Changes in T wave morphology during hypercalcemia and its relation to the severity of hypercalcemia.
The effect of hypercalcemia on T wave morphology, polarity, and amplitude was studied in 14 patients with a primary diagnosis of malignant lymphoma (8 patients), adult T-cell leukemia (5 patients), and Hodgkin's disease (1 patient). Hypercalcemia was severe to extreme in 11 (14.9-22.8 mg/dl), moderate in 1 (13.4 mg/dl), and mild in 2 (11.8 and 12.2 mg/dl) patients. Ten of the 11 patients (91%) with severe hypercalcemia showed inverted, biphasic, and notched T waves, mainly in the chest leads. Notched T waves were observed in all 10 of these patients in anterior to lateral, mid to lateral, or lateral chest leads. Biphasic and/or inverted T waves in anterior or anterior to midchest leads were present in 4 of these 10 patients who had extreme hypercalcemia (greater than 16 mg/dl). Changes in T wave morphology were not observed in moderate or mild hypercalcemia. T wave amplitude showed significant inverse correlation with serum calcium (T mV vs Ca, r = -0.60, p less than 0.001; T/R ratio vs Ca, r = -0.68, p less than 0.001; n = 35). Decrease in T wave amplitude was marked in severe hypercalcemia (p less than 0.0001) and moderate hypercalcemia, but there was no change in mild hypercalcemia. Changes in T wave morphology, polarity, and amplitude either appeared with development of hypercalcemia or disappeared with normalization of serum calcium level. It was concluded that in addition to shortening the QT interval, severe to extreme hypercalcemia can cause development of inverted, biphasic, or notched T wave with a marked decrease in amplitude of T waves.


Degradation testing of Mg alloys in Dulbecco's modified eagle medium: Influence of medium sterilization.
This work studies the in vitro degradation of Mg alloys for bioabsorbable implant applications under near physiological conditions. For this purpose, the degradation behaviour of Mg alloys in Dulbecco's modified eagle medium (DMEM) which is a commonly used cell culture medium is analysed. Unfortunately, DMEM can be contaminated by microorganisms, acidifying the medium and accelerating the Mg degradation process by dissolution of protective degradation layers, such as (Mgx,Cay)(PO4)z. In this paper the influence of sterilization by applying UV-C radiation and antibiotics (penicillin/streptomycin) is analysed with two implant material candidates: Mg-Gd and Mg-Ag alloys; and pure magnesium as well as Mg-4Y-3RE as a reference.


Brain-Machine Interface-Based Rat-Robot Behavior Control.
Brain-machine interface (BMI) provides a bidirectional pathway between the brain and external facilities. The machine-to-brain pathway makes it possible to send artificial information back into the biological brain, interfering neural activities and generating sensations. The idea of the BMI-assisted bio-robotic animal system is accomplished by stimulations on specific sites of the nervous system. With the technology of BMI, animals' locomotion behavior can be precisely controlled as robots, which made the animal turning into bio-robot. In this chapter, we reviewed our lab works focused on rat-robot navigation. The principles of rat-robot system have been briefly described first, including the target brain sites chosen for locomotion control and the design of remote control system. Some methodological advances made by optogenetic technologies for better modulation control have then been introduced. Besides, we also introduced our implementation of "mind-controlled" rat navigation system. Moreover, we have presented our efforts made on combining biological intelligence with artificial intelligence, with developments of automatic control and training system assisted with images or voices inputs. We concluded this chapter by discussing further developments to acquire environmental information as well as promising applications with write-in BMIs.


Basic mechanisms of calcium antagonists.
This paper reviews the mechanism of action of calcium antagonists and relates them to the cardiovascular diseases in which the drugs have a therapeutic role.


Constructing RNA Viruses for Long-Term Transcriptional Gene Silencing.
Recent discoveries have shown that self-replicating RNA viruses can produce small RNAs (sRNAs) in host cells. Given their potential to be modified to generate short-term transgene expression without integrating viral sequences into the host genome, these viruses could be used as safe delivery vehicles for sRNAs to induce long-term transcriptional gene silencing (TGS). This might open new avenues for therapeutic approaches, where a single administration would safely induce long-term therapeutic effects for various diseases. Here, we introduce and discuss the possible use of cytoplasmic alphaviruses, flaviviruses, Sendai virus (SeV), and nucleoplasmic Influenza A (IAV) and Borna disease (BoDV) viruses to induce long-term TGS.


A Ras GTPase associated protein is involved in the phototropic and circadian photobiology responses in fungi.
Light is an environmental signal perceived by most eukaryotic organisms and that can have major impacts on their growth and development. The MadC protein in the fungus Phycomyces blakesleeanus (Mucoromycotina) has been postulated to form part of the photosensory input for phototropism of the fruiting body sporangiophores, but the madC gene has remained unidentified since the 1960s when madC mutants were first isolated. In this study the madC gene was identified by positional cloning. All madC mutant strains contain loss-of-function point mutations within a gene predicted to encode a GTPase activating protein (GAP) for Ras. The madC gene complements the Saccharomyces cerevisiae Ras-GAP ira1 mutant and the encoded MadC protein interacts with P. blakesleeanus Ras homologs in yeast two-hybrid assays, indicating that MadC is a regulator of Ras signaling. Deletion of the homolog in the filamentous ascomycete Neurospora crassa affects the circadian clock output, yielding a pattern of asexual conidiation similar to a ras-1 mutant that is used in circadian studies in N. crassa. Thus, MadC is unlikely to be a photosensor, yet is a fundamental link in the photoresponses from blue light perceived by the conserved White Collar complex with Ras signaling in two distantly-related filamentous fungal species.


Phylogenetic analysis and heterologous expression of surface layer protein SlpC of Bacillus sphaericus C3-41.
The surface layer protein encoding genes from five mosquito-pathogenic Bacillus sphaericus isolates were amplified and sequenced. Negative staining of the S-layer protein extracted from the cell wall of wild-type B. sphaericus C3-41 was prepared. It showed a flat-sheet crystal lattice structure. Two genes encoding the entire and N-terminally truncated S-layer protein (slpC and DeltaslpC respectively), were ligated into plasmid pET28a and expressed in Escherichia coli. SDS-PAGE revealed that about 130 KD and 110 KD proteins could be expressed in the cytoplasm of recombinant E. coli BL21(pET28a/slpC) and E. coli BL21(pET28a/DeltaslpC) respectively. Furthermore, an intracellular sheet-like or fingerprint-shape structure was investigated in two recombinant strains, which expressed SlpC and DeltaSlpC protein respectively, by ultrathin microscopy study, but bioassay results suggested that the S-layer protein of wild B. sphaericus C3-41 and recombinant E. coli BL21 (pET28a/slpC) have no direct toxicity against mosquito larvae. These results should provide information for further understanding of the function of S-layer protein of pathogenic B. sphaericus.


The cloning and characterization of a second alpha-amylase of A. hydrophila JMP636.
The aim of this study was to identify, clone and characterize the second amylase of Aeromonas hydrophila JMP636, AmyB, and to compare it to AmyA. The amylase activity of A. hydrophila JMP636 is encoded by multiple genes. A second genetically distinct amylase gene, amyB, has been cloned and expressed from its own promoter in Escherichia coli. AmyB is a large alpha-amylase of 668 amino acids. Outside the conserved domains of alpha-amylases there is limited sequence relationship between the two alpha-amylases of A. hydrophila JMP636 AmyA and AmyB. Significant (80%) similarity exists between amyB and an alpha-amylase of A. hydrophila strain MCC-1. Differences in either the functional properties or activity under different environmental conditions as possible explanations for multiple copies of amylases in JMP636 is less likely after an examination of several physical properties, with each of the properties being very similar for both enzymes (optimal pH and temperature, heat instability). However the reaction end products and substrate specificity did vary enough to give a possible reason for the two enzymes being present. Both enzymes were confirmed to be alpha-type amylases. AmyB has been isolated, characterized and then compared to AmyA. The amylase phenotype is rarely encoded by more than one enzyme within one strain, this study therefore allows the better understanding of the unusual amylase production by A. hydrophila.


Seizure control status and associated factors among pediatric epileptic patients at a neurologic outpatient clinic in Ethiopia.
Childhood epilepsy is a major public health problem worldwide. Even though anti-seizure medications (ASM) have been demonstrated to control seizures, children with epilepsy continue to have frequent seizures. There is a scarcity of data on seizure control status among pediatric epileptic patients in Ethiopia. The aim of this study was to assess seizure control status and associated factors among pediatric epileptic patients. A hospital based cross-sectional study was done on 261 pediatric epileptic patients being followed up at the University of Gondar Comprehensive and Specialized Hospital, Northwest Ethiopia, from May 11 to August 11, 2019. The data were collected through caregiver interviews and patients' medical records. All independent variables with p value of ≤ 0.2 in univariate analysis were taken to multivariable analysis. Adjusted odds ratio (AOR) with a 95% confidence interval was computed to see the predictors of seizure control status. Level of statistical significance was declared if p-value < 0.05. From a total of 261 patients, 159 (60.9%) were males and had a mean age was 10.16 ± 4.62 years. More than half (57.1%) of participants were urban dwellers. Almost all (98.5%) were diagnosed with generalized tonic-clonic seizures. Majority (75.1%) of the patients were on mono-therapy. Forty-six (17.6%) of the patients reported adverse effects related to ASMs. Two hundred-three (77.8%) of the patients were adherent to their medications. Nearly half (49.0%) of the patients had controlled seizures. Urban residency (AOR: 2.12; 95% CI: 1.15-3.89; P = 0.016), adherence to medication (AOR: 3.92; 95% CI: 1.84-8.36; P < 0.001), use of combined ASM(AOR: 0.29; 95% CI: 0.14-0.59; P = 0. 001), durations of ASM use [2-5 years (AOR: 5.81; 95% CI: 2.89-11.70; P <0.001) and >5years (AOR: 4.80; 95% CI: 1.91-12.09; P = 0.001)]were significantly associated with seizure control status. Inadequate numbers of pediatric epileptic patients' at the Ethiopian neurologic clinic achieved seizure control. Coming from a rural area, non-adherence to ASMs, use of multiple ASMs, and the use of ASMs for <2years were found to have a significant association with poorer seizure control, needing special attention to get control of seizure. Caregivers should closely monitor and address any barriers that contribute to ASM non-adherence and adverse drug events.


