Mobile phones represent a pathway for microbial transmission: A scoping review.
Mobile phones have become an integral part of modern society. As possible breeding grounds for microbial organisms, these constitute a potential global public health risk for microbial transmission. Scoping review of literature examining microbial's presence on mobile phones in both health care (HC) and community settings. A search (PubMed&GoogleScholar) was conducted from January 2005-December 2019 to identify English language studies. Studies were included if samples from mobile phones were tested for bacteria, fungi, and/or viruses; and if the sampling was carried out in any HC setting, and/or within the general community. Any other studies exploring mobile phones that did not identify specific microorganisms were excluded. A total of 56 studies were included (from 24 countries). Most studies identified the presence of bacteria (54/56), while 16 studies reported the presence of fungi. One study focused solely on RNA viruses. Staphylococcus aureus, and Coagulase-Negative Staphylococci were the most numerous identified organisms present on mobile phones. These two species and Escherichia coli were present in over a third of studies both in HC and community samples. Methicillin-resistant S. aureus, Acinetobacter sp., and Bacillus sp. were present in over a third of the studies in HC settings. While this scoping review of literature regarding microbial identification on mobile phones in HC and community settings did not directly address the issue of SARS-CoV-2 responsible for COVID-19, this work exposes the possible role of mobile phones as a 'Trojan horse' contributing to the transmission of microbial infections in epidemics and pandemics.


Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats.
Catharanthus roseus L (C. roseus) has been used to treat a wide assortment of diseases including diabetes. The objective of our study was to evaluate the antimicrobial and wound healing activity of the flower extract of Catharanthus in rats. Wound healing activity was determined in rats, after administration (100 mg kg-1 day-1) of the ethanol extract of C. roseus flower, using excision, incision and dead space wounds models. The animals were divided into two groups of 6 each in all the models. In the excision model, group 1 animals were topically treated with carboxymethyl cellulose as placebo control and group 2 received topical application of the ethanol extract of C. roseus at a dose of 100 mg/kg body weight/day. In an incision and dead space model group 1 animals were given normal saline and group 2 received the extract orally at a dose of 100 mg kg-1 day-1. Healing was assessed by the rate of wound contraction, period of epithelization, tensile strength (skin breaking strength), granulation tissue weight, and hydoxyproline content. Antimicrobial activity of the flower extract against four microorganisms was also assessed The extract of C. roseus significantly increased the wound breaking strength in the incision wound model compared with controls (P < 0.001). The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly increased in comparison to control wounds (P < 0.001), Wet and dry granulation tissue weights, and hydroxyproline content in a dead space wound model increased significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus demonstrated sensitivity to C. roseus Increased wound contraction and tensile strength, augmented hydroxyproline content along with antimicrobial activity support the use of C. roseus in the topical management of wound healing.


Vertebral artery bypass.
The origin of the vertebral artery is a frequent site for the development of stenosing lesions. The flow deficit caused by the stenosis of one vertebral artery is normally compensated for by intracranial anastomosis between the carotid and basilar arteries or by the opposite vertebral artery. A number of patients, however, have inadequate intracranial anastomosis and hypoplasia or stenosis of the opposite vertebral artery, and symptoms of brain ischemia develop. We describe here four cases in which a new technique, a subclavian vertebral artery autogenous vein bypass graft, was used to deal with the diseased segment of the vertebral artery. Transient postoperative problems included lymphocele and Horner syndrome. All four bypasses were patent at the time of angiography one week postoperatively. All four patients were relieved of symptoms of vertebrobasilar insufficiency.


Pleural Myiasis Associated With Pleural Angiosarcoma.
Myiasis refers to a parasitic infestation of vertebrate mammals by dipterous larvae (maggots) of higher flies. Infections in humans typically occur in tropical and subtropical regions, regions with limited medical access, and areas with poor hygiene and living conditions. Infestations in humans have been described in subcutaneous, nasal, ocular, oropharyngeal, and orotracheal cases; however, reports of pulmonary myiasis in humans in the United States and other developed countries are extremely rare. We describe a patient with recently diagnosed primary pleural angiosarcoma who presented to our clinic for the management of a thoracostomy tube and was diagnosed with pleural myiasis.


Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.
To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO2 (etCO2) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO2 fluctuations of ≥5 mm Hg. Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO2 increase and 70 episodes of etCO2 decrease. During etCO2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO2 returned to baseline. During etCO2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO2 to baseline. An acute increase in etCO2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain.


Synthesis, structures and magnetic studies of hexanuclear lanthanide complexes: SMM behavior of the DyIII analogue and MCE properties of the GdIII analogue.
The synthesis, structure and magnetic properties of homometallic hexanuclear lanthanide complexes [Ln6(HL)4(tfa)4(S)2]·2NO3·x H2O·yMeOH (1, Ln = Gd, S = MeOH, x = 0, y = 0; 2, Ln = Tb, S = H2O, x = 2, y = 2; 3, Ln = Dy, S = MeOH, x = 0, y = 2; 4, Ln = Er, S = MeOH, x = 0, y = 2). [(H4L) = 6-((bis(2-hydroxyethyl)amino)-N'-(2-hydroxybenzylidene)picolinohydrazide) (tfa = trifloroacetylacetone)] are reported. These hexanuclear assemblies are made up of two trinuclear triangular sub-units linked through the oxygen atoms of two phenoxide bridging groups in a corner sharing arrangement. Magnetic studies reveal that 1 displays a magnetocaloric effect with a maximum value of -ΔSm = 21.03 J kg-1 K-1 at T = 3 K and under an applied field change ΔB = 5 T. Complex 3 shows slow relaxation of magnetization even under zero applied field although a clear maximum in the ac susceptibility plots cannot be seen. However, under an optimal applied field of 0.2 T, clear maxima are observed in the out-of-phase (χ''M) component of the ac susceptibility in the temperature range 3.5 K (2 kHz) to 10.5 K (10 kHz). The temperature dependence of the relaxation times could be fitted to the sum of Orbach, Raman and QTM relaxation processes affording the following parameters: τo = 3.4(9) × 10-8 s, Ueff = 94(2) K, BRaman = 16.43(1) K-n s-1, n = 3.2(3) and τQTM = 0.0044(3) s. 4, under an applied magnetic field of 0.2 T, shows slow relaxation of magnetization through a thermally activated Orbach process with Ueff = 18.2(9) K and τo = 3.5(3) × 10-8 s.


The DOMON domains are involved in heme and sugar recognition.
We expand the functionally uncharacterized DOMON domain superfamily to identify several novel families, including the first prokaryotic representatives. Using several computational tools we show that it is involved in ligand binding--either as heme- or sugar-binding domains. We present evidence that the DOMON domain along with the DM13 domain comprises a novel electron-transfer system potentially involved in oxidative modification of animal cell-surface proteins. Other novel versions might function as sugar sensors of histidine kinases of bacterial two component systems. Supplementary data are available at Bioinformatics online and also at ftp://ftp.ncbi.nih.gov/pub/aravind/domon/.


Construction and detection of a novel type of recombinant human rAAV2/2-ND4.
To construct a novel AAV-mediated gene delivery of the human ND4 complex I subunit and to detect its expression level in mitochondria for potential application in gene therapy for Leber's hereditary optic neuropathy (LHON). A novel type of normal human ND4 gene was synthesized artificially to contain a mitochondrial targeting sequence that induces the translocation of this gene into mitochondria. This recombinant adeno-associated virus type 2/ serotype 2 (rAAV2/2)-mediated NADH dehydrogenase subunit 4 (ND4) gene was constructed, purified, condensed, and amplified by PCR. The physical titer of rAAV2/2-ND4 was determined by slot-blot hybridization using a digoxigenin-labeled H1 probe. Expression of ND4 in mitochondria was evaluated by immunofluorescence. The constructed rAAV2/2-ND4 specifically amplified the target gene band of ND4 and the physical titer of ND4 gene was 1.0x 10(11) vg/mL, confirming that the recombinant adenovirus vector contained the ND4 target gene. Expression of the ND4 gene was detected in mitochondria by immunofluorescence. A new type of rAAV2/2-ND4 was successfully constructed and may have potential in gene therapy for LHON.


Supramolecular Catalysis of m-Xylene Isomerization by Cucurbiturils: Transition State Stabilization, Vibrational Coupling, and Dynamic Binding Equilibrium.
The ability of cucurbit[6]uril (CB6) and cucurbit[7]uril (CB7) to catalyze the thermally activated 1,2-methyl shift isomerization pathway of m-xylene in vacuum is investigated using infrequent metadynamics. CB6 is predicted to effectively and selectively catalyze the meta-to-para isomerization through stabilization of the transition state (TS) by van der Waals push (packing coefficient ≈74%), while inhibiting the meta-to-ortho pathway by molding effects of the cavity. Interestingly, despite the snug binding, a very low rate of host-guest vibrational energy transfer is revealed using a novel approach of host-guest partition of the mode-specific anharmonic relaxation rates and ab initio molecular dynamics. The weak vibrational coupling suggests that CB can act as a thermal buffer, possibly shielding encapsulated guests from outside vibrational perturbations such as solvent effects. This dynamic effect could provide an additional boost to the reaction rate by blocking the occurrence of reaction barrier recrossing caused by the friction with surrounding molecules. Finally, mean residence times of xylene into the hosts' cavity were estimated for a range of host-guest complexes, revealing a highly dynamic equilibrium allowing very high guest turnover rates that could minimize catalyst inhibition effects commonly suffered by other supramolecular catalysts.


12-O-tetradecanoylphorbol 13-acetate induces DNA cleavage at linker regions in mouse thymocytes.
A phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), induced the cleavage of nuclear DNA at linker regions in cultured mouse thymocytes. Similar DNA fragmentation was induced by 1-oleoyl-2-acetyl-glycerol, a synthetic diacylglycerol, but not by 4 alpha-phorbol-12,13 didecanoate. The DNA fragmentation was inhibited by 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine dihydrochloride, an inhibitor of protein kinase C, as well as actinomycin D and cycloheximide. It appears that TPA induces DNA cleavage through activation of protein kinase C and synthesis of yet unidentified protein(s). That the inhibition of DNA fragmentation was accompanied by a reduction in cell lysis suggests a causal relationship between DNA fragmentation and cell death.


