Expediting Time from Symptoms to Medical Contact Utilizing a Telemedicine Call Center.
No definitive solution has been forthcoming for the often dangerously long interval between symptom onset and seeking medical care in the prehospital setting. We examined the implementation of telemedicine technology and characterization of its utilizers for its efficacy in reducing this possibly life-threatening time lag. A retrospective observational study was performed on the working database of an operational telemedicine facility that included all subscribers. Time-to-contact measurements throughout 2012 were retrieved from its medical files, and data on age, gender, medical history, and main complaint were analyzed. Throughout 2012, 22,274 of a total of 46,556 calls (47.8%) were made ≤60 min from symptom onset. It is important that 26.9% of all calls (12,522/46,556) were made in <15 min. Significantly more males (10,794/22,229 [49%]) contacted in ≤60 min compared with females (11,480/24,327 [47%], p<0.03). Subjects <60 years of age (2,889/5,717 [51%]) called earlier than those >60 years (19,386/40,839 [47%], p<0.001). Patients with prior resuscitation and/or myocardial infarction contacted significantly more rapidly than those with other cardiac diseases. Over one-half of patients with cardiac complaints contacted the call center ≤60 min from symptom onset, as did those who suffered physical trauma, but not patients with gastrointestinal symptoms or pain elsewhere. A telemedicine system with rapid accessibility to a professional call center and prompt triage thereafter could be an additional promising strategy for shortening the interval between symptom onset and call for medical assistance. Implementation of a widespread telemedicine infrastructure may bridge the unmet gap between occurrence of symptoms to initiation of medical treatment.


Efficient Calculation of Electronic Structure Using O(N) Density Functional Theory.
We propose an efficient way to calculate the electronic structure of large systems by combining a large-scale first-principles density functional theory code, Conquest, and an efficient interior eigenproblem solver, the Sakurai-Sugiura method. The electronic Hamiltonian and charge density of large systems are obtained by Conquest, and the eigenstates of the Hamiltonians are then obtained by the Sakurai-Sugiura method. Applications to a hydrated DNA system and adsorbed P2 molecules and Ge hut clusters on large Si substrates demonstrate the applicability of this combination on systems with 10,000+ atoms with high accuracy and efficiency.


Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections.
Protozoa and bacteria transmitted by arthropods, including ticks and phlebotomine sand flies, may cause a wide range of canine vector-borne diseases. Dogs can be simultaneously or sequentially infected with multiple pathogens. Canine babesiosis caused by Babesia canis canis and Babesia canis vogeli is known to occur in Portugal. This study assessed, by means of blood smear examination, PCR and DNA nucleotide sequencing, the presence of Babesia spp. and co-infecting agents Leishmania, Anaplasma/Ehrlichia and Hepatozoon in 45 dogs from northern Portugal clinically suspected of babesiosis. Forty-four dogs (98%) had infection with B. canis canis and one with B. canis vogeli. Co-infections were detected in nine animals (20%). Eight dogs were found infected with two vector-borne agents: six with B. canis canis and Leishmania infantum; one with B. canis canis and Ehrlichia canis; and one with B. canis canis and Hepatozoon canis. Another dog was infected with three vector-borne pathogens: B. canis vogeli, E. canis and L. infantum. Overall, L. infantum was found in seven (16%), E. canis in two (4%), and H. canis in one (2%) out of the 45 dogs with babesiosis. Almost 90% of the 45 cases of canine babesiosis were diagnosed in the colder months of October (18%), November (27%), December (20%), February (13%) and March (9%). Co-infections were detected in February, March, April, May, October and November. Twenty-two (50%) out of 44 dogs infected with B. canis were found infested by ticks including Dermacentor spp., Ixodes spp. and Rhipicephalus sanguineus. Mortality (9%) included two co-infected dogs that died spontaneously and two with single infections that were euthanized. Babesia canis canis is the main etiological agent of canine babesiosis in northern Portugal. A higher sensitivity of Babesia spp. detection was obtained with PCR assays, compared to the observation of blood smears. Twenty percent of the dogs were co-infected with L. infantum, E. canis or H. canis. Furthermore, this is the first molecular identification of H. canis in dogs from northern Portugal.


Endeavor of Iontronics: From Fundamentals to Applications of Ion-Controlled Electronics.
Iontronics is a newly emerging interdisciplinary concept which bridges electronics and ionics, covering electrochemistry, solid-state physics, electronic engineering, and biological sciences. The recent developments of electronic devices are highlighted, based on electric double layers formed at the interface between ionic conductors (but electronically insulators) and various electronic conductors including organics and inorganics (oxides, chalcogenide, and carbon-based materials). Particular attention is devoted to electric-double-layer transistors (EDLTs), which are producing a significant impact, particularly in electrical control of phase transitions, including superconductivity, which has been difficult or impossible in conventional all-solid-state electronic devices. Besides that, the current state of the art and the future challenges of iontronics are also reviewed for many applications, including flexible electronics, healthcare-related devices, and energy harvesting.


Early development in Rett syndrome - the benefits and difficulties of a birth cohort approach.
Typically, early (pre-diagnostic) development in individuals later diagnosed with Rett syndrome (RTT) has been investigated retrospectively using parent reports, medical records and analysis of home videos. In recent years, prospective research designs have been increasingly applied to the investigation of early development in individuals with late phenotypical onset disorders, for example, autism spectrum disorder. In this study, data collected by the Danish National Birth Cohort lent itself to prospective exploration of the early development of RTT, in particular early motor-, speech-language, and socio-communicative behaviors, mood, and sleep. Despite limitations, this quasi prospective methodology proved promising. In order to add substantially to the body of knowledge, however, specific questions relating to peculiarites in early development could usefully be added to future cohort studies. As this involves considerable work, it may be more realistic to consider a set of indicators which point to a number of developmental disorders rather than to one.


Imaging structure sensitive catalysis on different shape-controlled platinum nanoparticles.
The structure sensitive catalytic activity for oxygen reduction reaction (ORR) on shape-controlled Pt nanoparticles (NPs) is directly imaged using scanning electrochemical microscopy (SECM). We synthesize and compare four types of Pt NPs: spherical, cubic, hexagonal, and tetrahedral-octahedral. Our SECM images show the hexagonal Pt NPs displaying the highest activity for ORR in two acid electrolytes. Meanwhile, cubic and tetrahedral-octahedral NPs drastically change their activity depending on specific adsorption of the different anions in solution. The NPs morphology produces predominant crystallographic planes at the surface of these shape-controlled Pt NPs, which are responsible for their different catalytic activity. Our results translate the studies on Pt single crystal electrodes present in the literature into Pt NPs that are useful as a catalyst in real fuel cells.


Intra-articular morphine after arthroscopic knee operation.
Reports on pain relief with intra-articular morphine after arthroscopic knee operation are conflicting. To assess the long-term antinociceptive effect of intraarticular morphine, we studied pain at rest, pain on standing and ability to walk for 7 days after intraarticular injection of bupivacaine 100 mg (group 1, n = 11), bupivacaine 100 mg and morphine 1 mg (group 2, n = 10) and bupivacaine 100 mg and morphine 3 mg (group 3, n = 10) at the end of operation. Pain and walking were assessed by visual analogue and walking scales, respectively. Pain was treated with morphine i.v. in the recovery room and Tylenol No. 3 after discharge. Assessments were made before operation, and 1, 3, 6 and 12 h after injection and on days 1-7 after operation. There were significant differences between the groups in pain scores (pain at rest, P < 0.05; pain on standing, P < 0.01). The pain scores in group 3 were lower than those in group 1. The differences in pain scores at rest were significant at 12 h and on day 1 after operation and differences in pain scores on standing were significant at 12 h and on days 1 and 2 after operation. The scores in group 2 were intermediate between those in groups 1 and 3. The walking scores in group 3 were significantly better than those in group 1 at 12 h. The amount of analgesics received in groups 2 and 3 was significantly less than that in group 1 until day 3 after operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term consistency in spatial patterns of primate seed dispersal.
Seed dispersal is a key ecological process in tropical forests, with effects on various levels ranging from plant reproductive success to the carbon storage potential of tropical rainforests. On a local and landscape scale, spatial patterns of seed dispersal create the template for the recruitment process and thus influence the population dynamics of plant species. The strength of this influence will depend on the long-term consistency of spatial patterns of seed dispersal. We examined the long-term consistency of spatial patterns of seed dispersal with spatially explicit data on seed dispersal by two neotropical primate species, Leontocebus nigrifrons and Saguinus mystax (Callitrichidae), collected during four independent studies between 1994 and 2013. Using distributions of dispersal probability over distances independent of plant species, cumulative dispersal distances, and kernel density estimates, we show that spatial patterns of seed dispersal are highly consistent over time. For a specific plant species, the legume Parkia panurensis, the convergence of cumulative distributions at a distance of 300 m, and the high probability of dispersal within 100 m from source trees coincide with the dimension of the spatial-genetic structure on the embryo/juvenile (300 m) and adult stage (100 m), respectively, of this plant species. Our results are the first demonstration of long-term consistency of spatial patterns of seed dispersal created by tropical frugivores. Such consistency may translate into idiosyncratic patterns of regeneration.


