Sterile Inflammation and Degradation Systems in Heart Failure.
In most patients with chronic heart failure (HF), levels of circulating cytokines are elevated and the elevated cytokine levels correlate with the severity of HF and prognosis. Various stresses induce subcellular component abnormalities, such as mitochondrial damage. Damaged mitochondria induce accumulation of reactive oxygen species and apoptogenic proteins, and subcellular inflammation. The vicious cycle of subcellular component abnormalities, inflammatory cell infiltration and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in cardiac dysfunction and HF. Quality control mechanisms at both the protein and organelle levels, such as elimination of apoptogenic proteins and damaged mitochondria, maintain cellular homeostasis. An imbalance between protein synthesis and degradation is likely to result in cellular dysfunction and disease. Three major protein degradation systems have been identified, namely the cysteine protease system, autophagy, and the ubiquitin proteasome system. Autophagy was initially believed to be a non-selective process. However, recent studies have described the process of selective mitochondrial autophagy, known as mitophagy. Elimination of damaged mitochondria by autophagy is important for maintenance of cellular homeostasis. DNA and RNA degradation systems also play a critical role in regulating inflammation and maintaining cellular homeostasis mediated by damaged DNA clearance and post-transcriptional regulation, respectively. This review discusses some recent advances in understanding the role of sterile inflammation and degradation systems in HF.


Molecular epidemiology of imported cases of leishmaniasis in Australia from 2008 to 2014.
Leishmaniasis is a vector borne disease caused by protozoa of the genus Leishmania. Human leishmaniasis is not endemic in Australia though imported cases are regularly encountered. This study aimed to provide an update on the molecular epidemiology of imported leishmaniasis in Australia. Of a total of 206 biopsies and bone marrow specimens submitted to St Vincent's Hospital Sydney for leishmaniasis diagnosis by PCR, 55 were found to be positive for Leishmania DNA. All PCR products were subjected to restriction fragment length polymorphism analysis for identification of the causative species. Five Leishmania species/species complexes were identified with Leishmania tropica being the most common (30/55). Travel or prior residence in a Leishmania endemic region was the most common route of acquisition with ~47% of patients having lived in or travelled to Afghanistan. Cutaneous leishmaniasis was the most common manifestation (94%) with only 3 cases of visceral leishmaniasis and no cases of mucocutaneous leishmaniasis encountered. This report indicates that imported leishmaniasis is becoming increasingly common in Australia due to an increase in global travel and immigration. As such, Australian clinicians must be made aware of this trend and consider leishmaniasis in patients with suspicious symptoms and a history of travel in endemic areas. This study also discusses the recent identification of a unique Leishmania species found in native kangaroos and a potential vector host which could create the opportunity for the establishment of a local transmission cycle within humans.


Development of a Radiographic Index for Periodontitis.
The use of radiographic indices is noticeably diminished due to the lack of simplicity and standardisation among the existing ones. The aim of this study was to introduce a radiographic index to aid clinicians in determining the extent and severity of interproximal alveolar bone loss (iABL), in relation to individual root lengths, among patients suffering from periodontitis. A retrospective analysis of 50 anonymised dental panoramic tomograms (DPTs) of patients with periodontitis was conducted. Visual interpretation of iABL was recorded by a single investigator and by 20 volunteering clinicians for the 'worst site' in each quintet. Results were compared to a gold standard quantification method. Intra-examiner and inter-examiner agreement were measured using the Kappa coefficient and the intra-class correlation coefficient, respectively. Validity was assessed using Cramér's V test. The mean intra-examiner agreement on the severity and pattern of iABL was 0.808 (K) and 0.802 (K), respectively. A stronger overall inter-examiner agreement was noted when the severity in contrast to the pattern of iABL and presence/absence of furcation involvement were analysed. The statistically significant total mean agreement values from this correlation coefficient were 0.892 and 0.739, respectively. A very strong association between all the visual interpretations carried out by all participants and the gold standard measurements was evident. Within the limitations of this study, the proposed radiographic index may serve as a simple, yet valid and reliable, adjunctive screening tool to further assist clinicians in determining the extent and severity of iABL in patients with periodontitis.


Instability of the Vertebrae Remains following Balloon Kyphoplasty.
Study Design Retrospective cohort study. Objectives The mechanism underlying the pain relief observed following balloon kyphoplasty (BKP) to vertebral compression fractures is reported to involve stabilization of the fractured vertebrae. However, whether fixation of the vertebrae was achieved immediately after BKP has not been investigated. The purpose of this study was to assess fixation of the vertebrae immediately after BKP and whether the instability was related to visual analog scale (VAS) scores. Methods Thirty-eight patients with vertebrae that were evaluated on lateral roentgenkymography within 1 week after BKP were recruited. Instability was defined as a cleft observed between the cement and end plate of the vertebra in the supine position that disappeared in the sitting position, and the posterior wall height of the vertebra was reduced in the sitting position. Results Instability of the vertebrae immediately after BKP was observed in 17 cases. VAS scores improved in all cases, and no significant differences were observed with or without instability. Conclusions The mechanism of rapid pain relief following BKP was not strong fixation but some degree of stabilization or other factors. We suggest that more research is needed about the mechanism of pain relief following BKP in the future.


Treatment of word retrieval deficits in aphasia. A comparison of two therapy methods.
The effects of two therapy methods in the treatment of picture naming problems are compared, using a within-patient design with 12 adult patients with chronic acquired aphasia. We contrast techniques that require the patient to process the meaning corresponding to the picture name (semantic treatment) with those that provide the patients with information about the phonological form of the name (phonological treatment). With each method, patients either had 4 sessions of treatment over one week, or 8 sessions over two weeks. Both methods caused day-by-day improvement that was specific to the actual items treated. Both methods resulted in significant improvement in naming when this was measured one week after the end of treatment, with a small, but significant advantage for the semantic treatment; this is mainly due to improvement that generalizes to untreated items. We conclude that specific and theoretically motivated treatment methods can cause significant improvement in the word retrieval ability of patients with chronic aphasia.


Could flank pain be an indicator of COVID-19 infection?
We describe the incidental detection of patients infiltrates due to COVID-19 in lung basal sections in patients undergoing abdominal computed tomography (CT) with flank pain attending the urology outpatient clinic during the current pandemic. We retrospectively analysed 276 patients admitted to the Siirt Training and Research Hospital Urology outpatients clinic between 15 March 2020 and 9 August 2020 with a complaint of flank pain and undergoing non-contrast abdominal CT. A total of 10 patients with COVID-19 compatible findings in CT were defined as the study group. A control group was formed from 10 patients with only urological pathologies (kidney stones, ureteral stones, and hydronephrosis) without a COVID-19 compatible appearance on CT. Ten (3.6 %) patients were identified with COVID-19 and pneumonic infiltrations in the basal regions of the lungs; diagnosis was made by cross-sectional abdominal CT. The visual analog scale (VAS) score of flank pain was significantly higher in the control group (p<0.001); these subjects had urological pathology and no evidence of COVID-19 in the basal regions of the lungs on abdominal CT. There were no signs of COVID-19 disease detected during the admissions procedure in the urology outpatient clinic, including fever, cough, and shortness of breath. During the COVID-19 pandemic, it is important to consider a diagnosis of COVID_19 in patients reporting non-severe flank pain if no urological pathology is evident on abdominal CT scans.


[Formula: see text]-linear resistivity from magneto-elastic scattering: Application to PdCrO2.
An electronic solid with itinerant carriers and localized magnetic moments represents a paradigmatic strongly correlated system. The electrical transport properties associated with the itinerant carriers, as they scatter off these local moments, have been scrutinized across a number of materials. Here, we analyze the transport characteristics associated with ultraclean PdCrO[Formula: see text]-a quasi-two-dimensional material consisting of alternating layers of itinerant Pd-electrons and Mott-insulating CrO[Formula: see text] layers-which shows a pronounced regime of T-linear resistivity over a wide range of intermediate temperatures. By contrasting these observations to the transport properties in a closely related material PdCoO[Formula: see text], where the CoO[Formula: see text] layers are band-insulators, we can rule out the traditional electron-phonon interactions as being responsible for this interesting regime. We propose a previously ignored electron-magneto-elastic interaction between the Pd-electrons, the Cr local moments and an out-of-plane phonon as the main scattering mechanism that leads to the significant enhancement of resistivity and a T-linear regime in PdCrO[Formula: see text] at temperatures far in excess of the magnetic ordering temperature. We suggest a number of future experiments to confirm this picture in PdCrO[Formula: see text] as well as other layered metallic/Mott-insulating materials.


miRNA-143 expression is associated with inflammation and time of exposure to amniotic fluid in experimental gastroschisis.
Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.


Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development.
MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) are protein-serine/threonine kinases that are activated by ERK or p38 and phosphorylate eIF4E, which is involved in cap-dependent translation initiation. However, Mnk1/2 double knockout (Mnk-DKO) mice show normal cell growth and development despite an absence of eIF4E phosphorylation. Here we show that the tumorigenesis occurring in the Lck-Pten mouse model (referred to here as tPten(-/-) mice) can be suppressed by the loss of Mnk1/2. Phosphorylation of eIF4E was greatly enhanced in lymphomas of parental tPten(-/-) mice compared with lymphoid tissues of wild-type mice, but was totally absent in lymphomas of tPten(-/-); Mnk-DKO mice. Notably, stable knockdown of Mnk1 in the human glioma cell line U87MG resulted in dramatically decreased tumor formation when these cells were injected into athymic nude mice. Our data demonstrate an oncogenic role for Mnk1/2 in tumor development, and highlight these molecules as potential anticancer drug targets that could be inactivated with minimal side effects.