Associations of variants of CNR1 with obesity and obesity-related traits in Chinese women.
The aim of this study was to investigate associations of two candidate gene SNPs of the endocannabinoid receptor type 1 gene (CNR1) with overweight, obesity and obesity-related traits in Chinese retired women. The study subjects were a subsample of the Taizhou Retiree Women Cohort, consisting of 2812 retired women aged 50-64 years recruited from Taizhou, Jiangsu, China. Neither rs2023239 nor rs806381 polymorphism was significantly associated with body mass index-defined overweight and obesity or waist-to-hip-ratio-defined obesity. For obesity-related traits, rs2023239 was significantly associated with glutamate pyruvate transaminase (GPT) (median, 18.00 vs 17.00 for TT and TC genotypes, respectively, P=0.043). The rs806381 also showed significant association with triglyceride (TG) (mean±SD, 1.46±0.20 vs 1.53±0.20 for GA and GG+AA genotypes, respectively, P=0.013) under the dominant genetic model. In conclusion, the rs2023239 and rs806381 polymorphisms of CNR1 were not associated with increased overweight and obesity risk. But the rs2023239 polymorphism was significantly associated with GPT, and the rs806381 polymorphism was significantly associated with TG.


Managing Essential Tremor.
Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: axis 1-defining syndromes based on the clinical features such as historical features, tremor characteristics, associated signs, and laboratory tests; and axis 2-classifying the etiology (Bhatia et al., Mov Disord 33:75-87, 2018). The management of this condition has two major approaches. The first is to exclude treatable etiologies, as particularly during the onset of this condition the presentation of a variety of etiologies can be with monosymptomatic tremor. Once the few etiologies with causal treatments are excluded, all further treatment is symptomatic. Shared decision-making with enabling the patient to knowledgeably choose treatment options is needed to customize the management. Mild to moderate tremor severity can sometimes be controlled with occupational treatment, speech therapy of psychotherapy, or adaptation of coping strategy. First-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is for selected cases. Invasive treatments for essential tremor should be considered for severe tremors. They are generally accepted as the most powerful interventions and provide not only improvement of tremor but also a significant improvement of life quality. The current standard is deep brain stimulation (DBS) of the thalamic and subthalamic region. Focused ultrasound thalamotomy is a new therapy attracting increasing interest. Radiofrequency lesioning is only rarely done if DBS or focused ultrasound is not possible. Radiosurgery is not well established. We present our treatment algorithm.


Thiazide diuretics for the treatment of children with idiopathic hypercalciuria and hematuria.
We describe our experience in 14 children with idiopathic hypercalciuria and hematuria who received a finite course of thiazide diuretics. Thiazides reduced urinary calcium excretion and resolved hematuria in all cases. Serum calcium concentration was not altered with treatment. Serum potassium concentration decreased, and total carbon dioxide content and uric acid concentrations increased in response to therapy but these changes did not necessitate discontinuation of treatment. Thiazides were discontinued electively after 16 +/- 15 months of treatment (range 3 to 40 months). Six children maintained normal urinary calcium excretion, while 8 displayed excessive calcium excretion for 16 +/- 4 months after treatment was stopped. Renal calculi were not detected in any patient during this interval but hematuria recurred in 4 children. These findings suggest that thiazides are safe and effective for resolving hypercalciuria and hematuria. Thiazides may be discontinued safely in some children, while others will require further treatment courses or prolonged continuous therapy.


[Comparative experiments of stripping sheep maxillary sinus mucosal with new-type stripper and umbrella detacher].
To compare the stripping length obtained through the model of 0.012 and 0.014 of the nickel-titanium dual-stage maxillary sinus mucosa stripper, and the umbrella detacher. Twenty-four goats (1.5-2 years old) were chosen, randomly divided into A, B, C groups, each group of eight. Group A was 0.012 model group, group B was 0.014 model group, group C was umbrella detacher group. Animal model was established, and maxillary sinus mucosa was stripped to the left and right sides of the bottom of the sinus in three groups. The data was measured when stripping to the limit or being perforated. The average length of group A was 12.41 mm±4.35 mm, two cases perforated. The average length of group B was 23.38 mm±4.84 mm, one case perforated. The average length of group C was 2.61 mm±0.30 mm. The population mean of stripping length in three groups was not all the same calculated by analysis of variance (P<0.01). There were significant differences in the stripping length of the three groups by the SNK test (P<0.05). The nickel-titanium dual-stage maxillary sinus mucosa stripper can achieve a larger mucosal stripping range. The stripper with a model of 0.014 has a moderate flexibility and safety, and it can strip a large area of sinus mucosa. .


Small calcification depiction in ultrasound B-mode images using decorrelation of echoes caused by forward scattered waves.
The purpose of this study is to propose a novel method to depict small calcifications in ultrasound B-mode images using decorrelation of forward scattered waves with no decrease in the frame rate. Since the waveform of an ultrasound pulse changes when it passes through a calcification location, the echo waveform from regions behind the calcification is quite different from that without a calcification. This indicates that the existence of a calcification is predictable based upon the waveform difference between adjacent scan lines by calculating cross-correlation coefficients. In addition, a high-intensity echo should return from the calcification itself. Therefore, the proposed method depicts the high-intensity echo positions with posterior low correlation coefficient regions. Eleven of 15 wires 0.2-0.4 mm in diameter were depicted using this method, yielding a sensitivity of 73.3% and a specificity of 100%, even though they might go undetected under clinical inspection of ultrasound B-mode images. This study suggests that an US device could perform well in terms of calcification detection.


Parental acceptability of contraceptive methods offered to their teen during a confidential health care visit.
To examine parental acceptability of contraceptive methods offered confidentially to their adolescent daughter. A random sample of 261 parents/guardians with a daughter aged 12-17 years completed a telephone survey examining the relationship between parental acceptability of seven contraceptive methods and adolescents' likelihood to have sex, parenting beliefs, parents' sexual health as teens, sexually transmitted infection knowledge, and demographic factors. Acceptability was highest for oral contraceptive pills (59%) and lowest for intrauterine device (18%). Parental acceptance of teens' autonomy was significantly associated with increased acceptability of all methods. Parental knowledge of sexually transmitted infections was poor, and 51% found it acceptable for clinicians to provide their sexually active teen with condoms. Parents were more accepting of oral contraceptive pills and condoms compared with intrauterine devices and implants. Parental recognition of their teen's autonomy was associated with greater parental acceptability of clinicians providing their adolescent with contraceptives (regardless of the specific type of method being offered).


The culture of chick forebrain neurons.
Dissociation of the forebrain of a single 8-day chick embryo produces > 10(7) neurons in nearly pure culture. Our methods allow 50-70% of these neurons to develop an axon and typical pyrimidal shape after 3-4 days in culture at low density (10(4) cells/cm2) by a stereotyped developmental sequence similar to that of rat hippocampal neurons. The culture method for chick forebrain neurons is unusually rapid, inexpensive, simple, and could be used in undergraduate laboratory exercises. The dissection and dissociation of the tissue are easy and rapid, requiring less than 30 min from cracking open the chicken egg to plating the cells. Axonal development by these neurons and growth for about a week do not require glial support. The neurons are grown on polylysine-treated culture surfaces in either CO2-dependent (Medium 199) or -independent (Liebovitz L15) media with 10% fetal bovine serum and a supplement based on the classic N2 supplement for neuronal culture.


Intramural thrombosis of giant aneurysms of the supraclinoid and subclinoid internal carotid artery. Report of 4 cases.
We describe our experience of wiring to induce intramural thrombosis of giant aneurysms of the carotid artery, partly intracavernous and partly intracranial, in which surgical occlusion of the neck was impossible.


Evaluation of overall costs of currently available small flexible ureteroscopes.
To perform a meta-analysis of the currently available data regarding the durability of flexible ureteroscopes to establish cost estimates for the purchase and use of five currently available, smaller than 9F, ureteroscopes. Healthcare costs have become increasingly germane to the determination of disease management strategies. Improved ureteroscope technology has expanded the role of these instruments. However, the initial purchase costs and high maintenance costs have become problematic with these fragile instruments. Ureteroscope durability data on the Storz 11274AA, Olympus URF-P3, Wolf 7325.172, ACMI AUR-7, and ACMI DUR-8 were collected from three prior studies. Combining the durability data and cost data regarding the initial purchase price and maintenance costs of these instruments, we calculated the overall costs associated with the use of each of the ureteroscopes for 25, 50, 75, and 100 cases during the first year (warranties included) and with subsequent use. The variability in the costs associated with the use of the currently available smaller than 9F ureteroscopes was significant. The initial instrument purchase price, durability, repair costs, and associated warranties all contributed to large discrepancies in the cost of performing ureteroscopy. In this model, during the first year of ownership, the projected cost of performing 100 ureteroscopic cases varied by a difference of 95% depending on the ureteroscope used. Physicians and institutions that perform ureteroscopy should strongly consider the purchase price, durability, repair cost, and associated warranties before the purchase of small flexible ureteroscopes.


Assessment of Impulsive and Continuous Low-Frequency Noise in Irish Waters.
As part of the European Union Marine Strategy Framework Directive (MSFD), member states are required to address noise pollution in the marine environment under Descriptor 11. This study aimed to provide a practical desk-based application of Descriptor 11 assessment, focusing on the main contributors of ocean noise pollution in Irish waters, seismic surveying and shipping. To highlight specific geographical areas subject to elevated levels of noise pollution, the proportion of days over a calendar year that seismic air guns were operational was calculated and the vessel density per 50-km(2) grids was determined across Ireland's exclusive economic zone (EEZ). Additionally, cetacean sighting data were used to determine the degree of spatial overlap between areas of elevated noise pollution and areas of cetacean abundance.


["Klebsiellae" infections (author's transl)].
Results are presented on the frequency of Klebsiellae recovery from biologic materials (urines, pleura or peritoneal exudates, cerebrospinal fluids, blood specimens) examined during one year. Tobramycin was the antibiotic with the highest in vitro activity against the isolates.


Bioaccumulation and chemical form of chromium in Leersia hexandra Swartz.
The chromium bioaccumulation ability of Leersia hexandra was assessed and the chromium distribution in the deferent chemical forms in plant tissues was determined. The hydroponic experimental results indicated that the maximum chromium concentration in the dry leaf matter of Leersia hexandra reached 4302 mg kg(-1). Chromium treatment could significantly increase the proportions of oxalic integrated chromium in leaves and residue chromium in roots, which might be related to the high resistance and bioaccumulation capacity for chromium in Leersia hexandra.


