New fungal protein from Pleurotus ferulae lanzi induces AMPK-mediated autophagy and G1-phase cell cycle arrest in A549 lung cancer cells.
A new protein, designated PFAP, with activity against non-small cell lung cancer (NSCLC), was isolated from Pleurotus ferulae lanzi, a medicinal and edible mushroom. The purification method involved hydrophobic interaction chromatography on a HiTrap Octyl FF column and gel filtration on a Superdex 75 column. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed a single band with a molecular weight of 14.68 kDa. Following de novo sequencing and liquid chromatography-tandem mass spectrometry, PFAP was identified as a protein consisting of 135 amino acid residues, with a theoretical molecular weight of 14.81 kDa. Tandem mass tag (TMT)™-based quantitative proteomic analysis and western blotting revealed that AMP-activated protein kinase (AMPK) was significantly upregulated in NSCLC A549 cells, following PFAP treatment. The downstream regulatory factor mammalian target of rapamycin (mTOR) was suppressed, resulting in the activation of autophagy and upregulated expressions of P62, LC3 II/I, and other related proteins. PFAP blocked NSCLC A549 cells in the G1 phase of the cell cycle via upregulating P53 and P21, while subsequently downregulating the expression of cyclin-dependent kinases. PFAP suppresses tumour growth via the same mechanism in a xenograft mouse model in vivo. These results demonstrate that PFAP is a multifunctional protein with anti-NSCLC properties.


Deep, percutaneous antecubital venipuncture: an alternative to surgical cutdown.
In a 6 month period, I encountered 18 instances in which deep percutaneous venipuncture seemed appropriate. In every instance, venipuncture was successfully accomplished, avoiding a cutdown procedure, as well as obviating the need for central venous catheter placement. The ease of cannulation and the minimization of trauma to the patient make this technique a useful alternative to surgical venous cannulation.


Allele-specific PCR for a cost-effective & time-efficient diagnostic screening of spinal muscular atrophy.
Genetic diagnosis of spinal muscular atrophy (SMA) is complicated by the presence of SMN2 gene as majority of SMA patients show absence or deletion of SMN1 gene. PCR may amplify both the genes non selectively in presence of high amount of DNA. We evaluated whether allele-specific PCR for diagnostic screening of SMA is reliable in the presence of high amount of genomic DNA, which is commonly used when performing diagnostic screening using restriction enzymes. A total of 126 blood DNA samples were tested in amounts ranging 80-200 ng, referred for the genetic diagnosis of SMA using both conventional PCR-RFLP and allele-specific PCR. The results from both methods showed agreement. Further, allele-specific PCR was found to be a time-efficient and cost-effective method. Our study demonstrated the accuracy of our allele-specific PCR and the results were comparable compatible with that of PCR-RFLP, indicating its practical application in SMA diagnostic screening.


Eating Behavior and Satiety With Virtual Reality Meals Compared With Real Meals: Randomized Crossover Study.
Eating disorders and obesity are serious health problems with poor treatment outcomes and high relapse rates despite well-established treatments. Several studies have suggested that virtual reality technology could enhance the current treatment outcomes and could be used as an adjunctive tool in their treatment. This study aims to investigate the differences between eating virtual and real-life meals and test the hypothesis that eating a virtual meal can reduce hunger among healthy women. The study included 20 healthy women and used a randomized crossover design. The participants were asked to eat 1 introduction meal, 2 real meals, and 2 virtual meals, all containing real or virtual meatballs and potatoes. The real meals were eaten on a plate that had been placed on a scale that communicated with analytical software on a computer. The virtual meals were eaten in a room where participants were seated on a real chair in front of a real table and fitted with the virtual reality equipment. The eating behavior for both the real and virtual meals was filmed. Hunger was measured before and after the meals using questionnaires. There was a significant difference in hunger from baseline to after the real meal (mean difference=61.8, P<.001) but no significant change in hunger from before to after the virtual meal (mean difference=6.9, P=.10). There was no significant difference in food intake between the virtual and real meals (mean difference=36.8, P=.07). Meal duration was significantly shorter in the virtual meal (mean difference=-5.4, P<.001), which led to a higher eating rate (mean difference=82.9, P<.001). Some participants took bites and chewed during the virtual meal, but the number of bites and chews was lower than in the real meal. The meal duration was reduced from the first virtual meal to the second virtual meal, but no significant difference was observed between the 2 real meals. Eating a virtual meal does not appear to significantly reduce hunger in healthy individuals. Also, this methodology does not significantly result in eating behaviors identical to real-life conditions but does evoke chewing and bite behavior in certain individuals. ClinicalTrials.gov NCT05734209, https://clinicaltrials.gov/ct2/show/NCT05734209.


Biological activities and health effects of terpenoids from marine fungi.
Recently, a great deal of interest has been developed by the consumers toward natural bioactive compounds as functional ingredients in the nutraceutical, cosmeceutical, and pharmaceutical products due to their various health beneficial effects. Hence, it can be suggested that bioactive functional ingredients from marine bioresources and their by-products are alternative sources for synthetic ingredients that can contribute to consumer's well-being, as a part of nutraceuticals and functional foods. Marine-derived fungi produce a vast array of secondary metabolites including terpenes, steroids, polyketides, peptides, alkaloids, and polysaccharides. These secondary metabolites serve many biopharmaceutical purposes. This chapter discusses about marine fungi-derived terpenoids and presents an overview of their beneficial health effects.


Federal Polices Influence Access to Primary Care and Nurse Practitioner Workforce.
Although most nurse practitioners (NPs) are aware of state-level regulations that influence practice, many are unaware of the ways that federal policies affect NP workforce supply and the delivery of primary care. In this investigation we provide an overview of federal initiatives enacted through the Patient Protection and Affordable Care Act that impact the NP workforce. We explore how the law supports NP workforce supply and settings in which NPs provide care. We then describe challenges that may prevent full utilization of the NP workforce. Examining both federal policies and state-level regulations is essential to achieving an increased NP workforce supply and improved access to care.


[Effect of retinol deficiency on the activity of phospholipase A lysosomal enzymes in rat testes].
In the testes homogenates of rats kept on a A-deficient ration and receiving additionally retinyl-acetate (control) and retinoic acid (experiment) the activity of the phospholipases A1 and A2, with 1-acyl-2(1-14C)-oleoyl-SN-glycero-3-galactosidase and acid phosphatase employed as a substrate, was investigated. In the testes of rats receiving retinyl-acetate the activity of the phospholipases A1 and A2 was greatly declining. An addition of retinyl to the testes homogenates of test rats contributed to re-establishing the activity of the phospholipases up to the control level. In the testes of rats receiving retinoic acid a reduced activity of the acid phosphatase and a rise of beta-galactosidase, as compared to their activity in controls was also demonstrable.


Analgesic use and pain in residents with and without dementia in aged care facilities: A cross-sectional study.
To investigate analgesic use and pain in people with and without dementia in Australian residential aged are facilities. A cross-sectional study of 383 residents of six residential aged are facilities was conducted. Nurses assessed self-reported and clinician-observed pain. Analgesic use data were extracted from medication charts. Logistic regression was used to investigate factors associated with analgesic use. Analgesics were administered to 291 (76.0%) residents in the previous 24 hours. The prevalence of analgesic use was similar among residents with and without dementia (79.3% vs 73.4%, P = 0.20). Residents with dementia had a higher prevalence of self-reported pain than those without dementia but similar prevalence of clinician-observed pain. In residents with dementia, high care residence and dementia severity were associated with analgesic use. The prevalence of analgesic use was similar among residents with and without dementia. Both self-reported and clinician-observed measures are needed in regular pain assessments.


[Maxillary first molar with two distobuccal root canals: a case report].
The root and canal anatomy of maxillary first molar is very complicated. The incidence of having two canals in the mesiobuccal root of maxillary first molar is higher than that in its distobuccal root. This article described a maxillary first molar with five root canals, including two canals in mesiobuccal and distobuccal roots.


Borderline Malignant Sebaceoma of the Auricle: A Case Report.
Sebaceoma is a rare benign tumor arising from the sebaceous gland of the skin. Sebaceoma often occurs on the head and neck but rarely on the ears. We present the case of a 78-year-old female patient with a two-year history of a protruding mass in her left ear. Physical examination revealed a well-circumscribed plaque in the crus of the helix of the left ear. A wide local excisional biopsy was taken, and the mass was subjected to histopathologic assessment. While the mass showed cytological findings indicating sebaceoma, it also presented malignant features architecturally and immunohistochemically. Based on these findings, the tumor was regarded as a sebaceoma of borderline malignancy. The online version contains supplementary material available at 10.1007/s12070-023-03552-4.


Molecular design of D-π-A-π-D small molecule donor materials with narrow energy gap for organic solar cells applications.
Developing novel materials present a great challenge to improve the photovoltaic performance of organic solar cells (OSCs). In this paper, we designed a series of the donor-π bridge-acceptor-π bridge-donor (D-π-A-π-D) structure molecules. These molecules consist of diketopyrrolopyrrole (DPP) moiety as core, 9-hexyl-carbazole moiety as terminal groups, and different planar electron-rich aromatic groups as π-bridges. The density functional theory (DFT) and time-dependent DFT (TD-DFT) computations showed that the frontier molecular orbital (FMO) energy levels, energy gaps, electron-driving forces (ΔEL-L), open-circuit voltage (Voc), fill factor (FF), reorganization energy (λ), exciton binding energy (Eb), and absorption spectra of the designed molecules can be effectively adjusted by the introduction of different π-bridges. The designed molecules have narrow energy gap and strong absorption spectra, which are beneficial for improving the photoelectric conversion efficiency of organic solar cells. In addition, the designed molecules possess large ΔEL-L, large Voc, and FF values and low Eb when the typical fullerene derivatives are used as acceptors. The FMO energy levels of the designed molecules can provide match well with the typical fullerene acceptors PC61BM, bisPC61BM, and PC71BM. Our results suggest that the designed molecules are expected to be promising donor materials for OSCs. All DFT and TD-DFT calculations were carried out using the Gaussian 09 code. The computational technique chosen was the hybrid functional B3LYP and the 6-31G(d,p) basis set. The benzene and chloroform solvent effects have been considered using the polarized continuum model (PCM) at the TD-DFT level. The simulated absorption spectra of designed molecules were plotted by using the GaussSum 1.0 program.


