Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy.
To determine magnetic resonance imaging (MRI) patterns of brain atrophy in parkinsonian syndromes, we applied voxel-based morphometry (VBM) to segmented gray matter, white matter, and cerebrospinal fluid compartments of T(1)-weighted brain volumes of 12 patients with probable multiple system atrophy-parkinson variant (MSA-P) and 12 Parkinson's disease patients, comparing them with 12 normal controls matched for age. In comparison to controls, a cortical atrophy pattern was observed in MSA-P patients with significant clusters of volume loss in primary sensorimotor cortices bilateral, supplementary motor areas bilateral, right premotor cortex, prefrontal cortex bilateral (middle frontal gyri) and insular cortices bilateral; subcortical atrophy occurred bilaterally in caudate nuclei and putamen as well as in the midbrain. Furthermore, an enlargement of the cerebrospinal fluid compartment was found in the lateral ventricles, third ventricle, perimesencephalic and cerebellomedullar cavities. In PD patients, significant atrophy only occurred in left caudate head with enlargement of left lateral ventricle. Comparing MSA-P to PD patients, MSA-P showed a similar cortical pattern of atrophy as compared to controls. We conclude that VBM reveals selective cortical atrophy in patients with MSA-P affecting primary and higher order motor areas as well as prefrontal and insular cortices. Further studies are required to determine clinical and/or subclinical correlates of cortical atrophy in MSA-P.


Empathy Assessment Scale.
Empathy is a prosocial ability and communication skill to feel, understand, and respond to emotions of others; it includes affective and cognitive behavioral aspects of therapeutic communication. For instance, physicians should communicate empathically with their patients. Thus, empathy levels of medical students should be improved during their education. It is important to comparatively evaluate the dimensions of empathy to have a clearer picture of this ability. The aim of this study is to determine the validity and reliability of the Empathy Assessment Scale (EAS) and its subscales. Data were collected between October and December in 2021 from 651 students studying medicine in Istanbul Medeniyet University. Item pool of the scale was developed by the researcher based on the literature review. Two counseling psychologists, two clinical psychologist, and two psychiatrists evaluated the items to detect the face and content validity in the final application form. Both explanatory and confirmatory factor analyses (EFA and CFA) were carried out. The Toronto Empathy Questionnaire was also applied for concurrent validity. IBM SPSS 25 and AMOS 24 were utilized to analyze the construct and concurrent validities, internal consistency, and test-retest reliabilities. KMO and Bartlett's sphericity tests showed that the dataset was suitable for factor analyses (KMO=0.812, Chi-square=5535.718, df=78). A three-factor structure with 13 items was confirmed by EFA, 67.1% of the variance was explained by these three factors. According to CFA, the factor loads of the items varied between 0.39 and 0.98 and data model fit was suitable according to the fit indices (CFI=0.95, TLI=0.91, RMSEA=0.049, SRMR=0.055, and Chi-square/df=1.316). Concurrent validity of the scale was also confirmed by the Pearson correlation (r=0.467, p<0.001). The test-retest reliability values (r) within four weeks interval were all above 0.60 at 0.01 significance level. Cronbach's alpha coefficients were 0.845 (EAS total scale score, 13 items), 0.696 (social interaction subscale score, 4 items), 0.802 (cognitive behavior subscale score, 5 items), and 0.964 (emotional identification subscale score, 4 items). EAS is a valid and reliable measurement tool to assess the empathy levels of individuals in three dimensions: Social interaction, cognitive behavior, and emotional identification. EAS can be used to evaluate the empathy levels for research, educational, and other interventional purposes.


Response of patients to the introduction of a private Magnetic Resonance Imaging service in Western Jamaica.
Magnetic Resonance Imaging (MRI) is one of today's fastest growing imaging modalities, spurred in part by rapid advances in technology and important new applications in patient care. It was introduced in Western Jamaica in March 2005 at a non-hospital-based facility called North Coast Imaging MRI Service. The study examined the socio-demographics, accessibility and affordability of the services to patients. A random sample of 100 patients was used and the research instrument was a questionnaire. The study was conducted between August and November 2008. The findings of the study showed that majority of the respondents lived in rural areas and were within the age group 30 - 59 years. One-half of the respondents resided in St. James, were employed; earned more than US$1,351.00 per month and could afford the cost of the MRI procedure. More than one half of the respondents indicated that it took 15 - 30 minutes to be examined after arrival at the Centre; most (81%) of the respondents indicated that the MRI procedure was adequately explained, and 99% indicated that questions about the procedure were satisfactorily answered. The MRI Scans performed at the North Coast Imaging MRI Service showed an increase of 157.49% in 2006 when compared with 2005, and 70.90% in 2007 when compared with 2006. Our findings suggest that the number of MRI scans done at the North Coast Imaging MRI Service is likely to increase. Although most of the respondents were able to afford the procedure there are concerns about persons in the lower socio-economic group who are unable to afford expensive diagnostic imaging tests such as MRI scans. There is an urgent need for government-owned hospital-based MRI Units in Jamaica to offer lower cost MRI scans to the public.


Measuring worker turnover in long-term care: lessons from the better jobs better care demonstration.
Turnover among direct-care workers (DCWs) continues to be a challenge in long-term care. Both policy makers and provider organizations recognize this issue as a major concern and are designing efforts to reduce turnover among these workers. However, there is currently no standardized method of measuring turnover to define the scope of the problem or to assess the effectiveness of interventions. This article draws on our experience of the Better Jobs Better Care Demonstration (BJBC) to explicate some important issues in measuring and interpreting turnover related to interventions designed to improve DCW jobs. We used turnover data from a selected group of BJBC providers (N = 9) to demonstrate some of the measurement issues we uncovered in developing a turnover tracking system for BJBC. We also illustrate how the data elements collected in the tracking system make it possible to construct measures that are useful at both policy and practice levels. Differences in definitions of turnover and the data elements used to construct the measure can have large effects on turn over rates, how they are used, and what they mean. Policy makers, researchers, and managers who need comparative turnover information to address the impending demand for DCWs should be aware that turnover measures differ, and they should take steps to ensure that measures they use have common definitions and data elements.


The Tcf21 lineage constitutes the lung lipofibroblast population.
Transcription factor 21 (Tcf21) is a basic helix-loop-helix transcription factor required for mesenchymal development in several organs. Others have demonstrated that Tcf21 is expressed in embryonic lung mesenchyme and that loss of Tcf21 results in a pulmonary hypoplasia phenotype. Although recent single-cell transcriptome analysis has described multiple mesenchymal cell types in the lung, few have characterized the Tcf21 expressing population. To explore the Tcf21 mesenchymal lineage, we traced Tcf21-expressing cells during embryogenesis and in the adult. Our results showed that Tcf21 progenitor cells at embryonic day (E)11.5 generated a subpopulation of fibroblasts and lipofibroblasts and a limited number of smooth muscle cells. After E15.5, Tcf21 progenitor cells exclusively become lipofibroblasts and interstitial fibroblasts. Lipid metabolism genes were highly expressed in perinatal and adult Tcf21 lineage cells. Overexpression of Tcf21 in primary neonatal lung fibroblasts led to increases in intracellular neutral lipids, suggesting a regulatory role for Tcf21 in lipofibroblast function. Collectively, our results reveal that Tcf21 expression after E15.5 delineates the lipofibroblast and a population of interstitial fibroblasts. The Tcf21 inducible Cre mouse line provides a novel method for identifying and manipulating the lipofibroblast.


Metformin use associated with lower risk of cancer in patients with diabetes mellitus type 2.
Aim In order to increase the database related to the antineoplastic potential of metformin, association between the use of metformin and risk of cancer occurence in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this cross-sectional study, medical records of patients with DM2 were reviewed for cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine consumption, glucose and HbA1c levels, duration of DM2, medication used in the treatment of DM2 and cancer occurence were collected and analyzed. Unpaired Student's t-test or Mann-Whitney U test were used for comparisons between treatment groups, and logistic regression to asses how well our set of predictor variables predicts occurence of carcinoma. P-value less than 0.05 was considered statistically significant. Results The mean age of 234 included patients was 66.8±11.5 years, and DM2 duration was 7± 6.49 years. Mean glucose value was 8.51±4.17mmol/L, and HbA1c 7.74±1.53. Metformin therapy was prescribed in 190 (81%) patients. Cancer was diagnosed in 16 (6.8%) patients: prostate cancer in eight (3.4%), breast cancer in four (1.7%), rectal cancer in two (0.9%) and cancer of the uterus and cervix in one patient. Age, duration of DM2 and BMI did not contribute significantly to the model, while metformin use was shown to be a significant independent predictor (OR=0.049; 95% CI=0.013-0.181; p=0.001). Conclusion Our findings support the hypothesis that the use of metformin compared to the use of other oral antidiabetic drugs is associated with a lower risk of cancer in patients with DM2.


Alpha oscillatory power decreases are associated with better memory for higher valued information.
Items associated with high value are often better remembered. Value may increase attention toward item in context associations. Alpha oscillations (8-13 Hz) are thought to underlie attention and their observation may reveal the role attention plays in value-based memory. In the current study, EEG is used to record brain activity while participants (n = 30) completed a source recognition memory task where items were associated with either high or low value backgrounds to determine whether greater attentional resources are deployed when encoding high value information. Participants demonstrated better memory for objects associated with high value backgrounds. Alpha oscillatory power in occipital/temporal brain regions exhibited greater desynchronization when encoding objects associated with high value that were later successfully recalled compared to those associated with low value. In addition, beta oscillatory power in midfrontal brain regions exhibited greater desynchronization during successful recall of high value objects compared to low value objects. Together these results suggest that more attentional resources are used to encode information that is associated with high value, which increases the likelihood of later successful memory recall.