Myoblastoma. Equine granular cell tumor.
A unilateral pulmonary granular cell tumor occurred in a Thoroughbred mare with longstanding respiratory disease wrongly attributed to chronic obstructive pulmonary disease. The clinical features, radiology and endoscopic appearance permitted an accurate diagnosis, which was supported by subsequent necropsy and histologic examination. Obstructive pulmonary disease was ruled out after measurement of arterial blood gases and maximum intrathoracic pressure changes, and after microscopic examination of the lung.


Exploring cancer screening in the context of unmet mental health needs: a participatory pilot study.
Cancer is the leading cause of preventable death in the Bronx, New York. Service providers in this mental health provider shortage area identified untreated mental illness as an important barrier to participation in cancer screening, a finding that supports existing literature. The Mental Health and Cancer (MHC) Connection partnership formed to investigate and address this issue. We sought to use an ecological framework to examine barriers and facilitators to obtaining mental health services in the Bronx, and to explore how lack of access to mental healthcare affects cancer screening. In this community-based participatory research (CBPR)-driven pilot study, semistructured, qualitative interviews based on an ecological framework were conducted with 37 Bronx-based service providers representing a range of professional perspectives. Data were analyzed using thematic content analysis and techniques from grounded theory. Similar barriers and facilitators were reported for mental healthcare and cancer screening utilization across ecological levels. Providers emphasized the impact of urban poverty-related stressors on the mental health of their clients, and affirmed that mental health issues were a deterrent for cancer screening. They also recognized their own inability to connect clients effectively to cancer screening services, and rarely saw this as part of their present role. Findings highlight how unmet mental health needs can affect cancer screening in impoverished urban contexts. Participants recommended improving linkages across healthcare and social service providers to address mental health and cancer screening needs simultaneously. Study results are being used to plan a collaborative intervention in the Bronx through the MHC Connection partnership.


Damaged first permanent molar: how conservative can we be?
It is a fact reported in the literature that the first permanent molar is the most frequently decayed tooth. Our treatment choice is based mainly on two clinical criteria: the degree of coronal decay and the damage to the pulp tissue. In the absence of pulp tissue necrosis, the following therapeutic gradient: indirect pulp capping, direct pulp capping, partial pulpotomy, cameral pulpotomy should be implemented with the objective of maintaining pulp vitality regardless the degree of maturity of the molar. In the case of pulp tissue necrosis, if the tooth is immature, stopping root construction and apical closure requires an apexification or endodontic regeneration technique. The prognosis of these necrotic teeth remains uncertain in the medium and long term (risk of fractures). This raises the question of the indication for avulsion of the first permanent molar (FPM). The main objectives of this article are to present the means of conservation and their limits. The decision to retain a FPM is based on several criteria, including assessment of pulpal status (which remains problematic, especially on immature permanent teeth) and the feasibility of coronal restoration. The decision to retain or extract a FPM must be the subject of a multidisciplinary discussion between a paediatric dental surgeon and a specialist qualified in dentofacial orthopaedics.


[Sensitivity of nosocomial purulent-septic infection causative agents to disinfection agents and antibiotics].
Study the sensitivity of nosocomial purulent-septic infection (PSI) causative agents to disinfectants (DA) and antibiotics (AB). Sensitivity to DA and AB of 209 PSI causative agent strains isolated from patients and the environment of 2 obstetric and 3 surgical hospitals was studied in 2009-2011. Sensitivity to DA of 94 strains and to AB of 189 strains of Pseudomonas aeruginosa isolated from patients with signs of PSI of reanimation and intensive therapy and surgical departments of a multi-field hospital was studied in 2012. Sensitivity to DA was determined on test-surfaces and in solution according to guidelines by V.V. Shkarin et al., 2010; sensitivity to AB - by disc-diffusion method. Among PSI causative agents resistant to DA the portion of poly-antibiotic resistant strains is higher than among microorganisms sensitive to DA, and among antibiotic resistant bacteria the number of strains resistant to DA is higher than among sensitive to antibiotics. The increase of resistance to DA and AB of P. aeruginosa strains is observed in parallel to the increase of volume of the antibacterial preparations used. The results obtained give evidence of the possibility of formation of combined (associated) resistance to DA and AB by nosocomial PSI causative agents against the background of increase of their consumption.


Revealing the origins of vortex cavitation in a Venturi tube by high speed X-ray imaging.
Hydrodynamic cavitation is useful in many processing applications, for example, in chemical reactors, water treatment and biochemical engineering. An important type of hydrodynamic cavitation that occurs in a Venturi tube is vortex cavitation known to cause luminescence whose intensity is closely related to the size and number of cavitation events. However, the mechanistic origins of bubbles constituting vortex cavitation remains unclear, although it has been concluded that the pressure fields generated by the cavitation collapse strongly depends on the bubble geometry. The common view is that vortex cavitation consists of numerous small spherical bubbles. In the present paper, aspects of vortex cavitation arising in a Venturi tube were visualized using high-speed X-ray imaging at SPring-8 and European XFEL. It was discovered that vortex cavitation in a Venturi tube consisted of angulated rather than spherical bubbles. The tangential velocity of the surface of vortex cavitation was assessed considering the Rankine vortex model.


Unilateral Optic Neuropathy due to a Sphenoid Mucocoele.
Isolated sphenoid sinus mucocoeles are rare; whereas, benign lesions usually discovered incidentally. These may present with headache, diplopia, visual loss or ocular motor nerve palsies, due to slow expansion and mass effects. Prompt endoscopic removal is the key to prevent permanent sequelae. We present the case of a 63-year femele, who presented with sudden loss of vision of the left eye, along with periorbital and retrobulbar pain for the last one month. She was found to have "no light perception" vision in the left eye and optic atrophy. Neuroimaging was performed, which revealed a sphenoid sinus mucocoele, impinging on the left optic nerve. Our ENT Department performed endoscopic sinus surgery and removed it, but her vision did not return at 6-month follow-up. Although very rare, sphenoid sinus mucocoeles should be considered in the differential diagnosis of any patient, who presents with sudden visual loss. Key Words: Sphenoid sinus, Mucocoele, Optic neuropathy, Visual loss.


Anti-tumor effect of Coriolus versicolor methanol extract against mouse B16 melanoma cells: in vitro and in vivo study.
Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo. In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.


Data Exploration of Social Determinants of Health, Health Access and Quality in a Global Health Setting.
Diseases have no borders, and global health operates from both within and beyond. Global health informatics can adopt an assets-oriented approach to mitigate concerns by maximizing global health data, principles, and resources combined with geographic information systems' use case mapping. This exploratory study utilizes an assets-oriented approach to analyze four global social determinants of health indicators, including Skilled Birth Attendance, Measles Immunization Coverage, Education (Female), and the Healthcare Access and Quality Index in relation to countries' income and geographical region. Data were extracted and analyzed from two publicly available datasets. Positive trends and variations were detected among all variables aggregated by countries' income category and geographical region. These findings pinpoint potential health assets that the discipline of nursing can leverage to build healthier global health communities.


Unemployment among women: examining the relationship of physical and psychological intimate partner violence and posttraumatic stress disorder.
Prior research has demonstrated that intimate partner violence (IPV) is associated with employment instability among poor women. The current study assesses the broader relationship between IPV and women's workforce participation in a population-based sample of 6,698 California women. We examined past-year IPV by analyzing specific effects of physical violence, psychological violence, and posttraumatic stress disorder (PTSD) symptoms as predictors of unemployment. Results indicated substantial rates of unemployment among women who reported IPV, with rates of 20% among women who experienced psychological violence, 18% among women who experienced physical violence, and 19% among women with PTSD symptoms. When the relationship was adjusted for demographic characteristics and educational attainment, PTSD (adjusted odds ratio [AOR] = 1.60; 95% confidence interval [CI] = 1.22, 2.09) and psychological violence (AOR = 1.78; 95% CI = 1.36, 2.32), but not physical violence, were associated with unemployment. Implications for supported employment programs and workplace responses to IPV are discussed.


A Dictionary Learning Method with Total Generalized Variation for MRI Reconstruction.
Reconstructing images from their noisy and incomplete measurements is always a challenge especially for medical MR image with important details and features. This work proposes a novel dictionary learning model that integrates two sparse regularization methods: the total generalized variation (TGV) approach and adaptive dictionary learning (DL). In the proposed method, the TGV selectively regularizes different image regions at different levels to avoid oil painting artifacts largely. At the same time, the dictionary learning adaptively represents the image features sparsely and effectively recovers details of images. The proposed model is solved by variable splitting technique and the alternating direction method of multiplier. Extensive simulation experimental results demonstrate that the proposed method consistently recovers MR images efficiently and outperforms the current state-of-the-art approaches in terms of higher PSNR and lower HFEN values.