Glossopharyngeal neuralgia secondary to vascular compression in a patient with multiple sclerosis: a case report.
Glossopharyngeal neuralgia is an uncommon, painful syndrome, characterized by paroxysms of pain in the sensory distribution of the 9th cranial nerve. Idiopathic glossopharyngeal neuralgia may be due to compression of the glossopharyngeal nerve by adjacent vessels, while secondary glossopharyngeal neuralgia is associated with identifiable lesions affecting the glossopharyngeal nerve at different levels of its neuroanatomic pathway. Glossopharyngeal neuralgia is rare in the general population, but is more common in patients with multiple sclerosis. A 56-year-old Caucasian woman with multiple sclerosis and migraine presented to our facility with intermittent lancinating pain to the right of her throat, tongue, and the floor of her mouth that had been occurring for the past year. The pain was intense, sharp, and stabbing, which lasted two to six seconds with radiation to the right ear. Initially, the attacks were infrequent, however, they had become more intense and frequent over time. Our patient reported weight loss, headache, painful swallowing, and the inability to maintain sleep due to painful attacks. A neurological examination revealed a right-handed woman with trigger points in the back of the tongue and throat on the right side. She also had dysphagia, hoarseness, and pain in the distribution of the right glossopharyngeal nerve. Mild right hemiparesis, hyperreflexia, dysmetria, and an ataxic gait were present. A magnetic resonance imaging scan of the brain was consistent with multiple sclerosis and magnetic resonance angiography demonstrated a loop of the posterior inferior cerebellar artery compressing the right glossopharyngeal nerve. She responded satisfactorily to carbamazepine. Microvascular decompression and Gamma Knife® radiosurgery were discussed in case of failure of the medical treatment; however, she declined these options. Glossopharyngeal neuralgia in multiple sclerosis may occur due to vascular compressive lesions and it should not be solely attributed to the underlying demyelinating process. Vascular compression of the glossopharyngeal nerve could independently cause glossopharyngeal neuralgia in patients with multiple sclerosis, and vascular imaging to exclude such a diagnosis is recommended.


Lysis of fresh human B-lymphocyte-derived leukemia cells by interferon-activated natural killer (NK) cells.
Fresh neoplastic B cells from 14 untreated patients with naturally occurring B-cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non-cultured, neoplastic B cells was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non-progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK-susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re-emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor-enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B-cell leukemias was the presence of significantly lower NK effector-cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.


Glycolytic activity is required for the onset of neural plate folding during neural tube closure in mouse embryos.
Physiological hypoxia is critical for placental mammalian development. However, the underlying mechanisms by which hypoxia regulates embryonic development remain unclear. We discovered that the expression of glycolytic genes partially depends on hypoxia in neuroepithelial cells of E8.25 mouse embryos. Consistent with this finding, inhibiting glycolysis during the early phase of neural tube closure (E8.0-8.5) resulted in a neural tube closure defect. In contrast, inhibiting the electron transport chain did not affect neural tube formation. Furthermore, inhibiting glycolysis affected cell proliferation, but not differentiation and survival. Inhibiting glycolysis repressed the phosphorylation of myosin light chain 2, and consequent neural plate folding. Our findings revealed that anaerobic glycolysis regulates neuroepithelial cell proliferation and apical constriction during the early phase of neural tube closure.


[Unilateral pulmonary vein atresia in early adulthood].
Unilateral pulmonary vein atresia is a rare condition in adults that may cause serious diagnostic problems because of unspecific clinical findings. A 28-year old female patient is described who presented with signs of recurrent pulmonary embolism with shortness of breathing, unilateral thoracic pain and several episodes of haemoptysis. Ventilation and perfusion scans showed a total lack of perfusion in the right lung with only slight disturbance of ventilation. However, no marked increase of pulmonary artery pressure and no signs of a recent thrombosis of peripheral veins were found. Transoesophageal echocardiography and pulmonary angiography in combination with aortography revealed the diagnosis of unilateral pulmonary vein atresia with abnormal branches of bronchial arteries. There is a considerably left-to-right shunt with return of flow from the bronchial arteries to the right and afterwards to the left pulmonary artery. Clinical, radiological and nuclear medical findings as well as therapeutical options are described.


Liver transplantation for hepatocellular carcinoma.
Hepatocellular carcinoma can only be cured by physical removal or destruction of the tumor before it has spread. This can be accomplished by the ablation of the tumor, surgical resection of the tumor-bearing liver, or by liver transplantation. Ablation and resection can only be performed in patients who will be left with sufficient liver volume to sustain normal hepatic function. Unfortunately, the same disease that caused the HCC also limits the amount of parenchymal loss that can be tolerated by the patient. Liver transplantation is an appealing treatment option because it has the potential to cure patient of both the cancer and the predisposinig liver disease. Excellent survival rates are possible in patients with early HCC who receive a transplant, but dismal results are seen when patients with advanced tumors are transplanted.Wide criteria for transplant allow for more patients to be cured of HCC, but this comes at the expense of a greater overall recurrence rate. The acceptable recurrence rate is not a concrete number, but this is a function of donor organ availability. A 50% cure rate is viewed as an excellent outcome for many accepted cancer operations; however, in the case of transplant for HCC, this would represent a poor use of the scarce donor resource when the same liver offers a 70% 5-year survival rate to a non-HCC patient. These issues and methods retarding tumor progression while on the transplant waiting list are reviewed herein.


Identification and characterization of human ARHGAP23 gene in silico.
ARHGAP family genes, such as FNBP2, SRGAP1/ARHGAP13, SRGAP2/ARHGAP14, ARHGAP4 and AHRGAP20/KIAA1391, encode GTPase activating proteins for Rho family proteins (RhoGAPs). Here, we identified and characterized the ARHGAP23 gene by using bioinformatics. KIAA1501 (AB040934.1) was a 5'-truncated partial cDNA derived from the ARHGAP23 gene. Complete coding sequence of human ARHGAP23 cDNA was determined by assembling BM806021 EST, BQ718622 EST, KIAA1501 partial cDNA, and AC115090.8 genome sequence corresponding to exons 7 and 25. ARHGAP23 gene encoded 1491-aa isoform 1 (without exon 23) and 1144-aa isoform 2 (with exon 23) due to alternative splicing. Isoform 2 was C-terminally truncated due to frame-shift within 23-bp exon 23. ARHGAP23 mRNA was expressed in placenta, prostate, hippocampus, brain medulla as well as in brain tumor, salivary gland tumor, head and neck tumor. Mouse 4933428G20 (NM_021493.1) was a 5'-truncated partial cDNA derived from Arhgap23 gene at mouse chromosome 11D. Human ARHGAP23, ARHGAP21 and Xenopus rGAP shared the common domain structure consisting of PDZ, Pleckstrin homology (PH), and RhoGAP domains. ARHGAP23-KIAA1684-MLLT6-RNF110-PIP5K2B-LASP1-PLXDC1-CACNB1 locus at human chromosome 17q12 and CACNB2-PLXDC2-LASP2-MLLT10-BMI1-PIP5K2A-KIAA1217-ARHGAP21 locus at human chromosome 10p12 were paralogous regions (paralogons) with internal inversion. MLLT6, MLLT10 and LASP1 genes are fusion partners of MLL gene in hematological malignancies, while RNF110, PIP5K2B, LASP1 and BMI1 genes are amplified in human tumors. Evolutionary recombination hotspots and oncogenomic recombination hotspots were co-localized around the ARHGAP23-CACNB1 locus and the ARHGAP21-CACNB2 locus.


New Minimally Invasive Intraoral Procedure for Condylar Fractures: Clinical Presentation and Considerations on Current Techniques.
Mandibular fractures are the third most prevalent maxillofacial traumatic events. Surgical approaches to the condyle are a debated topic. This study describes a mini-invasive technique for condylar fracture reduction. The patient of this study suffered multiple traumatic injuries including a carotid artery dissecting aneurysm, which contraindicated the standard open reduction and internal fixation technique. The novel minimally invasive technique involves intraoral access and fracture fragment realignment using a periosteal elevator, a molar occlusal splint, and intermaxillary fixation after intraoperative radiologic imaging confirmation of condyle reposition.The approach avoids skin incisions and tissue dissection, with good aesthetic outcomes and facial nerve preservation. This technique proved to be safe and simple to be less demanding for the patient, with a shorter recovery time than experienced with other techniques.The results suggest this technique is a good option for the surgical treatment of condylar neck fractures showing favorable rim morphology with primary stability after reduction.


Understanding of type 1 diabetes mellitus: what we know and where we go.
The incidence of type 1 diabetes mellitus (T1DM) in children and adolescents is increasing worldwide. Combined effects of genetic and environmental factors cause T1DM, which make it difficult to predict whether an individual will inherit the disease. Due to the level of self-care necessary in T1DM maintenance, it is crucial for pediatric settings to support achieving optimal glucose control, especially when adolescents are beginning to take more responsibility for their own health. Innovative insulin delivery systems, such as continuous subcutaneous insulin infusion (CSII), and noninvasive glucose monitoring systems, such as continuous glucose monitoring (CGM), allow patients with T1DM to achieve a normal and flexible lifestyle. However, there are still challenges in achieving optimal glucose control despite advanced technology in T1DM administration. In this article, disease prediction and current management of T1DM are reviewed with special emphasis on biomarkers of pancreatic β-cell stress, CSII, glucose monitoring, and several other adjunctive therapies.


