative specimen in the field of driving under the influence of drugs (DUID) and work place drug testing, its application has not been expanded to drug analysis in Korea. Oral fluid is easy to collect and handle and can provide an indication of recent drug abuse. In this study, we present an analytical method using GC-MS to determine tetrahydrocannabinol (THC) and its main metabolite 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in oral fluid. The validated method was applied to oral fluid samples collected from drug abuse suspects and the results were compared with those in urine. The stability of THC and THC-COOH in oral fluid stored in different containers was also investigated. Oral fluid specimens from 12 drug abuse suspects, submitted by the police, were collected by direct expectoration. The samples were screened with microplate ELISA. For confirmation they were extracted using automated SPE with mixed-mode cation exchange cartridge, derivatized and analyzed by GC-MS using selective ion monitoring (SIM). The concentrations ofTHC and THC-COOH in oral fluid showed a large variation and the results from oral fluid and urine samples from cannabis abusers did not show any correlation. Thus, detailed information about time interval between drug use and sample collection is needed to interpret the oral fluid results properly. In addition, further investigation about the detection time window ofTHC and THC-COOH in oral fluid is required to substitute oral fluid for urine in drug testing.


Detection of Feline Coronavirus in Feline Effusions by Immunofluorescence Staining and Reverse Transcription Polymerase Chain Reaction.
Feline coronavirus (FCoV), the pathogen for feline infectious peritonitis, is a lethal infectious agent that can cause effusions in the pleural and abdominal cavities in domestic cats. To study the epidemiology of FCoV in Taiwan, 81 FIP-suspected sick cats with effusive specimens were recruited to test for FCoV infection using immunofluorescence staining and reverse transcription-polymerase chain reaction as detection methods, and viral RNAs were recovered from the specimens to conduct genotyping and phylogenetic analysis based on the spike (S) protein gene. The results revealed that a total of 47 (47/81, 58%) of the sick cats were positive for FCoV in the effusion samples, of which 39 were successfully sequenced and comprised of 21 type I strains, 9 type II strains, and 9 co-infections. The signalment analysis of these sick cats revealed that only the sex of cats showed a significant association (odds ratio = 2.74, 95% confidence interval = 1.06-7.07, p = 0.03) with the infection of FCoV, while age and breed showed no association. FCoV-positive cats demonstrated a significantly lower albumin to globulin ratio than negative individuals (p = 0.0004). The partial S gene-based phylogenetic analysis revealed that the type I strains demonstrated genetic diversity forming several clades, while the type II strains were more conserved. This study demonstrates the latest epidemiological status of FCoV infection in the northern part of Taiwan among sick cats and presents comparisons of Taiwan and other countries.


[A case of transitional cell carcinoma of the bladder in a juvenile patient].
A 15-year-old male was referred to our hospital with the chief complaint of gross hematuria. Cystoscopic examination revealed a papillary tumor on the posterior wall. Transurethral resection of the bladder tumor was performed. Histological examination of the excised tumor showed transitional cell carcinoma, grade 1, pTa. Recurrence has not been observed for about 2 years after the operation. We investigated 54 previously reported Japanese cases of bladder cancer before age twenty including the present case.


Alternative radiochemical heavy ion activation methods for the production and separation of thallium radionuclides.
Heavy ion activation of natural gold foil with a 7Li beam results in the formation of carrier-free 199-201Pb radionuclides along with their corresponding decay products, 199-201Tl, in the matrix. At 49 MeV projectile energy, the production of 199Tl through its precursor 199Pb is maximal, while that of other. thallium radionuclides is minimal. Another way for the direct production of carrier-free thallium radionuclides is to irradiate natural platinum foil with a 7Li beam; on this case, production of 199Tl is maximal at 43 MeV projectile energy. The carrier-free thallium radionuclides have been separated from the bulk target matrix gold and platinum by liquid-liquid extraction using trioctylamine as a liquid anion exchanger.


Development and exploration of a new methodology for the fitting and analysis of XAS data.
A new data analysis methodology for X-ray absorption near-edge spectroscopy (XANES) is introduced and tested using several examples. The methodology has been implemented within the context of a new Matlab-based program discussed in a companion related article [Delgado-Jaime et al. (2010), J. Synchrotron Rad. 17, 132-137]. The approach makes use of a Monte Carlo search method to seek appropriate starting points for a fit model, allowing for the generation of a large number of independent fits with minimal user-induced bias. The applicability of this methodology is tested using various data sets on the Cl K-edge XAS data for tetragonal CuCl(4)(2-), a common reference compound used for calibration and covalency estimation in M-Cl bonds. A new background model function that effectively blends together background profiles with spectral features is an important component of the discussed methodology. The development of a robust evaluation function to fit multiple-edge data is discussed and the implications regarding standard approaches to data analysis are discussed and explored within these examples.


Does muscle imbalance affect fatigue after soccer specific intermittent protocol?
This study investigated the muscular strength imbalance dependence of the effect of fatigue induced by an exhaustive laboratory-based soccer-specific exercise on different hamstrings:quadriceps (H:Q) ratios of soccer players. Repeated measures. Twenty-one male professional soccer players (23.2±3.5 years) performed a pre-test to assess the concentric (con) and eccentric (ecc) strength of the knee extensors (KE) and flexors (KF) at 60° s⁻¹ and 180° s⁻¹. Then performed an exhaustive laboratory-based soccer-specific exercise and a post-test similar to the pre-test. The players were allocated into one of two groups in accordance to their conventional H(con):Q(con) (balanced group, BG=H(con):Q(con)>0.60; unbalanced group, UNBG=H(con):Q(con)<0.60). The KE(con) (BG=4%, p<0.05; UNBG=6%, p<0.01) and KF(con) (BG=7%, p<0.01; UNBG=8%, p<0.01) at 60° s⁻¹ were significantly reduced after exercise for both groups. However, KF(ecc) at 180° s⁻¹ was significantly reduced only in BG (16%, p<0.01). The H(con):Q(con) and H(ecc):Q(con) were significantly reduced after exercise in BG (0.65±0.03 vs. 0.62±0.04, p<0.05; 1.38±0.2 vs. 1.20±0.2, p<0.01; respectively), but not in UNBG (0.55±0.04 vs. 0.54±0.07; 1.19±0.1 vs. 1.13±0.2, respectively). The effect of fatigue induced by an exhaustive laboratory-based soccer-specific exercise on H(con):Q(con) and H(ecc):Q(con) in the dominant leg of professional soccer players is dependent on muscular strength balance. Thus, experimental designs and prevention programmes should consider that muscular strength balance might also module the game-induced fatigue of professional soccer players.


Surgical tool detection in cataract surgery videos through multi-image fusion inside a convolutional neural network.
The automatic detection of surgical tools in surgery videos is a promising solution for surgical workflow analysis. It paves the way to various applications, including surgical workflow optimization, surgical skill evaluation and real-time warning generation. A solution based on convolutional neural networks (CNNs) is proposed in this paper. Unlike existing solutions, the proposed CNN does not analyze images independently. it analyzes sequences of consecutive images. Features extracted from each image by the CNN are fused inside the network using the optical flow. For improved performance, this multi-image fusion strategy is also applied while training the CNN. The proposed framework was evaluated in a dataset of 30 cataract surgery videos (6 hours of videos). Ten tool categories were defined by surgeons. The proposed system was able to detect each of these categories with a high area under the ROC curve (0.953 ≤ Az ≤ 0.987). The proposed detector, based on multi-image fusion, was significantly more sensitive and specific than a similar system analyzing images independently (p = 2.98 × 10-6 and p = 2.07 × 10-3, respectively).


Bone mineral density in estrogen-deficient young women.
Osteoporosis primarily affects postmenopausal women. However, young women with estrogen deficiency also are at increased risk for low bone density. The aim of the study was to assess bone density and associated risk factors for reduced bone density in young, estrogen-deficient women using primary ovarian insufficiency (POI) as the disease model. We conducted a cross-sectional study at a tertiary care research center. We studied women with POI (n = 442), concurrent controls (n = 70), and matched controls from NHANES III (n = 353). We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry. Patients on average had 2-3% lower BMD at L1-L4, femoral neck, and total hip (P < 0.01 at all sites). The modifiable risk factors for BMD below the expected range for age (Z-score <-2) were: more than 1-yr delay in diagnosis of estrogen deficiency (P = 0.018), low (<32 ng/ml) vitamin D levels (P = 0.002), estrogen replacement nonadherence (P = 0.002), low calcium intake (P = 0.005), and lack of exercise (P = 0.005). As compared to Caucasians, African-American and Asian women with POI were 3.18 and 4.34 times more likely, respectively, to have Z-scores below -2 (P = < 0.0001 for both). Race was an overall risk factor, but on regression modeling, not an independent predictor of low bone density. Women with POI have lower bone density compared to regularly menstruating women. Compared to Caucasians, minority women with estrogen deficiency are more likely to have BMD below the expected range for age. This racial disparity appears to be related to a combined effect of several modifiable risk factors. Delay in diagnosis of POI also contributes to reduced bone density by delaying proper therapy.


