Intra-articular methotrexate versus corticosteroid injections in medium-sized joints of rheumatoid arthritis patients-an intervention study.
The effects of intra-articular methotrexate (I/A MTX) in knee synovitis in rheumatoid arthritis have been previously evaluated. I/A MTX has not been studied in other joints. Ultrasonography (US) has been little studied in monitoring the effect of I/A MTX. The aim of the study is to test the efficacy of I/A MTX in suppression of persistent synovitis in medium-sized joints (ankle, wrist, and elbow) in rheumatoid arthritis patients. Patients were divided into two groups: group 1 (methotrexate group): 56 patients in which 84 joints (32 ankles, 28 wrists, and 24 elbows) were injected intra-articularly by 10 mg of methotrexate in the targeted joint on a weekly basis for 8 weeks and group 2 (steroid group): 44 patients in which 70 joints (26 ankles, 24 wrists, and 20 elbows) were injected once by Triamcinolone acetonide 40 mg. Clinical, ultrasonographic, and power Doppler US (PDUS) evaluation was done before the first injection (W0), after 2 months (W8), and after 5 months (W20). Synovial thickness and the intra-articular power Doppler signal were graded on a semiquantitative scale from 0 to 3 during the US examination. Clinical parameters improved significantly in both groups between baselines and 2 months. In both groups, gray-scale US and power Doppler US showed that synovial thickness and intra-articular power signals were reduced significantly between W0 and W8. The improvement of clinical parameters continued in the methotrexate group up to W20, but in the corticosteroid group, clinical parameters at W20 were similar to clinical parameters at W0. In the methotrexate group, there was an insignificant increase in synovial thickness between W8 and W20 while there was a significant increase in power Doppler signals between W8 and W20, p < 0.05. In the corticosteroid group, there was a significant increase in both synovial thickening and power Doppler signals between W8 and W20, p < 0.001. In the MTX group, all patients at week 0 showed that the Doppler signal in grades 2 and 3 is 100%; at 8 weeks, most of the patients showed that the power Doppler in grade 0 is 76%; and at week 20, most of the patients showed that the power Doppler signal in grade 0 is 28% and in grade 1 is 47%, while in grades 2 and 3 is 23.6%, so there is an improvement compared to the baseline of treatment. Repeated I/A MTX resulted in a decrease in the degree of synovitis of medium-sized joints in RA patients both clinically and by power Doppler US.


Treatment of climacteric complaints with Org OD 14: a comparative study with oestradiol valerate and placebo.
Org OD 14 (7 alpha,17 alpha-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) is a steroid possessing mixed hormonal activity, which in earlier studies has been shown to alleviate climacteric complaints and to prevent post-menopausal osteoporosis without affecting the endometrium. The effects of Org OD 14 on climacteric complaints were compared with those of oestradiol valerate (E2V) and placebo in a randomized, double-blind, cross-over study in 20 women who had been oophorectomized and hysterectomized 3-6 yr earlier as part of their treatment for cervical cancer. Each patient was treated orally for a total period of 18 wk, comprising 6 wk on each preparation. Capsules of identical appearance were given; these contained either 2.5 mg Org OD 14, 2 mg E2V or placebo. The patients' scores for symptoms and mood items on standardized rating scales were recorded at the end of each 6-wk treatment period (i.e. on days 43, 85 and 127). There were no differences between the effects of Org OD 14 and E2V on symptoms and mood items, while both compounds were more effective than placebo. Our findings confirmed that Org OD 14 is effective in ameliorating oestrogen deficiency symptoms in climacteric women.


Single Local Application of TGF-β Promotes a Proregenerative State Throughout a Chronically Injured Nerve.
The lack of nerve regeneration and functional recovery occurs frequently when injuries involve large nerve trunks because insufficient mature axons reach their targets in the distal stump and because of the loss of neurotrophic support, primarily from Schwann cells (SCs). To investigate whether a single application of transforming growth factor-beta (TGF-β) plus forskolin or forskolin alone can promote and support axonal regeneration through the distal nerve stump. Using a delayed repair rat model of nerve injury, we transected the tibial nerve. After 8 wk, end-to-end repair was done and the repair site was treated with saline, forskolin, or TGF- β plus forskolin. After 6 wk, nerve sections consisting of the proximal stump, distal to the site of repair, and the most distal part of the nerve stump were removed for nerve histology, axon counts, and immunohistochemistry for activated SCs (S100), macrophages (CD68), cell proliferation (Ki67), p75NGFR, and apoptosis (activated caspase-3). TGF-β plus forskolin significantly increased the numbers of axons regenerated distal to the repair site and the most distal nerve sections. Both treatments significantly increased the numbers of axons regenerated in the most distal nerve sections compared to saline treated. Both treatments exhibited extended expression of regeneration-associated marker proteins. TGF-β plus forskolin treatment of chronically injured nerve improved axonal regeneration and increased expression of regeneration-associated proteins beyond the repair site. This suggests that a single application at the site of repair has mitogenic effects that extended distally and may potentially overcome the decrease in regenerated axon over long distance.


Surgery versus radiation therapy for stage IB2 cervical carcinoma: a population-based analysis.
The objective of the study was to examine outcomes in stage IB2 cervical cancer patients undergoing primary surgery versus radiation. Stage IB2 cervical cancer patients were identified from the Surveillance, Epidemiology and End Results Public-Use Database from 2000 to 2006. Patients were divided into those receiving radiation (radiation first) or surgery (surgery first) as initial treatment. Overall survival was calculated by Kaplan-Meier method and compared using log-rank test. In total, 770 patients were identified with stage IB2 cervical cancer; 369 received radiation, and 401 received surgery initially. The radiation-first group had larger mean tumor size than the surgery-first group (6.0 vs 5.5 cm, respectively; P < 0.0001). The overall survival was longer in the surgery-first group compared with the radiation-first group (72.0 vs 61.4 months, respectively; P < 0.0001). Patients undergoing surgery as initial treatment for stage IB2 cervical cancer appear to have improved outcomes in the current era of chemoradiation; however, given the lack of chemotherapy information, a randomized trial will be necessary to see if these results remain valid.


A questionnaire to assess premonitory symptoms of myocardial infarction.
To test the hypothesis that feelings of vital exhaustion precede the onset of myocardial infarction, and to develop a short questionnaire to assess these feelings, a prospective study was done among 3877 males, aged 39-65 years. During a 4.2-year follow-up period, 59 fatal or non-fatal infarctions occurred. The mean score of future coronary causes as determined by a questionnaire assessing feelings of vital exhaustion was significantly higher than the mean score of a control group matched for age, blood pressure, cholesterol and smoking. Given the validity of the model, it was possible to reduce markedly the size of the questionnaire.


Automatic Removal of False Connections in Diffusion MRI Tractography Using Topology-Informed Pruning (TIP).
Diffusion MRI fiber tracking provides a non-invasive method for mapping the trajectories of human brain connections, but its false connection problem has been a major challenge. This study introduces topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve the tracking accuracy. The accuracy of the tractography with and without TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine whether TIP could improve the accuracy. The results showed that TIP improved the tracking accuracy by 11.93% in the single-shell scheme and by 3.47% in the grid scheme. The improvement is significantly different from a random pruning (p value < 0.001). The diagnostic agreement between TIP and neuroanatomists was comparable to the agreement between neuroanatomists. The proposed TIP algorithm can be used to automatically clean-up noisy fibers in deterministic tractography, with a potential to confirm the existence of a fiber connection in basic neuroanatomical studies or clinical neurosurgical planning.


Ultrasound in the diagnosis of asymptomatic hyperuricaemia and gout.
The increase in serum urate concentrations (hyperuricaemia, ≥7.0mg/dL) creates crystals, which promote inflammation and joint lesions. Ultrasonography can reveal these urate deposits. The presence of crystals suggests that a patient with hyperuricaemia is actually experiencing asymptomatic gout, and that a patient with gout without subcutaneous tophi could experience tophaceous gout. The information offered by ultrasound (double contour sign and hyperechoic concretions mimicking clouds) enables a more specific classification of hyperuricaemia and gout. Additionally, this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricaemia and gout.


Physical illness encountered in patients with eating disorders.
Careful evaluation for medical illness with a severity rating scale of 276 eating-disorder patients admitted to hospital revealed that patients with anorexia and bulimia were at risk for developing medical complications. Severe cardiovascular complications were most likely to occur in eating-disorder patients who were also diuretic and/or laxative abusers. Forty percent of patients with bulimia had significant medical complications. The findings suggest that a medical work-up should be carefully undertaken in both anorexic and bulimic patients admitted to hospital. A mixed history of severe anorexia nervosa alternating with periods of bulimia was most likely to lead to severe life-threatening illness. Seventy percent of the bulimic patients admitted required some medical treatment. Five percent were considered severely medically ill, while 34% suffered from a significant medical disorder. Ten percent of patients with restrictive anorexia or anorexia alternating with binge/purge required intensive care unit (ICU) placement. Most illnesses requiring medical treatment were unknown to the patient and the patient's physician at the time of admission.


Respiratory syncytial virus (RSV) infection rate in personnel caring for children with RSV infections. Routine isolation procedure vs routine procedure supplemented by use of masks and goggles.
Respiratory syncytial virus (RSV) infections in hospitalized children were identified by indirect fluorescent antibody technique. Patients with RSV infections were assigned to one of two isolation categories. In one category, the health care workers entering the child's room did not wear masks and goggles; in the other category, the workers did wear masks and goggles. The RSV illness rate in health care workers using masks and goggles was 5%, but the rate for those not using masks and goggles was 61%. In the no mask/goggles group, the RSV illness rates in the health care workers correlated directly with the number of exposures. In this modest study, the use of masks and goggles was associated with a significant reduction of RSV illnesses in pediatric health care workers.


Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration.
Repeated treatment with haloperidol and sulpiride induced tolerance to the increases in homovanillic and dihydroxyphenyl acetic acids in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex of the rat. The threshold dose inducing this effect appeared to be lower in the striatum than in the limbic regions. Similar results were found in the frontal cortex by measuring dopamine utilization. Moreover, tolerance developed earlier in the striatum than in the limbic areas. The possible reasons are discussed for the differential development of tolerance in the various DA areas investigated.