Cytotoxic necrotizing factor 1 (CNF1) induces an inflammatory response in the urinary tract in vitro but not in vivo.
Cytotoxic necrotizing factor 1 (CNF1) is a well-defined virulence factor of uropathogenic Escherichia coli. We studied the role of CNF1 in uroepithelial cells as well as in children and adults with sporadic and recurrent UTI. Our study suggests that CNF1 may promote bacterial attachment and invasion and can induce an inflammatory response in the urinary tract in vitro but that its role in vivo is possibly minor in comparison with other virulence factors of the uropathogenic E. coli.


Rapid and complete dehalogenation of halonitromethanes in simulated gastrointestinal tract and its influence on toxicity.
Halonitromethanes (HNMs) as one typical class of nitrogenous disinfection byproducts in drinking water and wastewater are receiving attentions due to their high toxicity. This study applied a simulator of the human gastrointestinal tract to determine the dehalogenation processes of trichloronitromethane, bromonitromethane and bromochloronitromethane for the first time. Influence of digestion process of HNMs on gut microbiota and hepatotoxicity was further analyzed. Results showed that the three HNMs were rapidly and completely dehalogenated in the gastrointestinal tract, especially in the stomach (2 h retention Time) and small intestine (4 h retention Time). Mucin, cysteine, pancreatin and bile salts in the digestive juice played major roles in the dehalogenation process. HNMs and their dehalogenation products in the resulting fluids of stomach induced the highest toxicity followed by those in intestine and colon, exhibiting dose-dependent effects. Although most HNMs were degraded in the stomach and small intestine, residual HNMs entered into colon changed the microbial community. Abundance of several genera, such as Bacteroides, Lachnospiraceae_unassigned and Lactobacillus had high correlation with exposure concentration of HNMs. This study sheds new light on dehalogenation and toxic processes of HNMs by oral exposure, which provides basic data for their human health risk assessment.


Arrangement of C-tubule protofilaments in mammalian basal bodies.
The arrangement of C-tubule protofilaments was studied in basal bodies of respiratory epithelial cilia using tannic acid staining techniques. At the proximal end of the basal body, the C tubule consisted of 10 protofilaments arranged analogously to the 10 protofilaments of the B tubule. In the region of the basal foot, 5 of the C protofilaments sequentially terminated. First, the C10 and C9 filaments terminated. Then the C1 and C8 filaments terminated, and finally the C7 filament terminated leaving a curved sheet of 5 filaments C2-C6 coursing through the distal third of the basal body. This study validates previous suggestions that the C tubule is incomplete distally, and this study clearly demonstrates the extent and consistency of this incompleteness. This morphological study also raises again the question of the function of the C tubules of basal bodies in light of both the incomplete nature of the C tubule and the apparent minor role of the C tubule in providing attachment sites for the basal foot and the alar sheets.


Myeloid-derived suppressor cells ameliorate corneal alkali burn through IL-10-dependent anti-inflammatory properties.
This study aims to investigate the efficiency and the underlying mechanism of myeloid-derived suppressor cells (MDSCs) in corneal alkali burns (CAB). In the study, CD11b+ Gr-1+ cells from C57BL/6J mice bone marrow were cultured and induced. Cell activity and immunoregulatory function were assessed by flow cytometry in vitro. The optimal strategy of MDSCs therapy was assessed by slit-lamp microscopy, and flow cytometry in vivo. The therapeutic effects of MDSCs and the critical signaling pathway were investigated by hematoxylin-eosin (HE) staining, slit-lamp microscopy, flow cytometry, and immunofluorescence. The expression level of the NLRP3 inflammasome pathway was examined. The crucial biochemical parameters of MDSCs were examined by RNA-seq and qPCR to screen out the key regulators. The mechanism of MDSCs' therapeutic effects was explored using MDSCs with IL-10 knockout/rescue by slit-lamp microscopy, HE staining, and qPCR evaluation. The cell frequencies of macrophages and neutrophils in the cornea were examined by flow cytometry in vivo. The results demonstrated that the induced MDSCs meet the standard of phenotypic and functional characteristics. The treatment of 5 × 105 MDSCs conjunctival injection on alternate days significantly ameliorated the disease development, downregulated the NLRP3 inflammasome pathway, and decreased the cell frequencies of macrophages and neutrophils in vivo significantly. IL-10 was screened out to be the critical factor for MDSCs therapy. The therapeutic effects of MDSCs were impaired largely by IL-10 knock-out and saved by the IL-10 supplement. In conclusion, MDSCs therapy is a promising therapeutic solution for CAB. MDSCs fulfilled immunoregulatory roles for CAB by IL-10-dependent anti-inflammatory properties.


Restitution of the aortic valve: what is new, what is proven, and what is obsolete?
Restitution strategies of the insufficient aortic valve belong to the clinical armamentarium. To date, the accumulated body of evidence comprises 126 articles dealing with restitution strategies on the insufficient aortic valve with concomitant aortic surgery. In a cumulative analysis an almost identical number of reimplantation (506) and remodeling (489) procedures were found in the literature, whereas 357 patients underwent aortic valve resuspension. The cumulative results tend to favor the reimplantation technique in terms of longevity of the reconstruction, particularly in congenital degenerative disorders of the aortic wall, whereas remodeling appears to exhibit a more physiologic behavior of the reconstructed valve and re-suspension serves as a simplified approach particularly in acute type A dissection. Although restitution of the native aortic valve has its place in current treatment options, the accumulated worldwide numbers indicate that it is not yet routinely implemented in the vast majority of cardiac institutions.


Establishment of a low-tumorigenic MDCK cell line and study of differential molecular networks.
Influenza is an acute respiratory infection caused by the influenza virus, and vaccination against influenza is considered the best way to prevent the onset and spread. MDCK (Madin-Darby canine kidney) cells are typically used to isolate the influenza virus, however, their high tumorigenicity is the main controversy in the production of influenza vaccines. Here, MDCK-C09 and MDCK-C35 monoclonal cell lines were established, which were proven to be low in tumorigenicity. RNA-seq of MDCK-C09, MDCK-C35, and MDCK-W73 cells was performed to investigate the putative tumorigenicity mechanisms. Tumor-related molecular interaction analysis of the differentially expressed genes indicates that hub genes, such as CUL3 and EGFR, may play essential roles in tumorigenicity differences between MDCK-C (MDCK-C09 and MDCK-C35) and MDCK-W (MDCK-W73) cells. Moreover, the analysis of cell proliferation regulation-associated molecular interaction shows that downregulated JUN and MYC, for instance, mediate increased proliferation of these cells. The present study provides a new low-tumorigenic MDCK cell line and describes the potential molecular mechanism for the low tumorigenicity and high proliferation rate.


Measuring the Full-Field Electroretinogram in Rodents.
Electroretinography allows for noninvasive functional assessment of the retina and is a mainstay for preclinical studies of retinal function in health and disease. The full-field electroretinogram is useful for a variety of applications as it returns a functional readout from each of the major cell classes within the retina: photoreceptors, bipolar cells, amacrine cells, and retinal ganglion cells. Rodent models are commonly employed in ocular degeneration studies due to the fast throughput of these mammalian species and the conservation of the electroretinogram from the preclinic to the clinic. Here we describe approaches for in vivo electroretinography in rodent models.


On the transformation technique in pharmacokinetic curve fitting.
It is shown that when one nonlinear regression model is a reparametrization of a second model, the parameter estimates, and their standard errors, for one model can be obtained directly from those obtained from fitting the other model.


Changes in brain serotonin and 5-hydroxyindolacetic acid levels in the rabbit following tonic immobility.
The effect of tonic immobility on serotonin (5-hydroxytryptamine, 5-HT) and on 5- hydroxyindolacetic acid (5-HIAA) levels in different brain areas has been investigated, following two different schedules of treatment. The massed treatment consisted of a series of consecutive trials up to 15 min, the spaced treatment in 4 series of trials within 24 hours. Massed treatment produced a decrease in 5-HT in the mesencephalon and of 5-HIAA in the pons-medullary area, but similar changes were also elicited in animals treated with the procedure of induction not followed by immobility. The spaced treatment, which resulted in a potentiation of the immobility duration, i.e., sensitization, produced a reduction of 5-HT levels in the mesencephalon and of 5-HT turnover in the striatum. The procedure of the induction per se acts preferentially on 5-HIAA by increasing its levels. In the striatum, which appears selectively responsive to the spaced treatment of immobility, a negative correlation has been found between serotonin levels and immobility duration. Results suggest that elicitation of tonic immobility is associated with reduced levels of 5-HT in the brain.


Force and displacement-controlled tendon vibration in humans.
This study investigated how the mechanical characteristics of tendon vibration influence the responses of human muscle receptors. In this study, we used a tendon vibrator in which the force, displacement and frequency of vibration were precisely controlled. The tendon vibrator could produce large amplitude displacements, so it was also used to impose ramp-and-hold stretches to the tendon to help classify muscle spindle afferents. In normal human subjects, we recorded microneurographically from single muscle afferents during tendon vibration to determine how afferent responses are influenced by the force and the displacement applied to the tendon and how these influences of force and displacement change with vibration frequency. Our results indicate that the sensitivity of muscle spindle afferents to tendon vibration is enhanced by increasing force and displacement and decreased by increasing frequency. It is concluded that, in order to predict the afferent response to vibration, the mechanical characteristics of tendon vibration must be controlled. Controlling the mechanical characteristics of tendon vibration and understanding the effect of vibration on afferent discharge will be useful for furthering our understanding of the peripheral control of movement.


Muscle excitation, force response, and efficiency during explosive force production after diacutaneous fibrolysis on lateral gastrocnemius of recreational athletes.
Fibrous adhesions impair normal muscle mechanics. The present study aimed to assess lateral gastrocnemius muscle excitation, isometric force response, and neuromuscular efficiency during explosive force in plantarflexion before and after diacutaneous fibrolysis. Thirty-five recreational athletes were allocated in the intervention group (n = 20) treated with diacutaneous fibrolysis, while the sham group (n = 15) was treated with placebo diacutaneous fibrolysis. Force response synchronized with surface electromyography during a plantarflexion task was collected. Differences between Pre- and Post-diacutaneous fibrolysis were observed for all variables, except for the placebo group. Diacutaneous fibrolysis was effective to increase force, muscle excitation, and neuromuscular efficiency on lateral gastrocnemius.


