The clinical meaning of gastric-wall hyperactivity observed on sestamibi cardiac single-photon emission computed tomography.
To evaluate prospectively the incidence and clinical meaning, if any, of gastric-wall hyperactivity observed on sestamibi cardiac single-photon emission computed tomography (SPECT). This phenomenon is completely different from the well-known intraluminal gastric reflux of sestamibi. A group of 819 patients who underwent sestamibi cardiac SPECT was studied from January 2000 to October 2000. Gastric-wall activity was graded qualitatively. Only patients with gastric-wall activity near or equivalent to their heart activity were considered for subsequent analysis. The medical records of patient candidates were reviewed, and their family physicians were asked to respond to a questionnaire by telephone when further information was needed. We identified 13 patients with significant gastric-wall hyperactivity, which was more intense on rest images. Our review of the clinical data shows that all these patients were suffering from dyspepsia and were taking gastric medication. These 13 cases were assigned to 3 groups: gastroesophageal reflux, chronic functional dyspepsia and nonspecific gastritis. Significant gastric-wall hyperactivity is an infrequent observation on sestamibi cardiac SPECT. Our results indicate that the presence of significant gastric-wall hyperactivity is associated with dyspepsia. It is important to realize that this gastric-wall hyperactivity by its proximity to the inferior myocardial wall could in some circumstances lead to either false-negative or false-positive findings, representing a diagnostic problem. Although infrequent, this situation could be avoided by proper quality control, including a systematic review of the raw cine data before reading the images.


Social determinants of smoking, alcohol and drug use among Lithuanian School-aged children: results from 5 consecutive HBSC surveys, 1994-2010.
The aim of this study was to analyze the changes in the prevalence of smoking, alcohol and drug use among Lithuanian school-aged children in relation to the place of residence, family affluence, and family structure. MATERIAL AND METHODS. National surveys (26 556 anonymous questionnaires analyzed) of schoolchildren aged 11, 13, and 15 years were conducted in 1994, 1998, 2002, 2006, and 2010 in the framework of the international Health Behaviour in School-aged Children (HBSC) study. RESULTS. In 1994-2010, a significant increase in smoking prevalence was observed both among boys (11.3% to 21.5%, P<0.05) and girls (3.6% to 14.8%, P<0.05). Weekly alcohol consumption increased from 9.6% to 12.9% (P<0.05) among boys and from 4.3% to 7.9% (P<0.05) among girls. The prevalence of "ever use" of any psychoactive substance (data for 15-year-old group only) increased both in boys (14.6% to 33.5%) and girls (6.7% to 18.4%). Urban girls smoked more often than their rural peers. For both genders, such a residential gradient was observed in the use of alcohol and drugs. The respondents from intact families used drugs less frequently than the adolescents from not intact families. The adolescents from affluent families smoked less often, while the prevalence of alcohol and drug use was higher (except weekly alcohol use in girls). CONCLUSIONS. The study has demonstrated a significant increase in the prevalence of smoking, drinking, and drug use among Lithuanian school-aged children during the period of transition to market economy. This study provides some insight that should be addressed in equity-oriented control policies of substance use.


Depressive Symptoms Among Adolescents: Testing Vulnerability-Stress and Protective Models in the Context of COVID-19.
Adolescents who experience negative life events may be at risk for depression, particularly those with psychosocial vulnerabilities. We investigate longitudinally the impact of vulnerability/protective factors on the relation between a large-scale negative life event, the COVID-19 pandemic, and depressive symptoms. Adolescents (N = 228, Mage = 14.5 years, 53% female, 73% white) self-reported depressive symptoms 2-4 months before the pandemic (Time 1), and again 2 months following stay-at-home orders (Time 2). At T2, adolescents also completed measures of vulnerability, protective factors, and COVID-19-related distress. Depressive symptoms increased at T2, and COVID-19 distress interacted with resilience and negative cognitive style in predicting increases in T2 depression. Focusing on vulnerability and protective factors in adolescents distressed by large scale negative life events appears crucial.


Efficient Nanozyme-Triggered Pressure Sensor for Point-of-Care Immunoassay: Visual Sensing and Time Readout Device.
Point-of-care testing (POCT), with its portability and high sensitivity, is an analytical device for rapid on-site sensing and detection. In this study, a POCT device was designed for the portable detection of illegal additives by integrating a coil device that can visually sense color distance and a two-electrode electrochemical system. Real-time monitoring of pressure changes was achieved by driving CeO2@Pt/Au nanoparticle (NP)-labeled antibodies into a competitive immunoreaction, in which CeO2 and Pt/Au synergistically catalyzed the production of large amounts of O2 from H2O2, leading to a significant increase in gas within the closed chamber. Attractively, the coil device converted the pressure stimulus into visually readable change in distance for semi-quantitative detection of the target substance, while the electrical signal output caused by the changes of the solution around the electrodes achieved accurate and reliable quantification of the target. In addition, the proposed dual-mode pressure immunoassay device has acceptable selectivity, stability, and reproducibility. Herein, this portable device, which enables target concentration readings by converting pressure into multiple signals, provides an effective way to visualize POCT assays in resource-limited areas.


[Summary of the practice guideline 'Urolithiasis' (first revision) from the Dutch College of General Practitioners].
The Dutch College of General Practitioners has revised the practice guideline 'Urolithiasis'. In the acute phase, violent colic pain is treated with diclophenac or morphine. In the post-acute phase, imaging diagnostics are performed. Initially this is ultrasound examination and, ifindicated, an x-ray of the abdomen and at a later stage, a CT scan. The recommendation to consider the use oftamsulosin in the post acute phase is new. This alpha-1 blocking agent can enhance expulsion of the stone and contribute to the relief of pain.


Alveolar macrophage response to remote organ injury.
Intestinal reperfusion (IR)-induced pulmonary edema has been related to endogenous pulmonary thromboxane A2 (TxA2) release. This study examines the hypothesis that alveolar macrophages (aMphis) activated during IR are an important cellular source of TxA2 in this model. Anesthetized Sprague Dawley rats underwent 120 min of intestinal ischemia and 60 min of reperfusion (IR) or sham operation (Sham). aMphis were isolated by bronchoalveolar lavage and incubated in Krebs buffer for 30 min, after which the supernatant was analyzed for TxB2 (metabolite of TxA2) and prostaglandin E2. Other parameters of aMphi activation measured included lysosomal enzyme release (beta-glucuronidase), superoxide (O2-) release, and procoagulant activity. aMphis from animals sustaining IR generated more than twice as much TxA2 and prostaglandin E2 as did those isolated from controls (p < .05). Other evidence of aMphi activation included a nearly 100-fold increase in procoagulant activity, a 7-fold increase in beta-glucuronidase release, and a 2.5-fold increase in O2- release over that of controls (p < .05). These data suggest that TxA2 is a major eicosanoid product of aMphis during IR and that aMphis may be an important cellular participant in IR-induced pulmonary microvascular injury, either directly by releasing O2-, lysosomal enzymes, and pro-coagulant factors, or indirectly by generating TxA2.


The phylogenetic approach for viral infectious disease evolution and epidemiology: An updating review.
In the last decade, the phylogenetic approach is recurrent in molecular evolutionary analysis. On 12 May, 2019, about 2 296 213 papers are found, but typing "phylogeny" or "epidemiology AND phylogeny" only 199 804 and 20 133 are retrieved, respectively. Molecular epidemiology in infectious diseases is widely used to define the source of infection as so as the ancestral relationships of individuals sampled from a population. Coalescent theory and phylogeographic analysis have had scientific application in several, recent pandemic events, and nosocomial outbreaks. Hepatitis viruses and immunodeficiency virus (human immunodeficiency virus) have been largely studied. Phylogenetic analysis has been recently applied on Polyomaviruses so as in the more recent outbreaks due to different arboviruses type as Zika and chikungunya viruses discovering the source of infection and the geographic spread. Data on sequences isolated by the microorganism are essential to apply the phylogenetic tools and research in the field of infectious disease phylodinamics is growing up. There is the need to apply molecular phylogenetic and evolutionary methods in areas out of infectious diseases, as translational genomics and personalized medicine. Lastly, the application of these tools in vaccine strategy so as in antibiotic and antiviral researchers are encouraged.


Intrinsic tyrosine kinase activity is required for vascular endothelial growth factor receptor 2 ubiquitination, sorting and degradation in endothelial cells.
The human endothelial vascular endothelial growth factor receptor 2 (VEGFR2/kinase domain region, KDR/fetal liver kinase-1, Flk-1) tyrosine kinase receptor is essential for VEGF-mediated physiological responses including endothelial cell proliferation, migration and survival. How VEGFR2 kinase activation and trafficking are co-coordinated in response to VEGF-A is not known. Here, we elucidate a mechanism for endothelial VEGFR2 response to VEGF-A dependent on constitutive endocytosis co-ordinated with ligand-activated ubiquitination and proteolysis. The selective VEGFR kinase inhibitor, SU5416, blocked the endosomal sorting required for VEGFR2 trafficking and degradation. Inhibition of VEGFR2 tyrosine kinase activity did not block plasma membrane internalization but led to endosomal accumulation. Lysosomal protease activity was required for ligand-stimulated VEGFR2 degradation. Activated VEGFR2 codistributed with the endosomal hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)/signal-transducing adaptor molecule (STAM) complex in a ligand and time-dependent manner, implying a role for this factor in sorting of ubiquitinated VEGFR2. Increased tyrosine phosphorylation of the Hrs subunit in response to VEGF-A links VEGFR2 activation and Hrs/STAM function. In contrast, VEGFR2 in quiescent cells was present on both the endothelial plasma membrane and early endosomes, suggesting constitutive recycling between these two compartments. This pathway was clathrin-linked and dependent on the AP2 adaptor complex as the A23 tyrphostin inhibited VEGFR2 trafficking. We propose a mechanism whereby the transition of endothelial VEGFR2 from a constitutive recycling itinerary to a degradative pathway explains ligand-activated receptor degradation in endothelial cells. This study outlines a mechanism to control the VEGF-A-mediated response within the vascular system.