A Neurocomputational Account of How Inflammation Enhances Sensitivity to Punishments Versus Rewards.
Inflammation rapidly impairs mood and cognition and, when severe, can appear indistinguishable from major depression. These sickness responses are characterized by an acute reorientation of motivational state; pleasurable activities are avoided, and sensitivity to negative stimuli is enhanced. However, it remains unclear how these rapid shifts in behavior are mediated within the brain. Here, we combined computational modeling of choice behavior, experimentally induced inflammation, and functional brain imaging (functional magnetic resonance imaging) to describe these mechanisms. Using a double-blind, randomized crossover study design, 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions, one 3 hours after typhoid vaccination and one 3 hours after saline (placebo) injection. Participants learned to select high probability reward (win £1) and avoid high probability punishment (lose £1) stimuli. An action-value learning algorithm was fit to the observed behavior, then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning. Inflammation acutely biased behavior, enhancing punishment compared with reward sensitivity, through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula. Consequently, choice options leading to potential rewards were less behaviorally attractive, and those leading to punishments were more aversive. Our findings demonstrate the neural mediation of a rapid, state-dependent reorientation of reward versus punishment sensitivity during inflammation. This mechanism may aid the adaptive reallocation of metabolic resources during acute sickness but might also account for maladaptive, motivational changes that underpin the association between chronic inflammation and depression.


A numerical investigation of the hydrodynamic dispersion in triply periodic chromatographic stationary phases.
3D printed custom chromatographic stationary phases have recently been demonstrated. Using the Lattice Boltzmann Method, we compared the model-predicted chromatographic performance of random packing of monodisperse spheres, open tubular columns (OTC) and stationary phases based on three triply periodic minimal surfaces (TPMS): Schwarz Diamond (SD), Schoen Gyroid (SG) and Schwarz Primitive (SP). Three performance metrics were employed in this comparison: i) reduced plate height, ii) Darcy number, iii) kinetic performance factor. Each simulated geometry was unconfined with an impermeable stationary phase to remove wall effects and pore diffusion. The performance was studied for macro-porosities in the range 0.2 to 0.8, depending on the geometry. OTCs were found to have superior permeability to both random sphere packing and TPMS structures across the entire porosity range. At porosity greater than 0.366, the Schwarz Diamond medium achieved the lowest levels of band broadening and greatest kinetic performance. The reduced plate height of all stationary phase geometries was shown to increase with bed porosity. The kinetic performance was found to increase with porosity for TPMS structures, decrease with porosity for random packing and be independent of porosity for OTCs. This work illustrates that chromatographic stationary phase geometries based on TPMS structures are theoretically competitive with random packing and open tubular columns and their feasibility for practical chromatography should continue to be explored.


Combination therapy with anti-CD20 mAb and IL-10 gene to reverse type 1 diabetes by attenuating pancreatitis and inhibiting apoptosis in NOD mice.
To assess the combination therapy of anti-CD20 mabs and adenovirus-mediated interleukin-10 (IL-10) gene delivery on the prevention of type 1 diabetes (T1D) in non-obese diabetes (NOD) mice. In present study, we simultaneously blocked the B cell interactions and recovered the Th cell subset proportion by using through anti-CD20 Mab and adenovirus-mediated gene delivery of IL-10, respectively. After 9 consecutive days of combination therapy, various measurements, including hematoxylin-eosin staining (HE), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay (TUNEL), immunohistochemistry, ELISA, PCR and western blot were applied to further assess the efficacy. The results suggested that the combination intervention reduced the T1D-associated morbidity of NOD mice, promote insulin secretion, control blood glucose and ease pancreatitis. Moreover, the combination therapy might play a protective role in pancreatic β cells by suppressing the expression of TNF-α and Fas, blocking the Caspase-8 and Caspase-3 apoptotic pathways and activating the Bcl-2 anti-apoptotic pathway. Finally, the combination intervention may up-regulate the gene expression of CK-19 and PDX-1 and further accelerate the differentiation and proliferation of pancreatic β cells. Therefore, the combination intervention with anti-CD20 mabs and the IL-10 gene plays a role in the prevention of T1D to some extent in NOD mice.


Effect of acupuncture with donepezil based on syndrome differentiation on cognitive function in patients with mild-to-moderate Alzheimer's disease: a study protocol for a multicenter randomized controlled trial.
There has been a rapid increase in the worldwide prevalence of Alzheimer's disease (AD). Previous studies have shown that acupuncture can improve neurological and cognitive function; however, the utility of applying acupuncture in patients with AD remains unclear. This study protocol describes a clinical trial for evaluating the efficacy and safety of acupuncture based on syndrome differentiation with donepezil hydrochloride on cognitive function in patients with AD. This multicenter randomized controlled trial commenced on February 1, 2019, at the Shanghai Longhua Hospital of TCM, Shanghai Huashan Hospital of Fudan University, and Shanghai Mental Health Center, and will conclude on June 30, 2022. The study will recruit 184 patients randomly divided into an acupuncture group or a control group at a 1:1 ratio. All participants will receive donepezil hydrochloride (5 mg/day), and those in the acupuncture group will receive acupuncture based on syndrome differentiation with donepezil for 12 weeks. The primary outcome will be the post-treatment change in the Alzheimer's Disease Assessment Scale-cognition score at 12 weeks. The secondary outcomes will be the efficacy scores of the Minimum Mental State Examination, Alzheimer's Disease Cooperative Research Activity-Daily Life, and Quality of Life-Alzheimer's Disease. All assessments will be performed at baseline, after treatment (week 12), and at follow-up (weeks 24 and 36). This trial may provide high-quality evidence for the efficacy of acupuncture in the treatment of AD. The results of this study will be published in peer-reviewed journals. ClinicalTrials.gov NCT03810794 . Registered on 17 January 2019.


[Anatomico-echocardiographic comparisons of heart structures. Additional diagnostic cross-sections].
Possibilities of two-dimensional echocardiography using a number of additional cross-sections (right chambers sectioned longitudinally, four-chamber epigastric view, longitudinal cross-section of aortal arc) have been investigated. Heart structures were identified on the basis of comparisons with anatomical cross-sections of the heart in the preset planes. The study is based on sections from 34 hearts and findings of 46 echocardiographic investigations in normal subjects. Some methodological procedures for obtaining such echocardiograms are specified.


Photosensitive signal transduction induces membrane hyperpolarization in Paramecium bursaria.
The protozoan ciliate Paramecium bursaria exhibits membrane hyperpolarization in response to photostimulation, accompanied with an increased swimming speed. The external addition of cyclic nucleotide phosphodiesterase (PDE) inhibitors, either theophylline (1,3-dimethylxanthine) or 3-isobutyl-1-methylxanthin (IBMX), increased in both amplitudes of the membrane hyperpolarization and the increase in swimming speed. Moreover, the addition of membrane permeable cyclic nucleotide analogs, either 8-bromo-adenosine 3',5'-cyclic monophosphate (Br-cAMP) or 8-Br-guanosine 3',5'-cyclic monophosphate (Br-cGMP), increased these amplitudes. On the other hand, the addition of l-cis-diltiazem, known to block the conductance of cyclic nucleotide-gated channels, partially decreased both amplitudes of the membrane hyperpolarization and the increase in swimming speed. An enzyme immunoassay of cellular cyclic nucleotide contents showed that photostimulation induced a rapid increase in adenosine 3',5'-cyclic monophosphate (cAMP), but little increase in guanosine 3',5'-cyclic monophosphate (cGMP), raising the possibility that a rapid increase in cAMP mediates the light-induced hyperpolarization in P. bursaria.


[Anterolateral stabilization using the modified ellison technique-Treatment of anterolateral instability and reduction of ACL re-rupture risk].
The goal of the modified Ellison operation as a supplement to a conventional anterior cruciate ligament (ACL) reconstruction is to decrease anterolateral rotational instability of a knee joint after ACL rupture, to improve the stability and prevent ACL re-rupture. An ACL rupture with high risk of re-rupture (young age, high-performance sport, hyperlaxity, contralateral ACL rupture in history), increased subjective and objective anterolateral rotational instability of the knee after ACL rupture, ACL re-rupture. Gonarthrosis, additive instabilities (e.g. posterolateral, medial), non-anatomical ACL reconstruction with persistent instability, general contraindications to surgery (e.g. infections), chronic irritation of the knee joint. Supine position. Mark the typical landmarks. Incision from Gerdy's tubercle extending proximally along the iliotibial tract (ITT) to the lateral collateral ligament (approx. 5 cm). Incise the ITT in the line of its fibers about 10 mm anterior to its posterior border and continue the incision proximally to 5 mm proximal to the LCL. Make a parallel incision 10-12 mm anterior to the first incision. Use sharp subperiosteal dissection to elevate the strip of the ITT from Gerdy's tubercle. Secure the distal end of the ITT strip with a nonabsorbable suture (e.g. FiberWire No. 2, Arthrex, Naples, USA). Expose the LCL and pass the ITT strip deep to the LCL from proximal to distal and back to Gerdy's tubercle. Reattach the distal end of the strip of the ITT to its original position at Gerdy's tubercle with a bone anchor. The defect in the ITT can be closed with an absorbable suture (e.g. Vicryl, Ethicon, USA) in the proximal part. Layered closure. Knee brace for at least 6 weeks, movement limitation of 0‑0-90° for 6 weeks, 2 weeks 20 kg partial weight bearing. A total of 36 patients (mean age 18.9 years) with a high risk of ACL re-rupture have been treated with ACL reconstruction and modified Ellison procedure. Follow-up over 2 years. Of the patients 35 returned to the previous sports level, 1 patient suffered a re-rupture, 2 patients had cyclops resection and 1 patient contralateral ACL rupture.