Experiences with some new scales for use in general practice trials.
The proper assessment of depression in general practice requires the use of adequate and sensitive measurement of target symptoms. In a pilot trial of a new 50 mg formulation of clomipramine (Anafranil) various new techniques of measurement were explored, namely, the General Health Questionnaire, a series of visual analogue scales with a centre reference point and a new physician rating scale for depression.


Implementation of an interprofessional medication adherence program for HIV patients: description of the process using the framework for the implementation of services in pharmacy.
The community pharmacy center of the Department of Ambulatory Care and Community Medicine of the Policlinique Médicale Universitaire (PMU), Lausanne, Switzerland developed and implemented an interprofessional medication adherence program for chronic patients (IMAP). In 2014, a project was launched to implement the IMAP for HIV patients in a public non-academic hospital with the collaboration of community pharmacists in the Neuchâtel area (Switzerland). This article aims to describe the different implementation stages and strategies of the project. A posteriori description of the implementation process, including the conceptualization strategies and stages (exploration, preparation, operation, sustainability) using the Framework for the Implementation of Services in Pharmacy (FISpH). In 2014, an attending infectious disease physician and a nurse at a public hospital (Neuchâtel, Switzerland) contacted the PMU to implement the IMAP in their setting in collaboration with community pharmacies. Five volunteer community pharmacies in Neuchâtel were trained to deliver the program. Three factors were found to be essential to the successful launch and progress of the implementation project: the experience of the community pharmacy center of the PMU with the IMAP, the involvement of the PMU research team, and collaboration with an external start up (SISPha) to train and support pharmacists. During the operation stage, the most important strategy developed was that of regular meetings between all stakeholders. These allowed healthcare professionals to discuss the implementation progress, to address each stakeholder's expectations, and to exchange experiences to facilitate interprofessional collaboration and program delivery. Structural changes allowed the formalization of the activities at the hospital and in a community pharmacy. This formalization was identified as the transition step between the operation and the sustainability stages. The transfer of the IMAP for HIV patients to a non-academic setting and its implementation are feasible. However, implementation of a new model of pharmacy service such as IMAP implies a deep change in practice. A transitional external support and the allocation of sufficient resources to carry out the IMAP are essential for its long-term sustainability.


Cellular Signaling for Dental Physiological Functions.
Teeth are unique and multifaceted tissues that are necessary for routine functions, such as crushing food and constructing articulated sounds, as well as for esthetic symbols [...].


Selective damage to hyphal form through light-induced delivery of nitric oxide to Candida albicans colonies.
Candida albicans, an opportunistic fungal pathogen, causes severe to life-threatening infections in immunocompromised hosts (e.g. HIV patients, burn victims). Conversion of the commensal yeast form to the invasive hyphal form, triggered by environmental cues, initiates such episodes. Although the antifungal activity of nitric oxide (NO) has been established, very few convenient NO-donating systems for treating C. albicans infection have been reported. In this work, a biocompatible NO-donating material that delivers NO upon illumination with visible light has been employed to eradicate C. albicans in a dose-dependent way. Careful studies on the yeast and hyphal forms with this NO donor have revealed that the hyphal form is more susceptible to NO exposure than the yeast variety. Results of this work suggest that materials of this type could find use in thwarting invasion of the hyphal form of the fungus in cases of invasive C. albicans infection.


Carbon-chalcogen bond formation initiated by [Al(NONDipp)(E)]- anions containing Al-E{16} (E{16} = S, Se) multiple bonds.
Multiply-bonded main group metal compounds are of interest as a new class of reactive species able to activate and functionalize a wide range of substrates. The aluminium sulfido compound K[Al(NONDipp)(S)] (NONDipp = [O(SiMe2NDipp)2]2-, Dipp = 2,6-iPr2C6H3), completing the series of [Al(NONDipp)(E)]- anions containing Al-E{16} multiple bonds (E{16} = O, S, Se, Te), was accessed via desulfurisation of K[Al(NONDipp)(S4)] using triphenylphosphane. The crystal structure showed a tetrameric aggregate joined by multiple K⋯S and K⋯π(arene) interactions that were disrupted by the addition of 2.2.2-cryptand to form the separated ion pair, [K(2.2.2-crypt)][Al(NONDipp)(S)]. Analysis of the anion using density functional theory (DFT) confirmed multiple-bond character in the Al-S group. The reaction of the sulfido and selenido anions K[Al(NONDipp)(E)] (E = S, Se) with CO2 afforded K[Al(NONDipp)(κ2 E,O-EC{O}O)] containing the thio- and seleno-carbonate groups respectively, consistent with a [2 + 2]-cycloaddition reaction and C-E bond formation. An analogous cycloaddition reaction took place with benzophenone affording compounds containing the diphenylsulfido- and diphenylselenido-methanolate ligands, [κ2 E,O-EC{O}Ph2]2-. In contrast, when K[Al(NONDipp)(E)] (E = S, Se) was reacted with benzaldehyde, two equivalents of substrate were incorporated into the product accompanied by formation of a second C-E bond and complete cleavage of the Al-E{16} bonds. The products contained the hitherto unknown κ2 O,O-thio- and κ2 O,O-seleno-bis(phenylmethanolate) ligands, which were exclusively isolated as the cis-stereoisomers. The mechanisms of these cycloaddition reactions were investigated using DFT methods.


Compounding of Veterinary Drugs for Equine Practitioners.
Equine practitioners should follow these recommendations when using compounded medications: (1) the decision must be veterinary driven, based on a valid veterinarian-client-patient relationship and on evidence-based medicine; (2) compliance with the Animal Medicinal Drug Use Clarification Act of 1994; and (3) use limited to (a) horses for which no other method or route of drug delivery is practical; (b) those drugs for which safety, efficacy, and stability have been demonstrated; or (c) disease conditions for which a quantifiable response to therapy or drug concentration can be monitored.


Improved PET/MRI attenuation correction in the pelvic region using a statistical decomposition method on T2-weighted images.
Attenuation correction of PET/MRI is a remaining problem for whole-body PET/MRI. The statistical decomposition algorithm (SDA) is a probabilistic atlas-based method that calculates synthetic CTs from T2-weighted MRI scans. In this study, we evaluated the application of SDA for attenuation correction of PET images in the pelvic region. Twelve patients were retrospectively selected from an ongoing prostate cancer research study. The patients had same-day scans of [11C]acetate PET/MRI and CT. The CT images were non-rigidly registered to the PET/MRI geometry, and PET images were reconstructed with attenuation correction employing CT, SDA-generated CT, and the built-in Dixon sequence-based method of the scanner. The PET images reconstructed using CT-based attenuation correction were used as ground truth. The mean whole-image PET uptake error was reduced from - 5.4% for Dixon-PET to - 0.9% for SDA-PET. The prostate standardized uptake value (SUV) quantification error was significantly reduced from - 5.6% for Dixon-PET to - 2.3% for SDA-PET. Attenuation correction with SDA improves quantification of PET/MR images in the pelvic region compared to the Dixon-based method.


Multiparametric assay using HepaRG cells for predicting drug-induced liver injury.
The utility of HepaRG cells as an in vitro cell-based assay system for assessing drug-induced liver injury (DILI) risk was investigated. Seventeen DILI-positive and 15 DILI-negative drugs were selected for the assay. HepaRG cells were treated with each drug for 24h at concentrations that were 1.6-, 6.3-, 25-, and 100-fold the therapeutic maximum plasma concentration (Cmax). After treatment, the cell viability, glutathione content, caspase 3/7 activity, lipid accumulation, leakage of lactate dehydrogenase, and albumin secretion were measured. The sensitivity and specificity were calculated to assess the ability of the assay to predict DILI. Our multiparametric assay using HepaRG cells exhibited a 67% sensitivity and 73% specificity at a 100-fold concentration of Cmax and a 41% sensitivity and 87% specificity at a 25-fold concentration of Cmax. When a 25-fold Cmax cut-off was applied, approximately 70% of drugs exhibiting positive responses were classified into the high DILI risk category. HepaRG cells distinguished relatively safe drugs from their high-risk analogs. Our study indicates that HepaRG cells may be of use to (1) prioritize drug analogs, (2) analyze the mechanism of DILI, and (3) assess the risk for DILI in the early drug discovery stage.


Polarized growth in fungi: symmetry breaking and hyphal formation.
Cell shape is a critical determinant for function. The baker's yeast Saccharomyces cerevisiae changes shape in response to its environment, growing by budding in rich nutrients, forming invasive pseudohyphal filaments in nutrient poor conditions and pear shaped shmoos for growth towards a partner during mating. The human opportunistic pathogen Candida albicans can switch from budding to hyphal growth, in response to numerous environmental stimuli to colonize and invade its host. Hyphal growth, typical of filamentous fungi, is not observed in S. cerevisiae. A number of internal cues regulate when and where yeast cells break symmetry leading to polarized growth and ultimately distinct cell shapes. This review discusses how cells break symmetry using the yeast S. cerevisiae paradigm and how polarized growth is initiated and maintained to result in dramatic morphological changes during C. albicans hyphal growth.


