Effects of tannin-rich host plants on the infection and establishment of the entomopathogenic nematode Heterorhabditis bacteriophora.
Parasitized animals can self-medicate. As ingested plant phenolics, mainly tannins, reduce strongyle nematode infections in mammalian herbivores. We investigated the effect of plant extracts known to be anthelmintic in vertebrate herbivores on the recovery of the parasitic entomopathogenic nematode Heterorhabditis bacteriophora infecting African cotton leafworm (Spodoptera littoralis). Nematode infective juveniles (IJs) were exposed to 0, 300, 900, 1200, 2400 ppm of Pistacia lentiscus L. (lentisk), Inula viscosa L. (strong-smelling inula), Quercus calliprinos Decne. (common oak) and Ceratonia siliqua L. (carob) extracts on growth medium (in vitro assay). In control treatments, 50-80% of IJs resumed development to J4, young and developed adult hermaphrodites, whereas all extracts, except for C. siliqua at 300 ppm, impaired IJ exsheathment and development. The highest concentration of I. viscosa extract (2400 ppm) had the strongest effect, killing 95% of exposed nematodes. Surviving nematodes did not recover, remaining at the IJ stage. Over the whole cycle, I. viscosa extract inhibited recovery to 25% or less, and did not allow full development to adulthood, whereas 65% of IJs in the control treatment recovered and resumed development, 12% reaching complete maturation within 72 h of incubation. When herbivorous S. littoralis larvae were fed with different plant extracts in vivo, I. viscosa had the strongest effect at concentrations above 300 ppm, with 90% of insect-invading IJs not developing to parasitic stages, whereas in the control treatment, 85% of IJs resumed development. Exposure to C. siliqua extract also inhibited exsheathment and development of 75% of the IJs. Half of those that resumed development reached full maturation. P. lentiscus and Q. calliprinos extracts also inhibited development of 50% IJs. Our results suggest that H. bacteriophora can be used to study herbal medication against parasites in animals.


Primary Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) of the tongue in a child: A case report.
Ewing's sarcoma (ES) and primitive neuroectodermal tumor (PNET) are high grade malignant small round cell tumors presenting in both skeletal and extraskeletal anatomic locations. Actually, they are the same entity showing varying degrees of neuroectodermal differentiation. Very few cases of peripheral PNET (pPNET) of the tongue was reported in medical literature. Here, we first report a case of primary extraskeletal ES/pPNET in the tongue of a 9-years old girl. The result of immunohistochemical analysis showed the membranous positive for CD99 and Vimentin. The girl underwent radical surgical treatment and received six cycles of OPEC regimen adjuvantchemotherapy without radiotherapy, and now she is remaining tumor-free survival. The individual comprehensive therapy shows a good curative effect.


Bedside ultrasound for the detection of soft tissue foreign bodies: a cadaveric study.
The objective of this study was to evaluate the sensitivity and specificity of bedside ultrasound, as performed by emergency physicians with typical equipment, in detecting small, soft tissue foreign bodies, using a cadaveric model. This was a prospective study, using 6 unembalmed human cadavers and 6 ultrasound-credentialed, emergency medicine residency-trained physicians as sonographers. Incisions were made in 150 total sites of the extremities and each site was randomly assigned one of five groups: wood, metal, plastic, glass, or no foreign body. All foreign bodies were 2.5 mm3 in total volume or less, no longer than 5 mm in any dimension, and inserted to a depth of up to 3 cm. Ultrasound was performed with a SonoSite TITAN (SonoSite, Inc., Bothell, WA) ultrasound system using a L38/10-5 broadband linear array transducer. Sonographers were blinded to the number, type, and location of foreign bodies. A total of 900 ultrasound examinations were recorded. Overall sensitivity of ultrasound for foreign body detection was 52.6% (95% confidence interval [CI] 48.9%-56.2%), and overall specificity was 47.2% (95% CI 39.9%-54.5%). Positive predictive value was 79.9% (95% CI 76.3%-83.5%), and negative predictive value was 20.0% (95% CI 16.2%-23.7%). Sensitivity for individual sonographers ranged from 40.8% to 72.3% (average 52.6% +/- 13.3%), and specificity ranged from 30% to 66.7% (average 47.2% +/- 15.1%). Inter-observer reliability was poor. In our model, bedside ultrasound performed by emergency physicians was neither sensitive nor specific for the presence of small soft tissue foreign bodies.


Effect of plating medium and phage storage on mutant frequency and titer in the lambda cII transgenic mutation assay.
We examined several experimental parameters of the lambda cI/cII transgenic mutation assay. In the assay, clear plaque lambda phage mutants are identified in a positive selection scheme following rescue of the lambda/LIZ shuttle vector from frozen tissues of Big Blue" transgenic mice. Mutant frequency and titer of phage from various tissues of control and ENU-treated animals was essentially the same on LB or TB1 plating medium, and storage of isolated DNA at 4 degrees C for up to 4 months did not affect either mutant frequency or titer. Storage of packaged phage for 28 days at 4 degrees C did not affect titer. The mean mutant frequency of packaged phage stored 28 days at 4 degrees C was consistently higher than phage plated the same day as packaging (day 0), though the difference was statistically significant in only two of the four samples tested. Reconstruction experiments in which numerically defined titers of known cII mutants were plated on both G1217 and G1225 E. coli strains and incubated at 37 degrees C or 24 degrees C showed highest titers on G1217 at 37 degrees C. The fraction of the G1217, 37 degrees C titer seen in the other strains and conditions varied widely with the cII mutation.


Prostaglandins in the human fetal circulation in mid-trimester and term pregnancy.
Concentrations of prostaglandins in fetal and maternal plasma during mid-pregnancy and fetal plasma at term have been measured. Fetal levels at both gestations were higher than found in maternal blood. The stable chemical breakdown product of prostacyclin, 6-keto-prostaglandin F1 alpha, was consistently considerably higher in the fetus during mid-pregnancy compared with at term. Prostaglandin F levels were also significantly higher in mid-pregnancy, though there was no difference in the concentrations of the major circulating prostaglandin F metabolite, PGFM. Concentrations of prostaglandin E were similar at the two stages of pregnancy. The physiological significance of these findings is discussed.


Glassy Flux Protocol to Confine Lead-Free CsSnX3 Nanocrystals into Transparent Solid Medium.
Encapsulation of halide perovskites into a transparent solid medium is important for increasing their stability and rendering the exploration of new optoelectronic applications. Here, we describe a glassy flux protocol to confine lead-free cesium tin halide (CsSnX3) perovskite nanocrystals into a transparent chalcogenide glassy matrix by capitalizing on judiciously designed germanium-antimony-sulfur chalcogenide flux as a solvent to dissolve and recrystallize the target crystal phases. We show that CsSnX3 nanocrystals can be obtained in the form of a spherical shape, single crystalline, and with an arbitrary halide ratio through the use of cesium halide and tin(II) halide at precisely defined concentrations. The grain size and size distribution of CsSnX3 nanocrystals are rationally tuned by Ostwald-ripening-controlled crystallization of CsSnX3 supersaturated metastable glasses. The present work suggests that the traditional flux technique could be adopted inversely for materials discovery of new nanocomposites through a simple protocol of the dissolution of target nanocrystals into an inert transparent glassy flux.


Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?
The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been reported to lack effect in this model. The neuroplastic changes induced in acute and chronic animal models of epilepsy are known to affect the pharmacological profile of AEDs in vivo. Hence, we investigated whether brain slices from pentylenetetrazole (PTZ)-kindled animals could provide a more predictive screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline-injected and PTZ-kindled mice. Our data suggest that the use of slices from PTZ-kindled mice in the cortical wedge does not increase the predictive validity of the model as an in vitro screening model for AEDs. Traditionally, the incidence of certain seizure types is widely used as a measure to characterize drug action in animal models of epilepsy. In our study, the anticonvulsant effect of the AEDs was investigated in vivo using several observational parameters (i.e., incidence and duration of convulsions, latency to clonic convulsions, and severity of convulsions). We found that including the observational parameter "severity" offered important additional information about the drug profile that would otherwise be lost if only a single parameter as "incidence" was used.


Frequency and severity of infections in day care.
This study was undertaken to compare prospectively the frequency, nature, and severity of infections experienced by children in three types of child care arrangements: home care, group care (two to six children), and day care (seven or more children). Children were enrolled at birth and observed for 12 to 18 months. At entry there were 159 children in home care, 40 in group care, and 45 in day care. The families were telephoned every 2 weeks to record on a standardized form the type and severity of illnesses experienced during the previous interval. Severe illnesses were defined by high fever, duration exceeding 10 days, or physician visit. Children remaining in their original child care group for at least 1 year were compared with regard to the frequency and severity of illness. Children in group care and day care were more likely than children in home care to experience at least six respiratory infections, more than 60 days of illness, and more than four severe illnesses (P less than 0.01). Similarly, life table analyses showed that children in home care had fewer episodes of infection than did children in day care (P less than 0.01). Although no children were hospitalized because of acute infections during the first year of study, hospitalization for myringotomy and tube placement occurred in 21% of children in day care and 3% of children in home care (P less than 0.01).


Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial.
This randomized controlled trial tested the hypothesis that children with non-high-risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event-free survival. 392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6-mercaptopurine (25 mg/m2 /day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25 mg/m2 /day beginning on days 50 and/or 71 unless dose-limiting myelosuppression had occurred. In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty-seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five-year probability of event-free survival was 0.89 (95% CI: 0.85-0.93) in the experimental arm vs 0.93 (0.90-0.96) in the control arm (P = .13). The median accumulated length of 6-mercaptopurine treatment interruptions was 7 (IQR 2-12) in the experimental arm vs 4 (IQR 0-10) in the control arm (P = .002). This study found no benefit from individualized 6-mercaptopurine increments compared to standard therapy.