Quality of YouTube videos for three common pediatric hip conditions: developmental hip dysplasia, slipped capital femoral epiphysis and Legg-Calve-Perthes disease.
YouTube is an increasingly accessible platform for families to obtain health information from; however, it is unregulated. The aim of this article was to assess the quality, reliability and accuracy of YouTube videos related to three common pediatric hip conditions: development dysplasia of the hip (DDH), slipped capital femoral epiphysis (SCFE) and Legg-Calve-Perthes disease. YouTube was searched using a variety of keyword combinations. Videos were analysed using Journal of the American Medical Association, Global Quality Score and condition-specific scores created specifically for this study. Video duration and the number of views were also recorded. In total 120 videos were analysed, 40 for each of DDH, SCFE and Perthes disease. YouTube videos from physicians and academic institutions/hospitals are of significantly higher quality, reliability and accuracy than videos from patients, nonphysicians and commercial outlets. The higher quality for physician videos is associated with significantly longer video. Differences between the three pediatric orthopaedic conditions were not statistically significant. Videos of higher quality may be used as an adjunctive tool to strengthen clinical consultation. Parents and caregivers should be guided to videos from academic institutions or hospitals as a way of improving health literacy.


Incidence of regeneration of the chorda tympani nerve after middle ear surgery.
We retrospectively reviewed 52 patients who underwent middle ear surgery during which the chorda tympani nerves were severed and who then underwent secondary surgery 1 to 5 years later. In 22 patients (42.3%), regenerated chorda tympani nerves (entire length of the tympanic segment) were detected in the submucosal layer of the reconstructed eardrum during the secondary surgery. Before the secondary surgery, 16 patients (30.8%) showed threshold recovery on electrogustometry. When 5 regenerated nerves were observed by transmission electron microscopy, myelinated nerve fibers were detected in a small fascicle or connective tissue, but the number of myelinated axons was significantly decreased (7.4% to 84.6%; p = .01) compared with that in normal subjects (1,911 +/- 324; n = 4). There was a significant difference in the incidence of regeneration between the group with end-to-end anastomosis (5/5 or 100%) and that with nerve gap defects (17/47 or 36.2%; p <.05); this finding suggests that repair of the sectioned nerve produces a better incidence of regeneration than leaving the nerve unrepaired.


A New Residual Dense Network for Dance Action Recognition From Heterogeneous View Perception.
At present, part of people's body is in the state of sub-health, and more people pay attention to physical exercise. Dance is a relatively simple and popular activity, it has been widely concerned. The traditional action recognition method is easily affected by the action speed, illumination, occlusion and complex background, which leads to the poor robustness of the recognition results. In order to solve the above problems, an improved residual dense neural network method is used to study the automatic recognition of dance action images. Firstly, based on the residual model, the features of dance action are extracted by using the convolution layer and pooling layer. Then, the exponential linear element (ELU) activation function, batch normalization (BN) and Dropout technology are used to improve and optimize the model to mitigate the gradient disappearance, prevent over-fitting, accelerate convergence and enhance the model generalization ability. Finally, the dense connection network (DenseNet) is introduced to make the extracted dance action features more rich and effective. Comparison experiments are carried out on two public databases and one self-built database. The results show that the recognition rate of the proposed method on three databases are 99.98, 97.95, and 0.97.96%, respectively. It can be seen that this new method can effectively improve the performance of dance action recognition.


The role of sphingosine 1-phosphate in immunity and sepsis.
Sphingosine 1-phosphate (S1P) is a lipid metabolite with intra- and extracellular signalling properties. It activates five G protein-coupled cell surface receptors designated S1P-receptors type 1-5 (S1P1-5) that transmit extracellular signals into cells, and it modulates intracellular signalling as a cofactor. The analysis of sphingosine kinases (SphK) type 1 and 2, the key enzymes for S1P production, in different infection models point to an important role for the activation of different immune cells like macrophages, mast cells, and dendritic cells. S1P additionally influences local and systemic lymphocyte circulation and positioning, the vascular tone, and blood pressure. Modulation of S1P-mediated signalling pathways therefore results either in local immune cell activation or systemic immune suppression, or both. Pharmacological approaches that modulate certain S1P-mediated signalling pathways while leaving others untouched appear to be promising new avenues for next generation pharmaceuticals. This review summarizes current strategies to modulate S1P signalling for immune intervention with the clear focus on the specificity of the different principles applied. Known local and systemic effects of S1P on immunity are discussed as potential pharmaceutical targets to combat immune and autoimmune diseases and sepsis.


Establishment of an efficient in vitro regeneration protocol for rapid and mass propagation of Dendrobium chrysotoxum Lindl. using seed culture.
An efficient in vitro regeneration protocol from seed culture has been established successfully for Dendrobium chrysotoxum, an epiphytic orchid having tremendous ornamental and medicinal values. Seed germination response was encouraging in Mitra (M) medium enriched with different combinations of auxins and cytokinins. Medium supplemented with 0.4% activated charcoal (AC), 2 mg/L 6-benzyl amino purine (BAP), and 2 mg/L indole-3-acetic acid (IAA) produced best seed germination percentage in 2 weeks of culture. Incorporation of higher concentration of kinetin (KN) or BAP in combination with low auxin in medium induced pronounced shooting and leaf formation. Reduction in leaf development was evident when cytokinins exist singly in medium indicating synergistic effect of auxin and cytokinin in leaf induction. Presence of elevated level of indole-3-butyric acid (IBA) or 1-naphthalene acetic acid (NAA) with low cytokinin content in medium generated more in vitro rooting, though IBA was found to be more effective in rooting induction as compared to NAA. The in vitro protocol for asymbiotic seed germination developed from the present investigation can be used for rapid mass propagation of this highly important Dendrobium orchid species.


Fluid resuscitation after an otherwise fatal hemorrhage: II. Colloid solutions.
We developed a fixed-volume porcine hemorrhage model that simulates the rapid exsanguination of combat or civilian trauma victims. In this study we compared the ability of colloid resuscitation solutions to prevent death after an otherwise lethal hemorrhage in 100 swine. The shed blood was replaced in a 1:1 ratio with either autologous whole blood (WB), untyped swine fresh frozen plasma (FFP), typed FFP, 5% human serum albumin (ALB), or normal saline (NS). Survival rate analysis indicated that WB was significantly better than FFP (untyped), ALB, or NS but not better than typed FFP. The 24-hour survival rates were: WB = 90%, typed FFP = 79%, untyped FFP = 56%, ALB = 57%, and NS = 25%. All deaths in the untyped FFP group suddenly occurred during or within 15 minutes after treatment in a recovering animal. Deaths in the ALB group steadily occurred for up to 2 1/2 hours after treatment. Analysis of hemodynamic, arterial blood gas, and acid-base data indicated that WB and FFP provided a better acid-buffering capacity in surviving animals than NS or ALB. We conclude that compatible FFP is a better resuscitation agent than ALB after an otherwise fatal hemorrhage because FFP is a better acid buffer.


miR-410 acts as an oncogene in colorectal cancer cells by targeting dickkopf-related protein 1 via the Wnt/β-catenin signaling pathway.
Colorectal cancer (CRC) is a common malignancy with high morbidity. MicroRNAs (miRNAs or miRs) have been demonstrated to be critical post-transcriptional regulators in tumorigenesis. The current study aimed to investigate the effect of miR-410 on the proliferation and metastasis of CRC. The expression of miR-410 was examined in CRC cell lines. SW-480 and HCT-116 CRC cell lines were employed and transfected with miR-410 inhibitor or miR-410 mimics. The association between miR-410 and dickkopf-related protein 1 (DKK-1) was verified by luciferase reporter assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Cell migration and invasion capacity were determined by Transwell assay. The protein level of DKK1, β-catenin and phosphorylated glycogen synthase kinase-3β (pGSK-3β) were analyzed by western blotting. miR-410 was revealed to be upregulated in CRC cell lines. Further studies identified DKK-1 as a direct target of miR-410. In addition, knockdown of miR-410 promoted the expression of DKK, inhibited CRC cell proliferation, migration and invasion capacity, and induced cell apoptosis, while overexpression of miR-410 reversed these results. miR-410 silencing also decreased β-catenin and pGSK-3β levels. The current study indicated that miR-410 negatively regulates the expression of DKK-1 in vitro. miR-410 promotes malignancy phenotypes in CRC cell lines. This regulatory effect of miR-410 may be associated with the Wnt/β-catenin signaling pathway. Therefore, miR-410 could be used as a biomarker for predicting the progression of CRC.


Molecular characterization and expression analysis of toll-like receptors 5 and 22 from natural triploid Carassius auratus.
Innate immunity, as the most primitive and universal host defense in fish, constitutes an efficient first line of defense to combat invading microbes. Toll-like receptors (TLRs) play essential roles in the innate immunity, and TLR5 and TLR22 are two important TLRs that can recognize flagellin and double stranded RNA (dsRNA), respectively. In this study, we identified and characterized two TLRs genes of Qihe crucian carp (Carassius auratus) (designated as CaTLR5 and CaTLR22). The full-length cDNA sequence of CaTLR5 was cloned with 2972 bp including a 140 bp 5'-terminal untranslated region (UTR), a 183 bp 3'-UTR, and a 2649 bp open reading frame (ORF) encoding a deduced protein with 882 amino acids. The full-length cDNA of CaTLR22 was identified to be 3613 bp, consisting of a 228 bp 5'-UTR, a 547 bp 3'-UTR, and a 2838 bp ORF encoding a predicted protein of 945 amino acids. A typical TLR structure (an extracellular leucine-rich repeat domain, a transmembrane domain, and an intracellular Toll/IL-1 receptor domain) was found in CaTLR5 and CaTLR22. For either CaTLR5 or CaTLR22 gene, the mRNA expression levels varied in the different periods during the early stages of development. It was suggested that expression changes of gene CaTLR5 and CaTLR22 at mRNA levels were involved in developmental regulation in the early stages, and it was postulated that CaTLR5 and CaTLR22 play the important roles in immune defense in the early development stages of fish. Quantitative Real-Time PCR (qRT-PCR) revealed that CaTLR5 and CaTLR22 were constitutively expressed in all eleven tissues examined, although the mRNA expression level varied considerably among the different tissues. Following exposure to polyI:C, flagellin, and Aeromonas hydrophila, CaTLR5 and CaTLR22 were up-regulated in different tissues, and it was suggested that CaTLR5 and CaTLR22 were involved in the immune response of Qihe crucian carp against pathogenic invasions. The present findings will provide the valuable information for understanding the structure, function, expression, and the immune defense process of CaTLR5 and CaTLR22 in Qihe crucian carp, and provide new insights for developing the new strategies of disease control to protect fish against pathogens infection.