Initial development of conduction pattern of spontaneous action potential in early embryonic precontractile chick heart.
The conduction of spontaneous action potentials in the 7-10 somite embryonic developing chick hearts was monitored optically using a potential-sensitive merocyanine-rhodanine dye. Spontaneous optical action signals from 5 to 12 different regions of the primitive heart were recorded simultaneously. Short delays were observed among firing times of the absorption signals which were nearly synchronized among the different regions. From these delays, we estimated the conduction velocity of the spontaneous excitatory waves. Usually, in the 7-somite to the beginning of the 9-somite stage, (i) excitatory waves conducted radially over one side of the prebeating heart, at a uniform rate; (ii) the "radially" spreading electrical wave slowed considerably within the primordial fusion line at the midline of the heart; and (iii) this delay disappeared in the later period of the 9-somite stage to the 10-somite stage. These observations suggest that electrical coupling among the cells within the primordial fusion line is poor during the 7 to 9-somite stage, and that the coupling is strengthened by the late 9th or 10th somite stage.


Assessment of the Optic Foramen Shape and Size in Human Fetuses.
This study was aimed to obtain data on the dimensions of the optic foramen in human fetuses for early childhood surgeries. Twenty-five formalin-fixed fetuses (16 boys and 9 girls) with average age 21.68 ± 3.12 gestational weeks (range, 16-28 weeks) in the inventory of Anatomy Department, Faculty of Medicine were included in the study. The surface area, width, and height of the optic foramen were bilaterally measured using a digital image analysis software. The forms of the optic foramen were described as oval shaped (72%, 36 foramina) and round shaped (28%, 14 foramina). The surface area, width, and height of the optic foramen were found as 2.40 ± 1.02 mm, 1.83 ± 0.59 mm, and 1.58 ± 0.36 mm, respectively. The measurements of the parameters related to the optic foramen were not statistically different in terms of sides and sexes (P > 0.05). Linear functions for the height, width and surface area of the optic foramen were calculated as: y = 0.711 + 0.040 × weeks, y = -0.019 + 0.086 × weeks, and y = -0.400 + 0.129 × weeks, respectively. The linear functions in this study can be used to estimate the dimensions of the optic foramen. The calculated regression equations, representing the growth dynamic of the optic foramen showed that the surface area, width, and height were increasing according to gestational ages between 16 and 28 weeks. Microanatomical knowledge related to the optic foramen may be beneficial for surgeons to avoid iatrogenic injury in infants and for anatomists to understand the development of the fetal skull base.


A study of function after tibial cast bracing.
103 patients with fresh unilateral fractures of the tibial shaft were reviewed clinically and radiologically to assess the results of treatment by functional bracing. At review, 84 had returned to their previous employment and all but 22 could run. All had full knee movements, 85 per cent had a normal range or a mild loss of subtalar movement, and only 11 patients had greater than 25 per cent reduction of measured ankle movement. The average shortening measured radiologically was 0.5 cm. Angulation greater than 10 degrees was present in 1 patient. Factors leading to delayed union include comminution, severe displacement, open injuries and not bearing weight. The importance of early weight bearing is discussed.


Living Unrelated Versus Related Kidney Transplantation: A 25-Year Experience with 3716 Cases.
To evaluate the results of transplantation from living unrelated donors (LURD) versus living related donors (LRD) with a long term follow-up of 25-30 years. From 1984 to 2015, a total of3716 kidney transplantations (411 LRDs and 3305 LURDs) were enrolled to the study. Long-term survival of grafts and patients as well as the association between relation state and patients or grafts surveillance were the outcomes. A total of 3716 live donor kidney transplants (LRD, n = 411; LURD, n = 3305) were carried out over this period. The mean age of donors was 28 ± 54 years in the LURD group and 34.4 ± 11.7 years in LRD (P < . 001), while the mean age of the recipients was 35.6 ± 15.6 years and 27.6 ± 10.1 years for the two groups, respectively. Donor age was the only statistically significant predictor of graft survival rate (hazard ratio = 1.021, 95% confidence interval: 1.012-1.031). Between 1984 and 2015, patient survival and graft survival improved significantly also patient survival and graft survival was similar in LURDs compared with LRDs. It seems that the outcome of LURD and LRD is comparable in terms of patient and graft survival. Therefore, transplants from LURDs may be proposed as an acceptable management for patients with end stage renal disease.


Silencing of an anther-specific zinc-finger gene, MEZ1, causes aberrant meiosis and pollen abortion in petunia.
MEZ1 (MEiosis-associated Zinc-finger protein 1) was first isolated as an anther-specific cDNA from Petunia hybrida. In the present study, we report its functional characterization, including its spatial and temporal expression profiles and phenotypes in MEZ1-silenced plants. MEZ1 transcripts were specifically localized in pollen mother cells during early stages of anther development, and were later distributed in vegetative tissues in anthers. Silencing of MEZ1 by cosuppression resulted in several anomalies during male meiosis that included inability of chromosomes to condense, loss of meiotic synchrony, and premature and apparently uncontrolled cytokinetic events. Consequently, by the end of meiosis 8-10 cells, instead of the normal 4, with varying DNA contents were formed in the MEZ1-silenced meiocytes. Most of these aborted prematurely, and those that matured had a distinctive morphology. MEZ1-silenced plants were female sterile when pollinated with wild-type pollen but they infrequently produced a few seeds upon self-pollination. Resulting T1 plants had increased ploidy levels and exhibited severe anomalies during male meiosis, rendering them completely sterile. We discuss possible role of MEZ1 in the proper progression of plant meiosis.


Bending the Arc of Exercise and Recreation Technology Toward People With Disabilities.
Most of the published research on exercise and disability has focused on short-term efficacy studies targeting specific disability groups. These studies often use grant-related or other financial resources to temporarily remove the many barriers that people with physical/mobility disability experience when attempting to become physically active. In this commentary, we explore how technology can be used to promote more sustainable physical activity outcomes in the home and community using a set of 4 overlapping domains: Access, Usability, Adherence, and Health and Function. In addition, we describe how the order in which these domains should be addressed will vary depending on the needs of the target group and the context of their environment. Finally, we provide examples of various types of technologies (eg, hardware and software) that can support the "afterlife" of successful short-term exercise and rehabilitation trials in people with physical/mobility disability who desire to self-manage their own health and maintain a regular and sustainable pattern of physical activity across their life span.


Use of standard and anatomic-tilt lateral X-rays to determine distal radius volar angulation.
To determine the reliability of measurements of distal radius volar tilt using either standard lateral or anatomic tilt lateral (ATL) radiographs, and to compare the mean values obtained using each radiographic method. We obtained standard and 23° ATL plain radiographs of the distal radii of 20 patients with a distal radius fracture treated with a volar locking plate, and of 20 healthy individuals without a history of fracture of the wrist. Three orthopedic surgeons measured volar tilt twice with an interval of 4 weeks. We analyzed intraobserver and interobserver reliability and compared intraobserver means of volar tilts obtained using standard and ATL radiographs. The volar tilts measured using ATL radiographs in patients and healthy controls showed moderate to excellent intraobserver and interobserver reliability, whereas those determined using standard lateral radiographs showed poor to moderate intraobserver and interobserver reliability in patients and controls. However, the mean values of volar tilts measured in standard lateral radiographs and in ATL radiographs were similar in patients and not significantly different in healthy controls. Volar tilt measurements obtained using anatomic tilt lateral radiographs provided moderate to excellent reliability. However, we found no statistically significant difference between volar tilts determined using ATL and standard lateral radiographs. Accordingly, standard lateral and ATL radiographs are interchangeable with respect to volar tilt measurements. Diagnostic II.


Plasma thyroxine levels in Duchenne muscular dystrophy.
Some young Duchenne muscular dystrophy (DMD) patients (3-7 years) had total thyroxine (T4) levels and T4 to thyroxine binding globulin (TBG) ratios above the normal range and significantly increased free thyroxine indices (fT4I) which, however, remained within the normal range. Older DMD patients (7-11 years) had T4 and TBG levels and fT4I similar to normal. In both DMD groups the thyroxine binding index (TBI) values were in the normal range.


Hypoxic regulation of VEGF mRNA stability by RNA-binding proteins.
Vascular endothelial growth factor (VEGF), is a potent angiogenic factor whose expression is dramatically induced by hypoxia. We have previously demonstrated that the induction of VEGF by hypoxia is in large part the result of an increased stability of VEGF mRNA. The stabilization of VEGF mRNA by hypoxia is mediated by the binding of sequence-specific RNA-binding proteins. This review focuses on one such protein, HuR, an RNA-binding protein which we have recently shown is critical for the hypoxic stabilization of VEGF mRNA.


Aluminum and sulphate removal by a highly Al-resistant dissimilatory sulphate-reducing bacteria community.
A highly Al-resistant dissimilatory sulphate-reducing bacteria community was isolated from sludge of the wetland of Urgeiriça mine (community W). This community showed excellent sulphate removal at the presence of Al³⁺. After 27 days of incubation, 73, 86 and 81% of sulphate was removed in the presence of 0.48, 0.90 and 1.30 mM of Al³⁺, respectively. Moreover, Al³⁺ was simultaneously removed: 55, 85 and 78% of metal was removed in the presence of 0.48, 0.90 and 1.30 mM of Al³⁺, respectively. The dissociation of aluminium-lactate soluble complexes due to lactate consumption by dissimilatory sulphate-reducing bacteria can be responsible for aluminum removal, which probably precipitates as insoluble aluminium hydroxide. Phylogenetic analysis of 16S rRNA gene showed that this community was mainly composed by bacteria closely related to Desulfovibrio desulfuricans. However, bacteria affiliated to Proteus and Ralstonia were also present in the community.


Effect of Aerodiol administration on cerebral blood flow volume in postmenopausal women.
The aim of the study was to evaluate the acute effect of the intranasal 17beta-estradiol (Aerodiol, Servier, Chambray-les-Tours, France) administration on cerebral blood flow (CBF) volume. Eighteen healthy women who had been natural postmenopausal for at least 1 year were enrolled in the study. We conducted an experimental, randomized, placebo-controlled, crossover, double-blinded study of the acute effect of 17beta-estradiol on the internal carotid artery (ICA), vertebral artery (VA) and, CBF volume using color duplex sonography. There were significant increases in the ICA, VA flow volumes and CBF volume after 17beta-estradiol administration compared to placebo measurements. However, there was no statistically significant difference in flow velocities or pulsatility indices. Nasal 17beta-estradiol administration in postmenopausal women causes significant increases in CBF volume due to its vasodilatatory effect on ICA and VA.


