A real time, wearable ECG and continous blood pressure monitoring system for first responders.
The study of stress and fatigue among First Responders is a major step in mitigating this public health problem. Blood pressure, heart rate variability and fatigue related arrhythmia are three of the main "windows" to study stress and fatigue. In this paper we present a wearable medical device, capable of acquiring an electrocardiogram and estimating blood pressure in real time, through a pulse wave transit time approach. The system is based on an existent certified wearable medical device called "Vital Jacket" and is aimed to become a tool to allow cardiologists in studying stress and fatigue among first response professionals.


Mapping of linear and circular forms of mouse mammary tumor virus DNA with restriction endonucleases: evidence for a large specific deletion occurring at high frequency during circularization.
Rat hepatoma cells infected with mouse mammary tumor virus contain multiple forms of unintegrated viral DNA when grown in the presence of glucocorticoids. Using the DNA transfer procedure of Southern, we have prepared restriction endonuclease fragment maps of these forms of viral DNA. The maps indicate that: (i) the major species of viral DNA is a linear molecule of 5.9 X 10(6) Mr located in the cytoplasm; (ii) the nuclei contain covalently closed circular viral DNA of two distinct sizes (5.1 X 10(6) and 5.9 X 10(6) Mr) in addition to linear molecules (5.9 X 10(6) Mr); (iii) the linear molecule has specific termini; (iv) there is extensive homology between regions at or near termini of the linear molecule; (v) the predominant form of circular DNA lacks 1.2 kilobase pairs present in both the larger circular molecule and the linear molecule; and (vi) the sequences deleted from the majority of the circular DNA molecules are located at the ends of the linear DNA that are joined during circularization.


The effect of second trimester emergency cervical cerclage on perinatal outcome.
To evaluate the effectiveness of emergency cervical cerclage and to determine predictors of failure or success in women with cervical incompetence. Medical records were reviewed for clinical and demographic data, gestational age at time of cerclage, cerclage-delivery interval, gestational age at time of delivery; and birth weight. Predictors of success and failure were analyzed. Forty-three pregnant women between 18 and 25 weeks of gestation were recruited. The mean gestational age at time of cerclage was 21 weeks. The mean cerclage-delivery interval was 64 days. The mean gestation at delivery was 31 weeks and the mean neonatal birth weight was 2166 g. Whether cerclage done before or after 20 weeks, the difference in cerclage-delivery interval was insignificant while the difference in gestational age at time of delivery and neonatal birth weight was significant. Presence of infection, presence of symptoms, membranes through the cervix and dilated cervix >3 cm are frequently associated with failure. Emergency cervical cerclage is effective in prolonging pregnancy and improving neonatal outcome in patient with cervical incompetence. However, large prospective randomized controlled studies are recommended.


The Heart of the Killer Whale: Description of a Plastinated Specimen and Review of the Available Literature.
The killer whale (Orcinus orca, Linnaeus, 1958) is the largest extant delphinid. Despite its worldwide distribution in the wild and in dolphinariums, its anatomy remains relatively poorly described. In the present study, we describe the detailed morphology of a plastinated killer whale heart. The gross description of the arteries and veins reaching the organ and its coronary vessels are reported. Additional endoscopy and CT (computed tomography) scanning were performed to provide extensive measurements of its parts. In many aspects, the killer whale heart conformed to other delphinid heart descriptions, including position, relative size and shape and specific features such as extensive papillary muscles, trabecular endocardium and trabecula septomarginalis. These characteristics are representative of the delphinid family, suggesting that its functions and capacities are similar to that of other, smaller, dolphins and help understand the conditions in which these predators exert their remarkable physical performance necessary for their survival.


Factors influencing the supervision of nursing students administering medication: the registered nurse perspective.
Administering medication is an important function of registered nurses. It is therefore necessary that nursing students develop knowledge and skill in this field. Given the propensity for, and negative consequences of, medication errors, it is essential that nursing students are property supervised in this role. There is currently a paucity of research examining the practices of supervising medication administration by nursing students, particularly from the perspectives of registered nurses. The aim of this study was to explore the opinions and insights of registered nurses regarding the supervision of nursing students administering medication. Focus groups were conducted with registered nurses with experience of working with students in the clinical environment. Focus groups were transcribed verbatim and data analysis was conducted using the five stage framework approach. Four main themes were identified that reflected the participants' views of the factors most strongly influencing the provision of supervision: communication, busyness, attitudes, and pressure to conform. The participants identified the importance of providing student supervision and suggested strategies for improvement, such as a closer working relationship between the clinical facilitator and the registered nurses providing supervision.


Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia-reperfusion model.
Skeletal muscle injury after revascularization (ischemia-reperfusion) continues to be a major clinical problem. Although heparinization has been recommended, its action in an experimental model of I-R has not been evaluated. We investigated the ability of heparinization to decrease I-R injury in 10 anesthetized dogs (nonheparinized, n = 5; heparinized, n = 5), subjecting one gracilis muscle to 6 hours of ischemia followed by 1 hour of reperfusion while the identically prepared contralateral muscle served as a nonischemic control. Skeletal muscle infarction was determined by Tc-PYP uptake. Endothelial permeability was quantified by measurement of skeletal muscle 125I-Alb activity after intravenous injection. Interstitial hydrogen ion (H+) accumulation was determined by a miniature pH electrode inserted into the gracilis muscle. Isotopic activities from the ischemic muscle were calculated as a percentage of the contralateral nonischemic muscle (mean +/- SEM). Nonheparinized ischemic muscles had an increase in the activities of Tc-PYP and 125I-Alb of 684% +/- 149% and 742% +/- 130%, which were reduced to 218% +/- 54% and 378% +/- 85% by heparinization, respectively (p less than 0.05). During ischemia, the nonheparinized muscles accumulated 1223 +/- 121 nmol of H+ compared with 785 +/- 95 nmol in the heparinized animals (p less than 0.01). This significant reduction in I-R injury may be causally related to diminished endothelial permeability and H+ accumulation.


Isocaloric feeding and medium chain triglycerides fail to improve liver function tests in a patient with Crohn's disease and a high output stoma.
A patient with Crohn's disease complicated by multiple fistulae to the skin and bladder and a high-output stoma following previous multiple short bowel resections developed liver dysfunction during total parenteral nutrition. Isocaloric feeding based on calorimetry and changing from a long chain triglyceride emulsion to a mixture of medium and long chain triglyceride emulsion failed to improve liver function. Surgical removal of the affected small bowel resulted in a rapid improvement of the liver function despite continuation of total parenteral nutrition.


Transformer maze for the evaluation of the learning and memory in rodents.
Currently, different types of mazes are used to assess spatial learning and memory of rodents. The typical disadvantage is the inability to separate and exclude coincidences of the result of random choice with the correct one. The other problem is the impossibility of knowing whether the animal is guided by particular cues of the environment, or a map. Our novel transformer maze can be used to test learning and memory of rodents and their navigation. It is a multiple T-maze with passages in the interior walls. Its modular design allows to quickly change routes. The task can include external signals; for example, the colors of the interior walls, or it can be used without any cues. We compared Wistar and dopamine transporter heterozygous (DAT-HET) rats' behavior in this novel paradigm using the black color of the wall as a cue. Entering a cul-de-sac compartment was considered an error. While Wistar rats learned the rule abruptly with the total number of errors rapidly decreasing, DAT-HET rats' errors decreased gradually. We suppose that this reflects different strategies: insightful learning behavior is typical for Wistar rats, and trial-and-error learning is typical for DAT-HET rats. The diversity of the chains of choices gives us confidence that trained animals do not make a choice randomly and are guided precisely by the cues. Moreover, we propose to use the same arena for a task with route-based navigation without any cues, and for a task with a visible and invisible feeder to study the path integration navigation within one box. We suggest that the transformer maze could be a valuable tool for behavioral and pharmacological research to study learning, memory and navigation mechanisms.


Integrating technology assessment and medical practice evaluation into hospital operations.
The Johns Hopkins Program for Medical Technology and Practice Assessment, established in 1986, assesses the clinical efficacy, safety, and cost of specific technologies; evaluates the costs and benefits of alternative approaches to management of clinical problems; and examines the clinical and economic impact of health care program innovations. For example, program faculty have conducted analyses of clinical economic, and health policy issues related to radiographic contrast media. The director of the program chairs a committee that formulates guidelines for the appropriate use of low-osmolality contrast media and that will develop a mechanism to ensure compliance with guidelines. Program faculty are currently studying variations in the pre-, intra-, and postoperative management of patients with cataract and the relationship between such variations and outcomes. Faculty are also attempting to develop an improved mechanism for paying health maintenance organizations that enroll Medicare beneficiaries. Program activities have had a direct impact on decision making within the Johns Hopkins Health System.


Cloning and characterization of a new laccase from Bacillus licheniformis catalyzing dimerization of phenolic acids.
A new laccase gene (cotA) was cloned from Bacillus licheniformis and expressed in Escherichia coli. The recombinant protein CotA was purified and showed spectroscopic properties, typical for blue multi-copper oxidases. The enzyme has a molecular weight of approximately 65 kDa and demonstrates activity towards canonical laccase substrates 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), syringaldazine (SGZ) and 2,6-dimethoxyphenol (2,6-DMP). Kinetic constants KM and kcat for ABTS were of 6.5+/-0.2 microM and 83 s(-1), for SGZ of 4.3+/-0.2 microM and 100 s(-1), and for 2,6-DMP of 56.7+/-1.0 microM and 28 s(-1). Highest oxidizing activity towards ABTS was obtained at 85 degrees C. However, after 1 h incubation of CotA at 70 degrees C and 80 degrees C, a residual activity of 43% and 8%, respectively, was measured. Furthermore, oxidation of several phenolic acids and one non-phenolic acid by CotA was investigated. CotA failed to oxidize coumaric acid, cinnamic acid, and vanillic acid, while syringic acid was oxidized to 2,6-dimethoxy-1,4-benzoquinone. Additionally, dimerization of sinapic acid, caffeic acid, and ferulic acid by CotA was observed, and highest activity of CotA was found towards sinapic acid.