Psychobiological factors predicting the course of breast cancer.
Drawing on a carefully controlled sample of 52 women with a history of breast carcinoma and 34 healthy controls, this prospective study examined empirical associations between psychological factors and the progression of neoplastic disorders over a follow-up period averaging 624 days. Psychological variables were psychometrically assessed by self-report measures. A multiple regression analysis which controlled for disease stage at original diagnosis, age, total length of disease course, hematological factors, and blood chemistries measured at study onset showed neoplastic spread to be associated with a repressive personality style, reduced expression of negative affect, helplessness-hopelessness, chronic stress, and comforting daydreaming. The identified model of medical and psychological variables accounted for 56% of the observed variance. A psychobiological model of brain-body disregulation provided the best account of the observed associations between psychological functioning and the progression of disease. Future research is necessary to examine the role which psychological functioning may exert upon health-relevant behaviors that might blunt the benefits of professional health care.


Peritransplant Varicosis After Simultaneous Pancreas and Kidney Transplantation Is an Uncommon Cause of Late-Onset and Recurrent Gastrointestinal Bleeding.
Ectopic peritransplant varicosis represents an uncommon cause of late-onset gastrointestinal (GI) bleeding after simultaneous pancreas and kidney transplantation (SPK). We report on a 53-year-old female patient who suffered from recurrent upper GI bleeding seven years after SPK with persistent graft function. Upper endoscopy revealed perianastomotic angiodysplasias, treated by clipping and Argon-Plasma-Coagulation. Repeated endoscopy showed no signs of anastomotic ulcer. With persistent symptoms, computed tomography and angiography revealed extensive ectopic varicosis around the pancreas and duodenal graft. With no signs of portal hypertension, pancreas graft venous outflow impairment or arterio-venous fistula, the origin of variceal formation remained unknown. The extended finding did not allow for endovascular treatment by embolization. Surgery with extensive variceal ligation led to persistent cessation of hemorrhage and maintained stable graft function. In patients with unclear recurrent upper GI bleeding after SPK, one should consider ectopic peritransplant varicosis as an exceptional bleeding cause. If endoscopic treatments fail, angiography should be performed to rule out unusual causes of vascular complications. In case of extensive peritransplant varicosis, surgery may remain the only successful therapy, whenever possible including graft preservation in well-functioning grafts.


Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia.
Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA-; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.


Marrying into it: Siblings-in-law in the social support networks of adults with intellectual and developmental disabilities.
Although attention has been devoted to social supports provided by parents and siblings of adults with intellectual and developmental disabilities (IDD), much less is known about supports provided by the spouses of these siblings-the so-called siblings-in-law. This study examined the role of the sibling-in-law in the social support networks of their brother/sister-in-law with IDD and factors associated with providing greater amounts of tangible, informational and emotional support. Siblings-in-law of adults with IDD living predominately in the United States (N = 99) participated in a cross-sectional survey. Measures covered demographic and family background, perspectives towards having a brother/sister-in-law with IDD, supports provided and characteristics of the adult with IDD's social support network. Most siblings-in-law reported providing support to their brother/sister-in-law with IDD. Percentages of siblings-in-law providing support were similar to that of the spouse and the spouse's family in the area of emotional support and similar to percentages of paid professionals in tangible and informational supports. Across all three support types, the main predictor of increased sibling-in-law support levels was a decreased ability of the parents-in-law to care for their child with IDD. Other predictors (e.g. distance from brother/sister-in-law with IDD and disability 'insider' status) varied by support type. Findings highlight the role of siblings-in-law in the social support networks of adults with IDD, with implications for policy and practice.


Developmental defects of enamel in phenylketonuria patients.
The purpose of this study was to determine the prevalence of developmental defects of enamel in patients diagnosed with phenylketonuria (PKU). The study group consisted of 24 four- to 24-year-old subjects with PKU. The control group consisted of 24 healthy individuals. An examination for the detection of developmental defects of enamel was conducted at the university pediatric dentistry clinic by a single examiner. Data were analyzed using the chi-square test (P<.05) and odds ratios. The prevalence of developmental defects of enamel was 36 percent in the study group and 15 percent in the control group. The maxillary central incisors were the most affected teeth in patients with PKU, while the maxillary and mandibular first molars were the most affected teeth in the control group. Patients with PKU had a 3.3-fold greater chance of exhibiting developmental defects of enamel versus the healthy controls, which was statistically significant (P<.001). The study findings suggest that PKU increases the risk of developmental defects of enamel.


Four primordial modes of tRNA-synthetase recognition, determined by the (G,C) operational code.
In distinction to single-stranded anticodons built of G, C, A, and U bases, their presumable double-stranded precursors at the first three positions of the acceptor stem are composed almost invariably of G-C and C-G base pairs. Thus, the "second" operational RNA code responsible for correct aminoacylation seems to be a (G,C) code preceding the classic genetic code. Although historically rooted, the two codes were destined to diverge quite early. However, closer inspection revealed that two complementary catalytic domains of class I and class II aminoacyl-tRNA synthetases (aaRSs) multiplied by two, also complementary, G2-C71 and C2-G71 targets in tRNA acceptors, yield four (2 x 2) different modes of recognition. It appears therefore that the core four-column organization of the genetic code, associated with the most conservative central base of anticodons and codons, was in essence predetermined by these four recognition modes of the (G,C) operational code. The general conclusion follows that the genetic code per se looks like a "frozen accident" but only beyond the "2 x 2 = 4" scope. The four primordial modes of tRNA-aaRS recognition are amenable to direct experimental verification.


Long-term continuous mono-cropping of Macadamia integrifolia greatly affects soil physicochemical properties, rhizospheric bacterial diversity, and metabolite contents.
Macadamia integrifolia is the most economically important Proteaceae crop known for its edible nuts. The present study was conducted to examine the effect of continuous cultivation (for 1, 5, and 20 years) of M. integrifolia on soil quality, bacterial diversity, and metabolites. Soil rhizospheres from three different Macadamia rhizosphere orchards, 1-year monoculture orchard (CK), 5-year monoculture orchard (Y5), and 20-year monoculture orchard (Y20), were analyzed through metagenomic and metabolomic profiling. The soil physicochemical properties, including organic matter, and available nutrients (P, N, and K) were first increased significantly (p < 0.05) from the CK to the Y5 group and then decreased (p < 0.05) from the Y5 to the Y20 group. The soil pH continuously decreased (p < 0.05) over time from CK to Y20. Metagenomic profiling revealed that Actinobacteria, Acidobacteria, and Proteobacteria were the top three abundant phyla with their inconsistent relative abundance patterns from CK to Y20 (CK: 23.76%, Y5: 34. 06%, and Y20: 31.55%), (CK: 13.59%, Y5: 18.59%, and Y20: 21.35%), and (CK: 27.59%, Y5: 15.98%, and Y20: 17.08%), respectively. Furthermore, the Y5 rhizospheres had a higher number of beneficial bacterial genera belonging to Proteobacteria and Actinobacteria than the Y20 rhizospheres. The KEGG annotation analysis revealed that cellular processes, organism systems, metabolism, and genetic information were the most enriched functional categories. CAZy database screening indicated the highest enrichment of glycoside hydrolases following the glycoside transferases and carbohydrate-binding modules. Differential metabolite analysis revealed the highest number of metabolites (11) in the Y5 group than in the Y20 group (6). It is concluded that continuous monoculture of M. integrifolia improves the soil physicochemical properties, bacterial diversity, and metabolite contents in short-term planted orchards which, however, are deteriorated in long-term planted orchards.


Circulating interleukin-2 receptors are a group of multimeric proteins with immunoreactivity for interleukin-2 receptor alpha, beta, and gamma chains.
Soluble interleukin-2 receptor (sIL-2R) alpha chain serum levels as determined by enzyme-linked immunosorbant assay (ELISA) are commonly used to monitor various inflammatory and neoplastic disorders associated with lymphocytic proliferation and activation. The in vivo structure of this soluble receptor species, however, is not characterized. We investigated sera with elevated sIL-2R serum levels of patients with histologically proven cutaneous T cell lymphoma (CTCL) and high-dose IL-2-treated melanoma patients and healthy donors. Purified recombinant IL-2R alpha and beta chain molecules, produced by transfection of NIH/3T3 fibroblasts and CHO cells, served as positive controls for purification and detection procedures. For selective enrichment of IL-2R molecules from supernatants and sera, affinity columns were prepared by coupling recombinant IL-2 or monoclonal antibodies against the alpha and the beta chain of the IL-2R complex to cyanogen bromide-activated Sepharose. Western blotting with affinity-purified fractions under reducing and nonreducing conditions revealed proteins that showed immunoreactivity for IL-2R alpha, beta, and gamma chain using several detection antibodies against these molecules. We conclude that the composition of sIL-2R in vivo is more complex than that of recombinant sIL-2R and can include all three IL-2R chains.