Behavioral Health Treatment Patterns Among Employer-Insured Adults in Same- and Different-Gender Marriages and Domestic Partnerships.
This study examined specialty behavioral health treatment patterns among employer-insured adults in same- and different-gender domestic partnerships and marriages. The study used behavioral health service claims (2008-2013) from Optum to estimate gender-stratified penetration rates of behavioral health service use by couple type and partnership status among partnered adults ages 18-64 (N=12,727,292 person-years) and levels of use among those with any use (conditional analyses). Least-squares, logistic, and zero-truncated negative binomial regression analyses adjusted for age, employer and plan characteristics, and provider supply and for sociodemographic factors in sensitivity analyses. Generalized estimating equations were used to address within-group correlation of adults clustered in employer groups. Both women and men in same-gender marriages or domestic partnerships had higher rates of behavioral health service use, particularly diagnostic evaluation, individual psychotherapy, and medication management, and those in treatment had, on average, more psychotherapy visits than those in different-gender marriages. Behavioral health treatment patterns were similar between women in same-gender domestic partnerships and same-gender marriages, but they diverged between men in same-gender domestic partnerships and same-gender marriages. Moderation analysis results indicated that adults with same-gender partners living in states with fewer legal protections for lesbian, gay, bisexual, and transgender persons were less likely than adults with same-gender partners in LGBT-friendly states to receive behavioral health treatment. Sensitivity analyses did not affect findings. Behavioral health treatment patterns varied by couple type, partnership status, and gender. Results highlight the importance of increasing service acceptability and delivering inclusive, culturally relevant behavioral health treatment for lesbian, gay, and bisexual persons.


NLRP3 inflammasome expression in peripheral blood monocytes of coronary heart disease patients and its modulation by rosuvastatin.
Nucleotide‑binding oligomerization domain, leucine rich repeat, and pyrin domain‑containing protein 3 (NLRP3) inflammasome has been implicated in a series of physiological and pathological processes. However, its correlation in coronary heart disease (CHD) still remains to be elucidated. The present study aimed to determine the expression of NLRP3 inflammasome in peripheral blood monocytes (PBMCs) of stable angina pectoris (SAP) and acute myocardial infarction (AMI) patients. In addition, the effect of rosuvastatin on their activities was analyzed in vitro. A total of 60 participants with SAP (n=20), AMI (n=20) and non‑CHD controls (n=20) were enrolled. Fluorescence‑activated cell sorting, real‑time PCR, western blotting and enzyme‑linked immunosorbent assay were performed to reveal the role of NLRP3 inflammasome. NLRP3 inflammasome was expressed in the PBMCs, and revealed an increased expression along the downstream interleukin (IL)‑1β and IL‑18 in both SAP and AMI groups, compared to the control group. Moreover, there was a more marked increase in the expression of these indicators in AMI patients when compared to SAP patients. Interference with rosuvastatin in vitro revealed that the expression of NLRP3 inflammasome and its downstream cytokines were significantly downregulated in both SAP and AMI groups in a time‑dependent manner. The activation of NLRP3 inflammasome may be involved in the development of CHD, and rosuvastatin could attenuate the inflammatory process of atherosclerosis by downregulating NLRP3 expression and its downstream mediators. These findings indicated a potential role of NLRP3 in the pathogenesis and management of CHD, and also provided new insights into the mechanistic framework of rosuvastatin activity.


Bridging optical fiber communication and underwater wireless optical communication via third harmonic generation.
In this paper, we propose an optical module, consisting of an Erbium/Ytterbium co-doped fiber amplifier (EYDFA) and a cascaded periodically poled lithium niobate (cascaded-PPLN), to bridge the conventional telecommunication and the emerging underwater wireless optical communication (UWOC). Compared with using two discrete crystals to achieve the third harmonic generation (THG), using a cascaded crystal simplifies the optical system. Under a fundamental power of 5 W at 1550 nm, we have generated an optical power of 6.54 mW at 516 nm, corresponding to a conversion efficiency of 0.1308%. Furthermore, we added a 5-km single-mode fiber (SMF) before the EYDFA, and by adjusting the seed laser power, we successfully maintained the efficiency of the THG process and the output power of the green light. Afterwards, the nonlinearity of the THG process is analyzed, and a simplified nonlinear pre-compensation method has been proposed to tailor the 4-pulse amplitude modulation (PAM4) signals. In such case, the bit error rate (BER) of the modified PAM4 (m-PAM4) can reduce by 69.3% at a data rate of 12 Gbps. Finally, we demonstrate the practicality of our proposed system by achieving a 7-m UWOC transmission in a water tank at a data rate of 13.46 Gbps in an optical dark room. This result demonstrates the feasibility of the hybrid fiber/UWOC system, highlighting its potential for practical implementation.


Antifungal therapy and length of hospitalization in transplant patients with invasive aspergillosis.
The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed.


Venous thromboembolism and cancer: a two-way clinical association.
In recent years, a growing body of evidence has provided the convincing demonstration of a strong association between cancer and venous thromboembolism. This relationship is further supported by the risk of developing overt malignancy in patients with idiopathic venous thromboembolism. However, the cost-to-benefit ratio of an extensive diagnostic work-up aimed at identifying an occult cancer in patients with spontaneous thromboembolism still has to be demonstrated. During prolonged immobilization from any cause, and following surgical interventions, patients with cancer are at a remarkably higher risk of venous thromboembolism than patients free from malignant disorders. Standard heparin in adjusted doses or a low-molecular-weight heparin in doses commonly recommended for high risk surgical patients represent the prophylactic treatment of choice for cancer patients undergoing an extensive abdominal or pelvic intervention. Furthermore, the risk of thrombotic episodes is increased in cancer patients by chemotherapy and by the use of indwelling central venous catheters. Recent data suggest a positive benefit-to-risk ratio with the systematical use of fixed mini-dose of warfarin in both conditions. After experiencing an episode of thrombosis, cancer patients remain at risk of recurrence for as long as the cancer is active. Therefore, they should be protected by a long-term course of oral anticoagulation. The risk of recurrent thrombotic events despite adequate anticoagulation is higher in patients with cancer than in those without cancer. The routine use of long-term subcutaneous heparin therapy rather than oral anticoagulants should be reserved for patients in whom warfarin has been ineffective. Can antithrombotic drugs improve survival in cancer patients? In cancer patients affected by deep-vein thrombosis, the treatment with low-molecular-weight heparins has been reported to lower mortality at a higher extent than the standard heparin therapy. Such an observation suggests that these agents might develop an antineoplastic activity.


Inhibition of procollagen I degradation by colligin: a collagen-binding serpin.
Colligin is a collagen-binding glycoprotein localized to the endoplasmic reticulum (ER) and has been proposed to play a role in collagen biosynthesis. Its membership in the serpin family prompted us to examine its effect on procollagen degradation. We first showed that procollagen degradation can take place in the ER of L6 myoblasts by using brefeldin A to block transit from the ER. This degradation could be prevented by the serine protease inhibitors N-tosyl-L-lysine chloromethyl ketone (TLCK) and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK). To examine procollagen degradation in vitro, isolated liver microsomes were incubated with procollagen. Intact microsomes were unable to degrade labeled procollagen I, fibronectin, or the cytoplasmic proteins, phosphorylase b and the RI subunit of the cAMP-dependent protein kinase. However, when the microsomes were permeabilized by treatment with detergent, they became capable of degrading procollagen and fibronectin, but not the cytoplasmic proteins. The degrading activity was not due to cross-contamination by lysosomal or cytoplasmic, multicatalytic proteases. The proteolysis of procollagen chains in the treated microsomes was partially inhibited by TPCK, TLCK, and leupeptin. The most effective inhibitor was, however, colligin. In its presence, the breakdown of procollagen I, but not of fibronectin, was specifically inhibited. Colligin itself was not degraded by the microsomal preparations. The protein degrading activity was localized to the microsomal membranes, and showed a pH optimum of about 8.0. From these studies it is inferred that one of the roles of colligin may be to protect the procollagen I chains in the ER from degradation prior to their transport to the cis-Golgi compartment.


[A rare case of ectopic, normally functioning thyroid tissue presenting as a left submandibular mass].
This report describes the case of a 53-year-old female, who presented with a painless swelling in the left submandibular region which had gradually increased in size. Thirty years ago, this patient underwent subtotal thyroidectomy at another hospital and her thyroid function subsequently appeared normal. She presented no symptoms of hypothyroidism when she visited our hospital. A clinical diagnosis of a benign tumor arising from the submandibular gland was made with enhanced CT scan, MRI and technesium scintigraphy. The submandibular mass was surgically excised and the resected tissue revealed a well-delineated, encapsulated, solid and reddish-brown colored mass. Histological examination confirmed ectopic thyroid tissue with partial adenomatous goiter including vacuolated rich colloid in the thyroid follicles which suggested compensatory hyperplasia. Because this patient presented with post-operative hypothyroidism, we concluded that this ectopic lesion had continued to secrete thyroid hormone. Ectopic thyroid tissue should be considered in the differential diagnosis of swellings involving the submandibular area, especially if the ectopic tissue would be the only functioning thyroid tissue.


Alpha-Hederin Nanopore for Single Nucleotide Discrimination.
Various types of biological and synthetic nanopores have been developed and utilized for the high-throughput investigation of individual biomolecules. Biological nanopores made with channel proteins are so far superior to solid-state ones in terms of sensitivity and reproducibility. However, the performance of a biological nanopore is dependent on the protein in the channel structure its dimensions are predetermined and are difficult to modify for broader applications. Here inspired by the cytotoxic mechanisms of a saponin derivative, alpha-hederin, we report a nonproteinaceous nanopore that can be formed spontaneously in a lipid membrane. We propose the pore-forming mechanism of alpha-hederin in a cholesterol-rich lipid membrane and a strategy to control the pore-forming rate by a lipid partitioning method. The small diameter and effective thickness of alpha-hederin nanopores enabled us to discriminate ssDNA homopolymers as well as four types of nucleotides, showing its potential as a DNA sequencing tool.