Relationship of larval desiccation to Anopheles gambiae Giles and An. arabiensis Patton survival.
The relationship between mosquito 4th instar larval desiccation and survival to adulthood was explored by three methods in the laboratory. Two colonies of Anopheles arabiensis and one of Anopheles gambiae were studied. We found significant differences in tolerance to desiccation among all three stocks suggesting an intra- and interspecific genetic component to desiccation tolerance. An. arabiensis KGB, originating from Zimbabwe about 1975, had a much-reduced desiccation tolerance compared to An. gambiae G3, colonized in the Gambia in 1975, and An. arabiensis DONGOLA which originated in Sudan in 2004. Individuals of the G3 stock survived desiccation of times up to 40 min with survival of 0.52. The degree of difference in tolerance between G3 and DONGOLA was smallest and was detected by one of three experimental methods. Mass losses of individuals that were weighed individually and survived to adulthood averaged 27% and 29% for G3 and DONGOLA and 20% for the less tolerant KGB stock, respectively. Such differences in survival in transiently dry larval habitats may account in part for differences in the distribution of these species and karyotypes.


Application of laser-induced breakdown spectroscopy technique to hair tissue mineral analysis.
The concentration of the main minerals present in human hair is measured on several subjects by Calibration-Free Laser-Induced Breakdown Spectroscopy (CF-LIBS) and compared with the results obtained through a commercial analytical laboratory. The possibility of using CF-LIBS for mineral analysis in hair is discussed, as well as its feasibility for the fast and inexpensive determination of the occurrence of heavy-metal poisoning in hair.


Practice traits of physicians: a neglected quality assurance issue.
Many physicians are not aware of all elements involved with the quality of patient care although they probably often are the primary cause of breakdowns in care. The examples of physician-related inefficiencies in hospital activities cited in this article are daily sources of frustration and are not trivial to hospital personnel. Physicians need to recognize that QA committees function more effectively when they include multidisciplinary insights in the development of more sensible and functionally efficient systems of patient care, in the improvement of their work environments, and in the strengthening of professional relationships. Moreover, QA committees should educate medical staff members to recognize inappropriate practice styles which are major contributors to inappropriate utilization. Quality assurance committees should recognize that the long-standing tradition of allowing physicians to practice as they wish needs to be challenged when the behavior has been demonstrated to interfere with the quality and efficiency of patient care.


[Ecologic indexes in the surveillance system of Aedes aegypti (Diptera: Culicidae) in Cuba].
The ecological indexes called diversity (H') and equitability (J') of the mosquito species were determined in six of the most common reservoirs of the urban ecosystem in the Plaza de la Revolución municipality, City of Havana. Data analysis showed that according to the values of these indexes, the most dangerous reservoirs were tyres, larvitraps and artificial reservoirs in general. Reference is also made on the use of larvitraps in the surveillance system of Aedes aegypti and the detection and stabilization of mosquitoes such as Aedes mediovittatus and Culex migripalpus in the urban ecosystem. The variety of species ranged from 2 to 7 in the studied reservoirs which showed differences in the patterns of use of the resources in the urban ecosystem.


Comparative bioavailability study of a generic naltrexone tablet preparation.
The bioavailability of a generic preparation of naltrexone (Narpan) was compared with the innovator product, Trexan. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using the parameters area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the logarithmic transformed AUC0-infinity and the logarithmically transformed Cmax values of the two preparations. Also, no statistically significant difference was observed between the untransformed Tmax values. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of Narpan over those of Trexan was found to lie between 0.87 and 1.01, while that of the logarithmic transformed Cmax values was between 0.94 and 1.23, both being within the bioequivalence limit of 0.80-1.25. The numerical values of the elimination half-life (t1/2) obtained with the two preparations were also not significantly different and were comparable to those reported in the literature.


EncoderMap: Dimensionality Reduction and Generation of Molecule Conformations.
Molecular simulation is one example where large amounts of high-dimensional (high-d) data are generated. To extract useful information, e.g., about relevant states and important conformational transitions, a form of dimensionality reduction is required. Dimensionality reduction algorithms differ in their ability to efficiently project large amounts of data to an informative low-dimensional (low-d) representation and the way the low and high-d representations are linked. We propose a dimensionality reduction algorithm called EncoderMap that is based on a neural network autoencoder in combination with a nonlinear distance metric. A key advantage of this method is that it establishes a functional link from the high-d to the low-d representation and vice versa. This allows us not only to efficiently project data points to the low-d representation but also to generate high-d representatives for any point in the low-d map. The potential of the algorithm is demonstrated for molecular simulation data of a small, highly flexible peptide as well as for folding simulations of the 20-residue Trp-cage protein. We demonstrate that the algorithm is able to efficiently project the ensemble of high-d structures to a low-d map where major states can be identified and important conformational transitions are revealed. We also show that molecular conformations can be generated for any point or any connecting line between points on the low-d map. This ability of inverse mapping from the low-d to the high-d representation is particularly relevant for the use in algorithms that enhance the exploration of conformational space or the sampling of transitions between conformational states.


Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis.
Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.


Fully Automated MR Based Virtual Biopsy of Cerebral Gliomas.
The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use. MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma. The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT. This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.


[The successes and failures in the primary prevention of coronary disease].
The modification of major behavioural and environmental risk factors has helped reduce coronary heart disease. It seems, however, that prevention results were not so good as expected. It is assumed that the major cause of this apparent unsuccessful data is basically due to world population ageing, as it is known that coronary heart disease is much more frequent in older people. Therefore the current life expectancy shows that the preventive measures have indeed been successful. From the analysis and discussion of the preventive epidemiological recommendations and the identification of new risk factors, the Authors suggest new strategies for health promotion and particularly for coronary heart disease reduction.


The experience of caring for a family member with Alzheimer's disease.
The purpose of this phenomenological study was to describe the experience of caring for a family member with Alzheimer's disease or related disorder (ADRD) living at home among a diverse sample of 103 family caregivers. The study involved secondary analysis of in-depth transcribed interview data using van Kaam's rigorous four phase, 12-step psychophenomenological method. A total of 2,115 descriptive expressions were categorized into 38 preliminary structural elements. Eight essential structural elements emerged from an analysis of the preliminary structural elements. The eight elements were then synthesized to form the following synthetic structural definition: Caring for a family member living at home with ADRD was experienced as "being immersed in caregiving; enduring stress and frustration; suffering through the losses; integrating ADRD into our lives and preserving integrity; gathering support; moving with continuous change; and finding meaning and joy."


Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection.
The intact sciatic nerve contains levels of nerve growth factor (NGF) that are comparable to those of densely innervated peripheral target tissues of NGF-responsive (sympathetic and sensory) neurons. There, the high NGF levels are reflected by correspondingly high mRNANGF levels. In the intact sciatic nerve, mRNANGF levels were very low, thus indicating that the contribution of locally synthesized NGF by nonneuronal cells is small. However, after transection an increase of up to 15-fold in mRNANGF was measured in 4-mm segments collected both proximally and distally to the transection site. Distally to the transection site, augmented mRNANGF levels occurred in all three 4-mm segments from 6 h to 2 wk after transection, the longest time period investigated. The augmented local NGF synthesis after transection was accompanied by a reexpression of NGF receptors by Schwann cells (NGF receptors normally disappear shortly after birth). Proximal to the transection site, the augmented NGF synthesis was restricted to the very end of the nerve stump that acts as a "substitute target organ" for the regenerating NGF-responsive nerve fibers. While the mRNANGF levels in the nerve stump correspond to those of a densely innervated peripheral organ, the volume is too small to fully replace the lacking supply from the periphery. This is reflected by the fact that in the more proximal part of the transected sciatic nerve, where mRNANGF remained unchanged, the NGF levels reached only 40% of control values. In situ hybridization experiments demonstrated that after transection all nonneuronal cells express mRNANGF and not only those ensheathing the nerve fibers of NGF-responsive neurons.


Best Practices for Handling and Administration of Expressed Human Milk and Donor Human Milk for Hospitalized Preterm Infants.
The importance of human milk for the preterm infant is well established (1-3). However, the feeding of human milk to preterm infants is typically much more complicated than the mere act of breastfeeding (3, 4). The limited oral feeding skills of many preterm infants often results in human milk being administered via an enteral feeding tube (4). In addition, fortification is commonly required to promote optimal growth and development-particularly in the smallest of preterm infants (2, 4, 5). Consequently, a mother's own milk must be pumped, labeled, transported to the hospital, stored, tracked for appropriate expiration dates and times, thawed (if previously frozen), fortified, and administered to the infant with care taken at each step of the process to avoid microbial contamination, misadministration (the wrong milk for the wrong patient), fortification errors, and waste (1-5). Furthermore, the use of pasteurized donor human milk (DHM) for preterm infants when a mother's own milk is not available has been endorsed by many organizations (1). Therefore, appropriate procurement, storage, thawing (if received frozen), fortification, labeling, and administration must occur with the same considerations of preventing contamination and fortification errors while ensuring the correctly prepared final product reaches the correct patient (1). Many professional organizations have published best practices to provide hospitals with guidelines for the safe and accurate handling and preparation of expressed human milk (EHM) and DHM feedings for preterm infants (1-5). These best practices emphasize the importance of preparation location, trained staff, proper identification of human milk to prevent misadministration, and strategies to prevent fortification errors (1-6). The purpose of this mini-review article is to summarize current published best practices for the handling of human milk for preterm infants within the hospital setting (1-6). Emphasis will focus on the use of aseptic technique with proper sanitation and holding times/temperatures to limit microbial growth; use of technology to prevent misadministration of human milk and fortification errors as well as for tracking of expiration dates/times and lot numbers; and workflow strategies to promote safety while improving efficiencies (1-7).