The response of symptomatic gastrointestinal Kaposi's sarcoma to chemotherapy: a prospective evaluation using an endoscopic method of disease quantification.
We used an endoscopic method of quantification to evaluate the response of symptomatic gastrointestinal Kaposi's sarcoma (KS) prospectively in seven patients with acquired immune deficiency syndrome (AIDS) who were participating in chemotherapy trials for extensive cutaneous KS. The sums of the diameters of KS lesions in the esophagus, stomach, duodenum, and distal colon were used as a measure of extent of disease. Intravenous therapy [adriamycin/bleomycin/vincristine (N = 5), adriamycin (N = 1), or bleomycin/vincristine (N = 1)] was given every 2 wk for a mean of six cycles. Five of seven patients (71%) had a cutaneous response, whereas 9/15 (60%) gastrointestinal sites showed a remission. Sites of complete response all had an initial sum of lesion diameters less than or equal to 30 mm. Five of five patients with duodenal KS responded (3/5 complete), whereas just two partial responses were seen in five patients with gastric KS (4/5 with duodenal KS had sums of diameters less than or equal to 20 mm, whereas 4/5 with gastric KS had sums greater than or equal to 150 mm). Symptoms (abdominal pain, nausea/vomiting, hematemesis, diarrhea) resolved in all patients within two cycles of therapy. In summary: 1) the response rate of gastrointestinal KS to chemotherapy is similar to that of cutaneous KS; 2) the best response is seen in patients with less extensive disease and duodenal involvement; and 3) symptoms of gastrointestinal KS respond to chemotherapy even if the KS lesions do not resolve.


Research on the Differences in Phenotypic Traits and Nutritional Composition of Acer Truncatum Bunge Seeds from Various Regions.
Acer truncatum Bunge (ATB) is an excellent edible woody oil tree species since it bears a huge amount of fruit and has strong adaptability to be widely cultivated. Selecting an optimal cultivation region for ATB is crucial to improving China's woody oil industrialization. Chemical analysis, correlation analysis, and affiliation function values were used in the present research to systematically analyze the phenotypic traits, organic compound content, and seed oil chemical composition of the seeds of ATB from nine regions. The average contents of oil, protein, and soluble sugar in ATB seeds were 43.30%, 17.40%, and 4.57%, respectively. Thirteen fatty acids were identified from ATB seed oil, the highest content of which was linoleic acid (37.95%) and nervonic acid content was 5-7%. The maximum content of unsaturated fatty acids in ATB seed oil was 90.09%. Alpha-tocopherol content was up to 80.75 mg/100 g. The degree of variation in seed quality traits (25.96%) was stronger than in morphological traits (14.55%). Compared to environmental factors, the phenotypic traits of seeds contribute more to organic compounds and fatty acids. Combining the values of the indicator affiliation functions, Gilgarang, Tongliao, Inner Mongolia was selected as the optimal source of ATB for fruit applications from nine regions.


Pineal N-acetyltransferase activity in 10-day-old rats: a paradigm for studying the developing circadian system.
Pineal N-acetyltransferase (NAT) activity in 10-day-old rat pups was used to examine several aspects of the developing circadian timing system. When born and reared under constant darkness, 10-day-old animals manifested a clear daily rhythm of NAT activity whose phase was in time with the estimated circadian time of the mother (set by the lighting cycle during pregnancy). When pups were reared in constant darkness from birth by a foster mother whose circadian time was 180 degrees (12 h) out of phase with that of the natural mother, the resulting population profiles of NAT activity were arrhythmic. Analysis of the individual litter profiles from this experiment showed a variable postnatal influence of the maternal circadian system on the timing of the developing circadian system. Neither cross-fostering per se nor social interactions among litter mates contributed significantly to the apparent maternal influence. The magnitude of the postnatal maternal influence was not the same throughout development, but was most apparent during the first 5 days of life. Neonatal blinding (within 24 h of birth) did not appreciably alter the maternal influence. Extraretinal photoreception does not contribute to entrainment of the circadian clock during postnatal development, and retina-mediated photic entrainment is present by 10 days of age. The results indicate that pineal NAT activity monitored in 10-day-old rats provides a useful paradigm for studying the developing circadian system.


Fatal traumatic brain injury in older adults in Austria 1980-2012: an analysis of 33 years.
traumatic brain injury (TBI) is a significant public health problem. Developed countries report a significant increase of TBI in older adults in the past decades. The objective of this study was to investigate the changes in TBI-related mortality in older Austrians (65 years or older) between 1980 and 2012 (33 years) and to identify possible causes for these changes. data from Statistics Austria on mortality in Austria between 1980 and 2012 were screened and data on TBI-related mortality in adults aged 65 and older were extracted and analysed, based on the diagnostic codes of the International Classification of Diseases, 10th and 9th revision. Mortality rates were calculated for 5-year age groups; standardized mortality rates were calculated for the total. Mechanism of injury was analysed for all events, both sexes and individual age groups. between 1980 and 2012, 16,204 people aged 65 or older died from TBI in Austria; 61% of these were male. Fatal TBI cases and mortality rates increased in the oldest age groups (80 years or older). Half of the fatal TBI cases were caused by falls, 22% by traffic accidents and 17% by suicides. Rate of fall-related fatal TBI increased and rate of traffic accident-related fatal TBI decreased with age. preventive measures introduced in the past decades in the developed countries have contributed to a decrease in traffic injuries. However, falls in the older population are on the rise, mainly due to ageing of the population, throughout the reported period. It is important to take preventive measures to stop the epidemics of fall-related TBIs and fatalities in older adults.


Pediatric residency training in an era of managed care: an introduction to proceedings of a national conference.
On May 4, 1996, a conference sponsored jointly by the Division of Medicine of the Health Resources and Services Administration and the Ambulatory Pediatric Association brought together pediatric educators from academic medical centers and managed care organizations to address the challenges and opportunities for pediatric residency training, given current trends toward increasing managed care for children. This supplement is designed to bring the issues discussed there to a broader audience of pediatricians and educators. The contributions are written by the participants of that conference, with invited commentaries to add additional perspectives on each topic. The papers were reviewed by an editorial board of leaders in pediatric education with experience in relevant areas. This introduction describes the impetus for the conference and highlights a number of critical issues facing pediatric postgraduate training that are presented in greater depth in the contributions that follow. Finally, this paper summarizes the recommendations of the conference for meeting the challenges of training pediatricians in these areas.


NMR evidence for forming highly populated helical conformations in the partially folded hNck2 SH3 domain.
Recent studies of several proteins implied that the folding of beta-proteins may follow a nonhierarchical mechanism in which two major transitions are essential, i.e., the collapse of a random coil to form a nonnative helical intermediate, followed by a transformation into the native beta-structure. We report that the first hNck2 SH3 domain, assuming an all-beta barrel in the native form, can be reversibly transformed into a stable and nonnative helical state by acid-unfolding. We also conducted extensive NMR and mutagenesis studies that led to two striking findings: 1), NMR analysis reveals that in the helical state formed at pH 2.0, the first and last beta-strands in the native form become unstructured, whereas the rest is surprisingly converted into two highly populated helices with a significantly limited backbone motion; and 2), a conserved four-residue sequence is identified on the second beta-strand, a mutation of which suddenly renders the SH3 domain into a helical state even at pH 6.5, with NMR conformational and dynamic properties highly similar to those of the wild-type at pH 2.0. This observation implies that the region might contribute key interactions to disrupt the helical state, and to facilitate a further transformation into the native SH3 fold in the second transition.


Cardiac failure associated with hypocalcemia.
Rapid transfusion of citrated whole blood was associated with acute hypotension and a rising central venous pressure in a patient undergoing pelvic exenteration and hemipelvectomy. Evidence of cardiac failure was accompanied by a precipitous decrease in serum ionized calcium (Ca++) concentration. When the rate of blood transfusion was slowed, arterial blood pressure returned to the control level and serum Ca++ increased.


Phylogenetic niche conservatism and the evolutionary basis of ecological speciation.
Phylogenetic niche conservatism (PNC) typically refers to the tendency of closely related species to be more similar to each other in terms of niche than they are to more distant relatives. This has been implicated as a potential driving force in speciation and other species-richness patterns, such as latitudinal gradients. However, PNC has not been very well defined in most previous studies. Is it a pattern or a process? What are the underlying endogenous (e.g. genetic) and exogenous (e.g. ecological) factors that cause niches to be conserved? What degree of similarity is necessary to qualify as PNC? Is it possible for the evolutionary processes causing niches to be conserved to also result in niche divergence in different habitats? Here, we revisit these questions, codifying a theoretical and operational definition of PNC as a mechanistic evolutionary process resulting from several factors. We frame this both from a macroevolutionary and population-genetic perspective. We discuss how different axes of physical (e.g. geographic) and environmental (e.g. climatic) heterogeneity interact with the fundamental process of PNC to produce different outcomes of ecological speciation. We also review tests for PNC, and suggest ways that these could be improved or better utilized in future studies. Ultimately, PNC as a process has a well-defined mechanistic basis in organisms, and future studies investigating ecological speciation would be well served to consider this, and frame hypothesis testing in terms of the processes and expected patterns described herein. The process of PNC may lead to patterns where niches are conserved (more similar than expected), constrained (divergent within a limited subset of available niches), or divergent (less similar than expected), based on degree of phylogenetic relatedness between species.


The 4 Cs: a model for teaching dosage calculation.
Performing dosage calculation can be viewed as the ability to perform the 4 Cs: compute, convert, conceptualize, and critically evaluate. Ability to perform the 4 Cs is dependent on a variety of student and program factors. A model for teaching dosage calculation, grounded in research on mathematical success, is presented. Strategies for teaching dosage calculation based on this model are discussed.


Correspondence of Interactive Voice Response (IVR) reports of nicotine withdrawal, craving, and negative mood with questionnaire ratings.
This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of nicotine withdrawal, craving, and depressive symptoms. However, the sample size decreased on each day of IVR reporting due to attrition. Thus, an appealing aspect of daily assessment using an IVR system is that it can provide additional data that are not obtained with paper and pencil assessments given once per week, but it will be important for future studies to concentrate on improving adherence with the IVR system in this population.