Pre-eclampsia-associated differential expression of proteoglycans in the umbilical cord arteries.
The role of proteoglycans (PGs) of the umbilical cord arteries (UCAs) in the pathomechanism of pre-eclampsia is not known. Therefore we decided to compare the PGs of normal (control) UCAs and those of newborns delivered by mothers with pre-eclampsia. PGs were extracted in dissociative conditions, purified by Q-Sepharose anion exchange chromatography and lyophilized. They were analyzed by gel filtration and SDS-PAGE before and after treatment with chondroitinase ABC. It was found that the PG preparation from pre-eclamptic UCAs had a higher amount of sulphated glycosaminoglycans (in relation to protein) than in the case of control UCAs. The predominant PG fraction included small PGs with core proteins of 45 and 47 kD, immunologically related to biglycan (45 kD) and decorin (45 and 47 kD). The expression of decorin core proteins was increased and that of biglycan slightly decreased in pre-eclamptic UCAs. Some other putative small PG core proteins (56, 53, 49, 42, 38 and 34 kD) were also found. They were present in higher amounts in pre-eclamptic UCAs. Larger PGs (core proteins of 99-110 and >150 kD), were detected in lower amounts, both in control and particularly in pre-eclamptic material. Pre-eclampsia is associated with alterations in PG composition of the UCAs. They may affect the mechanical properties of this organ and disturb fetal blood circulation.


Role of plasmids in virulence-associated attributes and in O-antigen expression in Shigella dysenteriae type 1 strains.
The association of plasmids with virulence characters and O-antigen expression was studied in two virulent and seven avirulent mutant strains of Shigella dysenteriae type 1. Deletion of a 12-Mda segment from a 140-Mda plasmid in two smooth avirulent mutants made the derivatives avirulent in the Sereny test and non-invasive in HeLa cells. The mutants were unable to bind Congo red, and did not express the virulence marker antigen. Mutants completely lacking the 140-Mda plasmid also showed similar avirulent characters. However, rough mutants retained the ability to bind Congo red. Our results indicate that the essential gene(s) for virulence may be located on the 140-Mda plasmid, a small deletion from which may lead to avirulence. This deletion did not affect the protein antigen expression nor change their antigenicity. Analysis of lipopolysaccharide (LPS) patterns showed that strains containing the 6-Mda plasmid produced the complete LPS and were smooth, whereas strains containing either the 140- or a 4- or 2-Mda plasmid, in the absence of the 6-Mda plasmid, produced smaller amounts of O antigen and were rough. Western-blot analysis and crossed immuno-electrophoresis gave similar results. The 140-, 4-, or 2-Mda plasmid, in the absence of the 6-Mda plasmid, may code for non-specific galactosyl transferase-like activity which can add, non-specifically and at a reduced level, the galactose residue (the first sugar in the O antigen repeat unit) to the LPS core.(ABSTRACT TRUNCATED AT 250 WORDS)


Enhanced thermal shock resistance of ceramics through biomimetically inspired nanofins.
We propose here a new method to make ceramics insensitive to thermal shock up to their melting temperature. In this method the surface of ceramics was biomimetically roughened into nanofinned surface that creates a thin air layer enveloping the surface of the ceramics during quenching. This air layer increases the heat transfer resistance of the surface of the ceramics by about 10,000 times so that the strong thermal gradient and stresses produced by the steep temperature difference in thermal shock did not occur both on the actual surface and in the interior of the ceramics. This method effectively extends the applications of existing ceramics in the extreme thermal environments.


A Novel Implementation of Magnetic Levitation to Quantify Leukocyte Size, Morphology, and Magnetic Properties to Identify Patients With Sepsis.
We have developed a novel, easily implementable methodology using magnetic levitation to quantify circulating leukocyte size, morphology, and magnetic properties, which may help in rapid, bedside screening for sepsis. Our objectives were to describe our methodological approach to leukocyte assessment, and to perform a pilot investigation to test the ability of magnetic levitation to identify and quantify changes in leukocyte size, shape, density, and/or paramagnetic properties in healthy controls and septic patients. This prospective, observational cohort study was performed in a 56,000/y visit emergency department (ED) and affiliated outpatient phlebotomy laboratory. Inclusion criteria were admittance to the hospital with suspected or confirmed infection for the septic group, and we enrolled the controls from ED/outpatient patients without infection or acute illness. The bench-top experiments were performed using magnetic levitation to visualize the leukocytes. We primary sought to compare septic patients with noninfected controls and secondary to assess the association with sepsis severity. Our covariates were area, length, width, roundness, and standard deviation (SD) of levitation height. We used unpaired t test and area under the curve (AUC) for the assessment of accuracy in distinguishing between septic and control patients. We enrolled 39 noninfected controls and 22 septic patients. Our analyses of septic patients compared with controls showed: mean cell area in pixels (px) 562 ± 111 vs. 410 ± 45, P < 0.0001, AUC = 0.89 (0.80-0.98); length (px), 29 ± 2.5 vs. 25 ± 1.9, P < 0.0001, AUC = 0.90 (0.83-0.98); and width (px), 27 ± 2.4 vs. 23 ± 1.5, P < 0.0001, AUC = 0.92 (0.84-0.99). Cell roundness: 2.1 ± 1.0 vs. 2.2 ± 1.2, P = 0.8, AUC = 0.51. SD of the levitation height (px) was 72 ± 25 vs. 47 ± 16, P < 0.001, AUC = 0.80 (0.67-0.93). Septic patients had circulating leukocytes with especially increased size parameters, which distinguished sepsis from noninfected patients with promising high accuracy. This portal-device compatible technology shows promise as a potential bedside diagnostic.


Effects of microcarrier concentration in animal cell culture.
Results are presented which show how the microcarrier concentration affects the hydrodynamic environment in animal cell bioreactors. At low levels of agitation, no physical effects of microcarrier concentration were found. However, cell growth was strongly influenced by cell concentration. At high levels of agitation, a strong detrimental effect of microcarrier concentration was found. A new mechanism of hydrodynamic damage was identified which is second order in microcarrier concentration. The identification of this mechanism adds to the fundamental understanding of hydrodynamic phenomena in microcarrier bioreactors.


Endovascular Thrombectomy Treatment: Beyond Early Time Windows and Small Core.
Tremendous advancements in the treatment of acute ischemic stroke in the last 25 years have been based on the principle of reperfusion in early time windows and identification of small core infarct for intravenous thrombolysis and mechanical thrombectomy. Advances in neuroimaging have made possible the safe treatment of patients with acute ischemic stroke in longer time windows and with more specific selection of patients with salvageable brain tissue. In this review, we discuss the history of endovascular stroke thrombectomy trials and highlight the neuroimaging-based trials that validated mechanical thrombectomy techniques in the extended time window with assessment of penumbral tissue. We conclude with a survey of currently open trials that seek to safely expand eligibility for this highly efficacious treatment.


[Enzyme kinetic analysis of Oncomelania hupensis exposed to active ingredient of Buddleja lindleyana (AIBL)].
To analyze the enzyme kinetics of active ingredient of Buddleja lindleyana (AIBL) against Oncomelania hupensis, the intermediate host of Schistosoma japonicum. O. hupensis snails were placed in 1 000 ml of 3.55 mg/L AIBL solution for 24, 48 h and 72 h, respectively, and the enzyme kinetics of alanine aminotransferase (GPT) was determined by Reitman-Frankel assay, lactate dehydrogenase (LDH) by the chemical inhibition lactic acid substrate method, alkaline phosphatase (AKP) by the disodium phenyl phosphate colorimetric method, acetylcholine esterase (AChE) and malate dehydrogenas (MDH) by ELISA, and succinate dehydrogenase (SDH) by the phenazine methyl sulfate reaction method (PMS) in the soft tissues of O. hupensis before and after AIBL treatment. Following exposure to 3.55 mg/L AIBL solution for 24 h, the GPT, LDH, and AKP activities significantly improved in the soft tissues of O. hupensis, while the SDH and MDH activities were significantly lowered in the head-foot and liver. However, AIBL treatment did not cause significant effect on AChE activity in O. hupensis. AIBL causes significant damages to O. hupensis liver and can efficiently act on anaerobic and aerobic respiration loci, which will hinder energy metabolism, and cause inadequate energy supply in cells used for normal secretion, eventually leading to O. hupensis death.


A new animal model for menopausal transition: combination of ovariectomy and empty bottle stimulation.
Previous small animal models for menopausal transition are mainly performed to mimic the biochemical changes of patients with menopausal transition. The psychological symptoms in animal models are often overlooked. To mimic clinical situation, we developed a new mouse model of menopausal transition: the combination of bilateral ovariectomy (OVX) and empty bottle stimulation (EBS). After OVX and 21 days of EBS, behavioral test and pentobarbital-induced sleep test were carried out. Then all the animals were euthanized for further investigations. Compared with the control group, the combination of OVX and EBS group (OVX + EBS) showed higher bodyweight, lower organ index of uteri, and lower concentrations of serum estradiol. In addition, behavioral manifestations, sleep quality, and morphologic features in OVX + EBS group showed significant differences compared with the control group. OVX alone or EBS alone failed to include all the changes of OVX + EBS group. These findings indicate ovariectomy or EBS alone could not well mimic the symptoms of menopausal transition. The combination of bilateral ovariectomy and EBS offers an easy and repeatable method for building comprehensive menopausal transition model in mice.


The Asian perspective on HIFU.
High intensity focused ultrasound (HIFU) uses about 800 times the diagnostic ultrasound power, which converges at a focal point to deliver energy above 60 degrees Celsius resulting in cell death by means of coagulation necrosis and cavitation destruction. This article is a reflection of my journey in gynaecological surgery, from basic laparotomy to minimally invasive surgery (MIS) to virtual surgery of noninvasive technology. This work also states an opinion shared by a lot of MIS colleagues in Asia. I am indeed fortunate to witness the transformation, revolution and disruption of surgery in gynecology in my lifetime. I think HIFU has allowed us to achieve the basic tenets of surgery, one of less pain, minimal complications, optimal destruction of a diseased organ, and optimal conservation of the human body. In this article, I will focus on HIFU treatment of uterine fibroids and adenomyosis. Uterine fibroids or myomas are common benign growths of the uterus and occurs in 20% to 50% of reproductive females. Adenomyosis involves endometrial lining cells that invade into the body of the uterus, like rust into the body of a car. Both uterine fibroids and adenomyosis can cause pain, heavy menstrual bleeding, and anemia. They can compress surrounding organs as they grow, leading to urinary, bowel, vascular and obstructive complications. Fertility may also be compromised.