New tools to convert bacterial artificial chromosomes to a self-excising design and their application to a herpes simplex virus type 1 infectious clone.
Infectious clones are fundamental tools for the study of many viruses, allowing for efficient mutagenesis and reproducible production of genetically-defined strains. For the large dsDNA genomes of the herpesviridae, bacterial artificial chromosomes have become the cloning vector of choice due to their capacity to house full-length herpesvirus genomes as single contiguous inserts. Furthermore, while maintained as plasmids in Escherichia coli, the clones can be mutated using robust prokaryotic recombination systems. An important consideration in the design of these clones is the means by which the vector backbone is removed from the virus genome upon delivery into mammalian cells. A common approach to vector excision is to encode loxP sites flanking the vector sequences and rely on Cre recombinase expression from a transformed cell line. Here we examine the efficiency of vector removal using this method, and describe a "self-excising" infectious clone of HSV-1 strain F that offers enhancements in virus production and utility. Insertion of a fluorescent protein expression cassette into the vector backbone of the HSV-1 strain F clone, pYEbac102, demonstrated that 2 serial passages on cells expressing Cre recombinase was required to achieve > 95 % vector removal from the virus population, with 3 serial passages resulting in undetectable vector retention. This requirement was eliminated by replacing the reporter coding sequence with the CREin gene, which consists of a Cre coding sequence disrupted by a synthetic intron. This self-excising variant of the infectious clone produced virus that propagated with wild-type kinetics in culture and lacked vector attenuation in a mouse neurovirulence model. Conversion of a herpesvirus infectious clone into a self-excising variant enables rapid production of viruses lacking bacterial vector sequences, and removes the requirement to initially propagate viruses in cells that express Cre recombinase. The self-excising bacterial artificial chromosome described here allows for efficient production of the F strain of herpes simplex virus type 1.


[Customized 3D cutting guides : what applications in orthopedic surgery ?]
3D printing is a technology that has been evolving rapidly over the past twenty years. It is an additive manufacturing process which allows the creation of objects without geometry restrictions. This process has applications in orthopaedic surgery through personalized cutting guides and implants which offer the possibility to treat complex pathologies such as tumoral surgery, architectural defects of the acetabulum and malunions. Although their use cannot be recommended for routine knee and hip prosthetic surgery, their value in high tibial osteotomies seems promising. Despite its high cost, this technology is of growing interest in orthopaedic surgery.


A Reliable Approach for Fabricating Tissue-Mimicking Phantoms with Designated Dielectric Properties from 16 MHz to 3 GHz.
Tissue-mimicking dielectric phantoms are widely used to mimic the relative permittivity and conductivity of human tissues in various medical applications. The artificial material combinations determine the characterization of dialectic phantoms. However, a method that reliably determined the composition of artificial materials with designed values of dielectric properties and frequency is still lacking. In this work, we propose a method that easily determine the compositions of phantom to mimic the human tissues from 16 MHz to 3 GHz.


Teaching health in the 21st century.
School nurses have a broad scope of practice, including direct clinical care, as well as teaching health lessons. Students in the 21st century require educators who understand the current global needs of these learners. Effective health teaching meets these 21st-century needs. This article presents a background of 21st-century learning, with specific recommendations for teaching this generation of students.


The primary structure of turkey muscle acylphosphatase.
The complete primary structure of turkey muscle acylphosphatase has been determined. The sequence was derived from peptides obtained by digestion of the carboxymethylated protein with pepsin and thermolysin and by subdigestion of some of the cyanogen bromide fragments with trypsin and Staphylococcus aureus protease. Peptides were purified by preparative finger prints and/or preparative high-performance liquid chromatography. Sequencing of the various peptides was achieved by manual Edman degradation and by time-course analysis of amino acids released by carboxypeptidases. The amino-terminal blocking group (acetyl) was determined by fast atom bombardment mass spectrometry. This sequence was compared with that of horse muscle enzyme determined previously.


TRP channels coordinate ion signalling in astroglia.
Astroglial excitability is based on highly spatio-temporally coordinated fluctuations of intracellular ion concentrations, among which changes in Ca(2+) and Na(+) take the leading role. Intracellular signals mediated by Ca(2+) and Na(+) target numerous molecular cascades that control gene expression, energy production and numerous homeostatic functions of astrocytes. Initiation of Ca(2+) and Na(+) signals relies upon plasmalemmal and intracellular channels that allow fluxes of respective ions down their concentration gradients. Astrocytes express several types of TRP channels of which TRPA1 channels are linked to regulation of functional expression of GABA transporters, whereas TRPV4 channels are activated following osmotic challenges and are up-regulated in ischaemic conditions. Astrocytes also ubiquitously express several isoforms of TRPC channels of which heteromers assembled from TRPC1, 4 and/or 5 subunits that likely act as stretch-activated channels and are linked to store-operated Ca(2+) entry. The TRPC channels mediate large Na(+) fluxes that are associated with the endoplasmic reticulum Ca(2+) signalling machinery and hence coordinate Na(+) and Ca(2+) signalling in astroglia.


Dental patients with neurologic and psychiatric concerns.
Neurologic emergencies demand that the dentist stop all major procedures and remove all foreign objects from the patient's mouth, secure the ABCs, and do a quick secondary survey to identify possible causes while someone else activates the EMS. Psychiatric emergencies relate mostly to anxiety. They can be anticipated by a thorough medical history, which includes a DAS or DAS-R. Behavioral modifications provide the greatest long-term benefit. Pharmacologic intervention should be considered when other methods fail. It is important to recognize the possible morbidity increase when anxiety is not properly addressed as well as the differential diagnoses to be excluded in cases of sympathetic overexcitation. In preparation for any major dental work, it is important to take a thorough medical history in a nonthreatening environment, including medications, psychiatric history, and drug abuse history. Psychiatric emergencies can be prevented by reducing anxiety. Neurologic problems and drug overdoses can be detected earlier when a high index of suspicion is present, and premedication can be planned.


Effects of chromium propionate on growth, carcass traits, and pork quality of growing-finishing pigs.
An experiment was conducted to determine the effect of dietary Cr propionate (CrProp) on growth, carcass traits, and pork quality of crossbred finishing gilts. Dietary treatments were 0 or 200 ppb Cr (as CrProp; as-fed basis), and each treatment was replicated four times with five gilts per replicate pen. Gilts were fed diets containing 0.82% lysine from 73 to 80 kg BW and 0.64% lysine from 80 to 115 kg BW. At the end of the trial, carcass and pork quality data were collected from four gilts per replicate. Average daily gain, ADFI, and G:F were not affected (P = 0.76 to 0.96) by CrProp. Before delivery at the abattoir, shrink loss was determined after an 18-h fast (fasting shrink) and after hauling (shipping shrink) pigs for 2.66 h (209.2 km). Fasting, shipping, and overall shrink were not affected (P = 0.14 to 0.39) by CrProp. Carcass length was increased (P = 0.03) in pigs fed CrProp. Loin muscle area, 10th-rib backfat thickness, average backfat thickness, dressing percent, muscle score, fat-free lean, and percent lean were not affected (P = 0.18 to 0.95) by CrProp. Twenty-four-hour loin pH was increased (P = 0.10) in pigs fed CrProp, but 45-min loin and ham pH and 24-h ham pH were not affected (P = 0.39 to 0.83) by CrProp. Subjective (color, marbling, firmness, and wetness) and objective (Commission Internationale de l'Eclairage L*, a*, b*) assessments of the loin muscle (at the 10th-rib interface) were not affected (P = 0.62 to 0.99) by CrProp. Forty-eight-hour drip (P = 0.10) and 21-d purge loss (P = 0.01) were decreased in pigs fed CrProp, but cook and total loss (drip + cook loss) and shear force were not affected (P = 0.35 to 0.53) by CrProp. Plasma cortisol, glucose, and lactate concentrations were not affected (P = 0.28 to 0.97) by CrProp after transportation or during exsanguination. These data indicate that CrProp may improve some aspects of pork quality (loin pH, drip and purge loss) but not growth performance or carcass traits.


Psychotropic Medications-Induced Tardive Dyskinesia and Associated Factors Among Patients with Mental Illness in Ethiopia.
Tardive dyskinesia (TD) remains a significant burden especially among patients taking psychotropic medications, and it is associated with adverse effects that can lead to subjective suffering, stigma, poor compliance to medication, and poor quality of life. However, it is unrecognized and overlooked in clinical settings. So, this study aimed to assess the magnitude of tardive dyskinesia and associated factors among mentally ill patients attending follow-up treatment at Jimma University Medical Center Psychiatry clinic, Jimma, Southwest Ethiopia, 2019. Institutional-based cross-sectional study design was conducted in 417 samples. Participants were selected by systematic random sampling techniques. Data were collected by a semi-structured interviewer-administered questionnaire, and the document was reviewed to obtain the patient's profile. Tardive dyskinesia was assessed by using the Extrapyramidal Symptom Rating Scale after informed consent was obtained from respondents. Data entry was done by EpiData version 3.1, and analysis was done by using SPSS 22.0 statistical software. Binary logistic regression and multivariate logistic regression were used to see the association and to identify independent factors at a p-value of <0.05. Prevalence of drug-induced tardive dyskinesia was 15.4% (CI 95%: 12.0, 19.3). Female, age range between 30 and 44 years, having a diagnosis of major depressive disorder with the psychotic feature, taking chlorpromazine equivalent dose ˃600mg, and taking anticholinergic medications were variables positively associated with tardive dyskinesia, whereas cigarette smoking was negatively associated with tardive dyskinesia. The prevalence of drug-induced tardive dyskinesia in this study was high. Prescribing medications less than 600mg equivalent dose of chlorpromazine, giving attention for female patients, patients having a diagnosis of major depressive disorder, and reducing giving anticholinergic medications will be important measures for clinicians to reduce the occurrence of tardive dyskinesia.