Surgical Removal of Skull Base Meningiomas in Symptomatic Elderly Patients.
Meningiomas frequently occur in elderly patients, and surgical treatment is hazardous owing to multiple comorbidities. We report a series of elderly patients who were treated with surgical removal of meningiomas and compare them with a group of younger patients with similar tumors. A retrospective study of elderly patients with symptomatic skull base meningiomas and a matched control group of younger patients was performed. Medical records, operative reports, radiologic examinations, and follow-up data were reviewed. Main outcome measures were morbidity, mortality, and Simpson grade. The study included 46 patients (23 elderly [age >65 years], 23 younger [age <65 years]). Average age was 71 years in elderly patients and 48 years in younger patients. Mean follow-up period was 32 months and 49 months, respectively. Radical removal (Simpson grades I and II) was observed in 83% and 91%, respectively. Mortality was 8% and 4%, respectively. Definite cranial nerve lesions occurred in 8% and 26%, respectively; cerebrospinal fluid leaks occurred in 12.5% and 4%, respectively; hemiparesis occurred in 4% of patients in both groups. Glasgow Outcome Scale score of 5 was obtained in 87% and 65.2%, respectively. Elderly patients with symptomatic skull base meningiomas should be considered for surgical treatment owing to acceptable morbidity and mortality compared with younger patients. Previous comorbidities and involvement of neurovascular structures are important factors in the decision regarding extent of surgical resection.


Hsp90 inhibits α-synuclein aggregation by interacting with soluble oligomers.
Aggregated α-synuclein is one of the main components of the pathological Lewy bodies associated with Parkinson's disease (PD). Many other proteins, including chaperones such as Hsp90 and Hsp70, have been found co-localized with Lewy bodies and the expression levels of Hsp90 have been found to be increased in brains of PD patients. Although the role of Hsp70 in the aggregation of α-synuclein has been extensively studied, relatively little is known about the effect of Hsp90 on this process. Here, we have investigated if Hsp90 can prevent the aggregation of the A53T pathological mutant of α-synuclein in vitro. A detailed study using many biophysical methods has revealed that Hsp90 prevents α-synuclein from aggregating in an ATP-independent manner and that it forms a strong complex with the transiently populated toxic oligomeric α-synuclein species formed along the aggregation pathway. We have also shown that, upon forming a complex with Hsp90, the oligomers are rendered harmless and nontoxic to cells. Thus, we have clear evidence that Hsp90 is likely to play an important role on these processes in vivo.


Surface modification significantly changed the effects of nano-polystyrene on sediment microbial communities and nitrogen metabolism.
Nanoplastics are ubiquitous in the natural environment, and their ecological risks have received considerable attention. Surface modification is common for nanoplastics and an essential factor affecting their toxicity. However, studies on the potential effects of nanoplastics and their surface-modified forms on functional communities in aquatic systems are still scarce. This study investigated the effects of nano-polystyrene (nPS), amino-modified nPS (nPS-NH2), and carboxylated nPS (nPS-COOH) particles on sediment bacterial and fungal communities and their functions over a 60-day incubation period. The results showed that the fungal community was significantly inhibited by nPS-NH2 exposure, while the bacterial community diversity remained relatively stable in all nPS treatments. Proteobacteria and Ascomycota were the dominant phyla for the bacterial and fungal communities, respectively. Nitrification was inhibited in all nPS treatments, while denitrification was enhanced for nPS-NH2 and nPS-COOH treatments. The activity of four key denitrification enzymes (NAR, NIR, NOR, and NOS) was also significantly improved by nPS, resulting in increased nitrogen and nitrous oxide gas production, and decreased nitrate concentrations in the overlying water. This showed the total increased effect of nPS on the activity of denitrifiers. Our results suggest that surface modification significantly affects the effects of nPS on microbial communities and functions. The potential impacts of nPS on ecological functions should be elucidated with more attention.


ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis.
Anaplastic lymphoma kinase (ALK) inhibitor has shown dramatic efficacy in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangements in phase I trial. Herein we report two cases of NSCLC patients with leptomeningeal carcinomatosis (LM), treated with ALK inhibitor under emergent use of investigational new drug combined with intrathecal methotrexate treatment. Progression free survival was 10 months and 6 months, respectively, and little additional toxicities were observed. These results suggest that ALK inhibitor might be safely administered even in patients or those with metastases in central nervous system.


Peptide nanotube loaded with a STING agonist, c-di-GMP, enhance cancer immunotherapy against melanoma.
The activation of the stimulating factor of the interferon gene (STING) pathway can enhance the immune response within the tumor. Cyclic diguanylate monophosphate (c-di-GMP) is a negatively charged, hydrophilic STING agonist, however, its effectiveness is limited due to the poor membrane permeability and low bioavailability. Herein, we introduced KL-7 peptide derived from Aβ amyloid fibrils that can self-assemble to form nanotubes to load and deliver c-di-GMP, which significantly enhanced c-di-GMP's effectiveness and then exhibited a robust "in situ immunity" to kill melanoma cells. KL-7 peptide nanotube, also called PNT, was loaded with negatively charged c-di-GMP via electrostatic interaction, which prepared a nanocomposite named c-di-GMP-PNT. Treatment of RAW 264.7 cells (leukemia cells in mouse macrophage) with c-di-GMP-PNT markedly stimulated the secretion of IL-6 and INF-β along with phospho-STING (Ser365) protein expression, indicating the activation of the STING pathway. In the unilateral flank B16-F10 (murine melanoma cells) tumor-bearing mouse model, compared to PNT and c-di-GMP, c-di-GMP-PNT can promote the expression of INF-β, TNF-α, IL-6, and IL-1β. At the same time, up-regulated CD4 and CD8 active T cells kill tumors and enhance the immune response in tumor tissues, resulting in significant inhibition of tumor growth in tumor-bearing mice. More importantly, in a bilateral flank B16-F10 tumor model, both primary and distant tumor growth can also be significantly inhibited by c-di-GMP-PNT. Moreover, c-di-GMP-PNT demonstrated no obvious biological toxicity on the main organs (heart, liver, spleen, lung, and kidney) and biochemical indexes of mice. In summary, our study provides a strategy to overcome the barriers of free c-di-GMP in the tumor microenvironment and c-di-GMP-PNT may be an attractive nanomaterial for anti-tumor immunity. Supplementary material (synthesis and characterization of KL-7 peptide; the encapsulation rate and cumulative release rate of c-di-GMP-PNT; cytotoxicity of PNT, c-di-GMP, and c-di-GMP-PNT; anti-tumor effect of c-di-GMP-PNT (equivalent to 1 and 5 µg c-di-GMP per mouse); representative immunofluorescence images; and biosafety analysis) is available in the online version of this article at 10.1007/s12274-022-5102-z.


In vitro interaction of fluconazole and amphotericin B administered sequentially against Candida albicans: effect of concentration and exposure time.
This study investigated the potential antagonism of fluconazole on amphotericin B activity against Candida albicans when administered sequentially in vitro. Yeast cells were exposed to fluconazole for time periods ranging from 0 to 24 h before the addition of amphotericin B. The combination showed fungicidal (> or = 3 log 10 reduction in CFU/mL) activity. After 4 h of exposure to fluconazole, amphotericin B activity was partially inhibited at the lower concentration tested (0.25 x MIC). Amphotericin B activity was dramatically decreased by previous exposure to fluconazole for greater than or equal to 8 h at both the high and low concentrations tested. The activity of amphotericin B against yeast exposed to fluconazole for at least 8 h was indistinguishable from fluconazole alone and was fungistatic (< or = 2 log 10 reduction in CFU/mL). This inhibition of amphotericin B activity persisted for a very short period (< 6 h) after removal of fluconazole from the culture medium, indicating the need for continued exposure to fluconazole for lasting inhibition of amphotericin B activity.


Animal bites management in Northern Iran: Challenges and solutions.
Animal bite is considered a serious social, economic, and health risk for societies with poor animal bites and population management. The objective of this study was to propose a model for animal bites management in Golestan Province. The present study is a multi-method study conducted quantitatively and qualitatively. First, as a cross-sectional study, the animal bites in Golestan Province and the country were calculated and their trend was predicted. Secondly, in the qualitative study (content analysis), the challenges, barriers, and methods of animal bite control were extracted through conducting semi-structured interviews and focused group discussion meetings. Finally, the model of animal bite management was developed and it was confirmed by Round Delphi. The data were analyzed via content analysis using MAXQDA18. The participants in this study consisted of university professors, managers, and executive officers involved in animal bite and rabies control plans. This study revealed that the animal bite in Golestan Province had an upward trend, as in the country, and dogs were the main cause of bites (90%). The obstacles and challenges of current animal bites control program in eight areas were expressed by the participants. Also, the animal bite management model, which was obtained from the data of different stages of this study, included nine fields and 41 sub-fields. The fields of the animal bite management model included: providing a cultural package, resolving barriers to animal population control plans, wide coverage of dog vaccination, passing and enacting preventive laws, attracting financial support, constructing standard equipment, providing proper medical services, enhancing inter-departmental coordination, and controlling rabies in the wild. This model was confirmed in a Delphi round. Our study indicated that Golestan Province with an average bite higher than twice the country's average is one of the leading provinces in this regard. Thus, revising the animal bite and animal population control plans in this province is necessary. The model designed in this study can be used as a practical guide by policy makers and officials to manage animal bite and related consequences in this province.


A first-principles study on crystal structures and metallization of sodium-rich sulfides under high pressure.
We performed systematical theoretical simulations on phase diagrams, crystal structures, electron properties, and phonon features of Na-S system under high pressures. NaS, Na2S, and Na4S, were found to be stable under pressures. The superconducting transition critical temperature was estimated to nearly 0 K at 100 GPa in Na3S due to the weak electron-phonon coupling. Furthermore, by the comparison on the structures, the electron features, and alkali metal ions of stoichiometric proportion, we found that not only the pressure but also the number of sodium atoms in the formula unit of alkali metal atoms can promote the insulator-metal transformation in the alkali metal sulfides, such as Li-S, Na-S, and K-S systems.