A novel combined polyphenol-aldehyde crosslinking of collagen film-Applications in biomedical materials.
Despite its crucial role in directing cell fate in healthy and diseased tissues, improvements in physical-chemical properties and biocompatibility of type-I collagen are still needed. In this report, we described combined and facile method to modify collagen. The collagen film was first modified by procyanidins solution, in which, then subjected to further crosslinked by dialdehyde alginate, resulting in collagen-procyanidins-dialdehyde alginate film. The properties of the crosslinked collagen films were investigated and the results were discussed. Results from differential scanning calorimetry and thermo gravimetric analysis suggested that the thermal stabilities of the collagen-procyanidins-dialdehyde alginate film were significantly improved. The mechanical properties of collagen-procyanidins-dialdehyde alginate film in terms of elongation at break and tensile strength increased approximately 2-fold and 3-fold, respectively compare to pure collagen film. In addition, the resistance to collagenase degradation of collagen-procyanidins-dialdehyde alginate film was remarkably promoted. The results from methyltetrazolium assay and confocal laser scanning microscopy showed that no cytotoxicity of collagen film was introduced by the combined crosslinking method. Thus, the novel combined by procyanidins-dialdehyde alginate crosslinking method shown in this study provided a non-toxic and efficient crosslinking method that improved various properties of collagen film, which has great potential applications in biomedical materials.


Oral Squamous Cell Carcinoma Found Inline with the Fields of Repeat Stereotactic Radiosurgery for Recurrent Trigeminal Neuralgia.
A case of an extremely healthy, active, 96-year-old patient, nonsmoker, is reviewed. He was initially treated for left V1, V2, and V3 trigeminal neuralgia in 2001, at age 80, with stereotactic radiosurgery (SRS) with a dose of 80 Gy to the left retrogasserian trigeminal nerve. He remained asymptomatic for nine years until his trigeminal pain recurred in 2010. He was first treated medically but was intolerant to increasing doses of carbamazepine and gabapentin. He underwent a second SRS in 2012 with a dose of 65.5 Gy to the same retrogasserian area of the trigeminal nerve, making the total cumulative dose 125.5 Gy. In late 2016, four years after the 2nd SRS, he was found to have invasive keratinizing squamous cell carcinoma in the left posterior mandibular oral mucosa. Keratinizing squamous cell carcinoma is seen primarily in smokers or associated with the human papillomavirus, neither of which was found in this patient. A review of his two SRS plans shows that the left lower posterior mandibular area was clearly within the radiation fields for both SRS treatments. It is postulated that his cancer developed secondary to the long-term radiation effect with a very localized area being exposed twice to a focused, cumulative, high-dose radiation. There are individual reports in the literature of oral mucositis immediately after radiation for trigeminal neuralgia and the delayed development of malignant tumors, including glioblastoma found after SRS for acoustic neuromas, but there are no reports of delayed malignant tumors developing within the general radiation field. Using repeat SRS is an accepted treatment for recurrent trigeminal neuralgia, but physicians and patients should be aware of the potential effects of higher cumulative radiation effects within the treatment field when patients undergo repeat procedures.


Salvage of local recurrence after primary thermal ablation for small renal masses.
The management of renal tumors has evolved rapidly over the last two decades, with the ascendance of nephron-sparing surgery (NSS), largely spurred by the increased incidental detection of small renal masses (SRMs) and evidence that preservation of renal parenchyma reduces the risk of chronic kidney disease. The field of NSS itself has advanced beyond the standard of open partial nephrectomy, with the application of minimally invasive techniques, such as laparoscopy and thermal ablation. Energy-based ablative therapies, which include cryoablation and radiofrequency ablation, are associated with reduced morbidity and represent a nascent but promising alternative to surgical extirpation in the treatment of SRMs. However, thermal ablation is associated with a higher rate of local tumor recurrence when compared with surgical excision, indicating that salvage therapy will be a necessity for some patients. With recent studies indicating that surgical excision of previously ablated kidneys can be complicated by significant fibrosis, clinicians who advocate thermal ablation must be cognizant of the sequelae of this treatment modality and versed on the potential difficulties associated with salvage surgery. We provide, herein, an assessment of the efficacy and limitations of primary thermal ablation and strategies for salvage treatment of local recurrence in this growing patient population.


Stability of plasmid content in Salmonella wien in late phases of the epidemic history.
Prevalence, genetic characteristics, and EcoRI cleavage analysis of plasmids identified in clinical strains of Salmonella wien isolated in recent years showed that the plasmid content in this serotype has remained uniform and stable over more than a decade and also late in the epidemic history. No correlation between decrease in S. wien isolations and naturally occurring systematic changes in the DNA of its most common FIme plasmid was structurally detectable.


Non-volatile extractable analysis of prefilled syringes for parenteral administration of drug products.
The determination of extractable profiles for single-use technologies represents an important aspect of pharmaceutical production to minimize any possible compromise in drug product quality or potential risk to patients by identifying substances that may potentially leach from such devices. An approach for the extractable assessment of prefilled syringes, a promising alternative for parenteral administration of pharmaceutical products, is described herein. Four extraction solvents were selected: a mixture 2-propanol:water (1:1), was intended to represent aggressive conditions to extract a broad spectrum of extractables, including organic additives and substances which are poorly water-soluble. Extractions with buffers at three different working pH values spanning a range standardly used in pharmaceutical formulations were also evaluated to identify substances that require specific conditions for their extraction due to their individual chemical properties. Syringes from two different brands were analysed along with their corresponding plunger stoppers. Syringes were extracted at 40°C for 4days, the plunger stoppers were extracted with 2-propanol at 70°C for 24h according to ISO 10993-12:2012. Extractables were identified by UHPLC-MS on a quadrupole time of flight instrument using a non-targeted discovery strategy. A total of 25 compounds were identified, mostly polymer additives and their degradation products. The presented methodology represents a reference point for further studies focused on the characterisation of extractables and leachables from prefilled syringes.


Asthma: Chronopharmacotherapy and the molecular clock.
Bronchial asthma is characterized by chronic airways inflammation and reversible airflow limitation. In patients with asthma, symptoms generally worsen during the early hours of the morning, and pulmonary function often deteriorates at the same time, suggesting a role for chronopharmacotherapy. Several drugs for asthma have been developed based on chronopharmacology. Most medications employed for the chronotherapy of asthma are administered once at night with the goal of preventing chronic airway inflammation or development of airflow limitation. In addition to bronchodilators, the inhaled glucocorticosteroid ciclesonide is now available with once-daily dosing, which also improves patients' compliance. Numerous investigations have demonstrated the usefulness of chronotherapy for asthma, especially for patients with nocturnal asthma. This review focuses on chronotherapy of asthma, and also provides a molecular biological explanation for the influence of asthma medications on the clock genes.


The Joint Effect of pH Gradient and Glucose Feeding on the Growth Kinetics of Lactococcus lactis CECT 539 in Glucose-Limited Fed-Batch Cultures.
Two glucose-limited realkalized fed-batch cultures of Lactococcus lactis CECT 539 were carried out in a diluted whey medium (DW) using two different feeding media. The cultures were fed a mixture of a 400 g/l concentrated lactose and a concentrated mussel processing waste (CMPW, 101.72 g glucose/l) medium (fermentation I) or a CMPW medium supplemented with glucose and KH2PO4 up to concentrations of 400 g glucose/l and 3.21 g total phosphorus/l, respectively (fermentation II). For an accurate description and a better understanding of the kinetics of both cultures, the growth and product formation by L. lactis CECT 539 were both modelled, for the first time, as a function of the amounts of glucose (G) added and the pH gradient (VpH) generated in every realkalization and feeding cycle, by using an empirical polynomial model. With this modeling procedure, the kinetics of biomass, viable cell counts, nisin, lactic acid, acetic acid and butane-2,3-diol production in both cultures were successfully described (R 2 values > 0.970) and interpreted for the first time. In addition, the optimum VpH and G values for each product were accurately calculated in the two realkalized fed-batch cultures. This approach appears to be useful for designing feeding strategies to enhance the productions of biomass, bacteriocin, and metabolites by the nisin-producing strain in wastes from the food industry. Two glucose-limited realkalized fed-batch cultures of Lactococcus lactis CECT 539 were carried out in a diluted whey medium (DW) using two different feeding media. The cultures were fed a mixture of a 400 g/l concentrated lactose and a concentrated mussel processing waste (CMPW, 101.72 g glucose/l) medium (fermentation I) or a CMPW medium supplemented with glucose and KH2PO4 up to concentrations of 400 g glucose/l and 3.21 g total phosphorus/l, respectively (fermentation II). For an accurate description and a better understanding of the kinetics of both cultures, the growth and product formation by L. lactis CECT 539 were both modelled, for the first time, as a function of the amounts of glucose (G) added and the pH gradient (VpH) generated in every realkalization and feeding cycle, by using an empirical polynomial model. With this modeling procedure, the kinetics of biomass, viable cell counts, nisin, lactic acid, acetic acid and butane-2,3-diol production in both cultures were successfully described (R 2 values > 0.970) and interpreted for the first time. In addition, the optimum VpH and G values for each product were accurately calculated in the two realkalized fed-batch cultures. This approach appears to be useful for designing feeding strategies to enhance the productions of biomass, bacteriocin, and metabolites by the nisin-producing strain in wastes from the food industry.


Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.
Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients. The binding of diclofenac to albumin was investigated in the aqueous humor. In a diclofenac binding assay with albumin in the aqueous humor of individual patients, diclofenac was extracted from aliquots of the aqueous humor, and its total levels were measured using ultra high performance liquid chromatography (UHPLC). Free diclofenac levels were measured using ultrafiltration and UHPLC. The albumin-binding fraction of diclofenac was 0.8 or higher in the aqueous humor of some patients. Ibuprofen significantly inhibited diclofenac binding to site II of albumin in mimic aqueous humor, but not in pooled aqueous humor. This difference may have been due to the weak binding of diclofenac to site II in the pooled aqueous humor. Flurbiprofen was used instead of diclofenac. Flurbiprofen has been shown to bind more strongly than diclofenac to the same site of albumin. Thus, the inhibitory effect of ibuprofen on the binding of flurbiprofen to albumin was investigated in pooled aqueous humor. The results indicated that ibuprofen significantly inhibited the flurbiprofen binding. An effective diclofenac administration method may be established for clinical application by the instillation of an appropriate inhibitor of binding to the albumin site II.


Purification and characterization of a CMP-sialic:LcOse4Cer sialyltransferase from human colorectal carcinoma cell membranes.
Purified lactotetraosylceramide (Gal beta 1----3GlcNAc beta 1----3Gal beta 1----4Glc1-Cer) was tested for its ability to accept [14C]sialic acid from CMP-[14C]sialic into monosialoganglioside fractions in the presence of membrane fractions purified from human colorectal carcinoma cells (SW1116). Membrane fractions were isolated by three different methods: sucrose density centrifugation, CMP-agarose gel column chromatography, and LcOse4 gel chromatography. We optimized the incubation conditions for detergent dependency (taurocholate), pH (6.3), and acceptor concentration. The sialyltransferase activity was dependent on membrane protein and linear for time up to at least 4 h. The LcOse4 affinity chromatography of the crude microsomal membrane pellet from these cells yielded a membrane fraction that was 136-fold enriched in LcOse4 acceptor specific activity compared to cell homogenates. The apparent Km for the sialyltransferase activity with LcOse4Cer acceptor in the presence of affinity-purified membranes was 20 microM and the Vmax was 7 pmol h-1 (100 micrograms of protein)-1. Acceptor capabilities of other core structures were 5-20-fold lower: LcOse4Cer much greater than GgOse4Cer greater than nLcOse4Cer much greater than GbOse4Cer. The enzymatic activity was purified further (900-fold) by a combination of LcOse4 and CMP affinity gels. SDS-PAGE electrophoresis of this material showed a major set of closely migrating bands of Mr 58,000-54,000 compared to authentic proteins, as well as a minor band at 27,000. We analyzed picomole quantities of the radioactive product by convenient controlled short-term hydrolyses with an endoglycoceramidase and sialidases (from four different sources) in comparison to sialylated tetrasaccharides of known structure.(ABSTRACT TRUNCATED AT 250 WORDS)


Beryllium: Effect of Ultra-High Pressure on Resistance.
Beryllium, subjected to a pressure of 93 kb at 25 degrees C undergoes a change in structure, as indicated by a 45-percent decrease in resistance. At 55 kb a small change in the resistance-pressure relationship suggests another modification of the usual hexagonal-close-packed structure.


JTE-852, a novel spleen tyrosine kinase inhibitor, blocks antigen-induced allergic reactions in rats.
Conventional clinical treatments for allergy management remain suboptimal; new, orally available medications that improve a wide range of allergic signs have been desired. We previously demonstrated that JTE-852, a novel spleen tyrosine kinase inhibitor, potently and simultaneously suppresses secretion of granule contents, arachidonate metabolites, and cytokines from mast cells stimulated by immunoglobulin E-crosslinking. In the present study, we investigated the effects of JTE-852 in four rat models (sneezing, rhinorrhea, airway constriction, and airway inflammation) as representatives of allergy models. Rats were sensitized and challenged with antigen. Allergic reactions developed after challenge were detected. JTE-852 and current anti-allergic drugs (ketotifen, pranlukast, and prednisolone) were administered orally before challenge. JTE-852 showed significant blocking effects on antigen-induced allergic reactions in all models, indicating that JTE-852 in oral dosage form would improve a wide range of allergic signs. The current anti-allergic drugs, on the other hand, failed to display significant suppression in several models. Because JTE-852 suppresses the secretion of all three groups of allergic mediators from mast cells, it would be capable of targeting signs that current drugs cannot sufficiently relieve. We anticipate JTE-852 to be a promising new anti-allergic drug that is potentially more effective than conventional drugs.


Adaptive Domain Generalization Via Online Disagreement Minimization.
Deep neural networks suffer from significant performance deterioration when there exists distribution shift between deployment and training. Domain Generalization (DG) aims to safely transfer a model to unseen target domains by only relying on a set of source domains. Although various DG approaches have been proposed, a recent study named DomainBed (Gulrajani and Lopez-Paz, 2020), reveals that most of them do not beat simple empirical risk minimization (ERM). To this end, we propose a general framework that is orthogonal to existing DG algorithms and could improve their performance consistently. Unlike previous DG works that stake on a static source model to be hopefully a universal one, our proposed AdaODM adaptively modifies the source model at test time for different target domains. Specifically, we create multiple domain-specific classifiers upon a shared domain-generic feature extractor. The feature extractor and classifiers are trained in an adversarial way, where the feature extractor embeds the input samples into a domain-invariant space, and the multiple classifiers capture the distinct decision boundaries that each of them relates to a specific source domain. During testing, distribution differences between target and source domains could be effectively measured by leveraging prediction disagreement among source classifiers. By fine-tuning source models to minimize the disagreement at test time, target-domain features are well aligned to the invariant feature space. We verify AdaODM on two popular DG methods, namely ERM and CORAL, and four DG benchmarks, namely VLCS, PACS, OfficeHome, and TerraIncognita. The results show AdaODM stably improves the generalization capacity on unseen domains and achieves state-of-the-art performance.


Mind, medications & mental disorders: a spiritual approach.
In mental illness, individuals may choose faith-based counseling as primary treatment, with medical care as a supportive adjunct. Biblical Framework Counseling (BFC) is based on belief of the Bible's sufficiency to address the root causes of mental disorders that are not otherwise physiologically caused. Clients address underlying spiritual issues while medical care and pharmacotherapy adherence are encouraged to support symptom relief. Consultation between patient, BFC counselor and healthcare clinician is emphasized to optimize outcomes.


Creation of a list of homonyms in Brazilian Portuguese for linguistic processing tasks.
Purpose This paper presents procedures and steps to create a list of homonyms, their meanings and representative images. Methods One hundred and three homonyms in Brazilian Portuguese were secluded through searches in text books and dictionaries and the meanings were verified. The homonyms were analyzed and selected according pre-established criteria. Twenty-six homonyms with two meanings were selected and one image was used to represent each meaning. To test the instrument, twenty elementary school children in 4th (n = 10) and 5ht (n = 10) grades were selected from a private school in São Paulo. To identify the meanings of major and minor occurrence, the students gave their understanding of the words presented to them orally. The students were also asked to name the fifty-two images to determine the degree of recognition. Percentages of accuracy were calculated. Results Among the 26 homonyms, two were excluded because the students were unable to name them. Two images were little recognized and, therefore, replaced with others that better represented the homonyms. Conclusion A list of 24 homonyms and 48 images (one for each meaning) was developed. The results of the presentation of these items to elementary school children in the 4th and 5th grades proved the adequacy of the list. The material is seen as efficient for use in recognition tasks and can be applied in semantic priming tasks.


A Real-World, Observational Study of the Initiation, Use, and Effectiveness of Basal-Bolus or Premixed Insulin in Japanese People with Type 2 Diabetes.
Basal-bolus (BB) and premixed insulin regimens may lower fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), but are complex to use and associated with weight gain and hypoglycaemia. Although randomized controlled trials and prospective observational studies in insulin-naïve Japanese patients with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs) initiating these regimens have been conducted, real-world data are lacking. This study describes the characteristics of patients initiating these regimens in routine clinical practice and identifies the course and outcomes of therapy in the year following initiation. Adults with T2D initiating BB or premixed regimens following OAD therapies held in a Japanese electronic medical record database were identified (2010-2019). Subcohorts were determined by treatment changes during ≤ 12 months of follow-up (no change, intensified, switched, discontinued). Outcomes included change in glycated haemoglobin levels (HbA1c), probability of first reaching HbA1c < 7% (stratified by baseline OAD number, HbA1c and age), and hypoglycaemia incidence. The main cohorts comprised 1315 BB and 1195 premixed therapy initiators. Most individuals (67.9%) initiated BB as inpatients; 50.8% switched at a mean of 47.6 days. Mean HbA1c lowering was - 2.5% for BB and - 1.4% for premixed regimens (no change cohorts). Overall, a greater proportion achieved HbA1c < 7% if they were (at baseline) taking fewer OADs, in a lower HbA1c category, and aged ≥ 65 years. Hypoglycaemia incidence (< 70 mg/dl) was higher with BB than premixed regimens and lower in patients aged < 65 years. Greater HbA1c reductions, but a higher incidence of hypoglycaemia, were reported with BB versus premixed regimens, while both cohorts demonstrated clinically meaningful reductions in HbA1c during follow-up. After initiation, most premixed regimens remained unchanged, whereas switches from BB to less intensive regimens were numerous, in accordance with the use of BB for a limited duration to improve FPG and PPG control.


Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study.
Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan. We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint. The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant. Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.