Wuzi-Yanzong-Wan prevents oligoasthenospermia due to TAp73 suppression by affecting cellular junction remodeling in testicular tissue in mice.
Wuzi-Yanzong-Wan (WZYZW) is a classic Chinese herbal preparation, which has a significant clinical efficacy in tonifying the kidney and benefiting the sperm, and is widely used in the treatment of oligoasthenospermia with a long history. TAp73 inhibition results in the decrease of sperm quality, but the therapeutic mechanism of WZYZW on oligoasthenospermia caused by TAp73 gene inhibition remains elusive. The purpose of this study is to investigate whether TAp73 suppression leads to oligoasthenospermia and the application of WZYZW treatment in condition of TAp73 suppression. C57BL/6 male mice were injected with Pifithrin-α (2.5 mg/kg) intraperitoneally for 30 days to induce TAp73 suppression model, with WZYZW at 1.0, 2.0 and 4.0 g/kg were administrated in parallel. The blood, testis and epididymis were collected, with organ coefficient calculated. Makler sperm counter was used to analyze the density, motility, survival and malformation rate of sperm. Apoptosis of sperm was analyzed by flow cytometry. Serum hormone levels were determined using ELISA. HE staining and transmission electron microscopy (TEM) were used to observe histopathological changes of testis in blood-testis barrier (BTB), ectoplasmic specialization (ES) and other cell junctions. Expressions of cell adhesion factors including TAp73, Integrin-α6, N-cadherin, Nectin-2 and Occludin were determined by RT-PCR and western blotting. Compared to control mice, TAp73 inhibition dramatically decreased the epididymal coefficient, sperm quality, and serum testosterone (T) level, while increasing apoptosis in sperm in mice. HE staining and TEM showed that the tight junction (TJ) and apical ES structure were seriously abnormal in the testis in mice with TAp73 inhibition. Additionally, the expression of Occludin protein was elevated, while that of TAp73, Integrin-α6, N-cadherin, and Nectin-2 reduced in model mice. WZYZW treatment ameliorated testicular spermatogenic dysfunctions in TAp73 suppressed mice, restoring the decreased sperm quality, serum T level and testicular histopathological changes of TJ and ES, as well as decreasing sperm malformation rate and apoptosis. Moreover, WZYZW reversed the expressions of Occludin, TAp73, Integrin-α6, N-cadherin and Nectin-2 in TAp73 suppressed mice. By impairing spermatogenesis and maturation, TAp73 inhibition led to oligoasthenospermia in mice. WZYZW could rescue the oligoasthenospermia associated with TAp73 inhibition via affecting the dynamic remodeling of cellular junctions in testicular tissues in mice.


Immunogenic and antigenic epitopes of immunoglobulins. VIII. A human monoclonal rheumatoid factor having specificity for a discontinuous epitope determined by histidine/arginine interchange as residue 435 of immunoglobulin G.
A monoclonal human rheumatoid factor (RF-AN) reactive with human Fc gamma is shown to recognise a discontinuous epitope dependent on the presence of histidine (His) at residue 435. RF-AN is not reactive with IgG1 paraproteins having C gamma 2 or C gamma 3 domain deletions or IgG3m (5) or Ig3m (21) proteins having arginine (Arg) at residue 435. RF-AN is reactive with IgG1, 2, 4 and IgG3m (15,16) proteins having histidine at 435.


Solution degradant of mirabegron extended release tablets resulting from a Strecker-like reaction between mirabegron, minute amounts of hydrogen cyanide in acetonitrile, and formaldehyde in PEG during sample preparation.
During the related substances testing of mirabegron extended release tablets, an unknown peak was observed in HPLC chromatograms in a level exceeding the identification threshold. By using a strategy that combines LC-PDA/UV-MSn with mechanism-based stress studies, the unknown peak was rapidly identified as cyanomethyl mirabegron, a solution degradant that is caused by a Strecker-like reaction between the API, formaldehyde (an impurity in PEG), and HCN (an impurity in HPLC grade acetonitrile). The mechanism of the solution degradation chemistry was verified by stressing mirabegron with formaldehyde and trimethylsilyl cyanide (TMSCN, a synthetic reagent that generates HCN upon contact with water), in which the secondary amine group of mirabegron first reacts with formaldehyde to form the iminium ion intermediate; the latter then undergoes a nucleophilic attack by cyanide to yield the cyanomethyl mirabegron. The structure of the impurity was further confirmed through the synthesis of the impurity and subsequent structure characterization by 1D and 2D NMR. Due to the ubiquitous presence of formaldehyde in pharmaceutical excipients (e.g., PEG and polysorbate) and trace amount of HCN in HPLC grade acetonitrile, this type of solution degradation would likely occur in sample preparations of pharmaceutical finished products containing APIs with primary and secondary amine moieties. In a GMP environment, such an event may trigger undesirable out-of-specification (OOS) investigations; the results of this paper should help resolve such OOS investigations or even prevent these events from happening in the first place.


A real-time (PCR) for a real life…? Quantitative evaluation of BCL2/IGH in follicular lymphoma and its implications for clinical practice.
Follicular lymphoma (FL) is highly associated with the molecular rearrangement BCL2/IGH. Although BCL2/IGH has been studied many times in follicular lymphoma, its real clinical value remains controversial. In this study, we performed quantitative testing by real-time polymerase chain reaction in 56 FL patients with median follow-up of 44 months (range, 9-102 months); chemotherapy was administered in 52 of 56 cases. Pretreatment numbers of BCL2/IGH varied in wide ranges, with a median of 2947 (range, 0-1,261,013) copies/10(6) cellular equivalent in peripheral blood (PB) and 4650 copies/10(6) cellular equivalent (range, 1-1,056,813) in bone marrow (BM), the difference between PB and BM was significant (p = 0.006). Pretreatment of BCL2/IGH quantities were correlated to clinical parameters (e.g., age, stage, sex, lactate dehydrogenase, B symptoms, grade, bulky disease, chemotherapy regimen) and to progression free-survival. Advanced clinical stage (III and IV) and microscopic BM involvement were significantly associated with higher numbers of BCL2/IGH in PB (p < 0.05) and in BM (p = 0.05), regardless all or newly diagnosed patients were evaluated. High pretreatment burden of BCL2/IGH was associated with significantly shorter progression-free survival; p = 0.003 and p = 0.047 for PB and BM, respectively. In conclusion, pretreatment quantity of BCL2/IGH in PB or BM seems to mirror the extent of disease and can provide an auxiliary prognostic parameter in FL. Our results also support evidence of the negative prognostic value of microscopic BM involvement in FL.


The efficacy and acceptability of psychological interventions for adult PTSD: A network and pairwise meta-analysis of randomized controlled trials.
A comprehensive quantitative summary of the efficacy and acceptability of psychological interventions (PIs) for adult posttraumatic stress disorder (PTSD) is lacking. We conducted a systematic literature search to identify randomized controlled trials (RCTs) examining the efficacy and acceptability (all-cause dropout) of psychological interventions (i.e., trauma-focused cognitive behavior therapy [TF-CBT], eye movement desensitization and reprocessing [EMDR], other trauma-focused interventions and non-trauma-focused interventions). One hundred fifty-seven RCTs were included comprising 11,565 patients. Most research (64% of RCTs) accumulated for TF-CBT. In network meta-analyses, all therapies were effective when compared to control conditions. Interventions did not differ significantly in their efficacy. Yet, TF-CBT yielded higher short- (g = 0.17, 95% CI [0.03-0.31], number of comparisons kes = 190), mid- (i.e., ≤5 months posttreatment, g = 0.23, 95% CI [0.06-0.40], kes = 73) and long-term efficacy (i.e., >5 months posttreatment, g = 0.20, 95% CI [0.04-0.35], kes = 41) than non-trauma-focused interventions. There was some evidence of network inconsistencies, and heterogeneity in outcomes was large. In pairwise meta-analysis, slightly more patients dropped out from TF-CBT than non-trauma-focused interventions (RR = 1.36; 95% CI [1.08-1.70], kes = 22). Other than that, interventions did not differ in their acceptability. Interventions with and without trauma focus are effective and acceptable in the treatment of PTSD. While TF-CBT yields the highest efficacy, slightly more patients discontinued TF-CBT than non-trauma-focused interventions. Altogether, the present results align with results of most previous quantitative reviews. Yet, results need to be interpreted with caution in light of some network inconsistencies and high heterogeneity in outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assessment of Effective Antimicrobial Regimens and Mortality-Related Risk Factors for Bloodstream Infections Caused by Carbapenem-Resistant Acinetobacter baumannii.
This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses. Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375). The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.


[Effectiveness of oral hypoglycemic drugs in the metabolic control of patients with gestational diabetes].
Gestational Diabetes is characterized by different degrees of glucose intolerance that produce a series of fetal and perinatal alterations. During many years, in those cases of gestational diabetes that did not respond to nutritional interventions, the use of insulin was a proven treatment to achieve metabolic control and thus a better perinatal outcome. At present, some new oral hypoglycemic drugs, from the family of sulfonylureas and biguanides, have been shown to be safe, of low cost, and apparently effective in the metabolic control of this disease. We review the publications that propose the use of oral hypoglycemic drugs for the metabolic control of gestational diabetes that does not respond to nutritional measures.