[Staged complex treatment of paralytic lagophthalmos (case report)].
Paralytic lagophthalmos, resulting from facial nerve palsy, is a difficult medical and social issue that requires cooperation of different specialists. Complications that arise in paralytic lagophthalmos may cause significant vision loss and even eye loss. Various techniques of paralytic lagophthalmos correction are used to protect the cornea and restore eyelid anatomy and functions. These comprise palliative (conservative), surgical, and alternative treatments (such as botulinum toxin type A therapy). Surgical treatment of paralytic lagophthalmos patients often has to be staged and complex. This article presents a clinical case of a female patient with paralytic lagophthalmos complicated by corneal perforation. Her staged complex treatment included lower eyelid surgery, chemodenervation of the upper eyelid levator and optical reconstructive surgery. The following positive results were achieved: the protective function of the eyelids was restored, residual visual functions - preserved, the risk of eye loss - eliminated, and the asymmetry between the two halves of the face - corrected.


The use of a zirconia custom implant-supported fixed partial denture prosthesis to treat implant failure in the anterior maxilla: a clinical report.
Over the last decade, there has been a dramatic rise in patients' esthetic expectations with regard to both conventional and implant prosthodontics. The loss of hard and/or soft tissue dimensions, often unpredictably, around implants, can result in potential embarrassment due to the display of metal components. Patients are understandably reluctant to accept visibility of metal abutments and/or the implant substructures, especially in the esthetic zone, even if biologically sound. The use of 1-piece zirconia implant frameworks or, alternatively, custom zirconia abutments with a zirconia framework, has enabled both a good biological response as well as the ability to improve the esthetic outcome. This clinical report demonstrates the use of a 1-piece zirconia implant-supported fixed partial denture in the anterior maxilla, with minimal soft tissue dimension above the implant shoulder level, which dictated the need for prosthetic soft tissue augmentation.


Expression of TAp73α affects the therapy effect of chemotherapy drugs in gastric cancer.
The transcription factor TAp73, a transcriptionally active isoform of p73, has high structure and function similaritieswith its homolog p53, therefore, are thought to be a cancer therapy candidate target. However, there is still a controversy about the tumor suppressor role of TAp73, since it has been found in numerous studies that TAp73 expression is elevated in different cancers. Thus, we take effort to clarify the influence of TAp73 on gastric cancer (GC) chemotherapy. Multiple cell lines of GC such as SNU-1, SNU-3, and AGS were applied to investigate expression of TAp73. Flow cytometry was utilized to detect apoptosis, revealing how TAp73 overexpression affected anticancer drug (ACD). Additionally, we explored how TAp73 overexpression influenced apoptotic cells of neoplastic tissues and tumor size of nude mice in vivo. Our results indicated that TAp73 was down-regulated in GC cells after chemotherapy drugs treatment. Besides, enforced expression of TAp73 affects chemotherapeutic drugs induced GC cell apoptosis, which is dependent on p53. The expression of TAp73 was regulated by its transcription factor, E2F1, in response to chemotherapy drugs. Our in vivo xenograft results also suggested that transfection of TAp73 affects the tumor suppression effect of 5-FU. Consequently, the findings of our study demonstrate that E2F1 and TAp73α are oncogenic and throw light upon the underlying mechanism of their role against apoptosis.


Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension.
Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.


Accurate detection of paroxysmal atrial fibrillation with certified-GAN and neural architecture search.
This paper presents a novel machine learning framework for detecting PxAF, a pathological characteristic of electrocardiogram (ECG) that can lead to fatal conditions such as heart attack. To enhance the learning process, the framework involves a generative adversarial network (GAN) along with a neural architecture search (NAS) in the data preparation and classifier optimization phases. The GAN is innovatively invoked to overcome the class imbalance of the training data by producing the synthetic ECG for PxAF class in a certified manner. The effect of the certified GAN is statistically validated. Instead of using a general-purpose classifier, the NAS automatically designs a highly accurate convolutional neural network architecture customized for the PxAF classification task. Experimental results show that the accuracy of the proposed framework exhibits a high value of 99.0% which not only enhances state-of-the-art by up to 5.1%, but also improves the classification performance of the two widely-accepted baseline methods, ResNet-18, and Auto-Sklearn, by [Formula: see text] and [Formula: see text].


Zonal gene expression of chondrocytes in osteoarthritic cartilage.
To determine the chondrocyte metabolism in respective zones of osteoarthritic (OA) cartilage. OA cartilage was obtained from macroscopically intact areas of 4 knee joints with end-stage OA. The cartilage was divided into 3 zones, and gene expression profiles were determined in the respective zones by a custom-designed microarray that focused on chondrocyte-related genes. For the genes whose expression was significantly different among the zones, the expression was compared between OA and control cartilage in the respective zones by an analysis using laser capture microdissection and real-time polymerase chain reaction (PCR). For some genes, the correlation of expression was investigated in specific cartilage zones. A total of 198 genes (approximately 40% of those investigated) were found to be expressed at significantly different levels among the zones. Expression of 26 of those genes was evaluated by laser capture microdissection and real-time PCR, which confirmed the validity of microarray analysis. The expression of cartilage matrix genes was mostly enhanced in OA cartilage, at similar levels across the zones but at different magnitudes among the genes. The expression of bone-related genes was induced either in the superficial zone or in the deep zone, and positive correlations were found among their expression in the respective zones. The expression of 5 proteinase genes was most enhanced in the superficial zone, where their expression was correlated, suggesting the presence of a common regulatory mechanism(s) for their expression. In OA cartilage, the metabolic activity of chondrocytes differed considerably among zones. Characteristic changes were observed in the superficial and deep zones.


Event Study Design for Modeling Early Relaxation in Turkish Public with COVID-19 Vaccine.
Vaccination is crucial to fighting the coronavirus disease (COVID-19) pandemic. A large body of literature investigates the effect of the initiation of the COVID-19 vaccination in case numbers in Turkey, including the resistance and willingness to taking the vaccine. The effect of early relaxation in the Turkish public with the initiation of vaccination on new daily cases is unknown. This study performs an event study analysis to explore the pre-relaxation effect of vaccination on the Turkish public by using daily data of new cases, stringency index, and residential mobility. Two events are comparatively defined as the vaccination of the health personnel (Event 1) and the citizens age 65 and over (Event 2). The initial dates of these events are January 13 and February 12, 2021, respectively. The length of the estimation window is determined as 14 days for the 2 events. To represent only the early stages of the vaccination, the study period ends on April 12, 2021. Thus, whereas the event window of Event 1 includes 90 observations, Event 2 covers 60 observations. While average values of residential mobility, stringency index, and daily numbers of cases are 15.36, 71.03, and 11 978.93 in the estimation window for Event 1, these averages are 8.89, 70.88, and 17 303.20 in the event window. For Event 2, the same average values are 9.14, 69.38, and 7 664.93 in the estimation window and 8.25, 71.12, and 22 319.10 in the event window. When 14-day abnormal growth rates of the daily number of cases for Event 1 and Event 2 are compared, it is observed that Event 1 has negative growth rates initially and reaches a 7.59% growth at most. On the other hand, Event 2 starts with a 1.11% growth rate, and having a steady increase, it reaches a 23.70% growth in the last 14 days of the study period. The preliminary result shows that, despite taking more strict governmental measures, while residential mobility decreases, the daily number of COVID-19 cases increases in the early stages of vaccination compared to short pre-periods of it. This indicates that the initiation of vaccination leads to early behavioral relaxation in public. Moreover, the effect of Event 2 on the case numbers is more significant and immediate, compared to that of Event 1, which may be linked to the characteristic of the Turkish culture being more sensitive to the older adult population.


Is Rivaroxaban Associated With Shorter Hospital Stays and Reduced Costs Versus Parenteral Bridging to Warfarin Among Patients With Pulmonary Embolism?
We sought to compare the length of stay (LOS) and total costs for patients with pulmonary embolism (PE) treated with either rivaroxaban or parenterally bridged warfarin. This retrospective claims analysis was performed in the Premier Database from November 2012 to March 2015. Adult patients were included if they had a hospital encounter for PE (an International Classification of Diseases, Ninth Revision code = 415.1×) in the primary position, a claim for ≥1 diagnostic test for PE on day 0 to 2, and initiated rivaroxaban or parenteral anticoagulation/warfarin. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients receiving parenterally bridged warfarin. Length of stay, total costs, and readmission for venous thromboembolism (VTE) or major bleeding during the same or subsequent 2 months following the index event were compared between cohorts. Analysis restricted to patients with low-risk PE was also performed. Characteristics of the matched PE cohorts (n = 3466 per treatment) were well balanced. Rivaroxaban use was associated with a 1.36-day shorter LOS and $2304 reduction in total costs compared to parenterally bridged warfarin ( P < .001 for both). Rates of readmission for VTE were similar between cohorts (1.7% vs 1.6%; P = .64). No difference was observed between treatments for readmission for major bleeding (0.2% vs 0.2%; P > .99). In analyses restricted to low-risk patients (n = 1551 per treatment), rivaroxaban was associated with a 1.01-day and a $1855 reduction in LOS and costs, respectively ( P < .001 for both). Rates of readmission were again similar between treatments ( P > .56 for all). Rivaroxaban significantly reduced hospital LOS and costs compared to parenterally bridged warfarin, without increasing the risk of readmission.