Ileo-ileal intussusception of a sutured enterotomy site, 6days after laparotomy due to fetobezoar: A case report.
Postoperative small bowel obstruction due to intussusception is a rare entity but can lead to severe morbidity and even mortality. We present a case of this rare complication produced by an unusual cause. A 22year old male, who is a fruitarian, presented to the E.R on day 6 after laparotomy due to obstructing fetobezors that were removed via gastrotomy and enterotomy. In his readmission, he had severe, diffuse abdominal pain, distended abdomen and diffuse peritonitis. Abdominal computed tomography (CT) showed a large amount of fluid in the abdomen, distended small bowel loops, a small amount of free air around the stomach and a suspected ileo-ileal intussusception. The patient underwent emergent laparotomy which revealed an ileo-ileal intussusception with the sutured enterotomy site from the previous operation as the lead point. In addition, a minor dehiscence of the gastrotomy site was identified. A reduction of the intussusception was performed with resection of the enterotomy site and side to side anastomosis. The gastrotomy site was debrided and re-sutured. Recovery was uneventful. Postoperative intussusception, although rare, is potentially a dangerous complication, often not involving the site of the primary operation. To our knowledge this is the first report of an intussusception with a sutured enterotomy site as the lead point. Clinicians should be aware of this entity when assessing a patient with abdominal pain and distention after surgery with enterotomy or resection of bowel.


Quantification of phosphorylated cAMP-response element-binding protein expression throughout the brain of amphetamine-sensitized rats: activation of hypothalamic orexin A-containing neurons.
In the present study, using rats, we have examined acute, contextual, and sensitized patterns of activated or phosphorylated cAMP response element-binding protein (pCREB) expression in parallel, assaying across multiple nuclei that have been implicated in addiction. The paradigm used included a comparison of pretreatment dose of amphetamine upon patterns of cellular activation, following rechallenge. Because efferent orexinergic projections synapse on many targets through the mammalian brain, including mesotelencephalic regions and limbic systems involved in drug reward and reinforcement, we examined for coexpression of pCREB or c-Fos double labeling within orexin A-immunopositive neurons following sensitization. Acute challenge with amphetamine (1.5 mg/kg i.p.) resulted in an increase in the number of pCREB-immunoreactive (-IR) cells within the substantia nigra but a decrease of pCREB-IR cells in the central and medial subnuclei of the amygdala. Contextual re-exposure to the drug treatment environment altered pCREB expression, particularly in the basal ganglia and hypothalamus, although these effects were dictated by pretreatment dose of amphetamine. Sensitization to amphetamine resulted in robust increases in pCREB-IR cell numbers in the basal ganglia and lateral septum of rats that had been pretreated with high-dose (10 mg/kg i.p.) but not low-dose (2 mg/kg i.p.) amphetamine, despite a similar behavioral response. Orexin A-containing cells in the hypothalamus of sensitized rats did not coexpress pCREB; however, these cells double-labeled for c-Fos and orexin A. These data suggest that orexinergic neurons are activated during the expression of behavioral sensitization, although in a heterogenous manner with regard to afferent topologies and functional roles in the nervous system.


Toxicological implications of polymorphic drug metabolism.
The occurrence of genetic polymorphisms of drug metabolism means that populations contain subgroups (phenotypes) that differ sharply in their abilities to effect a number of metabolic reactions. Because of this, major interphenotype differences occur in responsiveness to drugs and toxic substances. The well established genetic polymorphisms of acetylation and hydrolysis illustrate the important association that exists between phenotype and propensity to develop toxic and exaggerated responses to some substances. Recently, for metabolic oxidation, a new genetic polymorphism of drug metabolism has been described and it promises to provide a better understanding of inter-individual variability in the metabolic handling of, and responsiveness to, drugs and toxic substances. The following effects of the polymorphism are described here: (a) its influence in determining variable presystemic metabolism and hence systemic drug availability; (b) its role in determining alternative toxic pathways of metabolism in individuals who have a genetically determined impairment of oxidative capacity and (c) its influence on the development of agranulocytosis associated with metiamide administration.


Irritating effects on man of air pollution due to cigarette smoke.
Sixty subjects were exposed to cigaretts smoke produced by a smoking machine in a climatic chamber. The irritating effects were recorded by questionnaire and related to concentrations of CO, formaldehyde, and acroleine. The eyes are most sensitive to these irritants, followed by the nose. Annoyance about air quality, and the desire to open the window or to leave the room proved to be other useful measures of sensitivity. With smoke produced by 10 cigarettes/30 m3 acroleine reaches 0.1 ppm, the threshold limit value for industries; simultaneously, CO and formaldehyde exceed the clean air standards for outdoor air. At this exposure level. 9 per cent of the subjects show a strong or very strong eye irritation, while 78 per cent "wish to leave the room." The most important of the measured irritants seems to be acroleine.


Urgent Off-Pump Coronary Bypass Grafting in Moyamoya Disease: A Case Report.
Moyamoya disease is a rare progressive cerebrovascular occlusive disease that predominantly occurs in countries in Northeast Asia. We report a 54-year-old male patient with moyamoya and coronary artery disease, on whom urgent off-pump coronary artery bypass grafting was performed after cardiopulmonary reanimation due to ventricular fibrillation. This patient had left main trunk disease, a Pudenz peritoneal catheter (Medtronic, Inc., Minneapolis, MN, USA) for liquor drainage, bilateral internal carotid artery occlusion, diffuse peripheral atherosclerotic artery disease, and chronic renal insufficiency. We prefer off-pump surgery to avoid the risk of intraoperative hypotension and minimize the risk of perioperative cerebral ischemic complications.


Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis.
The immune response after brain injury is highly complex and involves both local and systemic events at the cellular and molecular level. It is associated to a dramatic over-activation of enzyme systems, the expression of proinflammatory genes and the activation/recruitment of immune cells. The complement system represents a powerful component of the innate immunity and is highly involved in the inflammatory response. Complement components are synthesized predominantly by the liver and circulate in the bloodstream primed for activation. Moreover, brain cells can produce complement proteins and receptors. After acute brain injury, the rapid and uncontrolled activation of the complement leads to massive release of inflammatory anaphylatoxins, recruitment of cells to the injury site, phagocytosis and induction of blood brain barrier (BBB) damage. Brain endothelial cells are particularly susceptible to complement-mediated effects, since they are exposed to both circulating and locally synthesized complement proteins. Conversely, during neurodegenerative disorders, complement factors play distinct roles depending on the stage and degree of neuropathology. In addition to the deleterious role of the complement, increasing evidence suggest that it may also play a role in normal nervous system development (wiring the brain) and adulthood (either maintaining brain homeostasis or supporting regeneration after brain injury). This article represents a compendium of the current knowledge on the complement role in the brain, prompting a novel view that complement activation can result in either protective or detrimental effects in brain conditions that depend exquisitely on the nature, the timing and the degree of the stimuli that induce its activation. A deeper understanding of the acute, subacute and chronic consequences of complement activation is needed and may lead to new therapeutic strategies, including the ability of targeting selective step in the complement cascade.


Analgetic activity and in vitro binding constants of some N-alkyl-3-benzazocines.
A homologous series of 3-alkyl-1,2,3,4,5,6-hexahydro-8-hydroxy-6-methyl-3-benzazocines (2) has been synthesized. Analgetic activity and binding constants for the opiate receptor for 2 and for an analogous series of benzomorphans (1 and 3) are reported. In 1, hot-plate analgesic activity is lost on increase of the N-alkyl chain length from ethyl through butyl (lc-e) and regained with amyl (lf) and hexyl (lg). Compounds lc-e show that antagonist properties and binding constants are similar throughout the series. With 2, where there has been loss of steric constraints through removal of the 2,6-methano bridge of 1 and 3, greatly diminished analgetic activity and receptor affinity and no antagonist properties were observed. Like 1, however, greatest agonist activity was shown by the N-methyl (2c), amyl (2g), hexyl (2h), and heptyl (2i) homologs and there is a parallel of in vitro binding strength and analgetic activity.


Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection.
Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.


Kitaigorodsky revisited: polymorphism and mixed crystals of acridine/phenazine.
Non-stoichiometric molecular mixed crystals have potential as functional materials, the properties of which can be tailored by rationally changing their composition. The guidelines for their preparation were summarized over thirty years ago by Alexander Kitaigorodsky. Here those principles are revised in light of new studies on the acridine/phenazine system, and solvent-assisted grinding is presented as a convenient synthetic procedure to afford a more homogeneous product than traditional solvent-evaporation methods. Finally, the proposed prerequisite of crystal isostructurality/isomorphicity for the pure compounds, which seems to be violated in the present case, is discussed.


Plasma glucose and the action of calorie restriction on aging.
We tested the hypothesis that retardation of aging by caloric restriction is due in part to decreased levels of plasma glucose over the life span. Male C57BL/6 mice expressing a human GLUT4 minigene (transgenic [TG] mice) and their nontransgenic littermates (NTG mice) were maintained under specific pathogen-free conditions. Mice were fed ad libitum (A mice) or 40% less than ad libitum (R mice) from age 6 weeks. Over the life span there were three different levels of plasma glucose, with NTGA mice having the highest daily levels, TGR mice the lowest daily values, and TGA and NTGR mice having similar levels intermediate between these values. Despite differences in plasma glucose, the differences measured in longevity (50% and 10% survival), physiology and tissue pathology were associated with diet rather than with levels of plasma glucose. We conclude that decreased plasma glucose over the life span is not an important factor in the action of calorie restriction on aging processes.