The specialized mitotic behavior of human embryonic stem cells.
Human embryonic stem cells (hESCs) are self-renewing and pluripotent cells that originate from the inner cell mass of the blastocyst. Mitosis is fundamental to organism survival and reproduction and is responsible for the equal distribution of duplicated chromosomes into daughter cells. Mitotic dysfunction is associated with a wide variety of human diseases, not least cancer. hESCs have a unique cell cycle distribution, but it is unclear exactly how the mitotic activity of hESCs is related to their proliferation and differentiation. Here, we established a cell line of hESCs stably expressing GFP-α-tubulin and mCherry-H2B by lentiviral infection to analyze and visualize mitosis in detail. During metaphase, the mitotic spindle was smaller and wider and contained a greater proportion of astral microtubules than normal cells. In addition, spindle microtubules were more stable, and chromosome alignment was faster in hESCs than in somatic cells. We also found that the spindle assembly checkpoint was functional in hESCs. These findings thus reveal a specialized mitotic behavior of hESCs.


Effect of hygiene instrumentation on titanium abutments: a scanning electron microscopy study.
Implant abutments can be exposed to a variety of oral prophylaxis procedures. In this in vitro study, titanium abutments were subjected to five oral prophylaxis treatment modalities; a metal scaler, a plastic scaler, a rubber cup, a rubber cup with tin oxide, and an air-powder abrasive. The abutment surfaces were then examined under both light and scanning electron microscopes. The metal scaler was seen to roughen the titanium surface. All other modalities tested appeared to smooth the titanium surface by removing surface debris and rounding off the sharp machined grooves present on the untreated abutment surface.


The Occurrence Rate of Swallowing Disorders After Stroke Patients in Asia: A PRISMA-Compliant Systematic Review and Meta-Analysis.
Swallowing disorders (dysphagia) is common in stroke patients. However, the epidemiology of post-stroke dysphagia (PSD) is poorly described. We herein synthesize the data of eligible studies on occurrence rate of dysphagia in Asian populations with stroke. We searched the electronic databases (PubMed, Embase and Web of Science) to collect the studies on the prevalence of PSD. We used the Newcastle-Ottawa Scale (NOS) to estimate the quality of studies. The pooled dysphagia occurrence rate was obtained in Asian stroke patients. 40 studies (including 43 observations) from 2318 initial references were selected in the synthetic analysis. The pooled occurrence rate of dysphagia in post-stroke patients was 36.3% (95% CI, 33.3%-39.3%). Meta-regression analysis showed that the "country" and "developing level" may influence the pooled occurrence rate of PSD. Dysphagia is common in Asian post-stroke patients. Our meta-analysis may raise concern about evaluating and managing dysphagia in stroke patients.


Overexpression of B-type cyclins alters chromosomal segregation.
To identify genes which overexpression results into chromosomal instability (CIN), we developed a biological approach based on a yeast indicator strain in which CIN can be detected by a sectoring phenotype. Screening in this strain of a yeast genomic library cloned into a high copy vector led us to identify, among the clones generating 100% of sectoring colonies, Clb5, one of the six B-type cyclins present in yeast. Overexpression of cyclin B2 and cyclin B1, the two human homologs of Clb5, in the CIN indicator strain resulted also into a sectoring phenotype and induced, like overexpression of Clb5, an abnormal sensitivity to benomyl, indicating that overexpression of B-type cyclins alters the spindle checkpoint. In a series of 38 primary colorectal cancers, we detected in five tumors (13%) an accumulation of cyclin B1, which was neither related to mRNA overexpression nor to mutation within the coding region, and in five other tumors (13%) a 2-10-fold increase of cyclin B2 mRNA which was not related to gene amplification. These results suggest that overexpression of cyclins B, resulting from different mechanisms, could contribute, through an alteration of the spindle checkpoint, to the chromosomal instability observed in cancer.


Resistance to polymyxins: Mechanisms, frequency and treatment options.
Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes. The most important mechanism of resistance includes modifications of the bacterial outer membrane structure, including lipopolysaccharide. Lipopolysaccharide modification is mostly mediated by PmrA/PmrB and PhoP/PhoQ two-component regulatory systems. These mechanisms exist with some differences in many gram-negative bacterial species. Resistance to polymyxins is generally less than 10%. In specific regions, such as the Mediterranean basin, Korea and Singapore, they tend to be higher. Heteroresistance to polymyxins is associated with exposure to polymyxins and especially suboptimal therapeutic dosage. Polymyxin combination regimens, tigecycline and fosfomycin may be useful options for the treatment of polymyxin-resistant gram-negative infections.


Effects of sugammadex on the prevention of postoperative peritoneal adhesions.
Many materials and techniques have been used to prevent and repair intra-abdominal adhesions, but an effective solution has not been found. The aim of this study is to research the effect of sugammadex on intra-abdominal adhesions in an experimentally induced intra-abdominal adhesion model. Twenty-four female Wistar albino rats were included in the study. The experimental animals were randomly divided into three groups: the sugammadex group (Group SX, n = 8), the control group (Group C, n = 8), and the sham group (Group S, n = 8). After starvation for 1 night, the rats were injected with a 50 mg/kg intramuscular dose of ketamine and a 5 mg/kg intramuscular dose of xylazine for anesthesia. The rats in the SX group were given 3 mL sugammadex into the peritoneal cavity, while rats in the control group were given 3 mL 0.9% sodium chloride. In the sham group, the peritoneal cavity was opened, but no chemicals were administered. All rats were sacrificed on the 10(th) postoperative day. The adhesions were staged as 0, 1, 2, and 3 according to Evans et al.'s model. Our evaluation of macroscopic adhesion intensity found statistically significant differences between the groups. The sugammadex group was observed to have fewer adhesions in a statistically significant manner compared with the control group (p < 0.05). In our experimental intra-abdominal adhesion model in rats, we observed that sugammadex prevented postoperative intra-abdominal adhesions.


Early results of a novel technique: Hindfoot fusion in talus osteonecrosis prior to ankle arthroplasty: A case series.
The purpose of this study was to evaluate the clinical outcome of a two staged approach of subtalar arthrodesis followed by TAR for patients with ankle arthritis and AVN talus. Out of total 210 TARs performed at our institute; 7 patients underwent a two staged procedure between 2006 and 2010. All patients had over 3 years of follow up (except one). The clinical results were assessed using AOFAS, WOMAC, SF-36 and patient satisfaction scores. The mean follow up was 3 years. There was significant improvement in AOFAS and WOMAC (pain and stiffness) from pre-op to 3 years post-op (P<0.05). SF 36 scores improved from pre-op to 3 years post-op for 6/8 domains. 5 patients were satisfied at 3 years for overall surgical outcomes, 4 were satisfied with pain relief. Radiological signs of talar subsidence were noted in 2 patients at year 1. This did not progress at 3 years and did not deteriorate clinical outcome. We recommend our two staged approach to deal with this difficult clinical problem. We believe this approach is safe for TAR surgery where talar vascularity and bone quality is questionable leading to reduced talar subsidence, ischaemic pain and improvement in longevity of TAR. Evidence IV (Retrospective case series).


microFIND(®) approach to fluorescent in situ hybridization (FISH).
FISH technology has gained increasing attention in the management of cancer disease, either for predictive or prognostic indications. Molecular cytogenetics has greatly improved diagnostic capability of classical cytogenetics analysis of metaphase-based chromosome for the identification of genetic aberrations. The availability of a large number of fluorescent probes, each specific for different genetic lesions, together with a robust protocol for interphase FISH, provide the pathologist with the essential tools for an accurate evaluation of patient's disease. Hemato-oncological and many of the solid tumors have been comprehensively characterized by peculiar genetic defects and are now routinely evaluated by interphase FISH. Despite the reliability of the method, which has undergone only minor changes since the 1970s, FISH assay is still hampered by reagents cost, preventing its adoption in large-scale oncological screening. In this chapter we describe a major improvement of interphase FISH assay for cytological samples through the description of the miniaturized device microFIND(®) that offers, besides reduction of cost per assay, a completely novel vision to the FISH technology, thanks to the perspective of full automation of FISH assay using a dedicated robotic platform for microFIND(®) handling, (not presently described in the chapter).


Architectures and tools for innovative Health Information Systems: the Guide Project.
This paper describes the architecture of the Guide Project, a proposal for innovation of Health Information Systems, putting together medical and organizational issues through the Separation of Concerns paradigm. In particular, we focus on one building block of the architecture: the Guideline Management System handling the whole life cycle of computerized Clinical Practice Guidelines. The communication between the Guideline Management System and the other components of the project architecture is message-based, according to specific contracts that allow an easy integration of the components developed by different parties and, in particular, with legacy systems (i.e. existing electronic patient records). In turn, the Guideline Management System components are organized in a distributed architecture: an editor to formalize guidelines, a repository to store and publish them, an enactment system to implement guidelines instances in a multi-user environment and a reporting system able to completely trace any individual physician's guideline-based decision process. The repository is organized in different levels that can be international, national, regional, down to the specific health care organization, according to the healthcare delivery policy of a country. Different organizations can get Clinical Practice Guidelines from the repository, adapt and introduce them in clinical practice.


Telescoping pipeline vantage embolization devices with shield technology for the treatment of a giant, symptomatic dolichoectatic basilar trunk aneurysm.
Dolichoectatic basilar trunk aneurysms are exceedingly rare and carry a poor prognosis. Treatment strategies are often reserved for patients with severe and progressive symptoms. A patient in their 40s with a dolichoectatic basilar trunk aneurysm developed significant progression of the lesion and neurologic decline, necessitating treatment. He underwent flow diversion utilizing multiple telescoping Pipeline Vantage Embolization Devices with Shield Technology for treatment. At 1-year follow-up, the aneurysm was stable in size and the patient remained at his neurologic baseline. This case illustrates the need for continued development of next-generation endovascular devices as these aneurysms have limited management options.


Vaginal sensitivity to electric stimuli: theoretical and practical implications.
Vaginal sensitivity was investigated in a group of 60 volunteers by means of an electric stimulus and under nonerotic conditions. In comparison to the dorsum of the hand, the genital area has a low sensitivity for electric stimuli (p less than 0.001). Of the genital area, the vaginal wall measured 2 to 4 cm from the vaginal introitus was found to be very insensitive (p less than 0.05). Within the vaginal wall a relatively sensitive position to electric stimuli could be detected at the "12-hr position" (the anterior vaginal wall) (p less than 0.001). The study provides data underscoring previous anatomical and clinical research findings regarding the sensitivity of the anterior vaginal wall. The inefficiency of coitus for inducing female orgasm is discussed.