My personal experiences at the BEST Medical Center: A day in the clinic-the morning.
Dr. Ida Lystic is a gastroenterologist who trained at the OTHER (Owen T. Henry and Eugene Rutherford) Medical Center, after having completed her MD degree at the prestigious Harvey Medical School (recently renamed the Harvey Provider School). She accepted a faculty position at the BEST (Byron Edwards and Samuel Thompson) Medical Center. Dr. Lystic shares her experiences on a typical morning in gastroenterology clinic. Although her clinic start date was delayed by 2 months after becoming sick following a mandatory flu shot and having to complete more than 70 hours of compliance training modules, she is now familiar with the BEST system. Clinic scheduling priorities include ensuring that the staff can eat lunch together and depart at 5:00 pm. It is a continual challenge to find time to complete the electronic medical record after BEST changed from the SIMPLE (Succinct Input Making Patients Lives Electronic) system to LEGEND (referred to as Lengthy and Excessively Graded Evaluation and Nomenclature for Diagnosis by her colleagues). To maintain clinic punctuality, a compliance spreadsheet is e-mailed monthly to the Wait Time Committee. Their most recent corrective action plan for tardy physicians included placing egg timers on the doors and having nurses interrupt visits that exceed the allotted time. Administrative decisions have resulted in downsizing personnel. Patients are required to schedule their own tests and procedures and follow-up appointments-causing low patient satisfaction scores; however, the money saved lead to a large year-end bonus for the vice president of BEST Efficiency, who holds "providers" accountable for the poor patient experience. Although Dr. Ida Lystic and the gastroenterology clinic at "the BEST Medical Center" are creations of the authors' imagination, the majority of the anecdotes are based on actual events.


Nanofibrous polysaccharide hydroxyapatite composites with biocompatibility against human osteoblasts.
Regenerative medicine has a high demand for defined scaffold materials that promote cell growth, stabilize the tissue during maturation and provide a proper three dimensional structure that allows the exchange of nutrients. In many instances nanofiber composites have already shown their potential for such applications. This work elaborates the development of polysaccharide based nanofibers with integrated hydroxyapatite nanoparticles. A detailed study on the formation of electrospun nanofibres from aqueous mixtures of carboxymethyl cellulose polyethylene oxide was performed. The influence of different processing conditions and spinning solution properties using a nozzle-less electrospinning device was systematically studied. Optimized parameters were used to incorporate hydroxyapatite nanoparticles into the fibers. Nanofibers were additionally hydrophobized with alkenyl succinic anhydride (ASA) to render them insoluble in water. The nanofiber webs were thoroughly investigated with respect to morphology, chemical composition and inorganic content. Time dependent biocompatibility testing of the materials with human bone-derived osteoblasts showed no significant reduction in cell viability for the developed materials composed of carboxymethyl cellulose/polyethyleneoxide. Cells grown on hydrophobized materials show similar viability as those grown on a commercial collagen/apatite matrix.


Comparative Evaluation of Potential Dentinal Microcracks Related to Instrumentation alongside Bypassed Broken Instruments: An In Vitro Study.
To investigate the occurrence of microcracks in the canals containing broken instruments in the middle and apical thirds after instrumentation with various systems. One-hundred and fifty mature mandibular premolars with single straight canal were collected and stored in distilled water. Samples were checked out from any preexisting deformation or cracks, and then standardized in length. Thirty teeth were never instrumented (NI) as a control group, 60 teeth have received a broken instrument in the middle third, and 60 ones at the apical third. Teeth were placed in resin blocks with simulation of periodontal ligaments. After bypassing the instruments, samples were divided into four groups n = 30; first group was prepared manually MN until 25/0.02, while the other three groups were prepared until 25/0.04 using three different rotary systems; Race RC-2Shape TS-Hyflex CM HCM. Roots were cut transversely at levels of broken instruments and examined under 40× microscopic magnification. All the rotary groups produced microcracks. No significant difference of the partial cracks was observed among all groups at the middle and apical levels p >0.05. TS produced more complete cracks compared to each of NI, MN, RC at middle level and NI, MN at apical level; p <0.05. No significant differences of microcracks incidence were observed between two middle and apical levels among the five groups. Dentinal microcracks could be obviously resulted after rotary instrumentation alongside broken instruments, while manual shaping was less likely to cause microcracks. Manual files were less likely to induce microcracks alongside broken instruments in comparison with rotary files which could be considered much safer.


Recent advances of Sterculia gums uses in drug delivery systems.
Trees of the genus Sterculia produce polysaccharide-rich exudates, such as karaya gum (Sterculia urens), chicha gum (Sterculia striata), and Sterculia foetida gum. These anionic biomaterials are biodegradable, with high viscosity, low toxicity, and gelling properties in aqueous media. According to these properties, they show promising applications as a polymer matrix for use in drug delivery systems. For this application, both the chemically modified and the unmodified polysaccharide are used. This review focuses on analyzing the state of the art of recent studies on the use of Sterculia gums in a variety of pharmaceutical forms, such as tablets, hydrogels, micro/nanoparticles, and mucoadhesive films. Sterculia gums-based delivery systems have potential to be explored for new drug delivery systems.


Content-based image-retrieval system in chest computed tomography for a solitary pulmonary nodule: method and preliminary experiments.
The aim of this study was to develop a new diagnostic support system using content-based image-retrieval technology. In this article, we describe the mechanism and preliminary evaluation of this system for use with CT images of solitary pulmonary nodules. With the approval of the institutional review board of Shizuoka Cancer Center, we built a database that included CT images of 461 solitary pulmonary nodules. With this database, we developed a system that automatically extracts the pulmonary nodule when the nodule area is clicked, retrieves previous cases based on an image analysis of the extracted lesion, and generates reports of the pulmonary nodule semi-automatically. We compared the percentage of correct diagnoses with and without the system using 30 solitary pulmonary nodules, which were not included in the database, with one radiologist and two residents. As a per-user evaluation, the number of clicks required to extract the nodule region and the extracted regions was compared, and presented candidate cases were evaluated. As an evaluation of the retrieval results, the presented candidate cases were evaluated by comparing the number of diagnostic matches (benign/malignant) between the queries and four presented cases. Additionally, to evaluate the validity of the retrieval technology, the radiologist selected the most similar cases presented by the system and evaluated the visual similarity on a five-point scale. With this system, the percentage of correct diagnoses for the radiologist improved from 80 to 93%. For the two residents, the diagnostic accuracy improved from 66.7 to 80% and from 76.7 to 90%, respectively. The evaluation of the number of clicks required indicated that for 19 cases with the radiologist and 12 and 11 cases with the two residents, respectively, only one click was required to extract the region. When the extracted regions were compared between the radiologist and the residents, 22 and 19 cases had a Dice's Coefficient of 0.85 or higher, respectively. For the radiologist, the number of cases that matched the diagnosis (benign/malignant) averaged 3.7 ± 0.5 among 23 malignant cases and 1.7 ± 1.4 among 7 benign cases, while for the residents, these values were 3.6 ± 0.5 and 1.1 ± 0.9, and 3.4 ± 0.8 and 1.1 ± 1.3, respectively. With regard to visual evaluations by the radiologist, there were 15 similar cases and 11 somewhat similar cases. These results suggest that, despite some differences in the search results among the users, this system has been confirmed that it can improve the accuracy of diagnosis as it displays similar cases at high probability. In addition, with the use of this system, past cases and their reports can be effectively referred to. Therefore, this diagnostic-assistant system has the potential to improve the efficiency of the CT image-reading workflow.


Language proficiency and biologics access: a population study of psoriasis patients in the United States.
Language proficiency plays an important role in healthcare choices and access. Differences in access to biologic medications exist, but it is unknown how much English proficiency influences access in US psoriasis patients. To compare biologic medication use for psoriasis patients with differing English proficiency levels. Population study of US psoriasis patients using the 2013-2017 Medical Expenditure Survey. Among a total of 4,470,820 US psoriasis patients (weighted), 4,028,119 (90.1%) had perfect English proficiency, and 442,700 (9.9%) had less than perfect English proficiency. Among the total population, 422,523 (9.5%) had access to biologics. Among those who received biologics, 411,411 (97.4%) of those had perfect English proficiency, and 11,112 (2.6%) of those had less than perfect English proficiency. Multivariate logistic regression found that patients with less than perfect English proficiency were significantly less likely to have access to biologics [OR 0.015 (95% CI: 0.001-0.179); p = .002], after adjusting for insurance status, income, education, healthcare utilization, and other sociodemographic and clinical factors. Psoriasis disease severity not specified. Psoriasis patients with low English proficiency are significantly less likely to receive biologics than those with high English proficiency. Those with higher English proficiency are 61 times more likely to access biologics.


Clinical experience in mental health nursing: determining satisfaction and the influential factors.
Clinical exposure to the mental health environment has been identified as a major factor in promoting a more favourable attitude towards mental health nursing. However, little attention has been devoted to measuring specific aspects of the clinical placement experience. This paper presents the findings of a survey of 703 undergraduate nursing students designed to measure satisfaction and identify factors influencing satisfaction (length and type of placement, time spent with a preceptor). A questionnaire was administered to undergraduate nursing students in Victoria, Australia, at the conclusion of their clinical experience in mental health. The findings demonstrate a high level of satisfaction, particularly in feeling welcomed, well oriented and supported, and opportunities for patient care. Students' views were influenced by the duration and type of placement and time spent with a preceptor. These findings provide valuable information about characteristics of a positive clinical experience that should be considered in structuring clinical placements in the mental health field.