Mechanism of inhibitory action of the local anaesthetic trimecaine on the growth of algae (Chlorella vulgaris).
Using the model compound trimecaine, it was found that algicidal effects exhibited by the local anaesthetics of the acetanilide type were caused by two different mechanisms. The first inhibitory mechanism occurring at low concentrations of the anaesthetic is connected with the uncoupling of the photophosphorylations in algal chloroplasts and is accompanied by the enhancement of the oxygen evolving rate in algal photosynthesis. The second mechanism of inhibition of the photosynthesis in algae, taking place at higher concentrations of the anaesthetic, is connected with the damaging of the manganese containing protein on the donor side of photosystem 2 and is accompanied by a decrease of the oxygen evolving rate in algal photosynthesis.


IGF-1 regulation of type II collagen and MMP-13 expression in rat endplate chondrocytes via distinct signaling pathways.
Abnormal maturation and ossification of the endplate chondrocytes play a central role in the pathogenesis of degenerative disorders of the cervical spine. It is widely held that insulin like growth factor-1 (IGF-1) stimulates chondrocyte proliferation and inhibits chondrocyte terminal differentiation both in vitro and in vivo. However, the mechanism underlying such regulation is not fully understood. The present study aimed to determine the role of IGF-1 on the mRNA expression of collagen type II, alpha 1 (Col2a1) and matrix metallopeptidase 13 (MMP-13) in rat endplate chondrocytes. The possible pathways that transduce IGF-1 effects such as phosphatidylinositol-3 (PI-3)-kinase (PI3K) and mitogen activated protein kinase (MAPK) were also investigated in these cells. Cultured endplate chondrocytes harvested from rat cervical spines were treated with IGF-1 (100ng/ml), and the changes in Col2a1 and MMP-13 mRNA were monitored with real-time polymerase chain reaction (PCR). MMP-13 activity was also assayed. Activation of signaling proteins was evaluated by western blot analysis. Cells were also treated with pharmacological agents that block PI3K and MAPK signaling pathways. IGF-1 increased Col2a1 mRNA expression in rat endplate chondrocytes in a time- and dose-dependent manner. IGF-1 treatment resulted in a fourfold increase of Col2a1 mRNA with the effect maximizing at 24h. In contrast, IGF-1 treatment for 24h caused a roughly 50% reduction in MMP-13 mRNA. Similar effects were seen on the protein levels of type II collagen (col2) and MMP-13. Consistent with these results, IGF-1 also repressed MMP-13 activity. IGF-1 activated both the PI3K and the extracellular signal-regulated kinase (ERK) pathways as evidenced by phosphorylation of either Akt or ERK1/2 (respectively). The PI3K inhibitor Wartmannin significantly inhibited the IGF-1 effect on Col2a1 mRNA expression but did not affect IGF-1-induced repression of MMP-13 expression. In contrast, the ERK/MAPK inhibitor PD98059 significantly inhibited the effect of IGF-1 on MMP-13 mRNA repression and enhanced IGF-1-induced Col2a1 mRNA expression. In rat endplate chondrocytes the PI3K pathway mainly transduces IGF-1 effect on col2 expression while the ERK pathway mediates IGF-1 effect on MMP-13 expression.


Comment on "The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport".
O'Brien et al (Research Article, 24 February 2017, eaag1789) proposed a novel mechanism of primase function based on redox activity of the iron-sulfur cluster buried inside the C-terminal domain of the large primase subunit (p58C). Serious problems in the experimental design and data interpretation raise concerns about the validity of the conclusions.


Localization of cyclic adenosine 3',5'-monophosphate-responsive element (CRE)-binding proteins by southwestern histochemistry.
Regulation of gene transcription requires an interaction between specific segments of nuclear DNA and specific proteins. We describe a method to localize the specific DNA-binding proteins using haptenized double-stranded (ds) DNAs. To demonstrate this method, an oligodeoxynucleotide (oligo-DNA) with a consensus base sequence of cyclic adenosine monophosphate-responsive element (CRE) (TGACGTCA) with three TTA repeats at the 5' end was synthesized. Since the CRE sequence is palindromic, the oligo-DNA was allowed to self-anneal and form ds DNA with three TTA repeats at both ends. The CRE ds-oligo-DNA was irradiated with UV light to form haptenic thymine-thymine (T-T) dimers. The haptenized CRE ds-oligo-DNA reacted by Southwestern analysis with a distinct set of proteins, previously identified as CRE-binding proteins, ranging from 40-90 KD. When the haptenized CRE ds-oligo-DNA reacted with frozen sections fixed with 4% paraformaldehyde in PBS (pH 7.4) followed by enzyme immunohistochemical localization of the T-T dimers, nuclei of intestinal epithelial cells and brain cells were heavily stained. Nuclear staining was blocked when the sections were reacted with the haptenized CRE ds-oligo-DNA in the presence of an excess amount of non-haptenized CRE ds-oligo-DNA. This method, henceforth referred as Southwestern histochemistry, should be a useful tool to localize proteins that bind to a specific DNA sequence and regulate the transcriptional activity of genes.


Child-care satisfaction: linkages to work attitudes, interrole conflict, and maternal separation anxiety.
Analysis of a 20-item measure of child-care satisfaction (CCS) revealed 3 interpretable factors: Caregiver Communication, Dependability, and Attentiveness. These CCS factors were used, along with employer sensitivity to child-care needs and spousal support, in hierarchical multiple regressions to predict various measures of work attitudes and role strain. Replicated across 2 samples of employed women, the CCS factors demonstrated differential patterns of relationships in which Caregiver Attentiveness was associated with lower professional-self role conflict and higher levels of affective organizational commitment and job satisfaction, whereas Caregiver Communication was associated with lower levels of both professional-parent conflict and maternal separation anxiety. These findings support the position that CCS is central to the functioning of employed mothers in both work and family domains.


Suicide with the veterinary drug acepromazine.
A suicide case involving the veterinary drug acepromazine is described. After a single-step liquid alkaline extraction, acepromazine was identified in a chest-cavity blood sample using gas chromatography (GC) with nitrogen-phosphorus (NPD) and mass selective detectors. Acepromazine was then quantitated in the blood and other postmortem tissues by GC with NPD using chlorpromazine as the internal standard. Acepromazine concentrations in the chest-cavity blood, liver, brain, and bile were 0.6, 3.0, 0.4, and 6.5 micrograms/mL, respectively. The stomach contents contained a total of 2.5 mg acepromazine.


Comparison between ultrasonographic findings of benign and malignant canine mammary gland tumours using B-mode, colour Doppler, power Doppler and spectral Doppler.
The aim of this study was to evaluate whether the comparison between the ultrasonographic features of canine mammary tumours, assessed by B-Mode, colour Doppler, power Doppler, spectral Doppler, and histopathologic features, would help to differentiate if a tumour is benign or malignant. Ultrasonographic examinations of 104 tumours were performed. Volume, margins, presence of a capsule, echotexture and presence and distribution of the vascular flow of the tumours were evaluated. All the tumours were surgically removed, submitted for histopathologic examination and classified in two groups: Group I (benign tumours) and Group II (malignant tumours). Echotexture was the only parameter evaluated by B-Mode ultrasonography where significant differences were found (p<0.01), with tumours in Group I being homogeneous and tumours in Group II presenting greater heterogeneity. Presence of vascular flow was observed in most of the tumours from both groups and no differences between them were found. Regarding flow distribution, significant differences were observed between groups (p<0.05). In benign tumours, the most common vascular pattern was the peripheral, showing significant differences (p<0.05) compared to mixed and central patterns. In malignant tumours the mixed pattern was the most frequent. Also significant differences among other patterns (peripheral and central) were found. Concerning vascular resistivity and pulsatility indexes, there were no significant differences between the two groups. The echotexture and type of vascular flow pattern of canine mammary gland tumours may help, in a first examination of the tumour, to differentiate between benign and malignant tumours; however to reach a definitive diagnosis histological study is required.


Behavioral effects of zonisamide on L-DOPA-induced dyskinesia in Parkinson's disease model mice.
Zonisamide (ZNS; 1,2-benzisoxazole-3-methanesulfonamide) was initially developed and is commonly used as an anticonvulsant drug. However, it has also shown its beneficial effects on Parkinson's disease (PD), a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the midbrain. Recent clinical studies have suggested that ZNS can also have beneficial effects on L-DOPA-induced dyskinesia (LID), which is a major side effect of long-term L-DOPA treatments for PD. In the present study, we examined the behavioral effects of ZNS on LID in PD model mice. Acute ZNS treatment did not have any observable behavioral effects on LID. Contrastingly, chronic ZNS treatment with L-DOPA delayed the peak of LID and reduced the severity of LID before the peak but increased the duration of LID in a dose-dependent manner of ZNS compared to PD model mice treated with L-DOPA alone. Thus, ZNS appears to have both beneficial and adverse effects on LID.


Tricuspid Regurgitation: Disease State and Advances in Percutaneous Therapy.
Tricuspid regurgitation (TR) is a relatively common finding. There has been growing recognition of the morbidity and adverse prognosis of severe TR, which affects 1.6 million people in the US. However, symptomatic TR remains undertreated despite emerging therapeutic modalities. In this review, the pathophysiological and epidemiological features of TR are examined and the diagnosis, natural history, and clinical presentation are discussed. An overview of TR therapy is provided, including medical and surgical treatments, as well as novel percutaneous approaches. The currently available studies on percutaneous therapy demonstrate promise for transcatheter valve repair and replacement with favourable clinical outcomes and short-term durability. However, further study is needed.