Activation of extracellular signal-regulated kinase (ERK) and Akt by human serotonin 5-HT(1B) receptors in transfected BE(2)-C neuroblastoma cells is inhibited by RGS4.
Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins for heterotrimeric G proteins. One of the best-studied RGS proteins, RGS4, accelerates the rate of GTP hydrolysis by all G(i) and G(q) alpha subunits yet has been shown to exhibit receptor selectivity. Although RGS4 is expressed primarily in brain, its effect on modulating the activity of serotonergic receptors has not yet been reported. In the present study, transfected BE(2)-C human neuroblastoma cells expressing human 5-HT(1B) receptors were used to demonstrate that RGS4 can inhibit the coupling of 5-HT(1B) receptors to cellular signals. Serotonin and sumatriptan were found to stimulate activation of extracellular signal-regulated kinase. This activation was attenuated, but not completely inhibited, by RGS4. Similar inhibition by RGS4 of the protein kinase Akt was also observed. As RGS4 is expressed at high levels in brain, these results suggest that it may play a role in regulating serotonergic pathways.


Enhancing palliative care occupancy and efficiency: a quality improvement project that uses a healthcare pathway for service integration and policy development.
This article described our experience in implementing a quality improvement project to overcome the bed overcapacity problem at a comprehensive cancer centre in a tertiary care centre. We formed a multidisciplinary team including a representative from patient and family support (six members), hospice care and home care services (four members), multidisciplinary team development (four members) and the national lead. The primary responsibility of the formulated team was implementing measures to optimise and manage patient flow. We used the plan-do-study-act cycle to engage all stakeholders from all service layers, test some interventions in simplified pilots and develop a more detailed plan and business case for further implementation and roll-out, which was used as a problem-solving approach in our project for refining a process or implementing changes. As a result, we observed a significant reduction in bed capacity from 35% in 2017 to 13.8% in 2018. While the original length of stay (LOS) was 28 days, the average LOS was 19 days in 2017 (including the time before and after the intervention), 10.8 days in 2018 (after the intervention was implemented), 10.1 days in 2019 and 16 days in 2020. The increase in 2020 parameters was caused by the COVID-19 pandemic, since many patients did not enrol in our new care model. Using a systematic care delivery approach by a multidisciplinary team improves significantly reduced bed occupancy and reduces LOS for palliative care patients.


A glucose oxidase immunoenzyme stain for the detection of viral antigen or antibody on nitrocellulose transfer blots.
Separation of mixtures of proteins by polyacrylamide gel electrophoresis followed by transfer of the proteins to support media such as nitrocellulose and detection by immunologic procedures provides a powerful analytic tool for assaying the antibody specificity of antisera or for following the purification of antigens. This technique requires fewer assumptions about antigenic solubility or antibody reactivity than immunoprecipitation methods. We present a glucose oxidase immunoenzyme staining procedure for protein blots and illustrate its use for detecting antibody to several viruses. The glucose oxidase immunoenzyme stain has a lower background than some peroxidase stains. We have detected as little as 1 microgram/ml of antiviral antibody using this stain.


[Robot-assisted laparoscopic radical cystectomy].
Recent reports have demonstrated that robot-assisted laparoscopic cystectomy is technically feasible. However, wide-spread acceptance of this promising technique is limited due to long operating times and lacking long-term data especially on oncological outcome. After establishing robot-assisted laparoscopic prostatectomy (n=250) we report technical and functional results of a large series of patients undergoing laparoscopic cystectomy with the da Vinci surgical system (DVSS).27 patients (24 males) underwent laparoscopic radical cystectomy with the DVSS (Intuitive Surgical) between Jan 2004 and Dec 2006. Indications for cystectomy were muscle-invasive transitional cell carcinoma (TCC) or leiomyosarcoma of the urinary bladder (n=24) and bladder shrinking following prior radiotherapy for TCC (n=3). A pelvic lymphadenectomy was routine part of the procedure. Urinary diversions were ilieal conduits (n=19) and ileal neobladders (n=8). Mean operating time was 340 minutes (range 150-450) with a mean blood loss of 301 mL (range 50-550). The mean number of lymph nodes retrieved during lymphadenectomy was 23. Surgical margins were negative except in one case. After a mean follow-up of 10.2 months, 2 perioperative (anastomotic leakage, adhesions) and 3 postoperative complications (ileus, intestinal fistula) occurred. 6/7 patients reported satisfying erectile function following nerve-sparing surgery. Day-time continence was completely restored after a mean 3.5 months in 7/8 patients.Robot-assisted laparoscopic cystectomy is a safe procedure. Satisfying functional and oncological short-term results can be achieved within acceptable operating time limits.


Sources of variability for Doppler color flow mapping of regurgitant jets in an animal model of mitral regurgitation.
To determine whether Doppler color flow mapping could be used to quantify changing levels of regurgitant flow and define the technical variables that influence the size of color flow images of regurgitant jets, nine stable hemodynamic states of mitral insufficiency were studied in four open chest sheep with regurgitant orifices of known size. The magnitude of mitral regurgitation was altered by phenylephrine infusion. Several technical variables, including the type of color flow instrument (Irex Aloka 880 versus Toshiba SSH65A), transducer frequency, pulse repetition frequency and gain level, were studied. Significant increases in the color flow area, but not in color jet width measurements, were seen after phenylephrine infusion for each regurgitant orifice. For matched levels of mitral regurgitation, an increase in gain resulted in a 125% increase in color flow area. An increase in the pulse repetition and transducer frequencies resulted in a 36% reduction and a 28% increase in color flow area, respectively. Jet area for matched regurgitant volumes was larger on the Toshiba compared with the Aloka instrument (5.2 +/- 3.1 versus 3.2 +/- 1.2 cm2, p less than 0.05). Color flow imaging of mitral regurgitant jets is dependent on various technical factors and the magnitude of regurgitation. Once these are standardized for a given patient, the measurement of color flow jet area may provide a means of making serial estimates of the severity of mitral insufficiency.


Non-destructive analyses on a meteorite fragment that fell in the Madrid city centre in 1896.
The historical Madrid meteorite chondrite fell in 1896 showing thin melt veins with a 65% of brecciated forsterite fragments surrounded by a fine grained matrix formed by troilite, chromite and Fe-Ni blebs. It exhibits a delicate iron infill, neo-formation of troilite in pockets and shock veins and neo-formation of Na-feldspar formed at high temperature and fast quenching. The semi-quantitative mineral determinations were performed with IMAGEJ freeware and chemical mappings resulting in the following approximated compositions: olivine (~55%); augite (~10%); enstatite (~10%); plagioclase (~10%); chromite (~2%); troilite (~4%), kamacite-taenite α-γ-(Fe, Ni) (~7%) and merrillite (~7%). The specimen was also studied by computer tomography, micro-Raman spectroscopy and spectral cathodoluminescence. X-ray diffraction patterns were also recorded in non-destructive way on a polished surface because of the small size of the specimen. This combination of non-destructive techniques provides an improved knowledge on the Madrid-1896 meteorite compared to the previous study performed on the same specimen carried out twenty years ago by electron probe microanalysis and optical microscopy in destructive way. Limits of these techniques are the specimen's size in the analytical chambers and the threshold resolution of the microscopes analyzing shock veins micro-crystals.


Developing a flow control strategy to reduce nutrient load in a reclaimed multi-reservoir system using a 2D hydrodynamic and water quality model.
Blocking the natural bi-directional flow in an estuarine system using an artificial dyke has commonly caused serious water quality problems. In the southwestern part of South Korea, a parallel triple-reservoir system was constructed by blocking the mouth of three different rivers (Yeongsan, Okcheon, and Kumja), which were then interconnected using two open channels. This system has experienced a deterioration in water quality due to pollutants accumulated from the upper watershed, and has continually discharged pollutant loads to the outer ocean. Therefore, the objective of this study is to establish an effective dam operation plan for reducing nutrient loads released from the integrated reservoir. In this study, the CE-QUAL-W2 model, which is a 2-dimentional hydrodynamic and water quality model, was applied to predict the pollutant load released from each reservoir in response to different flow scenarios for the interconnecting channel. The model was calibrated using two novel methods: a sensitivity analysis to determine meaningful model parameters, and a pattern search to optimize the parameters. From the scenario analysis using flow control, it was determined that the total nitrogen (TN) and total phosphorus (TP) loadings could be reduced by 27.2% and 6.6%, respectively, under the optimal channel flow scenario by regulating the chlorophyll-a concentration in the reservoir. The results confirm that effective dam operation could contribute to a decrease in pollutant loads in the receiving seawater body. As such, this study suggests operational strategies for a multi-reservoir system that can be used to reduce the nutrient load being discharged from reservoirs.


Surveillance of HIV drug resistance in children receiving antiretroviral therapy: a pilot study of the World Health Organization's generic protocol in Maputo, Mozambique.
Between 2007 and 2008, the Mozambique Ministry of Health conducted an assessment of human immunodeficiency virus drug resistance (HIVDR) using World Health Organization (WHO) methods in a cohort of children initiating antiretroviral therapy (ART) at the main pediatric ART referral center in Mozambique. It was shown that prior to ART initiation 5.4% of children had HIVDR that was associated with nevirapine perinatal exposure (P < .001). Twelve months after ART initiation, 77% had viral load suppression (<1000 copies/mL), exceeding the WHO target of ≥ 70%; 10.3% had HIVDR at 12 months. Baseline HIVDR (P = .04), maternal prevention of mother-to-child transmission (P = .02), and estimated days of missed medication (P = .03) predicted HIVDR at 12 months. As efforts to eliminate pediatric AIDS are intensified, implementation of ritonavir-boosted protease inhibitor regimens in children with prevention of mother-to-child transmission exposure may reduce risk of virological failure in our setting.