A cohort study examining changes in treatment patterns for alcohol use disorder among commercially insured adults in the United States during the COVID-19 pandemic.
We know very little about how the pandemic impacted outpatient alcohol use disorder (AUD) care and the role of telemedicine. Using OptumLabs® Data Warehouse de-identified administrative claims, we identified AUD cohorts in 2018 (N = 23,204) and 2019 (N = 23,445) and examined outpatient visits the following year, focusing on week 12, corresponding to the March 2020 US COVID-19 emergency declaration, through week 52. Using multivariable logistic regression, we examined the association between patient demographic and clinical characteristics and receipt of any outpatient AUD visits in 2020 vs. 2019. In 2020, weekly AUD visit utilization decreased maximally at the pandemic start (week 12) by 22.5 % (2019: 3.8 %, 2020: 3.0 %, percentage point change [95 % CI] = -0.86[-1.19, -0.05]) but was similar to 2019 utilization by mid-April 2020 (week 16). Telemedicine accounted for 50.1 % of AUD visits by early July 2020 (week 27). Individual therapy returned to 2019 levels within 1 week (i.e., week 13) whereas group therapy did not consistently do so until mid-August 2020 (week 31). Further, individual therapy exceeded 2019 levels by as much as 50 % starting mid-October 2020. The study found no substantial differences in visits by patient demographic or clinical characteristics. Among patients with known AUD, initial outpatient care disruptions were relatively brief. However, substantial shifts occurred in care delivery-an embrace of telemedicine but also more pronounced, longer disruptions in group therapy vs. individual and an increase in individual therapy use. Further research needs to help us understand the implications of these findings for clinical outcomes.


Spray deposited polycrystalline MAPbBr3 thick films for hole-transport-material free solar cells.
A spray deposition procedure for the fabrication of polycrystalline MAPbBr3 thick films (20-100 μm) is developed and highly efficient (>5.5% under AM1.5 sunlight) hole-transport-material free perovskite solar cells are successfully made with 40 μm thick MAPbBr3 films.


Structure of factor H-binding protein B (FhbB) of the periopathogen, Treponema denticola: insights into progression of periodontal disease.
Periodontitis is the most common disease of microbial etiology in humans. Periopathogen survival is dependent upon evasion of complement-mediated destruction. Treponema denticola, an important contributor to periodontitis, evades killing by the alternative complement cascade by binding factor H (FH) to its surface. Bound FH is rapidly cleaved by the T. denticola protease, dentilisin. In this report, the structure of the T. denticola FH-binding protein, FhbB, was solved to 1.7 Å resolution. FhbB possesses a unique fold that imparts high thermostability. The kinetics of the FH/FhbB interaction were assessed using surface plasmon resonance. A K(D) value in the micromolar range (low affinity) was demonstrated, and rapid off kinetics were observed. Site-directed mutagenesis and sucrose octasulfate competition assays collectively indicate that the negatively charged face of FhbB binds within FH complement control protein module 7. This study provides significant new insight into the molecular basis of FH/FhbB interaction and advances our understanding of the role that T. denticola plays in the development and progression of periodontal disease.


Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB.
TIR-domain-containing adapter-inducing interferon-β (TRIF) is the sole downstream adaptor of Toll-like receptor (TLR)3, which is one of the major signaling pathways in immune cells leading to neuroinflammation in the central nervous system. Overexpression of TRIF may lead to activation of inflammatory responses, and contribute to pathophysiological progression in both acute and chronic neurodegenerative retinal diseases. In the present study, was aimed to elucidate the contributions of TRIF to optic nerve (ON) regeneration and retinal ganglion cell (RGC) survival following injury to the ON, a widely studied model of central nervous system injury and of degenerative diseases such as glaucoma. We used retrograde labeling with a fluorochrome, hydroxystilbamidine (Fluorogold) to evaluate RGC survival, and immunostaining with growth-associated protein-43 to evaluate axon regeneration in an ON crush model. Changes in microglial cytokines following RGC injury was examined with ELISA and real-time PCR. In vivo studies were carried out in wild-type and trif-/- mice. A Transwell co-culture system and migration test were used to mimic the crosstalk between microglia and RGCs. TRIF-associated downstream adaptors were determined by western blotting. Compared with wild-type (WT) mice, TRIF knockout (KO) mice displayed a robust ability to regenerate axons 3 or 7 days after nerve injury. In addition, RGC survival was considerably higher in trif-/- than in WT mice. ON lesion induced less microglial activation in trif-/- than in WT mice. and more WT microglia distorted and migrated toward the foramen opticum. In the transwell system, few trif-/- microglia migrated through the membrane when stimulated by the performed lesion on RGC axons in a transwell system. Inactivation of microglial cells in trif-/- mice was associated with reduced production of inflammatory cytokines, as detected with real-time RT-PCR and ELISA. Furthermore western blot analysis showed that activation of known downstream effectors of TRIF, including TBK1, IKKε and NF-κB, were significantly inhibited by TRIF deficiency. Our results indicate that TRIF deficiency promotes ON axon regeneration by attenuating microglial activation and consequently reducing the release of harmful cytokines via NF-κB inactivation.


The role of experience in the perception of phonetic detail in children's speech: a comparison between speech-language pathologists and clinically untrained listeners.
This study examined whether experienced speech-language pathologists (SLPs) differ from inexperienced people in their perception of phonetic detail in children's speech. Twenty-one experienced SLPs and 21 inexperienced listeners participated in a series of tasks in which they used a visual-analog scale (VAS) to rate children's natural productions of target /s/-/θ/, /t/-/k/, and /d/-// in word-initial position. Listeners rated the perceived distance between individual productions and ideal productions. The experienced listeners' ratings differed from the inexperienced listeners' ratings in four ways: They had higher intrarater reliability, showed less bias toward a more frequent sound, and were more closely related to the acoustic characteristics of the children's speech. In addition, the experienced listeners' responses were related to a different set of predictor variables. Results suggest that experience working as an SLP leads to better perception of phonetic detail in children's speech. Limitations and future research are discussed.


An investigation of the reliability of YouTube videos on undescended testis.
There are thousands of patient information videos published on YouTube, the most watched video sharing platform; however, most of these videos contain incomplete or incorrect information. Interestingly, some videos with incomplete or incorrect information have a higher view rate. This study aimed to evaluate the quality of patient information videos on 'undescended testis' published on YouTube. A search was conducted on YouTube using the keywords 'undescended testis' and 'cryptorchidism', and a total of 373 videos were found. Among these, 122 patient information videos presented in the English language were examined. Four different scoring systems were used to evaluate the quality of the videos: Patient Education Materials Assessment Tool for Audiovisual Materials, Global Quality Score, Journal of American Medical Association score, and modified DISCERN scoring system. Whether the videos contained accurate and sufficient information was evaluated using a scoring system developed based on the patient information booklet prepared by the European Association of Urology (EAU) on undescended testis. The median duration (sec), number of views and number of likes of the videos were 269 (11-2484), 589 (6-1.563561) and 7 (0-4.200), respectively. According to the EAU-patient information scoring (EAU-PIS), while 32 (26.2%) of the total 122 videos contained a good level of informativeness (score: 8-10), the view rate of these videos was only 4.1% among all videos. When the top 10 most watched videos were evaluated, their mean EAU-PIS was 5.9 ± 2.81, and these videos contained a moderate level of informativeness. On the positive side, 90% of all the videos recommended surgery as a treatment option. Although YouTube is a widely used video-sharing platform, it is also a website where people or institutions can easily upload non-standardized videos due to the absence of regulations. Therefore, although it is an easily accessible source of information, it has many gaps in terms of reliability. As shown in our study, the rate of videos with accurate information was very low. It would be beneficial for viewers to be aware of this and accept YouTube as a source where they can have a general idea about a subject in which they are interested rather than using it as a reference information site. In future, YouTube can become a reference source in the medical field, especially with the standardization of medical videos through the collaboration of various organizations.


The "winged" circular anal dilator in stapled hemorrhoidectomy.
Stapled hemorrhoidectomy is gaining popularity worldwide. One problem that is often encountered is difficulty with insertion of the circular anal dilator because of very protuberant and fatty buttocks and a narrow interischial tuberosity distance. We describe a modification of this device for easier introduction in such patients.


Effects of psychosocial interventions on self-efficacy of dementia caregivers: a literature review.
Self-efficacy plays an important role in mediating stressors and physical and psychological outcomes in dementia caregiving. This literature review aims to identify, summarize, and critically appraise current evidence on the psychosocial interventions used for enhancing the self-efficacy of caregivers of patients with dementia (PWD). A database search from two major web gateways was conducted to identify relevant research articles with an intervention for caregivers of patients with any type of dementia that included self-efficacy as an outcome measure. A total of 14 studies met the criteria. The key findings and characteristics of the interventions were summarized and analyzed. The results showed that caregivers' self-efficacy and other aspects could be improved by psychosocial interventions. The efficacy of the interventions for self-efficacy and other outcomes for caregivers and PWD were explored. Recommendations on the effects and significance of various psychosocial interventions for caregivers of PWD in enhancing self-efficacy were discussed.


Laryngectomy With or Without Partial Pharyngectomy: A Systematic Review.
Complications following the total laryngectomy with or without partial pharyngectomy with neck dissection for laryngeal and pyriform fossa malignancies like aspiration, pharyngocutaneous fistula wound infection, flap necrosis, haematoma, chyle fistula and carotid blowout can cause serious implication on the final outcome of the treatment, which leads to increased postoperative morbidity, hospital stay and hospital cost. A prospective study in the Department of Otolaryngology and Head-Neck Surgery, JSS Hospital, Mysore, from November 2014 to July 2016. 30 patients undergoing Total laryngectomy with or without partial pharyngectomy for laryngeal and pyriform fossa were included in this study. The presentation, diagnosis, and management of the complications that were occurred, were discussed. The age of the patients vary between 32 and 76. Also, male preponderance was seen with approximately M:F ratio 3:1. Out of these 30 patients, 6 patients developed complications. The most common complication was pharyngocutaneous fistula (2 patients, 6%), which was developed after the 7th day. It was managed conservatively in both patients, wound infection was a second complication (2, 6%). Other complications were drain failure (1, 3%) and chylous fistula (1, 3%). The Most common complications after total laryngectomy with or without partial pharyngectomy with neck dissection in our study were wound infection and pharyngocutaneous fistula. Assessment of risk factors, early recognition of complications per operative protocols with improvised techniques are necessary to reduce incidence of complication after total laryngectomy with or without partial pharyngectomy with neck dissection.