Spinal transection and the postnatal differentiation of slow myosin isoenzymes.
Newborn rats underwent cordotomy, and the myosin composition of individual muscles was investigated 3 months postoperatively. The results indicate that, after cordotomy, the myosin composition in the extensor digitorum longus and tibialis anterior muscles is normal, whereas in the soleus muscle the myosin has catalytic and molecular properties intermediate between those of adult fast and slow myosin. Together with histochemical data these results indicate that spinal transection causes a developmental arrest in the soleus muscle, at a stage corresponding to a mixed fiber population.


ICPD-a new peak detection algorithm for LC/MS.
The identification and quantification of proteins using label-free Liquid Chromatography/Mass Spectrometry (LC/MS) play crucial roles in biological and biomedical research. Increasing evidence has shown that biomarkers are often low abundance proteins. However, LC/MS systems are subject to considerable noise and sample variability, whose statistical characteristics are still elusive, making computational identification of low abundance proteins extremely challenging. As a result, the inability of identifying low abundance proteins in a proteomic study is the main bottleneck in protein biomarker discovery. In this paper, we propose a new peak detection method called Information Combining Peak Detection (ICPD ) for high resolution LC/MS. In LC/MS, peptides elute during a certain time period and as a result, peptide isotope patterns are registered in multiple MS scans. The key feature of the new algorithm is that the observed isotope patterns registered in multiple scans are combined together for estimating the likelihood of the peptide existence. An isotope pattern matching score based on the likelihood probability is provided and utilized for peak detection. The performance of the new algorithm is evaluated based on protein standards with 48 known proteins. The evaluation shows better peak detection accuracy for low abundance proteins than other LC/MS peak detection methods.


FIN13, a novel growth factor-inducible serine-threonine phosphatase which can inhibit cell cycle progression.
We have identified a novel type 2C serine-threonine phosphatase, FIN13, whose expression is induced by fibroblast growth factor 4 and serum in late G1 phase. The protein encoded by FIN13 cDNA includes N- and C-terminal domains with significant homologies to type 2C phosphatases, a domain homologous to collagen, and an acidic domain. FIN13 expression predominates in proliferating tissues. Bacterially expressed FIN13 and FIN13 expressed in mammalian cells exhibit serine-threonine phosphatase activity, which requires Mn2+ and is insensitive to inhibition by okadaic acid. FIN13 is localized in the nuclei of transiently transfected cells. Cotransfection of FIN13-expressing plasmids with a plasmid that expresses the neomycin resistance gene inhibits the growth of drug-resistant colonies in NIH 3T3, HeLa and Rat-1 cells. In transiently transfected cells, FIN13 inhibits DNA synthesis and results in the accumulation of cells in G1 and early S phases. Similarly, the induction of expression of FIN13 under the control of a tetracycline-regulated promoter in NIH 3T3 cells leads to growth inhibition, with accumulation of cells in G1 and early S phases. Thus, overexpression and/or unregulated expression of FIN13 inhibits cell cycle progression, indicating that the physiological role of this phosphatase may be that of regulating the orderly progression of cells through the mitotic cycle by dephosphorylating specific substrates which are important for cell proliferation.


Comparison of mesenchymal stem cells obtained by suspended culture of synovium from patients with rheumatoid arthritis and osteoarthritis.
Mobilization of mesenchymal stem cells (MSCs) from the synovium was revealed using a "suspended synovium culture model" of osteoarthritis (OA). The pathology of rheumatoid arthritis (RA) differs from that of OA. We investigated whether mobilization of MSCs from the synovium also occurred in RA, and we compared the properties of synovial MSCs collected from suspended synovium culture models of RA and OA. Human synovium was harvested during total knee arthroplasty from the knee joints of patients with RA (n = 8) and OA (n = 6). The synovium was suspended in a bottle containing culture medium and a culture dish at the bottom. Cells were harvested from the dish and analyzed. No significant difference was observed between RA and OA in the harvested cell numbers per g of synovium. However, the variation in the number of cells harvested from each donor was greater for RA than for OA. The harvested cells were multipotent and no difference was observed in the cartilage pellet weight between RA and OA. The surface epitopes of the cells in RA and OA were similar to those of MSCs. Mobilization of MSCs from the synovium was demonstrated using a suspended synovium culture model for RA. The harvested cell numbers, chondrogenic potentials, and surface epitope profiles were comparable between the RA and OA models.


Minimally Invasive Surgery for Pott's Puffy Tumor: Is It Time for a Paradigm Shift in Managing a 250-Year-Old Problem?
The aim of this study was to review the clinical outcomes and efficacy of endoscopic sinus surgery (ESS) in the management of Pott's puffy tumor (PPT). Literature PubMed review using a combination of MeSH terms and keywords was undertaken, combined with a single surgeon case series of 3 patients. A total of 29 (20 males, median age 25 years) cases were reviewed. The most common etiology was acute frontal sinusitis (62%), followed by a history of chronic rhinosinusitis (28%). Two patients presented with concomitant preseptal cellulitis and cutaneous fistula each, while another had pneumocephalus. The majority of cases (59%) had Draf 1 procedure. Three cases had Draf 3 procedure. Five cases were successfully treated by sinus balloon sinuplasty. Postoperatively, most patients had either oral or intravenous antibiotics of varying duration. There were no further complications following ESS. Both fistulas healed without requiring surgical debridement or closure. Some PPT cases can be managed endoscopically. The availability of powered angled instruments, high-definition video, and image guidance systems have provided the modern otolaryngologists with a credible alternative to traditional techniques. Furthermore, improved bioavailability of modern antibiotics may obviate the need for craniotomy and external drains.


Individual behavior and pairwise interactions between microswimmers in anisotropic liquid.
A motile bacterium swims by generating flow in its surrounding liquid. Anisotropy of the suspending liquid significantly modifies the swimming dynamics and corresponding flow signatures of an individual bacterium and impacts collective behavior. We study the interactions between swimming bacteria in an anisotropic environment exemplified by lyotropic chromonic liquid crystal. Our analysis reveals a significant localization of the bacteria-induced flow along a line coaxial with the bacterial body, which is due to strong viscosity anisotropy of the liquid crystal. Despite the fact that the average viscosity of the liquid crystal is two to three orders of magnitude higher than the viscosity of pure water, the speed of bacteria in the liquid crystal is of the same order of magnitude as in water. We show that bacteria can transport a cargo (a fluorescent particle) along a predetermined trajectory defined by the direction of molecular orientation of the liquid crystal. We demonstrate that while the hydrodynamic interaction between flagella of two close-by bacteria is negligible, the observed convergence of the swimming speeds as well as flagella waves' phase velocities may occur due to viscoelastic interaction between the bacterial bodies.


Cell-free culture conditioned medium elicits pancreatic β cell lineage-specific epigenetic reprogramming in mice.
There are several obstacles to overcome prior to achieving cellular reprogramming of pancreatic β cells in vitro and in vivo. The present study demonstrated that the transfer of epigenetic phenotypes was achieved in the cell-free conditioned medium (CM) of pancreatic insulinoma MIN6 cell cultures. The comparison of a subpopulation of MIN6, m14 and m9 cells indicated that MIN6-m14 cells were more prone to cellular reprogramming. Epigenetic profiling revealed that the transcription factor pancreas/duodenum homeobox protein 1 (Pdx1) was differentially associated among the clones. The culture of differentiated adipocytes in the CM of MIN6-m14 cells resulted in the induction of insulin mRNA expression, and was accompanied by epigenetic events of Pdx1 binding. The epigenetic profiling indicated that Pdx1 is preferentially associated with a previously uncharacterized region of the endoplasmic reticulum (ER) disulfide oxidase, ER oxidoreductin 1 gene. Therefore, the results of the present study indicated that the CM of MIN6 cells was able to induce a pancreatic β cell-like phenotype in differentiated adipocytes. These data provide additional support for the utility of cell-free CM for cellular reprogramming.


'Follow the Water': Microbial Water Acquisition in Desert Soils.
Water availability is the dominant driver of microbial community structure and function in desert soils. However, these habitats typically only receive very infrequent large-scale water inputs (e.g., from precipitation and/or run-off). In light of recent studies, the paradigm that desert soil microorganisms are largely dormant under xeric conditions is questionable. Gene expression profiling of microbial communities in desert soils suggests that many microbial taxa retain some metabolic functionality, even under severely xeric conditions. It, therefore, follows that other, less obvious sources of water may sustain the microbial cellular and community functionality in desert soil niches. Such sources include a range of precipitation and condensation processes, including rainfall, snow, dew, fog, and nocturnal distillation, all of which may vary quantitatively depending on the location and geomorphological characteristics of the desert ecosystem. Other more obscure sources of bioavailable water may include groundwater-derived water vapour, hydrated minerals, and metabolic hydro-genesis. Here, we explore the possible sources of bioavailable water in the context of microbial survival and function in xeric desert soils. With global climate change projected to have profound effects on both hot and cold deserts, we also explore the potential impacts of climate-induced changes in water availability on soil microbiomes in these extreme environments.