Kinetic and structural characterisation of the ubiquinol-binding site and oxygen reduction by the trypanosomal alternative oxidase.
The alternative oxidase (AOX) is a monotopic di‑iron carboxylate protein which acts as a terminal respiratory chain oxidase in a variety of plants, fungi and protists. Of particular importance is the finding that both emerging infectious diseases caused by human and plant fungal pathogens, the majority of which are multi-drug resistant, appear to be dependent upon AOX activity for survival. Since AOX is absent in mammalian cells, AOX is considered a viable therapeutic target for the design of specific fungicidal and anti-parasitic drugs. In this work, we have mutated conserved residues within the hydrophobic channel (R96, D100, R118, L122, L212, E215 and T219), which crystallography has indicated leads to the active site. Our data shows that all mutations result in a drastic reduction in Vmax and catalytic efficiency whilst some also affected the Km for quinol and oxygen. The extent to which mutation effects inhibitor sensitivity was also investigated, with mutation of R118 and T219 leading to a complete loss of inhibitor potency. However, only a slight reduction in IC50 values was observed when R96 was mutated, implying that this residue is less important in inhibitor binding. In silico modelling has been used to provide insight into the reason for such changes, which we suggest is due to disruptions in the proton transfer network, resulting in a reduction in overall reaction kinetics. We discuss our results in terms of the structural features of the ubiquinol binding site and consider the implications of such findings on the nature of the catalytic cycle. SIGNIFICANCE: The alternative oxidase is a ubiquinol oxidoreductase enzyme that catalyses the oxidation of ubiquinol and the reduction of oxygen to water. It is widely distributed amongst the plant, fungal and parasitic kingdoms and plays a central role in metabolism through facilitating the turnover of the TCA cycle whilst reducing ROS production.


Genome-wide scanning with SSLPs in the rat.
Genome-wide linkage analysis is a powerful tool for the identification of genes underlying single gene and complex genetic disorders. The most commonly used technique for performing genome wide scans for genetic studies in the rat is by analysis of simple sequence length polymorphism (SSLPs) or microsatellite markers. A sensitive and flexible method for high-throughput genotyping is described. Addition of an M13 tail to the SSLP primer eliminates the need for direct conjugation of the fluorescent dye to the primers, allowing for any combination of primer and fluorophor, and therefore for easy multiplexing of primers in the same reaction. With the use of three different dyes, it is possible to run more than five hundred genotypes in each run of the automatic sequencer. Automation in the fluorescent detection system and data tracking software for processing genotypes, contributes to the ability to genotype large number of samples rapidly and accurately.


Goose IRF7 is involved in antivirus innate immunity by mediating IFN activation.
Interferon regulatory factor (IRF) 3 and IRF7 are the most important nuclear transcription factors regulating type-I interferon (IFN) production in mammals and the IRF3 is missing in birds. Our previous study found that IFR7 is the most important IRF in chickens, however, its functions in geese remain unknown. We cloned goose IRF7 (GoIRF7) and conducted bioinformatics analyses to compare the chromosomal location and protein homology of IRF7 in different species. Overexpression of GoIRF7 in DF-1 cells induced the activation of IFN-β, and this activation correlated positively with the dosage of transfected plasmids. Overexpression of GoIRF7 in goose embryonic fibroblasts (GEFs) induced the expression of IFNs, proinflammatory cytokines, and IFN-stimulated genes (ISGs); it also inhibited replication of Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV). Our results suggest that GoIRF7 is an important regulator of IFNs, proinflammatory cytokines, and ISGs and plays a role in antiviral innate immunity in geese.


Late results of mitral valve repair with glutaraldehyde-treated autologous pericardium.
Mitral valve repair is an established surgical procedure for treating severe organic mitral regurgitation. The mechanisms of mitral regurgitation due to infective endocarditis include rheumatic disease and congenital diseases such as a lack of leaflet tissue, and thus additional material is required to create a functional coaptation surface. We review our experience with 139 patients who underwent mitral valve repair with glutaraldehyde-treated autologous pericardium to treat organic mitral regurgitation between March 1992 and November 2011. Mitral valve disease mainly consisted of infective endocarditis in 51 patients (active, n = 32; healed, n = 19) and rheumatic disease in 47. This procedure was also applied to 12 patients who required reoperation after mitral valve repair for degenerative, congenital, or rheumatic mitral regurgitation. The mean follow-up was 4.5 ± 4.3 years (maximum 19.1). Actuarial survival at 10 years was 84% ± 5%. Eleven reoperations proceeded at a mean of 68 months after surgery. The causes of reoperation were rheumatic disease progression (n = 4), infection (n = 3), patch dehiscence (n = 2), progressive fibrosis of the remaining mitral valve tissue after infective endocarditis (n = 1), and patch tear (n = 1). Mitral valves were replaced in 8 patients and re-repaired in 3 patients. The autologous pericardium was not calcified at the time of reoperation. The rate of freedom from reoperation was 82% ± 7% at 10 years. Mitral valves that might otherwise require replacement can be durably and predictably repaired using glutaraldehyde-treated autologous pericardium.


Ligand-Based Drug Design: Synthesis and Biological Evaluation of Substituted Benzoin Derivatives as Potential Antitumor Agents.
Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Kα complex interaction and antiproliferative activity. Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Kα and estrogen receptor alpha (ERα). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Kα and ERα demonstrated that the series accommodate binding to PI3Kα and/or ERα. The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.


Modeling study of polychlorinated dibenzo-p-dioxins and dibenzofurans behavior in flue gases under electron beam irradiation.
The efficiency of the electron beam treatment of industrial flue gases for the removal of sulfur and nitrogen oxides was investigated as applied to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) using methods of mathematical modeling. The proposed kinetic model of the process includes mechanism of PCDD/Fs decomposition caused by their interaction with OH radicals generated in the flue gases under the electron beam (EB) irradiation as well as PCDD/Fs formation from unburned aromatic compounds. The model allows to predict the main features of the process, which are observed in pilot plant installations, as well as to evaluate the process efficiency. The results of calculations are compared with the available experimental data.


Dual functional electrospun core-shell nanofibers for anti-infective guided bone regeneration membranes.
In clinic infection is the paramount cause for failure of guided bone regeneration (GBR) membranes. Therefore, it is crucial to develop anti-infective GBR membranes for clinical bone repair application. In this research, we successfully prepared electrospun core-shell nanofibers loaded with metronidazole (MNA) and nano-hydroxyapatites (nHA), which could be employed for anti-infective GBR membranes due to the achievement of dual functions with enhanced osteogenesis and slow MNA release. The nanofiber shell was composed of polycaprolactone and nHA, whilst the nanofiber core was gelatin and MNA. The MNA release and cell proliferation experiments showed that compared with directly MNA-loaded nanofibers, the core-shell nanofibers possessed slower MNA release profile, which resulted in the decrease in cytotoxicity of MNA to bone mesenchymal stem cells. The osteogenic measurements demonstrated that the core-shell nanofibers could enhance bone formation. Additionally, the anti-bacterial experiments indicated that the core-shell nanofibers could prevent colonization of anaerobic bacteria. In summary, the results in the present study revealed the potential of the core-shell electrospun nanofibers with dual functions of enhanced osteogenesis and anti-infection for optimal clinical application as GBR membranes.


Characterization of olanzapine (LY170053) in human liver slices by liquid chromatography/tandem mass spectrometry.
Olanzapine metabolism was investigated using incubation of olanzapine with human liver slices. The intent of the investigation was to identify olanzapine metabolites and determine if the human liver slice incubations could potentially produce quantities of the olanzapine glucuronides for future studies. Along with known Phase 1 olanzapine metabolites, N-desmethyl-, 2-hydroxymethyl-, and 4'-N-oxide-, a new hydroxylated species was detected. Detection of Phase 2 metabolites included known N-10-glucuronides, a quaternary glucuronide and a novel glucuronide conjugate. This investigation showed the feasibility of using human liver slices to produce sufficient quantities of olanzapine glucuronides for further studies.


Thermally-assisted photosensitized emission in a trivalent terbium complex.
Luminescent lanthanide complexes containing effective photosensitizers are promising materials for use in displays and sensors. The photosensitizer design strategy has been studied for developing the lanthanide-based luminophores. Herein, we demonstrate a photosensitizer design using dinuclear luminescent lanthanide complex, which exhibits thermally-assisted photosensitized emission. The lanthanide complex comprised Tb(III) ions, six tetramethylheptanedionates, and phosphine oxide bridge containing a phenanthrene frameworks. The phenanthrene ligand and Tb(III) ions are the energy donor (photosensitizer) and acceptor (emission center) parts, respectively. The energy-donating level of the ligand (lowest excited triplet (T1) level = 19,850 cm-1) is lower than the emitting level of the Tb(III) ion (5D4 level = 20,500 cm-1). The long-lived T1 state of the energy-donating ligands promoted an efficient thermally-assisted photosensitized emission of the Tb(III) acceptor (5D4 level), resulting in a pure-green colored emission with a high photosensitized emission quantum yield (73%).


Prenatal diagnosis of zellweger syndrome by fetal MRI: a case report.
Zellweger Syndrome (ZS) is a rare peroxisomal disorder also referred to as cerebrohepatorenal syndrome. ZS is an autosomal recessive disease often manifesting in the neonatal period with profound dysfunction of the central nervous system, liver and kidneys. Prenatal diagnosis of this syndrome is infrequent with imaging findings on fetal MRI rarely illustrated in the literature. This case highlights the pivotal role fetal MRI can play in identifying subtle features of the disease that are difficult to visualize on prenatal ultrasound. It is important for pediatric radiologists to be familiar with the most common imaging features of ZS on fetal MRI to expedite the diagnosis and help facilitate appropriate prenatal counseling.