Synthesis and spectral characterization of ternary mixed-vanadyl β-diketonate complexes with Schiff bases.
A new method to synthesize some mononuclear ternary oxovanadium(IV) complexes of the general formula [VO(β-dike)(SB)] (where Hβ-dike=acetylacetone; benzoylacetone or dibenzoylmethane, HSB=Schiff bases) has been explored by stepwise substitutions of acetylacetonate ion of VO(acac)(2) with Schiff bases. The substituted acetylacetone could be fractionated out with p-xylene as an azeotrope. The complexes were characterized by elemental analyses, molecular weight determinations, spectral (electronic, infrared, (1)H NMR, EPR and powder XRD) studies, magnetic susceptibility measurements and cyclic voltammetry. Molar conductance measurements indicated the complexes to be non-electrolytes in nitrobenzene. Bidentate chelating nature of β-diketones and Schiff base anions in the complexes was established by infrared and NMR spectra. Molecular weight determinations confirmed mononuclear nature of the complexes. The EPR spectra illustrated coupling of the unpaired electron with (51)V nucleus (I=7/2). Cyclic voltammograms of all the complexes displayed two-step oxidation processes. The oxidation peak potential corresponded to the quasireversible one-electron oxidation process of the metal center, yielding V(V) species. Transmission electron microscopy (TEM) indicated spherical particles of ∼200 nm diameter. The synthesized complexes are mixed-ligand complexes showing a considerable hydrolytic stability in which vanadium is having coordination number 5. A square pyramidal geometry around vanadium has been assigned in all the complexes.


N-cadherin adherens junctions mediate osteogenesis through PI3K signaling.
During endochondral ossification, the cartilage is surrounded by a layer of cells that constitute the perichondrium. Communication between osteoblasts in the perichondrium via N-cadherin adherens junctions is essential for endochondral bone growth. We observed that adherens junction molecule N-cadherin and its interacting partners p120, β-catenin and PTEN are expressed by cells present in the perichondrium. To study if N-cadherin mediated adherens junctions play a role in mediating signal transduction events during bone development, we utilized MC3T3E1 preosteoblasts plated at sub confluent (low) and confluent (high) densities to mimic adherens junction formation. When MC3T3E1 cells were plated at high density we observed an increase in phosphorylation of AKTSer473 and its downstream target GSK3Ser9, which coincided with an increase in Osterix, Osteomodulin and Osteoglycin gene expression. Using immunofluorescence, we identified N-cadherin, p120 and β-catenin localized at the membrane of MC3T3E1 cells. Treatment of confluent MC3T3E1 cells with an N-cadherin junction inhibitor-EGTA and a PI3K inhibitor LY294002 resulted in reduction of phosphorylation levels of AKT and GSK3 and expression of Osterix, Osteomodulin and Osteoglycin. Furthermore, utilizing an N-cadherin blocking antibody resulted in reduced AKT signaling and Osterix gene expression, suggesting that osteoblast junction formation is linked to activation of PI3K signaling, which leads to osteoblast differentiation. To further explore the strength of this linkage, we utilized a conditional knockout approach using Dermo1cre to delete β-catenin and PTEN, two important proteins known to be essential for adherens junctions and PI3K signaling, respectively. In the absence of β-catenin, we observed a decrease in adherens junctions and AKT signaling in the perichondrium. PTEN deletion, on the other hand, increased the number of cells expressing N-cadherin in the perichondrium. These observations show that N-cadherin mediated junctions between osteoblasts are needed for osteoblast gene transcription.


Damage analysis of a perfect broadband absorber by a femtosecond laser.
Plasmonic metamaterial absorbers are particularly important in different applications such as photodetectors, microbolometers and solar cells. In this paper, we propose a tungsten boride (WB, a refractory ceramic) based broadband metamaterial absorber whose optical properties is numerically analyzed and experimentally characterized. We have also analyzed the damage characteristics of this absorber using a femtosecond laser and compared with an ordinary Au metamaterial absorber. We observe that WB has almost the double absorption bandwidth with absorption more than 90% over the spectral range of 950 to 1400 nm when compared with the Au counterpart. Furthermore, we show that Au metamaterial is damaged at the power of around 36.4 mW whereas WB metamaterial is not damaged at that power (WB has high Tammann temperature than Au)-however the atom of WB material was knocked off by the bombardment of a femtosecond laser.


Mental health services in Israel: current state and future directions.
This paper reviews the current state of Israel's mental health system during a period when it may be possible to bring about significant change. It analyses its strengths and weaknesses, including the heavy influence of the psychiatric hospital and the lack of necessary community programs. The author stresses the need for an integrated planning process, based upon a vision of what the mental health system should look like and who it should be serving, and discusses how this process could occur.


Right heart thrombus in transit and peripherally inserted central catheters.
Right heart thrombus in transit or "free-floating right heart thrombus" is defined as thrombus(i) arising from the deep veins that embolises to the right atrium or right ventricle before reaching the pulmonary vasculature. It is almost always associated with pulmonary thromboembolism and is a medical emergency with reported mortality rates of over 40%. We present two cases of right heart thrombus in transit with pulmonary thromboembolism resulting from venous thrombosis associated with peripherally inserted central catheters that were managed with different approaches. The cases highlight that clinicians should have a low threshold to utilise imaging modalities such as computerised tomography and transthoracic echocardiography when there is an untoward change in physiological parameters among patients with peripherally inserted central catheters, particularly those with risk factors for peripherally inserted central catheter associated venous thrombosis. Furthermore, procedural optimisation surrounding peripherally inserted central catheters, such as insertion technique and choice of lumen size, is underscored.


Radiology as a Specialty in the Era of Artificial Intelligence: A Systematic Review and Meta-analysis on Medical Students, Radiology Trainees, and Radiologists.
Artificial intelligence (AI) is changing radiology by automating tasks and assisting in abnormality detection and understanding perceptions of medical students, radiology trainees, and radiologists is vital for preparing them for AI integration in radiology. A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, and Web of Science were searched up to March 5, 2023. Eligible studies reporting outcomes of interest were included, and relevant data were extracted and analyzed using STATA software version 17.0. A meta-analysis of 21 studies revealed that 22.36% of individuals were less likely to choose radiology as a career due to concerns about advances in AI. Medical students showed higher rates of concern (31.94%) compared to radiology trainees and radiologists (9.16%) (P < .01). Radiology trainees and radiologists also demonstrated higher basic AI knowledge (71.84% vs 35.38%). Medical students had higher rates of belief that AI poses a threat to the radiology job market (42.66% vs 6.25%, P < .02). The pooled rate of respondents who believed that "AI will revolutionize radiology in the future" was 79.48%, with no significant differences based on participants' positions. The pooled rate of responders who believed in the integration of AI in medical curricula was 81.75% among radiology trainees and radiologists and 70.23% among medical students. The study revealed growing concerns regarding the impact of AI in radiology, particularly among medical students, which can be addressed by revamping education, providing direct AI experience, addressing limitations, and emphasizing medico-legal issues to prepare for AI integration in radiology.


Biological predictors of radiosensitivity in head and neck squamous cell carcinoma.
The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation. The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed. Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis. P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation. The findings may improve patient-specific therapy according to individual tumor characteristics.


Psychoanalytical concepts of epilepsy.
As part of the anniversary issue of Epilepsy & Behavior looking back as aspects of the history of epilepsy, this article reviews psychoanalytical concepts of the pathogenesis of seizures and the so-called epileptic personality (epileptic constitution). It addresses the question whether these theories are completely invalid or do they have insights that are worth rediscovering. Special Issue: Epilepsy & Behavior's 20th Anniversary.


Metformin therapy and kidney disease: a review of guidelines and proposals for metformin withdrawal around the world.
We compared and contrasted guidelines on metformin treatment in patients with chronic kidney disease (CKD) around the world, with the aim of helping physicians to refine their analysis of the available evidence before deciding whether to continue or withdraw this drug. We performed a systematic research for metformin contraindications in: (i) official documents from the world's 20 most populated countries and the 20 most scientifically productive countries in the field of diabetology and (ii) publications referenced in electronic databases from 1990 onwards. We identified three international guidelines, 31 national guidelines, and 20 proposals in the scientific literature. The criteria for metformin withdrawal were (i) mainly qualitative in the most populated countries; (ii) mainly quantitative in the most scientifically productive countries (with, in all cases, a suggested threshold for withdrawing metformin); and (iii) quantitative in all, but one of the literature proposals, with a threshold for withdrawal in most cases (n = 17) and/or adjustment of the metformin dose as a function of renal status (n = 8). There was a good degree of consensus on serum creatinine thresholds; whereas guidelines based on estimated glomerular filtration rate thresholds varied from 60 mL/minute/1.73 m(2) up to stage 5 CKD. Only one of the proposals has been tested in a prospective study. In general, proposals for continuing or stopping metformin therapy in CKD involve a threshold (whether based on serum creatinine or estimated glomerular filtration rate) rather than the dose adjustment as a function of renal status (in stable patients) performed for other drugs excreted by the kidney.


Care planning with the electronic patient record.
Developing the electronic patient record is a key component of future national health strategy. This article focuses on the development of electronic patient care plans as a part of a wider electronic record within University College London Hospitals NHS Foundation Trust.


