Assess BA10 activity in slide-based and immersive virtual reality prospective memory task using functional near-infrared spectroscopy (fNIRS).
By using slide-based task in a laboratory setting, previous studies have found that activation of the rostral prefrontal cortex (BA10) is related to prospective memory performance. In this present study, we used immersive virtual reality (VR) technology to measure PM performance in a real-life task in a simulated virtual environment. Functional near-infrared spectroscopy was used simultaneously to record the rostral prefrontal cortex activities of the subjects. By comparing the data against the ones from the slide-based task, the result suggested that the activation of BA10 in the VR tasks were greater than the one in the slide-based tasks, and the VR tasks have the potential to identify the particular location of BA10 that is connected to the PM performance in our daily lives.


Linking transport and translation of mRNAs with endosomes and mitochondria.
In eukaryotic cells, proteins are targeted to their final subcellular locations with precise timing. A key underlying mechanism is the active transport of cognate mRNAs, which in many systems can be linked intimately to membrane trafficking. A prominent example is the long-distance endosomal transport of mRNAs and their local translation. Here, we describe current highlights of fundamental mechanisms of the underlying transport process as well as of biological functions ranging from endosperm development in plants to fungal pathogenicity and neuronal processes. Translation of endosome-associated mRNAs often occurs at the cytoplasmic surface of endosomes, a process that is needed for membrane-assisted formation of heteromeric protein complexes and for accurate subcellular targeting of proteins. Importantly, endosome-coupled translation of mRNAs encoding mitochondrial proteins, for example, seems to be particularly important for efficient organelle import and for regulating subcellular mitochondrial activity. In essence, these findings reveal a new mechanism of loading newly synthesised proteins onto endocytic membranes enabling intimate crosstalk between organelles. The novel link between endosomes and mitochondria adds an inspiring new level of complexity to trafficking and organelle biology.


[Expression of Bax and Bcl-2 gene in rat testis tissues induced by testicular denervation].
To detect the changes of the expression of Bax and Bcl-2 gene in the denervated testis, and to explore the possible mechanisms underlying the apoptosis of germ cells induced by testicular denervation at the genetic translation level. Eighteen mature SD rats (350-375 g) were equally divided into 3 groups: a sham operation group( SO) , a superior spermatic nerve group (SSN) and an inferior spermatic nerve group (ISN) , and the latter two received bilateral surgical removal of the superior spermatic nerve and the inferior spermatic nerve, respectively. The animals were killed I month after the operation. ISH SP-method was used to detect the expression of Bax and Bcl-2 protein. Significant up-regulation of Bax protein was detected in both the treatment groups 1 month after surgery( P <0. 05) , and the level of Bcl-2 protein remained unchanged. Bax gene is involved in the apoptosis of germ cells induced by testicular denervation.


Resolving kinesin stepping: one head at a time.
Kinesins are well known to power diverse long-range transport processes in virtually all eukaryotic cells. The ATP-dependent processive stepping as well as the regulation of kinesin' activity have, thus, been the focus of extensive studies over the past decades. It is widely accepted that kinesin motors can self-regulate their activity by suppressing the catalytic activity of the "heads." The distal random coil at the C terminus, termed "tail domain," is proposed to mediate this autoinhibition; however, a direct regulatory influence of the tail on the processive stepping of kinesin proved difficult to capture. Here, we simultaneously tracked the two distinct head domains in the kinesin-2 motor using dual-color super resolution microscopy (dcFIONA) and reveal for the first time their individual properties during processive stepping. We show that the autoinhibitory wild-type conformation selectively impacts one head in the heterodimer but not the other. Our results provide insights into the regulated kinesin stepping that had escaped experimental scrutiny so far.


Preparing the patient for a barium enema: a comparison of nurse and patient opinions.
The purpose of this research was to explore possible differences in nurse versus patient opinions about patient education information appropriate for the barium enema procedure. Twenty-eight nurses and 30 patients participated in the study. Findings showed that nurses believed a patient should have more information than the patients believed a patient needs, and that patients wanted only minimal detailed information about events that will happen during the procedure. Rather, patients were interested in knowing the benefits and purpose of the procedure while nurses believed that this information should be provided by the physician and not the nurse. Finally, nurses were dissatisfied, in general, about their patient education information that they have given to patients in the past for a barium enema procedure.


Validity of a single antibody-based lateral flow immunoassay depending on graphene oxide for highly sensitive determination of E. coli O157:H7 in minced beef and river water.
Considering the health risks of E. coli O157:H7 presence in food and water, an affordable and highly sensitive detection method is crucial. Herein, we report the first use of a single antibody-based fluorescent lateral flow immunoassay (FLFIA) depending on non-radiative energy transfer between graphene oxide and quantum dots for determination of E. coli O157:H7 in beef and river water. FLFIA showed a high sensitivity rate thousand-fold better than the conventional lateral flow (LF). In inoculated minced beef and river water samples, the limits of detection were 178 and 133 CFU g-1 or mL-1, respectively. Besides, it presented a high selectivity in the presence of other possible interfering bacteria. The single antibody approach reduced the assay cost to 60% less than the conventional LF. Alongside, the results could be read by portable LF readers or smartphones. These advantages offer FLFIA as a promising technology for pathogen detection in food and water.


Arabidopsis DOK1 encodes a functional dolichol kinase involved in reproduction.
Dolichol phosphate (Dol-P) serves as a carrier of complex polysaccharides during protein glycosylation. Dol-P is synthesized by the phosphorylation of dolichol or the monodephosphorylation of dolichol pyrophosphate (Dol-PP); however, the enzymes that catalyze these reactions remain unidentified in Arabidopsis thaliana. We performed a genome-wide search for cytidylyltransferase motif-containing proteins in Arabidopsis, and found that At3g45040 encodes a protein homologous with Sec59p, a dolichol kinase (DOK) in Saccharomyces cerevisiae. At3g45040, designated AtDOK1, complemented defects in the growth and N-linked glycosylation of the S. cerevisiae sec59 mutant, suggesting that AtDOK1 encodes a functional DOK. To characterize the physiological roles of AtDOK1 in planta, we isolated two independent lines of T-DNA-tagged AtDOK1 mutants, dok1-1 and dok1-2. The heterozygous plants showed developmental defects in male and female gametophytes, including an aberrant pollen structure, low pollen viability, and short siliques. Additionally, the mutations had incomplete penetrance. These results suggest that AtDOK1 is a functional DOK required for reproductive processes in Arabidopsis.


Overcoming challenges in delivering integrated motivational interviewing and cognitive behavioural therapy for bipolar disorder with co-morbid alcohol use: therapist perspectives.
Alcohol misuse is common in bipolar disorder and is associated with worse outcomes. A recent study evaluated integrated motivational interviewing and cognitive behavioural therapy for bipolar disorder and alcohol misuse with promising results in terms of the feasibility of delivering the therapy and the acceptability to participants. Here we present the experiences of the therapists and supervisors from the trial to identify the key challenges in working with this client group and how these might be overcome. Four therapists and two supervisors participated in a focus group. Topic guides for the group were informed by a summary of challenges and obstacles that each therapist had completed at the end of therapy for each individual client. The audio recording of the focus group was transcribed and data were analysed using thematic analysis. We identified five themes: addressing alcohol use versus other problems; impact of bipolar disorder on therapy; importance of avoidance and overcoming it; fine balance in relation to shame and normalising use; and 'talking the talk' versus 'walking the walk'. Findings suggest that clients may be willing to explore motivations for using alcohol even if they are not ready to change their drinking, and they may want help with a range of mental health problems. Emotional and behavioural avoidance may be a key factor in maintaining alcohol use in this client group and therapists should be aware of a possible discrepancy between clients' intentions to reduce misuse and their actual behaviour.


Accuracy of three-dimensional (3D) craniofacial cephalometric landmarks on a low-dose 3D computed tomograph.
The aim of this paper is to compare the accuracy of cephalometric landmark identification using three-dimensional CT (3D-CT) surface rendering with "high-dose" (200 mAs) and "low-dose" (35 mAs) CT protocols. The absorbed dose levels for radiosensitive organs in the maxillofacial region during the exposure for both 3D-CT protocols were also measured. The study population consisted of 15 human dry skulls examined with spiral 3D-CT. 12 cephalometric anatomical landmarks at 7 sites were identified on the 3D-CT surface renderings by 2 observers independently, twice each, using high-dose and low-dose protocols. In total, 1440 imaging measurements were made. Thermoluminescent dosemeters (TLDs) were placed at ten sites around the thyroid and submandibular glands and the eyes in an Alderson phantom for measuring the absorbed dose levels. The intraobserver mean distances between 3D landmarks were smaller for all sites with the high-dose protocol (P = 0.37). There was a significant difference among the observers (P = 0.000004). Interobserver mean distances between 3D landmarks were smaller for four of the seven sites with the low-dose protocol. However, the global interobserver mean distances between 3D landmarks for all sites were smaller with the high-dose protocol (P = 0.028). The low-dose protocol reduced the radiation dose to the thyroid by 6.12, to the submandibular salivary glands by 5.91 and to the eye by 5.44, resulting in a global reduction factor of 5.71. The accuracy in the landmark's identification was maintained when the milliampere-second values were reduced from 200 mAs to 35 mAs. We recommend use of the low-dose protocol for clinical 3D-CT cephalometric applications.


Regulation of GABAA Receptor Subunit Expression in Substance Use Disorders.
The modulation of neuronal cell firing is mediated by the release of the neurotransmitter GABA (γ-aminobuytric acid), which binds to two major families of receptors. The ionotropic GABAA receptors (GABAARs) are composed of five distinct subunits that vary in expression by brain region and cell type. The action of GABA on GABAARs is modulated by a variety of clinically and pharmacologically important drugs such as benzodiazepines and alcohol. Exposure to and abuse of these substances disrupts homeostasis and induces plasticity in GABAergic neurotransmission, often via the regulation of receptor expression. Here, we review the regulation of GABAAR subunit expression in adaptive and pathological plasticity, with a focus on substance use. We examine the factors influencing the expression of GABAAR subunit genes including the regulation of the 5' and 3' untranslated regions, variations in DNA methylation, immediate early genes and transcription factors that regulate subunit expression, translational and post-translational modifications, and other forms of receptor regulation beyond expression. Advancing our understanding of the factors regulating GABAAR subunit expression during adaptive plasticity, as well as during substance use and withdrawal will provide insight into the role of GABAergic signaling in substance use disorders, and contribute to the development of novel targeted therapies.