Black-white differences in cancer risk in Harare, Zimbabwe, during 1991-2010.
Data from 20 years of cancer registration in Harare (Zimbabwe) are used to investigate the risk of cancer in the white population of the city (of European origin), relative to that in blacks (of African origin). In the absence of information on the respective populations-at-risk, we calculated odds of each major cancer among all cancers, and took the odds ratios of whites to blacks. Some major differences reflect obvious phenotypic differences (the very high incidence of skin cancer-melanoma and nonmelanoma--in the white population), whereas others (high rates of liver cancer, Kaposi sarcoma and conjunctival cancers in blacks) are the result of differences in exposure to infectious agents. Of particular interest are cancers related to lifestyle factors, and how the differences in risk are changing over time, as a result of evolving lifestyles. Thus, the high risk of cancers of the esophagus and cervix uteri in blacks (relative to whites) and colorectal cancers in whites show little change over time. Conversely, the odds of breast cancer, on average four times higher in whites than blacks, has shown a significant decrease in the differential over time. Cancer of the prostate, with the odds initially (1991-1997) 15% higher in whites had become 33% higher in blacks by 2004-2010.


Two CYP93A enzymes play a dual role in isoflavonoid biosynthesis in Glycine max L.
Glycine max L. is rich in isoflavonoids with diverse biological activities. However, isoflavonoid biosynthetic pathway is not fully elucidated in soybean. In the present study, we investigated characteristics of all the thirteen CYP93 subfamily members, and found GmCYP93A1, GmCYP93A2, and GmCYP93A3 are closely clustered, preferentially expressed in roots, and highly inducible by elicitor. When expressed in yeast, GmCYP93A1 was active towards liquiritigenin, naringenin, and 3,9-dihydroxyptercarpan, GmCYP93A2 towards 3,9-dihydroxyptercarpan with strict substrate specificity, whereas GmCYP93A3 did not show any activity towards all the tested substrates. Both GmCYP93A1 and GmCYP93A2 could catalyze 3,9-dihydroxyptercarpan into daidzein and glycinol, with both hydroxylation and aryl migration activity. Site-directed mutagenesis assays revealed that mutation in Thr446 to Ser446 in heme-binding domain increased the enzyme activity of GmCYP93A1 towards 3,9-dihydroxyptercarpan, which highlights its key amino acid residues as shown with its molecular docking with 3,9-dihydroxyptercarpan and HEM. Overexpression of GmCYP93A1 and GmCYP93A2 in the soybean hairy roots reduced the content of daidzein, whereas knockdown of these two genes increased genistein content, indicating changes in expression level of GmCYP93A1 and GmCYP93A2 altered isoflavonoid flux in soybean. Our studies on the activity of GmCYP93A1 and GmCYP93A2 enriched diverse functions of CYP93 subfamily in soybean isoflavonoid pathway, which is valuable for further understanding and bioengineering of isoflavonoid pathway in soybean.


Bone conduction auditory steady state response: investigations into reducing artifact.
Auditory steady state responses (ASSRs) can be reliably recorded in sleeping neonates and can be used to estimate hearing thresholds in individuals with normal or impaired hearing. However, artifactual responses can contaminate recordings, particularly when recording bone conduction ASSRs. The aim of this investigation was to study the presence of electromagnetic artifact in bone conduction ASSRs and to investigate methods of reducing the amplitude of the artifact. Using a simulation of a patient, ASSR recordings were obtained to multiple frequency bone-conducted stimuli using the research MASTER system. ASSR stimuli were sinusoidal tones with the carrier frequencies 500, 1000, 2000, and 4000 Hz that were 100% amplitude modulated at 83, 87, 91, and 95 Hz, respectively. After the assessment of different equipment layouts, the effects of (1) altering the analog-to-digital conversion rates and (2) screening the transducer cable and B-71 transducer and connecting the screens to ground were investigated. For ASSR recordings, artifacts were observed at the modulation rates of the 1000-, 2000-, and 4000-Hz carrier frequencies. As expected, the artifact was proportional to stimulus intensity and was observed when using sampling rates of 1000 and 2000 Hz but not 1250 and 1600 Hz. Altering the electrode lead/transducer cable layout and orientation of the B-71 transducer significantly affected the amplitude of the artifact. Screening of the B-71 transducer and cable and connecting the screens to ground reduced the amplitude of the artifact to a level that was not significantly above background noise. A mu-metal screen had a significantly greater effect than aluminum or copper. If stimulus artifact is present in the recorded EEG, for certain choices of carrier frequency and sampling rate it is possible to record artifactual signals at the same modulation rates as those used to elicit ASSRs. This is problematic as the artifact may then be misinterpreted as an ASSR response. The results from this study have demonstrated that careful attention to equipment layout, choice of sampling rate, using grounded screens to screen the B-71 transducer and transducer cable can all be effective in reducing the level of stimulus artifact.


Gene therapy of endothelial nitric oxide synthase and manganese superoxide dismutase restores delayed wound healing in type 1 diabetic mice.
Nitric oxide (NO) deficiency contributes to diabetic wound healing impairment. The present study tested the hypothesis that increased cutaneous superoxide (O2-) levels in type 1 diabetic mice cause NO deficiency and delayed wound healing. Wound healing was markedly delayed in streptozotocin-induced type 1 diabetic mice compared with the normal controls. There were significantly reduced levels of endothelial NO synthase (eNOS) protein and constitutive NOS activity in diabetic wounds, whereas O2- levels were markedly increased. A single regimen of cutaneous gene therapy of eNOS or manganese superoxide dismutase (MnSOD) restored such healing delay, with a concomitant suppression of wound O2- levels and augmentation of both eNOS protein and constitutive NOS activity. Gene therapy of MnSOD also increased cutaneous MnSOD activity. Cutaneous O2- levels were also increased in Ins2(Akita) diabetic mice. In vitro glucose treatment of cutaneous tissues from normal mice for 24 hours increased O2- levels in a concentration-dependent manner. The enhanced cutaneous O2- levels induced by high glucose in both normal and diabetic mice were abolished by the NADPH oxidase inhibitor apocynin and the protein kinase C inhibitor chelerythrine. Furthermore, ex vivo gene transfer of dominant-negative HA-tagged N17Rac1, which inhibits NADPH oxidase subunit Rac1, significantly inhibited cutaneous O2- formation induced by high glucose in both normal and Ins2(Akita) diabetic mice. These results indicate that hyperglycemia augments cutaneous O2- levels, at least in part, via NADPH oxidase and protein kinase C pathways, resulting in impaired wound healing in type 1 diabetic mice. Gene therapy strategies aimed at restoring cutaneous NO bioavailability may provide an effective means to ameliorate delayed diabetic wound healing.


Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.
Estimation of the epidemiological burden of carotid atherosclerosis can serve as a basis for prevention and management of cardiovascular disease. We aimed to provide the first estimation on the prevalence, number of cases, and risk factors for carotid atherosclerosis in the general population globally and regionally. In this systematic review, meta-analysis, and modelling study, we searched PubMed, MEDLINE, Embase, Global Health, and China National Knowledge Infrastructure for articles published from database inception until May 7, 2019, with no language restrictions, for population-based studies that quantified prevalence of carotid atherosclerosis by means of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. Studies were eligible if they included bilaterally scanned carotid arteries using ultrasonography and defined increased carotid intima-media thickness as a thickness of 1·0 mm or more, carotid plaque as a focal carotid intima-media thickness of 1·5 mm or more encroaching into the lumen or at least 0·5 mm or 50% compared with the surrounding carotid intima-media thickness values, and carotid stenosis as 50% or more stenosis. Studies were excluded if the sample was not representative of the general population. We also included studies identified in our previous systematic review and meta-analysis of the prevalence of carotid atherosclerosis in China. We estimated age-specific and sex-specific prevalences of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. We used UN population data to generate the number of people affected in 2000, 2015, and 2020. We did random-effects meta-analyses to assess the effects of risk factors for increased carotid intima-media thickness and carotid plaque. We derived regional numbers of people living with increased carotid intima-media thickness and carotid plaque in 2015 using a risk factors-based model by WHO region. All analyses were done in populations aged 30-79 years due to availability of data. This systematic review and meta-analysis is registered online on PROSPERO, CRD42019134709. We identified 8632 articles through our database search, of which 515 were eligible for full-text review, including 37 articles from our previous study, and 59 articles were eligible for inclusion in our systematic review and meta-analysis. Overall, in people aged 30-79 years in 2020, the global prevalence of increased carotid intima-media thickness is estimated to be 27·6% (95% CI 16·9-41·3), equivalent to 1066·70 million affected people and a percentage change of 57·46% from 2000; of carotid plaque is estimated to be 21·1% (13·2-31·5), equivalent to 815·76 million affected people and a percentage change of 58·97% from 2000; and carotid stenosis is estimated to be 1·5% (1·1-2·1), equivalent to 57·79 million affected people and a percentage change of 59·13% from 2000. The prevalence of increased carotid intima-media thickness, carotid plaque, and carotid stenosis increased consistently with age and was higher in men than in women. Current smoking, diabetes, and hypertension were common risk factors for increased carotid intima-media thickness and carotid plaque. In 2015, the Western Pacific region had the largest share of global cases of increased carotid intima-media thickness (317·62 million [33·36%] of 952·13 million affected people) and carotid plaque (240·77 million [33·20%] of 725·25 million), whereas the African region had the smallest share of cases of increased carotid intima-media thickness (59·08 million [6·21%]) and the Eastern Mediterranean region had the smallest share of carotid plaque cases (44·59 million [6·15%]). A substantial global burden of carotid atherosclerosis exists. Effective strategies are needed for primary prevention and management of carotid atherosclerosis. High-quality epidemiological investigations on carotid atherosclerosis are needed to better address the global burden of carotid atherosclerosis at finer levels. None.