Genome-Wide Scan and Test of Candidate Genes in the Snail Biomphalaria glabrata Reveal New Locus Influencing Resistance to Schistosoma mansoni.
New strategies to combat the global scourge of schistosomiasis may be revealed by increased understanding of the mechanisms by which the obligate snail host can resist the schistosome parasite. However, few molecular markers linked to resistance have been identified and characterized in snails. Here we test six independent genetic loci for their influence on resistance to Schistosoma mansoni strain PR1 in the 13-16-R1 strain of the snail Biomphalaria glabrata. We first identify a genomic region, RADres, showing the highest differentiation between susceptible and resistant inbred lines among 1611 informative restriction-site associated DNA (RAD) markers, and show that it significantly influences resistance in an independent set of 439 outbred snails. The additive effect of each RADres resistance allele is 2-fold, similar to that of the previously identified resistance gene sod1. The data fit a model in which both loci contribute independently and additively to resistance, such that the odds of infection in homozygotes for the resistance alleles at both loci (13% infected) is 16-fold lower than the odds of infection in snails without any resistance alleles (70% infected). Genome-wide linkage disequilibrium is high, with both sod1 and RADres residing on haplotype blocks >2 Mb, and with other markers in each block also showing significant effects on resistance; thus the causal genes within these blocks remain to be demonstrated. Other candidate loci had no effect on resistance, including the Guadeloupe Resistance Complex and three genes (aif, infPhox, and prx1) with immunological roles and expression patterns tied to resistance, which must therefore be trans-regulated. The loci RADres and sod1 both have strong effects on resistance to S. mansoni. Future approaches to control schistosomiasis may benefit from further efforts to characterize and harness this natural genetic variation.


Mutations at sterol 14α-demethylases (CYP51A&B) confer the DMI resistance in Colletotrichum gloeosporioides from grape.
Grape anthracnose caused by the ascomycete fungus Colletotrichum gloeosporioides has been widely controlled by demethylation inhibitors (DMIs) for decades in China. The resistance status and mechanism of C. gloeosporioides against DMIs is not well understood. All difenoconazole-resistant (DfnR ) isolates from vineyards exhibited decreased fitness. Positive cross-resistance was detected between DMI triazoles. Sequence alignment results from the DfnR and DfnS isolates revealed that multiple mutations are distributed at CgCYP51A, concomitant with mutations at CgCYP51B. The half maximal effective concentration (EC50 ) values of single deleted and complemented mutants of CgCYP51A and CgCYP51B showed that ΔCgCYP51A became more sensitive to difenoconazole, but not ΔCgCYP51B. Furthermore, all single complemented mutants had a stronger biological fitness than the progenitor strain. All the defectives of ΔCgCYP51A and ΔCgCYP51B could be restored by complementation of the whole corresponding gene from the resistant strains. Relative gene expression of CgCYP51A and CgCYP51B in most of the mutants was greatly upregulated relative to the progenitor isolate when treated with difenoconazole at the same concentration. Moreover, the extension of five amino acids (GNETI) caused by mutation at the stop codon of CgCYP51A, concurrent with other seven amino acid substitutions and the synonymous mutation P10P (CCG → CCT), significantly enhanced DMI resistance. The DMI resistance of C. gloeosporioides selected in vineyards is conferred by mutations at CgCYP51s, and validated by a genetics method. The roles of CgCYP51A and CgCYP51B overlap, and are counter-balanced, but cannot be replaced reciprocally. © 2020 Society of Chemical Industry.


The pyrazine-binding protein and olfaction.
1. The present results provide circumstantial evidence, but not a proof, that the Pyrazine-binding Protein is an odorant carrier molecule of fundamental importance. 2. At first sight a role for a secretory protein in olfaction is not obvious. 3. Odorants freely diffuse in air, in water and in lipids, and the use of carrier proteins, would seem superfluous unless a very special combination with the odorant occurs [Gaupp E. (1902) In Anatomie des Frosches, 2nd Edn, pp. 673. Vieweg-Verlag, Braunschweig]. 4. The possibility should be considered that the Pyrazine-binding Protein and the urinary proteins belong to a large family of species-specific secretory molecules which, with the odorant bound, directly stimulate the receptor cell.


The use of a one-day luteinizing hormone assay for timing of artificial insemination in infertility patients.
A 1-day rapid assay for luteinizing hormone (RLH) was developed by combined alteration of incubation temperatures and immune-complex precipitation of a commercially available LH kit. The RLH assay, compared with the standard 3-day assay, had the following characteristics: standard curve slope values of --2.47 and --2.314; assay sensitivity of 5.5 and 3.8 mIU/ml of serum; average coefficients of variation for the standard curves of 13.6% and 14.1% and for serum controls of 10.6% and 13.1%, respectively. Two consecutive RLH assays of split samples were highly correlated (r = 0.9908; P less than 0.001), as were split aliquots measured by RLH or the 3-day assay (r = 0.993; P less than 0.001). When 52 samples from portions of 5 normal menstrual cycles were assayed in both systems, agreement was again high (r = 0.9871; P less than 0.001). Representative curves of both RLH and standard LH assays, together with other data, are presented to show the feasibility of applying this method for timing of artificial insemination.


Effects of different physical training protocols on ventricular oxidative stress parameters in infarction-induced rats.
Physical exercise is important in the prevention and treatment of cardiovascular diseases. Nevertheless, controversy remains around type and intensity of effort required for significant biochemical protective changes. This study investigates two exercise protocols on ventricular oxidative parameters in rats post-infarction. Thirty-six 2-month-old male Wistar rats were divided in two groups (n=18): Sham and acute myocardial infarction (AMI) conducted by blocking the coronary artery. Thirty days after AMI, animals were divided in 6 subgroups (n=6): sham, sham+continuous training (60 min), sham+interval training, AMI, AMI+continuous training, and AMI+interval training. Training was conducted in water (30-32°C) 5 times a week for 6 weeks. Animals were sacrificed 48 h after the last exercise routine. Left ventricles were used for oxidative stress analyses (antioxidant enzyme activity and level, oxidative damage) and HIF1α and cit c oxidase expression. After AMI, both exercise models decreased superoxide levels significantly. Training routines did not alter SOD expression and activity, though CAT expression increased with continuous training and GPX level diminished in both training groups, which coincided with the increase in GPX activity. Lipid damage decreased only in the continuous training group, while protein damage decreased only in the interval training group. Cytochrome C increased in both groups, while HIF-1 α dropped significantly after both exercise protocols. Significant improvement occurred in myocardium redox status in rats challenged with AMI after different training routines. However, continuous training seems to be more efficient in improving the parameters analyzed.


Effects of reduced sulfur compounds on Pd-catalytic hydrodechlorination of trichloroethylene in groundwater by cathodic H2 under electrochemically induced oxidizing conditions.
Reduced sulfur compounds (RSCs) poison Pd catalysts for catalytic hydrodechlorination of contaminants in anoxic groundwater. This study investigates the effects of RSCs on Pd-catalytic hydrodechlorination of trichloroethylene (TCE) in oxic groundwater. Water electrolysis in an undivided electrolytic cell is used to produce H2 for TCE hydrodechlorination under oxidizing conditions. TCE is efficiently hydrodechlorinated to ethane, with significant accumulation of H2O2 under acidic conditions. The presence of sulfide at concentrations less than 93.8 μM moderately inhibits TCE hydrodechlorination and H2O2 production. The presence of sulfite at low concentrations (≤1 mM) significantly enhances TCE decay, while at high concentration (3 mM) inhibits initially and enhances afterward when sulfite concentration declines to less than 1 mM. Using radical scavenging experiments and an electron spin resonance assay, SO3(•-), which is generated from sulfite under oxidizing conditions, is validated as the new reactive species contributing to the enhancement. This study reveals a distinct mechanism of effect of sulfite on TCE hydrodechlorination by Pd and H2 in oxic groundwater and presents an alternative approach to increasing resistance of Pd to RSCs poisoning.


Vagotomy or gastrectomy for elective treatment of benign gastric ulceration?
The results of elective gastrectomy and vagotomy with drainage for benign gastric ulcer are described in terms of operative mortality, recurrent ulceration, overall clinical results, and risk of malignancy. Although it has a slightly lower operative morbidity and mortality, the results of vagotomy with drainage are not sufficiently superior to abandon gastrectomy. Highly selective vagotomy, without drainage, provides good overall clinical results but has a high associated incidence of recurrent ulceration. Neither gastrectomy nor vagotomy with drainage have a distinct advantage in patients with combined gastroduodenal or prepyloric ulceration.


Short communication: thermal regimes in hollow stems of herbaceous plants-concepts and models.
Although there have been studies of the temperature regimes within flowers, micrometeorology within stems seems to have been overlooked. We present ideas, hypotheses, and a diagrammatic model on the biophysical and thermodynamic processes that interact in complex ways to result in elevated temperature regimes within hollow stems of herbaceous plants. We consider the effects of the ambient air around the stems, the possible importance of insolation, and greenhouse effects as influenced by stems' orientation and optical properties, i.e., reflection, absorption, emissivity, translucence, pigmentation, and thermal conductivity. We propose that greenhouse effects contribute significantly to and are influenced by the above phenomena as well as by the gross anatomy (volume:surface ratio; wall thickness), evapotranspiration, and the thermal properties of the gas mixture in the lumen. We provide examples of those elevated temperatures that can be several degrees Celsius above the temperature of the surrounding atmosphere.


Anatomy education in Ottoman-Turkish veterinary schools during 19th century and Papier-Mache models.
Veterinary medicine was recognized as a scientific discipline for the first time in 1762 in France. After a while, the first Ottoman-Turkish veterinary school was established in 1842, primarily for the improvement and welfare of army horses. There is not much detailed information about the content of the anatomy education and materials in the early days of veterinary schools apart from the anecdote that Gurlt's illustrated anatomy books were being used. The purpose of this study is to research anatomy education in the 19th century, when Ottoman-Turkish veterinary medicine was established, as well as the Papier-mâché models used in anatomy education, searching primary and secondary sources that can be accessed online. It has been determined that the normal and pathological anatomy models of humans and various domestic animals made by Dr. Auzoux were ordered to be used in the anatomy education of the newly established veterinary schools. The whereabouts of these models, which did not reference in publications until now, are unknown. However, examining these models is regarded to be crucial for understanding the veterinary anatomy perspective and educational content of the period.


Behavior of autotrophic denitrification and heterotrophic denitrification in an intensified biofilm-electrode reactor for nitrate-contaminated drinking water treatment.
An intensified biofilm-electrode reactor (IBER) was developed to treat nitrate-contaminated drinking water. Different running conditions were conducted to investigate the behavior of autotrophic denitrification (AD) and heterotrophic denitrification (HD) in the IBER. In AD process, the nitrate nitrogen coulomb-reduction rate was used to evaluate the performance of the reactor. The maximum NO(3)(-)-N removal efficiency was 6.8% at the current of 60 mA, while nitrate nitrogen coulomb-reduction rate was 0.024 mg C(-1). The optimum conditions for HD process were C/N=0.8 and HRT=8h, under which complete NO(3)(-)-N removal and no NO(2)(-)-N accumulation were observed. With the cooperative effect of AD and HD in the heterotrophic and autotrophic denitrification (HAD) process, large treatment capacity, high denitrification efficiency, and low nitrite and ammonia accumulation were achieved. The results proved that HAD process was superior to single AD and HD for nitrate removal in the IBER.


Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factor-kappaB signaling in HER2-overexpressing breast cancer cells.
Phytoestrogens are known to prevent tumor induction. But their molecular mechanisms of action are largely unknown. This study aimed to examine the effect of genistein and quercetin on proliferation and apoptosis in HER2-expressing breast cancer cells. The antiproliferative effects of phytoestrogens were tested by proliferation assays. Flow cytometry was performed to analyze the cell cycle. The effect of phytoestrogens on cell-signaling molecules was determined by Western blotting. Genistein and quercetin inhibited the proliferation of MCF-7 vec and MCF-7 HER2 cells. This growth inhibition was accompanied with an increase of subG(0)/G(1) apoptotic fractions. Genistein and quercetin induced extrinsic apoptosis pathway, up-regulating p53. Genistein and quercetin reduced the phosphorylation level of IκBα, and abrogated the nuclear translocation of p65 and its phosphorylation within the nucleus. Genistein and quercetin exert their antiproliferative activity by inhibiting NFκB signaling. Phytoestrogens could be potential useful compounds to prevent or treat HER2-overexpressing breast cancer.


Microbial taxonomic and functional attributes consistently predict soil CO2 emissions across contrasting croplands.
Despite distinct roles of soil microbes in regulating carbon (C) respiration in diverse environments, it remains unclear whether microbial taxonomic and functional attributes can consistently predict soil C emissions across contrasting ecosystems. Here, we conducted a large-scale sampling event across two contrasting croplands (rice and wheat-corn crop rotation) to identify specific soil microbial phylotypes and functional genes associated with soil respiration rates. The results of structural equation modeling indicated that bacterial community composition had a strong link with C respiration rates in the two contrasting cropland types; however, this link was weaker for fungal communities. More importantly, we found that the relative abundances of bacterial Solirubrobacterales_480-2, Myxococcales_mle1-27 and fungal Westerdykella had consistently negative correlation with respiration rates across paddy and upland soils. We also identified taxa that are significantly correlated to C respiration in the paddy (e.g. Methylocaldum) and upland soils (e.g. Kribbella), respectively. Further, we found multiple associations between functional genes involved in microbial C metabolism and soil respiration rates. Our findings provide novel insights into understanding microbial predictors of soil CO2 emissions in diverse croplands, which have important implications for improving C emission predictions in terrestrial ecosystems.


Histological, Histochemical and Immunohistochemical Evaluation of the Role of Bone Marrow-Derived Mesenchymal Stem Cells on the Structure of Periodontal Tissues in Carbimazole-Treated Albino Rats.
To elucidate the role of bone marrow-mesenchymal stem cells (BM-MSCs) on the structure of periodontal tissues in carbimazole (antithyroid drug) treated rats at different durations. 28 albino rats were divided into: Group I: received distilled water. Group II: received therapeutic dose of carbimazole. Group III: received carbimazole then single injection of BM-MSCs by the end of 3rd week. Group IV: received carbimazole and single injection of BM-MSCs at the beginning of the experiment. Specimens were examined by light microscope. New collagen and β-catenin-immunoreactivity area% were assessed histomorphometrically, and statistically using ANOVA test. Histological examination revealed normal periodontal tissues structure in Groups I & IV. Group II showed disorganized periodontal ligament fibers and different stainability of cementum and alveolar bone. Group III illustrated dense periodontal ligament fibers, normal stainability of cementum and most of alveolar bone. Masson's trichrome results of Groups I & IV illustrated large areas of new collagen in periodontal ligament, old collagen in cementum and intermingled old and new collagen in alveolar bone. Group II showed old collagen. Group III revealed only new collagen. β-catenin-immunoreactivity was strong in Groups I & IV, negative in Group II and moderate in Group III. Statistically, Group III showed highest mean of new collagen area% followed by Groups I, IV and II respectively. Highest mean of β-catenin-immunoreactivity area% was for Group I followed by Groups IV, III and II respectively. Carbimazole has damaging effects and BM-MSCs are capable to mend these destructive outcomes in time dependent manner.


[Proteomic code].
On the basis of recent fundamentally novel developments in the protein structure a proteomic code is suggested, that would potentially allow to describe sequence, structure, and function of proteins by a spectrum of elementary loop-n-lock units. All major characteristics of the nearly standard units are described, and first five "codons" of the proteomic code are presented with their respective unique sequences, structures, and functions. More such codons are to be discovered, and the general procedure for their identification is described.


De novo biosynthesis of N-acetyltyramine in engineered Escherichia coli.
N-acetyltyramine as a tyramine alkaloid has drawn great attention because of its excellent anti-free radical, antithrombotic, and antitumour activity. Therefore, it is an attractive compound. In this study, we reported for the first time the construction a synthetic pathway of N-acetyltyramine in engineered Escherichia coli. First, the tyrosine decarboxylase tdc gene and arylalkylamine N-acyltransferase aanat gene were introduced into E. coli to generate a recombinant N-acetyltyramine producer with L-tyrosine as substrate. Subsequently, overexpressing aroGfbr and TyrAfbr enhance the availability of L-tyrosine to achieve de novo biosynthesis of N-acetyltyramine from glucose. Finally, overexpressing the transketolase I tktA and phosphoenolpyruvate synthase ppsA genes improved the N-acetyltyramine production to 854 mg/L.


Effects of fish oil replacement by vegetable oil blend on digestive enzymes and tissue histomorphology of European sea bass (Dicentrarchus labrax) juveniles.
The impact of replacing circa 70% fish oil (FO) by a vegetable oil (VO) blend (rapeseed, linseed, palm oils; 20:50:30) in diets for European sea bass juveniles (IBW 96 ± 0.8 g) was evaluated in terms of activities of digestive enzymes (amylase, lipase, alkaline phosphatase, trypsin and total alkaline proteases) in the anterior (AI) and posterior (PI) intestine and tissue morphology (pyloric caeca-PC, AI, PI, distal intestine-DI and liver). For that purpose, fish were fed the experimental diets for 36 days and then liver and intestine were sampled at 2, 6 and 24 h after the last meal. Alkaline protease characterization was also done in AI and PI at 6 h post-feeding. Dietary VO promoted higher alkaline phosphatase activity at 2 h post-feeding in the AI and at all sampling points in the PI. Total alkaline protease activity was higher at 6 h post-feeding in the PI of fish fed the FO diet. Identical number of bands was observed in zymograms of alkaline proteases of fish fed both diets. No alterations in the histomorphology of PC, AI, PI or DI were noticed in fish fed the VO diets, while in the liver a tendency towards increased hepatocyte vacuolization due to lipid accumulation was observed. Overall, and with the exception of a higher intestine alkaline phosphatase activity, 70% FO replacement by a VO blend in diets for European sea bass resulted in no distinctive alterations on the postprandial pattern of digestive enzyme activities and intestine histomorphology.


Endorphins stimulate normal human peripheral blood lymphocyte natural killer activity.
Opioid peptides are present in peripheral blood, and may bind to human lymphocytes. In order to determine their influence on human lymphocytes we studied the effect of endogenous opioid peptides on human lymphocyte natural killer function. Beta-endorphin and several analogues (i.e., gamma-endorphin) are shown to enhance human peripheral blood natural killer function. The enhancement of natural killing by these opioid peptides was dose-dependent and naloxone (an opiate antagonist) reversible. In studying various analogues of beta-endorphin, beta-lipotropin and gamma-endorphin were approximately 3-5 times more effective at enhancing peripheral blood NK function than Leu-enkephalin and -endorphin. In addition, we observed that naloxone reversed human fibroblast interferon mediated enhancement of human blood lymphocyte natural killer function. These observations suggest that circulating endogenous opioid peptides may have a physiologic role in regulating human blood lymphocyte natural killing.


Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells.
The docosahexaenoic (DHA), a ω-3 fatty acid, could play a beneficial inhibition of the incidence and progress of a series of human diseases including cancer. It has been report that DHA is involved in cell apoptosis. Recent studies show that the signal transduction pathway links with bcl-2, bax, caspase-3 and MMP-9 molecules. Therefore, we tested the relationship between DHA and cell apoptosis in human hepatocellular carcinoma cells (Bel-7402 cells). We show here that DHA induces Bel-7402 cells apoptosis after pre-treating cells with DHA. DHA down-regulates the protein expression of Bcl-2 and Bim mRNA level, and up-regulates caspase-3 activity and Bax expression level. We also found that DHA inhibits Bel-7402 cells migration. Basic on our studies, DHA may play a role in tumor invasion and survival.


Underexposure of Seniors to Heart Failure Drug Therapy.
Little is known about exposure to heart failure (HF) treatment among seniors with ischemic heart disease. In a population of seniors, we: 1) estimated the association between age and exposure to HF drug therapy at 6, 12, 36 and 60 month intervals after HF diagnosis, and 2) determined the influence of the passage of time on exposure to drug therapy. Using the Quebec provincial administrative databases, we conducted a population-based inception cohort study that included all individuals aged ≥ 65 with a first HF diagnosis between 2000 and 2009 and an ischemic heart disease diagnosis in the year before HF diagnosis. We assessed exposure to HF drug therapy and to drug therapy at target doses at 6, 12, 36 and 60 month intervals after HF diagnosis. Adjusted prevalence ratios (aPR) between age at diagnosis and exposure to drug therapy and the influence of time (6-month periods) were assessed using multivariate modified Poisson regressions. Among the 86,428 seniors, those who were older were less likely to be exposed to both HF drug therapy and drug therapy at target doses at each time point, than were the younger ones (aged 65-69). The aPRs for exposure to drug therapy for the 90+ age group were 0.64, 0.64, 0.56 and 0.53 at the 6, 12, 36 and 60 month intervals, respectively. After HF diagnosis, exposure increased by a maximum of 8% per 6-month period. Increasing age is associated with a decrease in exposure to drug therapy, with only slight improvement in exposure after HF diagnosis.