Cellular automaton simulation of tumour growth -- equivocal relationships between simulation parameters and morphologic pattern features.
To develop an interpretation procedure which estimates simulation parameters (tumour cell motility, tumour cell adhesion, autocrine and paracrine growth control, stroma destruction) of simulated patterns solely based on morphometric features of the morphologic pattern. A cellular automaton computer simulation program was developed which produces morphologic patterns by growth of a seed of tumour cells. At the beginning of each simulation run certain simulation parameters are assigned to the tumour cells. After the run has been completed, the resulting pattern is evaluated by a set of morphometric features. Simulation parameters and resulting morphometric features of 27,800 simulations were stored in a database and were used for the evaluation of potential relationships. Correlation analysis showed highly significant correlations between morphometric features on the one hand and the preset simulation parameters (tumour cell motility, tumour cell adhesion, autocrine and paracrine growth control, stroma destruction) on the other. Correlation coefficients, however, varied from 0.72 to 0.99. When only one simulation parameter varied while all others were kept constant, morphometric features yielded a highly reliable estimate of the particular simulation parameter. When variability was extended to 4 simulation parameters, morphometric features were less effective in estimating the setting of the parameters. Though in all patterns tested several possible simulation parameter constellations could be ruled out, morphometric features were usually compatible with more than one set of simulation parameters thus preventing a straightforward interpretation. Though simulation parameters significantly and reproducibly influence the resulting morphologic pattern as characterized by morphometric features, estimates of the simulation parameters based on morphometric features yield equivocal results.


Proprioceptors and fast antennal reflexes in the ant Odontomachus (Formicidae, Ponerinae).
In ants, antennal movements support the stimulus perception of olfactory and mechanosensory sensilla, most of which are located on the distal part of the antenna. In addition, sensory hair plates, campaniform sensilla, and Janet's organ provide the ant with proprioceptive information about the position, velocity, and acceleration of their antennae. We describe the morphology of these proprioceptors and their afferent neurons with special reference to the trap-jaw ant genus Odontomachus. All these sensory neurons terminate in the dorsal lobe, the part of the brain that also contains antennal motor neurons and that controls antennal movements. Neurons originating from campaniform sensilla and Janet's organ send additional collaterals into the subesophageal ganglion. Particularly fast antennal movements occur during protective withdrawal of the antenna. Under natural conditions, antennal retraction in Odontomachus always precedes the rapid mandible strike. We have found no indication of monosynaptic coupling between the antennal proprioceptive afferents and the trigger motor neurons that release the mandible strike. Instead, complex neuronal interactions in the involved neuromeres are more likely to control the timing of the two reflexes. The normal behavioral sequence of antennal retraction can be reversed by artificially releasing the mandible strike earlier than normal. The significance of fast antennal reflexes and of proprioceptive control is discussed.


Regulation of TAK1/TAB1-mediated IL-1β signaling by cytoplasmic PPARβ/δ.
The peroxisome proliferator-activated receptor subtypes PPARα, PPARβ/δ, PPARγ are members of the steroid hormone receptor superfamily with well-established functions in transcriptional regulation. Here, we describe an unexpected cytoplasmic function of PPARβ/δ. Silencing of PPARβ/δ expression interferes with the expression of a large subset of interleukin-1β (IL-1β)-induced target genes in HeLa cells, which is preceded by an inhibition of the IL-1β-induced phosphorylation of TAK1 and its downstream effectors, including the NFκBα inhibitor IκBα (NFKBIA) and the NFκBα subunit p65 (RELA). PPARβ/δ enhances the interaction between TAK1 and the small heat-shock protein HSP27, a known positive modulator of TAK1-mediated IL-1β signaling. Consistent with these findings, PPARβ/δ physically interacts with both the endogenous cytoplasmic TAK1/TAB1 complex and HSP27, and PPARβ/δ overexpression increases the TAK1-induced transcriptional activity of NFκB. These observations suggest that PPARβ/δ plays a role in the assembly of a cytoplasmic multi-protein complex containing TAK1, TAB1, HSP27 and PPARβ/δ, and thereby participates in the NFκB response to IL-1β.


Thermal noise and mechanical loss of SiO2/Ta2O5 optical coatings at cryogenic temperatures.
Mechanical loss of dielectric mirror coatings sets fundamental limits for both gravitational wave detectors and cavity-stabilized optical local oscillators for atomic clocks. Two approaches are used to determine the mechanical loss: ringdown measurements of the coating quality factor and direct measurement of the coating thermal noise. Here we report a systematic study of the mirror thermal noise at 4, 16, 124, and 300 K by operating reference cavities at these temperatures. The directly measured thermal noise is used to extract the mechanical loss for SiO2/Ta2O5 coatings, which are compared with previously reported values.


[Antenatal diagnosis of a choledocal cyst].
Choledocal cyst is a rare anomaly that usually becomes symptomatic during childhood. Forty to sixty percent of choledocal cysts are diagnosed before 10 years old, usually when complications occur. Today, because of advances in sonographic imaging, some cysts can de diagnosed before birth. The major prognostic factor is the development of complications such as hepatic fibrosis. Early treatment, after postnatal ultrasonography assessment, can reduce the incidence of serious complications. The authors report a case of a choledocal cyst diagnosed at 23 weeks gestation.


Cambodia passes new limits on abortion.
According to international news sources, Cambodia's parliament approved a law limiting the circumstances under which abortions can be performed on October 6 [1997]. Members of parliament say the new law, the first ever passed regulating abortion in Cambodia, is intended to reduce maternal morality rates from abortions performed by unlicensed health practitioners under unsanitary conditions. Local news outlets report that the Cambodian Health Ministry estimates the maternal mortality at 4.7 deaths per 1000 live births. The rate in the US is 0.12 deaths per 1000 live births. The law requires that abortions be performed by licensed health professionals in hospitals and certified clinics within the first trimester of pregnancy, and that women under the age of 18 must obtain parental consent. The new law also sets harsh penalties for those who harm women during illegal procedures--up to 5 years in prison if a woman is injured and up to 10 years if she dies. Opponents of the law say they fear that the new restrictions will push abortion even further underground, as the hospital system cannot handle the current demand for abortion.


The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator.
Modification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 +/- 1.9 ml min-1 kg-1 to 3.5 +/- 0.6 ml min-1 kg-1 (mean +/- SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-beta-N-acetyl-glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 +/- 0.5 ml min-1 kg-1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gln) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.


Genome-wide scans for QTL affecting carcass traits in Hereford x composite double backcross populations.
A genome-wide scan for chromosomal regions influencing carcass traits was conducted spanning 2.413 morgans on 29 bovine autosomes using 229 microsatellite markers. Two paternal half-sib families of backcross progenies were produced by mating Hereford x composite gene combination (CGC) bulls to both Hereford and CGC dams. Progeny of the first sire (n = 146) were born in 1996 and progeny of the second sire (n = 112) were born in 1997. Each year cattle were fed out and slaughtered serially when they were between 614 and 741 d of age. Phenotypes measured at harvest were: live weight; carcass weight; fat depth; marbling; percentage kidney, pelvic, and heart fat (KPH); and rib eye area. Dressing percentage and USDA Yield Grade were calculated from these data. The phenotypes were adjusted to age-, live weight-, and fat depth-constant endpoints using analysis of covariance. The resulting residuals were analyzed by interval mapping to detect QTL. Within family, nominal significance was established by permutation analysis. Approximate genomewide significance levels were established by applying the Bonferroni correction to the nominal probability levels. Regression and error sums of squares and degrees of freedom were pooled across families when suggestive linkage identified in one family was confirmed in the other. The results indicate promising locations for QTL affecting live weight on BTA 17 and marbling on BTA 2 that segregate in Bos taurus. Also, previously identified linkage between central markers on BTA 5 and USDA Yield Grade was confirmed in one family. Greater marker saturation in these regions coupled with refined methods for data analysis will lead to more precise determination of QTL positions.