Glucuronidation of mycophenolic acid by Wistar and Mrp2-deficient TR- rat liver microsomes.
In humans, mycophenolic acid (MPA) is metabolized primarily by glucuronidation in the liver to mycophenolate ether glucuronide (MPAGe) and mycophenolate acyl glucuronide (MPAGa). We have previously reported that in perfused livers of TR(-) rats (lacking the Mrp2 transporter), the clearance and hepatic extraction ratio of MPA were significantly lower compared with control Wistar rats, suggesting a difference in the capacity of the TR(-) rats to metabolize MPA in situ. There is very little information regarding the phase II metabolic capabilities of TR(-) rats; therefore, the aim of this study was to investigate the in vitro glucuronidation of MPA in Wistar and TR(-) rat liver microsomal protein. A second aim was to determine whether MPAGa, cyclosporine (CsA), and/or its metabolites AM1, AM1c, and AM9 inhibit the metabolism of MPA to MPAGe in rat liver microsomes. MPAGe formation rates by Wistar and TR(-) microsomes were 0.48 and 0.65 nmol/min/mg, respectively (p = 0.33). K(m) values for control and TR(-) microsomes were 0.47 and 0.50 mM, respectively (p = 0.81). The mean (S.E.M.) ratios of MPAGe formation by Wistar rat liver microsomes incubated with 50 microM MPA plus inhibitor versus 50 microM MPA alone were MPAGa 1.2 (0.1), CsA 0.7 (0.1) (p < 0.05), AM1 2.2 (0.3) (p < 0.05), AM1c 1.2 (0.2), and AM9 1.0 (0.2). Our results suggest that lower in situ glucuronidation of MPA in TR(-) rats may be because of inhibition of glucuronidation by endogenous and exogenous compounds that accumulate in the transporter-deficient rat. Whereas CsA inhibits glucuronidation of MPA, its metabolite AM1 enhances MPAGe formation by rat liver microsomes.


Use of disposable GRC electrodes for the detection of phenol and chlorophenols in liquid chromatography.
In this study, a wall-jet flow cell with a GRC (graphite reinforced by carbon) electrode was designed for the amperometric detection of phenol and chlorophenols in liquid chromatography. The voltammetric responses of these analytes at the GRC electrodes are very similar to those at conventional glassy carbon electrodes. As the GRC electrodes were made of the same materials as commercially available mechanical pencil leads, they exhibit the advantages of low cost, simple surface renewability, lower residual current, and good electrode-to-electrode reproducibility, and thus can be used as disposable-type electrodes. Chromatographic separations of phenol, o-chlorophenol (o-CP), 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were achieved with an ODS column using a mobile phase containing a mixture of CH3CN and H20 (40:60) containing 25 mM L-(+)tartaric acid (pH = 4.5). Amperometric detections were based on the electrochemical oxidation of these compounds around +0.9 V vs. Ag/AgCl. Under the optimized conditions, linear calibrations were obtained in a range up to 100 microM for phenol, o-CP, 2,4-DCP, 2,4,6-TCP, and 200 microM for PCP, with the correlation coefficients r2 of 0.9992, 0.9997, 0.9986, 0.9992, and 0.9968, respectively. The chromatographic detection limits for the tested analytes were obtained at pmol levels.


Cerebral amyloid angiopathy--a disease or age-related condition.
Cerebral amyloid angiopathy is characterized by deposition of amyloid in the walls of leptomeninged and cerebral blood vessels. Its most common form, sporadic CAA that results from deposition of beta-amyloid peptide, which is the subject of this short review, is present in virtually all cases of Alzheimer disease and is also common among non-demented subjects where its prevalence increases with age. Stroke due to massive cerebral lobar hemorrhage is the main clinical presentation of CAA, but transient neurologic symptoms due to microhemorrhages may also occur. CAA is also a risk factor for cerebral infarction and there is increasing evidence that CAA contributes to cognitive impairment in the elderly, usually in association with white matter abnormalities on imaging. Although the definitive diagnosis of CAA is neuropathologic, reliable diagnosis can be reached clinically, based on the occurrence of strictly lobar hemorrhages, particularly in the cortico-subcortical area when using gradient-echo or T2*-weighted magnetic resonance imaging. Experimental studies have shown that the origin of the vascular amyloid is neuronal, and that age-related degenerative changes in the vessel walls prevent its clearance from the brain along perivascular spaces and promote Abeta aggregation and CAA formation. The entrapped Abeta aggregates are toxic to various vascular wall components, including smooth muscle cells, pericytes and endothelial cells, leading to their eventual destruction and predisposition of the vessel wall to rupture and hemorrhage. However, more research is necessary to decipher the mechanism of CAA formation and its relation to cognitive decline in the elderly.


[Biomechanical study of medical hard tissue adhesive bonding butterfly fracture fragment in middle part of fresh human tibia].
A medical hard tissue adhesive, octyl-a-cyanoacrylate, was tested in 6 fresh human tibiae. A 90 degrees butter-fly fracture fragment was made in the middle part of tibia by bandsaw. The compressive stress, torsional stress and angular deflection were assessed before and after osteoectomy respectively. After adhesive bonding, the compressive stress, torsional stress and angular deflection were tested again. The butterfly fracture fagment decreased the bending strength, torsion strength, yielding strength of tibia bone. In torsion test, the torque of tibia before osteoectomy is greater than bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In compression test, before adhesive bonding broken, the compressive curve slope of tibia before osteoectomy is greater than that of bonded tibia, the bonded tibia is greater than that of the unbonded tibia. In angular deflection test before adhesive bonding of broken,the curve slope of tibia before osteoectomy is not different from that of bonded tibia (P>0.05), the slope the bonded tibia is greater than the slope of unbonded tibia(P<0.05). The elastic modulus, rigidity coefficient and moment of area inertia show no statistical difference between the bonded tibia and intact tibia. The used of medical hard tissue adhesive to bond the fracture fragment could improve the bending strength, torsion strength, yielding strength of tibia bone. In operation, it can reduce the soft tissue injury when the fracture fragment is being fixed, and this will benefit bone healing.


APOL1 Nephropathy: From Genetics to Clinical Applications.
Rates of many types of severe kidney disease are much higher in Black individuals than most other ethnic groups. Much of this disparity can now be attributed to genetic variants in the apoL1 (APOL1) gene found only in individuals with recent African ancestry. These variants greatly increase rates of hypertension-associated ESKD, FSGS, HIV-associated nephropathy, and other forms of nondiabetic kidney disease. We discuss the population genetics of APOL1 risk variants and the clinical spectrum of APOL1 nephropathy. We then consider clinical issues that arise for the practicing nephrologist caring for the patient who may have APOL1 kidney disease.


A Cross-Sectional Study of the Trends in Cardiovascular Mortality Among African Americans With Hypertension.
Background and Objective In the United States, hypertension remains a significant cause of cardiovascular disease mortality and morbidity, affecting various racial and ethnic groups. High blood pressure is a common health concern, given its high frequency among all populations and racial groups in the United States; nevertheless, the condition remains untreated in most individuals. It affects a significant number of individuals in the African American community and contributes to a notable proportion of deaths. Arguably more prevalent, severe, and tends to occur earlier in African Americans compared to some other races. This lack of blood pressure control may contribute to the increasing mortality rates associated with hypertension-related cardiovascular diseases in the United States, while notable race and sex disparities persist. This study aims to compare the number of deaths caused by each cardiovascular disease (hypertension) in African Americans to those of people of other races. Methodology To understand the impact of hypertension on mortality rates among different racial groups, this study utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) dataset, which includes death certificates filed in the United States. The research focused on individuals aged 25 years or older with a mention of hypertension and cardiovascular disease as the underlying cause of death between 1999 and 2019. The study analyzed hypertension-associated deaths by different cardiovascular disease subtypes, such as ischemic heart disease, heart failure (HF), and cerebrovascular diseases that include acute ischemic attacks, which are the most frequent in the United States, with specific assessments for African Americans, White, and other races' decedents. Results The study findings indicated that African American males had higher mortality rates from cardiovascular diseases compared to African American females. The prevalence of hypertension was also higher among African Americans (87.47%) compared to Whites (30.33%), Asian/Pacific Islanders (40.26%), and American Indians/Alaska Natives (61.18%). Additionally, the study identified regional variations in mortality rates, with states like Arizona, California, Texas, Florida, and Washington having higher rates, while Vermont, North Dakota, and Wyoming had lower rates. The northwest region had lower mortality compared to the western and southwestern regions. Conclusions Within the studied period, there was an increase in the prevalence of mortality due to hypertension amongst African Americans when compared to other races. These findings underscore the pressing need to address the increasing prevalence of hypertension and mortality rates among African American. More efforts should focus on prevention of CVD and hypertension and the associated risk factors based on the World Health Organization (WHO) recommendations, which include the promotion of healthy lifestyle behaviors, improvement of access to quality healthcare, and implementation of culturally sensitive interventions tailored for African American communities.