Gene set analysis of SNP data: benefits, challenges, and future directions.
The last decade of human genetic research witnessed the completion of hundreds of genome-wide association studies (GWASs). However, the genetic variants discovered through these efforts account for only a small proportion of the heritability of complex traits. One explanation for the missing heritability is that the common analysis approach, assessing the effect of each single-nucleotide polymorphism (SNP) individually, is not well suited to the detection of small effects of multiple SNPs. Gene set analysis (GSA) is one of several approaches that may contribute to the discovery of additional genetic risk factors for complex traits. Complex phenotypes are thought to be controlled by networks of interacting biochemical and physiological pathways influenced by the products of sets of genes. By assessing the overall evidence of association of a phenotype with all measured variation in a set of genes, GSA may identify functionally relevant sets of genes corresponding to relevant biomolecular pathways, which will enable more focused studies of genetic risk factors. This approach may thus contribute to the discovery of genetic variants responsible for some of the missing heritability. With the increased use of these approaches for the secondary analysis of data from GWAS, it is important to understand the different GSA methods and their strengths and weaknesses, and consider challenges inherent in these types of analyses. This paper provides an overview of GSA, highlighting the key challenges, potential solutions, and directions for ongoing research.


[The role of structural elements of ColE1-related plasmids in replication control].
Effect of deletions downstream from the replication origin on copy number of ColE1 related (pBR322 derived) plasmids has been studied. Along with main control elements (RNAI of defined secondary structure, the repressor protein, effectiveness of promoter upstream of gene of RNA primer) replication is influenced by transcription level propagated into the replicon region from promoters even in distal parts of plasmid. Structure of the region adjacent to the ori is important for startpoint recognition specificity, so that deletion of this region reduces the effectiveness of replication.


Rapid diagnosis and management of thoracic aortic dissection and intramural haematoma: a prospective study of advantages of multiplane vs. biplane transoesophageal echocardiography.
The purposes of this study were to compare the accuracy of multiplane vs. biplane transoesophageal echocardiography (TEE) in the diagnosis of aortic dissection and aortic intramural haematoma, and to test whether these techniques provide all the diagnostic information required to make management decisions. Fifty-eight consecutive patients with clinically suspected aortic dissection were studied with multiplane TEE; all cases who required surgery underwent intraoperative monitoring with multiplane TEE. The following multiplane TEE data were analysed: the angle between current and 0 degrees plane at which each view was obtained; the success rate in the evaluation of true and false lumen, entry tear, coronary artery involvement, aortic regurgitation, pericardial effusion. Advantages of multiplane over biplane TEE have been evaluated by the demonstration of usefulness of views obtained in planes other than 0 degrees-20 degrees or 70 degrees-110 degrees, assuming that with manipulation of a biplane probe a 20 degrees arc could be added to the conventional horizontal and vertical planes. On the basis of TEE findings, aortic dissection was confirmed in 36 cases (18 type A, 12 type B, six intramural haematoma). The specificity and sensitivity of TEE in terms of the presence or absence of aortic dissection or intramural haematoma were 100%. An additional clinical value of multiplane over biplane TEE in the evaluation of ascending aorta, aortic arch, entry tears and coronary artery involvement was demonstrated. All cases with type A aortic dissection or intramural haematoma involving the ascending aorta had an operation that was performed immediately after the diagnosis (hospital mortality, 13%). Patients with type B aortic dissection were treated medically; 25% of these cases were operated later (hospital mortality, 0%). Multiplane and biplane TEE have excellent and similar accuracies in the evaluation of aortic dissection and intramural haematoma. Multiplane TEE improves the visualization of coronary arteries, aortic arch and entry tears; it appears to be an ideal method as the sole diagnostic approach before surgery in type A aortic dissection.


Can investments in manure technology reduce nutrient leakage to the Baltic Sea?
In this study, quantitative models of the agricultural sector and nutrient transport and cycling are used to analyse the impacts in the Baltic Sea of replacing the current Greening measures of the EU's Common Agricultural Policy with a package of investments in manure handling. The investments aim at improving nutrient utilization and reducing nitrogen leaching, based on the assumption that lagging farms and regions can catch up with observed good practice. Our results indicate that such investments could reduce nitrogen surpluses in agriculture by 18% and nitrogen concentrations in the Baltic Sea by 1 to 9% depending on the basin. The Greening measures, in contrast, are found to actually increase nitrogen leaching.


Long-term effects of immunosuppressants in steroid-dependent nephrotic syndrome.
In order to elucidate long-term effects of immunosuppressants, we studied 60 children with steroid-dependent nephrotic syndrome who were treated with three immunosuppressants: cyclophosphamide (n=34), chlorambucil (n=11), and cyclosporin A (n=15). Each relapse before and after the administration of immunosuppressants was evaluated longitudinally in terms of the relapse-free period and the maintenance dose of prednisolone required. The median follow-up period after immunosuppressants was 5.2 years (range 0.5-20.3 years). The relapse-free period was significantly longer in all groups after the initiation of immunosuppressants. However, the relapse-free period after subsequent relapses as compared with the previous relapse was longer in the cyclophosphamide group, similar in the chlorambucil group, and shorter in the cyclosporin A group. The prednisolone dosage at relapse was reduced in subsequent relapses after cyclophosphamide and chlorambucil treatment, but tended to be higher in later relapses after the initiation of cyclosporin A. These findings suggest that the effects of cyclophosphamide are long lasting, while those of chlorambucil and cyclosporin A are of short duration. Children who relapse after cyclosporin A treatment may experience a worse relapsing course.


[Comparative study of the effect of wei-yan-ning and furazolidone in the treatment of gastritis and gastric ulcer caused by pyloric Campylobacter].
Wei-Yan-Ning and Furazolidone were used separately in the treatment of 62 cases of gastritis and gastric ulcer caused by pyloric campylobacteria. The examinations one month later proved, through the gastrofiberscopy and pathological test as well as the urease test, that, among the 40 cases of Wei-Yan-Ning group, there were 25 cures (62.5%), prominent effect for 9 cases (22.5%), improvement for 3 cases (7.5%). The total effective rate was 92.5%. Among the 22 cases of the Furazolidone group, there were 7 cures (31.8%), prominent effect for 5 cases (22.7%), improvement for 4 cases (18.2%). The total effective rate was 72.7%. As for the improvement of symptom, the average time for the Wei-Yan-Ning group was 12.5 +/- 8.12 days; and the Furazolidone group was 21.63 +/- 7.87 days. Therefore, the effect of Wei-Yan-Ning group was superior to that of the Furazolidone group (P less than 0.05).


Efficient 946-nm Laser Operation of a Composite Nd:YAG Rod With Undoped Ends.
We present comparative studies on laser performance of diode end-pumped, composite Nd:YAG rods with undoped ends at 946 nm. Efficient heat removal in a composite rod can reduce the peak of rise in temperature in the active segment to 61% by theoretical calculation. The maximum, continuous-wave output power of 1.5 W, which is three times higher than a conventional noncomposite rod, was obtained at an absorbed pump power of 8 W because of the 55 deg reduction in temperature rise that was estimated experimentally. The performance and characteristics of composite rods in quasi-three-level laser operation are analyzed and discussed in detail, taking into account the reduction in reabsorption loss, which is strongly temperature dependent.


[Professional unemployment in Andalucia. Expectations and difficulties in the nursing profession].
The primary objective of this article is to know the professional, academic and formative expectations in Nursing and those problems which hinder the performance of this profession among the Andalucian public health centers. The authors carried out an extensive descriptive study during the years 1994-1996 based on a sampling of 1020 nursing professionals pertaining to the Andalucian Health Service. These samples were obtained by means of a random stratification by provinces and care level, with an affixation proportional to the size of the stratum, having a 95% confidence rate and a 3.5% error rate. The data were acquired by means of a self-administered questionnaire sent in by mail. Among the most significant results, the authors highlight that fact that the professional, academic and performance expectations among Andalucian Nursing professionals center on research and investigation (71.5%), postgraduate courses (75%), possible Licentiate in Nursing (82.4%) and some nursing specialty (78.7%). Among the difficulties identified for professional performance, the items which stands out were those derived from the absence of a legal definition for Nursing functions (90.8%).