A Cotton Annexin Affects Fiber Elongation and Secondary Cell Wall Biosynthesis Associated with Ca2+ Influx, ROS Homeostasis, and Actin Filament Reorganization.
Annexins play pivotal roles in a variety of cellular processes as well as in fiber development; however, the functional mechanisms of their activities are unclear. Here, an annexin gene that is preferentially expressed in fibers, GhFAnnxA, was found to be significantly associated with various cotton (Gossypium hirsutum) fiber traits. Transgenic analysis demonstrated that GhFAnnxA affected cotton fiber elongation and was involved in secondary cell wall (SCW) biosynthesis. Functional studies demonstrated that GhFAnnxA may act as a Ca(2+) conductance regulator and that reactive oxygen species (ROS) produced by Rbohs in a Ca(2+)-dependent manner may determine fiber elongation caused by elevated intracellular turgor and cell wall loosening. However, excessive hydrogen peroxide (H2O2) inhibited cotton fiber elongation in vitro. We speculate that a positive feedback loop involving ROS and Ca(2+) is regulated by GhCDPK1 and regulates fiber cell elongation. Furthermore, the convergence of actin filaments is altered by their interaction with GhFAnnxA, and this also may contribute to fiber elongation. Moreover, GhFAnnxA may affect SCW biosynthesis through changes in cell wall components caused by an increase in H2O2 levels. These results not only provide new insights into the signaling pathways of GhFAnnxA in fiber development but also clarify the role of ROS in fiber development.


Predictive value of PSA density in the diagnosis of prostate cancer in lebanese men.
Being the second most common cancer in men, prostate cancer detection relies on laboratory tests, imaging, and surgical procedures, although biopsy remains the mainstay in diagnosis of prostate cancer. No clear cut-off of prostate specific antigen density (PSAD) for suspecting prostate cancer has been established in the Lebanese population. Our primary objective was to evaluate the diagnostic strength of the PSAD value versus total prostate specific antigen (tPSA) level in the Lebanese men in correlation with biopsy outcome to avoid unnecessary prostate biopsy. A retrospective study of 347 patients with history of prostate biopsy done for cancer suspicion included tPSA, prostate volume, and prostate density values and results of prostate biopsy. Data was collected from Bahman hospital and statistical analysis of the mean values of tPSA, prostate volume and PSAD in different age groups was done. Significance of the results was tested using. On average, patients with negative biopsies were younger and they had lower tPSA levels, lower PSAD values and larger prostate volume compared to patients with positive biopsies. A PSAD cutoff of 0.185 ng/ml2 revealed the highest predictive strength for prostate cancer (6 times risk) compared with other parameters. These findings were mainly referred to patients with PSA > 10 ng/ml. A multifactorial approach must be conducted including all parameters in order to decide upon the need for prostate biopsy. PSAD proved to be a good marker in favor or against a prostate biopsy with a cut-off of 0.185 ng/ml2, especially in patients with tPSA level higher to 10 ng/ml. A multicenter study was recommended for better and more reliable results and more precise cut-offs.


A theoretical extension of the concept of energy through an empirical study.
A theoretical extension of the concept of energy through an empirical study This paper extends the concept of energy as a multifaceted concept of the experience of energy and proposes a theoretical model regarding the understanding of the experience of energy. The hybrid model of concept development (Schwartz-Barcott and Kim, 2000) was used in a qualitative empirical study with a sample of athletes and chronically ill individuals. The concept of energy presented is a global concept and can be placed within the much-discussed concept of fatigue. Focusing on energy implicates a resource approach to individuals experiencing fatigue. A theoretical model for the experience of energy emerging from this study includes the subconcepts of the feeling of energy, perceived energy capacity, energy management, and performance of activities. Two sets of strategies within the concept of energy management are identified as energy economizing and energy generating. This article explores the potential of the concept of energy in describing fatigue as a health problem. Implications for clinical practice and further theoretical development are suggested.


[Antegrade ejaculation after modified lumboaortic laparoscopic lymphadenectomy].
Testicular cancer affects young and fertile patients. Half of them are non seminomatous tumors. The management of this cancer in stage I includes: watchful waiting, chemotherapy and retroperitoneal lymph node dissection (RPLND). In the past, classic RPLND produced a high rate of anejaculation with the subsequent compromise to fertility. Currently, antegrade ejaculation is achieved in almost 90% of the cases with the modified technique. The objective of this work is to show the conservation of antegrade ejaculation and some surgical anal cortical features of the modified laparoscopic RPLND. From January 2003 to July 2006 24 patients with non-seminomatous testicular tumors underwent modified laparoscopic RPLND. Patients were asked about preservation of antegrade ejaculation six weeks after surgery. We also analyze surgical and oncological variables in the series. All surgeries where successfully completed laparoscopically. Mean age 29.8 years (15-50). Antegrade ejaculation was preserved in 91.6% (22/24) of the patients. Mean surgical time was 122 minutes (90-215). Mean hospital stay was 1.7 days (1-4). Mean number of lymph nodes excised was 13 (5-22). Metastatic lymph node involvement was found in 29% of the patients 17/24). There were no surgical complications. Laparoscopic approach is as effective as the classic open technique to maintain antegrade ejaculation and subsequent fertility Additionally, it has low morbidity the advantages of a minimally invasive approach and oncological outcomes are similar to the classic approach. For these reasons the laparoscopic approach should be the technique of choice for patients in who decision to undergo surgical staging is taken.


Patellar tendon graft reconstruction for midsubstance anterior cruciate ligament rupture in junior high school athletes. An algorithm for management.
Between 1976 and 1988 we treated 75 junior high athletes who had midsubstance ruptures of the anterior cruciate ligament and open physes. Thirty-eight children were initially treated conservatively and later had an intraarticular patellar tendon graft reconstruction, 2 patients underwent extraarticular reconstruction and then later had a patellar tendon graft intraarticular reconstruction, and 20 children had a patellar tendon graft reconstruction initially. In all 60 patients the tibial and femoral tunnels were drilled through the open physes. Minimum followup was 2 years (mean, 4.2). Fifty-five of the 60 children were able to return to their original sports; 5 were active in less strenuous sports. No incidence of abnormal growth related to the intraarticular reconstructive surgery was recorded. Three children tore their anterior cruciate ligament grafts more than 2 years after surgery. Our records showed that conservative treatment of the active junior high athlete with an anterior cruciate ligament rupture failed in each case because of recurrent giving way or meniscal tears. Definitive treatment with an intraarticular autogenous patellar tendon graft reconstruction yielded good to excellent results and eliminated subsequent instability episodes and meniscal tears in our study group.


Pneumatosis Intestinalis With Abdominal Wall Emphysema in Hypothermia.
In this report, we present a case in which intestinal and abdominal wall emphysema was observed, but the patient was unconscious due to hypothermia, making it difficult to determine the indication for surgery. Pneumatosis intestinalis (PI) is a pathological condition characterized by the presence of gas within the walls of the small or large intestine and is considered a surgical emergency when accompanied by manifestations of peritonitis on abdominal examination, metabolic acidosis, and lactic acid levels above 2.0 mmol/L. In this specific case, the patient's blood draw results indicated the requirement for an emergency laparotomy; however, the patient's unconscious state became a challenge to make decision on informed consenting. The case illustrates the difficulties encountered in making treatment decisions in critically ill patients and the necessity for thorough assessments and close monitoring of vital signs in such patients.


Reversible denaturation, self-aggregation, and membrane activity of Escherichia coli alpha-hemolysin, a protein stable in 6 M urea.
Escherichia coli alpha-hemolysin (HlyA) is an extracellular protein toxin (107 kDa) whose cell lytic activity may be preserved for months at -20 degreesC in the presence of 6 M urea, although it decays rapidly in urea-free buffers. This paper describes experiments addressed to unravel the role of urea in HlyA stabilization. Urea up to 8 M inhibits the Ca2+-binding and hemolytic activities of the protein, alters its secondary and tertiary structures, and reduces its tendency to self-aggregation. All these changes are largely reversed upon urea removal by dilution or dialysis, suggesting that they are interrelated. Furthermore, the extent of recovery of the native activities and structural features of alpha-hemolysin that follows urea removal increases with the concentration of urea during the previous phase. Thus, it seems that urea elicits the reversible transition of HlyA to a less active but more stable state whose structure differs significantly from that of the native protein. Moreover dialysis equilibration of the protein with buffers containing 3 M urea induces the formation of a molecular form of HlyA 5-10 times more active than the native protein in the absence of urea. This hyperactive intermediate appears to keep the native secondary structure of HlyA, but with a less compact tertiary structure, that increases the number of exchangeable Ca2+ ions under these conditions. Changes in the intrinsic fluorescence of HlyA also support the notion of a conformational change in the high-activity intermediate. The intermediate is only detected when assayed in the presence of Ca2+ and 3 M urea and can bind a large number of calcium ions (approximately 12 vs approximately 3 for the native protein); it shows a large tendency to self-aggregation and presumably, in the presence of membranes, a similar tendency to irreversible insertion, which may be the reason for its high lytic activity.


[Effects of aprotinin on the endochondral ossification process in growing rabbits].
Present study demonstrated that aprotinin, a natural inhibitor of proteases, interfered with the ossification process of epiphyseal and metaphyseal cartilages of growing rabbits. This biological effect may be induced by inhibition of tissue proteases, that acts on cartilage matrix to produce a substance which is an important component of the calcifying mechanism during enchondral ossification.


Biotyping respiratory Haemophilus species with the microbact system.
The biochemical characteristics of 114 respiratory Haemophilus isolates were examined by the Minitek and Microbact systems. The Microbact system was easy to use and read, although some of the less important reactions (glucose and xylose) were difficult to interpret on occasions. On the basis of the 3 crucial reactions--indole production, ornithine decarboxylase and urease activity--discrepancies between the two systems were minor. Given careful standardization of techniques the Microbact system is a suitable alternative to established techniques for the biotyping of H. influenzae and H. parainfluenzae.