Strategic Partnerships for Change in an Environmental Justice Community: The ENRRICH Study.
San Bernardino, California, is home to the San Bernardino Railyard (SBR), a major commerce hub with high associated air-pollution, identified as an environmental justice (EJ) issue by local community and air quality agencies. Alarmingly, one elementary school is located only a few hundred yards from SBR. The school, university researchers, and a local community-based organization (CBO) established a partnership to assess potential adverse health impacts in the children and develop interventions and mitigation plans. Study results comparing target school with a demographically matched school verified community concerns finding significantly poorer respiratory health in children attending school near the railyard. Partners are working with local and state collaboratives, the school board, and funding agencies to address the resulting needs of children through education, mitigation, and prevention in an environment where necessary systems changes involving the railyard are elusive. This paper shares lessons learned in moving toward change when addressing an EJ community's health challenges.


Clinical pharmacokinetics of tretinoin.
Recent reports of the dramatic antitumour effect of tretinoin (all-trans retinoic acid) in patients with acute promyelocytic leukaemia (APL) have generated a great deal of interest in the use of this drug as a chemopreventive and therapeutic agent. However, the biological efficacy of tretinoin is greatly impaired by (presumably) an induced hypercatabolism of the drug leading to reduced tretinoin sensitivity and resistance. Several pharmacokinetic studies have shown that plasma drug exposure [as measured by the plasma area under the concentration-time curve (AUC infinity)] declines substantially and rapidly when the drug is administered in a long term daily tretinoin regimen. These observations led to the hypothesis that the rapid development of acquired clinical resistance to tretinoin may have a pharmacological basis and result from an inability to present an effective drug concentration to the leukaemic cells during continuous treatment. The principal mechanisms proposed to explain the increased disappearance of tretinoin from plasma include: (i) decreased intestinal absorption; (ii) enhanced enzymatic catabolism; and (iii) the induction of cytoplasmic retinoic acid binding proteins (CRABP), which leads to increased drug sequestration. The most favoured explanation is that continuous tretinoin treatment acts to induce drug catabolism by cytochrome P450 (CYP) enzymes. Several strategies aimed at preventing or overcoming induced tretinoin resistance have been, and are being, planned. These strategies include intermittent dose administration, administration of pharmacological inhibitors of CYP oxidative enzymes, combination with interferon-alpha and intravenous administration of liposome-encapsulated tretinoin. As these strategies are now under investigation and the number of patients enrolled is small, further studies are needed to determine the efficacy and toxicity of these new schedules of drug administration. In this article we provide an overview of the relevant aspects of tretinoin physiology and pharmacokinetics, and summarise the current status of knowledge to help in the better optimisation of tretinoin administration.


Assignment of the gene for adenine phosphoribosyltransferase to human chromosome 16 by mouse-human somatic cell hybridization.
A series of mouse-human hybrids was prepared from mouse cells deficient in adenine phosphoribosyltransferase (EC 22.214.171.124) and normal human cells. The hybrids were made in medium containing adenine and alanosine, an antimetabolite known to inhibit de novo adenylic acid biosynthesis. The mouse cells, unable to utilize exogenous adenine, were killed in this medium, but the hybrids proliferated as a consequence of their retaining the human aprt gene. The hybrids were then exposed to the adenine analogs 2,6-diaminopurine and 2-fluoroadenine to select for cells that had lost this gene. Before exposure to the adenine analogs, the expression of human adenine phosphoribosyltransferase by the hybrids was strongly associated only with the presence of human chromosome 16, and afterwards this was the only human chromosome consistently lost. This observation suggests that the human aprt gene can be assigned to chromosome 16.


A blend of selected botanicals maintains intestinal epithelial integrity and reduces susceptibility to Escherichia coli F4 infection by modulating acute and chronic inflammation in vitro.
In the pig production cycle, the most delicate phase is weaning, a sudden and early change that requires a quick adaptation, at the cost of developing inflammation and oxidation, especially at the intestinal level. In this period, pathogens like enterotoxigenic Escherichia coli (ETEC) contribute to the establishment of diarrhea, with long-lasting detrimental effects. Botanicals and their single bioactive components represent sustainable well-recognized tools in animal nutrition thanks to their wide-ranging beneficial functions. The aim of this study was to investigate the in vitro mechanism of action of a blend of botanicals (BOT), composed of thymol, grapeseed extract, and capsicum oleoresin, in supporting intestinal cell health during inflammatory challenges and ETEC infections. To reach this, we performed inflammatory and ETEC challenges on Caco-2 cells treated with BOT, measuring epithelial integrity, cellular oxidative stress, bacterial translocation and adhesion, gene expression levels, and examining tight junction distribution. BOT protected enterocytes against acute inflammation: while the challenge reduced epithelial tightness by 40%, BOT significantly limited its drop to 30%, also allowing faster recovery rates. In the case of chronic inflammation, BOT systematically improved by an average of 25% the integrity of challenged cells (p < 0.05). Moreover, when cells were infected with ETEC, BOT maintained epithelial integrity at the same level as an effective antibiotic and significantly reduced bacterial translocation by 1 log average. The mode of action of BOT was strictly related to the modulation of the inflammatory response, protecting tight junctions' expression and structure. In addition, BOT influenced ETEC adhesion to intestinal cells (-4%, p < 0.05), also thanks to the reduction of enterocytes' susceptibility to pathogens. Finally, BOT effectively scavenged reactive oxygen species generated by inflammatory and H2O2 challenges, thus alleviating oxidative stress by 40% compared to challenge (p < 0.05). These results support the employment of BOT in piglets at weaning to help manage bacterial infections and relieve transient or prolonged stressful states thanks to the modulation of host-pathogen interaction and the fine-tuning activity on the inflammatory tone.


Morphological validation of a novel bi-material 3D-printed model of temporal bone for middle ear surgery education.
A new model of 3D-printed temporal bone with an innovative distinction between soft and hard tissues is described and presented in the present study. An original method is reported to quantify the model's ability to reproduce the complex anatomy of this region. A CT-scan of temporal bone was segmented and prepared to obtain 3D files adapted to multi-material printing technique. A final product was obtained with two different resins differentiating hard from soft tissues. The reliability of the anatomy was evaluated by comparing the original CT-scan and the pre-processed files sent to the printer in a first step, and by quantifying the printing technique in a second step. Firstly, we evaluated the segmentation and mesh correction steps by segmenting each anatomical region in the CT-scan by two different other operators without mesh corrections, and by computing distances between the obtained geometries and the pre-processed ones. Secondly, we evaluated the printing technique by comparing the printed geometry imaged using µCT with the pre-processed one. The evaluation of the segmentation and mesh correction steps revealed that the distance between both geometries was globally less that one millimeter for each anatomical region and close to zero for regions such as temporal bone, semicircular canals or facial nerve. The evaluation of the printing technique revealed mismatches of 0.045±0.424 mm for soft and -0.093±0.240 mm for hard tissues between the initial prepared geometry and the actual printed model. While other reported models for temporal bone are simpler and have only been validated subjectively, we objectively demonstrated in the present study that our novel artificial bi-material temporal bone is consistent with the anatomy and thus could be considered into ENT surgical education programs. The methodology used in this study is quantitative, inspired by engineer sciences, making it the first of its kind. The validity of the manufacturing process has also been verified and could, therefore, be extended to other specialties, emphasizing the importance of cross-disciplinary collaborations concerning new technologies.


Hospital Policy and Productivity - Evidence from German States.
Total factor productivity (TFP) growth allows for additional healthcare services under restricted resources. We examine whether hospital policy can stimulate hospital TFP growth. We exploit variation across German federal states in the period 1993-2013. State governments decide on hospital capacity planning (number of hospitals, departments, and beds), ownership, medical students, and hospital investment funding. We show that TFP growth in German hospital care reflects quality improvements rather than increases in output volumes. Second-stage regression results indicate that reducing the length of stay is generally a proper way to foster TFP growth. The effects of other hospital policies depend on the reimbursement scheme: Under activity-based (German Diagnosis-related Group) hospital funding, scope-related policies (privatization and specialization) come with TFP growth. Under fixed daily rate funding, scale matters to TFP (hospital size and occupancy rates). Differences in capitalization in East and West Germany allow to show that deepening capital may enhance TFP growth if capital is scarce. We also show that there is less scope for hospital policies after large-scale restructurings of the hospital sector. Copyright © 2016 John Wiley & Sons, Ltd.


HindIII/EcoRI RFLP of the human immunoglobulin IGHE gene detected with a C epsilon probe in the French and Tunisian populations.
Three different HindIII/EcoRI restriction fragment alleles of the human immunoglobulin IGHE gene have been detected with a C epsilon probe in the Tunisian population. Two of these alleles can be explained by a Negroid contribution in their gene pool.


Prevalence and associated factors of home delivery in Eastern Africa: Further analysis of data from the recent Demographic and Health Survey data.
The current study aimed to determine the magnitude of home delivery and its associated factors in East Africa using data from the Demographic and Health Survey. We pooled data from the Demographic and Health Survey of the 11 East African countries and included a total weighted sample of 126,107 women in the study. The generalized linear mixed model was fitted to identify factors associated with home delivery. Variables with adjusted odds ratio with a 95% confidence interval, and p value < 0.05 in the final generalized linear mixed model were reported to declare significantly associated factors with home delivery. The weighted prevalence of home delivery was 23.68% (95% confidence interval: [23.45, 23.92]) among women in East African countries. Home delivery was highest in Ethiopia (72.5%) whereas, it was lowest in Mozambique (2.8%). In generalized linear mixed model, respondent's age group, marital status, educational status, place of residence, living country, wealth index, media exposure, and number of children ever born were shown significant association with the home delivery in the East African countries. Home delivery varied between countries in the East African zone. Home delivery was significantly increased among women aged 20-34 years, higher number of ever born children, rural residence, never married, or formerly married participants. On the contrary, home delivery decreased with higher educational level, media exposure, and higher wealth index. Wide-range interventions to reduce home delivery should focus on addressing inequities associated with maternal education, family wealth, increased access to the media, and narrowing the gap between rural and urban areas, poor and rich families, and married and unmarried mothers.


