Synthesis, characterization, and antibacterial activity studies of two Co(II) complexes with 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid as a ligand.

Two new Cobalt(II) complexes 12 and 13 have been synthesized from 2-[(E)-(3-acetyl-4-hydroxyphenyl)diazenyl]-4-(2-hydroxyphenyl)thiophene-3-carboxylic acid (11) as a novel ligand. These three new compounds were characterized on the basis of their powder X-Ray Diffraction, UV-Vis, IR, NMR, elemental analysis and MS spectral data. DFT/B3LYP mode of calculations were carried out to determine some theorical parameters of the molecular structure of the ligand. The purity of the azoic ligand and the metal complexes were ascertained by TLC and melting points. The analysis of the IR spectra of the polyfunctionalized azo compound 11 and its metal complexes 12 and 13, reveals that the coordination patterns of the ligand are hexadentate and tetradentate respectively. Based on the UV-Vis electronic spectral data and relevant literature reports, the ligand and derived complexes were assigned the E (trans) isomer form. Likewise, octahedral and square-planar geometries were respectively assigned to the cobalt(II) complexes. The broth microdilution method was used for antibacterial assays through the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The ligand 11 displayed moderate antibacterial activity (MIC = 32-128 µg/mL) against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa and Klebsiella pneumoniae 22. The octahedral cobalt(II) complex 12 showed moderate activity against Pseudomonas aeruginosa (MIC = 128 µg/mL) and Klebsiella pneumoniae 22 (MIC = 64 µg/mL) and none against Staphylococcus aureus ATCC25923 and Escherichia coli ATCC25922, whereas the square-planar complex 13 displayed moderate activity only on Klebsiella pneumoniae 22 (MIC = 64 µg/mL).

APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure.

The apolipoprotein E ɛ4 allele is the primary genetic risk factor for the sporadic type of Alzheimer's disease. However, the mechanisms by which apolipoprotein E ɛ4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein ɛ4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers and 757 apolipoprotein E ɛ4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on (i) the main effects of apolipoprotein E ɛ4, and (ii) the interactions of apolipoprotein E ɛ4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E ɛ4 × age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E ɛ4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E ɛ4 carriers with lower years of education. We demonstrated that apolipoprotein E ɛ4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer's disease. This finding also suggests that apolipoprotein E ɛ4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index.

Using pulsatility responses to breath-hold maneuvers to predict readmission rates in continuous-flow left ventricular assist device patients.

BACKGROUND: Dynamic respiratory maneuvers induce heterogenous changes to flow-pulsatility in continuous-flow left ventricular assist device patients. We evaluated the association of these pulsatility responses with patient hemodynamics and outcomes. METHODS: Responses obtained from HVAD (Medtronic) outpatients during successive weekly clinics were categorized into three ordinal groups according to the percentage reduction in flow-waveform pulsatility (peak-trough flow) upon inspiratory-breath-hold, (%∆P): (1) minimal change (%∆P ≤ 50), (2) reduced pulsatility (%∆P > 50 but <100), (3) flatline (%∆P = 100). Same-day echocardiography and right-heart-catheterization were performed. Readmissions were compared between patients with ≥1 flatline response (F-group) and those without (NF-group). RESULTS: Overall, 712 responses were obtained from 55 patients (82% male, age 56.4 ± 11.5). When compared to minimal change, reduced pulsatility and flatline responses were associated with lower central venous pressure (14.2 vs. 11.4 vs. 9.0 mm Hg, p = 0.08) and pulmonary capillary wedge pressure (19.8 vs. 14.3 vs. 13.0 mm Hg, p = 0.03), lower rates of ≥moderate mitral regurgitation (48% vs. 13% vs. 10%, p = 0.01), lower rates of ≥moderate right ventricular impairment (62% vs. 25% vs. 27%, p = 0.03), and increased rates of aortic valve opening (32% vs. 50% vs. 75%, p = 0.03). The F-group (n = 28) experienced numerically lower all-cause readmissions (1.51 vs. 2.79 events-per-patient-year [EPPY], hazard-ratio [HR] = 0.67, p = 0.12), reduced heart failure readmissions (0.07 vs. 0.57 EPPY, HR = 0.15, p = 0.008), and superior readmission-free survival (HR = 0.47, log-rank p = 0.04). Syncopal readmissions occurred exclusively in the F-group (0.20 vs. 0 EPPY, p = 0.01). CONCLUSION: Responses to inspiratory-breath-hold predicted hemodynamics and readmission risk. The impact of inspiratory-breath-hold on pulsatility can non-invasively guide hemodynamic management decisions, patient optimization, and readmission risk stratification.

Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab-bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study.

BACKGROUND: Clinical benefits of atezolizumab plus bevacizumab (atezolizumab-bevacizumab) are observed only in a subset of patients with hepatocellular carcinoma and the development of biomarkers is needed to improve therapeutic strategies. The atezolizumab-bevacizumab response signature (ABRS), assessed by molecular biology profiling techniques, has been shown to be associated with progression-free survival after treatment initiation. The primary objective of our study was to develop an artificial intelligence (AI) model able to estimate ABRS expression directly from histological slides, and to evaluate if model predictions were associated with progression-free survival. METHODS: In this multicentre retrospective study, we developed a model (ABRS-prediction; ABRS-P), which was derived from the previously published clustering-constrained attention multiple instance learning (or CLAM) pipeline. We trained the model fit for regression analysis using a multicentre dataset from The Cancer Genome Atlas (patients treated by surgical resection, n=336). The ABRS-P model was externally validated on two independent series of samples from patients with hepatocellular carcinoma (a surgical resection series, n=225; and a biopsy series, n=157). The predictive value of the model was further tested in a series of biopsy samples from a multicentre cohort of patients with hepatocellular carcinoma treated with atezolizumab-bevacizumab (n=122). All samples in the study were from adults (aged ≥18 years). The validation sets were sampled between Jan 1, 2008, to Jan 1, 2023. For the multicentre validation set, the primary objective was to assess the association of high versus low ABRS-P values, defined relative to cross-validation median split thresholds in the first biopsy series, with progression-free survival after treatment initiation. Finally, we performed spatial transcriptomics and matched prediction heatmaps with in situ expression profiles. FINDINGS: Of the 840 patients sampled, 641 (76%) were male and 199 (24%) were female. Across the development and validation datasets, hepatocellular carcinoma risk factors included alcohol intake, hepatitis B and C virus infections, and non-alcoholic steatohepatitis. Using cross-validation in the development series, the mean Pearson's correlation between ABRS-P values and ABRS score (mean expression of ABRS genes) was r=0·62 (SD 0·09; mean p<0·0001, SD<0·0001). The ABRS-P generalised well on the external validation series (surgical resection series, r=0·60 [95% CI 0·51-0·68], p<0·0001; biopsy series, r=0·53 [0·40-0·63], p<0·0001). In the 122 patients treated with atezolizumab-bevacizumab, those with ABRS-P-high tumours (n=74) showed significantly longer median progression-free survival than those with ABRS-P-low tumours (n=48) after treatment initiation (12 months [95% CI 7-not reached] vs 7 months [4-9]; p=0·014). Spatial transcriptomics showed significantly higher ABRS score, along with upregulation of various other immune effectors, in tumour areas with high ABRS-P values versus areas with low ABRS-P values. INTERPRETATION: Our study indicates that AI applied on hepatocellular carcinoma digital slides is able to serve as a biomarker for progression-free survival in patients treated with atezolizumab-bevacizumab. This approach could be used in the development of inexpensive and fast biomarkers for targeted therapies. The combination of AI heatmaps with spatial transcriptomics provides insight on the molecular features associated with predictions. This methodology could be applied to other cancers or diseases and improve understanding of the biological mechanisms that drive responses to treatments. FUNDING: Institut National du Cancer, Fondation ARC, China Scholarship Council, Ligue Contre le Cancer du Val de Marne, Fondation de l'Avenir, Ipsen, and Fondation Bristol Myers Squibb Pour la Recherche en Immuno-Oncologie.