Clinical Evaluation of Modified Release and Immediate Release Tacrolimus Formulations.
The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index. For these reasons, it represents an agent that could benefit from modified release formulations to overcome these limitations. The objective of this review is to discuss the clinical evaluation of immediate and modified release tacrolimus formulations in renal transplant recipients. Clinical trials from early development of immediate release tacrolimus to formulation-specific post-marketing trials of modified release tacrolimus formulations are reviewed with an emphasis on key elements relating to trial design end endpoint assessment. Particular elements that can be addressed with formulation alterations, such as pharmacokinetics, pharmacogenomics, and toxicity and corresponding clinical evaluations are discussed. In addition, current knowledge gaps in the clinical evaluation of immediate and modified release tacrolimus formulations are discussed to highlight potential avenues for the future development of different tacrolimus formulations with outcomes relevant to the regulators, the transplant community, and to transplant recipients. This review shows that new formulations may alter tacrolimus bioavailability, alleviate certain adverse events while potentially enhancing patient convenience.


Periodic unitary synaptic currents in the mouse globus pallidus during spontaneous firing in slices.
Neurons in the external globus pallidus (GPe) are autonomous pacemakers, but their spontaneous firing is continually perturbed by synaptic input. Because GPe neurons fire rhythmically in slices, spontaneous inhibitory synaptic currents (IPSCs) should be evident there. We identified periodic series of IPSCs in slices, each corresponding to unitary synaptic currents from one presynaptic cell. Optogenetic stimulation of the striatal indirect pathway axons caused a pause and temporal resetting of the periodic input, confirming that it arose from local neurons subject to striatal inhibition. We determined the firing statistics of the presynaptic neurons from the unitary IPSC statistics and estimated their frequencies, peak amplitudes, and reliabilities. To determine what types of GPe neurons received the spontaneous inhibition, we recorded from genetically labeled parvalbumin (PV) and Npas1-expressing neurons. Both cell types received periodic spontaneous IPSCs with similar frequencies. Optogenetic inhibition of PV neurons reduced the spontaneous IPSC rate in almost all neurons with active unitary inputs, whereas inhibition of Npas1 neurons rarely affected the spontaneous IPSC rate in any neurons. These results suggest that PV neurons provided most of the active unitary inputs to both cell types. Optogenetic pulse stimulation of PV neurons at light levels that can activate cut axons yielded an estimate of connectivity in the fully connected network. The local network is a powerful source of inhibition to both PV and Npas1 neurons, which contributes to irregular firing and may influence the responses to external synaptic inputs.NEW & NOTEWORTHY Brain circuits are often quiet in slices. In the globus pallidus, network activity continues because of the neurons' rhythmic autonomous firing. In this study, synaptic currents generated by the network barrage were measured in single neurons. Unitary synaptic currents arising from single presynaptic neurons were identified by their unique periodicity. Periodic synaptic currents were large and reliable, even at the cell's natural firing rates, but arose from a small number of other globus pallidus neurons.


A plant/fungal-type phosphoenolpyruvate carboxykinase located in the parasite mitochondrion ensures glucose-independent survival of Toxoplasma gondii.
Toxoplasma gondii is considered to be one of the most successful intracellular pathogens, because it can reproduce in varied nutritional milieus, encountered in diverse host cell types of essentially any warm-blooded organism. Our earlier work demonstrated that the acute (tachyzoite) stage of T. gondii depends on cooperativity of glucose and glutamine catabolism to meet biosynthetic demands. Either of these two nutrients can sustain the parasite survival; however, what determines the metabolic plasticity has not yet been resolved. Here, we reveal two discrete phosphoenolpyruvate carboxykinase (PEPCK) enzymes in the parasite, one of which resides in the mitochondrion (TgPEPCKmt), whereas the other protein is not expressed in tachyzoites (TgPEPCKnet). Parasites with an intact glycolysis can tolerate genetic deletions of TgPEPCKmt as well as of TgPEPCKnet, indicating their nonessential roles for tachyzoite survival. TgPEPCKnet can also be ablated in a glycolysis-deficient mutant, while TgPEPCKmt is refractory to deletion. Consistent with this, the lytic cycle of a conditional mutant of TgPEPCKmt in the glycolysis-impaired strain was aborted upon induced repression of the mitochondrial isoform, demonstrating its essential role for the glucose-independent survival of parasites. Isotope-resolved metabolomics of the conditional mutant revealed defective flux of glutamine-derived carbon into RNA-bound ribose sugar as well as metabolites associated with gluconeogenesis, entailing a critical nodal role of PEPCKmt in linking catabolism of glucose and glutamine with anabolic pathways. Our data also suggest a homeostatic function ofTgPEPCKmt in cohesive operation of glycolysis and the tricarboxylic acid cycle in a normal glucose-replete milieu. Conversely, we found that the otherwise integrative enzyme pyruvate carboxylase (TgPyC) is dispensable not only in glycolysis-competent but also in glycolysis-deficient tachyzoites despite a mitochondrial localization. Last but not least, the observed physiology of T. gondii tachyzoites appears to phenocopy cancer cells, which holds promise for developing common therapeutics against both threats.


Untreated Sleep Apnea: An Analysis of Administrative Data to Identify Risk Factors for Early Nonadherence.
Discontinuation of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) is widely reported, but research has not adequately addressed nonadherence with diagnostic testing for sleep disorders and initiation of PAP. This study sought to identify drivers of nonadherence with diagnostic sleep testing and PAP treatment initiation among patients preauthorized for these services. This observational cohort study used preauthorization records from a sleep management program and administrative medical claims from a large commercial health insurer. Participants included adults preauthorized for sleep testing and a subset in whom OSA was diagnosed and who were preauthorized for PAP treatment. Outcome measures were nonadherence with diagnostic sleep testing and PAP treatment initiation, identified as lack of a claim for a preauthorized service within 3 months of preauthorization of that service. Risk factors for nonadherence included patient demographics, prescribing factors, signs and symptoms of OSA, comorbidities, and prior health service utilization. Of 51,749 patients preauthorized for diagnostic testing, 23.5% did not undergo testing. Among 19,968 patients preauthorized for PAP treatment, 11.1% did not initiate treatment. Testing and treatment ordered by primary care providers, residence outside the Midwest region, and two or fewer office visits within 6 months before preauthorization were strong predictors of nonadherence. Apnea-hypopnea index score < 30 events/h was also a strong predictor of nonadherence with treatment initiation. This study adds to existing knowledge about risk factors for nonadherence with sleep testing and treatment initiation following preauthorization. Health plans and providers should develop strategies to better engage patients with higher risk of nonadherence.


[The nuclear morphometric analysis and its clinical value in esophageal cancer].
The technique of computer-assisted morphometric analysis had been utilized to assess the prognosis for many cancers. However, there has not been the report about application of this method in esophageal cancer. The nuclear area (A) and nuclear roundness factor (NRF) of epithelial cells of 42 esophageal cancers and ten normal esophagus were measured by morphometry and the results were compared with the extent of the tumor (length, depth and lymph node metastasis), pathologic grades of the cancer, survival time of the patients, and so on. A and NRF of epithelial cells of esophageal cancer were significantly larger than those of normal esophagus (P < 0.001 and P < 0.05 respectively). In the esophageal cancer group, NRF of epithelial cells of patients with short survival time were significantly larger than those of long survival time (P < 0.05). NRF of epithelial cells of patients with lymphatic node metastasis were significantly larger than those of non-metastasis (P < 0.05). A and NRF of epithelial cells were not related with tumor length, invasive depth, and position, also not related with patient sex and age. The results confirmed that nuclear morphometry can play an important role in the diagnosis, differential diagnosis and prognosis of esophageal cancer.


Effects of dibenzothioline and silymarin on the dry weight of isolated hepatocytes of rats acutely poisoned with phalloidin and alpha-amanitin.
The protective action of dibenzothioline and silymarin in the acute intoxication by phalloidin and alpha-amanitin has been studied on the basis of their ability to attenuate changes in dry mass distribution and class-pattern of the hepatocytes, as evaluated by microinterferometry. Protective agents were given to male rats 30 min before toxin, and the animals were sacrificed 3.0 h later. Both dibenzothioline and silymarin markedly counteract the toxic action of phalloidin and alpha-amanitin on the hepatocyte population, as revealed by a substantial prevention (a) of the striking displacement of hepatocytes in the intervals among the classes as regards phalloidin poisoning, and (b) of the number decrease of hepatocyte classes due to disappearance of the heaviest ones, of the shift of hepatocytes to the lighter classes, of the appearance of very light cells, of the displacement of hepatocytes into the class intervals and of the decrease in nuclear dry mass as regards alpha-amanitin. It is suggested that dibenzothioline and silymarin exert their protective action by a non-specific stabilization of the cell membrane.


Altered passive eruption (APE) and active secondary eruption (ASE): differential diagnosis and management.
The process of tooth eruption consists of two phases, active and passive. While the distinction is unequivocal, the mechanism is ambiguous. This article compares and contrasts altered passive eruption (APE) and active secondary eruption (ASE). Although these phases present with similar clinical manifestations, each has its own etiology, physiogenesis, and pathogenesis. Furthermore, the differential diagnosis between the two, and that between other mirroring conditions, is essential for arriving at a definite diagnosis and correct treatment strategies, which may be similar but have different consequences. This article concludes with two case studies that show the management of APE and ASE, highlighting the treatment similarities and differences that are dependent on the specific etiology.