Technical modification of the nerve-sparing laparoscopy-assisted vaginal radical hysterectomy type 3 for better reproducibility of this procedure.
The goal of this work is to make the technique of nerve-sparing laparoscopy-assisted vaginal radical hysterectomy (LAVRH) type 3 easier and less time consuming. Compared with the original LAVRH type 3, laparoscopic preparation of the cardinal ligament is extended to the transection of the upper part of the rectovaginal ligament. In vaginal approach, the preparation begins not as originally with the bladder pillar and ureter, but with transection of the rest of the rectovaginal ligament followed by dorsal eversion of the uterus and, lastly, transection of the bladder pillar with preparation of the ureters. Thirty-two consecutive patients underwent the modified nerve-sparing LAVRH type 3. The mean operative time for the vaginal part of the procedure was 54.3 min, whereas for the original technique for LAVRH type 3, the mean operative time was 143.6 min. Prior transection of the rectovaginal ligament in the vaginal approach with dorsal eversion of the uterine fundus makes preparation of the ureter and transection of the bladder pillar easier and significantly less time consuming than in the original LAVRH type 3.


Actinomycin D inhibition of monoclonal antibody binding to nucleolar phosphoprotein 37/5.2 (B23).
Actinomycin D was found to block binding of a monoclonal antibody to nucleolar phosphoprotein 37/5.2 (B23) when incubated either simultaneously with or prior to addition of the antibody. Daunorubicin had no significant blocking activity of this antigen-antibody reaction. In comparative studies with a monoclonal antibody to nucleolar phosphoprotein 110/5.2 (C23), actinomycin D exhibited little blocking activity. When a 42-mer peptide containing the epitope of protein 37/5.2 (B23) was tested as the antigen, similar inhibition by actinomycin D of binding of the monoclonal antibody was found. These results provide evidence for binding of actinomycin D to a specific epitope of protein 37/5.2 (B23).


Autism Spectrum/Pervasive Developmental Disorder.
Autism spectrum disorder is a complex disorder that is becoming more prevalent. Because of this increased prevalence, primary care providers must become more knowledgeable about the disorder so they can provide appropriate screening, evaluation, and treatment as part of an interdisciplinary team and to serve patients and families within the medical home.


Protocol for CAROM: A machine learning tool to predict post-translational regulation from metabolic signatures.
This protocol describes CAROM, a computational tool that combines genome-scale metabolic networks (GEMs) and machine learning to identify enzyme targets of post-translational modifications (PTMs). Condition-specific enzyme and reaction properties are used to predict targets of phosphorylation and acetylation in multiple organisms. CAROM is influenced by the accuracy of GEMs and associated flux-balance analysis (FBA), which generate the inputs of the model. We demonstrate the protocol using multi-omics data from E. coli. For complete details on the use and execution of this protocol, please refer to Smith et al. (2022).


Novel rhamnose-binding lectins from the colonial ascidian Botryllus schlosseri.
In a full-length cDNA library from the compound ascidian Botryllus schlosseri, we identified, by BLAST search against UniProt database, five transcripts, each with complete coding sequence, homologous to known rhamnose-binding lectins (RBLs). Comparisons of the predicted amino acid sequences suggest that they represent different isoforms of a novel RBL, called BsRBL-1-5. Four of these isolectins were found in Botryllus homogenate after purification by affinity chromatography on acid-treated Sepharose, analysis by reverse-phase HPLC and mass spectrometry. Analysis of both molecular masses and tryptic digests of BsRBLs indicated that the N-terminal sequence of the purified proteins starts from residue 22 of the putative amino acid sequence, and residues 1-21 represent a signal peptide. Analysis by mass spectrometry of V8-protease digests confirmed the presence and alignments of the eight cysteines involved in the disulphide bridges that characterise RBLs. Functional studies proved the enhancing effect on phagocytosis of the affinity-purified material. Results are discussed in terms of phylogenetic relationships of BsRBLs with orthologous molecules from protostomes and deuterostomes.


Novel photoswitchable receptors: synthesis and cation-induced self-assembly into dimeric complexes leading to stereospecific [2+2]-photocycloaddition of styryl dyes containing a 15-crown-5 ether unit.
Styryl dyes 4a-e containing a 15-crown-5 ether unit and a quinoline residue with a sulfonatoalkyl or sulfonatobenzyl N-substituent were synthesized. The relationship between the photochemical behavior of these dyes and their aggregates derived from complexation with Mg(2+) in MeCN was studied using (1)H NMR and absorption spectroscopy. The E-isomers of 4a-e were shown to form highly stable dimeric (2:2) complexes with Mg(2+). Upon irradiation with visible light, the dimeric complexes undergo two competing photoreactions, viz., geometric E --> Z isomerization, resulting in an anion-capped 1:1 complex of the Z-isomer with Mg(2+) and stereospecific syn-head-to-tail [2+2]-cycloaddition, affording a single isomer of bis-crown-containing cyclobutane. The N-substituent in the dye has a dramatic effect on the photochemical behavior of the dimeric complex. Molecular dynamics and semiempirical quantum-chemical calculations were carried out to interpret the observed photocycloaddition in the dimer. Conformational equilibria for the dimer of (E)-4b were analyzed using (1)H NMR spectroscopy.


Identification of tyrosine 187 as a protein kinase C-delta phosphorylation site.
Protein kinase C-delta (PKC-delta) has been demonstrated to be phosphorylated on tyrosine residue(s) in many different biological systems (Li, W., Yu, J.-C., Michieli, P., Beeler, J. F., Ellmore, N., Heidaran, M. A., and Pierce, J. H. (1994) Mol. Cell. Biol. 14, 6727-6735; Li, W., Mischak, H., Yu, J.-C., Wang, L.-M., Mushinski, J. F., Heidaran, M. A., and Pierce, J. H. (1994) J. Biol. Chem. 269, 2349-2352; Denning, M. F., Dlugosz, A. A., Howett, M. A., and Yuspa, S. H. (1993) J. Biol. Chem. 268, 26079-26081). Tyrosine phosphorylation of PKC-delta has also been shown to occur in vitro when purified PKC-delta is coincubated with different tyrosine kinase sources. However, the tyrosine phosphorylation site(s) is currently unknown and the exact effect of this phosphorylation on its serine/threonine kinase activity and biological functions is still controversial. To directly investigate the potential role of PKC-delta tyrosine phosphorylation, tyrosine 187 was converted to phenylalanine (PKC-deltaY187F) by site-directed mutagenesis, and expression vectors containing PKC-deltaY187F cDNAs were transfected into both 32D myeloid progenitor cells and NIH 3T3 fibroblasts. The results showed that tyrosine 187 of PKC-delta became phosphorylated in vivo in response to 12-O-tetradecanoylphorbol-13-acetate stimulation or platelet-derived growth factor receptor activation. In vivo labeling and subsequent two-dimensional phosphopeptide analysis demonstrated that one phosphopeptide was absent in PKC-deltaY187F when compared to wild type PKC-delta, further substantiating that tyrosine 187 of PKC-delta is phosphorylated in vivo. Although the phosphotyrosine content of PKC-deltaY187F was reduced compared with PKC-deltaWT, the kinase activity of PKC-deltaY187F toward a PKC-delta substrate was not altered. Moreover, 12-O-tetradecanoylphorbol-13-acetate-mediated monocytic differentiation of 32D cells was not affected by expression of the PKC-deltaY187F mutant. Taken together, these results suggest that tyrosine phosphorylation of PKC-delta on 187 may not influence PKC-delta activation and known functions.


[The biological effect of verapamil on hypertrophic scar fibroblast].
To study the mechanism of calcium channel antagonist Verapamil on the treatment of hypertrophic scar and explore the possibility of further clinical application. After six strains of HSFB were cultured in vitro, we investigated HSFB proliferation by MTT method, investigated HSFB collagen synthesis by 3H-proline uptaken and Hydroxyproline colorimetric analysis, and investigated collagen gene expression by Northern Blot. Verapamil can inhibit HSFB proliferation, collagen synthesis and gene expression by a dose-depended manner, especially treated with 100 mumol/L Verapamil. By inhibiting I, III procollagen gene expression, Verapamil can inhibit the formation of hypertrophic scar.


Effects of aromatherapy massage on face-down posture-related pain after vitrectomy: a randomized controlled trial.
Postoperative face-down posturing (FDP) is recommended to optimize the effects of intraocular gas tamponade after vitrectomy. However, patients undergoing FDP usually experience physical and psychological burdens. This 3-armed, randomized, single-center trial investigated the effects of aromatherapy on FDP-related physical pain. Sixty-three patients under FDP were randomly allocated to one of three treatment groups: aromatherapy massage with essential oil (AT), oil massage without essential oil (OT), and a control group. The AT and OT groups received 10 minutes of massage by ward nurses trained by an aromatherapist, while the control group received usual care. Outcomes were assessed as short-term (pre- to post-intervention) and long-term (first to third postoperative day) changes in physical pain in five body regions using face-scale. The AT and OT groups both revealed similar short-term pain reductions after intervention, compared with the control group. Regarding long-term effects, neither group experienced significant effects until the second day. Significantly more pain reduction compared with usual care occurred on the third day, mainly in the AT group, though there were few significant differences between the AT and OT groups. In conclusion, this study suggests that simple oil massage is an effective strategy for immediate pain reduction in patients undergoing FDP, while aromatherapy may have a long-term effect on pain reduction.


Phenotypic heterogeneity of corneal endothelium in iridocorneal endothelial syndrome by in vivo confocal microscopy.
To present a case of iridocorneal endothelial (ICE) syndrome showing phenotypic heterogeneity of endothelial morphology between the 2 eyes of a patient as visualized by in vivo confocal microscopy (IVCM). Confocal microscopy using the Heidelberg Retina Tomograph (HRT)-3 with Rostock Cornea Module was performed bilaterally during routine follow-up on a 60-year-old lady being managed as a case of ICE syndrome with secondary glaucoma in the right eye. IVCM revealed endothelial changes in both eyes, which however varied in morphology. Endothelium of the right eye showed a "total ICE" pattern with "ICE-type of cells," that is, diffuse involvement with enlarged, pleomorphic "epithelioid" cells having hyper-reflective nuclei and no intervening areas of the normal endothelium. The left endothelium had broad areas of normal hexagonal endothelial mosaic interspersed with different types of ICE cells showing nipple-shaped evaginations, light dark reversal and central craters with hyper-reflective rims. This report with the help of IVCM demonstrates that though ICE syndrome is a clinical entity which classically has been considered predominantly unilateral, the endothelial changes can be bilateral and heterogeneous. The apparent heterogeneity in the present case may represent 2 different stages of the disease process at the level of the corneal endothelium-advanced disease OD and presymptomatic disease OS.