[Demand for paediatric emergency care in a community hospital].
To study the characteristics of paediatric emergency demand and care delivery in the emergency room of a community hospital. Analysis of the care demand and medical attention given to pediatric patients in an emergency room during 2006. Retrospective review of patients' medical reports. Emergency room, Hospital da Barbanza, Riveira, A Coruña, Spain. Random selection of 1330 patients from 3990 cases attended in 2006. Age, sex, time of arrival at the emergency room, type of pathology, medical-surgical area, destination on discharge, which medical staff signed the discharge, and length of stay in the emergency room. There were 731 men and 599 women. Demand was greater on the afternoon shift (45%). Discharge destination was mainly to home (94%), with the emergency medical staff signing it in 60.7% of cases and the pediatrician in 34.6%. Children aged 6 or more suffered mainly from trauma; and younger children, from infectious diseases. There were no statistically significant differences between age groups for length of stay in the emergency room, but patients attended by pediatricians stayed longer. There was a clear majority of little children, especially boys, in our study. Higher afternoon attendance probably occurs because of greater time availability of parents and children. Main causes of emergency pediatric care are infectious diseases and trauma. The child's home is the most frequent destination on discharge. The fact that most discharges are signed by the emergency doctor, together with the increase in emergency paediatric care in recent years, points to the need for constant updating of this medical area by emergency doctors.


Cognitive Function in Patients With Prostate Cancer Receiving Luteinizing Hormone-Releasing Hormone Analogues: A Prospective, Observational, Multicenter Study.
The effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in prostate cancer (PCa) patients is not well understood. We evaluated changes in CP after 6 months of medical castration with luteinizing hormone-releasing hormone (LHRH) analogues. We performed a prospective, observational, multicenter, open-label study of PCa patients scheduled to receive LHRH analogues for ≥6 months. We assessed 4 domains of CP at baseline and after 6 months of ADT: (1) working memory, assessed with the Wechsler Adult Intelligence Scale III (WAIS III) Digit Span subtest; (2) visual memory, assessed with an ad hoc visual memory test; (3) visuospatial ability, assessed with the Judgment of Line Orientation test and Mental Rotation of Three-Dimensional Objects test; and (4) nonverbal analytical reasoning, assessed with the WAIS III Matrix Reasoning test. Changes outside the baseline 95% confidence intervals were considered significant. A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test whereas 63 (20.4%) experienced significant changes on ≥1 test. Most of these patients showed a change on only 1 test, distributed evenly between improvement (58 patients, 18.8%) and worsening (56 patients, 18.2%). For individual tests, most patients (87.8%-91.8%) had no change from baseline; however, the significant changes (improvement vs deterioration) were as follows: WAIS III Digit Span subtest (6.3% vs 5.9%), visual memory (5.3% vs 5.7%), Judgment of Line Orientation test (5.3% vs 4.5%), Mental Rotation of Three-Dimensional Objects test (4.1% vs 4.1%), and WAIS III Matrix Reasoning test (4.8% vs 5.8%). CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.


Skeletal muscle adaptations to heat therapy.
The therapeutic effects of heat have been harnessed for centuries to treat skeletal muscle disorders and other pathologies. However, the fundamental mechanisms underlying the well-documented clinical benefits associated with heat therapy (HT) remain poorly defined. Foundational studies in cultured skeletal muscle and endothelial cells, as well as in rodents, revealed that episodic exposure to heat stress activates a number of intracellular signaling networks and promotes skeletal muscle remodeling. Renewed interest in the physiology of HT in recent years has provided greater understanding of the signals and molecular players involved in the skeletal muscle adaptations to episodic exposures to HT. It is increasingly clear that heat stress promotes signaling mechanisms involved in angiogenesis, muscle hypertrophy, mitochondrial biogenesis, and glucose metabolism through not only elevations in tissue temperature but also other perturbations, including increased intramyocellular calcium and enhanced energy turnover. The few available translational studies seem to indicate that the earlier observations in rodents also apply to human skeletal muscle. Indeed, recent findings revealed that both local and whole-body HT may promote capillary growth, enhance mitochondrial content and function, improve insulin sensitivity and attenuate disuse-induced muscle wasting. This accumulating body of work implies that HT may be a practical treatment to combat skeletal abnormalities in individuals with chronic disease who are unwilling or cannot participate in traditional exercise-training regimens.


Silencing of tomato CTR1 provides enhanced tolerance against Tomato leaf curl virus infection.
Tomato leaf curl virus (ToLCV) belonging to Begomovirus family of Geminivirus is known to cause one of the most destructive diseases in tomato. Amongst various ToLCVs, a monopartite Tomato leaf curl Joydebpur virus (ToLCJoV) is most prevalent in eastern part of India. In the present study, we observed induced expression of one of the negative regulators of ethylene signaling pathway gene (LeCTR1) in ToLCJoV infected plants. The Tobacco rattle virus (TRV) induced silencing of the LeCTR1 gene provided enhanced tolerance to ToLCJoV infections. The leaf curling as well as ROS accumulation was significantly reduced in the viral infected LeCTR1 silenced plants. Induction of several defense marker genes (NPR1, PR1, PR5, AOS2, EIN2, EIN3 and ERF5) reinforced enhanced tolerance against ToLCJoV infection in the LeCTR1 silenced tomato. Overall, the present study provides evidence that silencing of LeCTR1 can be deployed to protect tomato from ToLCJoV infections.


Helicase-dependent isothermal DNA amplification.
Polymerase chain reaction is the most widely used method for in vitro DNA amplification. However, it requires thermocycling to separate two DNA strands. In vivo, DNA is replicated by DNA polymerases with various accessory proteins, including a DNA helicase that acts to separate duplex DNA. We have devised a new in vitro isothermal DNA amplification method by mimicking this in vivo mechanism. Helicase-dependent amplification (HDA) utilizes a DNA helicase to generate single-stranded templates for primer hybridization and subsequent primer extension by a DNA polymerase. HDA does not require thermocycling. In addition, it offers several advantages over other isothermal DNA amplification methods by having a simple reaction scheme and being a true isothermal reaction that can be performed at one temperature for the entire process. These properties offer a great potential for the development of simple portable DNA diagnostic devices to be used in the field and at the point-of-care.


Decoherence dynamics of complex photon states in a superconducting circuit.
Quantum states inevitably decay with time into a probabilistic mixture of classical states due to their interaction with the environment and measurement instrumentation. We present the first measurement of the decoherence dynamics of complex photon states in a condensed-matter system. By controllably preparing a number of distinct quantum-superposed photon states in a superconducting microwave resonator, we show that the subsequent decay dynamics can be quantitatively described by taking into account only two distinct decay channels: energy relaxation and pure dephasing. Our ability to prepare specific initial quantum states allows us to measure the evolution of specific elements in the quantum density matrix in a very detailed manner that can be compared with theory.


Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae.
The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcus pneumoniae, Staphylococcus aureus, or Mycobacterium tuberculosis, the second residue of the peptidoglycan precursor, D-glutamate, is amidated into iso-D-glutamine by the essential amidotransferase MurT/GatD complex. Here, we present the structure of this complex at 3.0 Å resolution. MurT has central and C-terminal domains similar to Mur ligases with a cysteine-rich insertion, which probably binds zinc, contributing to the interface with GatD. The mechanism of amidation by MurT is likely similar to the condensation catalyzed by Mur ligases. GatD is a glutaminase providing ammonia that is likely channeled to the MurT active site through a cavity network. The structure and assay presented here constitute a knowledge base for future drug development studies.


[Feasibility and radicality of PEP-chemoradiation therapy in oral squamous cell carcinoma].
From 1981 to 1987, 26 patients with oral malignancies, previously untreated squamous cell carcinomas, were treated by chemoradiation therapy, which consisted of Linac irradiation (2 Gy/d) under continuous intraarterial administration of 1.6 mg/d peplomycin (PEP). Twenty of these 26 patients did not undergo resection of the primary sites during initial hospitalization. Radicality of the PEP chemoradiation therapy was assessed after a long-term follow-up. Patients of Stage I to IV numbered 4, 7, 1 and 8, respectively. Total dosage was 60 Gy of Linac irradiation under 80-110 mg infusion of PEP. Overall CR rate and actuarial 5-year-survival rate were 75% and 63%, respectively, while these rates were 92% and 83%, respectively, for the Stage I to III cases, but 50% and 29%, respectively, for the Stage IV patients. Actuarial 5-year-survival rate of the CR Stage I to III cases was 91%, significantly higher than that of Stage IV cases (66%). We conclude the following: (1) This treatment is not indicative for patients with only a limited evaluation of PR available in the early stage of the therapeutic course. (2) Limited or uncertain response might occur in Stage IV cases. (3) The prognosis for the great majority of Stage I to III patients, however, is excellent.


COVID-19 Vaccination-Induced Cholangiopathy and Autoimmune Hepatitis: A Series of Two Cases.
The coronavirus disease 2019 (COVID-19) pandemic has been associated with significant morbidity and mortality. Following the introduction of vaccines, various side effects have been reported. Whilst those reported may be attributed to the vaccine itself, at times, it may simply incite an immunological phenomenon. We present a case series of two patients who presented with symptoms of yellowing of the eyes and the skin along with fatigue, and tiredness, following vaccination for COVID-19. The diagnosis of post COVID-19-vaccination related hepatitis is one of the fewer, less understood, yet reported side effects associated with significant morbidity. The diagnosis of COVID-19 vaccination-related cholangitis is an outcome reported here for the first time to the best of our knowledge. It was alarming that both patients did not have any significant past history of medical ailments. A prompt assessment followed by investigations including liver biopsy assisted in a timely understanding of the phenomenon with complete resolution of the symptoms.