Isolation, chemical composition, and ultrastructural features of the cell membrane of the mycoplasma-like organism Spiroplasma citri.
Thin sections of Spiroplasma citri, a mycoplasma-like organism isolated from citrus infected with "Stubborn" disease, showed the organisms to be limited by a single trilaminar plasma membrane. An additional outer layer could, however, be frequently seen in freeze-etched preparations of unwashed cells. The organisms were found to be extremely sensitive to lysis by osmotic shock. The cell membrane of S. citri isolated in this way resembled that of mycoplasmas in ultrastructure and gross chemical composition. The isolated membranes showed the characteristic trilaminar shape in section and the typical particle-studded fracture faces in freeze-etched preparations. Protein and lipid formed over 80% of the total dry weight of the membrane, which had a density of ~1.180 g/cm(3). Cholesterol constituted over 20% of the total membrane lipid. Phosphatidyl-glycerol, synthesized by the organisms, was the major phospholipid. Significant amounts of hexosamine (15 to 35 mug/mg of membrane protein) could be found in the membrane preparations. Our results support the thesis that S. citri does not possess a cell wall, either of the gram-positive or the gram-negative type, though it may be coated by some other type of an envelope or by a slime layer, at least temporarily.


Hypoplastic left heart syndrome secondary to intrauterine rhabdomyoma necessitating single ventricle palliation.
Rhabdomyoma, a benign hamartomatous tumor of the cardiac embryonic myocyte, is the most common intrauterine cardiac tumor and accounts for 0.12% of prenatal fetal studies. Fetal cardiac rhabdomyomas increase in size during second and early third trimester and spontaneously regress postnatally. The clinical presentation is usually benign, however, compromise of the ventricular outflow tract leading to decreased cardiac output and fetal death have been reported. We present a case of large cardiac rhabdomyoma in a fetus that might have caused complete left ventricular outflow tract obstruction and development of hypoplastic left heart syndrome (HLHS) necessitating postnatal single ventricle palliation therapy. The clinical course and outcomes of prenatally diagnosed cardiac rhabdomyoma are reviewed and theories of the development of hypoplastic left heart syndrome are explored.


Imaging in vascular diseases of the lung.
The present review focuses on the recent developments in the field of pulmonary angiography and perfusion by means of computed tomography and magnetic resonance imaging. Computed tomography allows for a detailed analysis of large and small pulmonary vascular pathologies and simultaneously allows for evaluation of the lung parenchyma. Magnetic resonance imaging allows for large and small vessel evaluation as well as noninvasive pressure assessment. Furthermore, recently non-breath-hold contrast-enhanced and noncontrast-enhanced techniques have been developed making magnetic resonance imaging an ideal tool for comprehensive thoracic imaging, even in challenging patients. Noninvasive imaging using computed tomography and magnetic resonance imaging further increases their value in daily clinical practice when it comes to assessment of large and small pulmonary artery disease. As computed tomography is more easy to use and widely available, it remains the diagnostic modality of choice. However, magnetic resonance imaging is the modality of choice when a comprehensive angiographic and functional assessment is deemed necessary.


Evaluation of the Effects of Pharmacist Intervention for Adverse Drug Reaction Detection and Exacerbation Avoidance.
We evaluated the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, as well as the severity and outcome of reactions based on analyses of pharmacist involvement in a collaborative approach to medicine. Of 5436 cases with pharmacist involvement, adverse drug reaction prevention was seen in 440, accounting for 8.1%, and exacerbation avoidance in 213, accounting for 3.9%. We concluded that pharmacist involvement contributes to detect adverse drug reactions and avoid exacerbation, and improves pharmacotherapy safety. We also analyzed 131 cases in which the course after intervention was followed. When categorized by adverse drug reaction severity, Grade 1 and 2 were the same at 45.8%, Grade 3 at 8.4%, respectively. Those findings suggested that pharmacist intervention contributes to early detection of an adverse drug reaction. Also, the relationship between clues for detecting adverse drug reactions by a pharmacist and their severity showed that objective evaluations such as clinical laboratory test results, physical assessments and medication history were important for detecting reactions that became more serious. Patients recovered or recovering from an adverse reaction comprised 76.4%, indicating that pharmacist intervention contributed to exacerbation avoidance and improvement. Our findings revealed the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, and for safety improvement of pharmacotherapy. Additionally, we considered it necessary for the future pharmacist intervention to improve skills of assessing an adverse drug reaction objectively.


Minimizing table time in patients with claustrophobia using focused ferumoxytol-enhanced MR angiography (f-FEMRA): a feasibility study.
To assess the feasibility of a rapid, focused ferumoxytol-enhanced MR angiography (f-FEMRA) protocol in patients with claustrophobia. In this retrospective study, 13 patients with claustrophobia expressed reluctance to undergo conventional MR angiography, but agreed to a trial of up to 10 min in the scanner bore and underwent f-FEMRA. Thirteen matched control patients who underwent gadolinium-enhanced MR angiography (GEMRA) were identified for comparison of diagnostic image quality. For f-FEMRA, the time from localizer image acquisition to completion of the angiographic acquisition was measured. Two radiologists independently scored images on both f-FEMRA and GEMRA for arterial and venous image quality, motion artefact and diagnostic confidence using a 5-point scale, five being best. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the aorta and IVC were measured. The Wilcoxon rank-sum test, one-way ANOVA with Tukey correction and two-tailed t tests were utilized for statistical analyses. All scans were diagnostic and assessed with high confidence (scores ≥ 4). Average scan time for f-FEMRA was 6.27 min (range 3.56 to 10.12 min), with no significant difference between f-FEMRA and GEMRA in diagnostic confidence (4.86 ± 0.24 vs 4.69 ± 0.25, p = 0.13), arterial image quality (4.62 ± 0.57 vs 4.65 ± 0.49, p = 0.78) and motion artefact score (4.58 ± 0.49 vs 4.58 ± 0.28, p > 0.99). f-FEMRA scored significantly better for venous image quality than GEMRA (4.62 ± 0.42 vs 4.19 ± 0.56, p = 0.04). CNR in the IVC was significantly higher for steady-state f-FEMRA than GEMRA regardless of the enhancement phase (p < 0.05). Comprehensive vascular MR imaging of the thorax, abdomen and pelvis can be completed in as little as 5 min within the magnet bore using f-FEMRA, facilitating acceptance by patients with claustrophobia and streamlining workflow. A focused approach to vascular imaging with ferumoxytol can be performed in patients with claustrophobia, limiting time in the magnet bore to 10 min or less, while acquiring fully diagnostic images of the thorax, abdomen and pelvis.


Cumulative neurobehavioral and physiological effects of chronic caffeine intake: individual differences and implications for the use of caffeinated energy products.
The use of caffeine-containing energy products has increased worldwide in recent years. All of the top-selling energy drinks contain caffeine, which is likely to be the primary psychoactive ingredient in these products. Research shows that caffeine-containing energy products can improve cognitive and physical performance. Presumably, individuals consume caffeine-containing energy products to counteract feelings of low energy in situations causing tiredness, fatigue, and/or reduced alertness. This review discusses the scientific evidence for sleep loss, circadian phase, sleep inertia, and the time-on-task effect as causes of low energy and summarizes research assessing the efficacy of caffeine to counteract decreased alertness and increased fatigue in such situations. The results of a placebo-controlled experiment in healthy adults who had 3 nights of total sleep deprivation (with or without 2-hour naps every 12 hours) are presented to illustrate the physiological and neurobehavioral effects of sustained low-dose caffeine. Individual differences, including genetic factors, in the response to caffeine and to sleep loss are discussed. The review concludes with future directions for research on this important and evolving topic.


Evaluation of Wide Corneal Epithelial Remodeling after Small Incision Lenticule Extraction (SMILE) with Wide-Field Optical Coherence Tomography.
This study aims to assess the corneal epithelial remodeling within a 9 mm diameter zone induced by small incision lenticule extraction (SMILE) and evaluate its relationship with the refractive outcomes. A total of 64 eyes of 64 patients were included. Wide-field optical coherence tomography (OCT) was used to measure the epithelial thickness (ET) across a 9 mm diameter area, preoperatively, and after one day, one week, one month, three months, and six months postoperatively. The ET changes were compared among the different time points and analyzed zones. The ET increases from one week to three months and stabilized from three months to six months. Compared to the preoperative values, the mean ET changes at six months in central (2 mm), paracentral (2-5 mm), mid-peripheral (5-7 mm), and peripheral (7-9 mm) zones were 4.37, 4.36, 1.61, and -1.59 μm, respectively. The correlation between the epithelial thickening and the amount of myopia correction was positive in central (P = 0.001) and paracentral zones (P < 0.001) and negative in peripheral zone (P = 0.006). The intended diameter of the optical zone was negatively related to epithelial hyperplasia in the central (P = 0.020) and paracentral zone (P = 0.006), and the correlation was positive in the mid-peripheral zone (P = 0.001). The epithelial thickening of central zone (P = 0.012) and the difference of mean ET between central and paracentral zone (P = 0.020) were negatively related to the spherical equivalent at six months. An asymmetric lenticule-like pattern of epithelial remodeling occurred in 9 mm diameter cornea at six months after myopic SMILE. The epithelial remodeling may affect the refractive outcomes of SMILE.


Insulin resistance and obstructive sleep apnea: is increased sympathetic stimulation the link?
The science of sleep is in early stages of development, and the biochemical consequences of obstructive sleep apnea (OSA) are slowly being identified. Only recently have investigators begun to identify the commonalities and interaction between OSA and insulin resistance, the underlying pathology of type 2 diabetes. Obesity and increasing age play important parts in the natural history of both conditions, which frequently coexist. The purpose of this article is, first, to examine the extent and strength of studies that have investigated the association between OSA and increased insulin resistance or type 2 diabetes and, second, to propose a model that explains the association and cyclical interaction between OSA, obesity, and insulin resistance.


[Use of clopheline in premedication in cesarean section].
Changes in central hemodynamics have been determined and blood loss, the volume of infusion-transfusion therapy, analgesic expenditure, hourly diuresis, the state of the newborn (scored according to Apgar scale) have been studied in 38 women during cesarean section. 26 of them were given additionally 0.15 mg of clopheline in tablets one hour before surgery. The data obtained have shown that clopheline has a positive effect on anesthesia and results of cesarean section. Clopheline is suggested for premedication in uncomplicated cases.