Cyclosporin A in the oophorectomized rat: unexpected severe bone resorption.
Local factors, such as interleukin-1, may mediate the accelerated bone remodeling in the acute estrogen-deficient rat. Cyclosporin A (CsA), which in vitro inhibits some of these local factors, was administered to oophorectomized (OX) rats in an attempt to modify this high turnover state. Three groups of 15 rats were studied. Group A was sham operated, group B was OX, and group C was OX and received CsA (15 mg/kg per day) by gavage commencing 4 days postoophorectomy for 28 days. Estradiol levels were determined to confirm oophorectomy. Blood was sampled on days -7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), 1,25-(OH)2-vitamin D, PTH, and bone gla protein (BGP). Rats received tetracycline hydrochloride for bone histomorphometric labeling. All results were compared to group A. Body weight was increased in group B (p less than 0.003) but not in group C. There was no difference in Ca2+ or PTH between the groups. BGP levels were higher in group B by day 28 (p less than 0.005); BGP levels were increased in group C from days 7-28 (p less than 0.002). 1,25-(OH)2-vitamin D was significantly increased in group C (p less than 0.0001) but not in group B. Tibial bone histomorphometry revealed increased measurements of bone formation and osteoclast number without a loss of bone volume (BV/TV) in group B. Group C showed a dramatic increase in bone turnover with significant loss of BV/TV (p less than 0.001). In conclusion, CsA in the OX rat resulted in unexpected enhanced bone remodeling with high BGP levels and severe bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)


The Capnography Project.
Capnography is an essential tool used in the monitoring of patients during anesthesia and in critical care which, while required in most high-income countries, is unavailable in many low- and middle-income countries. Launched in 2020, the Smile Train-Lifebox Capnography Project aimed to find a "capnography solution" for resource-poor settings. The project was specifically interested in a capnography device that would meet the needs of the Smile Train partner hospitals to help monitor children requiring airway or cleft surgery. Project advisory and technical groups were formed and included representation from anesthesia practitioners from a balanced representation from all level of income countries, technical experts in capnography, and representatives from the Global Capnography Project (GCAP), the University of California at San Francisco Center for Health Equity in Surgery & Anesthesia (CHESA), and the World Federation of Societies of Anaesthesiologists (WFSA). Built upon the WFSA minimum capnometer specifications, a human centered design approach was used to develop a Target Product Profile. Seven manufacturers submitted 13 devices for consideration and 3 devices were selected for the testing phase. Each of these devices was evaluated for build quality, and clinical and usability performance. Based on the findings from the overall testing process, a combined capnography and pulse oximetry device by Zug Medical Systems was chosen. To accompany the new Smile Train-Lifebox capnograph, an international team of experienced anesthesiologists and educators came together to develop the necessary education materials. These materials were piloted in Ethiopia, subsequently modified, and endorsed by the education team. The device is now ready for distribution, with the accompanying education package, to the Smile Train network and beyond. In addition, a study is being planned to measure the impact of capnography introduction into operating rooms in resource-constrained settings.


Diabetes management during glucocorticoid therapy for nonendocrine disease.
To determine current attitudes about management of diabetes during glucocorticoid therapy for nonendocrine disease, as assessed by a pilot survey. A 27-item questionnaire was designed to determine areas of consensus and of disagreement on diabetes management during glucocorticoid therapy for nonendocrine disease and was mailed to 84 Chicago-area academic general internists, endocrinologists, pulmonologists or allergists, rheumatologists, and certified diabetes nurse-educators. The response rate was 55%. For new-onset "steroid diabetes," 43% of respondents agreed with use of insulin and 44% with use of sulfonylurea therapy. Respondents indicated 91 to 95% agreement on the desirability of self-monitoring of blood glucose on initiation of glucocorticoid therapy. For a fasting plasma venous glucose level of 150 mg/dL at the time of initiation of long-term glucocorticoid therapy, 54% of respondents disagreed with immediate increase of insulin in the case of a patient already taking insulin, and 80% disagreed with immediate substitution of insulin in the case of a patient on maximal glyburide therapy (P = 0.0053 for mean change of position). During tapering of glucocorticoid therapy, 75% of respondents approved close observation without immediate insulin reduction. Two anticipatory management plans, opposed by 54% and 45% of respondents, respectively, elicited strongly correlated attitudes: immediate increase of NPH insulin dosage during initiation of glucocorticoid therapy and immediate reduction of NPH insulin dose during tapering of glucocorticoids (r = 0.6296; P<0.0001). Finally, 78% perceived a paucity of objective information about diabetes management during glucocorticoid therapy for nonendocrine disease. The surveyed sample of practitioners reported a paucity of objective data about management of diabetes during glucocorticoid therapy for nonendocrine disease and conservatism in adjusting diabetes management during initiation and tapering of glucocorticoid therapy.


Are cervical vertebrae suitable for age estimation?
The ability of cervical vertebrae (CV) staging to contribute in forensic age estimation is being discussed controversially. The large variability of CV geometries in the end stage of development might be the reason for not reaching a performance competitive to hand or third molar methods. Here we study the geometry of adult CV and demonstrate that the description of their "typical" appearance is often not met. Lateral cephalograms from clinical routine of 320 subjects aged 20 years or above (median 24 years, 52% female) were evaluated. The criteria for the end stage of CV development (Hassel-Farman, Baccetti) were examined by assessing them in terms of metric measurements: (1) rectangular shape of C3/C4, (2) at least one of the height-width ratios of C3/C4 > 1 (both not <1), (3) significant concavities at the inferior margin of C2, C3 and C4. Metric data of the adults were also compared to those of 100 children aged 8-10 years (50% female). Adult CV often violated the criteria of rectangular shape (44% C3, 36% C4), of height-width ratio (16% C3, 35% C4) and inferior concavity (10% C2, 10% C3, 19% C4). All of the criteria for adult CV were fulfilled in only 24% of the subjects (95%CI 19-28%). The variability of measures of the CV shapes was large; e.g., the 95% reference ranges for the height-width ratios were 0.81-1.19 (C3) and 0.77-1.14 (C4). There was a material overlap of ranges of CV measures of adults and children. While hand bones and teeth have well-defined appearances in the end stage of development, adult CV have a large biological variance of shapes; it is hard to define their "typical" appearance. Moreover, measures of CV geometry do not strictly separate adults from children. These facts might reason the limited usefulness of CV in age estimation.


Fluorescence Light-Up Biosensor for MicroRNA Based on the Distance-Dependent Photoinduced Electron Transfer.
It is demonstrated that miRNAs exhibit significant regulatory roles in a series of biological processes and associated with diverse human diseases. Herein, we report a convenient fluorescent biosensor for the quantitative determination of miR-21, a key miRNA related to cardio-cerebrovascular diseases. Our proposal involves not only the rational design of single stranded DNA as the probe, successively including a C-rich sequence as the synthetic template of DNA/Ag nanoclusters (DNA/AgNCs), a complementary (Com) sequence to hybridize with the miR-21, and a G-rich sequence to form a complex of G-quadruplex/hemin but also the distance-dependent property of photoinduced electron transfer (PET) between the preformed DNA/AgNCs (electron donor) and G-quadruplex/hemin complex (electron acceptor). In the presence of the target miR-21, the initial flexible single strand Com in the probe turns to the rigid Com/RNA heteroduplexes, and then the PET could be interrupted owing to the extended distance between the electron donor and acceptor, accompanying with the fluorescence quenching and recovery of DNA/AgNCs. Therefore, a fluorescence light-up biosensor for miR-21 could be developed through the monitoring of the degree of fluorescence recovery of DNA/AgNCs. Preferential to other previous PET-based detection methods, we construct the biosensor by utilizing the distance dependent property for the first time and only need to adjust the sequences of Com in different miRNAs assays.


A review of our current understanding of parasite survival in silage and stored forages, with a focus on Fasciola hepatica metacercariae.
Fasciola hepatica, the parasitic liver fluke, is a re-emerging zoonotic infection and an important cause of morbidity and mortality in ruminant livestock worldwide. A significant animal welfare concern, fasciolosis also has a detrimental impact on food security, with the effects of sub-clinical infection on growth rate and milk yield estimated to cost the UK cattle industry £40.4 million annually. It is understood that up to 50% of infective F. hepatica metacercariae may overwinter on pasture and remain viable to infect grazing livestock the following spring. However, the infection risk posed by feeding grass silage to livestock remains largely unknown as the majority of previous studies are outdated in both experimental design and analysis of ensiled metacercariae viability. Anecdotal reports of fasciolosis outbreaks in housed livestock have reignited interest in F. hepatica metacercariae survival during modern ensiling processes and more importantly if they retain viability within stored forages. Consequently, a comprehensive review of the available literature is required in order to identify knowledge gaps and highlight future research opportunities regarding the role of silage in the transmission of F. hepatica.


Olfactory dysfunction and asthma as risk factors for poor quality of life in upper airway diseases.
The study of olfaction/quality of life (QoL) interaction has not been adequately discussed and remains to be further explored. Determination of clinical predictors for poor QoL may support consultation of respective patients. This study explores QoL of patients with olfactory dysfunction and evaluates associated clinical risk factors for QoL prediction. One hundred eight patients suffering from chronic rhinosinusitis (CRS) and allergic rhinitis (AR) and 30 healthy subjects were studied. Olfactory function was evaluated using objective olfactory test. All patients completed six validated questionnaires either specific for olfaction (Questionnaire of Olfactory Deficits [QOD]) and for assessing psychological state (Zung Anxiety Scale [ZAS], State-Trait Anxiety Inventory, Zung Depression Scale, and Beck Depression Inventory [BDI]) or a generic one (Short Form 36). Significantly poorer QoL and more severe anxiety and depression symptoms were observed in anosmic (all p < 0.001) and hyposmic patients compared with controls. Anosmic patients presented significantly worse results compared with hyposmic and normosmic patients. However, higher scores were observed in hyposmic compared with normosmic patients only in the QOD, ZAS, and BDI scale. Patients with CRS presented significantly poorer QoL than patients with AR only. The presence of nasal polyps or concomitant AR in patients with CRS did not show any differentiation in the results. Asthma was associated with significantly worse scores in all the psychometric questionnaires. Olfactory dysfunction was found to decrease QoL among patients. Anosmia, CRS disease, and asthma as clinical predictors were proved to be independently correlated with QoL, anxiety, and depression levels.