Twenty years of the methadone treatment protocol in Ireland: reflections on the role of general practice.
Opioid dependence, characterised by socio economic disadvantage and significant morbidity and mortality, remains a major public health problem in Ireland. Through the methadone treatment protocol (MTP), Irish general practice has been a leader in the introduction and expansion of Irish harm reduction services, including opioid substitution treatment (OST), needle and syringe programs (NSP) and naloxone provision. These services have been effective in engaging opiate users in treatment, reducing human deficiency virus (HIV) and hepatitis C virus (HCV) transmission and reducing-drug related morbidities. Challenges remain in relation to choice of substitution treatments, timely access to OST services, adequate coverage of NSP, naloxone provision and increasing drug-related deaths. A narrative review was conducted and designed to present a broad perspective on the Irish MTP and to describe its history and development in terms of clinical care, stakeholder views and changing trends. Three themes emerged from the analysis; The History of the Methadone Treatment Protocol, Service User and Provider Views and Challenges and Developments. Despite the initial concern about methadone maintenance treatment (MMT) in Ireland, increased participation by Irish GPs in the treatment of opioid dependence is observed over the last two decades. There are now over 10,000 people on methadone treatment in Ireland, with 40% treated in general practice. The MTP provides structure, remuneration and guidance to GPs and is underpinned by training, ongoing education and a system of quality assurance provided by the Irish College of General Practice (ICGP). Challenges include the negative views of patients around how methadone services are delivered, the stigma associated with methadone treatment, the lack of choice around substitution medication, waiting lists for treatment in certain areas and rates of fatal overdose. Twenty years of the MTP has been the mainstay of harm reduction services in Ireland. It has provided a network of specially trained GPs who provide methadone to over 10,000 patients across Ireland within a structured framework of training, quality assurance and remuneration. With the ongoing commitment of Irish specialists in the field of addiction medicine, further improvements to support and treat patients can be made.


Pancreatico-renal composite transplant: a new technique designed to decrease pancreatic graft thrombosis.
Pancreas graft thrombosis continues to be a major cause of graft loss. The removal of the donor spleen is accompanied by a significant reduction in pancreas graft blood flow. It is likely that reduced blood flow contributes to thrombosis in concert with other factors. We present a case of simultaneous pancreas and dual kidney transplantation wherein one donor kidney was anastomosed to the splenic vessels of the pancreas graft. The portal venous drainage of the pancreas graft was into the vena cava and duodenal segment was drained into the recipient's jejunum. Intraoperative blood flow determinations using an ultrasonic flow probe around the graft portal vein showed that the placement of the renal graft in the position of the donor spleen improved flow by approximately one-third (e.g. at 15 min after transplantation, 800 cc/min vs. 550 cc/min with the composite vascular pedicle clamped). The perfusion phase of a radionuclide scan on postoperative day 3 showed both transplanted kidneys had brisk and comparable visualization. The patient had an uneventful recovery and was discharged on the seventh postoperative day with normal blood glucose values and a serum creatinine of 1.2 mg/mL. A pancreatico-renal composite graft may decrease the incidence of thrombosis by improving pancreatic graft blood flow.


Thermophysical properties of sulfonium- and ammonium-based ionic liquids.
Experimental data for the density, viscosity, refractive index and surface tension of four sulfonium- and ammonium-based Ionic Liquids (ILs) with the common bis(trifluoromethylsulfonyl)imide anion were measured in the temperature range between 288.15 and 353.15 K and at atmospheric pressure. The ILs considered include butyltrimethylammonium bis(trifluoromethylsulfonyl)imide, [N4111][NTf2], tributylmethylammonium bis(trifluoromethylsulfonyl)imide, [N4441][NTf2], diethylmethylsulfonium bis(trifluoromethylsulfonyl)imide, [S221][NTf2], and triethylsulfonium bis(trifluoromethylsulfonyl)imide, [S222][NTf2]. Based on the gathered results and on data taken from literature, the impact of the cation isomerism and of the size of the aliphatic tails, as well as the effect resulting from the substitution of a nitrogen by a sulfur atom as the cation central atom, on the thermophysical properties of sulfonium- and ammonium-based ILs is here discussed. Remarkably, more symmetric cations present a lower viscosity for the same, and sometimes even for higher, alkyl chain lengths at the cation. Additional derivative properties, such as the isobaric thermal expansion coefficient, the surface thermodynamic properties and the critical temperature for the investigated ILs were also estimated and are presented and discussed.


How I do it: Novel technique to "Unmask" and treat congenital portosystemic venous connections in congenital heart disease.
Congenital portosystemic venous connections are rare vascular anomalies that connect the portal and systemic venous circulations. These vascular lesions can lead to complex and varied physiologic manifestations in single-ventricle patients as they progress through the various stages of palliation in the Fontan pathway. Specifically, these connections may be unmasked after a superior cavopulmonary anastomosis operation, but then "re-masked" after Fontan completion. We describe the complex physiology with an illustrative case report and present a novel method to unmask these pathologic connections after Fontan completion to facilitate transcatheter occlusion and resolve downstream symptoms.


Viral oncoprotein LMP1 disrupts p53-induced cell cycle arrest and apoptosis through modulating K63-linked ubiquitination of p53.
Disruption of the gatekeeper p53 tumor suppressor is involved in various virus-associated tumorigeneses, with aberrant ubiquitination as the major cause of p53 abnormalities in virus-associated tumors. Of note, wild-type p53 is accumulated in Epstein-Barr virus (EBV)-associated tumors, especially in nasopharyngeal carcinoma (NPC). We have previously identified that p53 is accumulated and phosphorylated by EBV oncoprotein latent membrane protein 1 (LMP1) in NPC. Here, we further found that LMP1 promoted p53 accumulation via two distinct ubiquitin modifications. LMP1 promoted p53 stability and accumulation by suppressing K48-linked ubiquitination of p53 mediated by E3 ligase MDM2, which is associated with its phosphorylation at Ser20, while increasing the levels of total cellular ubiquitinated p53. LMP1 also induced K63-linked ubiquitination of p53 by interacting with tumor necrosis factor receptor-associated factor 2 (TRAF2), thus contributing to p53 accumulation. Furthermore, LMP1 rescued tumor cell apoptosis and cell cycle arrest mediated by K63-linked ubiquitination of p53. Collectively, these results demonstrate aberrant ubiquitin modifications of p53 and its biological functions by viral protein LMP1, which has broad implications to the pathogenesis of multiple EBV-associated tumors.


Salmonella enterica serovar typhimurium invades fibroblasts by multiple routes differing from the entry into epithelial cells.
Fibroblasts are ubiquitous cells essential to tissue homeostasis. Despite their nonphagocytic nature, fibroblasts restrain replication of intracellular bacterial pathogens such as Salmonella enterica serovar Typhimurium. The extent to which the entry route of the pathogen determines this intracellular response is unknown. Here, we analyzed S. Typhimurium invasion in fibroblasts obtained from diverse origins, including primary cultures and stable nontransformed cell lines derived from normal tissues. Features distinct to the invasion of epithelial cells were found in all fibroblasts tested. In some fibroblasts, bacteria lacking the type III secretion system encoded in the Salmonella pathogenicity island 1 displayed significant invasion rates and induced the formation of lamellipodia and filopodia at the fibroblast-bacteria contact site. Other bacterial invasion traits observed in fibroblasts were the requirement of phosphatidylinositol 3-kinase, mitogen-activated protein kinase MEK1, and both actin filaments and microtubules. RNA interference studies showed that different Rho family GTPases are targeted by S. Typhimurium to enter into distinct fibroblasts. Rac1 and Cdc42 knockdown affected invasion of normal rat kidney fibroblasts, whereas none of the GTPases tested (Rac1, Cdc42, RhoA, or RhoG) was essential for invasion of immortalized human foreskin fibroblasts. Collectively, these data reveal a marked diversity in the modes used by S. Typhimurium to enter into fibroblasts.


Synthesis of (2,2-Diborylvinyl)arenes by Rhodium-Catalyzed Desulfanylative gem-Diborylation of 2-Arylvinyl Sulfides.
An unexpected gem-diborylation of 2-arylvinyl sulfides with bis(pinacolato)diboron proceeded efficiently with a rhodium catalyst. A wide range of (2,2-diborylvinyl)arenes are easily synthesized by this method using readily available reagents, including the alkenyl sulfides, that are prepared from general materials in one step. Mechanistic studies indicate that the reaction proceeds from either of the stereoisomers in a stepwise manner via borylative C-S bond cleavage and subsequent dehydrogenative borylation.


Secondary correction of bilateral cleft lip deformity with simultaneous Abbé flap and nasal repair.
For secondary repair of a bilateral cleft lip deformity with a short columella and defective upper lip, simultaneous correction of the lip and nose is ideal. We perform a nasal repair through a bilateral reverse-U incision and columella elongation using the upper lip. An Abbé flap is then transferred to the upper lip defect. This procedure enables total reconstruction of characteristic bilateral cleft lip deformities in one stage. We have applied this method to 15 patients (9 males and 6 females) with an average age of 18.7 years. Although some patients need jaw surgery, all have been satisfied with the results.


Phosphate exchange between high-energy phosphate compounds in resting crustacean muscle.
Single giant muscle fibres from Megabalamus psittacus was microinjected with ATP-32P or internally perfused with a solution containing 32P-PArg in an attempt to demonstrate, in the absence of inhibitiors, ATP utilization during mechanical activity with negative results. The rate constant of transfer of 32P from microinjected 32P-PArg to endogenous ATP was studied at two different temperatures, obtaining a Q10 of 1.08 +/- .012. It is concluded that the rate limiting step in the process of transference of phosphate in the resting muscle from balanus is the intracellular diffusion of PArg and not the rate at which the equivalent of Lohman's reaction in invertebrates proceeds.