Transient receptor potential (TRP) channels: Biosensors for redox environmental stimuli and cellular status.
Transient receptor potential (TRP) channels are a family of cation channels that depolarizes the membrane potential and regulates intracellular concentrations of cations such as Ca2+. TRP channels are also known to function as "biosensors" to detect changes of the surrounding environment and cellular status. Lines of evidence have unveiled that numerous proteins are subject to redox modification and subsequent signaling. For example, TRPM2, TRPC5, TRPV1, and TRPA1 are known as redox sensors activated by hydrogen peroxide (H2O2), nitric oxide (NO), and electrophiles. Thus, these channels facilitate the influx of cations which in turn triggers the appropriate cellular responses against environmental redox stimuli and cellular redox status. In this review, we focus on the recent findings regarding the functions of TRP channels in relation to other ion channels, and other proteins which also go through redox modification of cysteine (Cys) residues. We aim to understand the structural and molecular basis of the redox-sensing mechanisms of TRP channels in exerting various functions under physiological conditions as well as pathological conditions such as cancer malignancy. Their future potential as drug targets will also be discussed.


Prolonged persistence of lamivudine-resistant mutant and emergence of new lamivudine-resistant mutants two years after lamivudine withdrawal in HBsAg-positive chronic hepatitis patient: a case report.
Lamivudine can select resistant hepatitis B virus (HBV) tyrosine-methionine-aspartate-aspartate aminoacid motif (YMDD) mutants, which usually disappear in few months after lamivudine withdrawal. We report an unusual case of a male adult patient who showed a prolonged persistence of the M204I mutation up to 24 months after lamivudine withdrawal followed by the emergence of new distinct YMDD mutants (namely M204V, V207L). Only 42 months after lamivudine withdrawal wild-type YMDD motif became dominant over the YMDD mutants. To our knowledge, a so prolonged persistence of a YMDD mutant and also the emergence of new YMDD mutants many months after drug withdrawal are unusual.


Successful resection of a huge metastatic liposarcoma in the pericardium resulting in improvement of diastolic heart failure: a case report.
Although liposarcoma often metastasizes to various organs, cardiac metastasis, including to the pericardium, is rare. We present a case of a third recurrence of pericardial metastasis from the thigh, which required surgical resection because of cardiac failure. Surgery was effective for improving cardiac function and reintroducing chemotherapy. This is the first reported case of metastatic pericardial liposarcoma, which was successfully resected three times. We believe that aggressive surgical treatment, when it can resolve cardiac impairment, potentially leads to a more favorable prognosis.


Glycosphingolipid glycosyltransferase assay using sephadex G-50 chromatography in aqueous phase.
An assay method for glycosphingolipid glycosyltransferase activity using simple Sephadex G-50 gel permeation chromatography in an aqueous solvent has been developed. An acceptor glycosphingolipid and a donor radioactive nucleotide sugar were incubated with an enzyme source. The reaction mixture was loaded onto a Sephadex G-50 column previously equilibrated with 0.3% (w/v) Triton X-100, 0.1 M sodium chloride, and 0.02% (w/v) sodium azide. The radiolabeled reaction product was eluted by the same solvent in the excluded volume and was collected directly into a liquid scintillation vial, separated from other radioactive compounds. This assay method was utilized to determine the activity of cytidine 5'-monophosphate-N-acetylneuraminic acid:GM3 ganglioside sialyltransferase, which catalyzes the synthesis of GD3 ganglioside, and proved to be as reliable and sensitive as previously published assay procedures. In addition, this assay can be carried out in less time and is simpler than previously reported procedures.


Borderzone infarction and recurrent stroke in intracranial atherosclerosis.
Intracranial stenosis (ICAS) is a common cause of stroke worldwide and patients with symptomatic ICAS exhibit a high rate of recurrence, particularly in the early period after the initial event. In this study, we aimed to study the association between borderzone infarct and recurrent ischemic stroke in patients hospitalized with symptomatic ICAS. This is a retrospective single center study that included patients hospitalized with acute ischemic stroke in the setting of intracranial stenosis (50% or more and an acute ischemic stroke in the territory supplied by the stenosed artery) over a 32-month period. We excluded patients who did not receive a brain MRI or did not have an infarct on brain imaging. The primary predictor is infarct pattern (any borderzone vs. no borderzone infarct) and the primary outcome was recurrent cerebrovascular events (RCVE) within 90 days. We used unadjusted, and age and sex adjusted logistic regression models to determine associations between infarct pattern and RCVE at 90-days. Among 99 patients who met the inclusion criteria (4 tandem), the mean age was 70.1 ± 11.2 years and 41.4% were women; 43 had borderzone infarcts and 19 had RCVE. In adjusted binary logistic regression analysis, borderzone infarct was associated with increased risk of RCVE (adjusted OR 4.00 95% CI 1.33-11.99, p=0.013). The association between borderzone infarction and RCVE was not different among anterior circulation ICAD (adjusted HR 2.85 95% CI 0.64-12.76, p=0.172) vs. posterior circulation ICAD (adjusted HR 6.69 95% CI 1.06-42.11, p=0.043), p-value for interaction = 0.592. In real world post-SAMMPRIS medically treated patients with ICAD, the borderzone infarct pattern was associated with 90-day RCVE. Borderzone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for high-risk cohorts.


Continuous intraoperative neuromonitoring in thyroid surgery: Safety analysis of 400 consecutive electrode probe placements with standardized procedures.
Continuous intraoperative neuromonitoring (C-IONM) is a new technology and it is appropriate to analyze its safety. C-IONM was performed according to a standardized technique to control any adverse events and electrode positioning issues. Four hundred vagal nerve dissections were analyzed considering vagal nerve diameter, mean time effort for C-IONM probe positioning, and electrode dislocation rate. A significant superior dislocation rate in case of: (a) when a 3 mm automatic periodic stimulating (APS) electrode size was used in a vagal nerve diameter <2 mm; (b) anterior access; and (c) vagal nerve A subtype in relation (p < .05). No related additional local or systemic morbidity was registered in this series. There was a statistically significant positive relationship between increased diameter of vagal nerve and increased electromyography (EMG) amplitude (p = .03). There was also a significant increase of amplitude between initial and final vagal nerve stimulation in uneventful cases (p = .02). We analyzed the technical issues to achieve improved vagal nerve critical view of safety dissection, stimulation, and C-IONM probe placement. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1568-E1574, 2016.


Spatiotemporal effects of syncytial heterogeneities on cardiac far-field excitations during monophasic and biphasic shocks.
It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 x 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87+/-0.26, M-T = 6.71+/-0.83, B-L = 3.22+/-0.25, and B-T = 7.93+/-0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 x 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-L and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.


Amphotericin clearance in vitrectomized versus nonvitrectomized eyes.
Ocular clearance of amphotericin B after direct intravitreal injection was studied in a rabbit model. Unmodified phakic eyes, Candida-infected eyes, aphakic eyes, and aphakic vitrectomized eyes were employed. Using high pressure liquid chromatography to assess drug level, the half-lives of drug disappearance after single 10-microgram (microgram) intravitreal injections were 9.1, 8.6, 4.7, and 1.4 days, respectively. The disappearance slope for vitrectomized eyes was significantly different from all nonvitrectomized eyes with P less than 0.001. The rapid disappearance of amphotericin from vitrectomized eyes must be considered in clinical management of patients with fungal endophthalmitis.


Bone marrow-derived inducible microglia-like cells ameliorate motor function and survival in a mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. Neuroinflammation in the spinal cord plays a pivotal role in the pathogenesis of ALS, and microglia are involved in neuroinflammation. Microglia mainly have two opposite phenotypes involving cytotoxic and neuroprotective properties, and neuroprotective microglia are expected to be a novel application for the treatment of ALS. Therefore, to establish a clinically applicable therapeutic method using neuroprotective microglia, the authors investigated the effect of inducing neuroprotective microglia-like cells from bone marrow for transplantation into ALS model mice. Bone marrow-derived mononuclear cells were isolated from green fluorescent protein mice and cultured using different protocols of cytokine treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. Cells with a high potency of proliferation and differentiation into microglia were evaluated by gene analysis, flow cytometry and direct neuroprotective effects in vitro. These cells were named bone marrow-derived inducible microglia-like (BM-iMG) cells and transplanted into the spinal cords of ALS model mice, and behavioral tests, immunohistochemistry and gene expression profiling were performed. Three-day GM-CSF and 4-day GM-CSF + IL-4 stimulations were most effective in inducing BM-iMG cells from the bone marrow. Transplantation of BM-iMG cells improved motor function, prolonged survival and suppressed neuronal cell death, astrogliosis and microgliosis in the spinal cords of ALS mice. Moreover, neuroprotective genes such as Arg1 and Mrc1 were upregulated, whereas pro-inflammatory genes such as Nos2 and Il6 were downregulated. Intraspinal transplantation of BM-iMG cells demonstrated therapeutic effects in a mouse model of ALS. Further studies and clinical applications in patients with ALS are expected in the future.


(E)-5-(4-Chloro-benzyl-idene)-1-phenyl-4,5,6,7-tetra-hydro-1H-indazol-4-one: crystal structure and Hirshfeld surface analysis.
In the title compound, C20H15ClN2O, the non-aromatic six-membered ring adopts a distorted envelope conformation with methyl-ene-C atom nearest to the five-membered ring being the flap atom. The dihedral angle between the phenyl and chloro-benzene rings is 74.5 (1)°. The heterocyclic ring forms dihedral angles of 37.9 (1) and 64.3 (1)° with the phenyl and chloro-benzene rings, respectively. In the crystal, weak C-H⋯O inter-actions feature predominantly within the three-dimensional architecture. The inter-molecular inter-actions are further analysed with the calculation of the Hirshfeld surfaces highlighting the prominent role of C-H⋯O inter-actions, along with H⋯H (36.8%) and C⋯H/H⋯C (26.5%) contacts.