Molecular cloning and induction of nuclear receptors from insect cell lines.
Fragments of EcR and USP were cloned from two insect cell lines, Sf21 and High Five cells (derived respectively from Spodoptera frugiperda and Trichoplusia ni), using a PCR-based approach employing degenerate primers designed on the basis of conserved regions of nuclear receptors, together with 5'- and 3'-RACE. An additional orphan nuclear receptor, HR4 fragment, was cloned from High Five cells. Comparison of these fragments with Manduca sexta counterparts showed that the cloned SfEcR [ecdysone receptor (EcR) from Sf21 cells] had high similarity to MsEcR-B1, whereas the cloned SfUSP [ultraspiracle (USP) from Sf21 cells] and TnUSP (USP from High Five cells) matched more closely to MsUSP-2 than to MsUSP-1. The TnHR4 showed most similarity to a recently cloned Bombyx mori GRF. While EcR and USP were constitutively expressed in both cell lines, HR4 was barely detectable by Northern blot analysis in High Five cells. Treatment with 20-hydroxyecdysone (20E) and agonist RH-5992 enhanced transcription of EcR in both cell lines, while the transcription of USP was suppressed in High Five cells. Such suppressed USP transcription was not observed in Sf21 cells. Transcription of TnEcR could also be enhanced by ecdysone and 3-dehydroecdysone, whereas transcription of SfEcR was unchanged with these two ecdysteroid compounds. Induction of HR4 transcription was also observed with 20E, RH-5992, ecdysone and 3-dehydroecdysone. The protein synthesis inhibitor, cycloheximide, superinduced expression of EcR and HR4 and restored the 20E/RH-5992-suppressed expression of TnUSP in the cells. Northern blot analysis also revealed that PCR, using degenerate USP primers, was able to amplify some other orphan nuclear receptors and their expression was inducible by 20E and RH-5992 and some of them were superinducible by cycloheximide.


Preoperative bowel preparation versus no preparation before spinal surgery: A randomised clinical trial.
To investigate the effect of preoperative bowel preparation for patients undergoing spinal fusion surgery. Bowel preparation before major surgery is performed routinely to reduce the risk of postoperative complications related to gastrointestinal function. A randomised clinical trial was performed that included forty-five elective spinal fusion patients allocated to one control group and two treatment groups. The patients received preoperative bowel preparation with enema, suppository or no bowel preparation. The outcome measures were defecation within 72 hours postoperatively, defecation on the fifth postoperative day, postoperative constipation, nausea, pain, well-being and ambulation. There were significant differences in favour of no bowel preparation compared with suppository group for the primary outcome; days to first defecation. There was a tendency for the patients who received no bowel preparation to recover from constipation more quickly than patients in the bowel preparation groups. The majority of patients did not defecate until the fourth postoperative day. This randomised study found no benefit from bowel preparation before major spine surgery on gastrointestinal function. The use of bowel preparation is not evidence-based and not performing it should be considered before major spine surgery until the effect is known.


Learning Abilities and Disabilities: Generalist Genes, Specialist Environments.
Twin studies comparing identical and fraternal twins consistently show substantial genetic influence on individual differences in learning abilities such as reading and mathematics, as well as in other cognitive abilities such as spatial ability and memory. Multivariate genetic research has shown that the same set of genes is largely responsible for genetic influence on these diverse cognitive areas. We call these "generalist genes." What differentiates these abilities is largely the environment, especially nonshared environments that make children growing up in the same family different from one another. These multivariate genetic findings of generalist genes and specialist environments have far-reaching implications for diagnosis and treatment of learning disabilities and for understanding the brain mechanisms that mediate these effects.


Mechanisms of catalytic RNA molecules.
Ribozymes are folded catalytic RNA molecules that perform important biological functions. Since the discovery of the first RNA with catalytic activity in 1982, a large number of ribozymes have been reported. While most catalytic RNA molecules act alone, some RNA-based catalysts, such as RNase P, the ribosome, and the spliceosome, need protein components to perform their functions in the cell. In the last decades, the structure and mechanism of several ribozymes have been studied in detail. Aside from the ribosome, which catalyzes peptide bond formation during protein synthesis, the majority of known ribozymes carry out mostly phosphoryl transfer reactions, notably trans-esterification or hydrolysis reactions. In this review, we describe the main features of the mechanisms of various types of ribozymes that can function with or without the help of proteins to perform their biological functions.


Modeling of sound transmission from ear canal to cochlea.
A 3-D finite element (FE) model of the human ear consisting of the external ear canal, middle ear, and cochlea is reported in this paper. The acoustic-structure-fluid coupled FE analysis was conducted on the model which included the air in the ear canal and middle ear cavity, the fluid in the cochlea, and the middle ear and cochlea structures (i.e., bones and soft tissues). The middle ear transfer function such as the movements of tympanic membrane, stapes footplate, and round window, the sound pressure gain across the middle ear, and the cochlear input impedance in response to sound stimulus applied in the ear canal were derived and compared with the published experimental measurements in human temporal bones. The frequency sensitivity of the basilar membrane motion and intracochlear pressure induced by sound pressure in the ear canal was predicted along the length of the basilar membrane from the basal turn to the apex. The satisfactory agreements between the model and experimental data in the literature indicate that the middle ear function was well simulated by the model and the simplified cochlea was able to correlate sound stimulus in the ear canal with vibration of the basilar membrane and pressure variation of the cochlear fluid. This study is the first step toward the development of a comprehensive FE model of the entire human ear for acoustic-mechanical analysis.


In vivo bone formation following transplantation of human adipose-derived stromal cells that are not differentiated osteogenically.
A number of studies have shown in vivo bone regeneration by transplantation of osteogenic cells differentiated in vitro from adipose-derived stromal cells (ADSCs). However, the in vitro osteogenic differentiation process requires an additional culture period, and the dexamethasone that is generally used in the process may be cytotoxic. Here, we tested the hypothesis that ADSCs that are not differentiated osteogenically in vitro prior to transplantation would extensively regenerate bone in vivo when exogenous bone morphogenetic protein-2 (BMP-2) is delivered to the transplantation site. We fabricated a poly(dl-lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) composite scaffold with osteoactive HA that is highly exposed on the scaffold surface. This scaffold was able to release BMP-2 over a 4-week period in vitro. Human ADSCs cultured on BMP-2-loaded PLGA/HA scaffolds for 2 weeks differentiated toward osteogenic cells expressing alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) mRNA, while cells on PLGA/HA scaffolds without BMP-2 expressed only ALP. To study in vivo bone formation, PLGA/HA scaffolds (group 1), BMP-2-loaded PLGA/HA scaffolds (group 2), undifferentiated ADSCs seeded on PLGA/HA scaffolds (group 3), and undifferentiated ADSCs seeded on BMP-2-loaded PLGA/HA scaffolds (group 4) were implanted into dorsal, subcutaneous spaces of athymic mice. Eight weeks after implantation, group 4 exhibited a 25-fold greater bone formation area and 5-fold higher calcium deposition than group 3. Bone regeneration by transplanted human ADSCs in group 4 was confirmed by expression of human-specific osteoblastic genes, ALP, collagen type I, OPN, OCN, and bone sialoprotein, while group 3 expressed much lower levels of collagen type I and OPN mRNA only. This study demonstrates the feasibility of extensive in vivo bone regeneration by transplantation of ADSCs without prior in vitro osteogenic differentiation, and that a PLGA/HA composite BMP-2 delivery system stimulates bone regeneration following transplantation of undifferentiated human ADSCs.


Plasma Hyperosmolality Prolongs QTc Interval and Increases Risk for Atrial Fibrillation in Traumatic Brain Injury Patients.
Hyperosmotic therapy with mannitol is frequently used for treatment cerebral edema, and 320 mOsm/kg H2O has been recommended as a high limit for therapeutic plasma osmolality. However, plasma hyperosmolality may impair cardiac function, increasing the risk of cardiac events. The aim of this study was to analyze the relation between changes in plasma osmolality and electrocardiographic variables and cardiac arrhythmia in patients treated for isolated traumatic brain injury (iTBI). Adult iTBI patients requiring mannitol infusion following cerebral edema, and with a Glasgow Coma Score below 8, were included. Plasma osmolality was measured with Osmometr 800 CLG. Spatial QRS-T angle (spQRS-T), corrected QT interval (QTc) and STJ segment were calculated from digital resting 12-lead ECGs and analyzed in relation to four levels of plasma osmolality: A) <280 mOsm/kg H2O; B) 280-295 mOsm/kg H2O; C) 295-310 mOsm/kg H2O; and D) >310 mOsm/kg H2O. All parameters were measured during five consecutive days of treatment. 94 patients aged 18-64 were studied. Increased plasma osmolality correlated with prolonged QTc (p < 0.001), intensified disorders in STJ and increased the risk for cardiac arrhythmia. Moreover, plasma osmolality >313 mOms/kg H2O significantly increased the risk of QTc prolongation >500 ms. In patients treated for iTBI, excessively increased plasma osmolality contributes to electrocardiographic disorders including prolonged QTc, while also correlating with increased risk for cardiac arrhythmias.


Familial aggregation of early- and late-onset Parkinson's disease.
The role of heredity in early- versus late-onset Parkinson's disease (PD) is controversial. We estimated the degree of increased risk of PD in first-degree relatives of 221 PD probands with age of onset 50 years or younger and 266 PD probands with age of onset older than 50 years compared with the first-degree relatives of 409 control probands. Risk of PD was similar among first-degree relatives of early-onset PD probands (risk ratio [RR], 2.9; 95% confidence interval [CI], 1.6-5.0; p = 0.0002) and late-onset PD probands (RR, 2.7; 95% CI, 1.6-4.4; p = 0.0002) when each was compared with first-degree relatives of controls. However, siblings of early-onset PD probands were at markedly increased risk of PD compared with siblings of controls (RR, 7.9; 95% CI, 2.5-25.5; p = 0.0005), whereas parents of early-onset PD probands were not at significantly increased risk compared with parents of controls (RR, 1.7; 95% CI, 0.9-3.3; p = 0.2). In late-onset families, both siblings (RR, 3.6; 95% CI, 1.3-10.3; p = 0.02) and parents (RR, 2.5; 95% CI, 1.4-4.6; p = 0.003) were at increased risk compared with control relatives. This pattern is consistent with an autosomal recessive contribution to the inheritance of early but not late-onset PD. Genetic factors are important in both early- and late-onset PD, but specific genes and mode of inheritance may differ between the two groups.