Dynamic MR angiography in acute aortic dissection.
To evaluate the benefit (additional flow information), image quality, and diagnostic accuracy of a dynamic magnetic resonance angiography (MRA) combining high spatial and temporal resolution for the preinterventional assessment of acute aortic dissection. Nineteen patients (12 men, 7 women; aged 32-78 years) with acute aortic dissection underwent contrast-enhanced four-dimensional (4D) MRA and 3D conventional high-resolution MRA (3D MRA) within one examination on a 1.5 Tesla MR system. Both MRA datasets for each patient were evaluated and compared for image quality and visualization of vascular details on a 5-point scale (5 = excellent image quality, 1 = nondiagnostic image quality). In addition, presence and relevance of additional hemodynamic information (flow direction and organ perfusion delay) gained by dynamic MRA were assessed. Conventional 3D MRA provided significantly higher values for image quality of the aorta and aortic side branches compared with dynamic MRA (aorta: 4.3 versus 3.3; P = 0.006 side branches: 4.2 versus 3.3; P = 0.02). However, in 10 of the 19 patients (53%) the additionally available information on flow dynamics due to dynamic MRA (e.g., delayed perfusion of parenchymal organs) led to a change in therapy planning and realization. Dynamic MRA is a technique that combines functional flow and morphological information. Thus, the combination of 3D and dynamic MRA provides all requested information for treatment planning in patients suffering from acute aortic dissection.


Increased pathogenicity against coffee berry borer, Hypothenemus hampei (Coleoptera: Curculionidae) by Metarhizium anisopliae expressing the scorpion toxin (AaIT) gene.
Coffee berry borer (CBB) is the Worlds most devastating coffee pest causing an estimated US$500 million worth of losses annually through damage and control costs. Beauveria bassiana and Metarhizium anisopliae have been employed to control this pest but their low virulence (slow kill and large inoculums) is an important factor constraining their use. M. anisopliae (AaIT-Ma549) has been modified to express the scorpion toxin (AaIT) in insect hemolymph and this greatly increased pathogenicity against Manduca sexta and Aedes aegypti. Here, we demonstrate that AaIT-Ma549 was also dramatically more virulent against CBB, and we provide a much more comprehensive analysis of infection processes and post-mortality development than in the previous research. We evaluated several spore concentrations (10(1) through 10(7)spores/ml) of both the wild type and recombinant strain. At concentrations of 10(1), 10(2) and 10(3)spores/ml, the recombinant strain significantly increased mortality of CBB by 32.2%, 56.6% and 24.6%, respectively. The medial lethal concentration (LC(50)) was reduced 15.7-fold and the average survival time (AST) was reduced by 20.1% to 2.98+/-0.1 days with 10(7)spores/ml. This is the first occasion that an entomopathogenic fungus has been found to kill CBB in less than 3 days. However, AaIT-Ma549 produces significantly fewer spores on cadavers than the parental strain.


Erythroid Krüppel-like factor (EKLF) is active in primitive and definitive erythroid cells and is required for the function of 5'HS3 of the beta-globin locus control region.
Disruption of the gene for transcription factor EKLF (erythroid Krüppel-like factor) results in fatal anaemia caused by severely reduced expression of the adult beta-globin gene, while other erythroid-specific genes, including the embryonic epsilon- and fetal gamma-globin genes, are expressed normally. Thus, EKLF is thought to be a stage-specific factor acting through the CACC box in the beta-gene promoter, even though it is already present in embryonic red cells. Here, we show that a beta-globin gene linked directly to the locus control region (LCR) is expressed at embryonic stages, and that this is only modestly reduced in EKLF-/- embryos. Thus, embryonic beta-globin expression is not intrinsically dependent on EKLF. To investigate whether EKLF functions in the locus control region, we analysed the expression of LCR-driven lacZ reporters. This shows that EKLF is not required for reporter activation by the complete LCR. However, embryonic expression of reporters driven by 5'HS3 of the LCR requires EKLF. This suggests that EKLF interacts directly with the CACC motifs in 5'HS3 and demonstrates that EKLF is also a transcriptional activator in embryonic erythropoiesis. Finally, we show that overexpression of EKLF results in an earlier switch from gamma- to beta-globin expression. Adult mice with the EKLF transgene have reduced platelet counts, suggesting that EKLF levels affect the balance between the megakaryocytic and erythroid lineages. Interestingly, the EKLF transgene rescues the lethal phenotype of EKLF null mice, setting the stage for future studies aimed at the analysis of the EKLF protein and its role in beta-globin gene activation.


Quantum feedback control of atomic motion in an optical cavity.
We study quantum feedback cooling of atomic motion in an optical cavity. We design a feedback algorithm that can cool the atom to the ground state of the optical potential with high efficiency despite the nonlinear nature of this problem. An important ingredient is a simplified state-estimation algorithm, necessary for a real-time implementation of the feedback loop. We also describe the critical role of parity dynamics in the cooling process and present a simple theory that predicts the achievable steady-state atomic energies.


Bayés syndrome and acute cardioembolic ischemic stroke.
Bayés syndrome is an under-recognized clinical condition characterized by advanced interatrial block. Bayés syndrome is a subclinical disease that manifests electrocardiographically as a prolonged P wave duration > 120 ms with biphasic morphology ± in the inferior leads. The clinical relevance of Bayés syndrome lies in the fact that is a clear arrhythmological syndrome and has a strong association with supraventricular arrhythmias, particularly atypical atrial flutter and atrial fibrillation. Likewise, Bayés syndrome has been recently identified as a novel risk factor for non-lacunar cardioembolic ischemic stroke and vascular dementia. Advanced interatrial block can be a risk for embolic stroke due to its known sequelae of left atrial dilation, left atrial electromechanical dysfunction or atrial tachyarrhythmia (paroxysmal or persistent atrial fibrillation), conditions predisposing to thromboembolism. Bayés syndrome may be responsible for some of the unexplained ischemic strokes and shall be considered and investigated as a possible cause for cryptogenetic stroke. In summary, Bayés syndrome is a poorly recognized cardiac rhythm disorder with important cardiologic and neurologic implications.


Neonatal outcome after exposure to indomethacin in utero: a retrospective case cohort study.
This study was undertaken to determine the clinical outcome for neonates who were exposed to indomethacin during gestation. We identified 124 infants with in utero exposure to indomethacin and matched them to 124 infants whose mothers did not receive indomethacin. The two groups were matched for gestational age at birth, sex, and exposure to antenatal betamethasone. Sixty-two of the indomethacin-exposed infants were born within 48 hours of last exposure. These infants were also compared with their matched controls. There were no significant differences between the indomethacin-exposed infants and control infants in birth weight, Apgar scores, frequency of cesarean section deliveries, and multiple gestation. The incidence of respiratory distress syndrome, need for surfactant treatment, patent ductus arteriosus, necrotizing enterocolitis, and intraventricular hemorrhage was similar between the indomethacin-exposed group and the control group. Indomethacin-exposed infants who were born within 48 hours of last exposure had similar incidence of respiratory distress syndrome but greater need for surfactant treatment (P=.02) compared with controls. All other complication rates were similar. Indomethacin exposure in our study was not associated with increased neonatal complications for infants delivered within or beyond 48 hours of last exposure.


Photoinitiated Rearrangement of Aromatic Azides to 2-Aminonicotinates.
This study describes a one-pot photoinduced method for azepine synthesis and their subsequent rearrangement into pyridines. The rearrangement of the azepine, formed during photolysis, occurs due to both thermal and photochemical activation of the reaction. This requires an electron-donating substituent at the second position of the azepine and an electron-withdrawing substituent at the third position of the azepine. A reaction mechanism has been proposed to explain the role of water and the nature of the azepine substituents.


The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8+ T lymphocytes in endomyocardial biopsy derived T cell cultures.
Long-term survival of heart transplant recipients is limited by the development of transplant coronary artery disease (TCAD). We analysed whether the development of TCAD is correlated with the incidence of acute rejection episodes, with the formation of anti-HLA antibodies or with the composition and function of T lymphocyte cultures derived from endomyocardial biopsies. TCAD was assessed by visual analysis of annually performed coronary angiograms and defined as the presence of all vascular changes, including minor wall irregularities. One year after transplantation, 31 of the 77 patients studied had TCAD (40%). The median age and mean number of HLA mismatches in patients with or without TCAD were highly comparable. The patient groups did not differ in incidence of acute rejection episodes, nor in percentage of endomyocardial biopsies yielding T cell cultures. At 1 year after transplantation, lymphocyte cultures from 18/31 TCAD+ patients (58%) and 27/46 TCAD- patients (57%) were analysed. The TCAD+ patients had, compared with the TCAD- patients, a higher median percentage of CD8+ T cells (71% versus 25%, P = 0.06) and a lower median percentage of CD4+ T cells (4% versus 40%, P = 0.04). Similar differences were found in a longitudinal analysis of the culture results of endomyocardial biopsies (EMBs) obtained during the first year. The cytotoxic reactivity of the cultures against donor HLA class I or class II antigens was comparable in the two groups, although a difference in recognition of heart specific antigens remains possible. The fact that EMB-derived cultures from TCAD+ and TCAD- patients differed in T cell phenotype populations gives some support to the hypothesis that cellular immunological processes are involved in the development of TCAD. However, while the median values differed, the overlap of the percentages of CD8+ cells in cultures from TCAD- and TCAD+ patients shows that other factors besides CD8+ T cells also play a role.