Comparison of proximal isovelocity surface area method and pressure half time method for evaluation of mitral valve area in patients undergoing balloon mitral valvotomy.
The pressure half time (PHT) method is unreliable for measurement of mitral valve area (MVA) immediately after valvotomy. The proximal isovelocity surface area (PISA) method has been used to derive mitral valve area in patients with mitral stenosis. The aim of our study was to compare PISA method and PHT method in patients undergoing percutaneous balloon mitral valvotomy (BMV). The PISA was recorded from the apex and MVA was calculated using continuity equation by the formula 2pir(2) Vr/Vm, where 2pir(2) is the hemispheric isovelocity area, Vr is the velocity at the radial distance "r" from the orifice, and Vm is the peak velocity. A plain angle correction factor (theta)/180 was used to correct the inlet angle subtended by leaflet tunnel as a result of leaflet doming. MVA calculated using PISA method (r = 0.5217, P < 0.0001, SE = 0.016) and PHT (r = 0.6652, P < 0.0001, SE = 0.017) correlated well with 2D method in patients with mitral stenosis before BMV. After BMV, MVA by PISA method correlated well with 2D planimetry (r = 0.5803, P < 0.0001, SE = 0.053) but PHT showed poor correlation (r = 0.1334, P = 0.199, SE = 0.036). The variability of measurement of MVA was most marked with PHT method in the post-BMV period. The PISA method correlates well with 2D planimetry in patients with mitral stenosis before and after BMV and is superior to the PHT method in the post-BMV period where the latter may be unreliable.


Undergraduate surgical nursing preparation and guided operating room experience: A quantitative analysis.
The aim of this research was to determine if guided operating theatre experience in the undergraduate nursing curricula enhanced surgical knowledge and understanding of nursing care provided outside this specialist area in the pre- and post-operative surgical wards. Using quantitative analyses, undergraduate nurses were knowledge tested on areas of pre- and post-operative surgical nursing in their final semester of study. As much learning occurs in nurses' first year of practice, participants were re-tested again after their Graduate Nurse Program/Preceptorship year. Participants' results were compared to the model of operating room education they had participated in to determine if there was a relationship between the type of theatre education they experienced (if any) and their knowledge of surgical ward nursing. Findings revealed undergraduates nurses receiving guided operating theatre experience had a 76% pass rate compared to 56% with non-guided or no experience (p < 0.001). Graduates with guided operating theatre experience as undergraduates or graduate nurses achieved a 100% pass rate compared to 53% with non-guided or no experience (p < 0.001). The research informs us that undergraduate nurses achieve greater learning about surgical ward nursing via guided operating room experience as opposed to surgical ward nursing experience alone.


Salvage surgery for continent ileostomies (CI) after a first successful revision: more long-term blame on the reservoir than the nipple valve.
The aim of the study was to investigate the underlying cause of long-term complications in patients requiring at least one revision surgery of a continent ileostomy (CI) and to analyze functional outcome. Only patients with CI at least one revision were included in the retrospective data analysis. Four different classes of complications (Cl A-D) were defined: Cl A = Nipple valve (NV), Cl B = pouch, Cl C = outlet (stoma), and Cl D = afferent loop (AL). Associations between underlying disease and origin of complications were analyzed. Cumulative probabilities were calculated using Kaplan-Meier analysis. A total of 77 patients were identified with a follow-up of 30 years, requiring 133 surgeries for 148 complications (c.). Cl A 49 c. (33.1%), Cl B 50 c. (33.8%), Cl C 39 c. (26.4%), and Cl D 10 c. (6.8%). Cl A and C complications were not correlated to underlying disease, whereas Cl B and D complications were only found in ulcerative colitis (UC) and Crohn's disease (CD). The cumulative probability of a second revision showed a linear rise, reaching 62.5% after 20 years. Cl A and B complications both reached 42.1%. Eleven (14.3%) patients (10 Cl B) had pouch failure in a follow-up period of 11.5 ± 8.7 years (1-31 years), whereas 66 (85.7%) had successful revisional surgery. Overall CI survival was 78.8% at 44 years. CI survival is limited by inflammatory complications of the pouch based on the underlying disease and not by mechanical limitations of the NV. None.


[The expression levels of endothelin-1 and nuclear factor-kappaB in the lung tissue of acute pulmonary embolism and the effects of thrombolysis and dexamethasone].
To study the expression levels of endothelin-1(ET-1) and nuclear factor-kappaB (NF-kappaB) in lung vascular endothelium, bronchial and alveolar epithelia in acute pulmonary thromboembolism (APTE), and to explore the effects of thrombolytic (urokinase, UK) or ant-inflammatory therapy (dexamethasone, Dex) on their expressions. Forty rabbits were randomly divided into a control (C) group, a pulmonary thromboembolism (PTE) model group, an UK therapy group, a Dex therapy group, and an UK + Dex therapy group, with 8 rabbits each. The PTE model was established by intravenous injection of autologous blood clots. The pathological changes of the lung were examined with light microscope. By using immunohistochemistry, the expression levels of ET-1 and NF-kappaB P65 in lung vascular endothelium, bronchial and alveolar epithelia were examined. Histopathological study showed that lung injury was evident in the PTE, UK and Dex groups, but was mild in the UK + Dex group. In the PTE group, the expression levels of ET-1 in lung vascular endothelium, bronchial and alveolar epithelia were 0.331 +/- 0.036, 0.229 +/- 0.014 and 0.191 +/- 0.046, respectively, while the expression levels of NF-kappaB P65 were 0.245 +/- 0.036, 0.190 +/- 0.040 and 0.204 +/- 0.054, respectively. Their levels were significantly higher as compared to those of the control group and the UK + Dex group (all P < 0. 01). In the UK group, the ET-1 expression in lung vascular endothelium, bronchial and alveolar epithelia were 0.204 +/- 0.020, 0.163 +/- 0.017 and 0.137 +/- 0.013 respectively, significantly lower as compared to the PTE group (all P < 0. 05). In the Dex group, the NF-kappaB P65 expression was 0.175 +/- 0.024, 0.104 +/- 0.022 and 0.144 +/- 0.022 respectively, the difference being significant as compared with the PTE group (all P < 0. 05). In the UK + Dex group, the ET-1 expression was 0.186 +/- 0.033, 0.107 +/- 0.012 and 0.098 +/- 0.026 respectively, significantly different from the PTE group (all P < 0.05); the NF-kappaB P65 expression was 0.109 +/- 0.018, 0.062 +/- 0.023 and 0.093 +/- 0.019 respectively, significantly lower as compared with the PTE and the UK groups (all P < 0. 01). After APTE, thrombolytic and anti-inflammatory treatment could decrease acute lung injury induced by ET-1 and NF-kappaB activation. Thus, anti-inflammatory therapy and the use of ET-1 inhibitor or receptor antagonist should be considered in APTE.


Differential urine proteome analysis of a ventilator-induced lung injury rat model by label-free quantitative and parallel reaction monitoring proteomics.
Urine is a promising resource for biomarker research. Therefore, the purpose of this study was to investigate potential urinary biomarkers to monitor the disease activity of ventilator-induced lung injury (VILI). In the discovery phase, a label-free data-dependent acquisition (DDA) quantitative proteomics method was used to profile the urinary proteomes of VILI rats. For further validation, the differential proteins were verified by parallel reaction monitoring (PRM)-targeted quantitative proteomics. In total, 727 high-confidence proteins were identified with at least 1 unique peptide (FDR ≤ 1%). Compared to the control group, 110 proteins (65 upregulated, 45 downregulated) were significantly changed in the VILI group (1.5-fold change, P < 0.05). The canonical pathways and protein-protein interaction analyses revealed that the differentially expressed proteins were enriched in multiple functions, including oxidative stress and inflammatory responses. Finally, thirteen proteins were identified as candidate biomarkers for VILI by PRM validation. Among these PRM-validated proteins, AMPN, MEP1B, LYSC1, DPP4 and CYC were previously reported as lung-associated disease biomarkers. SLC31, MEP1A, S15A2, NHRF1, XPP2, GGT1, HEXA, and ATPB were newly discovered in this study. Our results suggest that the urinary proteome might reflect the pathophysiological changes associated with VILI. These differential proteins are potential urinary biomarkers for the activity of VILI.


Recovery of RNA from avian nucleated whole blood stored under field conditions: an evaluation of commercial methods.
1. Whole blood can be used to gain insights on several molecular mechanisms involved in animal physiology. However, its use to extract RNA from organisms that carry nucleated red blood cells is limited due to its high nuclease content and instability under field conditions. 2. Here, we evaluate three commercially available RNA preservation and extraction methods applied to avian whole-blood samples kept in different storage conditions to identify the most suitable ones for use in field studies. 3. Whole-blood starting volume was the most important factor; only samples with a starting volume of 50 µl yielded RNA, whereas all 100 µl samples failed to provide any RNA regardless of the method used. RNA concentration decreased with storage time in every method employed. Samples stored at -20°C yielded higher RNA concentration than the ones stored at 4°C, although some possible effects of freeze-thaw cycles were observed. 4. For two of the three methods, it is likely that DNA contamination and/or extensive degradation of RNA could have taken place. Only whole blood stored and extracted using the Quick RNA Whole Blood kit provided high-quality RNA in every condition tested.


Effect of organic volatiles from Saccharomyces on the spore germination of fungi.
Common volatile organic compounds (acetaldehyde, ethylacetate, ethanol, n-propanol, isobutanol, 2-methyl-butanol, 3-methyl butanol) tested singly and in combination inhibited the spore (conidium) germination of Helminthosporium oryzae, Cercospora personata, Cunnighamella blakesleeana, Colletotrichum capsici, and Alternaria solani.


Quantitative immunochemical evaluation of fish metallothionein upon exposure to cadmium.
Efficient implementation of an environmental biomarker requires multi-annual comparability over a wide geographical range. The present study improved the comparability of a quantitative competitive metallothionein (MT) enzyme-linked-immuno-sorbent-assay (ELISA) in the sentinel fish Lithognathus mormyrus by introducing to the assay recombinant MT and beta-actin standards. Commercial antibodies for cod MT and mammalian actin were implemented. In addition, a sensitive anti L. mormyrus MT antibody was produced, adequate only for solid phase immunochemical assays. Cadmium was applied to the fish through injection and feeding to serve as a testing platform of the ELISA. The results demonstrated high potential protective capacity of the liver against toxic levels of transition metals through increasing MT levels. MT transcript levels were evaluated also from fish sampled at polluted and relatively clean natural sites, indicating applicability of MT as biomarker of exposure to a multi-factorial pollution, in comparison to its low revealed sensitivity to controlled cadmium exposure.