Light microscopic histochemical detection of terminal galactose and N-acetylgalactosamine residues in rodent complex carbohydrates using a galactose oxidase--Schiff sequence and peanut lectin--horseradish peroxidase conjugate.
A technique was investigated for the direct visualization on paraffin sections of galactose and N-acetylgalactosamine residues terminating saccharide chains in complex carbohydrates. Sections were incubated with the enzyme galactose oxidase (GO), which oxidizes the C-6 hydroxyl of galactose or N-acetylgalactosamine (GalNAc) residues, and the resulting aldehyde was visualized by its reaction with Schiff's reagent. Submaxillary and sublingual glands, pancreas, stomach, duodenum, and ileum from mice and rats were stained with the GO-Schiff sequence and results were compared with staining by a peanut lectin-horseradish peroxidase (PL-HRP) conjugate that binds selectively to terminal galactose and preferentially to the terminal dimer beta-D-Gal-(1 leads to 3)-D-GalNAc. Three classes of reactive sites were revealed: 1) those reactive with both GO-Schiff and PL-HRP, 2) those stained with the GO-Schiff sequence but unreactive with PL-HRP, and 3) those GO-Schiff unreactive but PL-HRP positive. Based on the carbohydrate binding specificity of GO and PL, it is suggested that tissue complex carbohydrates in group one contain terminal beta-galactose residues with unmodified hydroxyls at C-2, C-4, and C-6, whereas those in group two contain terminal GalNAc residues. The structure of oligosaccharides in group 3 sites remains enigmatic.


Surveillance and treatment of dyslipidemia in the post-infarct patient: can a nurse-led management approach make a difference?
Lowering plasma lipid levels in patients in the months following hospital discharge for a myocardial infarction (MI) is clearly beneficial if recurrent cardiac events and mortality are to be prevented; traditionally, however, there has been a large gap between guidelines and levels achieved in routine practice. A randomized, open-label clinical trial was conducted to assess the impact of nurse-centred surveillance and treatment in achieving nationally recognized lipid targets in post-MI patients. This program had the following features: systematic telephone follow-up of patients discharged from the University of Sherbrooke (Sherbrooke, Quebec) after an MI; systematic lipid testing three months after discharge; close liaison with, and guidance of, patients' primary care physicians to intervene on results of this test if targets were not obtained; and continued monitoring of patients until lipid profiles consistent with consensus targets were achieved. The impact of this approach was tested and compared with that of a control group that continued to be followed by a primary care physician for up to 18 months. A total of 127 patients were randomly assigned into an intervention group (n=64) or a control group (n=63). The intervention group was followed by telephone for an average (+/-SD) of 4.4+/-2.0 months post-MI. At this point, when intervention was optimized, the mean low-density lipoprotein cholesterol (LDL-C) level was 2.19+/-0.65 mmol/L in the intervention group, and 87.3% of patients had LDL-C levels of less than 2.5 mmol/L. Patients from both experimental groups returned at 12 months and 18 months post-MI for a new blood lipid assessment. In total, 12.5% of patients in each group were lost to follow-up. At 12 months and 18 months, the mean LDL-C level was not different between the two groups, nor was there a significant difference in the proportion of patients achieving LDL-C levels of less than 2.5 mmol/L (51.6% in the intervention group and 65% in the control group at 18 months; P>0.05). When the combined end point of an LDL-C level of less than 2.5 mmol/L, a triglyceride level of less than 2.0 mmol/L and a total cholesterol to high-density lipoprotein cholesterol ratio of less than 4.0 was considered, the proportion of patients achieving this composite at 18 months was low and not different between the two groups (23.4% in the intervention group and 38.3% in the control group; P>0.05). Over 95% of patients in both groups were on a lipid-lowering medication, and more than 90% had complied with their medication regimen at 18 months. This trial did not support the role of nurse-managers and a system of telephone-based contacts to ensure the continuity of care and aggressive intervention when considering cardiovascular risk factors in post-MI patients. This trial also re-emphasized the important remaining treatment gap in secondary prevention of coronary artery disease, particularly if composite lipid end points are to be targeted.


The fate of unrevised stenoses in infrainguinal autologous vein grafts as detected by intraoperative duplex scanning.
Intraoperative infrainguinal autologous vein graft stenoses are common, and some authors advise revision of these stenoses. But the natural history of these lesions is not clear. This study was undertaken to determine the natural history of duplex-detected intraoperative stenoses with a nonrevision policy. Intraoperative duplex scanning was performed in 46 infrainguinal autologous vein bypasses. The surgeon was blinded for the results of the intraoperative duplex scan and no intraoperative graft revision or modification of the routine postoperative protocol was performed after the duplex scan. Intraoperative duplex parameters and patient and bypass characteristics were correlated with the occurrence of an early graft event (occlusion or revision of a patent graft within 6 weeks postoperatively), which was the study's primary endpoint. Early graft event rate was 37% (17/46). PSV ratio and PSV-max were the only parameters with a significant correlation with the occurrence of an early graft event. An intraoperatively measured PSV ratio of > or =3.0 was the best predictor of an early graft failure with a sensitivity of 71% (95% CI: 50-83%) and a specificity of 90% (95% CI: 78-97%). In 12 of the 15 (80%) grafts matching this criterion an early graft event occurred, while only 5 (16%) early graft events occurred in the remaining 31 grafts (ie, a negative predictive value of 84%). When a PSV ratio of > or =3.0 was used as a cutoff value to predict early postoperative graft events, the likelihood ratios for a positive and negative test result were respectively 6.82 (95% CI: 2.23-20.8) and 0.33 (95% CI: 0.16-0.69). Unrevised intraoperative duplex-detected stenoses in infrainguinal autologous vein graft stenoses are a serious threat to early graft patency. The presence of an intraoperatively detected graft stenosis with a PSV ratio > or =3.0 is a strong predictor of early graft failure.


Effect of pretreatment of food gluten with prolyl endopeptidase on gluten-induced malabsorption in celiac sprue.
We sought to determine whether prolyl endopeptidase (PEP) treatment of food gluten would obviate the intestinal dysfunction produced by small amounts of dietary gluten supplement in patients with celiac sprue. Twenty asymptomatic patients with histologically proven celiac sprue completed a randomized, double-blind, cross-over study involving two 14-day stages. Each patient consumed a low dose of a gluten supplement daily (5 g; equivalent to 1 slice of bread) in 1 stage and gluten pretreated with PEP in the other stage. Patients completed a daily symptom questionnaire and a D-xylose urine excretion and a 72-hour quantitative fecal fat were monitored before and after each stage. Despite clinical remission at baseline, 40% of patients had at least 1 abnormal celiac antibody, 20% had an abnormal urine xylose, and 63% had an abnormal fecal fat test result. There was no difference in symptoms as a function of the type of gluten consumed. In response to gluten not treated with PEP, an appreciable proportion of patients developed malabsorption of fat (7 of 17, 41%) or xylose (8 of 14, 57%). When the gluten was pretreated with PEP, fat malabsorption was avoided in 5 of 7 and xylose malabsorption in 4 of 8 of these same patients. A significant proportion of asymptomatic patients with celiac sprue have abnormal celiac antibodies and fat or carbohydrate malabsorption. Pretreatment of gluten with PEP avoided the development of fat or carbohydrate malabsorption in the majority of those patients who developed fat or carbohydrate malabsorption after a 2-week gluten challenge.


Management of recurrent ileocolic intussusception.
The aims of this study were to evaluate the need for surgical intervention for patients with recurrent ileocolic intussusception (RICI), especially for multiple recurrences, and to investigate whether early and late recurrence patterns were associated with surgery. Patients with ileocolic intussusception (ICI) during the years 2007-2019 were included. Demographic data, recurrences, and outcomes were analyzed. Early RICI was defined as recurrence within 48 h. Overall, 604 episodes of ICI were confirmed in 491 patients. The recurrence rate was 13.8%, with 113 episodes in 68 patients. There were no statistically significant differences in age, reduction success rate, operation, or pathological lead points (PLPs) between the recurrence and non-recurrence groups. There was no significant association between the number of recurrences and the presence of a PLP or between the number of recurrences and whether the recurrences were early or late. The presence of PLPs was not significantly associated with age or recurrence, but the reduction success rate was significantly lower (P < 0.001). Each recurrence should be managed as a first episode, regardless of early or late recurrence. Operative reduction should be considered when nonoperative reduction fails, a PLP is suspected, or there are signs of peritonitis. Treatment Study. Level III.


Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system.
Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society.


Human brain sulphotransferase and glucuronyltransferase.
The activities of cytosolic sulphotransferase (ST) and microsomal glucuronyltransferase (GT) were measured with 1-naphthol as the substrate in three frontal cortex, three temporal cortex, one parietal cortex, one occipital cortex and two cerebellar cortex specimens from human brain. The average activity was 11.7 +/- 4.2 pmol/min/mg protein/(ST) and 26.8 +/- 13.6 pmol/min/mg protein (GT). The kinetics of ST were studied varying the concentration of 1-naphthol in five brain specimens (temporal cortex, temporal subcortex, occipital cortex, cerebellum cortex and frontal cortex) whereas those of GT were studied in a sample obtained by pooling the microsomal fractions from the following eight brain tissues: one frontal cortex, four temporal cortex, one parietal cortex and two cerebellar cortex specimens. The Km of the first and second enzyme was 1.55 +/- 0.47 microM (mean +/- s.d.) and 121 microM, respectively. The Vmax values were 13.70 +/- 8.16 (mean +/- s.d.) pmol/min/mg protein (ST) and 103 pmol/min/mg protein (GT). Vmax/Km was ten times higher for ST than GT. These data suggest that ST is the predominant pathway at low concentrations of 1-naphthol whereas at higher concentrations, GT becomes the predominant pathway.


'Virtual pivot point' in human walking: Always experimentally observed but simulations suggest it may not be necessary for stability.
The intersection of ground reaction forces near a point above the center of mass has been observed in computer simulation models and human walking experiments. Observed so ubiquitously, the intersection point (IP) is commonly assumed to provide postural stability for bipedal walking. In this study, we challenge this assumption by questioning if walking without an IP is possible. Deriving gaits with a neuromuscular reflex model through multi-stage optimization, we found stable walking patterns that show no signs of the IP-typical intersection of ground reaction forces. The non-IP gaits found are stable and successfully rejected step-down perturbations, which indicates that an IP is not necessary for locomotion robustness or postural stability. A collision-based analysis shows that non-IP gaits feature center of mass (CoM) dynamics with vectors of the CoM velocity and ground reaction force increasingly opposing each other, indicating an increased mechanical cost of transport. Although our computer simulation results have yet to be confirmed through experimental studies, they already indicate that the role of the IP in postural stability should be further investigated. Moreover, our observations on the CoM dynamics and gait efficiency suggest that the IP may have an alternative or additional function that should be considered.


Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro.
Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs.


Hierarchical organization of axis I psychiatric disorder comorbidity through age 30.
Hierarchical models of psychopathology based on substantial numbers of lifetime diagnostic categories have not been sufficiently evaluated, even though such models have relevance for theories of disorder etiology, course, or prognosis. In this research, a hierarchical component model of 16 Axis I disorders is derived, and model elements are evaluated in terms of their ability to demonstrate distinct associations with several clinically-relevant variables. Participants were 816 randomly selected adolescents from the community who were repeatedly assessed for psychiatric disorders and associated risk and protective factors over a 14-year period. First-degree relatives were also interviewed to establish their lifetime psychiatric history. Patterns of lifetime comorbidity among 16 psychiatric disorders were described at five levels of organization. In addition to the broadest level that accounted for the most variance in disorder covariation, evidence was obtained at successive levels in the hierarchy for internalizing and externalizing broad-band domains that could be subdivided into more refined clusters. The validity and potential utility of the resultant hierarchical model were further supported by distinct associations that components at each level had with exposure to childhood adversities, psychiatric disorders among first-degree relatives, and psychosocial functioning at ~age 30. A large number of DSM Axis I disorders can be described within broad-band internalizing and externalizing domains, and further differentiation within these domains is possible and likely useful for some purposes. Implications of this research for conceptualizing relations among psychiatric disorders are discussed.


Trichobilharzia mergi sp. nov. (Trematoda: Digenea: Schistosomatidae), a visceral schistosome of Mergus serrator (L.) (Aves: Anatidae).
Parasitological investigations on red-breasted mergansers (Mergus serrator L.) in Iceland revealed digenean flukes of the family Schistosomatidae. Adult worms were detected in blood vessels of the large intestine and eggs were deposited in the mucosa and surrounded by granulomatous reactions. Traditional morphological methods showed that the flukes have very slender filiform bodies, males are equipped with a short gynaecophoric canal and both suckers and spatulate ends are present on each sex. Among characteristics of the flukes which render them morphologically distinct from other Trichobilharzia species are: i) males-well developed vesicula seminalis (v.s.) consisting of a short v.s. externa and a significantly longer (approx. 3 times) v.s. interna, unusually well developed genital papilla and localization of the first testis a relatively long distance posterior to the gynaecophoric canal; ii) eggs-small and elongated with slightly rounded poles and a short terminal spine. DNA taxonomic techniques confirmed that a new species had been identified, Trichobilharzia mergi sp. n. The sequence data were deposited in GenBank under the accession numbers JX456151 to JX456172. Comparison of the results with our previously published data on characterization of DNA of cercariae isolated from freshwater lymnaeid snails showed that larval development of T. mergi is associated with Radix balthica L. (=Radix peregra Müller, 1774;=Radix ovata Draparnaud, 1805).


Characterization of dihydrofolate reductase genes from trimethoprim-susceptible and trimethoprim-resistant strains of Enterococcus faecalis.
Enterococci are usually susceptible in vitro to trimethoprim; however, high-level resistance (HLR) (MICs, >1,024 microg/ml) has been reported. We studied Enterococcus faecalis DEL, for which the trimethoprim MIC was >1,024 microg/ml. No transfer of resistance was achieved by broth or filter matings. Two different genes that conferred trimethoprim resistance when they were cloned in Escherichia coli (MICs, 128 and >1,024 microg/ml) were studied. One gene that coded for a polypeptide of 165 amino acids (MIC, 128 microg/ml for E. coli) was identical to dfr homologs that we cloned from a trimethoprim-susceptible E. faecalis strain, and it is presumed to be the intrinsic E. faecalis dfr gene (which causes resistance in E. coli when cloned in multiple copies); this gene was designated dfrE. The nucleotide sequence 5' to this dfr gene showed similarity to thymidylate synthetase genes, suggesting that the dfr and thy genes from E. faecalis are located in tandem. The E. faecalis gene that conferred HLR to trimethoprim in E. coli, designated dfrF, codes for a predicted polypeptide of 165 amino acids with 38 to 64% similarity with other dihydrofolate reductases from gram-positive and gram-negative organisms. The nucleotide sequence 5' to dfrF did not show similarity to the thy sequences. A DNA probe for dfrF hybridized under high-stringency conditions only to colony lysates of enterococci for which the trimethoprim MIC was >1,024 microg/ml; there was no hybridization to plasmid DNA from the strain of origin. To confirm that this gene causes trimethoprim resistance in enterococci, we cloned it into the integrative vector pAT113 and electroporated it into RH110 (E. faecalis OG1RF::Tn916DeltaEm) (trimethoprim MIC, 0.5 microg/ml), which resulted in RH110 derivatives for which the trimethoprim MIC was >1, 024 microg/ml. These results indicate that dfrF is an acquired but probably chromosomally located gene which is responsible for in vitro HLR to trimethoprim in E. faecalis.


[The induction of stomach cancer in monkeys with N-methyl-N'-nitro-N-nitrosoguanidine].
Gastric tumors were detected in 2 out of 9 apes following MNNG treatment with a total dose of 800-848 mg/kg (40 mg/kg, thrice a month, 49-50 weeks, via gastric probe). The characteristics, course, symptoms and histologic patterns of the tumors proved comparable with similar neoplasms in humans.


Analytical and biological evaluation of high throughput screen actives using evaporative light scattering, chemiluminescent nitrogen detection, and accurate mass LC-MS-MS.
In this investigation the utility of evaporative light scattering detection (ELSD) combined with HPLC-MS was demonstrated as a key component of a bioassay-guided fractionation, or "biofractionation" technique, for the evaluation of high throughput screen actives. ELSD provided on-line analyte mass information that was critical for the classification of the samples. Chemiluminescent nitrogen detection (CLND) was also evaluated for sample concentration estimation for nitrogen-containing compounds, and accurate mass LC-MS-MS analysis was employed for rapid structural confirmation and elucidation of components previously identified as active via biofractionation.


[The correlation between radiological and haemodynamic pictures in the diagnosis of pulmonary hypertension in chronic obstructive diseases (author's transl)].
A comparison between the radiographical findings and the haemodynamic data was made in 53 cases of chronic bronchial obstruction. The results were used in an assessment of the reliability of standard chest X-rays in the diagnosis of pulmonary hypertension. Reference is also made to quantitative indices. Several cases are presented by way of example.


Sepsis-associated pulmonary complications in emergency department patients monitored with serial lactate: An observational cohort study.
Patients with severe sepsis and septic shock are at high risk for development of pulmonary complications, including acute respiratory distress syndrome (ARDS). Serial lactate monitoring is a useful tool to gauge global tissue hypoxia in emergency department (ED) patients with sepsis. We hypothesized that patients undergoing serial lactate monitoring (SL) would demonstrate a decreased incidence of pulmonary complications. This is a retrospective observational cohort study of adult severe sepsis and septic shock patients with elevated lactate presenting to a large academic ED. A total of 243 patients were assigned to SL (n=132) or no serial lactate monitoring (NL; n=111). The primary outcome was a composite of pulmonary complications: (1) ARDS development and (2) respiratory failure. Twenty-eight patients (21%) in the SL group and 37 patients (33%) in the NL group developed the primary outcome (P=.03). Multivariate analysis demonstrated an association between the NL group and development of pulmonary complications (adjusted odds ratio [aOR], 2.1; confidence interval [CI], 1.15-3.78). Emergency department mechanical ventilation was independently associated with development of ARDS (aOR, 3.5; 1.8-7.0). In the a priori subgroup of patients mechanically ventilated in the ED (n=97), those who developed ARDS received higher tidal volumes compared to patients who did not develop ARDS (8.7 mL/kg predicted body weight [interquartile range, 7.6-9.5] vs 7.6 [interquartile range, 6.8-9.0]; P<.01). Serial lactate monitoring is associated with a decrease in major pulmonary complications in severe sepsis and septic shock. Acute respiratory distress syndrome incidence is also influenced by ED-based mechanical ventilation. These results provide 2 potentially modifiable variables to be targeted in future studies to prevent pulmonary complications in this patient subset.


Glottic and supraglottic carcinoma: a retrospective comparison of radiotherapy alone with sandwich therapy in 366 patients.
From 1971 through 1982, 442 patients with laryngeal carcinoma were seen at the Leiden University Hospital. They were treated either with radiotherapy alone, sandwich therapy (pre- and postoperative radiotherapy) or by surgery followed by postoperative irradiation. Three hundred and sixty-six patients with glottic or supraglottic tumours could be analysed with respect to two different treatments, complications of treatment and some prognostic factors. Two endpoints of analysis were used: disease-free interval and survival to cancer death. In patients with glottic or supraglottic carcinoma, the survival of patients with advanced disease, treated with radiotherapy only, was worse as compared to the survival of the same category of patients who were treated with sandwich therapy (p less than 0.005). In patients with small glottic tumours, radiotherapy alone was mostly used. In small supraglottic tumours, the survival with both therapy policies was equal. Persistent hoarseness in patients with small glottic tumours, treated with radiotherapy only, is of predictive value for the development of a recurrence (p less than 0.001). There was no influence on prognosis of histological differentiation of the tumour. It appeared that interruption of radiotherapy for more than two days had an adverse effect on survival in patients with glottic carcinoma (p = 0.0001). Finally, the occurrence of second malignancies was analysed. It was found that 19% had a second malignancy. Almost 60% of them were lung cancers.