Is additional epidural sympathetic block in microvascular surgery contraindicated? A preliminary report.
The use of additional epidural sympathetic block during and after microvascular surgery in the lower extremities to prevent vasospasm is generally agreed on. However, a significant fall in the perfusion rate of the transplants was seen after application of bupivacaine (Marcain) via the epidural catheter. This effect has, to our knowledge, not been described before and is probably caused by the sympathectomy effect of this type of analgesia.


Upregulation of a histone-like protein in dormant Mycobacterium smegmatis.
The aerobic saprophyte Mycobacterium smegmatis, like its pathogenic counterpart M. tuberculosis, has the ability to adapt to anaerobiosis by shifting down to a dormant state. Here, we report the identification and molecular genetic characterisation of the first dormancy-induced protein in M. smegmatis. Comparative SDS-polyacrylamide gel electrophoresis of protein extracts of aerobically growing and dormant anaerobic M. smegmatis cultures revealed the upregulation of a 27-kDa protein in the dormant state. Peptide sequencing showed that the induced protein is a homologue of the histone-like protein H1p, predicted by the M. tuberculosis genome project. The corresponding hlp gene was cloned from M. smegmatis and sequenced. Disruption of the hlp gene eliminated the histone-like protein but did not affect the viability of the dormant culture.


Differential effects of petit mal anticonvulsants and convulsants on thalamic neurones: GABA current blockade.
1. Currents evoked by applications of gamma-aminobutyric acid (GABA) to acutely dissociated thalamic neurones were analysed by voltage-clamp techniques, and the effects of the anticonvulsant succinimides ethosuximide (ES) and alpha-methyl-alpha-phenylsuccinimide (MPS) and the convulsants tetramethylsuccinimide (TMS), picrotoxin, pentylenetetrazol (PTZ), and bicuculline methiodide were assessed. 2. TMS (1 microM-10 microM) reduced responses to iontophoretically applied GABA, as did picrotoxin (0.1-100 microM), PTZ (1-100 mM) and bicuculline (1-100 microM). 3. ES, in high concentrations (1-10 mM), reduced GABA responses to a lesser extent, and also occluded the reductions in GABA-evoked currents produced by TMS, picrotoxin, and PTZ. ES did not occlude the effects of bicuculline on GABA responses. Therefore, we propose that ES acts as a partial agonist at the picrotoxin GABA-blocking receptor. 4. MPS had no effect on GABA responses (at a concentration of 1 mM), and, like ES, occluded the GABA-blocking actions of TMS, apparently acting as a full antagonist. 5. The anticonvulsant actions of ES and MPS against TMS and PTZ-induced seizures may thus involve two independent mechanisms: (1) the occlusion of TMS and PTZ GABA-blocking effects; and (2) the previously described specific effect of ES and MPS on low-threshold calcium current of thalamic neurones. The latter cellular mechanism may be more closely related to petit mal anticonvulsant activity.


Inter-tumor heterogeneity and radiation dose-control curves.
This communication presents a theoretical analysis of the influence of inter-tumor heterogeneity on clinical radiation dose-response curves. Any clinically defined group of tumors consists of individuals each having a unique individual dose-control relation (I-TCP/D). This I-TCP/D relation is steep and is based on Poisson statistics. The population as a whole possesses a heterogeneous dose-control relation (H-TCP/D relation) that is a resultant of the weighted summation of the I-TCP/D curves, each weighted according to its relative frequency in the population. This summation leads to an H-TCP/D curve that is considerably flatter than the steep portion of any I-TCP/D curve. For any specified radiation regimen, three subclasses of tumors exist in any population: the stochastic fraction, which consists of those tumors whose individual tumor control probability lies between 99% and 1% and individual outcome is probabilistic; the refractory fraction, which consists of those tumors each of which has no prospect for control with the specified treatment; and the sensitive fraction, which consists of tumors each of which is absolutely controllable with the specific treatment. Based on plausible parameters, it is estimated that, for tumors associated with an overall tumor control probability of approximately 50%, some 70-85% of failures come from a predictably radioresistant fraction. To optimize and improve the radiation therapy of tumors with unsatisfactory local control, it is necessary to predictably identify the location of each individual in one of the three subclasses.


Early Harvest Effects on Hydrophilic Phenolic Components of Extra Virgin Olive Oils Cvs. 'Ayvalık', 'Memecik' and 'Topakaşı'.
The study was conducted to determine the effects of cultivar, harvest period and their interaction on the hydrophilic phenolic components extra virgin olive oils of the cultivars 'Ayvalık', 'Memecik' and 'Topakaşı'. Olives were collected at three different harvesting periods; (1) early harvest period-1 (Beginning of spotting), (2) early harvest period-2 (End of spotting), and (3) optimum harvest period. Oils were extracted using an abencor system. HPLC (High-performance liquid chromatograph) technique was used to quantify The phenolic compounds including: tyrosol (p-HPEA), hydroxytyrosol (3,4-DHPEA), luteolin, rutin, quercetin, catechin, sinapinic acid, p-coumaric acid, cinnamic acid, vanillin, vanillic acid, ferulic acid and gallic acid were quantified using HPLC. The results indicated that the effects of harvest period on the phenolic components were variety dependent. At the early harvest period-1, 'Memecik' and 'Topakaşı' had the highest efficiency in luteolin, cinnamic acid, vanillic acid, and ferulic acid contents, while 'Ayvalık' had the highest efficiency in hydroxytyrosol, sinapinic acid, p-coumaric, vanillin and ferulic acid contents. At the optimum harvest period, 'Ayvalık' had the highest efficiency in luteolin, tyrosol and gallic acid contents, while 'Topakaşı' had the highest efficiency in tyrosol, hydroxytyrosol and rutin content. The highest phenolic content was detected in the early harvest period-1. The content of tyrosol linearly increased with the progress of maturity harvest period, whereas the contents of the sinapinic acid, vanillin, vanilic acid and ferulic acid decreased. The oils of 'Memecik' variety had significantly higher phenolic content than those of 'Ayvalık' and 'Topakaşı' varieties.


A mathematical model for the force and energetics in competitive running.
A simple mathematical model for competitive running is developed. This model contains the force and energy reserves as key variables and it described their relationship and dynamics. It is made up of three submodels for the biomechanics of running the energetics and the optimization. The model for the energetics is an extension of the hydraulic model of Margaria and Morton. The key geometric parameters of this piecewise linear, three compartment model are determined on the basis of well known physiological facts and data.


Hebbian crosstalk and input segregation.
Hebbian synapses respond to input/output correlations, and thus to input statistical structure. However, recent evidence suggests that strength adjustments are not completely connection-specific, and this "crosstalk" could distort, or even prevent, learning processes. Crosstalk would then be a form of adjustment mistake, analogous to mistakes in polynucleotide copying. The mutation rate must be extremely low for successful evolution (which is a type of learning process), and similarly neural learning might require minimal crosstalk. We analyze aspects of the effect of crosstalk in Hebbian learning from pairwise input correlations, using the classical Oja model. In previous work we showed that crosstalk leads to learning of the principal eigenvector of EC (the input covariance matrix pre-multiplied by an error matrix that describes the crosstalk pattern), and found that, with positive input correlations, increasing crosstalk smoothly degrades performance. However, the Oja model requires negative input correlations to account for biological ocular segregation. Although this assumption is biologically somewhat implausible, it captures features that are seen in more complex models. Here, we analyze how crosstalk would affect such segregation. We show that, for statistically unbiased inputs, crosstalk induces a bifurcation from segregating to non-segregating outcomes at a critical value which depends on correlations. We also investigate the behavior in the vicinity of this critical state and for weakly biased inputs. Our results show that crosstalk can induce a bifurcation under special conditions even in the simplest Hebbian models, and that even the low levels of crosstalk observed in the brain could prevent normal development. However, during learning pairwise input statistics are more complex, and crosstalk-induced bifurcations may not occur in the Oja model. Such bifurcations would be analogous to "error catastrophes" in genetic models, and we argue that they are usually absent for simple linear Hebbian learning because such learning is only driven by pairwise correlations.


Major depression with melancholia: a comparison of middle-aged and elderly adults.
Patients admitted to an inpatient psychiatric service were screened to identify middle-aged (35 to 50 years of age) and elderly (60 years of age and over) patients suffering from a major depressive episode with melancholia. Thirty-seven subjects (18 middle-aged and 19 elderly) were identified. Criteria symptoms for depression and symptoms specifically associated with melancholic or endogenous depression did not differ across age groups, with few exceptions. Major depression with melancholia in this hospitalized population was symptomatically similar in the middle-aged and elderly. The syndrome is therefore relatively common on this inpatient service and should be easily recognized.


The evaluation of intensity of traffic noise in different points of town routes.
The aim of the study was measuring noise intensity in the selected points of traffic routes in the town of Lublin. Investigations were carried out at 11 points located in the centre of the town and at escape roads. Noise value levels showed variable intensity, the highest being observed in the morning and afternoon hours. The highest mean level of noise intensity was recorded at the crossing of Solidarności Avenue and Sikorskiego Street, and the lowest in Narutowicza Street.


Intra-individual physiological response of recreational runners to different training mesocycles: a randomized cross-over study.
Pronounced differences in individual physiological adaptation may occur following various training mesocycles in runners. Here we aimed to assess the individual changes in performance and physiological adaptation of recreational runners performing mesocycles with different intensity, duration and frequency. Employing a randomized cross-over design, the intra-individual physiological responses [i.e., peak ([Formula: see text]) and submaximal ([Formula: see text]) oxygen uptake, velocity at lactate thresholds (V2, V4)] and performance (time-to-exhaustion (TTE)) of 13 recreational runners who performed three 3-week sessions of high-intensity interval training (HIIT), high-volume low-intensity training (HVLIT) or more but shorter sessions of HVLIT (high-frequency training; HFT) were assessed. [Formula: see text], V2, V4 and TTE were not altered by HIIT, HVLIT or HFT (p > 0.05). [Formula: see text] improved to the same extent following HVLIT (p = 0.045) and HFT (p = 0.02). The number of moderately negative responders was higher following HIIT (15.4%); and HFT (15.4%) than HVLIT (7.6%). The number of very positive responders was higher following HVLIT (38.5%) than HFT (23%) or HIIT (7.7%). 46% of the runners responded positively to two mesocycles, while 23% did not respond to any. On a group level, none of the interventions altered [Formula: see text], V2, V4 or TTE, while HVLIT and HFT improved [Formula: see text]. The mean adaptation index indicated similar numbers of positive, negative and non-responders to HIIT, HVLIT and HFT, but more very positive responders to HVLIT than HFT or HIIT. 46% responded positively to two mesocycles, while 23% did not respond to any. These findings indicate that the magnitude of responses to HIIT, HVLIT and HFT is highly individual and no pattern was apparent.