Recrystallization by annealing in SiC amorphized with Ne irradiation.
Alpha-silicon carbide was irradiated with Ne+ ions at room temperature to various fluences up to 7.5 x 10(20) Ne+ m(-2) and then isochronally annealed under observation with a transmission electron microscope. In all cases, thin regions were completely amorphized by irradiation and epitaxial growth occurred from the residual crystalline region by subsequent annealing. Crystal nucleation occurred with annealing at 1000 degrees C in the cases of 3.8 x 10(20) and 7.5 x 10(20) Ne+ m(-2) irradiation, and at 1100 degrees C in the cases of 1.3 x 10(20) and 2.3 x 10(20) Ne+ m(-2) irradiation. Growth or formation of bubbles was observed with annealing at 1000 degrees C after 1.3 x 10(20), 2.3 x 10(20), and 3.8 x 10(20) Ne+ m(-2) irradiation.


MCP-1 expression is specifically regulated during activation of skeletal repair and remodeling.
Monocyte chemotactic protein-1 (MCP-1) belongs to the CC chemokine superfamily and plays a critical role in the recruitment and activation of leukocytes during acute inflammation. We hypothesize that MCP-1 is also an important chemokine that regulates the recruitment and activation of bone cells required for skeletal repair and remodeling. We used the ulnar stress fracture (SFx) model, which allows investigation of focal remodeling with a known time course and precise anatomical location. SFx were created in the right ulna of female Wistar rats using cyclic end loading. Unloaded animals were used as a control. Rats were killed 4 h and 1, 4, 7, and 14 days after loading (n = 10/group); RNA was extracted and converted to cDNA for quantitative PCR analysis using TaqMan gene expression assays. Four hours after loading, MCP-1 gene expression was increased ~30-fold (P < 0.001), remained elevated at 24 h (~12-fold, P < 0.001), then declined by day 14. Relative to the contralateral limb, expression of the receptors CCR1 and CCR2 increased over the 14 days, being significant by 4 days for CCR1 and 14 days for CCR2 (P < 0.05). Other inflammation-related chemokines (RANTES, MIP1a) were not increased at these early time points. Using in situ hybridization and immunohistochemistry in separate animal groups (n = 5/group, control, days 1, 4, 7), MCP-1 mRNA and protein were localized in periosteal osteoblasts associated with woven bone formation at the fracture exit point but not in osteocytes adjacent to the SFx. These data support an important role for MCP-1 in the early phase of SFx repair and activated remodeling.


Male contraception properties of a new synthetic steroid derivative (danazol) in Rattus rattus rufescens.
Chronic administration of Danazol (25 mg/kg body wt) caused lesions in the testes of Rattus rattus Rufescens. Depletion of spermatocytes, spermatids and spermatozoa was conspicuous. Impairment of Leydig cell function was correlated with reduced cell size and depressed accessory sex organ weights. Epididymal cell height was greatly reduced. The lumen was devoid of spermatozoa. Danazol administration inhibited the synthesis of RNA, protein, sialic acid in the testes and accessory sex organs. Total cholesterol of the testes was increased, whereas the acid phosphatase enzyme activity was reduced. Testosterone propionate did not enhance the growth of accessory sex organs in castrated rats receiving Danazol. In conclusion, Danazol inhibits the system of steroidogenesis and spermatogenesis in Rattus rattus, when treated chronically for a period of 40 days. These effects are reversible after 60 days of cessation of drug administration.


New approach to assessment of medication safety in a community hospital.
Use of medications for hospitalized patients is nearly universal, and medication-related injuries are common. Accurate assessment of harm is foundational to development of effective hospital medication safety plans. Using methods nearly identical to those in large national studies, the author examined incidence and typology of medication-related injury. This practice innovation provided a community hospital with its first systematic assessment of medication-related injury. The information gained provided a clearer picture of injury and promoted collaboration.


Soil classification predicts differences in prokaryotic communities across a range of geographically distant soils once pH is accounted for.
Agricultural land is typically managed based on visible plant life at the expense of the belowground majority. However, microorganisms mediate processes sustaining plant life and the soil environment. To understand the role of microbes we first must understand what controls soil microbial community assembly. We assessed the distribution and composition of prokaryotic communities from soils representing four geographic regions on the South Island of New Zealand. These soils are under three different uses (dairy, sheep and beef, and high country farming) and are representative of major soil classification groups (brown, pallic, gley and recent). We hypothesized that pH would account for major community patterns based on 16S profiles, but that land use and location would be secondary modifiers. Community diversity and structure was linked to pH, coinciding with land use. Soil classification correlated with microbial community structure and evenness, but not richness in high country and sheep and beef communities. The impact of land use and pH remained significant at the regional scale, but soil classification provided support for community variability not explained by either of those factors. These results suggest that several edaphic properties must be examined at multiple spatial scales to robustly examine soil prokaryotic communities.


RELATIONSHIP BETWEEN SENSORY ASSESSMENT AND RHEOLOGICAL PROPERTIES OF COSMETIC CREAMS.
One hundred and forty-four untrained judges ranked O/W creams on consistency, spreadability, and stickiness or tackiness, and the results were correlated with rheological characteristics obtained from flow curves. The ranking order for consistency corresponded, for all practical purposes, to the ranking order for shear stress needed to break down the internal structure of the sample (shear rates of 44 s-1 or less). The ranking for spreadability was related to plastic viscosity at 26-32°C. The judges showed poor agreement on the ranking for stickiness (tackiness) and no clear-cut relationship could be obtained between this property and rheological parameters. Consumer preference favored the sample with the highest consistency.


Hyperventilation-induced nystagmus in vestibular neuritis: pattern and clinical implication.
It was the aim of this study to investigate the pattern of evolution of hyperventilation-induced nystagmus (HIN) in vestibular neuritis (VN) and to determine whether HIN influences the dizziness outcome at the last follow-up visit. Fifty-three consecutive patients with VN underwent a quantitative vestibular function test including hyperventilation and the Korean version of the Dizziness Handicap Inventory during the acute period and the follow-up visit. The incidence of HIN was higher in the acute (62%, 33/53) than in the chronic (17%, 9/53) stages of VN. Approximately 70% (6/9) of patients who continued to have persistent HIN at the last follow-up reported dizziness compared to only 27% (12/44) of patients who had no HIN. Patients who complained of persistent dizziness were significantly more likely to have persistent HIN and high Korean Dizziness Handicap Inventory scores at the last follow-up compared with patients who did not suffer from dizziness. In terms of the degree of recovery of dizziness, patients with HIN initially beating toward the contralesional side exhibited significantly more improvement than patients with HIN initially beating toward the ipsilesional side. The presence of either HIN beating toward the ipsilesional side at the acute stage of VN or persistent HIN at the follow-up visit is associated with persistent dizziness.


Motor neuron disease mortality rates in New Zealand 1992-2013.
We determined the mortality rates of motor neuron disease (MND) in New Zealand over 22 years from 1992 to 2013. Previous studies have found an unusually high and/or increasing incidence of MND in certain regions of New Zealand; however, no studies have examined MND rates nationwide to corroborate this. Death certificate data coded G12.2 by International Classification of Diseases (ICD)-10 coding, or 335.2 by ICD-9 coding were obtained. These codes specify amyotrophic lateral sclerosis, progressive bulbar palsy, or other motor neuron diseases as the underlying cause of death. Mortality rates for MND deaths in New Zealand were age-standardized to the European Standard Population and compared with rates from international studies that also examined death certificate data and were age-standardized to the same standard population. The age-standardized mortality from MND in New Zealand was 2.3 per 100,000 per year from 1992-2007 and 2.8 per 100,000 per year from 2008-2013. These rates were 3.3 and 4.0 per 100,000 per year, respectively, for the population 20 years and older. The increase in rate between these two time periods was likely due to changes in MND death coding from 2008. Contrary to a previous regional study of MND incidence, nationwide mortality rates did not increase steadily over this time period once aging was accounted for. However, New Zealand MND mortality rate was higher than comparable studies we examined internationally (mean 1.67 per 100,000 per year), suggesting that further analysis of MND burden in New Zealand is warranted.


Secondary Amyloidosis in Leprosy.
A case of amyloidosis secondary to lepromatous leprosy has been discussed. He had proteinuria, Congo red retention 64 per cent (first hour), hyperglobulinaemia and renal biopsy revealed amyloid deposits. Factors responsible for amyloidosis are highlighted.


The use of the buccal fat pad flap for oral reconstruction.
Many congenital and acquired defects occur in the maxillofacial area. The buccal fat pad flap (BFP) is a simple and reliable flap for the treatment of many of these defects because of its rich blood supply and location, which is close to the location of various intraoral defects. In this article, we have reviewed BFP and the associated anatomical background, surgical techniques, and clinical applications. The surgical procedure is simple and has shown a high success rate in various clinical applications (approximately 90%), including the closure of oroantral fistula, correction of congenital defect, treatment of jaw bone necrosis, and reconstruction of tumor defects. The control of etiologic factors, size of defect, anatomical location of defect, and general condition of patient could influence the prognosis after grafting. In conclusion, BFP is a reliable flap that can be applied to various clinical situations.


Relationship of p53 to the control of apoptotic cell death.
While the centrality of aberrant cell proliferation in cancer was widely acknowledged long ago, it is only recently that the control of cell death has been recognized as an important target in carcinogenesis. Various lines of evidence now suggest that p53 is a positive regulator of cell death, and particularly of apoptosis. Initial studies have shown that the forced overexpression of wild-type p53 can induce apoptosis in a number of cell types, mostly of hematopoietic origin. Subsequent work has confirmed that non-manipulated, endogenous wild-type p53 is required for the efficient induction of apoptotic death by a variety of signals. In particular, the lack of functional p53 interferes with the ability of ionizing radiation, and probably other types of DNA damage, to elicit apoptosis. In addition, p53 function appears to contribute to the dependence of certain cell types on survival factors, and to the induction of apoptosis by viral proteins. The decision whether the activation of wild-type p53 will lead to a growth arrest or to apoptosis, as well as the extent to which a cell is at all responsive to p53, depends on the intracellular context. DNA damage, as well as the constitutive activation of certain growth-promoting genes, are likely to be among the determinants of this context. Illegitimate cell survival may be an important consequence of the loss of p53 function, and may contribute to the carcinogenic effects of p53 inactivation.