Stress sensitivity in paranoia: poor-me paranoia protects against the unpleasant effects of social stress.
The attributional theory of paranoia suggests that paranoid beliefs may protect individuals from low self-esteem and distress (Bentall et al. 2001). The current study tested this theory by investigating a hypothesis that paranoid beliefs in combination with low perceived deservedness of persecution (poor-me beliefs) confer protection against the distress caused by social but not activity related stress. Paranoid symptoms, perceived deservedness of persecution, self-esteem, mood, and stress levels of individuals diagnosed with schizophrenia spectrum disorders (N = 91) and healthy controls (N = 52) were assessed in the context of daily life using the experience sampling method. Individuals holding poor-me beliefs (poor-me individuals) showed blunted sensitivity to social but not activity stress. In contrast, individuals holding paranoid beliefs in combination with high perceived deservedness of persecution (bad-me individuals) showed heightened sensitivity to social stress. No consistent differences in reactions to activity stress emerged. Although both poor-me and bad-me individuals reported low self-esteem, this disturbance was particularly characteristic of bad-me individuals. The results suggest that poor-me paranoid beliefs may protect individuals against the distress associated with unpleasant social situations. The specificity of reactions to social stress is discussed in the context of wider literature. Future directions for research are suggested.


Characteristic features of patients with multiple accessory pathways.
Objective Only limited clinical and electrophysiological data concerning patients (pts) with multiple accessory pathways (MAP) in comparison to large control groups are available. The aim of our study was to analyse these data from the largest cohort of patients with multiple accessory pathways and a large control group. Method and results We analysed data from pts with MAP (group 1) and pts with a single accessory pathway (AP) (group 2) referred for radiofrequency catheter ablation (RFCA) at our tertiary centre. Group 1 consisted of 124 pts (M 62.10%, mean age 33.00 ± 5.26) with MAP and RFCA. Group 2 consisted of 376 pts (M 51.20%, mean age 35.87 ± 16.15) with a single accessory pathway and RF ablation. Group 1 exhibited a higher incidence of overt APs (P < 0.0001), Ebstein anomaly (P = 0.001), ventricular fibrillation (P = 0.012), antidromic atrioventricular re-entrant tachycardia (A AVRT) (P = 0.025) and male gender (P = 0.038). The mean age at the first documented atrioventricular re-entrant tachycardia (AVRT) episode was lower in pts with MAP than in pts with single APs: 16.79 ± 13.41 vs 20.84 ± 14.29, respectively (P = 0.001). Concealed accessory pathways (P < 0.0001) occurred more frequently in the control group. Group 1 had more right-lateral (P = 0.0001), mid-septal (P = 0.0001), left-posterior (P = 0.01), left-anterior (P = 0.013) and left-lateral localizations of AP (P < 0.037). Conclusions The MAP group included statistically significantly more men, Ebstein anomaly and overt APs. The mean age of the first episode of atrioventricular re-entrant tachycardia was lower in pts with MAP. Certain distribution patterns are apparent for single and MAP. Pts with MAP are at higher risk of VF and antidromic atrioventricular re-entrant tachycardia.


Lung transplant curriculum in pulmonary/critical care fellowship training.
Lung transplantation is an evolving specialty with the number of transplants growing annually. A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.


The antifungal pipeline: the need is established. Are there new compounds?
Our review summarizes and compares the temporal development (eras) of antifungal drug discovery as well as antibacterial ventures. The innovation gap that occurred in antibacterial discovery from 1960 to 2000 was likely due to tailoring of existing compounds to have better activity than predecessors. Antifungal discovery also faced innovation gaps. The semi-synthetic antibiotic era was followed closely by the resistance era and the heightened need for new compounds and targets. With the immense contribution of comparative genomics, antifungal targets became part of the discovery focus. These targets by definition are absolutely required to be fungal- or even lineage (clade) specific. Importantly, targets need to be essential for growth and/or have important roles in disease and pathogenesis. Two types of antifungals are discussed that are mostly in the FDA phase I-III clinical trials. New antifungals are either modified to increase bioavailability and stability for instance, or are new compounds that inhibit new targets. One of the important developments in incentivizing new antifungal discovery has been the prolific number of publications of global and country-specific incidence. International efforts that champion global antimicrobial drug discovery are discussed. Still, interventions are needed. The current pipeline of antifungals and alternatives to antifungals are discussed including vaccines.


Human immunodeficiency virus inhibition by lysed leukocyte ultrafiltrate.
The in vitro effect of partially purified lysed leukocyte ultrafiltrate (LLU) on LAV 1 strain of the human immunodeficiency virus (HIV) was investigated. Decrease of virus production as a function of LLU concentration was observed while the phenotype of cultured lymphocytes has remained unchanged. We observed the same depletion of helper-inducer T-cells in samples treated with LLU as well as in infected controls. LLU did not influence significantly the growth of cultured lymphocytes. Following the effect of LLU on RNA-dependent DNA polymerase, inhibition of the LAV 1 reverse transcriptase by LLU was observed. This inhibition was shown to be LLU dose-dependent, considering its content of proteins and orcinol-reactive material. Kinetic studies revealed that inhibition is reversible and competitive with the substrate (3HTTP) but not with template-primer (poly rA-oligo dT).


The Calcium-Induced Regulation in the Molecular and Transcriptional Circuitry of Human Inflammatory Response and Autoimmunity.
Rheumatoid arthritis synovial fibroblasts (RASFs) are fundamental effector cells in RA driving the joint inflammation and deformities. Celastrol is a natural compound that exhibits a potent anti-arthritic effect promoting endoplasmic reticulum (ER) stress mediated by intracellular calcium (Ca2+) mobilization. Ca2+ is a second messenger regulating a variety of cellular processes. We hypothesized that the compound, celastrol, affecting cytosolic Ca2+ mobilization could serve as a novel strategy to combat RA. To address this issue, celastrol was used as a molecular tool to assay the inflammatory gene expression profile regulated by Ca2+. We confirmed that celastrol treatment mobilized cytosolic Ca2+ in patient-derived RASFs. It was found that 23 genes out of 370 were manipulated by Ca2+ mobilization using an inflammatory and autoimmunity PCR array following independent quantitative PCR validation. Most of the identified genes were downregulated and categorized into five groups corresponding to their cellular responses participating in RA pathogenesis. Accordingly, a signaling network map demonstrating the possible molecular circuitry connecting the functions of the products of these genes was generated based on literature review. In addition, a bioinformatics analysis revealed that celastrol-induced Ca2+ mobilization gene expression profile showed a novel mode of action compared with three FDA-approved rheumatic drugs (methotrexate, rituximab and tocilizumab). To the best of our knowledge, this is a pioneer work charting the Ca2+ signaling network on the regulation of RA-associated inflammatory gene expression.


Models for mineralization kinetics with the variables of substrate concentration and population density.
The rates of mineralization of [14C]benzoate by an induced population of Pseudomonas sp. were measured at initial substrate concentrations ranging from 10 ng/ml to 100 micrograms/ml. Plots of the radioactivity remaining in the culture were fit by nonlinear regression to six kinetic models derived from the Monod equation. These models incorporate only the variables of substrate concentration and cell density. Plots of the mineralization kinetics in cultures containing low, intermediate, and high initial substrate concentrations were well fit by first-order, integrated Monod, and logarithmic kinetics, respectively. Parameters such as maximum specific growth rate, half-saturation constant, and initial population density divided by yield agreed between cultures to within a factor of 3.4. Benzoate mineralization by microorganisms in acclimated sewage was shown to fit logistic (sigmoidal), Monod, and logarithmic kinetics when the compound was added at initial concentrations of 0.1, 1.0, and 10 micrograms/ml, respectively. The mineralization of 10 micrograms of benzoate per ml in sewage also followed logarithmic kinetics in the absence of protozoa. It is concluded that much of the diversity in shapes of mineralization curves is a result of the interactions of substrate concentration and population density. Nonlinear regression with models incorporating these variables is a valuable means for analysis of microbial mineralization kinetics.


PTSD Psychotherapy Outcome Predicted by Brain Activation During Emotional Reactivity and Regulation.
Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms. At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.


Assessing the Safety of Human Pluripotent Stem Cells and Their Derivatives for Clinical Applications.
Pluripotent stem cells may acquire genetic and epigenetic variants during culture following their derivation. At a conference organized by the International Stem Cell Initiative, and held at The Jackson Laboratory, Bar Harbor, Maine, October 2016, participants discussed how the appearance of such variants can be monitored and minimized and, crucially, how their significance for the safety of therapeutic applications of these cells can be assessed. A strong recommendation from the meeting was that an international advisory group should be set up to review the genetic and epigenetic changes observed in human pluripotent stem cell lines and establish a framework for evaluating the risks that they may pose for clinical use.