Strategies in the development of recombinant vaccines for colon cancer.
A new era involving the evaluation of recombinant vaccines for colon cancer has begun with the concurrent emergence of insights and technologies in the fields of molecular biology and immunology. These advances include (I) the identification and cloning of an array of genes associated with the neoplastic process, such as oncogenes, suppressor genes, genes encoding oncofetal antigens, and tissue lineage determinants; (2) the development of a variety of viral and bacterial vectors to deliver and present gene products; (3) the identification of numerous T-cell costimulatory molecules and the knowledge of their mode of action; (4) the cloning and analysis of the modes of action of an array of cytokines and other immunomodulatory molecules; and (5) a more sophisticated knowledge of the mode(s) of antigen presentation and T-cell activation.


Assessing early signs of relapse in psychosis: review and future directions.
Relapse of psychosis is common and has profound adverse consequences. Early signs interventions assume that timely prediction of relapse allows preventative action to reduce the chance of full relapse. The utility of early signs in this context is critically reviewed. Cohort studies suggest that early signs (e.g. anxiety, insomnia) appear in the few weeks before relapse and have modest predictive validity (sensitivity 10%-80%, median 61%; specificity 38%-100%, median 81%), indicating that accuracy of relapse prediction needs improvement. Trials using early signs to target interventions show that targeted antipsychotic medication is less effective than adequately dosed maintenance medication but relapse rates are lower than when intervention is delayed until relapse. The relative value of more complex interventions including psycho-education and relapse prevention strategies is not yet clearly established because there are few trials, some with important design limitations. Basic symptoms are subtle, subjective, qualitative changes in experience claimed to precede psychosis. One retrospective cohort study and studies of "at risk mental states'" transition to psychosis indicate some predictive validity. We suggest that basic symptoms are potentially valuable additions to the range of early signs and deserve further investigation in the effort to enhance the predictive validity of the early signs syndrome.


Drooling of saliva in children with cerebral palsy-etiology, prevalence, and relationship to salivary flow rate in an Indian population.
The prevalence of drooling, the impact of various etiological factors on its severity, and its relationship to salivary flow rate were assessed in 113 individuals with cerebral palsy (CP). In this study, there were 74 males and 39 females with an age range of 6-18 years who were attending a special school in Chennai, India. The severity of drooling was assessed by visual examination; demographics and data regarding severity and control of drooling were collected via a questionnaire. Data regarding the type of CP and drugs taken by the children were obtained from the medical records maintained by the school. The unstimulated salivary flow rate of these children was determined through a passive method. The overall incidence of drooling was 48.7%, with 17.7% having severe drooling. Individuals with athetosis had the least severe amount of drooling. There was a significant relationship between ability to close the mouth and the severity of drooling. The severity of drooling was reduced with age. There was no significant difference in the mean salivary flow rate of those children who drooled and those who did not.


Pneumothorax in the Supine Patient: Subtle Radiographic Signs.
Routine posteroanterior chest radiographs and computed tomography scans are more sensitive for detecting pneumothoraces than anteroposterior chest radiographs. However, supine chest radiographs are commonly performed as part of the initial and routine assessment of trauma and critically ill patients. Rates of occult pneumothorax can be as high as 50% and have a significant impact in the mortality of these patients; thus, a prompt diagnosis of this entity is important. This pictorial essay will illustrate the pleural anatomy, explain the distribution of air within the pleural space in the supine position, and review the radiologic findings that characterize this entity.


Martian subsurface cryosalt expansion and collapse as trigger for landslides.
On Mars, seasonal martian flow features known as recurring slope lineae (RSL) are prevalent on sun-facing slopes and are associated with salts. On Earth, subsurface interactions of gypsum with chlorides and oxychlorine salts wreak havoc: instigating sinkholes, cave collapse, debris flows, and upheave. Here, we illustrate (i) the disruptive potential of sulfate-chloride reactions in laboratory soil crust experiments, (ii) the formation of thin films of mixed ice-liquid water "slush" at -40° to -20°C on salty Mars analog grains, (iii) how mixtures of sulfates and chlorine salts affect their solubilities in low-temperature environments, and (iv) how these salt brines could be contributing to RSL formation on Mars. Our results demonstrate that interactions of sulfates and chlorine salts in fine-grained soils on Mars could absorb water, expand, deliquesce, cause subsidence, form crusts, disrupt surfaces, and ultimately produce landslides after dust loading on these unstable surfaces.


Predicting higher-order mutational effects in an RNA enzyme by machine learning of high-throughput experimental data.
Ribozymes are RNA molecules that catalyze biochemical reactions. Self-cleaving ribozymes are a common naturally occurring class of ribozymes that catalyze site-specific cleavage of their own phosphodiester backbone. In addition to their natural functions, self-cleaving ribozymes have been used to engineer control of gene expression because they can be designed to alter RNA processing and stability. However, the rational design of ribozyme activity remains challenging, and many ribozyme-based systems are engineered or improved by random mutagenesis and selection (in vitro evolution). Improving a ribozyme-based system often requires several mutations to achieve the desired function, but extensive pairwise and higher-order epistasis prevent a simple prediction of the effect of multiple mutations that is needed for rational design. Recently, high-throughput sequencing-based approaches have produced data sets on the effects of numerous mutations in different ribozymes (RNA fitness landscapes). Here we used such high-throughput experimental data from variants of the CPEB3 self-cleaving ribozyme to train a predictive model through machine learning approaches. We trained models using either a random forest or long short-term memory (LSTM) recurrent neural network approach. We found that models trained on a comprehensive set of pairwise mutant data could predict active sequences at higher mutational distances, but the correlation between predicted and experimentally observed self-cleavage activity decreased with increasing mutational distance. Adding sequences with increasingly higher numbers of mutations to the training data improved the correlation at increasing mutational distances. Systematically reducing the size of the training data set suggests that a wide distribution of ribozyme activity may be the key to accurate predictions. Because the model predictions are based only on sequence and activity data, the results demonstrate that this machine learning approach allows readily obtainable experimental data to be used for RNA design efforts even for RNA molecules with unknown structures. The accurate prediction of RNA functions will enable a more comprehensive understanding of RNA fitness landscapes for studying evolution and for guiding RNA-based engineering efforts.


The impact of a notched peripheral intravenous catheter on the first attempt success rate in hospitalized adults: Block-randomized trial.
Peripheral intravenous cannulation is the preferred method to obtain vascular access, but not always successful on the first attempt. Evidence on the impact of the intravenous catheter itself on the success rate is lacking. Faster visualization of blood flashback into the catheter, as a result of a notched needle, is thought to increase first attempt success rate. The current study aimed to assess if inserting a notched peripheral intravenous catheter will increase first attempt cannulation success up to 90%, when compared to inserting a catheter without a notched needle. In this block-randomized trial, adult patients in the intervention group got a notched peripheral intravenous catheter inserted, patients in the control group received a traditional non-notched catheter. The primary objective was the first attempt success rate of peripheral intravenous cannulation. Intravenous cannulation was performed according to practice guidelines and hospital policy. About 328 patients were included in the intervention group and 330 patients in the control group. First attempt success was 85% and 79% for the intervention and control group respectively. First attempt success was remarkably higher in the intervention group regarding patients with a high risk for failed cannulation (29%), when compared to the control group (10%). This study was unable to reach a first attempt success of 90%, although first attempt cannulation success was higher in patients who got a notched needle inserted when compared to those who got a non-notched needle inserted, unless a patients individual risk profile for a difficult intravenous access.


Treatment of established asthma in a murine model using CpG oligodeoxynucleotides.
Allergen immunotherapy is an effective but underutilized treatment for atopic asthma. We have previously demonstrated that CpG oligodeoxynucleotides (CpG ODN) can prevent the development of a murine model of asthma. In the current study, we evaluated the role of CpG ODN in the treatment of established eosinophilic airway inflammation and bronchial hyperreactivity in a murine model of asthma. In this model, mice with established ovalbumin (OVA)-induced airway disease were given a course of immunotherapy (using low doses of OVA) in the presence or absence of CpG ODN. All mice then were rechallenged with experimental allergen. Untreated mice developed marked airway eosinophilia and bronchial hyperresponsiveness, which were significantly reduced by treatment with OVA and CpG. CpG ODN leads to induction of antigen-induced Th1 cytokine responses; successful therapy was associated with induction of the chemokines interferon-gamma-inducible protein-10 and RANTES and suppression of eotaxin. Unlike previous studies, these data demonstrate that the combination of CpG ODN and allergen can effectively reverse established atopic eosinophilic airway disease, at least partially through redirecting a Th2 to a Th1 response.