Essential role of STAT-3 dependent NF-κB activation on IL-6-mediated downregulation of hepatic transporters.
IL-6 markedly decreases the expression of numerous hepatic transporters. We previously demonstrated that IL-6-mediated downregulation of transporters occurs through STAT3, with partial involvement of PXR. However, while IL-6-mediated induction of STAT3 occurs rapidly, repression of transporter expression is not observed until 6 h post-treatment. This temporal mismatch suggested that the downregulation of transporters following IL-6 at 6 h might require additional signaling downstream of STAT3. Since NF-κB has been implicated in endotoxin-mediated downregulation of transporters, we hypothesized that NF-κB may be similarly involved in suppressing transporter expression following IL-6. Our objective was to investigate whether IL-6-mediated changes in transporter expression occur through STAT3-dependent NF-κB activation, and whether PXR is involved. PXR null (-/-) or wild type (+/+) mice were pre-dosed with the NF-κB inhibitor PHA408 or vehicle 30 min prior to receiving a single dose of IL-6 or saline. Mice were euthanized after 6 h and transporter expression was analyzed using qRT-PCR. IL-6 imposed downregulation of Abcb1a, Abcb1b, Abcc3, Abcg2 and Cyp3a11 in both PXR (+/+) and PXR (-/-) mice, while downregulation of Abcb11, Abcc2, Slc10a1, and Slco2b1 was only significant in PXR (+/+) mice. PHA408 pretreatment fully inhibited NF-κB activation in PXR (+/+) but only partially inhibited NF-κB in PXR (-/-). Inhibition of NF-κB attenuated IL-6-mediated changes in transporters in PXR (+/+) mice. Transient transfection assays did not detect significant activation of human or mouse PXR by PHA408. Our findings suggest that IL-6 imposes significant downregulation of numerous ABC and SLC transporters in the liver via collaborative STAT3/NF-κB activation. Since drug transporters play an integral role in the pharmacokinetics of numerous clinically relevant drugs, understanding the signaling pathways involved in transporter regulation during inflammation will contribute to a better understanding of drug-disease interactions.


Stress and anxiety effects on positive skin test responses in young adults with allergic rhinitis.
Anxiety and psychological stress affect allergy-related immune function. How these relations influence the evaluations of patients with allergic rhinitis is unknown. To examine whether anxiety and stress exposure affect skin prick test (SPT) responses to common allergens for which patients with atopy showed no prior positive SPT response. Patients with allergic rhinitis, evidenced by clinical history and SPT results, were admitted twice to a hospital research unit for 4 hours. In a crossover design, SPT wheals were assessed before and after the Trier Social Stress Test and then the following morning; for comparison, SPT wheals were assessed before and after a laboratory session without a stressor. Analyses focused on wheal responses for common allergens that tested negative (wheal size <3 mm larger than saline) from SPTs performed at multiple baseline assessments. After the Trier Social Stress Test, more anxious patients with atopy had a higher incidence of positive SPT reactions to antigens that previously tested negative. Anxiety was unrelated to positive SPT incidence under nonstressful conditions. Based on clinical symptom reports, newly positive SPT reactions after the stressor were apparently corrections of previously false-negative SPT reactions. The SPT wheal responses for allergens previously testing negative were enhanced after a stressor. Histamine (positive control) or saline (negative control) SPT responses were not affected. A laboratory stressor affected allergen SPT responses in more anxious patients with allergic rhinitis. In addition to clinical history, assessment of anxiety and current stress at the time of the SPT may provide valuable information about a patient's allergic status and aid in clinical decision making.


The comparison of outcome and cost of three protocols for childhood non-high risk acute lymphoblastic leukemia in China.
To compare the outcome and treatment cost of three protocols for childhood non-high risk acute lymphoblastic leukemia (ALL), and evaluate the feasibility of less intensive treatment protocol for low income families. Two hundred forty-three children were newly diagnosed ALL in a university hospital from May 1999 to August 2006. Three protocols were offered to the patients: China-98 protocol, or modified ALLIC BFM2002 protocol, or an in-house Reduced Intensity Protocol (or also known as Economic Protocol). Among 243 patients, 19 abandoned treatment, 3 transferred to other hospitals, 48 were high-risk and were treated with the high risk protocol, and 4 had mature B-ALL. A total of 169 cases were enrolled on non-high risk protocols: 46 treated on China-98 protocol, 73 on modified ALLIC BFM2002 and 50 from low income families on Economic Protocol. The event-free survival (EFS) at 4 years was 80.4% (95%CI, 68.8-92.2%), 83.5% (95%CI, 73.5-93.5%), and 72.8% (95%CI, 59.3-86.3%) for China-98 protocol, modified ALLIC BFM2002, and Economic Protocol respectively. The hospitalization costs (range and median) were significantly different between protocols: US$ 8,700-25,500 (12,500), US$ 6,900-16,400 (9,900), US$ 3,100-6,800 (4,300) for China-98 protocol, modified ALLIC BFM2002, and Economic Protocol respectively. This report from China has systematically reviewed the outcome and costs of protocols for ALL having different dose intensity. The reduced intensity protocol appears to achieve reasonable EFS (72.8% at 4 years) for non-high risk ALL at a much lower cost. This is especially important for low income families in developing countries.


Microinjection and Micropipette-Controlled Phagocytosis Methods for Neutrophils.
The ability to microinject substances into the cytosol of living neutrophils opens the possibility of manipulating the chemistry within the cell and also of monitoring changes using indicators which otherwise cannot be introduced into the cell. However, neutrophils cannot be microinjected by the conventional glass pipette insertion method. Here we outline two techniques which work well with neutrophils, namely, SLAM (Simple Lipid-Assisted Microinjection) and electromicroinjection. As these methods utilize micropipettes, we also include a simple method which uses a micropipette to deliver a phagocytic stimulus to a specific cell at a defined time, enable detailed study of the phagocytic process from particle contact to particle internalization.


[Symptoms of SARS-CoV-2 infections in children of day care age].
The symptoms of SARS-CoV‑2 infections in children are mostly mild; however, the symptoms are highly variable. There are only a few studies on non-hospitalized children. The clinical picture described in hospitalized children cannot be transferred to non-hospitalized children and the frequency of certain symptoms in children may thus be overestimated. Furthermore, most studies include a broad age group (up to 18 years). The symptoms of younger children have so far been described in less detail. The paper aims to describe the frequency of COVID-19 symptoms in younger children (1-6 years old). Data of the two modules COALA (Corona: Anlassbezogene Untersuchungen in Kitas) and CATS (Corona-KiTa surveillance) of the Corona-KiTa study are evaluated and the results of the two studies are compared and discussed against the background of the different methodologies. In the COALA study, the type and frequency of symptoms of children infected with SARS-CoV‑2 are evaluated and compared to symptoms of children who tested negative for SARS-CoV‑2. Symptom frequencies of SARS-CoV‑2 infected children of the COALA study are compared with data collected from surveillance data (CATS). The COALA study investigated 30 SARS-CoV‑2 outbreaks in day care centers where at least 1 SARS-CoV‑2 case was reported between October 2020 and June 2021. Using a prospective study design, day care children who were infected with SARS-CoV‑2 and their contact persons were studied over a period of 12 days (including regular SARS-CoV‑2 testing, retrospective interviews and daily symptom reporting). The results from the COALA study were compared with data from COVID-19 surveillance cases (CATS) for the same age group and time period. In Germany, SARS-CoV‑2 cases are reported to the local health authorities by physicians and laboratories. When reporting cases symptoms can be reported as well. From the COALA study, interview and reported symptom data were available for 289 children from the participating day care centers. Of 39 children with a SARS-CoV‑2 infection (wild-type, α‑variant), 64% had at least 1 symptom; of the children who tested negative for SARS-CoV‑2, 40% had at least 1 symptom. In both groups, rhinitis was the most common symptom (36% vs. 25%, n. s.). From the surveillance data (CATS), clinical information was available for 84,371 SARS-CoV‑2 positive children; fever was most common (27%) along with rhinitis (26%). Severe symptoms such as dyspnea were rarely reported in the outbreak investigations and in the surveillance data (3% and 1%, respectively). Day care-aged children infected with SARS-CoV‑2 usually have mild or asymptomatic courses. Their symptoms are similar to those of children who tested negative for SARS-CoV‑2 from the same day care centers; thus, the observed COVID-19 symptoms are nonspecific. Combining data from the two modules is useful: findings from a very large database, as provided by the surveillance data, are complemented by findings from day care center outbreaks, where detailed prospective data on infected children can be compared with those of children who tested negative for SARS-CoV‑2.


The roles of microRNAs in Wilms' tumors.
Wilms' tumor is the most common renal tumor in children in which diffusely anaplastic or unfavorable histology foreshadows poor prognosis. MicroRNAs are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. Accumulating evidence shows that microRNA dysregulation takes part in the pathogenesis of many renal diseases, such as chronic kidney diseases, polycystic kidney disease, renal fibrosis, and renal cancers. In Wilms' tumor, dysregulation of some key oncogenic or tumor-suppressing microRNAs, such as miR-17~92 cluster, miR-185, miR-204, and miR-483, has been documented. In this review, we will summarize current evidence on the role of dysregulated microRNAs in the development of Wilms' tumor.


Regulation of mycotoxin biosynthesis inAlternaria.
The genusAlternaria is responsible for different plant diseases such as tobacco brown spot, tomato blight, and citrus seedling chlorosis but can also be present during storage of grain. The objective of the present paper is to summarize the knowledge concerning regulation of secondary metabolism inAlternaria, particularA alternata (A tenuis). The paper mainly deals with regulation of polyketide biosynthesis, one of the major pathways leading to the biosynthesis of mycotoxins inAlternaria.The mostly studiedAlternaria mycotoxins are dibenzopyrones such as alternariol (AOH) and alternariol monomethyl ether (AME) and altenuene along with the tetramic acid tenuazonic acid.The biosynthesis ofAlternaria mycotoxins has been reviewed by Stinson (12). Most information is available for the biosynthesis of the polyketides AOH / AME while a few biosynthetic studies have been accomplished for tenuazonic acid (11).