Utility and Safety of Skin Tests in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): A Systematic Review.

BACKGROUND: Determination of culprit drug in drug reaction with eosinophilia and systemic symptoms (DRESS) is crucial. Skin tests have been used, although it remains unclear how sensitive these are. OBJECTIVE: To determine the value of skin tests in the assessment of drug causality in DRESS. METHODS: A systematic literature search was conducted for publications from 1996 onward of skin tests (skin prick test = SPT, patch test = PT, intradermal test = IDT) performed in clearly defined DRESS cases. Outcomes of testing, drug culpability assessments, and challenge test data were extracted. RESULTS: A total of 17 articles met inclusion criteria. In 290 patients with DRESS, patch testing was most frequent (PT = 97.2% [n = 282], IDT = 12.4% [n = 36], SPT = 3.1% [n = 9]). Positive results were noted in 58.4% (n = 160 of 282) of PTs, 66.5% of IDTs, and 25% of SPTs. When confidence of drug causality was high (n = 73 of 194), testing did not correlate well with clinical suspicion: PTs, 37.6%; IDTs, 36.5%. Direct comparison of skin testing with provocation testing (n = 12) showed 83.3% correlation. Positive IDT results were reported in 8 negative PT cases. CONCLUSIONS: Skin tests, particularly PTs and IDTs, have been reported as tools for diagnosis of causal drugs in DRESS. Heterogeneity in methodology, results analysis, and reporting of cohorts make meta-analysis to determine sensitivity and specificity of published literature impossible and highlight weaknesses in the field. We propose that international collaboration is essential to harmonize the methodology and reporting measures from hypersensitivity testing studies in larger cohorts.

Potential Biomarker Identification by RNA-Seq Analysis in Antibiotic-Related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Pilot Study.

One of the most severe forms of cutaneous adverse drug reactions is "drug reaction with eosinophilia and systemic symptoms" (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst incidence of DRESS is relatively low, between 1:1000 and 1:10 000 drug exposures, antibiotics are a commoner cause of DRESS and absence of confirmatory diagnostic test can result in unnecessary avoidance of efficacious treatment. We therefore sought to identify potential biomarkers for development of a diagnostic test in antibiotic-associated DRESS. Peripheral blood mononuclear cells from a "discovery" cohort (n = 5) challenged to causative antibiotic or control were analyzed for transcriptomic profile. A panel of genes was then tested in a validation cohort (n = 6) and compared with tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel consisting of 6 genes (STAC, GPR183, CD40, CISH, CD4, and CCL8) showed high sensitivity and specificity (100% and 85.7%-100%, respectively) for identification of the culprit drug in these cohorts of antibiotic-associated DRESS. Further work is required to determine whether the same panel can be repeated for larger cohorts, different medications, and other T-cell-mediated drug hypersensitivity reactions.

Impact of neurofibromatosis type 1 in an adult community population.

Background: Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome with varying manifestations and severity. Adult NF1 patients often experience fragmented care, so we sought to characterize the health and demographic features of a community-based population of adults with NF1 and hypothesized that lack of a specialty clinic for adult NF1 patients correlates with unmet needs. Methods: Retrospective case-control study of all adult cases of NF1 among 4.06 million medical records in a Pacific Northwest population. 122 case charts were reviewed to ascertain NF1 disease features, comorbidities, and severity of disease. A 1:1 control cohort was selected by matching case/control by age, sex, and ZIP code to compare demographic features and health status. Results: Adult NF1 patients were less likely to have private insurance, be employed, and have children, but were equally likely to be married. One half of cases had disease features compromising health and well-being, and care involved 26 different specialties. Excluding neurofibromas, 43% of cases had cancer compared to 10% of controls [P < .0001, OR 5.38 (2.53-11.4)]. Only 27% of women ages 30-50 had undergone age-appropriate enhanced breast cancer surveillance. Behavioral health problems were found in 60% of NF1 patients compared to 37% of controls [P < .001, OR 2.61 (1.52-4.50)]. 93% of cases referred to a NF1 specialty center underwent a change in management upon establishing care. Conclusions: NF1 patients may benefit from coordinated management of care in a specialty center.