Purely absorptive three-dimensional infrared spectroscopy.
We demonstrate a method to collect purely absorptive three-dimensional (3D) fifth-order vibrational spectra on the model system CO(2) in H(2)O. The six beam interferometer is described, as well as a method to experimentally determine the phase of the 3D spectrum. The measured spectra agree very well with simulations of the data based on the cumulant expansion. There are five peaks corresponding to different paths up and down the vibrational ladder. The positions, signs, and amplitudes of the peaks agree with theoretical predictions, and the intensities of the peaks scale linearly with concentration. Based on the concentration dependence and agreement between the simulations and measurements, we conclude that cascaded lower order signals contribute negligibly to the observed signal.


Repair of bone defects using adipose-derived stem cells combined with alpha-tricalcium phosphate and gelatin sponge scaffolds in a rat model.
This study aimed to evaluate the potential of adipose-derived stem cells (ASCs) combined with a modified α-tricalcium phosphate (α-TCP) or gelatin sponge (GS) scaffolds for bone healing in a rat model. Bone defects were surgically created in the femur of adult SHR rats and filled with the scaffolds, empty or combined with ASCs. The results were analyzed by histology and histomorphometry on days seven, 14, 30, and 60. Significantly increased bone repair was observed on days seven and 60 in animals treated with α-TCP/ASCs, and on day 14 in the group treated with GS/ASCs, when compared with the groups treated with the biomaterials alone. Intense fibroplasia was observed in the group treated with GS alone, on days 14 and 30. Our results showed that the use of ASCs combined with α-TCP or GS scaffolds resulted in increased bone repair. The higher efficacy of the α-TCP scaffold suggests osteoconductive property that results in a biological support to the cells, whereas the GS scaffold functions just as a carrier. These results confirm the potential of ASCs in accelerating bone repair in in vivo experimental rat models. These results suggest a new alternative for treating bone defects.


Relation of DNA ploidy to genetic aberrations detected by chromosomal CGH and FISH in gastric adenocarcinomas.
We analyzed DNA copy number aberrations (DCNAs) by chromosomal comparative genomic hybridization (CGH) in 93 consecutive sporadic gastric adenocarcinomas. In addition, numerical aberrations in chromosomes 7, 11, 17, and 18 were evaluated by fluorescence in situ hybridization (FISH). Gastric cancers were divided on the basis of nuclear DNA content measured by laser scanning cytometry (LSC) into two groups, 36 DNA diploid (1.0 <or= DNA index (DI) < 1.2) and 57 aneuploid (DI >or= 1.2) cancers. The most frequent gain and loss of DNA copy number were found at 8q21-23 and 19p13.3, respectively, in both diploid and aneuploid cancers. Diploid cancers were further divided on the basis of genetic aberrations into major type and subtype cancers. The diploid cancer group included nine subtype cancers that showed large numbers of DCNAs; the mean number of DCNAs detected by CGH was 26.7 per tumor. This value was much larger in these diploid subtype cancers than diploid major type cancers (mean, 5.2 per tumor, p<0.0001). These nine cancers were also characterized by large intercellular variations in chromosome copy numbers that were not detected in the 27 major diploid type cancers. The aneuploid cancer group included only three subtype tumors that showed only a small number of DCNAs (mean, 3 per tumor) and minimal intercellular variations in chromosomal copy number. These data indicate that gastric adenocarcinomas can be divided into three types; aneuploid, major diploid type and diploid subtype cancers. Large-scale studies are necessary to clarify the differences in biological characteristics and underlying genetic mechanisms between these types.


Photoswitch nucleic acid catalytic activity by regulating topological structure with a universal supraphotoswitch.
We demonstrated the generality of a strategy for photoswitching the activity of functional oligonucleotides by modulating their topological structure. Our strategy was proved to be versatile because it can be used to photoregulate functional oligonucleotides, e.g., ribozymes and DNAzymes, which have two binding arms and a catalytic loop. Repeated reversible photoregulation of RNA cleavage by a ribozyme or a DNAzyme was achieved by attaching two photoresponsive strands, artificial oligomers involving azobenzene moieties and nucleobases capable of forming a duplex as the supraphotoswitch. Individual strands were attached to the 3' and 5' ends of a RNA-cleavage oligonucleotide. Thus, the topological structure of the ribozyme or DNAzyme was constrained, and RNA cleavage was greatly suppressed when the supraphotoswitch duplex formed (OFF state). In contrast, RNA cleavage resumed when the supraphotoswitch duplex dissociated (ON state). Light irradiation was used to repeatedly switch the supraphotoswitch between the ON and OFF states so that RNA cleavage activity could be efficiently photoregulated. Analysis of the regulatory mechanism showed that topological constraints suppressed the RNA cleavage by causing both structural changes at the catalytic site and lower binding affinity between the RNA substrates and the functional oligonucleotides.


Atomic Force Microscopy Stiffness Mapping in Human Aortic Smooth Muscle Cells.
Aortic smooth muscle cells (SMCs) play a vital role in maintaining mechanical homeostasis in the aorta. We recently found that SMCs of aneurysmal aortas apply larger traction forces than SMCs of healthy aortas. This result was explained by the significant increase of hypertrophic SMCs abundance in aneurysms. In this study, we investigate whether the cytoskeleton stiffness of SMCs may also be altered in aneurysmal aortas. For that, we use atomic force microscopy (AFM) nano-indentation with a specific mode that allows subcellular-resolution mapping of the local stiffness across a specified region of interest of the cell. Aortic SMCs from a commercial human lineage (AoSMCs, Lonza) and primary aneurysmal SMCs (AnevSMCs) are cultured in conditions promoting the development of their contractile apparatus, and seeded on hydrogels with stiffness properties of 12 kPa and 25 kPa. Results show that all SMCs exhibit globally a lognormal stiffness distribution, with medians in the range 10-30 kPa. The mean of stiffness distributions is 16 kPa in aneurysmal SMCs and 12 kPa in healthy cells, but the differences are not statistically significant due to the large dispersion of AFM nano-indentation stiffness. We conclude that the possible alterations previously found in aneurysmal SMCs do not affect significantly the AFM nano-indentation stiffness of their cytoskeleton.


Scarless fetal healing. Therapeutic implications.
The purpose of this report is to call attention to the fetal wound healing process as a blueprint for ideal tissue repair. Wound healing in the fetus is fundamentally different from healing in the adult. Fetal tissue repair occurs rapidly and in the absence of scar formation. Because scarring and fibrosis dominate some diseases in every area of medicine, an understanding of fetal wound healing should help develop therapeutic strategies to avert the devastating consequences of excessive scar formation.


Vehicle safety characteristics in vulnerable driver populations.
National data suggest drivers who are younger, older, and have lower socioeconomic status (SES) have heightened crash-related injury rates. Ensuring vulnerable drivers are in the safest vehicles they can afford is a promising approach to reducing crash injuries in these groups. However, we do not know the extent to which these drivers are disproportionately driving less safe vehicles. Our objective was to obtain population-based estimates of the prevalence of important vehicle safety criteria among a statewide population of drivers. We analyzed data from the NJ Safety and Health Outcomes warehouse, which includes all licensing and crash data from 2010-2017. We borrowed the quasi-induced exposure method's fundamental assumption-that non-responsible drivers in clean (i.e., only one responsible driver) multi-vehicle crashes are reasonably representative of drivers on the road-to estimate statewide prevalence of drivers' vehicle characteristics across four driver age groups (17-20; 21-24; 25-64, and ≥65) and quintiles of census tract median household income (n = 983,372). We used NHTSA's Product Information Catalog and Vehicle Listing platform (vPIC) to decode the VIN of each crash-involved vehicle to obtain model year, presence of electronic stability control (ESC), vehicle type, engine horsepower, and presence of front, side, and curtain air bags. The youngest and oldest drivers were more likely than middle-aged drivers to drive vehicles that were older, did not have ESC, and were not equipped with side airbags. Additionally, across all age groups drivers of higher SES were in newer and safer vehicles compared with those of lower SES. For example, young drivers living in lowest-income census tracts drove vehicles that were on average almost twice as old as young drivers living in highest-income tracts (median [IQR]: 11 years [6-14] vs. 6 years [3-11]). Vehicle safety is an important component of seminal road safety philosophies that aim to reduce crash fatalities. However, driver groups that are overrepresented in fatal crashes-young drivers, older drivers, and those of lower SES-are also driving the less safe vehicles. Ensuring drivers are in the safest car they can afford should be further explored as an approach to reduce crash-related injuries among vulnerable populations.