[Induction of labour and breech presentation: experience of a French maternity ward].
For a few years, we can notice a progressive increase in the practice of systematic caesarean delivery as far as breech delivery is concerned. This is true notably since the publication of Hannah's "Term Breech Trial" in 2000 which recommends systematic caesarean delivery in the case of breech presentation. But the conclusions of this North-American study are questionable, knowing that French practice is often quite different from Hannah's study. In the maternity ward of the French hospital Robert-Debré, Paris, vaginal delivery may be authorized as far as breech presentation is concerned if defined obstetrical criteria are met. Labour can be induced when a maternal or fetal indication exists. In the following study, we tried to assess our practice. Our retrospective study included 624 patients with a breech presentation, of which 501 within the group of spontaneous labour (group 1) and 123 within the group of cervical preparation and induced labour (group 2), for the period going from 1 January 2000 to 31 December 2008. The results do comfort our attitude since they show equivalent results in terms of delivery mode and neonatal issues between breech presentations with spontaneous labour on one hand, and with labour induced by cervical maturation on the other hand. The primary objective of this study was to evaluate an unusual operating practice in a well-trained level 3 obstetrical team. The results do comfort our attitude since they show equivalent results in terms of delivery mode and neonatal issues between breech presentations with spontaneous labour on one hand, and with labour induced by cervical maturation on the other hand. It seems however difficult to extrapolate our results and apply them to usual practice due to the lack of power of a retrospective and non-randomized study. Setting up a randomized and prospective study seems however difficult because of the medical and ethical problems it would raise.


Does the Protrusion of Corticobasal Implants in the Maxillary Sinuses Affect Sinus Health? A Retrospective Study.
The aim of this retrospective study is to investigate the effect of corticobasal implant penetration in the nasal and maxillary sinuses on sinus health and implant survival rate in cases of severely atrophid ridges. This retrospective study was conducted on thirty patients with 172 implants who underwent corticobasal implant treatment between 2014 and 2018. Implants were divided into two groups according to the penetration depths (Group A, <4 mm; Group B, 4 mm). Inclusion criteria for the study included: (A) patients with severe maxillary ridge resorption with an immediately loaded corticobasal implant-supported prosthesis that showed implant protrusion inside the maxillary sinus on cone-beam computed tomography (CBCT); and (B) patients with a preoperative and postoperative follow-up CBCT scan using the same standard technique and machine. (C) Patients without any history of sinusitis before implant insertion patients who fulfilled the inclusion criteria were recalled for follow-up. The presence of sinus complications was clinically assessed according to the clinical practice guidelines for adult sinusitis of the American Academy of Otolaryngology-Head and Neck Surgery and Radiologically using CBCT. Moreover, patient satisfaction was evaluated using yes-or-no questions. The result was statistically analyzed using Fisher's Exact test. Despite the differences in implant penetration depths, no clinical signs of sinusitis were evident in any patient. One patient presented with transient epistaxis after the surgery, and 2 patients with nine implants revealed nonsignificant thickening of the sinus membrane radiologically (p = 0.055). All implants showed optimum bone-implant contact with a 100% survival rate. A significant relationship was reported between the thickness of the membrane and the patient's gender, hypertension, and smoking habits. (p = 0.001*, p = 0.002*, and p = 0.034*, respectively). Penetration of corticobasal implants in the maxillary sinus did not compromise the health of the maxillary sinus or implant survival rate. Limited posterior maxillary bony support and maxillary sinus pneumatization present challenges in implant dentistry and increase the possibility of implant protrusion inside the maxillary and nasal cavities. Hence, studying the effect of this protrusion on the maxillary sinuses' health and implant survival is highly significant.


Fractures of the orbital floor.
The charts of 324 patients treated for 363 orbital floor fractures between 1965 and 1973 were reviewed retrospectively. Of these, 38 (11 percent) were isolated floor fractures, 27 (8 percent) were rim and floor fractures, 168 (46 percent) were trimalar fractures and 130 (35 percent) were associated with complex facial fractures. On initial examination, 31 percent of the patients were found to have diplopia and 4 percent enophthalmos. Orbital prolapse was suspected in 31 percent of the patients. Thirty-seven percent of the patients had demonstrable ocular injury at the time of initial examination. Treatment was surgical in 336 of the fractures and non-surgical in 29. Of the surgical patients 140 had no support placed, 120 had antral support only, 51 had both antral support and orbital implant, and 20 had an orbital implant only. Postoperatively the incidence of diplopia was 8 percent in all patients, and 7 percent had enophthalmos. A smaller group followed for more than five months, were found to have diplopia in 17 percent and enophthalmos in 11 percent. Of the 29 patients treated non-surgically, none had persistent diplopia.


Pathophysiological mechanisms of HIV-induced defects in haematopoiesis: pathology of the bone marrow.
Bone marrow biopsies of 96 HIV1-infected patients were analysed histologically and by immuno- and enzyme histochemical techniques. Independently of the stage of disease, the bone marrow frequently exhibits hypercellularity and features of dysplastic haemopoiesis combined with mesenchymal alterations. In situ immunohistochemical analysis shows that there is a marked reduction in expression of the proliferation-associated nuclear antigen recognized by the Ki67 antibody. Comparison with non-infected controls reveals that there is a reduction in CD34+/myeloperoxidase-/naphthol AS-D chloroacetate- progenitor cells and an overproportional decrease in CD8+ lymphocytes in the bone marrow. Double staining revealed the presence of gag-coded HIV1 proteins in the above-mentioned CD34+ progenitor cells, in myelopoiesis cells, megakaryocytes and above all, in CD68+/acid phosphatase+ and alkaline phosphatase+ bone marrow reticular cells. From the latter results, it was concluded that HIV1-infected reticular cells may be disturbed in their ability to produce factors responsible for the short-range regulation of haemopoietic activity.


XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival.
The scaffold protein XB130 regulates cell growth, survival, and migration. Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5. We hypothesized that XB130 and Tks5 form a macromolecular complex to mediate signal transduction cascades for the regulation of cell growth and survival. Coimmunoprecipitation demonstrated that XB130 and Tks5 interact endogenously and form a complex with Src tyrosine kinase. Structure-function studies showed that the fifth SH3 domain of Tks5 binds to the N-terminus of XB130, which contains polyproline-rich motifs. Cell growth and survival studies revealed that down-regulation of XB130 and/or Tks5 reduced cell proliferation, resulting in cell cycle inhibition at the G1 phase and increased caspase 3 activity and apoptosis. Moreover, cell proliferation and survival were increased by overexpression of XB130 or Tks5 but decreased when XB130/Tks5 binding was disrupted by overexpression of XB130 N-terminal deleted mutant and/or Tks5 fifth SH3 domain W1108A mutant. Furthermore, down-regulation of XB130 and/or Tks5 inhibited serum- and growth factor-induced Src activation and downstream phosphorylation of PI3K and Akt. Our results suggest that Tks5, similar to XB130, plays a role in cell proliferation and cell survival and that the interaction between XB130 and Tks5 appears to be critical for regulation of Src-mediated cellular homeostasis.


Anaphylactic shock caused by impurities in orgotein preparations.
Previously reported allergic reactions to orgotein (superoxide dismutase) injections has assigned responsibility to this molecule, which is obtained from bovine liver. We report an anaphylactic shock probably caused by impurities contained in an orgotein preparation. Prick test to Peroxinorm (orgotein), BSA, and cow liver extract were positive but resulted negative with chymotrypsin, milk, meat and cow epithelium extracts. Tryptase levels determined 3, 24 hours and 15 days after the shock measured 6.32, 0.81 and 0.84 U/L respectively. Detection of specific IgE to Peroxinorm, BSA and chymotrypsin by ELISA was negative and positive to cow liver. Specific IgE to milk and cow epithelium by Pharmacia CAP system was negative. Immunoblotting with Peroxinorm revealed IgE specific bands at an apparent M.W of 67, 51, 56 and 16 kDa; immunoblotting with cow liver revealed bands at 72, 56, 50 and 36 kDa; immunoblotting with BSA and chymotypsin were negative. This case emphasises the role that 20 % of impurities of the pharmaceutical preparation may have in immediate hypersensitivity reactions.


Devolution or centralization? Differences in the development of nurse education commissioning policy among the UK nations.
An overview of the different systems for the commissioning of nurse education in the various UK countries is contextualized in the policy concerns of development and marketization driven by Government Working Papers 9 and 10. The different systems for commissioning nurse education in the various UK countries are described, with a particular focus on the English consortia system and its level of efficiency. It is argued that while the mechanism of consortia is being used to marketize nurse education commissioning in England, in the other three nations the commissioning process has actually become more centralized. This centralization is contrary to the policy of development, yet it is suggested here that the consortia mechanism adopted in England has not been followed in the other UK nations, as it has not yet proved an independently efficient method of commissioning.


3D Printing and Computer-Aided Design for Precision Osteotomy-Aided Modules in Bone Biomechanical Study.
Precise and shape-matching osteotomy models are determinants of the experimental homogeneity in the assessment of orthopedic biomechanical properties. At present, however, publications on detailed description of osteotomy in bone biomechanical study are scanty. The purposes of this study were to design a new method of osteotomy-aided module production for bone biomechanical study with the help of three-dimensional (3D) printing and computer-aided design (CAD) and to test the accuracy of osteotomy. Fourteen fourth-generation composite femurs were analyzed. The composite bone was scanned using computed tomography (CT) scanner and loaded in Mimics for reconstruction and, then, imported into 3-Matic software to design intertrochanteric region, distal femur, and rotation control lever models. 3D printer was used to print each component. After assembling Sawbones and osteotomy modules, a horizontal band-saw was used to create fracture models. The volume and mass of intermediate fragments were calculated and analyzed. Satisfactory osteotomies of all composite Sawbones were achieved. The mean volume and mass of intermediate fragments were 21.0 ± 1.5 mm3 and 19.0 ± 1.2 g, respectively. Range of deviation from average of volumes was -1.9 - 2.8 mm3 and most of these deviations fall within the range of -1.4 - 2.1 mm3. Range of deviation from average of mass was -2.0 - 1.6 g and most of these deviations fall within the range of -1.4 - 1.6 g. One-dimensional histogram of deviation from average shows the precise and stable osteotomy performed based on the modules accordingly. A new method of osteotomy-aided module production for bone biomechanical study with the help of 3D printing and CAD was designed and the accuracy of osteotomy was verified. This method is expected to achieve homogeneity and standardization of osteotomy in bone biomechanical study.