Visualization of the basement membrane zone of the bladder by optical coherence tomography: feasibility of noninvasive evaluation of tumor invasion.
Imaging techniques with high resolution are evolving rapidly for medical applications and may substitute invasive diagnostic techniques. The use of ultrahigh resolution optical coherence tomography (UHR-OCT) to image healthy and morphologically altered bladder tissue with virtual histology is evaluated ex vivo to define parameters necessary for future, diagnostically relevant in vivo systems. Here, special focus is on the visualization of the basement membrane zone. Optical coherence tomography examinations were performed by using a modified commercial OCT system comprising a Ti:sapphire femtosecond laser to support an enhanced resolution of 3 microm axial x 10 microm lateral. Tomograms of 142 fresh human bladder tissue samples from cystectomies, radical prostatectomies, and transurethral tumor resections were recorded and referenced to histologic sections using standard hematoxylin and eosin staining. OCT of normal bladder mucosa allows for a clear differentiation of urothelium and lamina propria. The basement membrane zone is identified as a narrow, low-scattering band between these layers. This allows for reliable exclusion of invasion. Healthy urothelial tissue, carcinoma in situ, and transitional cell carcinoma can be differentiated using this imaging technique. Sensitivity of UHR-OCT for malignant bladder tissue could be determined to be 83.8%, and specificity to be 78.1%. UHR-OCT is considered promising in the attempt to strive for fluorescence cystoscopy-guided virtual histology as a means of supporting therapeutic decisions for bladder neoplasia.


Increased levels of interferon-induced (2'--5') oligo-isoadenylate synthetase in mature T-lymphocytes and in differentiated Friend-erythroleukemic cells.
The level of (2'--5') oligo-isoadenylate synthetase was measured in lymphocytes at different stages of maturation within the T cell lineage and in Friend-erythroleukemic cells induced to differentiate by 1.5% Me2SO. The level of (2'--5') oligo-isoadenylate synthetase was higher in the peripheral mature T-lymphocytes than in the thymocytes. Further fractionation of the thymic population by peanut agglutinin showed higher levels of the synthetase activity in the mature PNA- cells than in the immature PNA+ cells. The activity of the enzyme in the immature thymic subpopulation could be stimulated in vitro after treatment with interferon. On the other hand, these cells did not produce the mitogen-induced immune interferon (gamma-type). Human peripheral mononuclear cells exhibited high levels of the (2'--5') oligo-isoadenylate synthetase, as well as the leukemic cells from patients with chronic lymphatic leukemia; extremely low levels of the enzyme were detected in some of the patients with acute lymphatic leukemia. In cultures of Friend cells, induced to differentiate by Me2SO, the level of the (2'--5') oligo A synthetase was low in rapidly growing cells and increased by a factor of 8--10 as the cells reached the stationary phase. This increase was completely prevented if anti-interferon antiserum was added to the medium concomitant with the Me2SO, suggesting that the increase in the level of (2'--5') oligo A synthetase is mediated by secretion of interferon by the cells. The inhibition of induction of the synthetase during differentiation, caused by the antiserum, was accompanied by a reduction in hemoglobin accumulation, whereas adding (2'--5') ApApA core to the cells together with Me2SO increased slightly hemoglobin accumulation.


Microalbuminuria is associated with unfavourable cardiac geometric adaptations in essential hypertensive subjects.
We sought in this study to examine the relationship between microalbuminuria and cardiac geometry since a slight increased urinary albumin excretion (UAE) and increased left ventricular (LV) mass have both been identified as predictors of cardiovascular events in hypertensive subjects. For this purpose, microalbuminuria was determined in three non-consecutive 24-h urine samples as UAE of 20-200 mg/24 h in a group of 249 untreated hypertensive subjects. Echocardiographic classification of patients into LV geometric patterns was based on relative wall thickness values and on gender-specific values for LV mass index (LVMI). The group of patients with microalbuminuria (n = 119) was matched for age, sex, body mass index, smoking status and plasma cholesterol level with the group of patients without microalbuminuria (n = 130). Subjects with microalbuminuria had significantly increased LVMI (111 vs 90 g/m(2), P < 0.0001), relative wall thickness (0.46 vs 0.41, P < 0.001) and office systolic and diastolic blood pressure (161 vs 148 and 101 vs 97 mmHg, respectively, P < 0.005). For the pooled population, UAE was positively correlated to LVMI (r = 0.46, P < 0.001) and relative wall thickness (r = 0.47, P < 0.001). In the entire population, normal LV geometry, concentric LV remodelling, eccentric and concentric LV hypertrophy was found in 34%, 33%, 12% and 21%, respectively. The prevalence of normal LV geometry was significantly higher in normoalbuminuric compared with microalbumnuric subjects (55 vs 14%, P < 0.001) while the prevalence of concentric LV hypertrophy was significantly higher in microalbuminuric compared with normoalbuminuric subjects (32 vs 5%, P < 0.0001). Multiple regression analysis revealed that concentric LV hypertrophy was significantly associated with increased values of UAE and mean arterial pressure. In conclusion, the higher prevalence of unfavourable LV geometric patterns in hypertensive subjects with microalbuminuria compared with those without microalbuminura, may account for the worse cardiovascular outcomes associated with the presence of an increased UAE in hypertensive subjects.


Flaviata longa, a new species in Flaviata Lu & Qin and new synonymies in Empoasca (Matsumurasca) Anufriev (Hemiptera: Cicadellidae: Empoascini).
A new species of genus Flaviata Lu & Qin, Flaviata longa sp. nov. is described from Yunnan (southwest China). An identification key for males of all known species in this genus is provided. Photographs and illustrations of adults and male genitalia of the new species are also given. New synonymies for two species in the leafhopper subgenus Empoasca (Matsumurasca) Anufriev of Empoascini are proposed: E. (M.) southerni Zhang, 2014 = E. (M.) clypealata Qin & Zhang, 2011; E. (M.) qini Zhang, 2014 = E. (M.) quadrialata Qin & Zhang, 2011.


Cytofluorescence localization of adriamycin in the nervous system. IV. cellular uptake of the drug in peripheral nerve following various modes of injection to bypass the blood-nerve and the perifascicular barriers.
Adriamycin (Doxorubicin) is a powerful anthracyclic compound, which is widely used in the treatment of malignant diseases. In the rat a single systemic injection of the drug can induce pronounced lesions in peripheral ganglia, whereas in other parts of the peripheral nervous system (PNS) no changes have been reported. Since adriamycin can be directly traced in tissue sections by fluorescence microscopy it is very well suited for experimental studies on the relation between cytotoxic effects and distribution of the drug following various modes of administration. We have previously shown that after an intravenous (i.v.) injection there is an absence of adriamycin-induced nuclear fluorescence in the endoneurium of mouse sciatic nerve (Bigotte et al. 1982 b). This could either be due to barrier effects in endoneurial vessels and the perineurium or to a lacking capacity of the endoneurial cell population to take up and retain adriamycin. In the present study the blood-nerve and the perifascicular diffusion barriers were therefore bypassed by endoneurial microinjections of adriamycin. After this mode of administration, Schwann cells, endoneurial mast cells, endothelial cells, and pericytes became labeled. Experimental damage of these barriers induced by ligation of the nerve also resulted in a diffusion of the drug into the endoneurial area and labeling of the same cells. The absence of nuclear binding in the endoneurium of mouse sciatic nerves after i.v. injection of adriamycin is therefore most probably due to a low or absent passage of the drug from the blood into the endoneurium, i.e., a combined barrier action of endoneurial vessels and the perineurium. Other experiments with epineurial application of the drug showed that thin intramuscular (i.m.) nerve branches differ from the sciatic nerve fascicles in allowing small amounts of adriamycin to enter the endoneurium. The present observations are of interest since it can be assumed that patients receiving adriamycin as a cytostatic drug may suffer nerve lesions whenever defects of nerve barriers are present.


Mechanism of strength increase for a hydrothermal porcelain.
The objectives of this study were to verify the formation of a hydrolyzed surface layer on Duceram LFC, to determine the effects of such a layer on mechanical material properties, and to identify a specific mechanism responsible for any strength increase observed. Specimens were fabricated from dentin porcelain by a vibration blotting technique and were prepared to have either blunt or sharp surface flaws. Half of the specimens underwent accelerated aging. Specimens were fractured in three-point flexure to measure their strength, and fractographic analysis was used to determine fracture toughness and residual surface stress. Surface hardness and elastic modulus were measured using a microindentation method. Porcelain surface topography was examined using atomic force microscopy, and Fourier transform infrared spectroscopy was used to determine the composition of the surface layer. The aging treatment modified the porcelain surface topography but did not create a layer with increased hydroxyl ion content. Porcelain strength increased upon aging, and the increase was proportional to initial flaw severity. The apparent fracture toughness of sharp flaw specimens increased to match that for specimens containing blunt flaws upon aging. Surface hardness and elastic modulus decreased upon aging. Previous studies on the strength increase of hydrothermal porcelain were contradictory because a variety of specimen preparation procedures were used. This study resolves the apparent contradiction by determining the effect of specimen preparation on material strength.


Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells.
The morphology of human fetal liver cells treated with both oncostatin M and dexamethasone was strikingly different from those of cells treated with either oncostatin M or dexamethasone alone. Cotreatment with oncostatin M and dexamethasone resulted in the appearance of numerous large vacuoles. The size of the vacuoles varied among individual cells, ranging from 0.05 to 20 mum depending on the cell. Electron microscopy indicated that swollen large vacuoles in the human fetal liver cells were generally electron lucent. On the other hand, relatively small vacuoles about 2 mum in diameter were discrete structures that contained electron-dense material, such as partially degraded cytoplasmic membrane, cytoplasm, or organelle components. An autophagosome-like organelle was formed in cytoplasm. Electron microscopic analysis indicated direct fusion among the vacuoles formed in the cytoplasm of human fetal liver cells. To our knowledge, this is the first report of large swollen vacuoles formed in cells by the cooperative effects of oncostatin M and dexamethasone.