The Key Points of Maintenance Therapy for Dental Implants: A Literature Review.
Dental implants require lifelong maintenance and care. Success is defined by biologic factors (presence of inflamed soft tissues surrounding dental implants and radiographic changes in the crestal bone levels) and mechanical factors (stability of the implant fixture and implant supported restoration, etc). Most implant failures are initiated by incipient stages of inflammatory processes, which lead to peri-mucositis and peri-implantitis. The evidence regarding the value of maintenance protocol regarding implants is sparse compared with the one for teeth. This article addresses the existing literature on processes for oral hygiene for implant care.


Gender, economics and culture: diversity and the international evolution of smoking prevalence.
To examine whether the observed diversity between national patterns of smoking prevalence could require modification of the World Health Organization (WHO) linear model for an international 'smoking pandemic' (a worldwide epidemic) to address data from non-western countries. We conducted secondary research using current measures in three publicly available databases: Globalink, the International Labour Organization and the World Bank (all Internet-accessible). The measures we used are the separate percentage data for men and women on: smoking and employment and national income per capita (US$) and percentage growth per annum. Regression analysis showed that women smokers were more frequent in countries with higher national income, but women were less likely to smoke in countries of rapid growth. Men were less likely to smoke in countries with higher national income, but more likely to smoke in countries of rapid growth. Two principle components together explained 62% of all the variance in the international data. The largest factor was positively correlated with the percentage of employed females, the percentage of female smokers and national income per capita, but negatively correlated with the percentage of male smokers and percentage annual. growth. The effect of female employment was not continuous, but above a threshold of 51%, was associated with a higher prevalence of female smoking. The smaller, second factor was only weakly correlated with any smoking variables. In his 1994 model (subsequently adopted by the WHO) Lopez looked at historical trends in 'stages' of smoking prevalence. These have been associated with 'stages' of economic development. We extended this analysis to look at a dynamic change (% annual growth) and a social indicator (employment). Male and female smoking is affected differentially by economic change and by level of income. These are also strongly related to the percentage of women in employment. This has implications for workplace policies on smoking.


Is the composition of exhaled breath condensate a key to explain the course of COVID-19 in children?
The relative resistance of children to severe course of the novel coronavirus infection remains unclear. We hypothesized that there might be a link between this phenomenon and observation from our previous studies concerning an inhibitory or cytotoxic effect of exhaled breath condensate (EBC) on endothelial cell cultures in children. Since we could not find any data on the similar effect caused by EBC in adults, the aim of our study was to evaluate and compare the biological activity of EBC in adults and children in an experimental in vitro model. Furthermore, in order to identify a putative agent responsible for these properties of EBC in children, we attempted to analyse the composition of selected EBC samples. The influence of EBC samples on metabolic activity of endothelial cell line C-166 was assessed using colorimetric tetrazolium salt reduction assay (MTT assay). Selected EBC samples were fractionated using size exclusion chromatography and subjected to mass spectrometry analysis. Exhaled breath condensates in healthy children, but not in adults, revealed a cytotoxic effect on in vitro cell cultures. This effect was most significant in condensate fraction, which contained a prominent 4.8 kDa peak in the mass spectra. Breath condensates of healthy children contain the factor which reveals the inhibitory/cytotoxic effect on endothelial cell cultures. Although the physiological role of this agent remains unclear, its identification may potentially be useful in ongoing research on SARS-CoV-2/COVID-19.


Resonant fiber-optic strain and temperature sensor achieving thermal-noise-limit resolution.
In the area of fiber-optic sensors (FOSs), the past decade witnessed great efforts to challenge the thermal-noise-level sensing resolution for passive FOS. Several attempts were reported claiming the arrival of thermal-noise-level resolution, while the realization of thermal-noise-level resolution for passive FOSs is still controversial and challenging. In this paper, an ultrahigh-resolution FOS system is presented with a sensing resolution better than existing high-resolution passive FOSs. A fiber Fabry-Perot interferometer as the sensing element is interrogated with an ultra-stable probe laser by using the Pound-Drever-Hall technique. Both strain and temperature measurements are carried out to validate the performance of the sensor. The measured noise floor agrees with the theoretical thermal noise level very well.


Selective Serotonin Reuptake Inhibitors and Fertility: Considerations for Couples Trying to Conceive.
Depression and anxiety are prevalent disorders and are often treated with selective serotonin reuptake inhibitors (SSRIs). Infertility is also common among couples, and rates of depression and anxiety are elevated in this population, but the impact of SSRIs on fertility has received modest attention. This review explores the literature available on SSRIs, fertility, and infertility-treatment outcomes to assist clinicians in better counseling their patients. A literature search was performed using the search terms infertility, fertility, antidepressants, and SSRIs to identify studies that investigated the relationship between SSRI use and fertility or infertility-treatment outcomes. Twenty relevant articles were identified, 16 of which were original research studies. The studies varied in design, quality, and outcome measures, limiting meta-analysis. The prevalence of antidepressant use ranged from 3.5%-10% in reproductive-age women, with infertile populations reporting less use. The two studies examining the impact of SSRIs in fertile women had conflicting results. Six of the seven studies in infertility patients found no significant association between SSRIs and treatment outcomes; three observed a trend, however, toward reduced fecundability or negatively influenced fertility biomarkers. One study found treatment increased pregnancy rates. In males, most studies were of relatively poor quality, though six of the seven studies found SSRIs to have an adverse effect on semen parameters. There is insufficient evidence at present to propose that SSRIs reduce fertility or influence infertility-treatment outcomes. SSRIs may have an adverse impact on sperm quality, but further research is warranted.


Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.
The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.


A Novel MIMO⁻SAR Solution Based on Azimuth Phase Coding Waveforms and Digital Beamforming.
In multiple-input multiple-output synthetic aperture radar (MIMO⁻SAR) signal processing, a reliable separation of multiple transmitted waveforms is one of the most important and challenging issues, for the unseparated signal will degrade the performance of most MIMO⁻SAR applications. As a solution to this problem, a novel APC⁻MIMO⁻SAR system is proposed based on the azimuth phase coding (APC) technique to transmit multiple waveforms simultaneously. Although the echo aliasing occurs in the time domain and Doppler domain, the echoes can be separated well without performance degradation by implementing the azimuth digital beamforming (DBF) technique, comparing to the performance of the orthogonal waveforms. The proposed MIMO⁻SAR solution based on the APC waveforms indicates the feasibility and the spatial diversity of the MIMO⁻SAR system. It forms a longer baseline in elevation, which gives the potential to expand the application of MIMO⁻SAR in elevation, such as improving the performance of multibaseline InSAR and three-dimensional SAR imaging. Simulated results on both a point target and distributed targets validate the effectiveness of the echo separation and reconstruction method with the azimuth DBF. The feasibility and advantage of the proposed MIMO⁻SAR solution based on the APC waveforms are demonstrated by comparing with the imaging result of the up- and down-chirp waveforms.


Nonagenarian hip fracture: treatment and complications.
Hip fracture is a common yet serious injury sustained by the elderly patient and represents one of the major healthcare challenges today. The aim of this study was to better define the unique characteristics of treating nonagenarian peritrochanteric hip fractures and their subsequent complications during hospital stay. Seven hundred twenty-two patients underwent surgery for isolated fracture around the femoral neck. These patients were divided into one of three age groups: A, <50 years; B, 51-89 years; and C, >90 years. We performed a retrospective chart review to compare these groups in terms of patient characteristics, comorbidities, postoperative complications, fracture type, type of surgery performed, and mortality rate. There was no difference in time to surgery between groups. Comorbidities were similar in groups B and C but were higher than group A. Nonagenarians received a significantly greater percentage of hemiarthroplasties compared with those aged 51 years to 89 years. Cardiac complications were significantly higher in group C. In patients with sustained cardiac complications, the odds ratio for mortality was 15.88. Our results suggest that groups B and C were not significantly different pre- or intraoperatively. Nevertheless, there is an increase in cardiac complications and mortality in nonagenarians postoperatively. Nonagenarians should undergo similar treatment in the operating room compared with less elderly patients with the caveat that older patients, especially those with cardiac disease, may be more at risk for complication. The surgeon must evaluate the elderly patient with a hip fracture on a case-by-case basis, while ignoring chronological age. III, prognostic study.


Preparation of an novel botanic biopreservative and its efficacy in keeping quality of peeled Penaeus vannamei.
A novel botanic biopreservative was successfully prepared by the combination of the bamboo leaves extracts and ebony extracts, designated as ebony-bamboo leaves complex extracts (EBLCE), whose antimicrobial activity was assessed according to an inhibition zone method against 10 common pathogenic and spoilage microorganisms. It was found that EBLCE was more effective from all the chosen microorganisms, as compared by potassium sorbate. Due to its excellent antimicrobial activity, and some additional properties like edibility, safety and economy, EBLCE was selected for further study to evaluate the efficacy in prolonging shelf life and improving the quality of peeled Penaeus vannamei during storage at 4 °C, based on periodical microbiological, chemical and sensory analysis. As a result, EBLCE was observed to prevent spoilage of peeled P. vannamei efficiently as reflected by a distinct decrease in total viable count, pH and total volatile basic nitrogen, as well as a slower decline in the sensory evaluation scores. Therefore, a prolonged shelf life of 16 days was obtained for EBLCE pre-treated peeled shrimps with comparison of 6 days for the control group, demonstrating EBLCE as a promising alternative for preserving food.