Transvaginal sacrospinous ligament suture rectopexy for obstructed defecation symptoms: 1-year outcomes.
The current study was aimed at investigating the safety, efficiency, and durability of transvaginal sacrospinous ligament suture rectopexy in women with obstructed defecation symptoms (ODS) and significant rectal hypermobility/folding. This was a prospective case series study performed during December 2018 to July 2020. Women presenting to our center with pelvic organ prolapse electing for surgical treatment were screened for ODS utilizing the PFDI-20 questionnaire. Patients were eligible for inclusion if they reported OD symptoms accompanying >50% of bowel movements (BMs), BM frequency ≥3 per week, stool type 3 or 4 based on the Bristol stool chart, absence of dyssynergic Valsalva, and dynamic ultrasound indicating a rectal compression ratio >25%. Patients underwent transvaginal sacrospinous ligament rectopexy and were followed up at 2 and 12 months postoperatively. A total of 20 patients underwent the procedure and completed the follow-up. Statistically significant improvements were observed in all OD symptoms and subjective improvement (94.7% ± 13.4 and 90.6% ± 18) at 2 and 12 months after the surgery respectively. Mean rectal compression ratio, detected via ultrasound, improved from 45.5% ± 18.4 preoperatively to 9.2% ± 13.7 at 2 months (p < 0.0001) and 19.6% ± 14.4 at 12 months (p < 0.0012). Surgical failure, defined as combined subjective (ODS >50% of bowel movements) and anatomical failure (rectal compression ratio >25%), occurred in 2 patients. Transvaginal sacrospinous ligament suture rectopexy was safe, feasible, and effectively treated ODS within this cohort of women undergoing POP surgery with rectal hypermobility confirmed by dynamic ultrasound.


Catalpol rescues cognitive deficits by attenuating amyloid β plaques and neuroinflammation.
This study sought to investigate the anti-amyloid β (Aβ) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model. The effects of catalpol on Aβ formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APPswe/PS1ΔE9 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aβ deposits, and NF-κB pathway activity. Aβ peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions. Catalpol potently inhibited Aβ fibril and oligomer formation. In microglial cells stimulated by Aβ, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aβ-exposed microglia on HT22 cells. Treatment with catalpol in APPswe/PS1ΔE9 mice downregulated neuroinflammation production, decreased Aβ deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APPswe/PS1ΔE9 mice. The administration of catalpol protected neurons by preventing neuroinflammation and Aβ deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.


A structural equation modeling approach to the study of stress and psychological adjustment in emerging adults.
Today's society puts constant demands on the time and resources of all individuals, with the resulting stress promoting a decline in psychological adjustment. Emerging adults are not exempt from this experience, with an alarming number reporting excessive levels of stress and stress-related problems. As a result, the present study addresses the need for a comprehensive model of emerging adult adjustment in the context of stress and coping variables and highlights the importance of accounting for differences between males and females in research concerning stress, social support, coping, and adjustment. Participants for this study are 239 college students (122 males and 117 females), the majority of whom are Caucasian. Results of structural equation modeling suggest that stress, social support, coping, and adjustment show unique patterns of relationships for males versus females. For both males and females, stress and social support show similar relationships to adjustment. In contrast, social support is related only to coping behaviors in females. Finally, social support appears to be a more important variable for female adjustment, whereas other coping behaviors appear to be more pertinent to male adjustment. Limitations and suggestions for future research will be discussed.


Urine Desmosine as a Novel Biomarker for Bronchopulmonary Dysplasia and Postprematurity Respiratory Disease in Extremely Preterm or Low Birth Weight Infants.
This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants. This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis. Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], p = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], p = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], p = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144). Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants. · Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants..


[Support of treatment safety by nursing personnel when dealing with emergency situations in long-term care facilities : Results of a qualitative empirical study].
A significant number of emergency responses and hospitalizations of nursing home residents are considered avoidable and result in an unnecessary burden or health risk for residents. One cause of these unnecessary emergency responses lies in the lack of confidence of nursing personnel in their own actions and decisions. The goal of the NOVELLE project is to develop recommendations for action for certain emergency situations that enable nursing personnel to make operationalized decisions and empower them to take confident action. The challenges for nursing professionals to act with confidence in emergency situations were collated and assessed through a qualitative interview study. The results of this study are presented.


HDL-cholesterol, apolipoproteins A1 and B. Age and index body weight.
Some data of previous literature have emphasized a negative correlation between plasma apo A1, HDL cholesterol and coronary heart disease. The present paper stresses a high negative correlation existing both in females and males between values of index body weight (IBW) and plasma levels of HDL cholesterol and apo A1. No correlation has been found between age and, respectively, HDL cholesterol, apo A1 and apo B.


Measuring Plasmodium falciparum Erythrocyte Invasion Phenotypes Using Flow Cytometry.
Having the ability to rapidly, accurately, and robustly measure Plasmodium falciparum merozoite invasion is a critical component in effective assessment of a blood stage vaccine's mechanism of action. Being able to measure invasion of erythrocytes accurately, objectively and in a high throughput fashion is of critical importance. Here, we describe a simple and robust flow cytometry method that allows for the measurement of the key invasion parameters of parasite multiplication rate and erythrocyte selectivity-both important determinants of disease severity-from the schizont to the ring stage of the parasite's life-cycle, thus separating invasion from growth of the parasite. Importantly, this method is able to accurately detect low levels of parasitemia and heterogeneity within the population that can be missed by enzymatic methods. Lastly, this method has been successfully adapted and employed in field based research settings for parasitemia measurements in vivo, ex vivo, and in vitro and to measure invasion inhibition by antibodies and the use of alternative pathways for invasion.


Mirabegron Reduces Urinary Frequency and Improves Overactive Bladder Symptoms at 3 Months After 125I-brachytherapy for Prostate Cancer: An Open-Labeled, Randomized, Non-Placebo-Controlled Study.
To evaluate the additional effects of mirabegron to alpha-1 adrenergic antagonist on lower urinary tract symptoms of patients who underwent 125I-brachytherapy for prostate cancer. Patients who underwent 125I-brachytherapy for prostate cancer (cT1-cT3aN0M0) in a single institute between September 2016 and October 2018 were enrolled in the randomized, non-placebo, open-labeled, paralleled study. Patients were randomly distributed (1:1) to combination group (tamsulosin (0.2 mg/day) plus mirabegron (50 mg/day)) or tamsulosin-alone group after 125I -brachytherapy by envelope method. The primary endpoint was the change from baseline in mean voided volume per micturition 3 months after 125I brachytherapy. The secondary endpoints included the changes from baseline of International Prostate Symptom Score, Overactive Bladder Symptom Score, and Expanded Prostate Cancer Index Composite scores and 24 hours urinary frequency after 3 months after 125I brachytherapy. The mean changes in volume voided per micturition in the combination (n = 108) and tamsulosin-alone (n = 110) groups were -62.5 (standard deviation, ±53.8) and -68.0 (standard deviation, ±52.7), respectively (P = .17). The change in Overactive Bladder Symptom Score in combination group (P = .02) was more moderate than in tamsulosin-alone group; and 24 hour urinary frequency in combination group was lower (P = .03) than in tamsulosin-alone group. Retention rates within 3 months after 125I-brachytherapy in the mirabegron and tamsulosin-alone groups were 7.3% (9/122) and 6.0% (7/118), respectively (P = .80). Tamsulosin and mirabegron combination therapy after 125I-brachytherapy did not improve voided volume per micturition compared to tamsulosin-only treatment. However, it could improve frequent urination and overactive bladder symptoms.


Effect of workplace dietary intervention on salt intake and sodium-to-potassium ratio of Japanese employees: A quasi-experimental study.
Excess salt intake is a major risk factor for hypertension and cardiovascular disease. Modifying workplace environments has been recognized to be important for reducing salt intake. However, studies examining the effects of improving the workplace environment regarding salt reduction are limited. This study aimed to evaluate the effects of workplace dietary intervention on employees' salt intake and sodium-to-potassium (Na/K) ratio. A quasi-experimental study was conducted. Two small business establishments in Saitama Prefecture, Japan, were allocated as the intervention (n = 69) and comparison (n = 68) workplaces, respectively. The 1-year intervention involving healthy lunch and nutrition education was implemented in the intervention workplace. Spot urine samples, physical assessments, and self-administered questionnaire data were collected at baseline, 6 months, and 1 year after the start of the intervention. Analysis of covariance was conducted to investigate differences in the salt intake or Na/K ratio between the study workplaces at year 1. Educational status and rotating work schedules were included as covariates. Salt intake in the intervention workplace decreased significantly from 10.7 to 9.3 g (-1.4 g change; 95% confidence interval [CI]: "-2.4, -0.5"). The adjusted difference in changes in salt intake between workplaces was statistically significant (-3.7 g change; 95% CI: "-5.2, -2.3"). Although no significant change was observed in the Na/K ratio in the intervention workplace (3.37-3.08; -0.29 change; 95% CI: "-0.59, 0.01"), the adjusted difference in changes between the workplaces was statistically significant (-0.60 change; 95% CI: "-1.03, -0.17"). Providing healthy lunch and nutrition education may be effective approaches to reduce employees' salt intake and Na/K ratio.


Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function.
Age-related macular degeneration (AMD) is a multifactorial disease, which is characterized by loss of central vision, affecting one in three people by the age of 75. The Y402H polymorphism in the complement factor H (CFH) gene significantly increases the risk of AMD. We show that Y402H-AMD-patient-specific retinal pigment epithelium (RPE) cells are characterized by a significant reduction in the number of melanosomes, an increased number of swollen lysosome-like-vesicles with fragile membranes, Cathepsin D leakage into drusen-like deposits and reduced lysosomal function. The turnover of C3 is increased significantly in high-risk RPE cells, resulting in higher internalization and deposition of the terminal complement complex C5b-9 at the lysosomes. Inhibition of C3 processing via the compstatin analogue Cp40 reverses the disease phenotypes by relieving the lysosomes of their overburden and restoring their function. These findings suggest that modulation of the complement system represents a useful therapeutic approach for AMD patients associated with complement dysregulation.


Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells.
We previously demonstrated that phospholipase D (PLD) expression and PLD activity are upregulated during neuronal differentiation. In the present study, employing neural stem cells from the brain cortex of E14 rat embryos, we investigated the role of Rho family GTPases in PLD activation and in neurite outgrowth of neural stem cells during differentiation. As neuronal differentiation progressed, the expression levels of Cdc42 and RhoA increased. Furthermore, Cdc42 and PLD1 were mainly localized in neurite, whereas RhoA was localized in cytosol. Co-immunoprecipitation revealed that Cdc42 was bound to PLD1 during differentiation, whereas RhoA was associated with PLD1 during both proliferation and differentiation. These results indicate that the association between Cdc42 and PLD1 is related to neuronal differentiation. To examine the effect of Cdc42 on PLD activation and neurite outgrowth, we transfected dominant negative Cdc42 (Cdc42N17) and constitutively active Cdc42 (Cdc42V12) into neural stem cells, respectively. Overexpression of Cdc42N17 decreased both PLD activity and neurite outgrowth, whereas co-transfection with Cdc42N17 and PLD1 restored them. On the other hand, Cdc42V12 increased both PLD activity and neurite outgrowth, suggesting that active state of Cdc42 is important in upregulation of PLD activity which is responsible for the increase of neurite outgrowth.


Differential expression of the actin gene family of Strongylocentrotus purpuratus.
Molecular probes that individually recognize the 3' nontranslated regions of six actin genes were utilized in RNA gel blot hybridizations to detect RNAs complementary to each gene in embryonic and adult tissues of Strongylocentrotus purpuratus. In addition the probes were used in DNA excess filter hybridizations to estimate the relative contribution of the different actin genes. All six genes produce relatively stable mRNAs, and each displays a characteristic and distinct pattern of expression. On the basis of their expression in the egg, early embryos, or in adult coelomocytes, it is concluded that genes termed CyI, CyIIa, CyIIb, CyIIIa, and CyIIIb encode cytoskeletal actin proteins. Actin gene M gives rise to mRNAs that are found only in tissues containing muscle. Actin genes CyI, CyIIa, CyIIb, and M are expressed in both adult and embryonic tissues, giving rise to transcripts 2.1-2.2 kb in length. Expression of genes CyIIIa and CyIIIb is confined to the embryo. Gene CyIIIa provides the major embryonic actin mRNA, which is 1.8 kb in length. Three of the cytoskeletal actin genes are linked over a 30-kb distance in the S. purpuratus genome. We show that the actin genes included in this linkage group are not coordinately expressed.


Is it worthwhile to operate on subclinical right varicocele in patients with grade II-III varicocele in the left testicle?
To determine whether repair of subclinical varicoceles in the right testicle results in significant seminal improvement in patients with clinical left varicocele. Patients were divided into two groups: Group I (unilateral varicocelectomy) and Group II (bilateral varicocelectomy-subclinical left varicocele). The mean sperm concentration before treatment was higher in Group I (21.01 +/- 19.1) compared to Group II (5.7 +/- 10.7) (p = 0.04). An increase in volume was detected in the left testicle of patients in Group I (17 +/- 7.9 vs. 22.81 +/- 8.2; p = 0.04) and in the right testicle of patients in Group II (18.4 +/- 6.2 vs. 22.3 +/- 6.5; p = 0.04). Although the mean postoperative sperm concentration in Group I increased slightly (25.7 +/- 22.8), the mean sperm concentration in Group II increased significantly (30.32 +/- 9.8; p = 0.03). Pregnancy rate was higher in Group II (66.7%) compared to Group I (33.3%). Even a small, subclinical unrepaired varicocele continues to have a detrimental effect on bilateral testis function in a patient with grade II-III left varicocele.


CT findings in left paraduodenal herniae.
Computed tomography (CT) was used to evaluate mass effect on the greater curvature of the stomach in two children with histories of intermittent, recurrent vomiting. The paraduodenal herniae were identified on CT in both of these patients as small bowel interposed between the stomach and the body of the pancreas.


Spatial Distribution and Habitat Selection of Sarda Cattle in a Silvopastoral Mediterranean Area.
The beef livestock system in Sardinia is based on suckler cows, often belonging to autochthonous breeds, such as the Sarda breed, and they often graze silvopastoral areas. Besides beef meat, silvopastoral systems (SPSs) provide several Ecosystem Services (ESs), such as timber provision, harvested as wood, and watershed protection. Livestock distribution is a critical factor for the sustainable use of SPSs (e.g., to avoid uneven grazing patterns) and information on patterns of spatial use are required. A study was conducted to determine: (i) the spatial distribution and (ii) the habitat selection of Sarda cattle grazing in a Mediterranean silvopastoral area. Over different seasons, 12 free-roaming adult Sarda cows were fitted with Global Positioning System (GPS) Knight tracking collars to calculate an index mapping of the incidence of livestock in the landscape (LRI) and a preference index (PI) for different areas. Since the PI data were not normally distributed, the Aligned Rank Transform (ART) procedure was used for the analysis. LRI was able to represent the spatial variability in resource utilization by livestock as a LRI map. Overall, the areas where the animals drank and received supplementation were strongly preferred by the cows, reaching PI values in the summer of 19.3 ± 4.9 (median ± interquartile range), whereas areas with predominantly rocks were strongly avoided (the worst PI value in the spring was 0.2 ± 0.6). Grasslands were, in general, used in proportion to their presence in the area, with slightly increased use in the spring (PI 1.1 ± 0.5). Forest area was avoided by cows, except in the spring when it was used in proportion to their presence in the area.


Id proteins at the cross-road of development and cancer.
A large body of evidence has been accumulated that demonstrates dominant effects of Id proteins on different aspects of cellular growth. Generally, constitutive expression of Id not only blocks cell differentiation but also drives proliferation. In some settings, it is sufficient to render cells immortal or induce oncogenic transformation. The participation of Id proteins in advanced human malignancy, where they are frequently deregulated, has been dramatically bolstered by the recent discovery that Id exert pivotal contributions to many of the essential alterations that collectively dictate malignant growth. Relentless proliferation associated with self-sufficiency in growth signals and insensitivity to growth inhibitory signals, sustained neoangiogenesis, tissue invasiveness and migration capabilities of tumor cells all share dependency on the unlimited availability of Id proteins. It is remarkable that many of these features recapitulate those physiologically propelled by Id proteins to support normal development. We propose that the participation of Id in multiple fundamental traits of cancer may be the basis for unprecedented therapeutic opportunities.


Comparing delivery channels to promote nutrition-sensitive agriculture: A cluster-randomized controlled trial in Bangladesh.
We use a randomized controlled trial in rural Bangladesh to compare two models of delivering nutrition content jointly to husbands and wives: deploying female nutrition workers versus mostly male agriculture extension workers. Both approaches increased nutrition knowledge of men and women, household and individual diet quality, and women's empowerment. Intervention effects on agriculture and nutrition knowledge, agricultural production diversity, dietary diversity, women's empowerment, and gender parity do not significantly differ between models where nutrition workers versus agriculture extension workers provide the training. The exception is in an attitudes score, where results indicate same-sex agents may affect scores differently than opposite-sex agents. Our results suggest opposite-sex agents may not necessarily be less effective in providing training. In South Asia, where agricultural extension systems and the pipeline to those systems are male-dominated, training men to deliver nutrition messages may offer a temporary solution to the shortage of female extension workers and offer opportunities to scale and promote nutrition-sensitive agriculture. However, in both models, we find evidence that the presence of mothers-in-law within households modifies the programs' effectiveness on some nutrition, empowerment, and attitude measures, suggesting that accounting for other influential household members is a potential area for future programming.


Recovery of valuable metals from spent lithium-ion batteries through biomass pyrolysis gas-induced reduction.
The development of spent lithium-ion batteries (LIBs) recycling technologies can effectively alleviate environmental pressure and conserve metal resources. We propose a win-win strategy for pyrolysis gas reduction by lignocellulosic biomass, ensuring gas-induced reduction by spatial isolation of biomass and lithium transition metal oxides (LiTMOX (TM = Ni, Co, Mn)), and avoiding the separation of solid carbon and TMOX (TM = Ni, Co, Mn). In the spent LiCoO2 batteries, the lithium recovery efficiency reaches 99.99% and purity reaches 98.3% at 500 °C. In addition, biomass pyrolysis gas reduction is also applicable to treat spent LiMn2O4 and LiNi0.6Co0.2Mn0.2O2 batteries. Thermodynamic analysis verifies that CO dominates the gas reduction recovery process. DFT calculation indicates that the gas reduction induces the collapse of the oxygen framework of LiTMOX (TM = Ni, Co, Mn). Everbatt-based economic and environmental analysis illustrates that this is an environment-friendly and energy-saving method.


[Influence of Minkeqing oral liquid on IL-6, IL-8, ET-1, TX-B2 in blood and to observe bronchoalveolar lavage fluid of the rat with inhalating ovalbumin].
To observe the effect on infantile allergic cough with Minkeqing oral liquid (Minkeqing) and to study its cell molecular biologic mechanism. The rat model was induced by inhalating ovalbumin; then the effects of Minkeqing on IL-6, IL-8, ET-1, TX-B2 in the blood and the bronchoalveolar lavage fluid (BALF) of the animal model were observed. Minkeqing could reduce the levels of IL-6,IL-8,ET-1,Tx-B2 in the blood and BALF of the animal model. Minkeqing has the significant function of inhibiting the release of inflammatory mediums.