Subunit fusion of two yeast D-amino acid oxidases enhances their thermostability and resistance to H2O2.
D-amino acid oxidases from Rhodosporidium toruloides and Trigonopsis variabilis (RtDAO and TvDAO) are both yeast homodimeric flavoenzymes. Two of their cDNA genes were connected by a hexanucleotide linker and heterologously expressed in E. coli to produce the corresponding double DAOs (dRtDAO and dTvDAO) with two subunits fused into a single polypeptide. The specific activities of double DAOs remained similar to those of native dimeric DAOs, although the catalytic efficiencies (k(cat)/K(M)) were decreased due to higher K(M) values. The T(m) value for dRtDAO was shifted 5 degrees C higher while that for dTvDAO was increased only by 2 degrees C, in comparison with the corresponding native counterparts. In the presence of 10 mM H(2)O(2), dRtDAO and dTvDAO exhibited half-lives of about 60 and 40 min, respectively, which were 2- and 1.5-fold, respectively, longer than their native DAOs. These yeast DAOs can therefore be thermally and oxidatively stabilized by linking their subunits together.


Effect of CaCl2 as activity stabilizer on purification of heparinase I from Flavobacterium heparinum.
Heparinase I has been purified from F. heparinum by a novel scheme with 10mM CaCl(2) added in crude extracts of cells. The enzyme was purified to apparent homogeneity through ammonium sulfate precipitation, Octyl-Sepharose chromatography, CM-52 chromatography, SP-650 chromatography, and Sephadex G-100 gel filtration chromatography. The specific activity of the purified enzyme was 90.33 U/mg protein with a purification fold of 185.1. The yield was 17.8%, which is higher than any previous scheme achieved. The molecular weight of the purified enzyme was 43 kDa with a pI of 8.5. It has an activity maximum at pH range of 6.4-7.0 and 41 degrees C. CaCl(2) is a good stabilizer of the purified enzyme in liquid form toward either storaging at 4 degrees C or freezing-thawing.


Eyes of the Beholders: First-year medical students' perceptions of surgeons and the field of surgery.
Medical students have negative perceptions of surgery prior to their clerkships. To explore possible explanations, we examined the association between these perceptions, individual identity and vulnerability to stereotype threat (ST). All first-year medical students at a single school received an electronic survey which assessed identity groups, vulnerability to ST and perceptions of surgeons/surgery. Multi-method analyses examined these associations. Women held more negative than positive views about the field of surgery (p = 0.007) but not surgeons. Students vulnerable to ST had negative views about both surgeons (p < 0.0001) and surgery (p = 0.007). They were also less interested in pursuing a surgical career compared to non-vulnerable students (56% vs. 80% p = 0.03). For some students, negative views of surgeons and surgery appear to be associated with individual identity and ST. Future research should aim to confirm these findings and identify strategies to develop positive perceptions for these populations.


The impact of noise and missing fragmentation cleavages on de novo peptide identification algorithms.
Proteomics aims to characterise system-wide protein expression and typically relies on mass-spectrometry and peptide fragmentation, followed by a database search for protein identification. It has wide ranging applications from clinical to environmental settings and virtually impacts on every area of biology. In that context, de novo peptide sequencing is becoming increasingly popular. Historically its performance lagged behind database search methods but with the integration of machine learning, this field of research is gaining momentum. To enable de novo peptide sequencing to realise its full potential, it is critical to explore the mass spectrometry data underpinning peptide identification. In this research we investigate the characteristics of tandem mass spectra using 8 published datasets. We then evaluate two state of the art de novo peptide sequencing algorithms, Novor and DeepNovo, with a particular focus on their performance with regard to missing fragmentation cleavage sites and noise. DeepNovo was found to perform better than Novor overall. However, Novor recalled more correct amino acids when 6 or more cleavage sites were missing. Furthermore, less than 11% of each algorithms' correct peptide predictions emanate from data with more than one missing cleavage site, highlighting the issues missing cleavages pose. We further investigate how the algorithms manage to correctly identify peptides with many of these missing fragmentation cleavages. We show how noise negatively impacts the performance of both algorithms, when high intensity peaks are considered. Finally, we provide recommendations regarding further algorithms' improvements and offer potential avenues to overcome current inherent data limitations.


The optimal time of starting adjuvant chemotherapy after curative surgery in patients with colorectal cancer.
Postoperative adjuvant chemotherapy (AC) is now well-accepted as standard for high-risk stage II and stage III colorectal cancer (CRC) patients, however the optimal time to initiate AC remains elusive. A comprehensive literature search was performed using the PubMed and Embase databases. The Hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate primary endpoints. All analyses were conducted using Stata software version 12.0 with the Random-effects model. A total of 30 studies were included in our study. Upon comparison on overall survival (OS), we identified that delaying the initiation of AC for > 8 weeks after operation was significantly associated with poor OS (HR: 1.37; 95% CI: 1.27-1.48; P < 0.01). The poor prognostic value of AC delay for > 8 weeks was not undermined by subgroup analysis based on region, tumor site, sample size and study quality. No obvious differences were observed in survival between AC within 5-8 weeks and ≤ 4 weeks (HR: 1.03; 95% CI: 0.96 -1.10; P = 0.46). Moreover, two studies both highlighted that the survival benefit of AC was still statistically significant when AC was applied 5-6 months after surgery compared with the non-chemotherapy group. Delaying the initiation of AC for > 8 weeks after surgery was significantly associated with poor OS. AC started within 8 weeks after surgery brought more benefits to CRC patients. There were no obvious differences in survival benefits between AC within 5-8 weeks and ≤ 4 weeks. Compared to patients not receiving AC after surgery, a delay of approximately 5-6 months was still useful to improve prognosis.


Erythropoiesis in the thymus of the spotless starling, Sturnus unicolor.
Although previously described in other avian species, intrathymic erythropoiesis is a remarkable feature of the thymus of Sturnus unicolor. In discrete stages of the life cycle of this species, erythroblasts and mature erythrocytes occupy large areas of the thymic cortex and cortico-medullary border. Simultaneously, degenerated thymocytes and epithelial-reticular cells occur in the same areas. The relationship between intrathymic erythropoiesis, degeneration of cortical lymphocytes and epithelial-reticular cells, and macrophage activity is discussed and related to a possible functional role of sex hormones in this phenomenon.


Study of mechanisms of electric field-induced DNA transfection. V. Effects of DNA topology on surface binding, cell uptake, expression, and integration into host chromosomes of DNA in the mammalian cell.
Neumann and coworkers (Neumann, E., M. Schaefer-Ridder, Y. Wang, and P. H. Hofschneider. 1982. EMBO J. 1:841-845) have shown that the efficiency of pulsed electric field (PEF)-induced DNA transfection of mouse L-cells by the thymidine kinase gene is several times higher for the linear DNA than for the closed circular DNA. Transfection of Escherichia coli bacteria by several plasmids indicates that the transfection efficiency was much higher for the closed circular/supercoiled (sc-) and circular/relaxed (cr-) DNA than for the linearized (In-) DNA (Xie, T. D., L. Sun, H. G. Zhao, J. A. Fuchs, and T. Y. Tsong. 1992. Biophys. J. 63:1026-1031). To resolve these conflicting observations, we have systematically examined electrotransfection of NIH3T3 mouse fibroblast by the plasmids, pRSVcat, pRSVneo, and pRSVgpt. Mg(2+)-facilitated surface binding of DNA before, and DNA uptake by 3T3 cells after treatment with PEF, were monitored by 3H-labeled plasmids. Transfection efficiency was evaluated by both the transient expression of chloramphenicol acetyltransferase (cat) activity 2-3 days after, and the permanent expression of neomycin phosphotransferase (neo) and xanthine-guanine phosphoribosyltransferase (gpt) genes in the transformants 2 weeks after the PEF treatment. Our results indicate that cell surface binding and PEF-induced cell uptake of DNA did not depend on the topology of DNA. However, both the transient and the permanent expression of the plasmids were three to five times more efficient for the cr-DNA and the sc-DNA than for the in-DNA. These results indicate that electrotransfection of cells involves several steps: the cation-dependent binding of DNA to the cell surface, the electric field-driven DNA entry into the cells, the transient expression of DNA, and the integration of DNA into the host chromosomes. For understanding mechanisms of electrotransfection, only the DNA binding to the cell surface and the electric field assisted membrane-crossing of DNA are relevant. Both the expression of the loaded DNA and the DNA integration into the host chromosomes depend more on the properties of the cell and its interactions with a foreign gene. Since these properties and interactions will be similar irrespective of the method chosen to facilitate DNA transfer, they are not relevant for the study of mechanisms of electrotransfection. Our results also support the idea that the PEF-induced cellular uptake of DNA is mainly by the electrophoresis of the surface bound DNA across the plasma membrane.


Subclinical cardiological involvement in Sicilian patients with pure congenital muscular dystrophy.
Congenital muscular dystrophies (CMD) are a heterogeneous group of diseases characterized by a marked weakness, generalized hypotonia, joint contractures and a muscle biopsy suggestive of dystrophic changes. The aim of this study has been to assess the prevalence of heart involvement in merosin-positive CMD patients examined by echocardiography and Doppler. A total of 10 merosin-positive CMD patients and 100 healthy children were evaluated by echocardiography and Doppler examinations and the results were compared. Three out of 10 patients showed a reduction of the ejection fraction and of the shortening fraction; in 1 case, a dilatation of left ventricular diastolic diameter was observed. In the 10 patients examined by echocardiography and Doppler, a heart involvement has been observed in 25% of cases.


[The study of joint inheritance of mutations impairing the structure of meiotic chromosomes in rye Secale cereale L].
Genetic analysis has demonstrated that meiotic mutations mei8 (irregular condensation and fragmentation of meiotic chromosomes) and mei10 (chromosome overcompaction) are nonallelic. Mutation mei10 exhibits digenic inheritance (with a segregation ratio of 13:3) in the combinations of crosses studied. It is assumed that the phenotypic expression of mutation mei10 is suppressed by the effect of recessive gene lch1 or lch2 (long chromosomes), both of which have been revealed in one of the parental lines (Mc10). These genes determine weak condensation of meiotic chromosomes. In double mutants mei8 mei10, the mutations are expressed independently of each other. Gene mei10 is linked with gene mei8 (r = 36.8 +/- 5.38%); genes lch1 and lch2 are not linked either with them or with each other. Taking into account the data on the linkage between genes mei10 and sy10 and between mei8 and sy10, the order of genes in the linkage group is shown to the following: mei8-sy10-mei10.