Randomized phase 2 trial comparing JNJ-9375, a thrombin-directed antibody, with apixaban for prevention of venous thrombosis.
JNJ-9375 is an antibody against exosite 1 on thrombin, inhibits substrate binding but not catalytic activity. To examine the possibility that JNJ-9375 attenuates thrombosis without affecting hemostasis, we compared the efficacy and safety of JNJ-9375 and apixaban. In this double-blind, double-dummy phase 2 trial, 308 patients undergoing knee arthroplasty were randomized to receive either a single postoperative intravenous infusion of JNJ-9375 in doses ranging from 0.3 to 1.8 mg/kg or apixaban (2.5 mg twice daily). The primary efficacy endpoint was the incidence of venous thromboembolism (assessed by mandatory unilateral venography or confirmed symptomatic events). The primary safety outcome was the composite of major, clinically relevant nonmajor, and minimal bleeding. Thrombin times were measured to assess JNJ-9375 activity. A total of 239 of the 308 patients (77.6%) were included in the modified intention-to-treat analysis. Of these, 238 had evaluable venograms and one had symptomatic deep-vein thrombosis confirmed by ultrasound. Despite dose-dependent thrombin time prolongation, the primary efficacy outcome occurred in 59 of 190 patients (31.1%) in the combined JNJ-9375 groups as compared with 6 of 49 patients (12.2%) given apixaban (odds ratio 3.2; two-sided 80% confidence interval 1.8-5.8; P = .011). The excess events with JNJ-9375 compared with apixaban were consistent across all JNJ-9375 dosing cohorts and there was no evidence of improved efficacy with higher JNJ-9375 doses. There were no major bleeds with JNJ-9375 or apixaban, and rates of any bleeding were similar with the highest and lowest JNJ-9375 doses. JNJ-9375 was safe but less effective than apixaban. This may reflect weak thrombin inhibition or inability of JNJ-9375 to attenuate the growth of thrombi that formed before drug administration.


Brief motivational feedback and cognitive behavioral interventions for prevention of disordered gambling: a randomized clinical trial.
The purpose of the current study was to evaluate feasibility and efficacy of two promising approaches to indicated prevention of disordered gambling in a college population. Randomized clinical trial with assignment to a personalized feedback intervention (PFI), cognitive-behavioral intervention (CBI) or assessment-only control (AOC). PFI was delivered individually in a single session and included feedback regarding gambling behavior, norms, consequences and risk-reduction tips, delivered in a motivational interviewing style. CBI was delivered in small groups over four to six sessions and included functional analysis and brief cognitive correction, as well as identification of and alternatives for responding to gambling triggers. College campus. At-risk or probable pathological gamblers (n = 147; 65.3% male; group assignment: PFI, n = 52; CBI, n = 44; AOC, n = 51). Self-reported gambling quantity, frequency, consequences, psychopathology, normative perceptions and beliefs. Relative to control, results at 6-month follow-up indicated reductions in both interventions for gambling consequences (PFI d = 0.48; CBI d = 0.39) and DSM-IV criteria (PFI d = 0.60; CBI d = 0.48), reductions in frequency for PFI (d = 0.48). CBI was associated with reduced illusions of control, whereas PFI was associated with reduced perceptions of gambling frequency norms. Reductions in perceived gambling frequency norms mediated effects of PFI on gambling frequency. A single-session personalized feedback intervention and a multi-session cognitive-behavioral intervention may be helpful in reducing disordered gambling in US college students.


Altered gene expression profile in the kidney of vitamin D receptor knockout mice.
The kidney is a primary target organ of the vitamin D endocrine system, and both vitamin D-deficiency and vitamin D receptor (VDR) ablation lead to impaired renal functions. As an initial step to understand the molecular basis underlying the renal dysfunctions resulted from VDR inactivation, we used DNA microarray technology to search for changes in the gene expression profile in the kidney of VDR knockout mice. Three independent DNA microarray experiments were performed using Affymetrix GeneChips, which included two replicate comparisons between VDR null and wild-type littermates, and a third comparison between 1,25-dihydroxyvitamin D(3)-treated and vehicle-treated wild-type mice. Based on the assumption that VDR inactivation and vitamin D stimulation cause opposite changes in the expression of vitamin D target genes, we identified 95 genes that displayed the same changes in the two VDR-null/wild-type comparisons but an opposite change in the third assay, of which 28 genes were up-regulated and 67 were down-regulated in VDR null mice. These genes can be divided into several functional categories involved in vitamin D and steroid metabolism, calcium metabolism and signaling, volume and electrolyte homeostasis, signal transduction, transcriptional regulation, cell adhesion, metabolism, immune response, and other functions. These data provide a basis for further investigations into the molecular bases underlying the physiological abnormalities associated with VDR- and vitamin D-deficiency.


100 years of animal welfare regulation and of experiments with animals in Germany, effects and reasons.
The first regulations (1883) have been renewed twice (1933, 1972) and will soon be renewed once again (1986). They have always been influenced by two motivations: men's feeling of responsibility for animals on one hand and antiscientism or public suspicion against scientists on the other hand. The general rules concerning animal welfare (anaesthesia, reduction of number and harm, species selection etc.) have been constant for 100 years, but governmental control increases by the establishment of special licences (for each project, for the responsible scientist, for the location) by regular controls of the laboratories, by installing a permanent animal welfare officer in the institutions, by protocols, special taxes and increasing penalties. Out of different public ethical concepts about the use of animals, the law for the present agrees with those permitting to use animals for "reasonable purposes". But now the public opinion wants to change to "only for necessary" purposes; this especially concerns animal experiments causing severe pain. Philosophers and public have difficulties to find consentaneous reasons for the "necessity" of basic research. Each basic research in biology must be accepted as necessary because life is multifactorially organized and can be analyzed sufficiently only by random-like strategies to test not monocausally evidenthypotheses alone, but all reasonable possibilities.


Potentially harmful excipients in neonatal medicines: a pan-European observational study.
We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure. All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient. European neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.


Association of Obstructive Sleep Apnea With Cardiovascular Outcomes in Patients With Acute Coronary Syndrome.
Background The prognostic significance of obstructive sleep apnea ( OSA ) in patients with acute coronary syndrome ( ACS ) in the contemporary era is unclear. We performed a large, prospective cohort study and did a landmark analysis to delineate the association of OSA with subsequent cardiovascular events after ACS onset. Methods and Results Between June 2015 and May 2017, consecutive eligible patients admitted for ACS underwent cardiorespiratory polygraphy during hospitalization. OSA was defined as an apnea-hypopnea index ≥15 events·h-1. The primary end point was major adverse cardiovascular and cerebrovascular event ( MACCE ), including cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularization, or hospitalization for unstable angina or heart failure. OSA was present in 403 of 804 (50.1%) patients. During median follow-up of 1 year, cumulative incidence of MACCE was significantly higher in the OSA group than in the non- OSA group (log-rank, P=0.041). Multivariate analysis showed that OSA was nominally associated with incidence of MACCE (adjusted hazard ratio, 1.55; 95% CI, 0.94-2.57; P=0.085). In the landmark analysis, patients with OSA had 3.9 times the risk of incurring a MACCE after 1 year (adjusted hazard ratio, 3.87; 95% CI, 1.20-12.46; P=0.023), but no increased risk was found within 1-year follow-up (adjusted hazard ratio, 1.18; 95% CI, 0.67-2.09; P=0.575). No significant differences were found in the incidence of cardiovascular death, myocardial infarction, and ischemia-driven revascularization, except for a higher rate of hospitalization for unstable angina in the OSA group than in the non- OSA group (adjusted hazard ratio, 2.10; 95% CI, 1.09-4.05; P=0.027). Conclusions There was no independent correlation between OSA and 1-year MACCE after ACS . The increased risk associated with OSA was only observed after 1-year follow-up. Efficacy of OSA treatment as secondary prevention after ACS requires further investigation.


Ocular findings in several metabolic diseases.
Changes in ocular findings have been noted in association with several metabolic diseases. In homocystinuria the crystalline lens in the majority of cases is subluxated inferiorly, while in Marfan's syndrome the dislocation was upward. In cystinosis, slit-lamp examination reveals numerous gold crystal-like cystine deposits in both the cornea and bulbar conjunctiva. Patients with galactosemia have cataracts of the "oil drop" type, which usually can be seen with an ophthalmoscope even though the opacity is not dense. Eight patients with Lowe's syndrome who were observed had cataracts, and four of them had severe glaucoma. Three of five patients with glycogen storage disease Type I had yellowish deposits in the macular and paramacular areas, thought to be due to hypercholesterolemia.


Expression of some selected cytokeratins and Ki67 protein in prostatic tumor: can these be used as tumor markers.
Diagnosis of prostatic diseases with Immunohistochemistry still faces challenges because of the peculiar histology of the prostate and difference(s) in reactivity of Monoclonal antibodies (MoAb) to benign and malignant changes. Thirty (30) archived paraffin embedded tissue samples from primary prostate tumors (15 Benign Prostatic Hyperplasia (BPH) and 15 Cancer of the prostate (CaP)) were sectioned at thickness of 5 µm and confirmed as BPH or CaP. Sections from each sample were stained by Immunohistochemistry using the Streptavidin-biotin method and using CK5/6, CK7, CK8,CK20 and Ki67 antibodies (Zymed Antibody products). Appropriate positive and negative controls for each antibody were setup alongside the test slides. BPH samples were reactive to Ck5/6 (93.3%), Ck7 (80%) and Ck8 (100%). Only 13.3% of BPH samples were reactive to Ki67. The reactivity of Ck5/6, 7, 8 in CaP is a contrast with only 3(20%) of samples positive with Ck5/6, 2(13.3%) positive with Ck7 and 14(93.3%) with Ck8. While reactivity of Ck 8 is similar in BPH and CaP, no reaction was recorded in Ck 20 in both BPH and CaP. Ki67 was only reactive in 2(13.3) of BPH samples and 15(100%) of CaP. Only Ck 8 was expressed in both BPH and CaP. There was co-expression of Ck5/6, 7,8 and Ki67 in 13.3%; Ck7 and Ki67 in 13.3% in both BPH and CaP. The various cytokeratins are individually expressed in both BPH and CaP. Ck5/6 and Ck7 are co-expressed and may be used in the diagnosis of BPH, Ck5/6,7,8 and Ki67 are co-expressed in Prostatic adenocarcinoma and squamous cell carcinoma of the prostate while Ck8 and Ki67 are co-expressed and may be used for diagnosis of Prostatic adenocarcinoma alone.