Pulmonary alveolar proteinosis and first successful whole lung lavage in Sri Lanka: a case report.
Pulmonary alveolar proteinosis is a rare disease characterized by accumulation of lipoproteinaceous material within alveoli. There are three clinically distinct forms: congenital, acquired and secondary. Whole lung lavage is currently the gold standard therapy for severe cases of pulmonary alveolar proteinosis. In Sri Lanka this is the first reported successful whole lung lavage for a patient with pulmonary alveolar proteinosis. We describe the case of a 15-year-old Sri Lankan girl who presented with symptoms of progressive shortness of breath and dry cough for 6 months' duration. She had a history of exposure to silica in her household environment. High-resolution computed tomography revealed crazy paving appearance in both lungs suggestive of pulmonary alveolar proteinosis. An open lung biopsy revealed intra-alveolar granular amphophilic material which was strongly periodic acid-Schiff positive and diastase resistant, which is consistent with pulmonary alveolar proteinosis. She was followed up for 2 years with periodical segmental bronchoalveolar lavages which showed minimal improvement in her symptoms as well as in exercise desaturation. Due to severe dyspnea and hypoxemia on exertion, she underwent whole lung lavage. It resulted in a marked improvement in her symptoms, exercise desaturation, and chest X-ray results. Whole lung lavage was successfully performed for the first time in Sri Lanka for a patient with pulmonary alveolar proteinosis.


A model of bacterial-antimicrobial interactions: the case of oropharyngeal and gastrointestinal microflora.
The normal human oropharyngeal and gastrointestinal microflora is a complex ecosystem in a symbiotic relationship with the host. The microflora helps to prevent invasion of pathogens and participates in several metabolic processes. On the other hand, under certain conditions members of the normal microflora can cause serious infections. Administration of antimicrobial agents may cause severe alterations in the normal microflora. Suppression of the anaerobic flora has been associated with decreased colonization resistance, i.e. the resistance of the normal host to the implantation of exogenous microorganisms.


Studies on Cellular Response of Escherichia coli to UDP-Galactose Accumulation.
Cellular responses to intracellular accumulation of UDP-galactose (UDP-Gal) were investigated for D-galactose-induced lysis of an Escherichia coli galE mutant. The mutant, ara-207, showed dramatic lysis in a nutrient broth supplemented with D-galactose after 3h of cultivation when transformation of normal rod cells into bulged- and spheroplast-like cells was clearly observed under electron microscope. UDP-Gal had been already detected with the optimal level at 2 h of cultivation, followed by a drastic decrease in its level as well as a significant increase in the level of active (inhibitor-free) UDP-sugar hydrolase (USH) together with the bacterial lysis. Significant loss of UTP, UDP, and UDP-N-acetylglucosamine agreed with the in vivo activity of USH thus produced. Addition of D-sorbitol did not restrict UDP-Gal accumulation but did mostly protect ara-207 against the above morphological changes of the cells in which overproduction of USH was repressed over 3 to 4 h of cultivation. These results suggested that accumulation of UDP-Gal could have some growth inhibitory effect on E. coli cells but the compound was not directly involved with the following lytic process via spheroplast formation. A possibility was taken into account, that the accumulation of UDP-Gal caused overproduction of USH, which may provoke inhibition of bacterial peptidoglycan synthesis.


Alignment of adherence and risk for HIV acquisition in a demonstration project of pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention-effective adherence.
Adherence is essential for pre-exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most efficient when its use is aligned with periods of risk - a concept termed prevention-effective adherence. The objective of this paper is to describe prevention-effective adherence and predictors of adherence within an open-label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project). We offered PrEP to HIV-uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as "PrEP as a bridge to ART"). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with <100% condom use before six months of ART, low if they reported sex but had 100% condom use and/or six months of ART and very low if no sex was reported. We assessed prevention-effective adherence by cross-tabulating PrEP use with HIV risk and used multivariable regression models to assess predictors of ≥4 and ≥6 doses/week. Results A total of 985 HIV-uninfected participants initiated PrEP; 67% were male, median age was twenty-nine years, and 67% reported condomless sex in the month before enrolment. An average of ≥4 doses and ≥6 doses/week were taken in 81% and 67% of participant-visits, respectively. Adherence sufficient to protect against HIV acquisition was achieved in 75-88% of participant-visits with high HIV risk. The strongest predictor of achieving sufficient adherence was reporting sex with the study partner who was living with HIV; other statistically significant predictors included no concerns about daily PrEP, pregnancy or pregnancy intention, females aged >25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months of follow-up, ART use >6 months by the partner living with HIV and problem alcohol use. Over three-quarters of participant-visits by HIV-uninfected partners in serodiscordant couples achieved prevention-effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.


[Aortic and mitral valve endocarditis after infection of the pacemaker pocket].
The case of a 76-year-old diabetic patient with known aortic valve sclerosis is reported. One week after implantation of a permanent pacemaker system (indication: 2nd degree AV-block type Mobitz) he developed fever. Large endocarditic vegetations were found on the aortic and mitral valve (blood cultures: were positive for Staphylococcus aureus). Also from the pacemaker bed Staphylococcus aureus was isolated and an antibiotic treatment including vancomycin was started. Nevertheless the patient developed insufficiencies of both the aortic and mitral valves and became hemodynamically unstable. Due to cerebral embolisms and further deterioration of the patient's overall clinical state the already planned operative replacement of the aortic and mitral valve could not be performed. The patient died because of left ventricular failure after pacemaker infection which was complicated by endocarditis.


Modification with Metallic Bismuth as Efficient Strategy for the Promotion of Photocatalysis: The Case of Bismuth Phosphate.
A BiPO4 nanostructure modified with Bi nanoparticles rich in oxygen vacancies in the surface and subsurface was prepared through a one-pot solvothermal treatment utilizing the weak reductive ability of ethylene glycol (EG). The presence of Bi nanocrystals and oxygen vacancies is beneficial for the separation and consumption of photogenerated electrons and holes where Bi nanocrystals act as active sites for the formation of (.) OH and oxygen vacancies are active sites for (.) O2 (-) formation. The enhanced photocatalytic activity is ascribed to the synergistic effect of Bi nanocrystals and surface oxygen vacancies.


Evaluating the Impact of Hospital Efficiency on Wellness in the Military Health System.
Like all health care delivery systems, the U.S. Department of Defense Military Health System (MHS) strives to achieve top preventative care and population health outcomes for its members while operating at an efficient level and containing costs. The objective of this study is to understand the overall efficiency performance of military hospitals and investigate the relationship between efficiency and wellness. This study uses data envelopment analysis and stochastic frontier analysis to compare the efficiency of 128 military treatment facilities from the Army, Navy, and Air Force during the period of 2011 to 2013. Fixed effects panel regression is used to determine the association between the hospital efficiency and wellness scores. The results indicate that data envelopment analysis and stochastic frontier analysis efficiency scores are congruent in direction. Both results indicate that the majority of the MHS hospitals and clinics can potentially improve their productive efficiency by managing their input resources better. When comparing the performance of the three military branches of service, Army hospitals as a group outperformed their Navy and Air Force counterparts; thus, best practices from the Army should be shared across service components. The findings also suggest no statistically significant, positive association between efficiency and wellness over time in the MHS.


Chemical laser operation and n-butane absorption of DF R branch lines.
Laser emission on the R branch lines of DF has been demonstrated. The emission is much weaker than the P branch radiation from the same laser but is useful for absorption coefficient measurements or excitation of C-H bonds. Absorption coefficients of normal butane at the laser frequencies have been measured and are shown to be potentially useful for remote sensing of the atmosphere and studies of vibrationally excited molecules.


Research activities in toxicology and toxicological requirements of the FDA for food and color additives.
The Center for Food Safety and Applied Nutrition of the Food and Drug Administration has published guidelines for the safety assessment of direct food and color additives. These guidelines are to be updated beginning in 1988. The safety of a food and color additive must be established prior to marketing by an evaluation of probable exposure of consumers and appropriate toxicological information. "Safe" and "safety" are defined as a reasonable certainty that a substance is not harmful under the intended conditions of use. A number of tests are used in determining the safety of food additives. Some of these are: subchronic toxicity studies, chronic toxicity studies, carcinogenicity, reproduction, teratogenicity, and occasionally short-term tests for carcinogenicity. The Center also has a research program in toxicology which in part focuses on diet/toxicity interaction and risk assessment. Examples of such activities are investigation of the teratogenicity of textured vegetable protein and of the potential of zinc to prevent or ameliorate such effects, the development of whole rat embryo cultures as a model to investigate the mechanisms by which teratogens may act, and a program in pharmacokinetics and molecular toxicology to aid in studying assumptions underlying risk assessment.


Down- and up-converting dual-mode YPO4:Yb(3+),Tb(3+) nanocrystals: synthesis and spectroscopic properties.
Tetragonal YPO4 nanocrystals doped with Yb(3+) and Tb(3+) ions were synthesized by 900 °C annealing of precursors obtained with a co-precipitation method in the presence of glycerine. These materials exhibited intense green luminescence under ultraviolet excitation and up-conversion emission from the (5)D3 and (5)D4 Tb(3+) excited states after irradiation with near infrared light (λ = 980 nm). The structure and morphology of the products were analysed by recording X-ray diffraction patterns and transmission electron microscopy images. The obtained nanomaterials were single-phased with spherical shaped nanocrystals that had an average size of 18 ± 3 nm. The spectroscopic properties of YPO4:Yb(3+),Tb(3+) nanocrystals were investigated based on their excitation and emission spectra. The time-resolved luminescence traces were measured, and the luminescence lifetimes of Tb(3+) and Yb(3+) ions were calculated. The most effective dopant concentrations were determined to be 5% Yb(3+) and 15% Tb(3+), which exhibited the most intense ultraviolet excited emission and up-conversion. Because the integral intensity was observed to be dependent on the power of the pumping laser, a cooperative energy transfer (CET) mechanism underlying the observed up-conversion was proposed.