Assessment of biomechanical behavior of immature non-vital incisors with various treatment modalities by means of three-dimensional quasi-static finite element analysis.
The objectives of this study were to evaluate the stress distribution and risk of fracture of a non-vital immature maxillary central incisor subjected to various clinical procedures using finite element analysis (FEA). A three-dimensional model of an immature central incisor was developed, from which six main models were designed: untreated immature tooth (C), standard apical plug (AP), resin composite (RC), glass-fibre post (GFP), regeneration procedure (RET), and regeneration with induced root maturation (RRM). Mineral trioxide aggregate (MTA) or Biodentine® were used as an apical or coronal plug. All models simulated masticatory forces in a quasi-static approach with an oblique force of 240 Newton at a 120° to the longitudinal tooth axis. The maximum principal stress, maximum shear stress, risk of fracture, and the strengthening percentage were evaluated. The mean maximum principal stress values were highest in model C [90.3 MPa (SD = 4.4)] and lowest in the GFP models treated with either MTA and Biodentine®; 64.1 (SD = 1.7) and 64.0 (SD = 1.6) MPa, respectively. Regarding the shear stress values, the dentine tooth structure in model C [14.4 MPa (SD = 0.8)] and GFP models [15.4 MPa (SD = 1.1)] reported significantly higher maximum shear stress values compared to other tested models (p < 0.001), while no significant differences were reported between the other models (p > 0.05). No significant differences between MTA and Biodentine® regarding maximum principal stress and maximum shear stress values for each tested model (p > 0.05). A maximum strain value of 4.07E-03 and maximum displacement magnitude of 0.128 mm was recorded in model C. In terms of strengthening percentage, the GFP models were associated with the highest increase (22%). The use of a GFP improved the biomechanical performance and resulted in a lower risk of fracture of a non-vital immature maxillary central incisor in a FEA model.


Targeted silencing of MART-1 gene expression by RNA interference enhances the migration ability of uveal melanoma cells.
Uveal melanoma (UM) is the most common primary intraocular malignancy and the leading potentially fatal primary intraocular disease in adults. Melanoma antigen recognized by T-cells (MART-1) has been studied extensively as a clinically important diagnostic marker for melanoma, however, its biological function remains unclear. In the present study, the UM cell line SP6.5, which showed a high level of MART-1 expression, was subjected to small interfering RNA-mediated silencing of MART-1. Silencing of MART-1 expression increased the migration ability of SP6.5 cells and down-regulated the expression of the metastasis suppressor NM23. Our results suggest that MART-1 is a candidate target for the development of therapeutic strategies for UM and in particular for the suppression of metastasis associated with this malignancy.


Electrophysiological characterization of membrane transport proteins.
Active transport in biological membranes has been traditionally studied using a variety of biochemical and biophysical techniques, including electrophysiology. This review focuses on aspects of electrophysiological methods that make them particularly suited for the investigation of transporter function. Two major approaches to electrical recording of transporter activity are discussed: (a) artificial planar lipid membranes, such as the black lipid membrane and solid supported membrane, which are useful for studies on bacterial transporters and transporters of intracellular compartments, and (b) patch clamp and voltage clamp techniques, which investigate transporters in native cellular membranes. The analytical power of these methods is highlighted by several examples of mechanistic studies of specific membrane proteins, including cytochrome c oxidase, NhaA Na(+)/H(+) exchanger, ClC-7 H(+)/Cl(-) exchanger, glutamate transporters, and neutral amino acid transporters. These examples reveal the wealth of mechanistic information that can be obtained when electrophysiological methods are used in combination with rapid perturbation approaches.


The effects of obesity and metabolic abnormalities on severe COVID-19-related outcomes after vaccination: A population-based study.
Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% received one or more doses of vaccine, respectively. In the UK Biobank, participants are followed from the vaccination date until October 18, 2021. We found that obesity and metabolic abnormalities (namely, hyperglycemia, hyperlipidemia, and hypertension) were modifiable factors for severe COVID-19 in vaccinated patients (all p < 0.05). When metabolic abnormalities were present, regardless of obesity, the risk of severe COVID-19 was higher than that of metabolically normal individuals (all p < 0.05). Moreover, pharmacological interventions targeting such abnormalities (namely, antihypertensive [adjusted hazard ratio (aHR) 0.64, 95% CI 0.48-0.86; p = 0.003], glucose-lowering [aHR 0.55, 95% CI 0.36-0.83; p = 0.004], and lipid-lowering treatments [aHR 0.50, 95% CI 0.37-0.68; p < 0.001]) were significantly associated with a reduced risk for this outcome. These results show that more proactive health management of patients with obesity and metabolic abnormalities is critical to reduce the incidence of severe COVID-19 after vaccination.


Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy.
177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination regimes of programmed death-ligand 1 (PD-L1) inhibition and concomitant 177Lu-PSMA therapy have been proposed to increase the response rate. However, the interplay of immune landscape and 177Lu-PSMA therapy efficacy is poorly understood. Between March 2018 and December 2021, a total of 168 patients were referred to 177Lu-PSMA therapy in our department and received a mean total dose of 21.9 GBq (three cycles in mean). All patients received baseline PSMA positron emission tomography to assess the PSMA uptake. The histopathological specimen of the primary prostate tumor was available with sufficient RNA passing quality control steps for genomic analysis in n=23 patients. In this subset of patients, tumor RNA transcriptomic analyses assessed 74 immune-related features in total, out of which n=24 signatures were not co-correlated and investigated further for outcome prognostication. In the subset of patients who received 177Lu-PSMA therapy, PD-L1 was not significantly associated with OS (HR per SD change (95% CI) 0.74 (0.42 to 1.30); SD: 0.18; p=0.29). In contrast, PD-L2 signature was positively associated with longer OS (HR per SD change 0.46 (95% CI 0.29 to 0.74); SD: 0.24; p=0.001; median OS 17.2 vs 5.7 months in higher vs lower PD-L2 patients). In addition, PD-L2 signature correlated with PSA-response (ϱ=-0.46; p=0.04). The PD-L2 signature association with OS was significantly moderated by L-Lactatdehydrogenase (LDH) levels (Cox model interaction p=0.01). Higher PD-L2 signature might be associated with a better response to 177Lu-PSMA therapy and warrants further studies investigating additional immunotherapy. In contrast, PD-L1 was not associated with outcome. The protective effect of PD-L2 signature might be present only in men with lower LDH levels.


Psychometric Properties of the Chinese Version of the Brief State Rumination Inventory.
State rumination, unlike trait rumination which is described as a persistent and stable response style, is usually triggered by a specific stressful event and causes negative emotions within a short period of time. The measurement methods of trait rumination, such as the ruminative response scale (RRS), are therefore not fully applicable to state rumination. Recently, researchers have developed the brief state rumination inventory (BSRI) to characterize state rumination, addressing the gap in the field of accurate measurement of state rumination. To develop such an effective tool in the Chinese context, we developed a Chinese version of the BSRI and tested its psychometric properties. Two studies were conducted to address the research goal. In Study 1, we recruited 512 subjects, each of whom completed the Chinese version of the BSRI, RRS, emotional regulation questionnaire (ERQ), depression-anxiety-stress scale (DASS), and positive and negative affect scale (PANAS). Results showed that the scores of the BSRI were positively correlated with all other scale scores (ps < 0.001), and the correlation with the RRS was the highest, indicating that the BSRI showed good convergent validity. Additionally, the Cronbach's alpha coefficient for the Chinese version of the BSRI was 0.93. Study 2 aimed to examine the ecological validity of the Chinese version of the BSRI. We recruited another 54 subjects who were randomly divided into two groups, with 27 in the rumination induction group and 27 in the distraction group, and recorded the BSRI scores of the two groups before and after a specific experiment. We found there was a significant increase in BSRI scores after rumination induction (t = 3.91, p < 0.001), while there was no significant difference in the concrete distraction group before and after the experiment (t = 0.70, p = 0.48). In sum, the Chinese version of the BSRI showed good reliability and validity for assessing state rumination in the general Chinese population.


[LAPAROSCOPIC APPROACH AND SURGICAL CONSIDERATIONS IN RESECTION OF A LARGE EPIPHRENIC ESOPHAGEAL DIVERTICULUM].
Epiphrenic diverticulum of the esophagus is an uncommon finding. Small diverticula are usually asymptomatic in nature. Large diverticula may present with dysphagia, chest or upper abdominal discomfort, vomiting, irritating cough or halitosis. There are a few different surgical approaches to epiphrenic diverticulum resection. It can be performed with an abdominal or a thoracic approach and in an open or a laparoscopic manner. In this case report we present a 70 years old male patient with a giant epiphrenic diverticulum and dysphagia. The patient was operated upon via a laparoscopic abdominal approach with intra-operative endoscopic assistance and underwent a diverticulum resection. We present a review of the different kinds of esophageal diverticula, the mechanism of their formation, and the surgical considerations associated with choosing the appropriate surgical approach.


Outcomes of Revision Hip Arthroplasty Using the Supine Anterior-Based Muscle Sparing Approach.
In the United States, the number of revision total hip arthroplasty (THA) cases is projected to grow from 50,000 in 2014 to 85,000 by 2030. The anterior-based muscle sparing approach (ABMS) has been described as a viable approach for primary THA, but little has been written in the revision setting. This study compares the supine ABMS approach to alternative approaches in revision THA. A retrospective review was performed on 149 revision THAs from 2016 to 2019. The ABMS, modified Müller Hardinge (MMH), and posterolateral (PL) approaches were studied. Age, reason for arthroplasty, length of operation, length of stay, blood loss, and complications were extracted. Clinical outcomes were measured by the Hip Disability and Osteoarthritis Outcome Score, Modified Harris Hip Score, University of California Los Angeles activity score, and Veterans RAND 12 Mental/Physical scores. Approaches included 52 ABMS (33.8%), 58 MHH (37.7%), and 39 PL (25.3%). Complexity of cases and patient demographics were equivalent for each cohort. Extensile approaches were used in 12 of the 52 ABMS, 26 of the 58 MMH, and 13 of the 39 PL revisions, including acetabular cages, open reduction internal fixation for periprosthetic fracture, extended trochanteric osteotomy, hardware removal, and/or pelvic discontinuity. There were no differences for blood loss, length of stay, complications, and outcome scores between approaches. We found no difference in complications or clinical outcome scores between the ABMS, MMH, and PL approaches for revision THA. The supine ABMS approach provides adequate extensile exposure of the femur and acetabulum for complex revisions and is a reliable approach for revision THA.