Endoscopic management of sinonasal vascular tumors without embolization: Our experience with vessel ligation

Objective@#To present our surgical experience and technique in performing endoscopic sinus surgery for vascular sinonasal tumors without pre-operative embolization using intraoperative ligation of the external carotid artery or its distal branches.@*Methods@#Design: Retrospective Series. Setting: Tertiary Private Teaching Hospital. Participants: Seven Patients. @*Results@#Out of 7 patients (5 males, 2 females, aged 12 to 64 years old) with non-embolized vascular sinonasal tumors, 2 had juvenile angiofibroma, 3 had a benign vascular tumor (hemangiopericytoma, hemangioma and a vasoformative solitary fibrous tumor), and 2 had a malignancy (rhabdomyosarcoma, squamous cell carcinoma). Four (57.1%) had external carotid artery ligation, two (28.6%) had internal maxillary artery ligation and one (14.2%) had sphenopalatine artery ligation. The mean intraoperative blood loss was 2447.1 mL (range 900mL to 5,000mL) and average operation duration was 7.6 hours (range 2.9 hours to 14.5 hours). The average amount of transfused blood products was 1785.7mL (zero to 3,000mL). The average hospital stay was 7 days (range 2 to 13 days) with one post-operative complication (ICU admission for hypotension from intraoperative blood loss). @*Conclusion@#Intraoperative ligation of the ECA or its distal branches to disrupt the vascular supply of sinonasal tumors may provide a viable means of preventing excessive intraoperative blood loss in patients with non-embolized vascular sinonasal tumors.

Network analysis of England single parent household COVID-19 control policy impact; a proof-of-concept study

Lockdowns have been a key infection control measure for many countries during the COVID-19 pandemic. In Englands first lockdown, children of single parent households (SPHs) were permitted to move between parental homes. By the second lockdown, SPH support bubbles between households were also permitted, enabling larger within-household networks. We investigated the combined impact of these approaches on household transmission dynamics, to inform policymaking for control and support mechanisms in a respiratory pandemic context. This network modelling study applied percolation theory to a base model of SPHs constructed with population survey estimates of SPH family size. To explore putative impact, varying estimates were applied regarding extent of bubbling and proportion of Different-parentage SPHs (DSPHs) (in which children do not share both the same parents). Results indicate that the formation of giant components (in which Covid-19 household transmission accelerates) are more contingent on DSPHs than on formation of bubbles between SPHs; and that bubbling with another SPH will accelerate giant component formation where one or both are DSPHs. Public health guidance should include supportive measures that mitigate the increased transmission risk afforded by support bubbling among DSPHs. Future network, mathematical and epidemiological studies should examine both independent and combined impact of policies.

Neuroinflammation predicts disease progression in progressive supranuclear palsy.

INTRODUCTION: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP. METHODS: Seventeen patients with PSP-Richardson's syndrome underwent a baseline multimodal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, [18F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals' estimated rate of progression to identify the prognostic value of baseline imaging markers. RESULTS: PCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression. CONCLUSIONS: Molecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.

In vivo PET imaging of neuroinflammation in familial frontotemporal dementia.

INTRODUCTION: We report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes. METHODS: Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [11C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [18F]AV-1451. The familial FTD PET data were compared with healthy controls. RESULTS: Patients with familial FTD across all mutation groups showed increased [11C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [18F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations. DISCUSSION: This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.