Methods in laboratory investigation. Application of the indirect enzyme-linked immunosorbent assay microtest to the detection and surveillance of human t cell leukemia-lymphoma virus.
An ELISA assay for the detection of human T cell leukemia-lymphoma virus antibodies in human sera has been developed that has considerable advantages over previous techniques and equals the sensitivity of radioimmunoassay. Tests of normal and antibody-positive sera from leukemia patients indicate that this method should prove useful in the seroepidemiologic research for human T cell leukemia-lymphoma virus in the human population for probing the mode of its transmission and its clinical association with various T cell malignancies.


The effect of anticonvulsants on the dexamethasone suppression test.
Rates of non-suppression on the DST were compared in 19 psychiatric inpatients and anticonvulsants and 38 psychiatric inpatients not on anticonvulsants who were matched for age, sex, and diagnosis. Patients on anticonvulsants had a significantly higher rate of nonsuppression.


HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States Veterans.
United States Veterans are at excess risk for type 2 diabetes, but population differentials in risk have not been characterized. We determined risk of type 2 diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the VA New York Harbor (VA NYHHS) during 2004-2014. Prediabetes was based on American Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several possible criteria used to define prediabetes. We evaluated transition to type 2 diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox proportional hazards regression was used to relate HbA1c levels, lipid profiles, demographic, anthropometric and comorbid cardiovascular factors to incident diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to normoglycemic Veterans (HbA1c: 5.0-5.6%; 31-38 mmol/mol), risks for diabetes were >2-fold in the moderate prediabetes risk group (HbA1c: 5.7-5.9%; 39-41 mmol/mol) (HR 2.37 [1.98-2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0-6.4%; 42-46 mmol/mol) (HR 5.59 [4.75-6.58]). Risks for diabetes were increased with elevated VLDL (≥40mg/dl; HR 1.31 [1.09-1.58]) and TG/HDL (≥1.5mg/dl; HR 1.34 [1.12-1.59]), and decreased with elevated HDL (≥35mg/dl; HR 0.80 [0.67-0.96]). Transition to diabetes in Veterans was related in age-stratified risk score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5-year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the highest quartile (5-year risk, 21.9%) of the risk score. This investigation identified substantial differentials in risk of diabetes in Veterans, based on a readily-derived risk score suitable for risk stratification for type 2 diabetes prevention.


Glutamate transmission rather than cellular pacemaking propels excitatory-inhibitory resonance for ictogenesis in amygdala.
Epileptic seizures are automatic, excessive, and synchronized neuronal activities originating from many brain regions especially the amygdala, the allocortices and neocortices. This may reflect a shared principle for network organization and signaling in these telencephalic structures. In theory, the automaticity of epileptic discharges may stem from spontaneously active "oscillator" neurons equipped with intrinsic pacemaking conductances, or from a group of synaptically-connected collaborating "resonator" neurons. In the basolateral amygdalar (BLA) network of pyramidal-inhibitory (PN-IN) neuronal resonators, we demonstrated that rhythmogenic currents are provided by glutamatergic rather than the classic intrinsic or cellular pacemaking conductances (namely the h currents). The excitatory output of glutamatergic neurons such as PNs presumably propels a novel network-based "relay burst mode" of discharges especially in INs, which precondition PNs into a state prone to burst discharges and thus further glutamate release. Also, selective activation of unilateral PNs, but never INs, readily drives bilateral BLA networks into reverberating discharges which are fully synchronized with the behavioral manifestations of seizures (e.g. muscle contractions). Seizures originating in BLA and/or the other structures with similar PN-IN networks thus could be viewed as glutamate-triggered erroneous network oscillations that are normally responsible for information relay.


Development of an instrument for medical students' self-assessment of facets of competence for patient-centred care.
To develop a facets of competence self-assessment instrument (FOCSI) with operationalised items for ten competence facets required for patient-centred care at the beginning of residency. We conducted focus groups and cognitive interviews with final-year medical students to develop items that match students' clinical experience. We tested 50 items in two samples and analysed model fit and internal consistency of all possible combinations to identify the optimal ten-item-solution. Item analysis was performed as well as correlation with six personality traits. An optimal ten-item solution for the self-assessment instrument emerged for sample 1 (n = 101, 27.2 ± 3.5 years, 75.2 % female). We validated the model fit with sample 2 (n = 135, 27.7 ± 3.9 years, 66.7 % female): χ2(35) = 49.3, p = .055, CFI = .94, RMSEA = .055, SRMR = .058, Cronbach's alpha = .78. The personality factors 'Conscientiousness' and 'Extraversion' correlate positively with most FOCSI items. The operationalised FOCSI items support undergraduate medical students close to graduation in realistic self-assessment of facets of competences for patient-centred care in their transition to residency. Realistic self-assessment of facets of competence will provide medical students with the opportunity to monitor their competence development as part of self-directed learning for gaining adaptive expertise in professional, patient-centred care.


Anatomical variants of sphenoid sinuses pneumatisation: a CT scan study on a Northern Italian population.
Sphenoid bone may be affected by different variants of pneumatisation, which have a relevant importance from a clinical and surgical point of view. The description of such variants in different populations may give useful information. However, few articles describe the variability of sphenoid pneumatised structures and none of them focuses on Northern Italian population. Variants of pneumatisation of sphenoid bone were described in a sample of 300 Northern Italian patients who underwent a CT scan. More than fifty-seven percent of patients showed a form of anatomical variant: the most common form was the pneumatised pterygoid processes (39.6%), followed by dorsum sellae (32.9%) and clinoid processes (20.3%), without statistically significant differences between males and females (p > 0.01). In 26.3% of patients, a combined pneumatisation of these three structures was observed, being the combination pterygoid processes-dorsum sellae the most frequent (11.3%). In 9.3%, all the three sphenoid structures were affected. This article is the first description of the prevalence of different variants of pneumatisation in a Northern Italian population: the occurrence of such forms has to be acknowledged for their possible clinical and surgical consequences.


MRI of the wrist and finger joints in inflammatory joint diseases at 1-year interval: MRI features to predict bone erosions.
The aim of this study was to assess the ability of MRI determined synovial volumes and bone marrow oedema to predict progressions in bone erosions after 1 year in patients with different types of inflammatory joint diseases. Eighty-four patients underwent MRI, laboratory and clinical examination at baseline and 1 year later. Magnetic resonance imaging of the wrist and finger joints was performed in 22 patients with rheumatoid arthritis less than 3 years (group 1) who fulfilled the American College of Rheumatology (ACR) criteria for rheumatoid arthritis, 18 patients with reactive arthritis or psoriatic arthritis (group 2), 22 patients with more than 3 years duration of rheumatoid arthritis, who fulfilled the ACR criteria for rheumatoid arthritis (group 3), and 20 patients with arthralgia (group 4). The volume of the synovial membrane was outlined manually before and after gadodiamide injection on the T1-weighted sequences in the finger joints. Bones with marrow oedema were summed up in the wrist and fingers on short-tau inversion recovery sequences. These MRI features was compared with the number of bone erosions 1 year later. The MR images were scored independently under masked conditions. The synovial volumes in the finger joints assessed on pre-contrast images was highly predictive of bone erosions 1 year later in patients with rheumatoid arthritis (groups 1 and 3). The strongest individual predictor of bone erosions at 1-year follow-up was bone marrow oedema, if present at the wrist at baseline. Bone erosions on baseline MRI were in few cases reversible at follow-up MRI. The total synovial volume in the finger joints, and the presence of bone oedema in the wrist bones, seems to be predictive for the number of bone erosions 1 year later and may be used in screening. The importance of very early bone changes on MRI and the importance of the reversibility of these findings remain to be clarified.


Recent insights into viral infections as a trigger and accelerator in alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which only symptomatic medication is available, except for the recently FDA-approved aducanumab. This lack of effective treatment urges us to investigate alternative paths that might contribute to disease development. In light of the recent SARS-CoV-2 pandemic and the disturbing neurological complications seen in some patients, it is desirable to (re)investigate the viability of the viral infection theory claiming that a microbe could affect AD initiation and/or progression. Here, we review the most important evidence for this theory with a special focus on two viruses, namely HSV-1 and SARS-CoV-2. Moreover, we discuss the possible involvement of extracellular vesicles (EVs). This overview will contribute to a more rational approach of potential treatment strategies for AD patients.


Australian midwives' experience of delivering a counselling intervention for women reporting a traumatic birth.
this paper describes midwives' experiences of learning new counselling skills and delivering a counselling intervention entitled 'Promoting Resilience on Mothers Emotions' (PRIME). a descriptive exploratory approach was used. Data collected included semi-structured interviews (n=42), midwife diary entries (18 pages) and web based postings (169 pages). Data were analysed using manual thematic method. the intervention study was conducted in two tertiary maternity hospitals in the Australian states of Queensland (QLD) and Western Australia (WA) during a 17 month period, from August 2008 to December 2009. midwives were employed as research assistants and trained to deliver a counselling intervention to women reporting a traumatic birth experience. Eighteen of a possible 20 Australian midwives participated in this study. PRIME is a midwife-led counselling intervention based on cognitive-behavioural principles and designed to ameliorate trauma symptoms. It is offered face-to-face within 72 hours of childbirth and by phone around six weeks post partum. participating midwives felt confronted by the level of emotional distress some women suffered as a consequence of their birth experience. Four major themes were extracted: The challenges of learning to change; Working with women in a different way; Making a difference to women and me; and A challenge not about to be overcome. the advanced counselling skills the midwives acquired improved their confidence to care for women distressed by their birthing experience and to personally manage stressful situations they encountered in practice.