CdS QDs: Facile synthesis, design and application as an "on-off" sensor for sensitive and selective monitoring Cu2+, Hg2+ and Mg2+ in foods.
A new yellow CdS quantum dots (CdS QDs) with 59% quantum yield were synthesized successfully by one-pot method using thioglycolic acid as stabilizer, thiourea and sodium sulfide as double reducing agents. Based on CdS QDs, a novel "on-off" sensor for detecting Cu2+, Hg2+ and Mg2+ in foods has been constructed in the presence of glutathione (GSH). The fluorescence intensity of CdS QDs is improved about 1.5-fold by GSH, then quenched linearly by Cu2+, Hg2+ and Mg2+ owning to the electron transfer or ligand competition. Interestingly, without GSH, CdS QDs has no fluorescence response to Hg2+ at all, and with GSH, linear ranges of Cu2+ and Mg2+ is not only broader, but sensitivities are improved 16.9-fold for Cu2+ and 8.5-fold for Mg2+. GSH-CdS QDs sensor discloses a more sensitive, efficient and selective methodology for monitoring Cu2+, Hg2+ and Mg2+ in further heavy metal pollution and food safety.


Origin of low Young modulus of multicomponent, biomedical Ti alloys - Seeking optimal elastic properties through a first principles investigation.
Multicomponent, biomedical β-Ti alloys offer ultra-low Young modulus values that are related to a unique and poorly understood reduction of C44 and C' elastic constants in comparison with binary systems. The elastic properties of such materials are difficult to control due to the large variations occurring even for a small change in chemical composition, which cannot be explained using existing theories. In this article, we investigate the above issues through systematic ab initio elastic constants calculations for a series of binary, ternary and quaternary Ti alloys. Special attention is paid to examining the reliability of the methodology adopted and to clarifying the atomic scale mechanisms that affect the mechanical properties of the systems analysed. It was found that the lower boundary of the polycrystalline Young modulus of Ti-Nb-base β phase is close to 50 GPa, and strongly depends on two specific electronic hybridisations related to niobium and simple metals addition that control C44 and C'. Based on the relationship established between electronic structure and mechanical properties, we propose several quaternary alloys whose directional <100> Young modulus values are equal or similar to that of human bones. Some electronic-based guidelines for designing new multicomponent β-Ti alloys are also formulated.


The Emerging Roles of Tripartite Motif Proteins (TRIMs) in Acute Lung Injury.
Acute lung injury (ALI) is an inflammatory disorder of the lung that causes high mortality and lacks any pharmacological intervention. Ubiquitination plays a critical role in the pathogenesis of ALI as it regulates the alveolocapillary barrier and the inflammatory response. Tripartite motif (TRIM) proteins are one of the subfamilies of the RING-type E3 ubiquitin ligases, which contains more than 80 distinct members in humans involved in a broad range of biological processes including antivirus innate immunity, development, and tumorigenesis. Recently, some studies have shown that several members of TRIM family proteins play important regulatory roles in inflammation and ALI. Herein, we integrate emerging evidence regarding the roles of TRIMs in ALI. Articles were selected from the searches of PubMed database that had the terms "acute lung injury," "ubiquitin ligases," "tripartite motif protein," "inflammation," and "ubiquitination" using both MeSH terms and keywords. Better understanding of these mechanisms may ultimately lead to novel therapeutic approaches by targeting TRIMs for ALI treatment.


[Analysis on epidemiologic characteristics of viral diarrhea among infants in Taiyuan, Shanxi province, 2007-2008].
To study the epidemiologic characteristics of virus-induced acute diarrhea in children under 5 years old in Taiyuan, Shanxi province. Stool specimens and clinical data were collected from 346 inpatients with acute diarrhea from children less than 5 years old. Rotavirus-positive specimens were identified by ELASA kit. Calicivirus and astrovirus were detected by reverse transcription-polymerase chain reaction (RT-PCR). Adenovirus was done by polymerase chain reaction (PCR). Of the 346 specimens, the percentage of samples with Rotavirus, Calicivirus, Astrovirus, and Adenovirus was 40.8%, 7.5%, 6.4% and 3.2%. Among 141 rotavirus positive samples, serotype G1 (42.6%) was the predominant strain. More than 95% of viral diarrhea patients under hospitalization occurred among children younger than 2 years. Rotavirus is the major pathogen contributing to the acute diarrhea. The disease generally peaks at autumn/winter. The predominant rotavirus strain circulated was G1P[8].


Working Memory Is Complex and Dynamic, Like Your Thoughts.
Working memory is where thoughts are held and manipulated. For many years, the dominant model was that working memory relied on steady-state neural dynamics. A neural representation was activated and then held in that state. However, as often happens, the more we examine working memory (especially with new technology), the more complex it looks. Recent discoveries show that working memory involves multiple mechanisms, including discontinuous bouts of spiking. Memories are also dynamic, evolving in a task-dependent manner. Cortical rhythms may control those dynamics, thereby endowing top-down "executive" control over our thoughts.


[A 30-year-old man with a puddle of pleural effusion].
The pleural effusion found in urinothorax is traditionally classified as transudate. In some cases, however, the Light-criteria can show an exudate. We describe the case of a 30-year-old man who attended the emergency department with shortness of breath and severe, diffuse, chest pain; this occurred two days after he had undergone a left-sided percutaneous nephrolithotomy by a urologist. A chest X-ray showed pleural effusion in the left basal region. Based on the Light-criteria, this effusion was an exudate. We made the diagnosis of urinothorax following percutaneous nephrolithotomy. When urinothorax is suspected, biochemical analysis can reveal either a transudate or an exudate. The pleural fluid/serum creatinine ratio can be a valuable addition to the Light-criteria in this setting. The Light-criteria should always be interpreted in a clinical context.


Measurements of HIV viral loads from different levels of the respiratory tract.
The lung is a common site of disease in HIV infection. Virus has been detected in BAL fluid (BALF) and saliva. However, the relationship between viral loads detected at different levels of the respiratory tract is unknown. We measured simultaneous HIV viral loads in parotid saliva (PS), bronchial fluid (BF), BALF, and plasma by reverse transcription polymerase chain reaction in 20 HIV-infected individuals. HIV was detected in 53% of BALF samples, 15% of BF samples, 5% of PS samples, and 88% of plasma samples. Viral loads in plasma and BALF samples were positively correlated. There were significantly higher levels of HIV viral load in both plasma and BALF in subjects with CD4 counts of < 200 cells/ microL compared to those with higher counts. Antiretroviral therapy (ART) was associated with lower BALF and plasma viral loads, and the effect in BALF was independent of the plasma viral load. Interestingly, smoking also was associated with lower levels of both BAL and BF viral loads, independent of the plasma viral load. These data demonstrate that while HIV can be detected in the respiratory tract, the viral load is influenced by both local factors (ie, level of the respiratory tree and cigarette smoking) and systemic factors (ie, ART and peripheral CD4 count).


Correction: X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Free and protein-bound rat serum peptides.
Some of the free serum peptides circulate in blood bound to the serum proteins. Conditions used in protein precipitation influence the peptide affinity to the protein. The lability of the bonds between peptides and their carrier proteins may be of physiological importance.


Adenovirus vector-based vaccine for infectious diseases.
Replication-incompetent adenovirus (Ad) vectors have been widely used as gene delivery vehicles in both gene therapy studies and basic studies for gene function analysis due to their highly advantageous properties, which include high transduction efficiencies, relatively large capacities for transgenes, and high titer production. In addition, Ad vectors induce moderate levels of innate immunity and have relatively high thermostability, making them very attractive as potential vaccine vectors. Accordingly, it is anticipated that Ad vectors will be used in vaccines for the prevention of infectious diseases, including Ebola virus disease and acquired immune deficiency syndrome (AIDS). Much attention is currently focused on the potential use of an Ad vector vaccine for coronavirus disease 2019 (COVID-19). In this review, we describe the basic properties of an Ad vector, Ad vector-induced innate immunity and immune responses to Ad vector-produced transgene products. Development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccines to several infectious diseases are also discussed.


Facile synthesis and high d33 of single-crystalline KNbO3 nanocubes.
Single-crystalline KNbO(3) nanocubes with orthorhombic phase were prepared in a large scale by a simple one-step molten salt route without using any surfactant as template; the nanostructures exhibited high piezoelectric properties such as d(33)=105 pC/N and k(p)=0.34 as piezoelectric materials.


A randomized controlled trial on the digital socio-emotional competence training Zirkus Empathico for preschoolers.
In this randomized controlled trial (RCT), the digital socio-emotional competence training Zirkus Empathico was tested in 74 Central European children (5.1 (0.9) years; 34 females) within a longitudinal design (three time points: T1 = pre-training; T2 = immediately following 6-week training, T3 = 3-month follow-up). The pre-registered primary outcome was empathy, secondary outcomes included emotion recognition, prosocial behavior, and behavioral problem reduction; furthermore, children's neural sensitivity to facial expressions quantified with event-related potentials. Compared to controls (N = 38), Zirkus Empathico participants (N = 36) showed increases in empathy (d = 0.28 [-0.17, 0.76]), emotion recognition (d = 0.57 [0.01, 1.06]), prosocial behavior (d = 0.51 [0.05, 0.99]) and reduced behavioral problems (d = 0.54 [0.08, 1.03]). They also showed larger P3 amplitudes to happy vs. angry and neutral facial expressions post-training. Thus, Zirkus Empathico may be a promising digital training for social competence in preschoolers.


The simultaneous examination of economic and social factors in destination selection: employing objective and subjective measures.
This research examines the role of social and economic factors in the past selection of destinations made by migrants living in Rhode Island. Results indicate that social ties play a more important role in the selection of destinations with low levels of opportunity than they do in the movement to high opportunity areas. An important aspect of the study was the simultaneous investigation of both objective and subjective measures of social and economic factors in the selection of low and high growth destinations. The analysis suggests that the simultaneous consideration of objective and subjective factors provides a more refined accounting of the potential influence of social and economic factors in the selection of destinations. The findings hold when age is introduced as a control.