Chemical Amination via Cycloaddition of Graphene for Use in a Glucose Sensor.
Graphene was chemically aminated via cycloaddition. Aziridine-ring linkages were formed by covalently modifying the C-C double bonds in graphene. The aminated graphene presents an enhanced hydrophilicity, the contact angle with water decreases from 80.5 degrees to 58.5 degrees. And the conductivity of aminated graphene exhibits exponential decay as the reaction time increase. If the reaction time is 90 min, the resistance of aminated graphene was increased from -32 Ω to -2744 Ω. Because the amino group has good biocompatibility, the aminated graphene is designed for use as an enzyme sensor platform, such as glucose sensor based on glucose oxidase. The aminated graphene exhibited a good detection response for glucose. The increase in device current is about 12% in 1.2 mg/mL glucose solution.


Empirical study of supervised gene screening.
Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1) unsupervised gene screening; (2) supervised gene screening; and (3) statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1) genes passed different supervised screenings may be considerably different; (2) concordance may vary, depending on the underlying data structure and percentage of selected genes; (3) evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4) concordance cannot be improved by supervised screening based on reproducibility.


Metabolic basis to Sherpa altitude adaptation.
The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature.


Supporting the deliverers of care: strategies to support nurses and prevent burnout.
AIDS, with the number of cases and death toll increasing every day, puts caregivers at great risk for burnout. In order to prevent the detrimental consequences of burnout and to meet the challenge of this catastrophic illness, strategies need to be implemented. This overview not only explores the sources of stress related to AIDS but also presents strategies for the prevention of burnout. It is the author's belief that through solidarity caregivers will be better equipped to overcome the stress of caring for people with AIDS without experiencing burnout in the process.


Free sterols in senile human brain.
Autopsy material of 18 patients, who died between 66-86 years of age and of 4 ones, who died between 20 and 38 years of age was investigated. The white matter of frontal lobe, corpus callosum and cerebellum was studied using histological and biochemical methods. According to the results of neuropathological studies, the material of aged patients was divided into two subgroups: patients with vascular changes only and brains with senile atrophy of Alzheimer type. Chemical changes in all aging brain regions studied included higher proportion of desmosterol and differences in the pattern of cholesterol isomers. These findings are interpreted as suggesting some chemical transformations of cellular membranes in the cerebral white matter of the aging. The above mentioned changes were almost identical despite presence of the signs of Alzheimer's type senile atrophy, therefore it is not possible to explain their significance in developing of dementia process.


Histology of aberrant crypt foci in the human colon.
Aberrant crypt foci (ACF) have been identified in the methylene-blue stained mucosa of the human colon. Some lines of evidence suggest that ACF may be precursors of colon cancer. The objective of the present study was to establish morphological criteria able to define and classify ACF in histological sections. Twenty-four colectomy specimens were collected after operation for colorectal cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in a 0.2% solution of methylene blue in saline for 5-10 min. The strips were measured, put on a glass slide and observed under a light microscope at x25. One hundred and fourteen ACF identified by topology were sectioned parallel to the muscularis mucosae. Eighty-four ACF were evident at histological examination and could be classified into three main groups: group A (61 ACF, 72.6%) including foci whose epithelial cells had regular nuclei, with only mild or focal crowding but no stratification, no mucin depletion and no dysplasia; group B (16 ACF, 19.1%), in which features of hyperplasia were evident; and group C (seven ACF, 8.3%) including foci with enlarged, crowded and stratified nuclei, mucin depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in five cases, moderate in two) representing microadenomas. Finally, hyperplastic foci were significantly larger than foci of group A and C. Group B ACF were also more frequent in the rectum than in the colon. In conclusion, selected histological features allow the definition of groups of ACF, which may represent sequential steps in the development of human colorectal tumours.


Phenolic content, antioxidant capacity and antimicrobial activity of leaf extracts from Pistacia atlantica.
The aim of this study was to investigate the secondary metabolites related to Pistacia atlantica Desf as well as their biological activities. Results show that using ethanol as a solvent exhibited the highest content of total phenolics and flavonoids (68.23 mg GAE g-1 of DW and 44 mg RE g-1 of DW), followed by aqueous one (20.07 mg GAE g-1 of DW and 15 mg RE g-1 of DW). Good correlation (Data not shown) was obtained between the DPPH radical-scavenging activities and total phenolics contents. Many similarities were observed between the results of the DPPH (IC50 = 32 and 200 μg mL-1) and ABTS (IC50 = 42 and 300 μg mL-1) assays. All tested extracts contained phenolic compounds exhibited an antimicrobial effect against Gram-positive and Gram-negative bacteria. Further, researches for identification and purification of phenolic compounds are required.


[Tutorial session using cross sections of upper and lower limbs in human gross anatomy course].
We performed tutorial education in gross anatomy using thick serial cross sections (3-4 cm) of one of the upper or lower limbs of a cadaver donated for use in the macroscopic dissection course. Group learning (four people) proceeded with the extraction of the point in question from an arbitrary section. Consequently students obtained a deeper understanding of the cross sectional structure of an upper or lower limb and further deepened their understanding of the three-dimensional structure of limbs. Each group collected clinical images of the part corresponding to the selected section to present, thus bringing together the relationship between the anatomical knowledge studied from the specimen and the related disease. A questionnaire survey after the practicum suggested that the practice of using serial cross sections and the presentation of relevant images using Microsoft PowerPoint were effective means of the study. Useful points on the student's understanding were collected with respect to the following three opinions: Fresh aspects, Grasp of the position, and Three-dimensional views. Moreover, the dissection program in gross anatomy combined with thick cross sections was thought to be helpful in that not only was observing the cross structure but also to dissect it if necessary, with the students obtaining a deeper understanding of the structure as a result. In our anatomy practice thereafter, the practicum was done with awareness of the issues faced by the students in mind. It was concluded that the practicum that uses the cross sections is an effective means in gross anatomy education.


Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations.
Coenzyme Q(10) (CoQ(10)) is found in blood and in all organs. CoQ(10) deficiencies are due to autosomal recessive mutations, ageing-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer and muscular and cardiovascular diseases have been associated with low CoQ(10) levels, as well as different ataxias and encephalomyopathies. We review the efficacy of a variety of commercial formulations which have been developed to solubilise CoQ(10) and promote its better absorption in vivo, and its use in the therapy of pathologies associated with low CoQ(10) levels, with emphasis in the results of the clinical trials. Also, we review the use of its analogues idebenone and MitoQ. This review covers the most relevant aspects related with the therapeutic use of CoQ(10), including existing formulations and their effects on its bioavailability. CoQ(10) does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ(10) absorption. Oral CoQ(10) is a viable antioxidant strategy in many diseases, providing a significant to mild symptomatic benefit. Idebenone and MitoQ are promising substitutive CoQ(10)-related drugs which are well tolerated and safe.


Randomized clinical trial in healthy individuals on the effect of viscous fiber blend on glucose tolerance when incorporated in capsules or into the carbohydrate or fat component of the meal.
Addition of viscous fiber to foods has been shown to significantly reduce postprandial glucose excursions. However, palatability issues and the variability in effectiveness due to different methods of administration in food limits it use. This study explores the effectiveness of a viscous fiber blend (VFB) in lowering postprandial glycemia using different methods of incorporation. Two acute, randomized, controlled studies were undertaken: Study 1: Twelve healthy individuals (mean ± SD, age: 36 ± 13 years, body mass index [BMI]: 27 ± 4 kg/m(2)) consumed 8 different breakfasts. All meals consisted of 50 g of available carbohydrate from white bread (WB) and 10 g margarine. Zero, 1, 2, or 4 g of the VFB was baked into WB or mixed with the margarine. Study 2: Thirteen healthy individuals (mean ± SD, age: 39 ± 17 years, BMI: 25 ± 5 kg/m(2)) consumed 6 test meals, consisting of 50 g of available carbohydrate from WB. Six capsules containing either cornstarch or VFB were taken at 4 different time points during the glucose tolerance test. After obtaining a fasting finger-prick blood sample, volunteers consumed the test meal over a 10-minute period. Additional blood samples were taken at 15, 30, 45, 60, 90, and 120 minutes from the start of the meal. For study 2, an additional fasting sample was obtained at -30 minutes. Study 1: Irrespective of VFB dose, glucose levels were lower at 30 and 45 minutes when VFB was mixed into the margarine compared to the control (p < 0.05). Incremental areas under the curve were significantly lower compared to control when 4 g of VFB was mixed into the margarine. Study 2: There was no effect of the VFB on postprandial glucose levels when administered in capsules. Incorporation of VFB into margarine was more effective in lowering postprandial glycemia than when the VFB was baked into bread and no effect when given in capsules.


In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria. Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone. This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] which are involved in bone resorption. We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens. We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen. Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days. At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting. Cytokine mRNA was not detected in the tissue over the calvaria of control animals. In contrast, P. gingivalis and A. actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6). P. gingivalis was more potent than A. actinomycetemcomitans in inducing cytokine expression. In contrast, S. gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction. These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines. There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues.


Compound or Specially Designed Flaps in the Lower Extremities.
Novel and combined tissue transfers from the lower extremity provide new tools to combat soft tissue defects of the hand, foot, and ankle, or fracture nonunion. Flaps can be designed for special purposes, such as providing a gliding bed for a grafted or repaired tendon or for thumb or finger reconstruction. Propeller flaps can cover soft tissue defects of the leg and foot. In repairing severe bone and soft tissue defects of the lower extremity, combined approaches, including external fixators, one-stage vascularized bone grafting, and skin or muscle flap coverage of the traumatized leg and foot, have become popular.