Electrodiagnostic approach to cranial neuropathies.
This article is a general review of cranial nerve conduction studies, including techniques as well as interpretation of data. The needle examination of various cranial innervated muscles is also reviewed. The nerve conduction studies include the blink, masseter (jaw jerk), and masseter inhibitory reflexes, which evaluate the trigeminal (blink and jaw jerk) and facial nerves (blink), as well as trigeminal, facial, and spinal accessory motor stimulation. The needle examination techniques for certain voluntary muscles innervated by cranial nerves V, VII, X, XI, and XII are also described.


Expression profiling identifies strain-specific changes associated with ethanol withdrawal in mice.
Mice that exhibit characteristics of physical dependence following ethanol exposure serve as useful models of alcoholism in humans. The DBA/2J and C57BL/6J inbred strains differ in their behavioral response to ethanol withdrawal. Alterations in gene expression are believed to underlie neuroadaptation to ethanol dependence and tolerance. Therefore, the differences in ethanol withdrawal severity observed between the DBA/2J and C57BL/6J strains may be related to differential regulation of gene expression. We have used cDNA microarrays to determine the gene expression profile in the hippocampus of DBA/2J and C57BL/6J mice during withdrawal after chronic and acute ethanol exposure. Of the 7634 genes surveyed, approximately 2% were consistently differentially expressed by at least 1.4-fold in DBA/2J mice during chronic ethanol withdrawal. Less than 1% of the genes showed altered expression in C57BL/6J mice under the same conditions, or in DBA/2J mice during acute ethanol withdrawal. Strain- and treatment-specific patterns of altered expression were observed for multiple genes associated with the Janus kinase/signal transducers and activators of transcription and the mitogen activated protein kinase pathways. Genes associated with both pathways are regulated in DBA/2J mice during chronic ethanol withdrawal, and to a lesser extent during acute ethanol withdrawal. Only those genes associated with the mitogen-activated protein kinase (MAPK) pathway exhibited changes in expression in C57BL/6J mice during ethanol withdrawal. Furthermore, genes associated with retinoic acid-mediated signaling show differential expression exclusively in C57BL/6J mice. These findings represent significant differences in cellular adaptation to ethanol between the DBA/2J and C57BL/6J strains.


[Relapsing meningitis and confusion: limbic encephalitis revealing Hodgkin's disease].
An observation of limbic encephalitis associated with Hodgkin's disease is compared with rare cases of the literature. The clinical presentation was relapsing episodes of febrile cognitive disorders with confusion and meningitis, curable after treatment of Hodgkin's disease. Recent concepts on limbic encephalitis are discussed. A seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease. The treatment of Hodgkin's disease led to perfect recovery of cognitive function, so that the patient could drive his car. Lymphoproliferative disease, such as Hodgkin's disease, is a possible diagnosis in patients with limbic encephalitis. A dysimmune process underlying Hodgkin's disease might be operating in this association.


Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.
High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.


Use of ecotoxicity test and ecoscores to improve the management of polluted soils: case of a secondary lead smelter plant.
With the rise of sustainable development, rehabilitation of brownfield sites located in urban areas has become a major concern. Management of contaminated soils in relation with environmental and sanitary risk concerns is therefore a strong aim needing the development of both useful tools for risk assessment and sustainable remediation techniques. For soils polluted by metals and metalloids (MTE), the criteria for landfilling are currently not based on ecotoxicological tests but on total MTE concentrations and leaching tests. In this study, the ecotoxicity of leachates from MTE polluted soils sampled from an industrial site recycling lead-acid batteries were evaluated by using both modified Escherichia coli strains with luminescence modulated by metals and normalized Daphnia magna and Alivibrio fischeri bioassays. The results were clearly related to the type of microorganisms (crustacean, different strains of bacteria) whose sensitivity varied. Ecotoxicity was also different according to sample location on the site, total concentrations and physico-chemical properties of each soil. For comparison, standard leaching tests were also performed. Potentially phytoavailable fraction of MTE in soils and physico-chemical measures were finally performed in order to highlight the mechanisms. The results demonstrated that the use of a panel of microorganisms is suitable for hazard classification of polluted soils. In addition, calculated eco-scores permit to rank the polluted soils according to their potentially of dangerousness. Influence of soil and MTE characteristics on MTE mobility and ecotoxicity was also highlighted.


Ectopic crypt foci in conventional and serrated colorectal polyps.
Despite almost pathognomonic status of ectopic crypt foci (ECF) in the diagnosis of traditional serrated adenoma (TSA), there are few systematic studies on their prevalence in other types of colon polyps or in adenomas adjacent to colorectal cancer (CRC). We calculated ECF in all the polyps (n=922) removed in the colonoscopy in Oulu University Hospital in 2001. Moreover, to study ECF in precursor lesions next to CRCs, we re-examined a previously described cohort of 148 CRCs. ECF were seen in 53 (5.7%) polyps representing 28 (6.5%) tubular adenomas (TAs), 14 (53.8%) tubulovillous adenomas (TVAs), 2 (100.0%) villous adenomas (VAs) and 9 (100.0%) TSAs. In all TSAs and VAs, the density of ECF was higher than in TVAs and TAs. An adjacent precursor lesion was recognised in 28 of 148 (18.9%) CRCs. Twenty-four (85.7%) of these contained ECF. ECF can most frequently be observed in TSAs but also in many TVAs, VAs and TAs, reflecting a histological overlap between serrated and conventional polyps. Especially, precursor lesions adjacent to CRC frequently contain ECF.


No duty owed to the relatives of a victim of a person with mental illness.
To review the case of an acutely psychotic person who was discharged into the care of a friend whom he killed later the same day, and to consider the reasoning of the High Court in the subsequent negligence action of the victim's relatives. By a narrow interpretation, the High Court found that the exercise of the powers and duties in relation to the involuntary detention of a mentally ill person as prescribed by the Mental Health Act were inconsistent with a common law duty of care to another person or the relatives of another person.


The influence of sterols on pentachlorophenol-induced charge transfer across lipid bilayers studied by alternating current methods.
The frequency dependence of membrane admittance has been determined for a series of phosphatidylcholine/sterol/n-decane bilayers in the presence of an aqueous environment containing pentachlorophenol. Variations in the results among membranes can be related to differences in the kinetic parameters of a kinetic model of pentachlorophenol-induced charge transport by characterizing both measurements and model behavior in terms of a common equivalent circuit. The kinetic model assumes a three-layer structure for the membrane and immediate environment. Data from membranes formed with beta-hydroxysterols having a flat ring structure and an intact side-chain (cholestanol, cholesterol, 7-dehydrocholesterol), after correction for sterol-induced membrane thinning, suggest that these sterols affect charge translocation by altering both interior fluidity and surface dipolar fields. The effects almost cancel for the case of cholesterol. These sterols also affect interfacial processes, either by inhibiting proton exchange between the aqueous and lipid environments, or by suppressing the adsorption of pentachlorophenol anions. Stigmasterol, coprostanol and epicholesterol cause only minor alterations in both translocation and interfacial processes. None of the sterols investigated has a significant influence on the capacitance of the interfacial region.


Computer-designed prostheses for orbitocranial reconstruction.
Three-dimensional imaging is an adjunct to preoperative evaluation and surgical management in some patients with complex anatomic defects of various etiologies. Deformities defined by conventional computerized tomography can be viewed as accurate three-dimensional images calculated from the original scan. The images are viewed on a high-resolution video monitor and can be photographed for a permanent record. A computer-controlled milling device can use these data to fabricate prostheses. The prostheses aid reconstructive surgery through use as an alloplastic implant, as a template to fashion autogenous bone grafts, or as a model for tissue removal. We have utilized three-dimensional imaging in combination with computer-assisted prosthesis manufacture in six patients with complex orbitocranial deformities. Four patients have undergone reconstructive surgery with satisfactory results and no complications thus far. The use of computer-designed prostheses adds a new aspect to orbitocranial reconstructive surgery that facilitates increased accuracy in the correction of anatomic defects.


Prolyl isomerase, Pin1: new findings of post-translational modifications and physiological substrates in cancer, asthma and Alzheimer's disease.
The peptidyl prolyl cis/trans isomerase Pin1 specifically binds phosphorylated Ser/Thr-Pro protein motifs and catalyzes the cis/trans isomerization of the peptide bond. Accumulating studies have revealed that Pin1 isomerase activity is regulated by its post-translational modifications, including phosphorylation and oxidation. Various transcription factors and regulators have been identified as substrates for Pin1. It enhances AP-1 activity via isomerization of both c-Jun and c-Fos for cellular proliferation and stabilizes the oncosuppressors p53 and p73 against DNA damage at the checkpoint. We demonstrated the association between the intracellular form of Notch1 (NIC) and Pin1 by analyzing Pin1/p53 double-knockout mice. Pin1 also regulates the post-transcriptional level of some cytokines, associated with asthma, that possess 3' untranslated region AU-rich elements (AREs) via interaction withAUF1, the nucleoprotein in the ARE-binding complex. Pin1 has been identified as the molecular partner of tau and amyloid precursor protein (APP), the key factors of Alzheimer's disease (AD). It interacts with the phosphorylated Thr-231 of tau and regulates its activity to bind microtubules. It further interacts with the phosphorylated Thr-668 of APP and affects its metabolism. Thus, Pin1 is probably involved in the pathogenesis of human diseases, including cancer, asthma, and AD, presenting an attractive target for future therapeutical drugs.


Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care.
Cardiac troponin is the standard marker for diagnosis of acute myocardial infarction and risk stratification of patients who present to an emergency department with signs and symptoms of acute cardiac ischemia. Over the past few years, the analytical sensitivity of assays for cardiac troponin has improved significantly to the point where a detectable amount of troponin can be measured in essentially all healthy subjects. Recent studies have shown that use of a highly sensitive troponin assays may provide value to traditional markers of primary disease risk for patients, i.e., for those who have no history of heart disease. There are barriers to the adoption of cardiac troponin for screening high risk cohorts such as the elderly, diabetics and perhaps even the asymptomatic population. Strategies used for the assignment of cutoff concentrations in acute care, i.e., the 99 th percentile, may not be appropriate for primary care as changes over baseline levels may provide more accurate information of risk than cross-sectional results. A review of biological variation has shown that cardiac troponin as a biomarker has low index of individuality, indicating that reference values are of little utility. Whether or not cardiac troponin can be released in reversible injury is a debate that could have significance for detecting minor myocardial injury. A major hurdle for use of troponin in primary care is the lack of assay standardization and nomenclature for the different generations of troponin assays. Standardization requires knowledge of what is released after cardiac injury and what the various cardiac troponin assays are measuring. Currently it is not clear if the cardiac troponin release after ischemic injury is identical to that in circulation of healthy individuals. This may affect the design of future assays and standardization approaches. There is potential that a marker of myocardial injury such as troponin can add to the value of existing indicators and biomarkers of cardiovascular disease risk. Additional analytical and clinical validations are needed to fully elucidate cardiac troponin metabolism and resolve ongoing clinical and laboratory issues. While these issues are directed to the use of troponin in primary care, most of these concepts are relevant to the use of troponin in acute coronary syndromes as well.


Relationship between tightness of the hip joint and shoulder/elbow injury in high school baseball pitchers: a prospective study.
Some studies have reported that upper limb tightness is a risk factor for shoulder/elbow pain in high school baseball pitchers; but there has been insufficient research on the relationship between lower limb tightness and shoulder and elbow pain in pitchers. This study aimed to clarify the correlation among pre-season hip range of motion (ROM) and shoulder and elbow disorders in high school baseball pitchers. We surveyed 125 high school pitchers. Hip ROM was measured in the supine and prone positions. After the season, based on their answers to the self-recorded questionnaire, a "shoulder or elbow injury" was defined as any condition resulting in the pitcher being considered disabled for ≥ 8 days. An independent t-test and logistic regression analysis were used for statistical analysis. Eleven disabled pitchers (9%) were identified during the season. In the injured group, the ROM of the plant side hip with 90° flexed external rotation was smaller than that in the non-injured group. Preseason limited ROM in the plant side hip with 90° flexed external rotation was a risk factor for the occurrence of shoulder/elbow pain in the season.


Endomyocardial biopsy in pediatric heart transplant recipients: a useful exercise? (Analysis of 1,169 biopsies).
The objective of this study was to define the diagnostic yield for endomyocardial biopsy (EMB) procedures performed for various indications in a large pediatric heart transplant population. Endomyocardial biopsy procedure has been employed as the 'gold standard' for rejection surveillance. Previous studies have questioned the value of surveillance EMB beyond the early post-transplant period. We retrospectively reviewed data on 82 pediatric heart transplant recipients with serial EMB. A total of 1,169 EMB were performed during a follow-up period of 2-149 months (median 41 months). EMB were classified by age at transplantation, time from transplant, immunosuppressive regimen used [tacrolimus vs. cyclosporin A (CsA)] and indication, i.e. surveillance, follow-up after rejection or lowering of immunosuppression, non-specific clinical symptoms and graft dysfunction. During the first year after heart transplantation, surveillance EMB demonstrated significant rejection [International Society for Heart and Lung Transplantation (ISHLT) grade > or = 3A] in 18% of biopsies with the yield being 14-43% for all other indications. Surveillance EMB 1-5 yr post-transplantation were found to have a lower diagnostic yield in infants (4%, vs. 13% in children) and in patients with favorable first-year rejection history (9% vs. 17% in 'frequent rejectors'). Tacrolimus-based immunosuppression was associated with significantly less rejection, but only in the first year post-transplantation (14% in tacrolimus vs. 24% in CsA surveillance EMB, p = 0.035). Surveillance EMB remains an important diagnostic tool for rejection surveillance during the first 5 years after pediatric heart transplantation. Endomyocardial biopsy is particularly warranted after reduction of immunosuppression and for monitoring for ongoing rejection after treatment of acute rejection episodes.


Longitudinal charge nurse leadership development and evaluation.
The study's aim was to examine longitudinal outcomes of a leadership program for permanent and relief charge nurse from 1996 to 2012 using action research and Kouzes and Posner's The Leadership Challenge conceptual frameworks. Charge nurses hold significant oversight of patient safety, quality, and team functioning. This study contributes knowledge regarding charge nurse leadership and organization outcomes associated with these essential roles over time. Data were collected over 6 time periods using Kouzes and Posner's The Leadership Practices Inventory (LPI) and internally developed action research tools. Surveys were aligned with leadership and work environment changes to examine outcomes. Charge nurse leadership LPI mean ratings improved. Relief charge nurses reached similar LPI outcomes by 2012, with no statistical differences in mean or domain scores. Action research methods facilitated executive decision making during change processes. Demographics shifted with younger charge nurses with less practice experience serving as charge nurses in the most recent years. Charge nurse leadership reported significant gains despite institutional changes and uneven delivery of educational interventions.


Impact of asymptomatic prostatitis on re-operations due to urethral stricture or bladder neck contracture developed after TUR-P.
To evaluate the relationship between pathologically proven prostatic inflammation (PI) and re-operation rates due to urethral stricture (US) or bladder neck contracture (BNC) after transurethral resection of prostate (TUR-P). We have retrospectively reviewed the data of 917 consecutive TUR-P cases. Eligible patients (n = 276) were grouped with respect to presence of PI on TUR-P pathology; Group1: PI (+) (n = 67, 24.3%), and Group2: PI (-) (n = 209, 75.7%). The "re-operation" was defined as internal urethrotomy or bladder neck resection performed for BNC or US. Groups were compared with respect to descriptive data and need for re-operation. Logistic regression analysis was performed to estimate the independent risk factors for the development of BNC and US. P values under 0.05 were considered significant. Of the patients, 38 (13.8%) needed re-operation while 238 (86.2%) did not. The re-operation rate in Group1 was significantly higher than Group2 (29.8 vs. 8.6%, P < 0.001). In logistic regression analysis, duration of initial TUR-P and PI were found to be independent risk factors for development of BNC or US after TUR-P. Prostatic inflammation on TUR-P pathology is an independent variable affecting the development of US or BNC. Our results should be supported by prospective studies including higher number of patients.


Monitoring of organochlorine and organophosphorus pesticide residues in water during different seasons of Tighra reservoir Gwalior, Madhya Pradesh, India.
Analysis of pesticides during different seasons for pesticidal contamination in water samples of Tighra reservoir was carried out on gas chromatograph-electron capture detector with capillary columns following multiresidual analytical technique. Organochlorine pesticides, viz., hexachlorobenzene (HCB), alpha-benzene hexachloride (BHC), beta-BHC, γ-BHC, heptachlor, aldrin, alpha-endosulfan, beta-endosulfan, p,p-DDE, dieldrin, o,p-dichlorodiphenyldichloroethane (DDD), p,p-DDD, p,p-dichlorodiphenyltrichloroethane (DDT), and endrin, and organophosphorus pesticides, viz., choloropyrifos, methyl parathion, diazion, dicholorovos, ethion, malathion, and parathion, were detected in water samples during different seasons. However, the pesticide concentration varied during different seasons at different sites. The prominent reason of contamination is the use of pesticides (both organochlorine and organophosphorus) in the agricultural fields near Tighra reservoir. On the basis of our observations, more extensive monitoring studies need to be carried out, covering all wetlands of Madhya Pradesh to enforce the policies for the restricted application of pesticides in agricultural fields adjacent to wetlands.


Identification of the binding sites to monoclonal antibodies on A/USSR/90/77 (H1N1) hemagglutinin and their involvement in antigenic drift in H1N1 influenza viruses.
We have determined nucleotide sequences of the HA1 portion of the hemagglutinin (HA) gene of the parental A/USSR/90/70 (H1N1) virus and its eight variants selected in vitro with six monoclonal antibodies to study antigenic determinants. The HA1 gene of one of the variants (B-1-23) was cloned in bacteria and its nucleotide sequence was determined by the Maxam-Gilbert method. The nucleotide sequence of the variant was confirmed by the dideoxy chain termination method. The gene sequences of the other viruses were determined by the latter method. Three variants with reduced reactivity in HI test only with the selecting antibodies possessed one amino acid substitution. On the other hand, most other variants which had the changed reactivity to multiple antibodies in HI test possessed more than one substitution. Comparison of the amino acid sequences of the HA1 molecule, deduced from the nucleotide sequences, suggested that the monoclonal antibodies W18 and 264 reacted with epitopes located on the area involving amino acid residues 125C and 189-190, respectively, whereas, the antibodies 22 and 70 reacted with epitopes involving amino acid residues 129, 132, and 157. The epitope recognized by antibody 110 overlapped with that of W18, and the epitope recognized by antibody 385 was located on the area involving at least amino acid residues 129, 159, and 189, which overlapped with some of the above epitopes. The sequence analysis with B-1-23 variant selected with antibody 264 clearly showed that in A/USSR/77 viruses, a single substitution at amino acid residue 190 effectively changes the epitope and caused a significant antigenic variation detectable by postinfection ferret sera.


Altered mucosal and plasma polyunsaturated fatty acids, oxylipins, and endocannabinoids profiles in Crohn's disease.
Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn's disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD.