APAs Constraints to Voluntary Movements: The Case for Limb Movements Coupling.
When rhythmically moving two limbs in either the same or in opposite directions, one coupling mode meets constraints that are absent in the other mode. Isodirectional (ISO) flexion-extensions of the ipsilateral hand and foot can be easily performed with either the hand prone or supine. Instead, antidirectional (ANTI) movements require attentive effort and irresistibly tend to reverse into ISO when frequency increases. Experimental evidence indicates that the direction dependent easy-difficult dichotomy is caused by interference of the anticipatory postural commands associated to movements of one limb with voluntary commands to the other limb. Excitability of the resting wrist muscles is subliminally modulated at the period of ipsilateral foot oscillations, being phase-opposite in the antagonists and distributed so as to facilitate ISO and obstacle ANTI coupling of the hand (either prone or supine) with the foot. Modulation is driven by cortical signals dispatched to the forearm simultaneously with the voluntary commands moving the foot. If right foot oscillations are performed when standing on the left foot with the right hand touching a fixed support, the subliminal excitability modulation is replaced by overt contractions of forearm muscles conforming the APAs features. This suggests that during hand-foot ANTI coupling the voluntary commands to forearm muscles are contrasted by APAs commands of opposite sign linked to foot oscillations. Correlation between the easy-difficult dichotomy and the APAs distribution is also found in coupled adduction-abduction of the arms or hands in the transverse plane and in coupled flexion-extension of the arms in the parasagittal plane. In all these movements, APAs commands linked to the movement of each limb reach the motor pathways to the contralateral muscles homologous to the prime movers and can interfere during coupling with their voluntary activation. APAs are also generated in postural muscles of trunk and lower limbs and size-increase when the movement frequency is incremented. The related increase in postural effort apparently contributes in destabilizing the difficult coupling mode. Motor learning may rely upon more effective APAs. APAs and focal contraction are entangled within the same voluntary action. Yet, neural diseases may selectively impair APAs, which represent a potential target for rehabilitation.


Characterization of Naphthenic Acids and Other Dissolved Organics in Natural Water from the Athabasca Oil Sands Region, Canada.
With growth of the Canadian oil sands industry, concerns have been raised about possible seepage of toxic oil sands process-affected water (OSPW) into the Athabasca River (AR). A sampling campaign in fall 2015 was undertaken to monitor for anthropogenic seepage while also considering natural sources. Naphthenic acids (NAs) and thousands of bitumen-derived organics were characterized in surface water, groundwater, and OSPW using a highly sensitive online solid phase extraction-HPLC-Orbitrap method. Elevated NA concentrations and bitumen-derived organics were detected in McLean Creek (30.1 μg/L) and Beaver Creek (190 μg/L), two tributaries that are physically impacted by tailings structures. This was suggestive of OSPW seepage, but conclusive differentiation of anthropogenic and natural sources remained difficult. High NA concentrations and bitumen-derived organics were also observed in natural water located far north of the industry, including exceedingly high concentrations in AR groundwater (A5w-GW, 2000 μg/L) and elevated concentration in a tributary river (Pierre River, 34.7 μg/L). Despite these evidence for both natural and anthropogenic seepage, no evidence of any bitumen-derived organics was detected at any location in AR mainstem surface water. The chemical significance of any bitumen-derived seepage to the AR was therefore minimal, and focused monitoring in tributaries will be valuable in the future.


Evaluation of a predoctoral clinical psychology internship program by intern graduates.
This investigation is a replication and extension of an earlier study by Stout, Holmes, and Rothstein (1977) of the predoctoral clinical psychology intern graduates at the William S. Hall Psychiatric Institute. The interns were surveyed (N = 63) with regard to how adequately their internship experience prepared them for their current professional work as practicing clinical psychologists. Questionnaire data (n = 44) from graduates are analyzed in terms of the demographics of each intern's work situation, ratings of how well their internship prepared them in the areas of interprofessional relationships, teaching psychodiagnostic evaluations, psychological treatment, administration, consultation, and research. Several recommendations are offered by the intern graduates for refinement of the clinical psychology internship.


Formation of P-C bonds under unexpectedly mild conditions. Phosphoryl migration and metal coordination of diphenylphosphinomethyl-oxazolines and -thiazolines.
The heterocycles 2-methyl-2-oxazoline (mox) and 2-methyl-2-thiazoline (mth) react with Ph2PCl under mild conditions, in the presence of NEt3 which promotes their phosphorylation by stabilization of their enamino tautomers mox(e) and mth(e), respectively, and which also behaves as HCl scavenger. Depending on the reaction conditions, three different phosphine ligands were obtained in good yields from mox: the monophosphine Ph2PCH2C=NCH2CH2O (1ox) and the isomeric diphosphines Ph2PCH=COCH2CH2NPPh2 (2ox) (X-ray structure) and (Ph2P)2CHC=NCH2CH2O (3ox). The formation of these ligands involves phosphoryl migration reactions, which were studied by NMR spectroscopy. The synthesis and the X-ray structures of the corresponding diphenylphosphinothiazolines Ph2PCH2C=NCH2CH2S (1th) and Ph2CH=CSCH2CH2NPPh2 (2th) are also reported but the thiazoline analog of the geminal diphosphine 3ox was not observed. The metal complexes [Pt(3ox-H)2] x 4 CH2Cl2 (4 x 4 CH2Cl2), [Pt(Me)I(1ox)] (5), [Pt(Me)2(1ox)] (7), [Pd(dmba-C,N)(1th)]OTf x 0.25 Et2O (8 x 0.25 Et2O), [Pd(dmba-C,N)(1th-H)] (9), and [9 x {Pd(dmba-C,N)Cl}] x 2.5 C6H6 (10 x 2.5 C6H6) have been prepared and structurally characterized by X-ray diffraction.


Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge.
As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019-2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019-2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.


Infant male circumcision: healthcare provider knowledge and associated factors.
The emerging science demonstrates various health benefits associated with infant male circumcision and adult male circumcision; yet rates are declining in the United States. The American Academy of Pediatrics and the Centers for Disease Control and Prevention recommend that healthcare providers present evidence-based risk and benefit information for infant male circumcision to parent(s) and guardian(s). The purpose of this study was to assess providers' level of infant male circumcision knowledge and to identify the associated characteristics. An online survey was administered to healthcare providers in the family medicine, obstetrics, and pediatrics medical specialties at an urban academic health center. To assess infant male circumcision knowledge, a 17 point summary score was constructed to identify level of provider knowledge within the survey. Ninety-two providers completed the survey. Providers scored high for the following knowledge items: adverse event rates, protects against phimosis and urinary tract infections, and does not prevent hypospadias. Providers scored lower for items related to more recent research: protection against cervical cancer, genital ulcer disease, bacterial vaginosis, and reduction in HIV acquisition. Two models were constructed looking at (1) overall knowledge about male circumcision, and (2) knowledge about male circumcision reduction in HIV acquisition. Pediatricians demonstrated greater overall infant male circumcision knowledge, while obstetricians exhibited significantly greater knowledge for the HIV acquisition item. Providers' knowledge levels regarding the risks and benefits of infant male circumcision are highly variable, indicating the need for system-based educational interventions.


Recombinant non-collagenous domain of alpha2(IV) collagen causes involution of choroidal neovascularization by inducing apoptosis.
Vascular endothelial cells receive proangiogenic or antiangiogenic signals from components of extracellular matrix (ECM) depending upon the situation and many molecular signals can have opposite effects in different vascular beds. Tissue inhibitor of metalloproteinase 1 is antiangiogenic in several tissues, but promotes retinal neovascularization. When cleaved from native collagens, several of the non-collagenous domains (NC1) of basement membrane collagens have antiangiogenic effects in some tissues, but this is context dependent for the NC1 of the alpha 1 chain of collagen IV. It is critical to examine effects in several well-defined model systems before assuming that an ECM component is universally antiangiogenic. In this study, we examined the effects of a recombinant fragment of NC1 of the alpha 2 chain of type IV collagen (alpha2(IV)NC1) in a well-characterized model of ocular neovascularization. Intravitreous or periocular injections of alpha2(IV)NC1 caused selective apoptosis of endothelial cells participating in neovascularization resulting in suppression of neovascularization when the peptide was given prior to onset of new vessel sprouting. Importantly, when the peptide was given after neovascularization had already developed, it caused the new vessels to regress. This suggests that alpha2(IV)NC1, which has previously been shown to suppress tumor angiogenesis in xenograft models, is also a strong antiangiogenic agent in the choroid and is a therapeutic candidate for treatment of neovascular age-related macular degeneration.