The Sock Test for evaluating activity limitation in patients with musculoskeletal pain.
Assessment within rehabilitation often must reflect patients' perceived functional problems and provide information on whether these problems are caused by impairments of the musculoskeletal system. Such capabilities were examined in a new functional test, the Sock Test, simulating the activity of putting on a sock. Intertester reliability was examined in 21 patients. Concurrent validity, responsiveness, and predictive validity were examined in a sample of 337 patients and in subgroups of this sample. Intertester reliability was acceptable. Sock Test scores were related to concurrent reports of activity limitation in dressing activities. Scores also reflected questionnaire-derived reports of problems in a broad range of activities of daily living and pain and were responsive to change over time. Increases in age and body mass index increased the likelihood of Sock Test scores indicating activity limitation. Pretest scores were predictive of perceived difficulties in dressing activities after 1 year. Sock Test scores reflect perceived activity limitations and restrictions of the musculoskeletal system.


Solar potential scaling and the urban road network topology.
We explore the scaling of cities' solar potentials with their number of buildings and reveal a latent dependence between the solar potential and the length of the corresponding city's road network. This scaling is shown to be valid at the grid and block levels and is attributed to a common street length distribution. Additionally, we compute the buildings' solar potential correlation function and length in order to determine the set of critical exponents typifying the urban solar potential universality class.


Measurement of choroidal melanoma basal diameter by wide-angle digital fundus camera: a comparison with ultrasound measurement.
To compare the measurement of the basal diameter of choroidal melanoma, an important parameter for planning treatment and as a prognostic factor, by standardized ophthalmic ultrasound versus that obtained using a wide-angle fundus camera. The longest and shortest basal diameters of 104 consecutive choroidal melanomas of patients seen at the ocular oncology service of the Hadassah University Hospital were measured by B-scan ultrasound and compared with those measured by a wide-angle fundus camera (Panoret-1000). Each diameter was measured thrice by two ophthalmic photographers, and intra-observer and interobserver reproducibility were calculated as well. The measurements of both the long and short diameters of the choroidal melanomas were significantly larger when measured by Panoret-1000 as compared with the B-scan ultrasound. There was no significant difference among the three measurements of each of the photographers. The interobserver reproducibility between the two photographers was high. Our findings can be attributed to the larger extent of the pigmentation of the melanoma compared to its recognized elevation. Since pigmentation of choroidal melanoma is easier to recognize than its elevation, we assume that measurement by a wide-angle fundus camera is more accurate in pigmented tumors, and should be adopted for measuring the basal diameter of choroidal melanomas in planning treatment and follow-up.


Rapid determination of vitamin C by NIR, MIR and FT-Raman techniques.
Rapid spectroscopic determination of vitamin C in food and pharmaceutical products using infrared and Raman techniques was proposed. In this study, near-infrared (NIR), Fourier transform near-infrared (FT-NIR), Fourier transform infrared-attenuated total reflectance (FTIR-ATR), diffuse reflectance (DRIFTS), Fourier transform infrared-photoacoustic (FTIR-PAS) and FT-Raman spectroscopy were used in conjunction with partial least squares (PLS) regression to quantify vitamin C in powdered mixtures and solutions. Results indicate that the methods adopted have high prediction correlation. R2 values were 0.999 for FTIR-ATR, 0.976 for DRIFTS, 0.966 for FTIR-PAS, 0.988 for NIR, 0.992 for FT-NIR and 0.95 for FT-Raman, with an overall prediction error of 0.2-3.0%. The time required to complete an experiment ranged from 5 s (NIR) to 3 min (FT-Raman). The FTIR and FT-Raman techniques can be complementary tools for qualitative and quantitative characterization of the samples. Infrared and Raman techniques can be used to quantify vitamin C in foods and pharmaceutical products.


Progress in active specific immunotherapy of prostate cancer.
Treatments available for metastatic prostate cancer have failed to demonstrate significant curative potential. Current efforts are now directed towards developments of novel strategies for the treatment of metastatic prostate cancer. Cancer immunotherapeutic strategies utilize patient immune system components to kill cancer cells. This review discusses progress in active specific immunotherapeutic approaches as potential alternative methods in the treatment of metastatic prostate cancer. Various methods of augmenting the immune response against prostate cancer are discussed including systemic cytokine adjuvant therapy, cytokine gene transduced tumor vaccines, non-antigen specific immunization, DNA and peptide vaccines plus adjuvants, as well as dendritic cell-based cancer vaccines.


Intense bitterness of molecules: Machine learning for expediting drug discovery.
Drug development is a long, expensive and multistage process geared to achieving safe drugs with high efficacy. A crucial prerequisite for completing the medication regimen for oral drugs, particularly for pediatric and geriatric populations, is achieving taste that does not hinder compliance. Currently, the aversive taste of drugs is tested in late stages of clinical trials. This can result in the need to reformulate, potentially resulting in the use of more animals for additional toxicity trials, increased financial costs and a delay in release to the market. Here we present BitterIntense, a machine learning tool that classifies molecules into "very bitter" or "not very bitter", based on their chemical structure. The model, trained on chemically diverse compounds, has above 80% accuracy on several test sets. Our results suggest that about 25% of drugs are predicted to be very bitter, with even higher prevalence (~40%) in COVID19 drug candidates and in microbial natural products. Only ~10% of toxic molecules are predicted to be intensely bitter, and it is also suggested that intense bitterness does not correlate with hepatotoxicity of drugs. However, very bitter compounds may be more cardiotoxic than not very bitter compounds, possessing significantly lower QPlogHERG values. BitterIntense allows quick and easy prediction of strong bitterness of compounds of interest for food, pharma and biotechnology industries. We estimate that implementation of BitterIntense or similar tools early in drug discovery process may lead to reduction in delays, in animal use and in overall financial burden.


[A grading scale for endovascular treatment of intracranial aneurysms].
To investigate the factors influencing the embolizing plan and result of intracranial aneurysms, and to establish a new grading scale for endovascular treatment of intracranial aneurysms. The clinical data of 156 aneurysms in 151 patients, 67 males and 84 females, aged 4-80, were prospectively collected to analyze the influences of sex, age, aneurysmal DSA manifestation (including location, shape, longest diameter, neck width and sac-neck ratio) and whether or not embolizing in acute phase on the therapeutic alternatives and immediate embolizing results. Logistic regression analyses showed that aneurysmal location (OR = 3.734, P = 0.018), neck width (OR = 16.279, P = 0.000) and sac-neck ratio (OR = 4.090, P = 0.003) were predictive factors of the therapeutic alternatives, and the longest diameter (OR = 2.725, P = 0.024), neck width (OR = 2.600, P = 0.033) and sac-neck ratio (OR = 3.144, P = 0.003) were predictive factors of the embolizing results. Aneurysmal location (0 for internal carotid system, and 1 for vertebro-basilar system), the longest diameter (0 for < 8 mm, and 1 for > or = 8 mm), neck width (0 for < 4 mm, and 1 for > or = 4 mm or without neck) and sac-neck ratio (0 for > 1.2, and 1 for < or = 1.2 or without neck) were regarded as grading items to establish the intracranial aneurysm endovascular scale (IAES), which ranked the intracranial aneurysms into four grades. The zero and first grades were ordinary aneurysms, and the second to fourth grades were complicated aneurysms. IAES helps the clinicians to determine the individualized embolizing plan and predict the embolizing effect.


[Therapeutic effect of baicalin in treatment of renal interstitial fibrosis in rats with unliateral ureteral obstruction and related mechanisms].
To investigate the therapeutic effect of baicalin at different doses administered for different periods of time in the treatment of renal interstitial fibrosis in rats with unliateral ureteral obstruction (UUO) and related mechanisms. Sixty-four Sprague-Dawley rats were randomly divided into sham-operation, model, low-dose baicalin, and high-dose baicalin groups, and each group was further randomly divided into 7-day and 14-day groups (n=8 each). Left ureteral ligation was used to establish the rat model of UUO. Hematoxylin and eosin staining was used to observe the pathological changes in the kidney. ELISA was used to measure the serum levels of transforming growth factor-β1 (TGF-β1), Notch1, and Jagged1. Immunohistochemistry was used to measure the expression of TGF-β1 and Notch1. The Pearson correlation analysis was used for correlation analysis. Hematoxylin and eosin staining showed inflammatory cell infiltration and edema in renal interstitium, tubular dilation and structure disorder, degeneration and necrosis of renal tubular epithelial cells, and a basically normal structure of the glomeruli on days 7 and 14 in the model group, and these lesions were alleviated in the low- and high-dose baicalin groups. Compared with the sham-operation group, the model group had a significantly higher serum level of TGF-β1 and a significantly higher number of TGF-β1-positive cells in renal tissues on days 7 and 14 (P<0.05). Compared with the model group at the same time points, the high- and low-dose baicalin groups had a significantly lower serum level of TGF-β1 and a significantly lower number of TGF-β1-positive cells in renal tissues on days 7 and 14 (P<0.05). The serum level of Jagged1 showed no significant differences between any two groups on days 7 and 14 (P>0.05). The serum level of TGF-β1 was positively correlated with that of Notch1 (r=0.650, P<0.01), and the serum level of Notch1 was positively correlated with that of Jagged1 (r=0.727, P<0.01). TGF-β1 level in renal tissues was also positively correlated with the number of Notch1-positive cells (r=0.743, P<0.01). Baicalin can alleviate renal interstitial fibrosis in UUO rats, probably by inhibiting Notch1 signaling pathway and the expression of TGF-β1.