Intraperitoneal chemotherapy with melphalan.
We administered melphalan by the intraperitoneal route to investigate its toxicity and pharmacokinetics. The drug was instilled with 2 litres of fluid and allowed to dwell in the peritoneal cavity for 4 hours. No local toxicity was detected by clinical examination, laboratory tests, or histologic examination. The intraperitoneal route allowed the dose to be increased to approximately three times the maximum dose tolerated intravenously before drug leaking into the systemic circulation produced dose-limiting myelosuppression. The peak peritoneal concentration averaged 93-fold greater than the plasma concentration, and total drug exposure for the peritoneal cavity averaged 63-fold greater than that for plasma. Tumor regressions were observed in patients with ovarian carcinoma and gastrointestinal adenocarcinomas. This study shows that from the pharmacologic point of view, if any portion of the tumor can be reached by intraperitoneal instillation, then there is a very strong rationale for the administration of melphalan by the intraperitoneal route, rather than the oral or intravenous route, for the treatment of tumors confined to the peritoneal cavity.


Semifluorinated Alkylphosphonic Acids Form High-Quality Self-Assembled Monolayers on Ag-Coated Yttrium Barium Copper Oxide Tapes and Enable Filamentization of the Tapes by Microcontact Printing.
A custom-designed semifluorinated phosphonic acid, (9,9,10,10,11,11,12,12,13,13,14,14,15,15,16,16,16-heptadecafluorohexadecyl)phosphonic acid (F8H8PA), and a normal hexadecylphosphonic acid (H16PA) were synthesized and used to generate self-assembled monolayers (SAMs) on commercially available yttrium barium copper oxide (YBCO) tapes. In this study, we wished to evaluate the effectiveness of these monolayer films as coatings for selectively etching YBCO. Initial films formed by solution deposition and manual stamping using a non-patterned polydimethylsiloxane stamp allowed for a comparison of the film-formation characteristics. The resulting monolayers were characterized by X-ray photoelectron spectroscopy (XPS), contact angle goniometry, and polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). To prepare line-patterned (filamentized) YBCO tapes, standard microcontact printing (μ-CP) procedures were used. The stamped patterns on the YBCO tapes were characterized by scanning electron microscopy (SEM) before and after etching to confirm the effectiveness of the patterning process on the YBCO surface and energy-dispersive X-ray spectroscopy (EDX) to obtain the atomic composition of the exposed interface.


Neutron powder-diffraction study of phase transitions in strontium-doped bismuth ferrite: 1. Variation with chemical composition.
We report results from a study of the crystal and magnetic structures of strontium-doped BiFeO3using neutron powder diffraction and the Rietveld method. Measurements were obtained over a wide range of temperatures from 300-800 K for compositions between 10%-16% replacement of bismuth by strontium. The results show a clear variation of the two main structural deformations-symmetry-breaking rotations of the FeO6octahedra and polar ionic displacements that give ferroelectricity-with chemical composition, but relatively little variation with temperature. On the other hand, the antiferromagnetic order shows a variation with temperature and a second-order phase transition consistent with the classical Heisenberg model. There is, however, very little variation in the behaviour of the antiferromagnetism with chemical composition, and hence with the degree of the structural symmetry-breaking distortions. We therefore conclude that there is no significant coupling between antiferromagnetism and ferroelectricity in Sr-doped BiFeO3and, by extension, in pure BiFeO3.


The use of sentinel node biopsy in breast cancer patients undergoing skin sparing mastectomy and immediate autologous reconstruction.
Intraoperative frozen section examination of the sentinel node in breast cancer patients is associated with a high number of incorrect negative results with the sentinel node becoming positive in the permanent examination and necessitating a secondary axillary lymph node dissection. A reoperation of the axilla following skin-sparing mastectomy and immediate autologous tissue reconstruction may compromise the vascular pedicle of the flap and should be avoided. Eighty breast cancer patients underwent skin-sparing mastectomy with immediate autologous reconstruction and sentinel node biopsy followed by axillary lymph node dissection irrespective of the result of the frozen section of the sentinel node. The goal of the study was to identify a subgroup of patients with incorrect negative sentinel node(s) in the frozen section who may forego a secondary axillary lymph node dissection due to a low risk of positive nonsentinel nodes. Frozen section examination of the sentinel node was negative in 58 patients and positive in 22 patients. Permanent histologic examination revealed tumor in 13 of 58 (22.4 percent) sentinel node(s) found negative in the frozen section. None of these 13 patients showed positive nodes in the axillary specimen, whereas nine of 22 patients with their metastases in the sentinel node found through intraoperative frozen section examination had additional positive nonsentinel node(s) (p = 0.001). Patients with incorrect negative sentinel node(s) found in the frozen section examination had a significantly decreased risk for additional positive nonsentinel node(s) compared with patients with sentinel node metastases found in the frozen section. However, to avoid a secondary axillary lymph node dissection, the authors suggest performing sentinel node biopsy before mastectomy under local anesthesia to have the permanent result of the sentinel node available before a planned reconstruction.


The emergence of personal growth amongst healthcare professionals who care for dying children.
ABSTRACTObjective:Compassion fatigue, burnout, and vicarious traumatization are prominent topics in the current literature on the impact of the rewarding but challenging work of healthcare professionals who care for patients with life-limiting illnesses. The positive effects of caregiving constitute a newly emerging outcome that has been relatively unexplored in the pediatric literature, and yet they may play an important role in contributing to the satisfaction and well-being of the healthcare professionals who care for children who have a life-limiting illness. This paper reports the results of a secondary analysis of qualitative interview transcripts that explored the experiences of hospital-based pediatric healthcare providers caring for children with varied life-limiting illnesses. In-depth qualitative interviews were conducted with 25 healthcare professionals (9 social workers, 8 nurses, and 8 physicians). The majority of participants were women (80%), with an age range between 20 and 60 years, and most (84%) had the experience of caring for more than 15 dying children. Thematic analysis was conducted using interpretive description and constant comparison. Every healthcare professional interviewed experienced personal growth as a result of their providing care for dying children. Three dimensions of personal growth were most consistently reported: (1) new or altered life perspectives, (2) enhanced personal resources, and (3) benevolence. A deeper understanding of the phenomenon of personal growth could help healthcare organizations to implement innovative approaches that would counterbalance compassion fatigue, and thereby enhance both healthcare provider well-being and child and family outcomes.


Can the attending anesthesiologist accurately predict the duration of anesthesia induction?
In a prospective, observational study, the attending anesthesiologists' prediction of anesthesia release time (ART) of the patient to the surgical team was highly correlated with actual ART (r = 0.77; P < or = 0.001). However, this was true only in the aggregate (n = 1265 patients). Indeed, offsetting degrees of under- and over-predicting (24% each) reduced accuracy to only 53% per individual case. For example, under-prediction was associated with ASA physical status IV, a regional anesthetic technique, age >65 yr, and the use of invasive hemodynamic monitoring (P = 0.006). In fact, as the degree of case difficulty increased, the correlation coefficient between predicted and actual ART decreased, indicating a poor predictive value with more difficult inductions (r = 0.82 to r = 0.44; P < or = 0.004). We conclude that knowledge of the presence of specific factors that lead to inaccurate predictions of time required for induction of anesthesia may enhance the accuracy of the operating room schedule.


[Survey on the occupational musculoskeletal disorder and its risk factors among male steelworkers].
To study the prevalence of occupational musculoskeletal disorders (OMSD) of male steelworkers and explore its occupational and individual risk factors. 1620 male workers from a steel mill were selected as subjects through random cluster sampling in 2010. A revised Nordic Musculoskeletal disorder standard questionnaire and a questionnaire from National Institute for Occupational and Health of the Netherlands were used to ask and record the OMSD and its risk factors. The questionnaires were filled in by the workers. Annual prevalence of OMSD in different parts of the body were counted according to different age, working years and educational level, logistic regression was used to analyze its influence factors. OMSD in these workers primarily located in waist, neck and shoulders, annual prevalence were 51.0% (825), 48.5% (785) and 37.7% (610) respectively. Annual prevalence of other body parts were 28.0% (454) for back, 23.6% (383) for knee, 21.0% (341) for wrist, 17.9% (290) for ankle/foot, 14.1% (229) for elbow and 12.7% (205) for coxa. The annual prevalence of OMSD for each part tended to increase with age, mainly in waist and neck. Of the different age groups ≤ 24, 25 - 29, 30 - 34, 35 - 39, 40 - 44, 45 - 49, ≥ 50, the annual prevalence in waist was 26.4% (43/163), 37.8% (71/188), 52.8% (162/307), 55.6% (160/288), 53.8% (99/184), 55.9% (80/143), 61.6% (204/331) respectively (χ(2) = 72.5, P < 0.05); correspondingly, the annual prevalence in neck was 22.7% (37/163), 40.4% (76/188), 50.2% (154/307), 48.6% (140/288), 56.0% (103/184), 53.1% (76/143), 57.7% (191/331) respectively (χ(2) = 65.3, P < 0.05). The annual prevalence of OMSD increased with the working years. Of the different working years groups ≤ 4, 5 - 9, 10 - 14, 15 - 19, 20 - 24, 25 - 29, ≥ 30, the annual prevalence in waist was 30.2% (85/281), 46.2% (66/143), 56.4% (162/287), 56.8% (137/241), 50.6% (78/154), 59.2% (90/152), 60.7% (173/285) respectively (χ(2) = 71.3, P < 0.05);correspondingly, the annual prevalence in neck was 28.8% (81/281), 49.0% (70/143), 52.6% (151/287), 50.2% (121/241), 51.9% (80/154), 53.9% (82/152), 59.3% (169/285) respectively (χ(2) = 61.5, P < 0.05). The annual prevalence of OMSD decreased with education level. Of the different groups of education level (junior high school level and below, senior high school level, university level or above), the OMSD prevalence in waist was 61.5% (176/286), 61.9% (359/692), 44.2% (272/615) respectively (χ(2) = 26.0, P < 0.05);correspondingly, the annual prevalence in neck was 56.3% (161/286), 50.0% (346/692), 42.3% (260/615)respectively (χ(2) = 21.2, P < 0.05). Univariate logistic regression showed that the work load factors such as the working years ≥ 30 (OR = 3.562, 95%CI: 2.514 - 5.046), maintain substantial stoop for a long time (OR = 2.003, 95%CI: 1.612 - 2.488), often stooping with vast scale (OR = 1.897, 95%CI: 1.557 - 2.312), and torso repeating same action many times per minute (OR = 1.870, 95%CI: 1.529 - 2.288) could increase the annual prevalence of OMSD in waist most likely (P < 0.05). The working years ≥ 30 (OR = 3.597, 95%CI: 2.535 - 5.105), neck leaning forward (OR = 2.455, 95%CI: 2.010-2.99), neck leaning back (OR = 1.999, 95%CI: 1.569 - 2.546), and neck rotation (OR = 2.381, 95%CI: 1.907 - 2.972) were main risk factors causing OMSD in neck (P < 0.05). The most serious musculoskeletal disorders of male steelworkers were waist and neck pain. Personal factors such as age, working years, work load factors such as harmful working postures, manual heavy lifting, and labour organizational factors such as work overtime were the main risk factors of musculoskeletal disorders to the male steelworkers.