MicroRNA‑873 inhibits the progression of thyroid cancer by directly targeting ZEB1.
Recent evidence has revealed that certain microRNAs (miRNAs) are dysregulated in thyroid cancer (TC), which has been associated with the pathogenesis and development of TC. Therefore, improved understanding of the detailed roles of miRNAs that are aberrantly expressed in TC may aid the development of valuable therapeutic methods for the management of patients with this malignancy. In this study, miRNA‑873‑5p (miR‑873) expression in TC tissues and cell lines was detected by reverse‑transcription quantitative polymerase chain reaction (RT‑qPCR). MTT and cell invasion assays were performed to investigate the effects of miR‑873 overexpression on TC cell proliferation and invasion in vitro. Bioinformatics analysis, luciferase reporter assay, RT‑qPCR and western blot analysis were employed to evaluate whether zinc finger E‑box‑binding homeobox 1 (ZEB1) is a direct target of miR‑873 in TC cells. The present study reported that miR‑873 was weakly expressed in human TC tissues and cell lines. Functionally, miR‑873 overexpression suppressed TC cell proliferation and invasion in vitro. Mechanistically, ZEB1 was predicted to be a putative target of miR‑873. In addition, miR‑873 was proposed to directly bind to the 3'‑untranslated region of ZEB1 and decrease its expression in TC cells at the mRNA and protein levels. Furthermore, ZEB1 expression was significantly upregulated in TC tissues and negatively correlated with miR‑873 expression. Furthermore, ZEB1 restoration partially reversed the suppressive effects of miR‑873 overexpression on TC cell proliferation and invasion. These results demonstrated that miR‑873 may serve tumour‑suppressive roles in the progression of TC, and its suppressive effects could be mediated by the inhibition of ZEB1. Therefore, miR‑873 may be a valuable therapeutic target in the management of patients with TC.


Effects of dual arterial blood supply on liver regeneration in the graft and the host following heterotopic auxiliary liver transplantation.
This study aimed to investigate the effect of the dual arterial blood supply method used in auxiliary liver transplantation on the regeneration of grafted and host liver. A total of 72 male Sprague-Dawley rats were randomly assigned to three experimental groups, namely the 68% hepatectomy group (group A), the 68% hepatectomy with dual arterial blood supply group (group B) and the auxiliary liver transplantation with dual arterial blood supply group (group C). Group C was further divided into the host liver subgroup (group Ca) and the transplanted liver subgroup (group Cb). Six animals from each group were sacrificed at 1, 2 and 7 days after surgery. The calculation of the liver regeneration rate (LRR) was based on measuring liver weight. Liver function was assessed by measuring serum alanine aminotransferase (ALT) levels. Immunohistochemistry was employed to detect the expression of proliferating cell nuclear antigen (PCNA). Apoptotic changes in the grafts and host livers were evaluated using TUNEL staining. The LRR in each group exhibited a tendency to increase over time. At each time point, the LRR of transplanted livers in group C exhibited no significant difference from that of host livers in group C (P>0.05). The ALT levels for each group exhibited a time-dependent decreasing tendency. The ALT level in group C was significantly higher compared to that in groups A and B at each time point (P<0.05). The expression of PCNA in transplanted and host livers in group C was significantly lower compared to that in groups A and B at the same time point (P<0.001). Although the number of apoptotic cells in each group varied at different time points, there was no statistically significant difference (P>0.05). In auxiliary liver transplantation with the dual arterial blood supply method, the capacity of the liver regeneration in the grafts was similar to that of the host livers. Therefore, this technique may reduce the potential risk of graft liver atrophy caused by functional competition.


IncI1 plasmids associated with the spread of CMY-2, CTX-M-1 and SHV-12 in Escherichia coli of animal and human origin.
Fourteen plasmids carrying blaCTX -M-1, blaSHV -12 or blaCMY -2 genes from Escherichia coli of both avian and human origin were analysed. IncI1 plasmids were largely predominant. Plasmid mutilocus sequence typing and comparative analysis revealed that the blaCMY -2 -ST12-IncI1 plasmids from avian E. coli were identical to those previously found in Salmonella from humans, but different to those associated with human E. coli. The IncI1-ST3 plasmids carrying blaCTX -M-1 or blaSHV -12 were related to those previously identified in avian E. coli, but different to those identified in human E. coli. Overall, no plasmids shared by E. coli of both origin (human/avian) were identified; however, further investigations are needed.


Uncommon breast metastatic site and eribulin responsiveness in a heavily pretreated patient.
During the last decades, the introduction of new cytotoxics and targeted therapies resulted in a prolongation of survival and a minimization of toxicity in the treatment of metastatic breast cancer. However, to date, there was no standard of care following second-line therapy in this setting. In Phase III EMBRACE study, eribulin obtained a statistically significant improvement in the overall survival of pretreated metastatic breast cancer patients. This case report describes a heavily chemo-pretreated woman with important bone, nodal, hepatic and choroidal involvement from breast cancer who had a remarkable, unexpected and lasting disease response after treatment with eribulin. This case underlines how this well-tolerated monochemotherapy may be able to obtain a prolonged disease control and a good clinical outcome.


Quality and Safety in Health Care, Part LXIX: Introduction to the Responsibilities of the Chief Medical Officer.
The chief medical officer (CMO) is a key member of the administration of most large health care systems. The CMO helps with communication between the medical staff and the nonphysician administrators. The CMO typically plays an important role in utilization review, ensuring compliance with laws and regulations, peer review, credentialing, and privileging. One of the most important roles of the CMO has been to improve quality and safety while keeping costs under control, although now many institutions also have quality and safety officers. In addition, the CMO plays a major role in advising the administration regarding clinical equipment purchases, including those for emerging technologies, and in long-range clinical planning.


Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease.
Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase 1 clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T-cell activation via costimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with 2 escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg. Abatacept was well-tolerated with no dose-limiting toxicities. Of the 16 evaluable patients, 44% achieved a clinical partial response per 2005 National Institutes of Health Consensus Criteria. Importantly, abatacept resulted in a 51.3% reduction in prednisone usage in clinical responders (mean baseline, 27 vs 14 mg; P = .01). Increased PD-1 expression on circulating CD4 (P = .009) and CD8 (P = .007) T cells was observed in clinical responders. In summary, abatacept was safe and led to a marked improvement in National Institutes of Health cGVHD scores and a significant reduction in prednisone use. In this cohort of heavily pretreated patients, the results suggest abatacept may be a promising therapeutic agent for SR-cGVHD, and a phase 2 trial has been initiated. This trial was registered at www.clinicaltrials.gov as #NCT01954979.


[Adaptive remodeling of temporomandibular joint following anterior disc displacement and treatment decision making].
Anterior disc displacement (ADD) of temporomandibular joint (TMJ) is one of the common oral diseases. The TMJ can be remodeled after disc displacement. The author's recent studies show that remodeled bilaminar zone is similar to the disc in composition and functions. The remodeled condyle can match the disc-like bilaminar zone. The new disc-condylar relationship can, to a certain extent, restore the function of the TMJ. Based on these studies, the author believes that the adaptive remodeling in TMJ has important guiding significance for clinical treatment and discusses the views of the treatment decision for various stages of temporomandibular disorders.


Memristive Devices with Highly Repeatable Analog States Boosted by Graphene Quantum Dots.
Memristive devices, having a huge potential as artificial synapses for low-power neural networks, have received tremendous attention recently. Despite great achievements in demonstration of plasticity and learning functions, little progress has been made in the repeatable analog resistance states of memristive devices, which is, however, crucial for achieving controllable synaptic behavior. The controllable behavior of synapse is highly desired in building neural networks as it helps reduce training epochs and diminish error probability. Fundamentally, the poor repeatability of analog resistance states is closely associated with the random formation of conductive filaments, which consists of oxygen vacancies. In this work, graphene quantum dots (GQDs) are introduced into memristive devices. By virtue of the abundant oxygen anions released from GQDs, the GQDs can serve as nano oxygen-reservoirs and enhance the localization of filament formation. As a result, analog resistance states with highly tight distribution are achieved with nearly 85% reduction in variations. In addition the insertion of GQDs can alter the energy band alignment and boost the tunneling current, which leads to significant reduction in both switching voltages and their distribution variations. This work may pave the way for achieving artificial neural networks with accurate and efficient learning capability.


After spouses depart: emotional wellbeing among nonmigrant Mexican mothers.
Nonmigrant family members play a central role in facilitating Mexico-U.S. migration by maintaining families, sustaining social relationships, and overseeing household economic organization in sending communities. This study investigates changes to the emotional wellbeing of nonmigrant mothers when their partners reside in the United States. We hypothesize that partner migration affects mothers' wellbeing through three pathways: directly via the toll of spousal separation, and indirectly via changes to the economic profile of the sending household and through changes to mothers' household responsibilities. We test these relationships using data on 2813 mothers aged 18-44 in 2002 and measured in three waves (2002, 2005, 2009) of the Mexican Family Life Survey. We employ a fixed-effect estimation strategy that improves causal attribution of women's wellbeing to spousal residential location. We find evidence of increases in some forms of distress-sadness, crying, difficulty sleeping-when spouses are in the United States but no meaningful increase in depressive symptomology. Though partner emigration shifts several aspects of women's lives in sending households, changes to household resources or time allocation do not account for the moderate shifts in emotional duress associated with spousal absence. Importantly, additional tests reveal that we would observe large and significant associations between spousal migration and mothers' emotional wellbeing using a less rigorous estimation strategy, raising caution about the interpretation of cross-sectional studies evaluating wellbeing in sending homes.