Barriers and facilitators to being physically active on a rural U.S. Northern Plains American Indian reservation.
The objective of the present study was to identify barriers to and facilitators of physical activity among American Indian adults living on a rural, U.S. Northern Plains reservation using the nominal group technique (NGT). NGT is a method of data generation and interpretation that combines aspects of qualitative (free generation of responses) and quantitative (systematic ranking of responses) methodologies. Adults participated in one of two NGT sessions asking about either barriers to (n = 6), or facilitators of (n = 5), being physically active. Participants nominated and ranked 21 barriers and 18 facilitators. Barriers indicated lack of knowledge of how to fit physical activity into a daily schedule, work, caring for family members, and prioritizing sedentary pursuits. Other responses included environmental barriers such as lack of access and transportation to a gym, unsafe walking conditions, and inclement weather. Facilitators to following recommendations included knowledge of health benefits of physical activity and the perception of physical activity as enjoyable, including feeling good when working out. Environmental facilitators included being outdoors walking and biking as well as parks and exercise facilities. Responses provided direction for locally designed community-based programs to promote facilitators and decrease barriers to individual's engagement in physical activity.


Characteristics of apoptosis induction by the alkaloid emetine in human tumour cell lines.
Cytotoxic and apoptosis-inducing effects of the alkaloid emetine from Psychotria ipecacuanha (Rubiaceae) were studied in human cell lines. In Jurkat T-cells emetine leads to phosphatidylserine exposure, mitochondrial depolarisation, and DNA fragmentation. Furthermore, activation of several caspases (caspase-3, -9/6, and -8) was demonstrated in a fluorescent caspase assay. Bcl-2 over-expressing cells are less sensitive to emetine while caspase-8-deficient Jurkat T-cells react similarly to wild-type cells. This indicates that apoptosis induction is mediated via the mitochondrial pathway. By using hepatoma cell lines with differing p53 expression, it was concluded that p53 does not seem to play a role in apoptosis induction by emetine. Alterations of protein profiles during emetine-induced apoptosis were analysed by 2D-PAGE and MALDI-TOF-MS. A new protein spot was apparent after treatment with emetine: It could be identified as the N-terminal fragment lamin B1, which is released after cleavage by caspase-6.


The application of multiple metrics in deformable image registration for target volume delineation of breast tumor bed.
For postoperative breast cancer patients, deformable image registration (DIR) is challenged due to the large deformations and non-correspondence caused by tumor resection and clip insertion. To deal with it, three metrics (fiducial-, region-, and intensity-based) were jointly used in DIR algorithm for improved accuracy. Three types of metrics were combined to form a single-objective function in DIR algorithm. Fiducial-based metric was used to minimize the distance between the corresponding point sets of two images. Region-based metric was used to improve the overlap between the corresponding areas of two images. Intensity-based metric was used to maximize the correlation between the corresponding voxel intensities of two images. The two CT images, one before surgery and the other after surgery, were acquired from the same patient in the same radiotherapy treatment position. Twenty patients who underwent breast-conserving surgery and postoperative radiotherapy were enrolled in this study. For target registration error, the difference between the proposed and the conventional registration methods was statistically significant for soft tissue (2.06 vs. 7.82, p = 0.00024 < 0.05) and body boundary (3.70 vs. 6.93, p = 0.021 < 0.05). For visual assessment, the proposed method achieved better matching result for soft tissue and body boundary. Comparing to the conventional method, the registration accuracy of the proposed method was significantly improved. This method provided a feasible way for target volume delineation of tumor bed in postoperative radiotherapy of breast cancer patients.


miR-31 Links Lipid Metabolism and Cell Apoptosis in Bacteria-Challenged Apostichopus japonicus via Targeting CTRP9.
The biological functions of microRNAs (miRNAs) have been studied in a number of eukaryotic species. Recent studies on vertebrate animals have demonstrated critical roles of miRNA in immune and metabolic activities. However, studies on the functions of miRNA in invertebrates are very limited. Here, we demonstrated that miR-31 from Apostichopus japonicus disrupts the balance of lipid metabolism, thus resulting in cell apoptosis by targeting complement C1q tumor necrosis factor-related protein 9 (AjCTRP9), a novel adipokine with pleiotropic functions in immunity and metabolism. Lipidomic analysis suggested that the intercellular lipid metabolites were markedly altered, and three ceramide (Cer) species synchronously increased in the AjCTRP9-silenced coelomocytes. Moreover, exogenous Cer exposure significantly induced apoptosis in the coelomocytes in vivo, in agreement with findings from miR-31 mimic- or AjCTRP9 small-interfering RNA-transfected coelomocytes. Furthermore, we found that the imbalance in sphingolipid metabolism triggered by the overproduction of Cers ultimately resulted in the activation of the apoptosis initiator caspase-8 and executioner caspase-3. Our findings provide the first direct evidence that miR-31 negatively modulates the expression of AjCTRP9 and disturbance of Cer channels, thus leading to caspase-3- and caspase-8-dependent apoptosis, during the interactions between pathogens and host.


Evaluation of somatic embryos of alfalfa for recombinant protein expression.
Somatic embryos of alfalfa can accumulate higher levels of recombinant proteins comparing to vegetative organs. Somatic embryos may be explored as a new system for new protein production for plants. Plants have been explored via genetic engineering as an inexpensive system for recombinant protein production. However, protein expression levels in vegetative tissues have been low, which limits the commercial utilization of plant expression systems. Somatic embryos resemble zygotic embryos in many aspects and may accumulate higher levels of proteins as true seed. In this study, somatic embryo of alfalfa (Medicago sativa L.) was investigated for the expression of recombinant proteins. Three heterologous genes, including the standard scientific reporter uid that codes for β-glucuronidase and two genes of interest: ctb coding for cholera toxin B subunit (CTB), and hIL-13 coding for human interleukin 13, were independently introduced into alfalfa via Agrobacterium-mediated transformation. Somatic embryos were subsequently induced from transgenic plants carrying these genes. Somatic embryos accumulated approximately twofold more recombinant proteins than vegetative organs including roots, stems, and leaves. The recombinant proteins of CTB and hIL-13 accumulated up to 0.15 and 0.18 % of total soluble protein in alfalfa somatic embryos, respectively. The recombinant proteins expressed in somatic embryos also exhibited biological activities. As somatic embryos can be induced in many plant species and their production can be scaled up via different avenues, somatic embryos may be developed as an efficient expression system for recombinant protein production.


Stroke: bowel dysfunction in patients admitted for rehabilitation.
to assess the prevalence of diminished frequency of bowel movements, lumpy or hard stools, intestinal constipation, straining, incomplete evacuation, incontinence (bowel dysfunctions) in patients with brain injury resulting from cerebrovascular accident, either self-reported or reported by their caregivers; to describe the type and frequency of such dysfunctions; and the prevalence of laxative use both before and after stroke. cross-sectional study with 98 hospitalized patients admitted for rehabilitation between December 2009 and May 2010. the prevalence of bowel dysfunctions before stroke was 23.96% whereas after the lesion it was 55.21% (p<0.0001). As reported by patients/caregivers, the chances of developing bowel dysfunctions increase sevenfold after stroke, 95% CI (2.44-24.26). The most frequent dysfunctions before stroke were intestinal constipation (73.91%) and diminished frequency of bowel movements (17.39%). After stroke, constipation remains to be the most frequent dysfunction reported (50%), followed by diminished frequency of bowel movements (26.79%), incomplete evacuation (12.50%), and lack of privacy (5.36%). The use of laxatives was 19,15% after the lesion, but not statisticaly significant (p=0.0736). Bowel dysfunctions increases significantly after stroke. Therefore, further studies are needed to better understand and characterize such dysfunctions, which are scarcely described in the literature.


The effect of excessive weight reduction on peripheral and central nervous functions. A study in obese patients treated by gastric banding.
Twenty-four obese patients were studied before and 3, 6, and 12 months after gastric banding to see if the excessive weight reduction caused any dysfunction of the peripheral or central nervous system or both. Postoperatively the patients were assumed to be able to keep their intake to 800-1000 kcal/day together with a multivitamin supplement. Electromyography, electroneurography and vibratory thresholds were used to assess the peripheral, somatosensory and visual evoked potentials to assess the central nervous and synaptic functions. Regular clinical and neurological assessments were made as well as laboratory examinations including total potassium estimations to calculate lean body mass. The mean weight loss and the mean lean body mass reduction amounted to 20.5% and 18.4% at 3 months, and to 30.3% and 10.2% at 12 months, respectively. Electromyography showed signs of acute denervation in the anterior tibial muscle in one patient 3 and 6 months after operation, but restitution after 12 months despite continuous weight loss. In the left peroneal nerve the electroneurography showed a trend with slight successive reduction of the conduction velocity in the postoperative period. No abnormalities of the vibratory thresholds were found postoperatively. Somatosensory and visual evoked potentials were normal in all patients and no significant changes were observed during the postoperative period. The present study did not reveal any significant dysfunction of the peripheral or central nervous system as a result of excessive weight loss in obese adults undergoing weight reducing surgery.


The quality of parenting in reproductive donation families: A meta-analysis and systematic review.
This review examined whether the absence of a genetic link with one or both parents in families using reproductive donation induced a different quality of parenting from that found in families with spontaneous conception or autologous assisted reproductive technology (AUT-ART), where the genetic mother carries the pregnancy and both parents have a genetic link with their children. MEDLINE, PsycINFO and PubMed were searched for English-language studies published from January 1993 to October 2021. A total of 45 studies were included in the systematic review, and 11 in the meta-analysis. The meta-analysis showed that in reproductive donation families, where there was no genetic link between parents and children, there were higher positive parental values (P = 0.007) and lower negative parental values (P = 0.007) than for parents and children in families that had spontaneously conceived. No statistically significant differences emerged when the reproductive donation families were compared with the AUT-ART families. The study showed that the quality of parenting was not conditioned by the presence or absence of a genetic link; instead, it was influenced by the processes underlying family building, such as the desire to have a child, the involvement of both parents in the childcare and the quality of disclosure.