Feasibility of using audio computer-assisted self-interview (ACASI) screening in routine HIV care.
We evaluated the feasibility of implementing audio computer-assisted self-interviews (ACASI) as part of routine clinical care at two community hospital-based HIV clinics in New York City. Between June 2003 and August 2006, 215 patients completed 1001 ACASI sessions in English or Spanish prior to their scheduled clinical appointments. Topics covered included antiretroviral therapy adherence, depression symptoms, alcohol and drug use, and condom use. Patients and providers received feedback reports immediately after each session. Feasibility was evaluated by quantitative analysis of ACASI responses, medical chart reviews, a brief patient questionnaire administered at the conclusion of each computer session, patient focus groups, and semi-structured provider interviews. ACASI interviews frequently identified inadequate medication adherence and depression symptoms: at baseline, 31% of patients reported < or =95% adherence over the past three days and 52% had symptoms of depression (CES-D score > or =16). Substance abuse problems were identified less frequently. Patients were comfortable with the ACASI and appreciated it as an additional communication route with their providers; however, expectations about the level of communication achieved were sometimes higher than actual practice. Providers felt the summary feedback information was useful when received in a timely fashion and when they were familiar with the clinical indicators reported. Repeated ACASI sessions did not have a favorable impact on adherence, depression, or substance use outcomes. No improvements in HIV RNA suppression were observed in comparison to patients who did not participate in the study. We conclude that it is feasible to integrate an ACASI screening tool into routine HIV clinical care to identify patients with inadequate medication adherence and depression symptoms. Repeated screening was not associated with improved clinical outcomes. ACASI screening should be considered in HIV clinical care settings to assist providers in identifying patients with the greatest need for targeted psychosocial services including adherence support and depression care.


Chordoma of skull base presenting as nasopharyngeal mass.
While the nasopharynx is most commonly regarded by the otolaryngologist as a primary site of neoplastic involvement, it is also an avenue of spread of base-of-the-skull tumors presenting as bulging nasopharyngeal masses. Chordoma is a relatively rare tumor of the skull base and sacrum thought to originate from embryonic remnants of the notochord. Chordomas arising from the skull base/clivus are typically locally aggressive with lytic bone destruction. The optimal treatment may be photon/proton radiotherapy alone or combined with a gross total resection, when feasible. We report a case of intracranial chordoma presenting as nasopharyngeal mass.


Inflammatory response of macrophages cultured with Helicobacter pylori strains was regulated by miR-155.
MicroRNA-155 plays an important role in the inflammatory response macrophages, while present studies identified that miR-155 was up-expressed in gastritis induced by Helicobacter pylori. We found that miR-155 was over expressed in macrophages infected with H. pylori in vivo or in vitro. Subsequently, inflammatory cytokines IL-23, IL-10, TNF-α and IL-8 were increased significantly, and the expression of CD80, CD86 or COX2, NOS2. Were enhanced in H. pylori infection macrophages by regulated with miR-155mimics. Furthermore, the apoptosis of macrophages induced by H. pylori was increased obviously due to the over-expression of miR-155. Therefore, these observations indicated that miR-155 may act as a inflammatory promoter in H. pylori infected macrophages. These findings contribute us to understand the functions of miR-155 in gastritis induced by H. pylori furtherly.


The effect of grazing on winter survival of midday gerbil (Meriones meridianus) of different genders.
The objective of this study was to investigate the effects of grazing on midday gerbil (Meriones meridianus) population characteristics and survival of animals of different genders. The experiment used a randomized complete block design and was conducted in Alxa Left Banner, Inner Mongolia, China, in 2002 (The agricultural reclamation plots set up in 1994). From April 2006 to October 2010, midday gerbils were live-trapped in 3 light grazing plots, 3 overgrazed plots, and 3 grazing exclusion plots. The quantity of vegetation was investigated in the two different grazing intensity areas and grazing exclusion area to determine the relationship between gerbils and plant food availability. The results suggested that there was higher gerbil density, individual body mass, and daily body mass growth rate in the grazing exclusion sites than the other sites across the whole year. Females had higher survival in grazing exclusion areas than in other treatments, but the males' survival showed the opposite pattern. Our results indicated that grazing negatively influenced the midday gerbil population by reducing food availability. Grazing influenced the survival rates of male midday gerbils positively, but had negative effects on females. The reason for gendered differences in survival rates of midday gerbils requires further investigation.


Optimization of spatial pipeline with multi-hoop supports for avoiding resonance problem based on genetic algorithm.
The reasonable layout of hoops can effectively avoid the excitation frequency of engine rotors and greatly reduce the vibration level of pipeline systems. In this study, a spatial pipeline supported by multi-hoops was taken as the object, the method of using genetic algorithm to efficiently obtain the optimal layout of hoops to avoid resonance was investigated. The finite element model of the pipeline system was created as the basic model of optimization, spring elements were applied to simulate the mechanical characteristics of hoop and the influence of spring element direction on the vibration characteristics of pipeline system were mainly described. In the optimization of avoiding resonance for spatial pipelines, the optimization goal was to maximize the first-order natural frequency, the positions of the hoops were converted into the node number as design variables, and the final optimization model of pipeline to avoid resonance was determined on the premise of reasonably setting of constraint conditions for design variables. The genetic algorithm was utilized to solve the optimization model, and two optimization methods were proposed, which were named as "genetic algorithm calling finite element model" and "genetic algorithm updating stiffness matrix" respectively. Finally, a case study was carried out to display the proposed methods. The maximum deviation between the calculation and the test results is less than 1.5% for the first three order natural frequencies, which proves the rationality of the created finite element model of spatial pipeline. Furthermore, the optimization practices show that the reasonable hoop layout of the pipeline system can be obtained by the two optimization methods, but the efficiency of the optimization performed by "genetic algorithm updating stiffness matrix" is much higher than that of "genetic algorithm calling finite element model".


Bacteriophages and viruses as a support for organic synthesis and combinatorial chemistry.
Display of polypeptide on the coat proteins of bacteriophages and viruses is a powerful tool for selection and amplification of libraries of great diversity. Chemical diversity of these libraries, however, is limited to libraries made of natural amino acid side chains. Bacteriophages and viruses can be modified chemically; peptide libraries presented on phage thus can be functionalized to yield moieties that cannot be encoded genetically. In this review, we summarize the possibilities for using bacteriophage and viral particles as support for the synthesis of diverse chemically modified peptide libraries. This review critically summarizes the key chemical considerations for on-phage syntheses such as selection of reactions compatible with protein of phage, modification of phage "support" that renders it more suitable for reactions, and characterization of reaction efficiency.


Young people and alcohol: an econometric analysis.
To analyse the determinants of youth drinking behaviour within an economic -theoretical framework. The paper focuses especially on the effects of (a) having parents willing to supply alcohol, (b) living in a single-parent household, (c) having parents who are currently unemployed and (d) having received education about alcohol, narcotics and tobacco. A Swedish cross-sectional survey data on 833 individuals aged 12-18 years was used to analyse the effects of the above variables on participation in drinking, frequency of drinking, intensity of drinking and binge drinking. Separate analyses were conducted for beer, wine and spirits. Care was taken in using appropriate econometric methods for the questions posed (negative binomial regression, censored regression and probit regression). Having parents willing to supply alcohol increased frequency (P < 0.05) of beer, wine and spirits consumption, intensity (P < 0.05) of wine, spirits and illicit alcohol consumption, and increased probabilities (P < 0.10) of binge drinking and participation in drinking (P < 0.05). No effects were seen from living in a single-parent household. Having received education about alcohol, narcotics and tobacco had a negative association only with intensity (P < 0.10) of beer consumption. Having a father who was currently unemployed was associated with an increased (P < 0.05) probability of binge drinking but a reduced (P < 0.05) frequency of wine consumption. The positive effect of having parents willing to supply alcohol could reflect that these individuals face lower acquisition costs or lower psychological costs in consumption. It could also reflect a price effect, if the individual receives the alcohol free from his or her parents.