Application of Pictet-Spengler Reaction to Indole-Based Alkaloids Containing Tetrahydro-β-carboline Scaffold in Combinatorial Chemistry.
Indole-based alkaloids are well-known in the literature for their diverse biological properties. Polysubstituted optically active tetrahydro-β-carboline derivatives functionalized on C-1 position are the common structural motif in most of the indole-based alkaloids, as well as highly marketed drugs. The stereoselective Pictet-Spengler reaction is one of the currently most important synthetic techniques used for the preparation of these privileged tetrahydro-β-carboline scaffolds. To date, there are numerous research reports that have been published on the synthesis of the tetrahydro-β-carboline scaffold both on solid phase, as well as in solution phase. Moreover rapid growth has been observed for the enantioselective synthesis of tetrahydro-β-carboline scaffold using chiral organocatalysts. In this Review, efforts have been taken to shed light on the latest information available on different strategies to synthesize tetrahydro-β-carboline both on solid phase and in solution phase during the last 20 years. Furthermore, we believe that the present synthetic methodologies covered in this Review will help to improve the status of this privileged tetrahydro-β-carboline scaffold in its use for drug discovery.


Accumulation of extracellular glutamate and neuronal death in astrocyte-poor cortical cultures exposed to glutamine.
The function of astrocytes in cerebral cortex may be studied by comparing the properties of conventional, astrocyte-rich cultures with astrocyte-poor cultures in which astrocyte proliferation has been stringently suppressed. Exposure of astrocyte-poor, but not astrocyte-rich, cultures to fresh medium containing 2 mM glutamine resulted in the death of most neurons within 24 h. This study was undertaken to understand the basis for the apparent toxicity of glutamine in astrocyte-poor cultures. The toxicity of glutamine was found to be mediated by glutamate, which demonstrated an LD50 as a neurotoxin in astrocyte-poor cultures of 2 microM. Exposure of astrocyte-poor (but not astrocyte-rich) cultures to fresh medium containing glutamine for 17.5-24 h resulted in the accumulation of substantial quantities of glutamate (255 +/- 158 microM; mean +/- standard deviation) coincident with the death of neurons in the cultures. Exposure of astrocyte-poor cultures to glutamate in the absence of glutamine did not result in the accumulation of extracellular glutamate. Both the neuronal death and the extracellular glutamate accumulation in astrocyte-poor cultures exposed to glutamine could be blocked by N-methyl-D-aspartate (NMDA) antagonists. These observations suggest that astrocytes as well as glutamine may play an important role in the pathogenesis of glutamate neurotoxicity in the central nervous system.


The Yantai model of community care for rural psychiatric patients.
The main characteristics of the Yantai model are (a) a three-tier (county, township, village) management structure; (b) the vertical integration of community mental health workers, including a professional advisory group of psychiatrists from the central psychiatric hospital, groups of community psychiatrists at small county psychiatric hospitals, non-psychiatric physicians who run psychiatric out-patient clinics at township general hospitals, and village paramedics ('village doctors') who supervise patients in the community; (c) ongoing training of all community mental health workers; (d) registration and yearly follow-up of all patients with mental illnesses in the community; (e) provision of home-care services to a proportion of acutely ill patients; and (f) most of the cost of the service is borne by the state. The network of services provided by this model makes it convenient for patients to obtain treatment and, if necessary, go into hospital; it reduces the economic burden on the family and the community; it combines treatment, prevention, rehabilitation, and supervision under one administrative network; and it decreases the overall level of psychopathology and psychosocial dysfunction in the community.


Modification of mouse hemopoietic cell proliferation in vivo by a hemoregulatory pentapeptide (HP 5b). Relation to circadian rhythms.
The effects on murine hemopoietic cell proliferation of hemoregulatory peptide 5b, a synthetic factor which inhibits granulopoiesis, have been studied in vivo by 3H-thymidine labeling, cell cycle analyses by flow cytometry and total cell counts per femur. Single injections of the peptide seemed to obliterate the normal circadian rhythm of bone marrow cell proliferation. By autoradiography, the main effect was an inhibition of myelopoietic cell proliferation, although erythropoiesis was also affected. This occurred in two ways: a) an immediate effect observed in the first 24 h after a single injection, and b) a delayed effect observed 6-12 days after a week of peptide infusion which could be a result of stem cell inhibition. A secondary accumulation of cells with G2 phase DNA content was seen regularly. Thus the hemoregulatory peptide seems to influence hemopoietic cell proliferation and has its main effect on myelopoiesis. However, inhibition is less marked than observed previously in stem cells.


The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients.
To investigate the effects of N-acetylcysteine (NAC) when given as an early treatment to critically ill patients on the serum total anti-oxidant potential (TAP) and urine micro-albumin:creatinine (M:Cr) ratio. Prospective, placebo controlled double blinded clinical trial. General intensive care unit in a teaching hospital. Sixty critically ill patients were recruited but ten were withdrawn due to less than 48 h of ICU stay. After envelope randomisation, patients received either NAC (n = 23): a bolus of 150 mg/kg in 250 ml of 5% dextrose followed by a continuous infusion of 12 mg/kg per h in 500 ml of 5% dextrose over 24 h or, as controls (n = 27), the equal volume of placebo. Treatment lasted for a minimum of 3, up to a maximum of 5, days. Blood and urine samples were collected on admission (0 h) and then 6 hourly up 18 h. There was no significant difference between NAC and placebo groups regarding the required length of inotropic support, mechanical ventilation and ICU stay. There was no significant difference in TAP or M:Cr ratio over 18 h or between the groups. Our results suggest that NAC had no significant effects on the progress of the TAP and the urinary albumin excretion in our patients, which may suggest that NAC at the given dose has no clinical relevance as an early treatment in the critically ill.


Vibrational energy relaxation of azide in water.
Vibrational lifetimes of the asymmetric stretch fundamental of azide anion in normal and heavy water have been measured experimentally, with results in the range of a few picoseconds. This is an interesting problem for theoretical study because of the competition between intramolecular (relaxation to the other excited vibrational states of azide) and purely intermolecular (relaxation to azide's ground vibrational state) pathways. In addition it is important to understand the origin of the solvent isotope effect. Building on the seminal work of Morita and Kato [J. Chem. Phys. 109, 5511 (1998)], the authors develop a simple model based on a two-dimensional description of the azide stretching vibrations. A novel aspect of their theory is the use of an "on-the-fly" optimized quantum mechanical/molecular mechanical approach to calculate the system-bath coupling. Their theoretical lifetimes are in good agreement with experiment for azide in both normal and heavy water. They find that the predominant relaxation pathway is intramolecular. The solvent isotope effect arises from the different librational frequencies in normal and heavy water.


Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in invasive isolates from southern and eastern Mediterranean countries.
Efforts aimed at curtailing the ever increasing spread of methicillin-resistant Staphylococcus aureus (MRSA) require effective information of its epidemiology. However, knowledge about the situation in southern and eastern countries of the Mediterranean is incomplete since reports have been sporadic and difficult to compare. Over a 36 month period from 2003 to 2005, the ARMed project collected more than 5000 susceptibility test results of invasive isolates of S. aureus from blood cultures routinely processed within participating laboratories servicing 62 hospitals situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, the median MRSA proportion was 39% (interquartile range: 27.1% to 51.1%). The highest proportions of MRSA were reported by Jordan, Egypt and Cyprus, where more than 50% of the invasive isolates were methicillin-resistant. Considerable variation was identified in the proportion of MRSA in hospitals within the same country. It appears that most of the countries in the Mediterranean region are experiencing a surge in MRSA infections. This requires a greater focus to identify relevant drivers of resistance and implement effective practices in order to address them, especially improved infection control and antibiotic consumption practices.


Dickkopf-1 inhibits Wnt3a-induced migration and epithelial-mesenchymal transition of human lens epithelial cells.
Posterior capsular opacification (PCO) is a major post-operative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) contributes to PCO. We previously indicated that Wnt3a induces the EMT of human lens epithelial cells (LECs) and plays an important role in the development of PCO. The present study aimed to test the potential effect of Dickkopf-1 (Dkk1) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkk1 was reduced in the rabbit PCO model, and Dkk1 injected into the eyes post-surgical manipulation prevented PCO formation. Cultured HLE-B3 cells were then transfected with Wnt3a in the presence or absence of Dkk1. Dkk1 treatment restored the epithelial phenotype and reversed the expression of EMT-associated proteins induced by Wnt3a. Dkk1 suppressed LEC migration and the expression of matrix metalloproteinase-1 (MMP-1), and the activity of MMP-2 and MMP-9. Dkk1 inhibited the nuclear accumulation of β-catenin, which is the key regulator of the canonical Wnt signaling. Our results indicate that Dkk1 inhibits Wnt3a-induced migration and the EMT of human LECs.The results contribute to the prevention of PCO formation and development.


Changing trends in surgery for stress urinary incontinence.
Currently, a number of different stress urinary incontinence (SUI) procedures exist. The relatively recent adoption of the midurethral sling into clinical practice has changed the surgical management of SUI. This critical evaluation of the trends in SUI surgery emphasizes the public health burden of SUI surgery, provides insight into modern clinical practice, determines whether these trends reflect evidence-based data, and highlights potential areas for future research. Trends in SUI surgery have shown a rise in the use of midurethral mesh slings with a concomitant decrease in retropubic procedures. The rates of other types of SUI surgery remain quite low. Although the overall rate of slings has increased dramatically, limited population-based data exist regarding specific types of midurethral slings, such as retropubic vs. transobturator vs. mini-slings. There is a need for continued evaluation of these trends in response to heightened public awareness of the potential risks of synthetic mesh. The midurethral sling has become the gold standard surgery for SUI. It will be important to evaluate future trends in SUI surgery given the dynamic changes in new techniques for midurethral slings and long-term evidence regarding the effectiveness and risks of specific sling types.