Serum adipokines and vitamin D levels in patients with type 1 diabetes mellitus.
Adiponectin, leptin and resistin are adipokines that play important roles in the regulation of lipid and carbohydrate metabolism in type 2 diabetes (T2DM). However, their influence in type 1 diabetes mellitus is still unknown. The aim of this study was to measure serum adiponectin, leptin and resistin levels and to investigate their relationships with vitamin D and other clinical and laboratory parameters in patients with type 1 diabetes. Fifty subjects with type 1 diabetes and 50 healthy age- and sex-matched subjects were selected from the Endocrinology Outpatient Clinic of Cairo University Pediatrics Hospital. Enzyme-linked immunosorbent assay was used to measure the levels of leptin, adiponectin and resistin. Vitamin D levels were measured using electro-chemiluminescence immunoassay. There were no significant differences in adiponectin and leptin levels between diabetic and control subjects (p = 0.6 and p = 0.5 respectively). Resistin levels were significantly higher in the diabetic group compared to controls (p < 0.001) and in postpubertal patients compared to prepubertal patients (p < 0.04). Serum resistin in type 1 diabetes showed a negative correlation with vitamin D (p < 0.001) and a positive correlation with glycated hemoglobin (HbA1c) (p = 0.006), while other adipokines were not interrelated. These results strongly support a role of resistin and vitamin D deficiency in the pathophysiology of type 1 diabetes. Vitamin D may be involved in resistin regulation through an unknown mechanism. Further studies are recommended to understand resistin regulation in type 1 diabetes.


Quartic scaling MP2 for solids: A highly parallelized algorithm in the plane wave basis.
We present a low-complexity algorithm to calculate the correlation energy of periodic systems in second-order Møller-Plesset (MP2) perturbation theory. In contrast to previous approximation-free MP2 codes, our implementation possesses a quartic scaling, O(N4), with respect to the system size N and offers an almost ideal parallelization efficiency. The general issue that the correlation energy converges slowly with the number of basis functions is eased by an internal basis set extrapolation. The key concept to reduce the scaling is to eliminate all summations over virtual orbitals which can be elegantly achieved in the Laplace transformed MP2 formulation using plane wave basis sets and fast Fourier transforms. Analogously, this approach could allow us to calculate second order screened exchange as well as particle-hole ladder diagrams with a similar low complexity. Hence, the presented method can be considered as a step towards systematically improved correlation energies.


Assessing the carbon emission performance of digital greening synergistic transformation: evidence from the dual pilot projects in China.
Digital greening synergistic transformation (DGST) is a new engine for achieving dual carbon targets. Using panel data from 281 Chinese cities between 2003 and 2019, this study investigates the effect and transmission mechanism of the DGST on carbon emission performance. It is based on the quasi-natural experiments of the dual pilot projects "Broadband China" and "Low-carbon City", as well as the multi-period difference-in-difference method. The empirical findings are as follows: (1) DGST, represented by the dual pilot projects, effectively enhances carbon emission performance. Compared to the isolated "Broadband China" and "Low-Carbon City" pilot projects, establishing dual pilot projects generates a more pronounced carbon emission reduction effect through synergistic effects. (2) In terms of dynamic effects, the carbon emission reduction effect in dual pilot cities appears in the first year following initiation, indicating a certain temporal aspect to this effect. (3) Mechanism analysis reveals that the impact of DGST on carbon emission performance is channeled through two pathways: industrial structural adjustment and low-carbon technology innovation. (4) The positive impact of DGST on carbon emission performance exhibits heterogeneity, primarily present in cities with higher levels of financial technology, human capital, and new infrastructure development. It implies that the implementation of DGST necessitates adequate human, financial, and material support. In conclusion, this research contributes empirical evidence for further exploring policy synergies, offering support for achieving dual carbon targets through DGST.


Rotary blood pumps as definitive treatment for severe heart failure.
Rotary blood pumps are increasingly recognized as mainstream therapy for severely symptomatic heart failure. Carefully targeted refinements in patient selection and postoperative care have substantially reduced the adverse event burden. These improvements translate into better survival and quality of life in comparison with medical management. Medium-term outcomes now compete favorably with cardiac transplantation, although evidence-based outcome data indicate that transplant and 'lifetime' left ventricular-assist device (LVAD) candidates are fundamentally different. Significant challenges remain in relation to neurological injury and right heart failure, which may continue to limit exercise capacity. In the meantime, both physician awareness and patient access to LVAD technology remain limited. The debate is rarely between cardiac transplant or lifetime LVAD. It should focus on the choice between pump versus palliative care for the thousands of patients of all age groups who are judged ineligible for transplantation. Comprehensive healthcare systems must consider contemporary evidence and provide the most symptomatic of heart failure patients with effective care. Cardiac resynchronization therapy is no longer the ceiling for this.


Morphologic multiplicity of smooth muscle cell monolayers from extreme lung parenchyma of high-altitude-hypoxia sheep.
Chronic hypoxia causes lung pathology but little is known about how morphologic changes occur or about the progenitor cells of lung remodeling. Since the alveolar region is the first site of environmental challenge, smooth muscle cell (SMC) monolayers derived from close to the alveoli were studied for morphologic patterns. Thus we aimed to deduce any impact of environmental challenge on juxta-alveolar cells and identify phenotypical changes that are suspect precedence to lung pathologies such as cancer. METHODS.: Lung tissues from freshly sacrificed adult sheep that had been kept in high altitude hypoxia for approximately 4 months were used. The lung tissues were studied for macroscopic signs of pathology. Lung parenchymal explants from approximately 0.5-1.5 mm to the lung edge were cultured for isolation of upper generation SMCs which are closer to the air/blood interphase. The cells were characterized by fluorescence immunohistochemistry using a monoclonal antibody against alpha-smooth muscle actin. The monolayer morphologies of the derived stable cell lines were compared. We observed that the distal lung parenchyma of the chronically hypoxic sheep yielded six distinct smooth muscle cell morphological varieties: apoptotic, sub-confluent, spindle-form, hill and valley, swirl, and rhomboid monolayers. The control sheep lungs yielded two varieties of smooth muscle cells: swirl and hill-and-valley monolayer formations at confluence. All the cell lines were jointly generated from the terminals of the vascular and bronchiolar trees. Chronic high altitude hypoxia appears to induce morphological variation in juxta-alveolar smooth muscle cells in the ovine lung.


[Effects of andrographolide on the expression of procoagulant and fibrinolytic inhibition factors in rat type II alveolar epithelial cells stimulated by lipopolysaccharide].
To determine the effect of andrographolide (AD) on the expression of procoagulant and fibrinolytic inhibitory factors in rat type II alveolar epithelial cells (AEC II) stimulated by lipopolysaccharide (LPS). The AEC II cells RLE-6TN in the logarithmic growth phase were divided into 5 groups: the normal control (NC) group, the LPS group, and the 6.25, 12.5, and 25 mg/L AD groups (AD 6.25 group, AD 12.5 group, AD 25 group). The NC group was cultured with RPMI 1640 conventional medium. In the LPS group, 5 mg/L LPS was added to the RPMI 1640 conventional medium for stimulation. Cells in the AD groups were treated with 6.25, 12.5, and 25 mg/L AD in advance for 1 hour and then given LPS to stimulate the culture. The cells and cell culture supernatant were collected 24 hours after LPS stimulation. The protein and mRNA expressions of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibition-1 (PAI-1) in cells were detected by Western blotting and real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). The levels of procollagen III peptide (PIIIP), thrombin-antithrombin complex (TAT), antithrombin III (AT-III) and activated protein C (APC) in the cell supernatant were detected by enzyme linked immunosorbent assay (ELISA). Compared with the NC group, the protein and mRNA expressions of TF and PAI-1 in the LPS group were significantly increased, and the protein and mRNA expressions of TFPI were significantly reduced. At the same time, the levels of PIIIP and TAT in the cell supernatant were significantly increased, the levels of AT-III, APC were significantly reduced. Compared with the LPS group, the protein and mRNA expressions of TF and PAI-1 in AD 6.25 group, AD 12.5 group, AD 25 group were significantly reduced [TF/GAPDH: 0.86±0.08, 0.45±0.04, 0.44±0.04 vs. 1.32±0.10, TF mRNA (2-ΔΔCt): 2.59±0.25, 2.27±0.05, 1.95±0.04 vs. 4.60±0.26, PAI-1/GAPDH: 2.11±0.07, 1.45±0.04, 0.86±0.09 vs. 2.56±0.09, PAI-1 mRNA (2-ΔΔCt): 3.50±0.22, 2.23±0.29, 1.84±0.09 vs. 6.60±0.27, all P < 0.05], while the protein and mRNA expressions of TFPI were significantly increased [TFPI/GAPDH: 0.78±0.05, 0.81±0.03, 0.84±0.07 vs. 0.36±0.02, TFPI mRNA (2-ΔΔCt): 0.46±0.09, 0.69±0.07, 0.91±0.08 vs. 0.44±0.06, all P < 0.05]. Also the levels of PIIIP and TAT in the cell supernatant were significantly reduced, and the levels of AT-III and APC were significantly increased [PIIIP (μg/L): 13.59±0.23, 12.66±0.23, 10.59±0.30 vs. 15.82±0.29, TAT (ng/L): 211.57±6.41, 205.69±4.04, 200.56±9.85 vs. 288.67±9.84, AT-III (μg/L): 102.95±3.86, 123.92±2.63, 128.67±1.67 vs. 92.93±3.36, APC (μg/L): 1 188.95±14.99, 1 366.12±39.93, 1 451.15±29.69 vs. 1 145.55±21.07, all P < 0.05]. With the increase of the dose of AD, the above-mentioned promotion and inhibition effects became more obvious. In the AD 25 group, TF, PAI-1 protein and mRNA expressions decreased, TFPI mRNA expression increased, PIIIP level in the supernatant decreased and AT-III, APC levels increased compared with AD 6.25 group, the difference was statistically significant, and the decrease of PAI-1 protein expression and PIIIP level in the supernatant were also statistically significant compared with AD 12.5 group. Andrographolide in the dose range of 6.25-25 mg/L can dose-dependently inhibit the expression and secretion of procoagulant and fibrinolytic inhibitor-related factors in AEC II cells RLE-6TN stimulated by LPS, and promote the secretion of anticoagulant factors. 25 mg/L has the most obvious effect.