BNT162b2 mRNA Vaccine-Induced Immune Response in Oral Fluids and Serum.
The COVID-19 vaccine is currently being administered worldwide to address the ongoing pandemic. Although these vaccines have proven effective in preventing severe disease, the level of immunity required to prevent respiratory mucosal infection remains less well understood. Therefore, it is desirable to develop a noninvasive screening strategy such as oral fluid to monitor secreted antibodies longitudinally as potential surrogates of mucosal immunity. We evaluated the anti-spike protein antibodies in gingival crevicular fluid (GCF) and saliva and compared them to immune responses in the blood of 50 healthy health care workers following 2 doses of intramuscular Pfizer/BioNTech-BNT162b2 vaccine. The antibodies to SARS-CoV-2 spike and subdomain proteins (RBD, S1, S2, and NTD) were significantly higher in serum than oral fluids but showed a greater detection rate and higher median titres in GCF than saliva. For all tested SARS-CoV-2 antigens, IgG in GCF (as opposed to saliva) showed a more significant and stronger correlation with IgG in serum. Serum-neutralising antibodies (Nab) titres also displayed a significant and stronger correlation with anti-spike protein and their subdomains in GCF than saliva. Interestingly, the time post-second dose of vaccine and sex had a similar influence on IgG in serum and GCF. However, interferon (IFN)-γ-producing T-cell responses showed no association with SARS-Cov-2 IgG antibodies in serum, GCF, or saliva and neutralisation antibodies in serum. The correlation matrix of all measured parameters grouped serum and GCF IgG parameters separately from salivary IgG parameters indicating that GCF better represents the humoural response in serum than saliva. Within limitations, we propose that GCF could be a less invasive alternative to serum and more appropriate than saliva to detect antibody responses by current COVID-19 vaccines if the GCF collection procedure could be standardised. Further research is needed to investigate the suitability of GCF for community immune surveillance for vaccines.


Contribution of advances in immunology to vaccine development.
During the last 10 years, investigation of the bovine immune system has generated knowledge and reagents that can now be applied to study the mechanisms of immunity to disease and the identity of antigens recognized by protective immune responses. Such studies can indicate which antigens are likely to be effective in subunit vaccines and also highlight the type of antigen delivery system that will be required for a vaccine to induce a protective immune response. In the case of bovine RSV, studies of immune responses in the target host have demonstrated that both antibody and CTL responses play an important role in immunity. Both the F and G glycoproteins have been identified as targets of protective antibodies, and systems have been established that will allow the identification of the viral antigens recognized by CTL. Further studies of CD4+ T-cell responses to the virus are required to determine whether or not components of the response have the potential to enhance disease and, therefore, need to be avoided in vaccination strategies.


A protocol for the routine measurement of lactate and pyruvate in cord blood.
The influence of the site of sampling and the delay in sample collection on cord blood concentrations of lactate and pyruvate were investigated. A delay in sample collection of greater than 1 min after cord clamping could invalidate the results obtained. Samples from umbilical artery had higher lactate values (mean 3.13 mmol/l) than paired vein samples (mean 2.32 mmol/l) but there were no significant differences in lactate values between different sites sampled within the umbilical vein. A calculation was devised to circumvent the need to take cord blood samples immediately after delivery.


S-layer nanoglycobiology of bacteria.
Cell surface layers (S-layers) are common structures of the bacterial cell envelope with a lattice-like appearance that are formed by a self-assembly process. Frequently, the constituting S-layer proteins are modified with covalently linked glycan chains facing the extracellular environment. S-layer glycoproteins from organisms of the Bacillaceae family possess long, O-glycosidically linked glycans that are composed of a great variety of sugar constituents. The observed variations already exceed the display found in eukaryotic glycoproteins. Recent investigations of the S-layer protein glycosylation process at the molecular level, which has lagged behind the structural studies due to the lack of suitable molecular tools, indicated that the S-layer glycoprotein glycan biosynthesis pathway utilizes different modules of the well-known biosynthesis routes of lipopolysaccharide O-antigens. The genetic information for S-layer glycan biosynthesis is usually present in S-layer glycosylation (slg) gene clusters acting in concert with housekeeping genes. To account for the nanometer-scale cell surface display feature of bacterial S-layer glycosylation, we have coined the neologism 'nanoglycobiology'. It includes structural and biochemical aspects of S-layer glycans as well as molecular data on the machinery underlying the glycosylation event. A key aspect for the full potency of S-layer nanoglycobiology is the unique self-assembly feature of the S-layer protein matrix. Being aware that in many cases the glycan structures associated with a protein are the key to protein function, S-layer protein glycosylation will add a new and valuable component to an 'S-layer based molecular construction kit'. In our long-term research strategy, S-layer nanoglycobiology shall converge with other functional glycosylation systems to produce 'functional' S-layer neoglycoproteins for diverse applications in the fields of nanobiotechnology and vaccine technology. Recent advances in the field of S-layer nanoglycobiology have made our overall strategy a tangible aim of the near future.


Inhibition of P-glycoprotein enhances transport of imipramine across the blood-brain barrier: microdialysis studies in conscious freely moving rats.
Recent studies indicate that efflux of antidepressants by the multidrug resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) may contribute to treatment-resistant depression (TRD) by limiting intracerebral antidepressant concentrations. In addition, clinical experience shows that adjunctive treatment with the P-gp inhibitor verapamil may improve the clinical outcome in TRD. Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of the tricyclic antidepressant imipramine and its active metabolite desipramine across the BBB. Intracerebral microdialysis in rats was used to monitor brain levels of imipramine and desipramine following i.v. imipramine administration, with or without pretreatment with one of the P-gp inhibitors verapamil or cyclosporin A (CsA). Plasma drug levels were also determined at regular intervals. Pretreatment with either verapamil or CsA resulted in significant increases in imipramine concentrations in the microdialysis samples, without altering imipramine plasma pharmacokinetics. Furthermore, pretreatment with verapamil, but not CsA, led to a significant elevation in plasma and brain levels of desipramine. The present study demonstrated that P-gp inhibition enhanced the intracerebral concentration of imipramine , thus supporting the hypothesis that P-gp activity restricts brain levels of certain antidepressants, including imipramine. These findings may help to explain reports of a beneficial response to adjunctive therapy with verapamil in TRD.


Female sexual function before and during the severe acute respiratory syndrome coronavirus-2 pandemic: a systematic review and Meta-analysis of longitudinal studies.
PurposeTo compare the female sexual function before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic using the Female Sexual Function Index (FSFI).MethodsRelevant studies were retrieved by online databases and manual searching reporting FSFI scores before and during the SARS-CoV-2 pandemic. The methodological quality of reviewed articles was evaluated using the Newcastle-Ottawa Scale, and heterogeneity with the I2 statistic. The standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were calculated by random-effect meta-analyses.ResultsFour studies met the inclusion criteria reporting 1002 sexually active non-pregnant women comparing results of the 19-item FSFI. The meta-analysis of the overall FSFI score showed an SMD (95% CI) of -1.16 (-1.97 to -0.35), comparing the pandemic with the pre-pandemic scores. In addition, SMD scores for the FSFI domains were also significantly lower during the pandemic for arousal -0.80 (-1.13 to -0.48), orgasm -0.66 (-1.07 to -0.25), satisfaction -0.59 (-0.97 to -0.22), and pain -0.35 (-0.54 to -0.16), whereas there were not significant differences for desire and lubrication domains. There was a low risk of bias and the sensitivity analysis suggests that results are robust.ConclusionThe available studies showed a lower overall FSFI score during the pandemic, suggesting an increased risk of female sexual dysfunction compared to prepandemic results. Also, there were increased risks of sexual arousal, orgasm, satisfaction, and pain disorders. However, there were no alterations in the desire and the lubrication domains. Limitations are related to the heterogeneity populations, and pandemic confounding and aggravating factors.


N-Acetylcysteine amide (NACA) and diNACA inhibit H2O2-induced cataract formation ex vivo in pig and rat lenses.
Oxidative stress plays a central role in cataract formation suggesting that antioxidants might slow cataract progression. The anticataract activity of N-acetylcysteine amide (NACA) and (2 R, 2 R')-3,3'-disulfanediyl bis(2-acetamidopropanamide) (diNACA) and/or N-acetylcysteine (NAC), were evaluated in porcine and rat lens models. Cataractogenesis via oxidation was induced with H2O2 and/or glucose oxidase (GO). Porcine lenses were incubated in 0.1 mM, 1 mM, or 10 mM NAC, NACA or diNACA for 24 h. Lenses were then transferred to media containing 0.75 mM H2O2 and 4.63U of GO in order to maintain a constant H2O2 level for an additional 8 h. At the end of incubation, lenses were imaged under darkfield microscopy. Separately, rat lenses were extracted from 3-week-old Wistar rats and incubated with either 10 mM NACA or 10 mM diNACA for 24 h prior to treatment with 0.2U GO to generate a steady source of ∼0.6 mM H2O2. Rat lenses were analyzed by LC-MS/MS to quantify changes in cysteine, cystine, glutathione (GSH) or oxidised glutathione (GSSG) levels in the lens epithelium, cortex or core. Pre-treatment with NACA or diNACA followed by oxidation with H2O2 and/or GO to stimulate cataract formation afforded rapid assessment in ex vivo porcine (32 h) and rat (48 h) lens models. Pre-treatment of isolated porcine lenses with 0.1 mM, 1 mM or 10 mM of either NAC, NACA or diNACA followed by H2O2/GO treatment resulted in reduced lens opacity relative to the lenses exposed to H2O2/GO, with NACA and diNACA reducing opacities to a greater extent than NAC. Rat lenses incubated with 10 mM NACA or 10 mM diNACA without exposure to H2O2 showed no signs of opacities. Pre-treatment of rat lenses with 10 mM NACA or 10 mM diNACA, followed by GO cataract induction resulted in reduced opacities compared to control (GO alone). LC-MS/MS analyses revealed that NACA, but not diNACA, increased cysteine, cystine and GSH levels in rat lens epithelium and cortex regions. Taken together, both NACA and diNACA inhibited cataract formation to a greater extent than NAC (all at 1-10 mM) in an ex vivo porcine lens model. Both NACA and diNACA (both at 10 mM) reduced cataract formation in rat lenses. Based on LC-MS/MS analyses, NACA-induced reduction in opacity observed in rat lenses was attributed to enhanced cysteine and GSH levels while the diNACA-induced reduction in opacity induced did not consistently increase cysteine, cystine and GSH levels and, therefore, appears to involve a different antioxidant mechanism. These screening studies warrant further testing of NACA and diNACA as anticataract agents.