Endoscopic sinus surgery perioperative outcomes after intravenous tranexamic acid:A double blind randomized controlled trial

Objective@#To determine the effect of a single intravenous dose of tranexamic acid on intraoperative bleeding, duration of surgery and surgical field visualization during endoscopic sinus surgery. @*Methods@# Study Design: Double-blind, randomized, placebo-controlled trial. Setting: Tertiary Government Hospital in Quezon City Participants: 10 patients aged 18-75 years old diagnosed with chronic rhinosinusitis with or without nasal polyposis and unresponsive to medical treatment, who underwent endoscopic sinus surgery from September 2016 to August 2017, were randomly allocated to treatment group and control group respectively. The “odd” numbers were assigned to the treatment group (intravenous Tranexamic acid) given 1 dose of 100mg/ml (500mg tranexamic acid per 5 ml) tranexamic acid slow intravenous drip 1 hour prior to the procedure, while the “even” numbers assigned to the control group received the same amount of normal saline solution.@*Results@#The mean duration of surgery of the tranexamic group was 185 minutes (standard deviation, SD 55.23) and the control group was 122.6 minutes (SD 42.03) showing no significant difference (p=.08). The mean blood loss of the tranexamic group was less at 240ml (SD 108.39) compared with the control group at 290ml (SD 74.16), although there was no statistically significant difference (p=.42). Intraoperative surgical field assessed by the surgeon based on the Boezart grading scale showed that 2 (40%) of the tranexamic group had higher bleeding score compared with the placebo group. However, this was not found to be statistically significant (p=.460). Due to the small sample size, a type II error occurred with alpha level of 0.05 and estimated power of 0.0885, with not enough basis to refute that a single dose of intravenous tranexamic acid has no effect in improving surgical field visualization during endoscopic sinus surgery. No drug side effects were noted after administration until after surgery.@*Conclusion@#Single dose intravenous tranexamic acid in functional endoscopic sinus surgery decreased mean intraoperative blood loss (but this was statistically insignificant), but its effect on surgical field visualization cannot totally be assessed due to small sample size. There was also no change in the observed duration of surgery. No untoward side effects associated were noted from administration of the drug until after the surgery finished.

The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum.

Dourine is caused by Trypanosoma equiperdum via coitus with an infected horse. Although dourine is distributed in Equidae worldwide and is listed as an internationally important animal disease by the World Organization for Animal Health (OIE), no effective treatment strategies have been established. In addition, there are no reports on drug discovery, because no drug screening system exists for this parasite. A new T. equiperdum strain was recently isolated from the genital organ of a stallion that showed typical symptoms of dourine. In the present study, we adapted T. equiperdum IVM-t1 from soft agarose media to HMI-9 liquid media to develop a drug screening assay for T. equiperdum. An intracellular ATP-based luciferase assay using CellTiter-Glo reagent and an intracellular dehydrogenase activity-based colorimetric assay using WTS-8 tetrazolium salt (CCK-8 reagent) were used in order to examine the trypanocidal effects of each compound. In addition, the IC50 values of 4 reference trypanocidal compounds (pentamidine, diminazene, suramin and melarsomine) were evaluated and compared using established assays. The IC50 values of these reference compounds corresponded well to previous studies involving other strains of T. equiperdum. The luciferase assay would be suitable for the mass screening of chemical libraries against T. equiperdum because it allows for the simple and rapid-evaluation of the trypanocidal activities of test compounds, while a simple, inexpensive colorimetric assay will be applicable in developing countries for the evaluation of the drug sensitivity of epidemic trypanosome strains.

DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP.

PhIP is an abundant heterocyclic aromatic amine (HCA) and important dietary carcinogen. Following metabolic activation, PhIP causes bulky DNA lesions at the C8-position of guanine. Although C8-PhIP-dG adducts are mutagenic, their interference with the DNA replication machinery and the elicited DNA damage response (DDR) have not yet been studied. Here, we analyzed PhIP-triggered replicative stress and elucidated the role of the apical DDR kinases ATR, ATM and DNA-PKcs in the cellular defense response. First, we demonstrate that PhIP induced C8-PhIP-dG adducts and DNA strand breaks. This stimulated ATR-CHK1 signaling, phosphorylation of histone 2AX and the formation of RPA foci. In proliferating cells, PhIP treatment increased the frequency of stalled replication forks and reduced fork speed. Inhibition of ATR in the presence of PhIP-induced DNA damage strongly promoted the formation of DNA double-strand breaks, activation of the ATM-CHK2 pathway and hyperphosphorylation of RPA. The abrogation of ATR signaling potentiated the cell death response and enhanced chromosomal aberrations after PhIP treatment, while ATM and DNA-PK inhibition had only marginal effects. These results strongly support the notion that ATR plays a key role in the defense against cancer formation induced by PhIP and related HCAs.

Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes.

BACKGROUND: Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. METHODS: Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. RESULTS: Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. CONCLUSIONS: Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features.

Perception of Personal Dental Appearance and Dental Aesthetic Index Score Among 18- to 20-year-old College Students in Rural South India.

PURPOSE: To assess the correlation between self-perceived dental appearance and dental malocclusion among 18- to 20-year-old college students in Virajpet, Karnataka. MATERIALS AND METHODS: A stratified random sample consisting of 280 18- to 20-year-old college students in Virajpet were recruited for the study. A pretested Oral Aesthetic Subjective Impact Scale (OASIS) and Visual Analogue Scale (VAS) were used to assess the subjects' perception of dental aesthetics. Malocclusion was clinically assessed using the Dental Aesthetic Index (DAI). The data were tabulated and analysed using SPSS version 16. The Spearman rankorder correlation coefficient was employed to determine the correlation between self-perceived dental appearance and dental malocclusion. RESULTS: Of the 280 students, 41.8% were females and 58.2% were males. The mean OASIS score was 23.93 (±3.72), the VAS score was 69.61 (±15.78) and DAI 24.80 (±6.29). CONCLUSION: There was a negative correlation between perception of personal dental appearance and the DAI scores in this group.

Ethnic variation of selected dental traits in Coorg.

PURPOSE: In a country like India, in addition to the great innate diversity, there are distinct migrant populations with unique dental traits. AIM: To assess the distribution and degree of expression of cusp of Carabelli of maxillary first permanent molars and shoveling trait of maxillary central incisors, between three ethnic groups of Coorg, namely Kodavas, Tibetans, and Malayalees. MATERIALS AND METHODS: A cross-sectional, indirect, anthropometric, study was carried out among 15- to 30-year-old subjects belonging to three different ethnic origins. A random sample consisting of 91 subjects were recruited for the study. The shovel trait of incisors and the Carabelli trait of molars were recorded according to the classification given by Hrdliƈka and Sousa et al., respectively. STATISTICAL ANALYSIS: The Kruskal-Wallis test was employed to determine the difference in three populations for shoveling and Carabelli traits. Mann-Whitney Test was used for pair-wise comparisons of three populations. RESULT: Of the total 91 subjects, 31 were Kodavas, 30 Malayalees and 30 Tibetans. There was a statistically significant difference in shoveling trait among the three ethnic groups. For Carabelli traits, there was no statistically significant difference among three ethnic groups. CONCLUSION: The present study findings showed that Tibetans have a higher degree of shoveling trait than the selected South Indian ethnic groups.

Perceptions of dental students in India about smoking cessation counseling.

Smoking kills 900,000 people every year in India. Many studies have shown that counseling from a health professional is an effective method of helping patients quit. The aim of this study was to evaluate the knowledge and attitudes of dental students in Karnataka, India, towards smoking cessation counseling. A questionnaire study was conducted among a convenience sample of 329 dental students comprised of III year and IV year students and interns in three dental colleges in Karnataka, India. Of the 329 students who completed the questionnaire, twenty-two (7 percent) were current smokers, and fifteen (5 percent) were ex-smokers. Although 94 percent responded they were giving antismoking advice to their patients, only 47 percent said they had been taught antismoking advice suitable for patients. While a majority (95 percent) planned to advise patients about tobacco use in their professional careers, significantly fewer (66 percent) indicated that such counseling would help patients to quit. This study of dental students and interns found that a majority intended to provide smoking cessation counseling in their professional career and agreed it is part of their professional role.