Development and Validation of a Prediction Model for Infant Fat Mass.
To develop and validate a prediction model for fat mass in infants ≤12 kg using easily accessible measurements such as weight and length. We used data from a pooled cohort of 359 infants age 1-24 months and weighing 3-12 kg from 3 studies across Southern California and New York City. The training data set (75% of the cohort) included 269 infants and the testing data set (25% of the cohort) included 90 infants age 1-24 months. Quantitative magnetic resonance was used as the standard measure for fat mass. We used multivariable linear regression analysis, with backwards selection of predictor variables and fractional polynomials for nonlinear relationships to predict infant fat mass (from which lean mass can be estimated by subtracting resulting estimates from total mass) in the training data set. We used 5-fold cross-validation to examine overfitting and generalizability of the model's predictive performance. Finally, we tested the adjusted model on the testing data set. The final model included weight, length, sex, and age, and had high predictive ability for fat mass with good calibration of observed and predicted values in the training data set (optimism-adjusted R2: 92.1%). Performance on the test dataset showed promising generalizability (adjusted R2: 85.4%). The mean difference between observed and predicted values in the testing dataset was 0.015 kg (-0.043 to -0.072 kg; 0.7% of the mean). Our model accurately predicted infant fat mass and could be used to improve the accuracy of assessments of infant body composition for effective early identification, surveillance, prevention, and management of obesity and future chronic disease risk.


The limited clinical value of home urine testing by diabetic patients.
To investigate the value of home urine glucose testing in assessing chronic diabetic glucose control, the authors compared patients' glycosuria patterns with their mean blood glucose (MBG) levels calculated from glycosylated hemoglobin (Hb Alc). One hundred and twenty-one patients who regularly checked their urines reported on the frequencies of glycosuria over the preceding ten weeks. There was substantial overlap in the glycosuria patterns of patients at different levels of MBG. Glycosuria was not detectable in only 44% of patients with good control (MBG less than or equal to 150 mg/dl). The probability of such good control given no glycosuria was only 26%. Similarly, frequent glycosuria was reported by only 27% of patients with poor control (MGB greater than 250 mg/dl). The probability of such poor control given frequent glycosuria was only 34%. Because home urine testing cannot reliably identify good or poor control, it has a very limited role in assessing patients' chronic glucose control.


Cross-cultural communication in an intensive therapy unit.
Communication should have no barriers, but in an intensive therapy unit (ITU) a human's ability to communicate effectively is often severely disrupted due to disease and treatment. This is further highlighted in patients who do not speak the native language of the place where they are nursed. Problems of this nature have been emphasised as more patients are contracted for specialist surgery from countries where it is less possible to perform the surgery required, due to economic, social or cultural reasons. Patients' and nurses' opinions on communications are discussed and a translation booklet is suggested as an aid to communication cross-culturally.


Fast effectiveness of a solubilized low-dose budesonide nasal spray in allergic rhinitis.
Budesonide, a poorly water-soluble corticosteroid, is currently marketed as a suspension. Budesolv is a novel aqueous formulation containing dissolved budesonide showing increased local availability in preclinical models. Budesolv contains ~85% less corticosteroid than the marketed comparator. The study (EudraCT:2018-001324-19) was designed to assess non-inferiority of Budesolv compared to Rhinocort® Aqua 64 (RA) and early onset of action. In a three-way cross-over double-blinded randomized trial, Budesolv 10 was compared to RA and placebo in grass pollen allergic rhinoconjunctivitis volunteers (n = 83 (ITT); n = 75 (PP)). On day 1, participants entered the Vienna Challenge Chamber (VCC) for 6 hours; first treatment took place at 1:45 hours after entry. Participants treated themselves for further 6 days; on day 8, the last treatment was applied before entering the VCC. Subjective symptom scores, nasal airflow and nasal secretion were measured regularly during allergen challenge. Budesolv 10 was equally effective compared to RA with respect to TNSS and nasal airflow after eight days of treatment with a strongly reduced dose (more than 80% reduction). After first dose, only Budesolv 10 showed a significant reduction of nasal and respiratory symptoms starting 90 minutes (P < .05) and 15 minutes (P < .05) after application onwards, respectively, demonstrating an early onset of efficacy. A clinically significant 1 point reduction in nasal symptom score was reached at 195 minutes (P < .05) after application. The novel preservative-free, aqueous low-dose budesonide formulation is highly efficacious even after an initial single treatment. Thus, Budesolv 10 appears to be an effective acute treatment for allergic rhinitis as well as for AR comorbidities like mild asthma and conjunctivitis.


CD30-positive anaplastic large cell lymphoma (ALCL) of T-cell lineage in a 14-month-old infant with perinatally acquired HIV-1 infection.
CD30-positive anaplastic large cell lymphoma (ALCL) has been described in adults with HIV-1 infection but is extremely rare in HIV-1-infected infants and children. A 14-month-old girl with congenitally acquired HIV-1 infection presented with fever and a tender, erythematous, cystic mass on the right labium majorum. The mass was biopsied. Histologic examination and immunohistochemistry were performed. Histologic examination showed Touton-like giant cells resembling histiocytes and focally abundant neutrophils obscuring the lymphoid infiltrate. Immunocytochemistry revealed a CD30-positive ALCL of T-cell lineage. Although non-Hodgkin's lymphoma is known to be associated with HIV-1 infection in children, large cell lymphomas of T-cell lineage are extremely rare in this population. Early diagnosis should be aggressively pursued in an HIV-1-infected child who presents with a fever and cutaneous mass.


Effect of mutation of cysteinyl residues in yeast Cu-metallothionein.
Metallothioneins have been isolated from Saccharomyces cerevisiae CUP1 mutants generated by Wright et al. (Wright, C. F., Hamer, D. H., and McKenney, K. (1986) Nucleic Acids Res. 14, 8489-8499). In the mutant metallothioneins, pairs of cysteinyl residues have been converted to seryl residues. The mutant proteins differ only in the positions of the double substitutions; each mutant molecule contains 10 cysteinyl residues. Each mutant protein lacks the first 8 residues at the amino terminus from the decoded gene sequence of the CUP1 locus. Mutant molecules consist of 53 residues analogous to the wild-type metallothionein and are designated 9/11, 24/26, 36/38, and 49/50 (in reference to the sequence positions of the Cys----Ser conversions). The properties of the mutant metallothioneins are vastly different, and host cells harboring the different plasmid-encoded mutant molecules show marked differences in sensitivity to CuSO4. Growth inhibition was observed at CuSO4 concentrations up to mM in cells containing the 9/11, 24/26, and 36/38 molecules, but not for cells containing protein 49/50. A CuSO4 concentration of 5 mM was required to inhibit the growth of yeast containing either 49/50 or the wild-type metallothionein. In the purified proteins the copper binding stoichiometry of each molecule, except protein 24/26, was nearly 8 mol eq. Protein 24/26 bound 5.5 copper ions/molecule. The Cu(I) chelator bathocuproine disulfonate reacted with over 50% of the copper ions in proteins 9/11, 24/26, and 36/38, but less than 10% of the copper ions in proteins 49/50 and wild-type metallothionein were reactive. The thiolates in 9/11, 24/26, and 36/38 were also more reactive in a disulfide exchange reaction with dithiodipyridine compared with the sulfhydryls in 49/50 and the wild-type molecules. The four mutant copper proteins are luminescent and exhibit a similar quantum yield. The cluster structures contributing to the particular electronic transitions are markedly more sensitive to oxygen in proteins 9/11, 24/26, and 36/38 compared with 49/50 and the wild-type molecules. The air-sensitive proteins exhibit a tertiary fold not recognized by polyclonal antibodies directed to a conformational epitope on yeast Cu-metallothionein. Protein 49/50 cross-reacts with the antibody in a concentration-dependent fashion similar to the wild-type protein. Mutation of 2 cysteinyl residues in the carboxyl portion of metallothionein does not significantly alter properties of the molecule, whereas mutation of several cysteines in the amino-terminal portion of the molecule yields a different conformation.


Cloning of the cDNA encoding human C/EBP gamma, a protein binding to the PRE-I enhancer element of the human interleukin-4 promoter.
The positive regulatory element-I (PRE-I) is a strong enhancer element essential for expression of the human interleukin-4 (IL-4)-encoding gene. In order to identify transcription factors binding to PRE-I, we screened a cDNA expression library from human Jurkat T-cells. A cDNA encoding the human CCAAT/enhancer binding protein-gamma (hC/EBP gamma) was cloned. The deduced amino acid (aa) sequence of HC/EBP gamma contains 150 aa with high homology to mouse Ig/EBP-1 and rat C/EBP gamma. The mRNA of hC/EBP gamma is expressed at a high level in Jurkat T-cells in three forms generated via differential polyadenylation. DNA-binding experiments with recombinant protein produced in bacteria demonstrate that hC/EBP gamma binds to PRE-I, but not to unrelated DNA fragments. Our data also show that hC/EBP gamma may cooperate with Fos to bind PRE-I.


[Further training in rheumatology-Current status 2022].
For the continued existence of the specialty of internal medicine and rheumatology and the assurance of a qualitative patient care, attractive further education for motivated resident physicians is of central importance. Continuing training in rheumatology takes place primarily in the inpatient setting, although reliable figures on outpatient and inpatient further education positions are not yet available. Further training in rheumatology is predefined by the model further training regulations (Musterweiterbildungsverordnung; MWBO) 2018, which have now been implemented by most state medical associations, in some cases with state-specific changes. Based on the MWBO of 2018, a model curriculum was developed by the German Society of Rheumatology (DGRh) for further training in the specialty of internal medicine and rheumatology. This model curriculum is intended to provide orientation for trainees and trainers as well as to facilitate structured rheumatology training in inpatient and outpatient settings.