The Role of Epidermal Growth Factor Receptor Family of Receptor Tyrosine Kinases in Mediating Diabetes-Induced Cardiovascular Complications.
Diabetes mellitus is a major debilitating disease whose global incidence is progressively increasing with currently over 463 million adult sufferers and this figure will likely reach over 700 million by the year 2045. It is the complications of diabetes such as cardiovascular, renal, neuronal and ocular dysfunction that lead to increased patient morbidity and mortality. Of these, cardiovascular complications that can result in stroke and cardiomyopathies are 2- to 5-fold more likely in diabetes but the underlying mechanisms involved in their development are not fully understood. Emerging research suggests that members of the Epidermal Growth Factor Receptor (EGFR/ErbB/HER) family of tyrosine kinases can have a dual role in that they are beneficially required for normal development and physiological functioning of the cardiovascular system (CVS) as well as in salvage pathways following acute cardiac ischemia/reperfusion injury but their chronic dysregulation may also be intricately involved in mediating diabetes-induced cardiovascular pathologies. Here we review the evidence for EGFR/ErbB/HER receptors in mediating these dual roles in the CVS and also discuss their potential interplay with the Renin-Angiotensin-Aldosterone System heptapeptide, Angiotensin-(1-7), as well the arachidonic acid metabolite, 20-HETE (20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid). A greater understanding of the multi-faceted roles of EGFR/ErbB/HER family of tyrosine kinases and their interplay with other key modulators of cardiovascular function could facilitate the development of novel therapeutic strategies for treating diabetes-induced cardiovascular complications.


QUANTITATIVE GENETICS OF SURVIVAL AND GROWTH IN IMPATIENS CAPENSIS.
When variation in life-history characters is caused by many genes of small effect, then quantitative-genetic parameters may quantify constraints on rate and direction of microevolutionary change. I estimated heritabilities and genetic correlations for 16 life-history and morphological characters in two populations of Impatiens capensis, a partially self-pollinating herbaceous annual. The Madison population had little or no additive genetic variance for any of these characters, while the Milwaukee population had significant narrowsense heritabilities and genetic correlations for several traits, including adult size, which is highly correlated with fitness. All genetic correlations among fitness components were positive, hence there is no evidence for antagonistic pleiotropy among these traits. Dissimilarity of heritabilities in the two populations supports theoretical predictions that long-term changes in genetic variance-covariance patterns may occur when population sizes are small and selection is strong, as may occur in many plant species.


Internet accessibility and usage among urban adolescents in Southern California: implications for web-based health research.
The World Wide Web (WWW) poses a distinct capability to offer interventions tailored to the individual's characteristics. To fine tune the tailoring process, studies are needed to explore how Internet accessibility and usage are related to demographic, psychosocial, behavioral, and other health related characteristics. This study was based on a cross-sectional survey conducted on 2373 7th grade students of various ethnic groups in Southern California. Measures of Internet use included Internet use at school or at home, Email use, chat-room use, and Internet favoring. Logistic regressions were conducted to assess the associations between Internet uses with selected demographic, psychosocial, behavioral variables and self-reported health statuses. The proportion of students who could access the Internet at school or home was 90% and 40%, separately. Nearly all (99%) of the respondents could access the Internet either at school or at home. Higher SES and Asian ethnicity were associated with higher internet use. Among those who could access the Internet and after adjusting for the selected demographic and psychosocial variables, depression was positively related with chat-room use and using the Internet longer than 1 hour per day at home, and hostility was positively related with Internet favoring (All ORs = 1.2 for +1 STD, p < 0.05). Less parental monitoring and more unsupervised time were positively related to email use, chat-room use, and at home Internet use (ORs for +1 STD ranged from 1.2 to 2.0, all p < 0.05), but not related to at school Internet use. Substance use was positively related to email use, chat-room use, and at home Internet use (OR for "used" vs. "not used" ranged from 1.2 to 4.0, p < 0.05). Self-reported health problems were associated with higher levels of Internet use at home but lower levels of Internet use at school. More physical activity was related to more email use (OR = 1.3 for +1 STD), chat room use (OR = 1.2 for +1 STD), and at school ever Internet use (OR = 1.2 for +1 STD, all p < 0.05). Body mass index was not related to any of the Internet use-related measures. In this ethnically diverse sample of Southern California 7(th) grade students, 99% could access the Internet at school and/or at home. This suggests that the Internet is already a potential venue for large scale health communication studies. Adolescents with more psychosocial risk factors or detrimental health behaviors were more likely to use the Internet. Therefore, if used properly, Internet interventions could effectively address the high risk populations. Additional research is needed to gain a more complete understanding of the positive and negative consequences of Internet use among adolescents.


Hidden Markov models-based system (HMMSPECTR) for detecting structural homologies on the basis of sequential information.
HMMSPECTR is a tool for finding putative structural homologs for proteins with known primary sequences. HMMSPECTR contains four major components: a data warehouse with the hidden Markov models (HMM) and alignment libraries; a search program which compares the initial protein sequences with the libraries of HMMs; a secondary structure prediction and comparison program; and a dominant protein selection program that prepares the set of 10-15 "best" proteins from the chosen HMMs. The data warehouse contains four libraries of HMMs. The first two libraries were constructed using different HHM preparation options of the HAMMER program. The third library contains parts ("partial HMM") of initial alignments. The fourth library contains trained HMMs. We tested our program against all of the protein targets proposed in the CASP4 competition. The data warehouse included libraries of structural alignments and HMMs constructed on the basis of proteins publicly available in the Protein Data Bank before the CASP4 meeting. The newest fully automated versions of HMMSPECTR 1.02 and 1.02ss produced better results than the best result reported at CASP4 either by r.m.s.d. or by length (or both) in 64% (HMMSPECTR 1.02) and 79% (HMMSPECTR 1.02ss) of the cases. The improvement is most notable for the targets with complexity 4 (difficult fold recognition cases).


Case Report: A Fatal Case of Malignant Posterior Reversible Encephalopathy Syndrome in the Setting of Diabetic Ketoacidosis.
Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome that typically presents with headache, visual disturbances, seizures, and altered consciousness. Its hallmark radiological features involve subcortical white matter lesions on magnetic resonance imaging (MRI), predominantly in the parietal and occipital lobes. While generally reversible with favorable outcomes, a minority of cases may progress to malignant cerebral edema and herniation, resulting in death. We present an unusual case of a 47-year-old woman who developed malignant PRES associated with severe diabetic ketoacidosis (DKA). Despite aggressive medical and surgical treatments, the patient's condition worsened, indicating the potential for devastating outcomes in malignant PRES. This case adds to the limited body of literature that suggests the need for vigilance in monitoring patients with severe glycemic disturbances for neurological complications, such as PRES. It also highlights the importance of early recognition and aggressive management in improving neurological outcomes in malignant PRES. Further research is warranted to understand the underlying mechanisms better and identify optimal treatment strategies for this rare but potentially life-threatening condition.


Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak bases.
The aim of the present study was to investigate if treatment with lysosomotropic weak bases could increase the intracellular retention of radiohalogens and thereby increase the therapeutic effect of radionuclide tumor targeting. Four different lysosomotropic bases, chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated for their ability to increase radiohalogen retention in vitro. The two most promising substances, chloroquine and ammonium chloride, were studied in several cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody (Z(HER2:4))(2). The uptake and retention of radionuclides was found to be substantially increased by simultaneous treatment with the lysosomotropic bases. The effect was, however, more pronounced in the epidermal growth factor:epidermal growth factor receptor (EGF:EGFR) system than in the (Z(HER2:4))(2):HER2 system. The therapeutic effect of ammonium chloride treatment combined with (211)At-EGF was also studied. The effect obtained after combined treatment was found to be much better than after (211)At-EGF treatment alone. The encouraging results from the present study indicate that the use of lysosomotropic weak bases is a promising approach for increasing the therapeutic effect of radionuclide targeting with radiohalogens.


The IL-33/ST2 Axis in Immune Responses Against Parasitic Disease: Potential Therapeutic Applications.
Parasitic infections pose a wide and varying threat globally, impacting over 25% of the global population with many more at risk of infection. These infections are comprised of, but not limited to, toxoplasmosis, malaria, leishmaniasis and any one of a wide variety of helminthic infections. While a great deal is understood about the adaptive immune response to each of these parasites, there remains a need to further elucidate the early innate immune response. Interleukin-33 is being revealed as one of the earliest players in the cytokine milieu responding to parasitic invasion, and as such has been given the name "alarmin." A nuclear cytokine, interleukin-33 is housed primarily within epithelial and fibroblastic tissues and is released upon cellular damage or death. Evidence has shown that interleukin-33 seems to play a crucial role in priming the immune system toward a strong T helper type 2 immune response, necessary in the clearance of some parasites, while disease exacerbating in the context of others. With the possibility of being a double-edged sword, a great deal remains to be seen in how interleukin-33 and its receptor ST2 are involved in the immune response different parasites elicit, and how those parasites may manipulate or evade this host mechanism. In this review article we compile the current cutting-edge research into the interleukin-33 response to toxoplasmosis, malaria, leishmania, and helminthic infection. Furthermore, we provide insight into directions interleukin-33 research may take in the future, potential immunotherapeutic applications of interleukin-33 modulation and how a better clarity of early innate immune system responses involving interleukin-33/ST2 signaling may be applied in development of much needed treatment options against parasitic invaders.