Early luteal phase treatment with mifepristone (RU 486) for fertility regulation.
Mifepristone (RU 486) is an antiprogestin which interacts with progesterone at the receptor level. Administration of mifepristone immediately after ovulation does not upset the menstrual cycle. However, the maturation and function of the endometrium is inhibited and uterine contractility is changed. To test if these effects are sufficient to prevent implantation, 21 women agreed to use one single treatment with 200 mg mifepristone on day luteinizing hormone (LH) + 2 monthly as their only contraceptive method. The women were treated for 1-12 months. The time of the LH peak was determined in the urine by the women themselves using a rapid LH test (Ovu-quick, Organon). The overall number of cycles studied was 169. In 12 cycles the women were unable to detect the LH peak. In these cycles no treatment was given and the women advised to use barrier methods during the time to menstruation. The remaining 157 cycles with a detectable LH peak were all ovulatory based on plasma progesterone measurement. One pregnancy occurred. On the basis of the time of the LH peak, it was retrospectively calculated that in 124 cycles at least one act of intercourse occurred during the period 3 days before to 1 day after ovulation. The probability of pregnancy in this period of the menstrual cycle is thus 0.008. The women did not complain of any treatment-related side-effects apart from slight bleeding for 2-3 days starting a few days after the day of treatment in 35% of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS)


Multifunctional Fe3O4@C-based nanoparticles coupling optical/MRI imaging and pH/photothermal controllable drug release as efficient anti-cancer drug delivery platforms.
Multifunctional nanomedicines featuring high drug loading capacity, controllable drug release and real-time self-monitoring are attracting increasing attention due to their potential to improve cancer therapeutic efficacy. Herein, a new kind of Fe3O4@C-based nanoparticles modified with isoreticular metal organic frameworks (IRMOF-3), folic acid (FA) and detachable polyethylene glycol (PEG) under tumor microenvironment was developed. The core-shell structured Fe3O4@C was synthesized via the one-pot solvothermal reaction and the IRMOF-3 layers were coated on the outer shell of Fe3O4@C through layer-by-layer coating method. The FA and PEG were conjugated on the surface of nanoparticles by reacting with the amine groups provided by IRMOF-3. The as-synthesized nanoparticles showed stable photothermal effect, superparamagnetic properties and blue fluorescence characteristic under 360 nm irradiation. The in vitro experiments showed that the drug loaded nanoparticles exhibit pH-dependent drug release property, and PEGylation was proved effective in suppressing burst drug release (only 8.0% of drugs were released within 95 h). The confocal laser scanning microscopy study revealed that the as-synthesized nanoparticles could serve as a cell imaging agent and the cell internalization can be significantly enhanced after FA modified. The IRMOF-3 modified nanoparticles showed negligible cytotoxicity and the drug loaded nanoparticles showed pH/photothermal-stimuli enhanced cytotoxicity in vitro. It is believed that the present smart drug delivery platforms will hold great potential in imaging guided drug delivery and cancer therapy.


Antiviral prophylactic intervention for chronic hepatitis C virus in patients undergoing liver transplantation.
It is not clear whether prophylactic antiviral therapy is indicated in patients undergoing liver transplantation for chronic decompensated hepatitis C virus (HCV) infection. To compare the benefits and harms of different prophylactic anti-viral therapies for patients undergoing liver transplantation for chronic HCV infection. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until August 2010. Only randomised clinical trials irrespective of language, blinding, or publication status and comparing various prophylactic antiviral therapies (alone or in combination) in the prophylactic treatment of patients undergoing liver transplantation for chronic HCV infection. Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) or hazard ratio (HR) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case analysis. A total of 477 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in eleven trials to various interventions and controls. The proportion of genotype I varied between 49% to 88% in the five trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. There was no significant differences in the patient survival, graft rejection, re-transplantation, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation, primary graft non-function, intensive therapy unit stay, hospital stay, or quality of life. Life-threatening adverse events were not reported in either group in any of the comparisons. Up to 91% of patients required reduction in dose and up to 36% of patients required cessation of treatment in the various comparisons because of adverse events or because of patient's choice to stop treatment. There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or re-transplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary.


Photonic crystal-based smart contact lens for continuous intraocular pressure monitoring.
Glaucoma is a very common disease after cataracts and is dangerous enough to cause irreversible blindness. However, often the main symptom of glaucoma is difficult to recognize because it may be absent or appear late, so the risk of blindness is greater. Intraocular pressure (IOP) is a well-known primary factor indicating glaucoma. In this study, we demonstrate a smart IOP sensor embedded in a contact lens that works through visual color changes without an external power source such as a battery or RF-based wireless power transfer. A microhydraulic amplification mechanism is adopted to enhance the range of color change from a photonic crystal (PC)-based flexible membrane whose lattice distance between nanostructures varies according to the morphology changes of an eyeball caused by IOP. The performance of the sensor is quantitatively demonstrated using an artificial silicone eye model for in vitro evaluation and a porcine eyeball for ex vivo verification. It has a limit of detection (LOD) of 3.2 and 5.12 mmHg, which was measured and evaluated using a spectrometer and a smartphone camera, respectively. The results prove that our sensor embedded in the contact lens can continuously monitor the IOP change using color change, and a smartphone camera can be used as a quantitative IOP measurement system in a noninvasive manner without an expensive optical spectrometer.


Effect of packing on changes in erythrocyte osmotic fragility and malondialdehyde concentration in donkeys administered with ascorbic acid.
Experiments were performed with the aim of investigating the effect of packing on erythrocyte osmotic fragility (EOF) and malondialdehyde (MDA) concentration in donkeys, and the effect of ascorbic acid (AA). Twelve apparently healthy donkeys raised under the traditional extensive system served as experimental subjects. Six donkeys administered orally with AA (200 mg/kg) and subjected to packing were used as experimental animals, whilst six others not administered with AA served as controls. Blood samples were collected pre- and post-packing from all the donkeys for the determination of MDA and EOF. At 0.3% Sodium Chloride (NaCl) concentration, the percentage haemolysis was 93.69% ± 2.21% in the control donkeys and the value was significantly (P < 0.05) higher than the value of 71.31% ± 8.33%, recorded in the experimental donkeys. The post-packing MDA concentration obtained in the control donkeys was 39.62 µmol ± 4.16 µmol, and was not significantly different (P > 0.05) from the value of 35.97 µmol ± 2.88 µmol recorded in the experimental donkeys. In conclusion, the increase in haemolysis obtained in the donkeys suggested that packing induced oxidative stress, which was ameliorated by AA administration.


[A bibliographic review about education for the elective cardiosurgical patients: does an educational activity during the preoperative period improve wellness and quality of life of the postoperative period?].
It's well known that a preoperative educational activity facilitates the course of the postoperative period with a reduction of anxiety, pain and stress. Nevertheless at the present effectiveness of such activity is still underestimated. The current literature agrees that a correct educational training represents an important nursing care activity, but up to date, the scientific evidences are not yet diffused in our hospitals. To investigate the efficacy of a preoperative educational training on adult cardiosurgical patients (age > 18), on wellness and improvement of postoperative quality of life. Accurate literature investigation on Medline, Trip database, Joanna Briggs Institute website and EBN Study Center Policlinico S.Orsola-Malpighi (Italy) website, was performed on a 5 years period (2003 - 2007). Level II recommendations about some educational aspects were highlighted: time of learning, knowledge, ability and correct performance of the exercises.


Research note: simultaneous histochemical determination of three fiber types in single sections of broiler skeletal muscles.
A staining procedure used for simultaneously determining three different fiber types in single sections of bovine, porcine, or ovine skeletal muscle was modified for use with broiler skeletal muscle. The modification involved acid-preincubation of muscle sections at a pH of 4.15 followed by staining for reduced nicotinamide adenine dinucleotide (NADH) tetrazolium reductase enzyme and for acid-stable myosin-adenosine triphosphatase enzyme activity, respectively. Four broiler muscles were selected for fiber-type determination of fast (alpha), slow (beta), red, aerobic (R), or white, anaerobic (W) properties. The anterior latissimus dorsi muscle was composed almost entirely of beta-R fibers while the pectoralis superficialis muscle was composed almost entirely of alpha-W fibers. The sartorius and posterior latissimus dorsi muscles were much more heterogeneous in fiber-type distribution, exhibiting all three types of fibers (alpha-W, alpha-R, and beta-R).


Association between dietary fibre:carbohydrate intake ratio and insulin resistance in Japanese adults without type 2 diabetes.
An easily understandable index that measures the quality of carbohydrate may aid people in adopting dietary habits that improve their glucose tolerance. We aimed to evaluate the relationship between a ratio of dietary fibre to carbohydrate intakes (fibre:carbohydrate ratio (F:C-R)) and glucose tolerance cross-sectionally and longitudinally. Subjects were 190 Japanese men and women without type 2 diabetes (mean age 55·4 years) who participated in a 5-month diet and exercise programme. We compared baseline anthropometric, dietary and metabolic profiles between those with higher F:C-R and those with lower ratios. Multivariable regression analyses were performed to examine the associations between the F:C-R and homoeostasis model of assessment for insulin resistance (HOMA-IR) and HbA1c at baseline and between changes in the F:C-R and changes in HOMA-IR and HbA1c over the 5-month period. At baseline, the higher F:C-R group had significantly lower body weight, lean body mass, fasting insulin level and HOMA-IR as compared with the lower F:C-R group. The two groups had similar intakes of carbohydrate and fat, whereas protein intake was greater in the high F:C-R group. Baseline F:C-R was not significantly associated with HOMA-IR or HbA1c at the beginning of the study in multivariable models. Increases in the ratio during the 5-month programme was associated with reductions in HbA1c (P<0·001). These findings highlight the potential utility of the F:C-R in strategies aimed at type 2 diabetes prevention.