Allergic contact dermatitis to antibacterial agents.
Topical antibiotics are frequently introduced in therapy by various specialists, e.g., dermatologists-venereologists, ENT specialists, proctologists, ophthalmologists, and others. In dermatology, topical antibiotics are used in the treatment of superficial inflammatory skin lesions, acne and rosacea. These agents are also used in the prevention of inflammatory lesions after surgical and corrective procedures. Long-term and uncontrolled application of topical antibiotics, on the skin with impaired protective barrier in particular, implies a risk for the development of hypersensitivity to these agents. Considering the very wide utilization of these agents, hypersensitivity to topical antibiotics poses a major problem worldwide. The groups at a high risk of contact sensitivity to topical antibiotics include patients with chronic venous insufficiency, chronic ulcers and chronic otitis externa, as well as individuals at occupational exposure to antibiotics, e.g., human medicine and veterinary medicine professionals, pharmaceutical industry workers, cattle breeders, etc. When long-term therapy fails to result in improvement in the above mentioned chronic states, the possibility of allergic reactions to topical agents should be taken in consideration. Cross-sensitivity, which is frequently associated with the use of topical aminoglycoside antibiotics, poses a significant problem.


AML M1 and M2 with eosinophilia and AML M4Eo: diagnostic and clinical aspects.
AML with eosinophilia belongs to the morphologic cytogenetic entity M1/M2 t(8;21) with the involvement of the genes AML1/ETO. These eosinophils differ only slightly from normal eosinophils with one rare exception i.e. Auer rods in eosinophils which has only been found on peroxidase staining: This subtype belongs to the good prognosis group of AML. AML with inv(16) (mostly M4Eo) per se is a morphologic-cytogenetic entity with inv(16),--rarely t(16;16), and the genes MYL 11/CBF beta involved. The eosinophils show special abnormalities. AML with inv(16) also belongs to the good prognosis group of AML.


Removal of Cr(VI) from wastewaters in a tubular electrochemical reactor.
This work aimed at studying the electrochemical reduction of the hexavalent chromium Cr(VI) by means of a tubular reactor operating under both continuous and batch regimes. It is shown that chromium (VI) reduction to chromium (III) was exerted not only by the oxidation of iron to Fe(II) released from the steel sacrifice anodes immersed in an acid solution to aid the overall process. Also, it is shown that there was an additional contribution to chromium reduction from an ancillary reaction at the cathode, where Fe(III) ions generated after the Cr(VI) reduction are again reduced to Fe(II), this being interpreted as a catalytic effect taking place. The results are presented at pH values of 1, 1.3, 1.7, and 2: it became clear that the variable affected the solubility of the species generated in solution. The initial chromium hexavalent concentration was 1000 mg L(- 1) and it was found that after treatment times ranging from 320 to 25 minutes this could reach values as low as 0.5 mg L(- 1), depending on the operating conditions.


Lessons learned from the investigation and management of an outbreak of Shigella flexneri associated with a restaurant in London, 2019-2020.
Foodborne outbreaks of Shigella flexneri infection are uncommon in the UK. In November 2019, the United Kingdom Health Security Agency investigated an outbreak of S. flexneri associated with a fast-food restaurant in London. Epidemiological investigations included case ascertainment and interviewing suspected cases using enhanced surveillance questionnaires. Whole-genome sequencing (WGS) was used for characterisation of human isolates. Environmental investigations included a review of food safety processes at the implicated restaurant, administration of exposure questionnaires and stool sampling of staff. Between November 2019 and February 2020, 17 cases were confirmed as part of the outbreak by WGS in London. Among these, 15 were linked to the implicated restaurant. A review of the food safety processes at the restaurant was satisfactory. Despite initial suboptimal coverage of stool screening of staff, all staff members working at the restaurant during the sampling period were screened and an asymptomatic food handler tested positive for S.flexneri with the outbreak WGS profile. The individual underwent microbiological clearance, and no further cases were reported. It was not possible to confirm the direction of transmission for the community cases or the staff member. We report an outbreak of S. flexneri in a fast-food restaurant in London with previous inspection ratings indicating good compliance with food safety and hygiene standards. WGS was crucial in identifying cases linked to the outbreak. This outbreak highlights the importance of prompt testing of food handlers in outbreaks suspected to be associated with food businesses.


Recurrent Aphthous Stomatitis Caused by Cytomegalovirus, Herpes Simplex Virus, and Candida Species in a Kidney Transplant Recipient: A Case Report.
Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.


Asymmetric microtubule pushing forces in nuclear centering.
Dynamic properties of microtubules contribute to the establishment of spatial order within cells. In the fission yeast Schizosaccharomyces pombe, interphase cytoplasmic microtubules are organized into antiparallel bundles that attach to the nuclear envelope and are needed to position the nucleus at the geometric center of the cell. Here, we show that after the nucleus is displaced by cell centrifugation, these microtubule bundles efficiently push the nucleus back to the center. Asymmetry in microtubule number, length, and dynamics contributes to the generation of force responsible for this unidirectional movement. Notably, microtubules facing the distal cell tip are destabilized when the microtubules in the same bundle are pushing from the proximal cell tip. The CLIP-170-like protein tip1p and the microtubule-bundling protein ase1p are required for this asymmetric regulation of microtubule dynamics, indicating contributions of factors both at microtubule plus ends and within the microtubule bundle. Mutants in these factors are defective in nuclear movement. Thus, cells possess an efficient microtubule-based engine that produces and senses forces for centering the nucleus. These studies may provide insights into mechanisms of asymmetric microtubule behaviors and force sensing in other processes such as chromosome segregation and cell polarization.


HLA class II donor specific antibodies are associated with graft cirrhosis after liver transplant independent of the mean fluorescence intensity level.
The importance of donor-specific antibodies (DSA) after liver transplantation (LT) for graft and patient survival is an ongoing controversy. So far it has not been elucidated when and in how far DSA are harmful for graft and patient survival. Therefore, we had the aim to investigate the association of DSA with complications after LT. Data of 430 LT recipients were collected and statistically analyzed. Detection of HLA antibodies (Ab) was performed by Luminex assay. DSA were detected in 81 patients (18.8%). These were mainly HLA class II Ab (81.5%). HLA class II Ab show a higher MFI (median: 5.300) compared to HLA class I Ab (median: 2.300). There is no association between MFI levels and development of complications after LT. However, cirrhosis occurred significantly more often in DSA positive patients (18%) than in patients without detectable DSA (9%, P = 0.027). All DSA positive patients with cirrhosis of the graft showed HLA class II antibodies (OR: 3.028; 95% CI: 1.51-6.075; P = 0.002). Occurrence of HLA class II DSA after LT is associated with graft cirrhosis and may indicate a higher risk to develop graft damage independent on MFI and requires an individualized risk management.


[Expression of COL1a1 and COL3a1 in the capsule of children with developmental dislocation of the hip].
The etiology of developmental dislocation of the hip (DDH) remains uncertain, but some research has shown that this disorder is closely related to hip joint laxity. This study examined the expression of collagens type I and III mRNA and protein in the hip capsule of children with DDH in order to investigate the roles of collagens type I and III in hip joint laxity. Nine children with DDH and nine age and gender-matched normal children (control group) were enrolled. Semiquantitative RT-PCR method was used to detect mRNA expression of COL1a1 and COL3a1 in the hip capsule. Western-Blot method was used to detect protein expression of COL1a1 and COL3a1 in the hip capsule. The quantitative analysis of the COL1a1 and COL3a1 was performed by professional image software and the results were analyzed with standard statistical methods. mRNA and protein expression of COL1a1 in the DDH group was significantly lower than that in the control group (P<0.01). Compared with the control group, COL1a3 mRNA expression in the DDH group decreased significantly (P<0.01), but COL1a3 protein expression was not significantly different. The decreased collagen I mRNA and protein expression in the hip capsule might contribute to hip joint laxity in children with DDH. Collagen type III may not be associated with hip joint laxity in DDH.