The effects of arm elevation on the 3-dimensional acromiohumeral distance: a biplane fluoroscopy study with normative data.
Narrowing of the subacromial space has been implicated in several shoulder pathologies. However, the location of the minimum distance points during clinical testing has not been defined. We sought to measure the in vivo minimum distance and location of the minimum distance points on the acromion and proximal humerus during arm elevation. Eight healthy male subjects (mean age, 30 years) underwent a dynamic in vivo biplane fluoroscopy assessment of scaption and forward elevation. For each frame, the 3-dimensional position and orientation of the humerus and scapula were determined, and the acromiohumeral distance (AHD) was measured as the shortest distance between the acromion and proximal humerus. The minimum AHD was 2.6 ± 0.8 mm during scaption and 1.8 ± 1.2 mm during forward flexion at elevation angles of 83° ± 13° and 97° ± 23°, respectively. The minimum distance point was located on the articular surface of the humeral head from the neutral arm position until 34° ± 8° for scaption and 36° ± 6° for forward flexion. Upon further elevation, the minimum distance point was located within the footprint of the supraspinatus muscle until 72° ± 12° for scaption and 65° ± 8° for forward flexion. At greater elevation angles, the minimum distance points were between the acromion and the proximal humeral shaft, distal from the greater tuberosity. The shortest AHD was at approximately 90° of arm elevation. The AHD was no longer measured intra-articularly or within the supraspinatus footprint above approximately 70° of arm elevation.


55-year-old woman • unilateral nasal drainage • salty taste • nasal redness • recent COVID-19 nasal swabs • Dx?
► unilateral nasal drainage ► salty taste ► nasal redness ► recent COVID-19 nasal swabs.


Association between bone mineral density and hearing loss in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder, predominantly characterized by bone fragility. In half of the patients, progressive hearing loss develops, which is associated with abnormal bony changes involving the middle ear ossicles and stapes footplate. In the present study, we investigated whether the development of hearing loss in OI may be related to the overall aberrant bone quality. Observational study. Following audiologic evaluation, 56 adult OI patients were classified as presenting normal hearing or conductive/mixed or pure sensorineural hearing loss. Areal bone mineral density (BMD) (aBMD) was measured using lumbar spine (LS) and whole body (WB) dual X-ray absorptiometry. By means of peripheral computed tomography, volumetric BMD (vBMD) and morphometric bone parameters were determined at distal and proximal radius, providing separate results for trabecular and cortical bone. The obtained bone parameters were compared between normal-hearing OI patients and those with either conductive/mixed or pure sensorineural hearing loss. Z scores demonstrated decreased LS aBMD, WB aBMD, and trabecular vBMD in OI adults compared to the healthy population. Patients with conductive/mixed hearing loss had lower trabecular vBMD compared to those with normal hearing or pure sensorineural loss at both whole-group and between-relatives comparisons. It is hypothesized that OI patients with lower BMD might be more susceptible to accumulating microfractures, which may interfere with the bone remodeling inhibition pathways in the temporal bone and, therefore, contribute to stapes footplate fixation and a conductive hearing loss component.


Update of students' and lecturers' perspectives on online learning in dental education after a five-semester experience due to the SARS-CoV-2 (COVID-19) pandemic: insights for future curriculum reform.
The coronavirus disease (COVID-19) pandemic has accelerated digital transformation in dental education, resulting in a shift from face-to-face teaching to online learning. While online learning could be a common strategy in various fields, the challenge for dental education is that it depends on the requirements of clinical experience to achieve competence in performing the dental treatment. This cross-sectional study aimed to analyse students' and lecturers' perceptions towards online learning after five semesters of experience using a questionnaire survey. Since the spring term of 2020, the theoretical part of the curriculum has been conducted in the form of online learning using a combination of synchronous and asynchronous formats. In the following semesters, more theoretical content was shifted back from online learning to face-to-face courses. Preclinical and clinical students enrolled in the dental curriculum during the spring term 2022 semester and all lecturers with at least one year of teaching experience in face-to-face and online learning formats were asked to fill out an online questionnaire regarding the aspects of handling, didactic benefit, motivation, and overall assessment. Students and lecturers rated the implementation of online learning as mostly positive, but pointed out that established 'face-to-face' learning could not be replaced. Moreover, the students reported personal benefits in terms of daily planning. Lecturers also benefitted as their experience increased in online teaching. For future curriculum, students demanded 49.5% (25.1) ((mean (standard deviation) of theoretical part in terms of online learning), while lecturers demanded only 34.1% (24.1). Despite having no prior need for online learning, students and lecturers showed a positive perspective on online learning which should be considered in the implementation and planning of future dental education. However, in terms of practical training, it cannot replace face-to-face education in dentistry.


Structure-activity relationship study of novel necroptosis inhibitors.
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. It can be induced in a FADD-deficient variant of human Jurkat T cells treated with TNF-alpha. 5-(1H-Indol-3-ylmethyl)-2-thiohydantoins and 5-(1H-indol-3-ylmethyl)hydantoins were found to be potent necroptosis inhibitors (called necrostatins). A SAR study revealed that several positions of the indole were intolerant of substitution, while small substituents at the 7-position resulted in increased inhibitory activity. The hydantoin ring was also quite sensitive to structural modifications. A representative member of this compound class demonstrated moderate pharmacokinetic characteristics and readily entered the central nervous system upon intravenous administration.


ATP selection in a random peptide library consisting of prebiotic amino acids.
Based upon many theoretical findings on protein evolution, we proposed a ligand-selection model for the origin of proteins, in which the most ancient proteins originated from ATP selection in a pool of random peptides. To test this ligand-selection model, we constructed a random peptide library consisting of 15 types of prebiotic amino acids and then used cDNA display to perform six rounds of in vitro selection with ATP. By means of next-generation sequencing, the most prevalent sequence was defined. Biochemical and biophysical characterization of the selected peptide showed that it was stable and foldable and had ATP-hydrolysis activity as well.


Human alpha1-glycoprotein acid as chiral selector in the enantioseparation of midodrine and deglymidodrine racemates by HPLC.
Human alpha1-acid glycoprotein (alpha1-AGP) has been used as a chiral stationary phase (CSP) for the enantioseparation of midodrine and deglymidodrine racemates in the same HPLC run. The imobilized AGP resulted as the best chiral selector for the enantioresolution of two compounds. Due to the modification of alpha1-AGP characters as a result of changing the composition of the mobile phase, an attempt study of the watery mobile phase (ionic strength and pH of the buffer, nature and concentration of the organic modifier) allowed for an increase in the enantioselectivity of the chromatographic system and an optimization of the resolution base-line of both enantiomeric pairs.


Diagnosis of isolated sagittal synostosis: are radiographic studies necessary?
Isolated sagittal synostosis can be diagnosed easily on clinical grounds. This study was designed to determine if children could be operated on based solely on a clinical diagnosis or whether such an approach would result in any potentially unnecessary surgeries. Records of 114 consecutive children operated on for isolated nonsyndromic sagittal synostosis over a 14-year period (1987-2000) were reviewed to see whether the clinical findings were in concordance with the intraoperative findings and histopathology of the sagittal suture. The age at surgery ranged from 1.9 to 81.3 months (median 4.3 months). Preoperative skull radiographs were done in 78 children and computer tomography (CT) scans of the head in 12 children. One hundred percent of the skull radiographs and 83.3% of the CT scans were completed prior to referring the children to a pediatric neurosurgeon. CT scans confirmed the diagnosis in all patients in whom it was available. For the rest, pathology reports and/or operative records were available for 108 (94.7%) children and were confirmatory for sagittal craniosynostosis in all. Accurate diagnosis of isolated sagittal synostosis can be made clinically, and operative correction can proceed without a need for radiological investigations, unless the clinical features are not completely typical. This approach could result in significantly reduced radiation exposure for the developing brain and could provide economic benefits to health care providers.


Range of motion in the avian wing is strongly associated with flight behavior and body mass.
Avian wing shape is highly variable across species but only coarsely associated with flight behavior, performance, and body mass. An underexplored but potentially explanatory feature is the ability of birds to actively change wing shape to meet aerodynamic and behavioral demands. Across 61 species, we found strong associations with flight behavior and mass for range of motion traits but not wing shape and strikingly different associations for different aspects of motion capability. Further, static morphology exhibits high phylogenetic signal, whereas range of motion shows greater evolutionary lability. These results suggest a new framework for understanding the evolution of avian flight: Rather than wing morphology, it is range of motion, an emergent property of morphology, that is predominantly reshaped as flight strategy and body size evolve.


Direct Oral Anticoagulants in the Setting of Catheter Ablation of Atrial Fibrillation: State of art.
Atrial fibrillation (AF) represents the arrhythmia of greatest clinical impact and catheter ablation of AF (CAAF) has become the most effective strategy for rhythm control in selected patients. Therefore, appropriate anticoagulation strategies are of paramount importance for patients undergoing CAAF, especially those at high risk, such those with high CHA2DS2VASc scores. Optimal management of anticoagulation before, during, and after CAAF is crucial. Several studies have evaluated the use of different anticoagulation strategies in the periprocedural period. Randomized controlled trial seem to suggest that in patients undergoing CAAF, uninterrupted (or minimally interrupted) direct oral anticoagulants (DOACs) provides an alternative to continuous vitamin K antagonists strategy, with low thromboembolic and bleeding risk.


Accuracy and outcome of sonographically guided intra-articular sodium hyaluronate injections in patients with osteoarthritis of the hip.
The aim of this study was to evaluate the accuracy and outcome of sonographically guided intra-articular sodium hyaluronate injections in patients with osteoarthritis of the hip. The prospective study involved 10 patients who had the diagnosis of unilateral hip osteoarthritis. The mean age of the patients was 63.2 years (range, 27-80 years). Depending on patient body weight, either a 3.5- to 5-MHz convex transducer or a 5- to 12-MHz linear transducer was used to examine each affected joint. Every subject received 3 injections of sodium hyaluronate, 1 per week for 3 consecutive weeks. With real-time sonographic monitoring, each joint was penetrated with a 20-gauge Chiba needle. Contrast medium was injected initially, and proper intra-articular placement was verified with computed tomography before the hyaluronate injection. Each patient's outcome was assessed on the basis of visual analog scale results and Western Ontario and McMaster Universities osteoarthritis index findings that were recorded before the set of injections and 2, 4, and 6 months after the third injection. Computed tomography confirmed accurate placement in all 30 injections in the study. The visual analog scale and the Western Ontario and McMaster Universities osteoarthritis index scores showed that 80% of the patients had less pain in the joint at 6 months after the last injection. Sonographically guided intra-articular injection of sodium hyaluronate for patients with hip osteoarthritis is easy to perform and is a safe, economical, and well-tolerated form of treatment. In contrast to fluoroscopic or computed tomographic guidance, the sonographic technique exposes neither the patient nor the physician to radiation.