Congenital hydrocephalus and cerebellar agenesis.
In a sibship of three brothers, two expired shortly after birth with congenital hydrocephalus, and necropsy of one revealed cerebellar agenesis and absence of the foramina of Luschka and Magendie. The non-specificity of the Dandy-Walker anomaly is discussed, and it is suggested that the present patients demonstrate another form of heritable hydrocephalus, possibly on an X-linked recessive basis.


Infant outcome, fetal growth, and pregnancy care: relationships in Indonesian university obstetrics.
The risk of perinatal death is displayed for '56 growth combinations', then contracted into 16 gestational age/birthweight categories (GA/BW) with additional control for antenatal visits (AV;CARE) for 36 000 singleton birth deliveries monitored in Indonesia from 1978-1980. For virtually all GA/BW combinations, the risk of perinatal death (PD) drops impressively with pregnancy care (Care effect on PD). Fetal growth curves are then displayed by infant outcome, the BW difference being the deficit birthweight (DBW) that may serve as a specific life-death growth standard (LDGS)--a reference system in relation to which fetal growth curves, to be controlled for factors other than infant outcome, may be studied. By controlling for maternal education and pregnancy care, the fetal growth curve associated with high pregnancy care and low education (HIAV/LOED) is more favorable than that for low pregnancy care and high education (LOAV/HIED). In Indonesia then, pregnancy care is more important than formal education in the reduction of not only perinatal mortality but also low birthweight (Care effect on fetal growth).


[HIV testing of the general population: international recommendations and actual risks for HIV infections in health occupations].
Austria has the highest HIV-test rate per 1,000 inhabitants in the European Union. This may be related to beliefs held by the health care personnel that knowledge of the HIV-serostatus of a patient (e.g. via preoperative routine testing) serves as a protective measure against occupational HIV-infection for themselves. International guidelines recommend universal screening for HIV in health-care settings only when the undiagnosed prevalence of HIV is > 0.1 %, or the diagnosed prevalence is > 0.2 %. HIV poses a small, but real risk to health-care personnel. Worldwide, 106 cases of occupational HIV-infection have been documented (since the beginning of counting in the 1990s until 2002): in Austria there have been 4 cases of occupational HIV-infection in 15 years of documentation. There is no convincing evidence that knowledge of the serostatus of a patient leads to changes in the behaviour of health-care workers. For low-prevalence countries, such as Austria, a rather focused testing-strategy is recommended.


Regulation of fibronectin gene expression by cyclic AMP and phorbol myristate acetate in HT-1080 human fibrosarcoma cells.
We studied the regulation of fibronectin (FN) gene expression by cAMP and phorbol-12-myristate-13-acetate (PMA) in HT-1080 human fibrosarcoma cells. Dibutyryl cAMP increased FN synthesis and mRNA levels, while PMA inhibited the cAMP-induced FN synthesis. In transient transfection assays, cAMP increased FN promoter activity, while PMA paradoxically enhanced the cAMP-induced promoter activity. Stable transfection experiments, however, showed that neither cAMP or PMA alone nor together affected FN promoter activity. These results suggest that PMA antagonizes the cAMP-induced FN gene expression and that both the action of cAMP and the inhibition of its action by PMA may occur at the posttranscriptional level in HT-1080 cells.


Single-cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation.
Stem cell technologies provide new opportunities for modeling cells in health and disease and for regenerative medicine. In both cases, developmental knowledge and defining the molecular properties and quality of the cell types is essential. In this study, we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into functional midbrain dopaminergic (mDA) neurons. We found that laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3β inhibition plus FGF8b, improved midbrain patterning. In addition, neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high-quality molecularly defined midbrain cell types, including mDA neurons. Our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly defined hESC-derived cell types in Parkinson disease.


Assessment of pulmonary arterial stiffness in patients with cirrhosis: A prospective cohort study.
In the current literature, several studies show that PAS (pulmonary artery stiffness) is associated with RV (right ventricular) dysfunction, PAH (pulmonary arterial hypertension), and disease severity in subjects with structural cardiac disease, HIV (human immunodeficiency virus), and chronic lung disease. Hence, our main aim was to use PAS to show the early changes in the pulmonary vascular region in subjects with cirrhosis. In this prospective cross-sectional study, 39 subjects who were being followed up with cirrhosis and 41 age- and sex-matched healthy subjects were included in this study. For each case, the PAS value was obtained by dividing mean peak velocity of the pulmonary flow by the PfAT (pulmonary flow acceleration time). The measured PAS was 23.62 ± 5.87 (Hz/msn) in cirrhotic participants and 19.09 ± 4.16 (Hz/msn) in healthy cases (P < .001). We found a positive statistical significance between PAS and RVSP (right ventricle systolic pressure)/sPAP (systolic pulmonary arterial pressure) (r = .395; P = .013). PAS was an independent predictor that was associated with cirrhosis disease according to multivariate LR (logistic regression) analysis (OR: 1.209; 95% CI: 1.059-1.381; P = .005). Based on the study results, we consider that PAS may help in the early detection of findings in the pulmonary vascular area, even if the RV function findings or sPAP is within the normal range.


Common bile duct stone caused by a fish bone: report of a case.
Investigations to determine the cause of jaundice in an 83-year-old man led to the diagnosis of incomplete obstruction of the common bile duct due to stone formation around an ingested fish bone. Abdominal ultrasound and computed tomography performed preoperatively revealed evidence of chronic cholecystitis with a gallstone and calcification in the common bile duct. Endoscopic retrograde choangiopancreatography showed stone formation in the common bile duct. After normalizing the serum bilirubin level by endoscopic retrograde bile duct drainage, we performed cholecystectomy and choledocholithotomy, which revealed stone formation around an ingested bone in the common bile duct. To the best of our knowledge based on a computer-assisted search, this is only the third report of the formation of a choledocal stone around an ingested fish bone. We reviewed the literature on choledocholithiasis caused by a foreign body, in an attempt to classify this entity according to the pathways through which a foreign body can migrate into the common bile duct.


5-Hydroxytryptamine binding to butanol extracts from myelin fragments.
The myelin fraction of rat brain stem was treated with butanol-water mixtures, and the extracted proteolipids were separated by Sephadex LH20 column chromatography. 2 peaks of proteolipids eluted in chloroform-methanol 4/1 showed the binding capacity for C14 - 5-HT. This finding suggests the necessity of the more careful investigations for the probability of proteolipids as receptor proteins in the central nervous system.


Development and application of loop-mediated isothermal amplification for detecting the highly benzimidazole-resistant isolates in Sclerotinia sclerotiorum.
Resistance of benzimidazole fungicides is related to the point mutation of the β-tubulin gene in Sclerotinia sclerotiorum. The point mutation at codon 198 (GAG → GCG, E198A) occurs in more than 90% of field resistant populations in China. Traditional detection methods of benzimidazole-resistant mutants of S. sclerotiorum are time-consuming, tedious and inefficient. To establish a suitable and rapid detection of benzimidazole-resistant mutants of S. sclerotiorum, an efficient and simple method with high specificity was developed based on loop-mediated isothermal amplification (LAMP). Eight sets of LAMP primers were designed and four sets were optimized to specially distinguish benzimidazole-resistant mutants of S. sclerotiorum. With the optimal LAMP primers, the concentration of LAMP components was optimized and the reaction conditions were set as 60-64 °C for 60 min. This method had a good specificity, sensitivity, stability and repeatability. In the 1491 sclerotia, 614 (41.18%) were positive by LAMP, and 629 (42.19%) positive by MIC. Therefore, the LAMP assay is more feasible to detect benzimidazole-resistant mutants of S. sclerotiorum than traditional detection methods.


Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages.
CTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution. To gain insight into how these DNA elements are conserved and spread through the genome, we defined the full spectrum of CTCF-binding sites, including a 33/34-mer motif, and identified over five thousand highly conserved, robust, and tissue-independent CTCF-binding locations by comparing ChIP-seq data from six mammals. Our data indicate that activation of retroelements has produced species-specific expansions of CTCF binding in rodents, dogs, and opossum, which often functionally serve as chromatin and transcriptional insulators. We discovered fossilized repeat elements flanking deeply conserved CTCF-binding regions, indicating that similar retrotransposon expansions occurred hundreds of millions of years ago. Repeat-driven dispersal of CTCF binding is a fundamental, ancient, and still highly active mechanism of genome evolution in mammalian lineages.


Identifying Retrocecal Appendicitis on Point-of-Care Ultrasound (POCUS).
Retrocecal appendicitis may be challenging to find. We present the first case series in which retrocecal appendicitis was found on point-of-care ultrasound (POCUS). In each of the five cases, appendicitis was found by a pediatric emergency physician in the right periumbilical region or right upper quadrant. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The POCUS practitioner should scan both the right upper and right lower quadrant of the abdomen in search of appendicitis, as well as in search of signs of perforation.