Implementierung eines neonatalen Schmerzassessmentinstruments auf einer neonatologischen Intensivstation - Ein Qualitätsentwicklungsprojekt.
Implementation of a Neonatal Pain Assessment Instrument at a Neonatal Intensive Care Unit - A Quality Improvement Project Abstract. Background: Optimal pain management is necessary in order to not jeopardize the development of preterm neonates. Aim: Implementation and evaluation of systematic and best possible pain assessment with the Bernese Pain Scale for Neonates for all preterm and sick neonates of a neonatal intensive care unit by nursing staff. Methods: The educational concept is based on three key strategies: knowledge translation (group- and one-on-one training), reflection (case conferences) and clinical training. The frequency of the use of the Pain Score was recorded before (T0) and after implementation (T1) and six months after completion of the project (T2). Results: Before the implementation (T0) the use of the Bernese Pain Scale was regulated by an internal guideline but its application could not be verified during the baseline period (fulfillment rate of 0 %). After implementation (T1) at least one assessment per shift per neonate could be achieved in 99.1 % of the cases. Nurses conducted 210 assessments on 38 neonates in T1. In follow-up (T2) six months after implementation fulfillment rate of 100 % in 34 neonates was achieved with 188 pain assessments. Conclusions: This implementation strategy was successful in establishing the assessment instrument in clinical practice.


The Impact of Telemedicine Visits on the Controlling High Blood Pressure Quality Measure During the COVID-19 Pandemic: Retrospective Cohort Study.
Telemedicine visit use vastly expanded during the COVID-19 pandemic, and this has had an uncertain impact on cardiovascular care quality. We sought to examine the association between telemedicine visits and the failure to meet the Controlling High Blood Pressure (BP) quality measure from the Centers for Medicare & Medicaid Services. This was a retrospective cohort study of 32,727 adult patients with hypertension who were seen in primary care and cardiology clinics at an urban, academic medical center from February to December 2020. The primary outcome was a failure to meet the Controlling High Blood Pressure quality measure, which was defined as having no BP recorded or having a last recorded BP of ≥140/90 mm Hg (ie, poor BP control). Multivariable logistic regression was used to assess the association between telemedicine visit use during the study period (none, 1 telemedicine visit, or ≥2 telemedicine visits) and poor BP control; we adjusted for demographic and clinical characteristics. During the study period, no BP was recorded for 2.3% (486/20,745) of patients with in-person visits only, 27.1% (1863/6878) of patients with 1 telemedicine visit, and 25% (1277/5104) of patients with ≥2 telemedicine visits. After adjustment, telemedicine use was associated with poor BP control (1 telemedicine visit: odds ratio [OR] 2.06, 95% CI 1.94-2.18; P<.001; ≥2 telemedicine visits: OR 2.49, 95% CI 2.31-2.68; P<.001; reference: in-person visits only). This effect disappeared when the analysis was restricted to patients with at least 1 recorded BP (1 telemedicine visit: OR 0.89, 95% CI 0.83-0.95; P=.001; ≥2 telemedicine visits: OR 0.91, 95% CI 0.83-0.99; P=.03). Increased telemedicine visit use is associated with poorer performance on the Controlling High Blood Pressure quality measure. However, telemedicine visit use may not negatively impact BP control when BP is recorded.


The Impact of Breast Cancer Treatment Delays on Survival Among South African Women.
In high-income settings, delays from breast cancer (BC) diagnosis to initial treatment worsen overall survival (OS). We examined how time to BC treatment initiation (TTI) impacts OS in South Africa (SA). We evaluated women enrolled in the South African BC and HIV Outcomes study between July 1, 2015 and June 30, 2019, selecting women with stages I-III BC who received surgery and chemotherapy. We constructed a linear regression model estimating the impact of sociodemographic and clinical factors on TTI and separate multivariable Cox proportional hazard models by first treatment (surgery and neoadjuvant chemotherapy (NAC)) assessing the effect of TTI (in 30-day increments) on OS. Of 1260 women, 45.6% had upfront surgery, 54.4% had NAC, and 19.5% initiated treatment >90 days after BC diagnosis. Compared to the surgery group, more women in the NAC group had stage III BC (34.8% vs 81.5%). Living further away from a hospital and having hormone receptor positive (vs negative) BC was associated with longer TTI (8 additional days per 100 km, P = .003 and 8 additional days, P = .01, respectively), while Ki67 proliferation index >20 and upfront surgery (vs NAC) was associated with shorter TTI (12 and 9 days earlier; P = .0001 and.007, respectively). Treatment initiation also differed among treating hospitals (P < .0001). Additional 30-day treatment delays were associated with worse survival in the surgery group (HR 1.11 [95%CI 1.003-1.22]), but not in the NAC group. Delays in BC treatment initiation are common in SA public hospitals and are associated with worse survival among women treated with upfront surgery.


Saving the leftovers: models for banking cord blood stem cells.
Each year there are over four million live births in the United States. Each birth produces umbilical cord blood stem cells, which are usually discarded. The author argues that rather than discarding the umbilical cord, this valuable resource of cord blood should be banked and used for research and therapeutic purposes. Umbilical cord blood could provide a solution to the critical need to find matching donors for hematopoietic transplants in patients who have no matching bone marrow donors. Creating a system of universal donation to a public bank will greatlyincrease the number of donors and therefore, the number of matches for patients. Such a system will facilitate the development and use of new technologies and transplant procedures, while providing an opportunity for treatment to individuals who would otherwise not be able to find suitable donors.


Exploiting our knowledge of NF-kappaB signaling for the treatment of mammary cancer.
Nuclear Factor-kappaB (NF-kappaB) has been implicated in the lobuloalveolar development of the mammary gland. In breast cancer its activation has been linked to tumor progression via stimulation of cell proliferation, pro-survival, and angiogenesis pathways and metastasis. Whether NF-kappaB activation in the immune system influences mammary cancer remains unclear. In addition to the constitutive activation frequently found in mammary carcinoma tissue, radio- and chemotherapeutic agents used in the treatment of mammary cancer can lead to activation of NF-kappaB. This effect has been postulated to contribute to the development of resistance to these agents and suggests the use of NF-kappaB inhibitors as sensitizers for therapy. The review describes principle targets and drugs used to inhibit NF-kappaB function and discusses future perspectives in the use of these inhibitors for the treatment of mammary cancer.


Acute Myocardial Infarction in Hemophilia A with HIV and Hyperhomocysteinemia- a rare case report.
Patients with hemophilia have a hypocoagulable state and less chances of thrombus formation. Therefore, expected to have a lower cardiovascular mortality than the general population. The lower cardiovascular mortality can be explained by less chances of thrombus formation due to hypocoagulability. Here we present a case of a 42-year-old male patient presented with severe chest pain radiating to back for 4 days. ECG was suggestive of recent acute anteroseptal myocardial infarction. There was a history of receiving intravenous recombinant factor VIII, 1 hour prior to the onset of chest pain for knee joint swelling. The occurrence of acute coronary syndromes in patients with hemophilia A is uncommon and rarely reported. Here we report a patient of severe hemophilia A who developed acute myocardial infarction after administration of recombinant factor VIII.


[Medical management of post-obstruction diuresis syndromes].
The presence of urinary tract obstruction affects the proximal urinary tract by altering renal filtration and excretion functions, resulting in accumulation of electrolytes. Many pathophysiological mechanisms are also involved during obstruction and may be expressed secondarily. For example, relief of obstruction, which restores free flow of urine, is accompanied by marked diuresis and electrolyte disorders. The post-obstruction diuresis syndrome can lead to dehydration, or even shock and acute renal failure. Strict and specialized monitoring is required during the post-obstruction phase. Medical management is designed to avoid serious haemodynamic and metabolic disorders.


NGF enhances sensory axon growth induced by laminin but not by the L1 cell adhesion molecule.
Neurotrophins and cell adhesion molecules regulate axon guidance, but their potential coordinate interactions are not well defined. In particular, it has been difficult to define the role of signaling from different surface molecules in neurotrophin-induced axon growth because of the strong dependence of embryonic neurons on this class of molecules for survival. We have addressed this issue using Bax deficient neurons, which do not require neurotrophins for survival. The L1 neural cell adhesion molecule and laminin each supported NGF-independent axon growth of cultured sensory neurons from dorsal root ganglia of embryonic Bax(-/-) mice. However, nerve growth factor (NGF) stimulated additional axon growth of sensory neurons on laminin but not on L1 substrates. Inhibition of the small GTPase RhoA by the dominant-negative mutant RhoA(T19N) restored NGF responsiveness of axon growth on L1 to Bax(-/-) neurons. Constitutively activated RhoA(Q63L) did not affect axon growth on L1 but inhibited NGF-stimulated axon growth on laminin. Consistent with the concept that RhoA was downregulated by NGF in neurons on laminin but not L1, the RhoA inhibitor C2IN-C3 toxin stimulated axon growth on L1 in wild-type DRG neurons in NGF. These results demonstrate a novel substrate-dependent regulation of NGF-induced growth of embryonic sensory axons mediated by RhoA GTPase.