Traumatic brain injury in patients aged ≥65 years versus patients aged ≥80 years: a multicenter prospective study of mortality and medical resource utilization.
This study aimed to determine whether there is a difference in mortality and medical resource utilization between geriatric (aged ≥65 years) and super-geriatric patients (aged ≥80 years) with traumatic brain injury (TBI). We obtained comprehensive data (demographics, injury characteristics, injury severities, and outcomes) of geriatric and super-geriatric TBI patients from an emergency department-based injury surveillance system database from 2011 to 2016. Multivariate logistic regression analysis was performed to compare the mortality and nonroutine discharge (NRDC) status between both groups. Among 442,533 TBI patients, 48,624 were older than 65 years. A total of 48,446 patients (37,140 geriatric and 11,306 super-geriatric) without exclusion criteria were included in the final analysis. Both overall in-hospital mortality (adjusted odds ratio, 1.88; 95% confidence interval [CI], 1.28 to 2.74; P=0.001) and NRDC (adjusted odds ratio, 1.35; 95% CI, 1.07 to 1.71; P=0.011) were significantly higher in the super-geriatric group. In the stratified analysis, there were no significant differences in NRDC rate for all stratifications of treatment timing (emergency department vs. ward admission), but mortality remained to be significant for all stratifications. Super-geriatric TBI patients showed a significantly higher risk-adjusted overall mortality and more inadequate medical resource utilization than did geriatric TBI patients. However, super-geriatric patients were more likely to undergo NRDC after admission; thus, further research about age-related health inequalities is needed in the treatment of super-geriatric patients.


Drug-induced urinary calculi.
Urinary calculi may be induced by a number of medications used to treat a variety of conditions. These medications may lead to metabolic abnormalities that facilitate the formation of stones. Drugs that induce metabolic calculi include loop diuretics; carbonic anhydrase inhibitors; and laxatives, when abused. Correcting the metabolic abnormality may eliminate or dramatically attenuate stone activity. Urinary calculi can also be induced by medications when the drugs crystallize and become the primary component of the stones. In this case, urinary supersaturation of the agent may promote formation of the calculi. Drugs that induce calculi via this process include magnesium trisilicate; ciprofloxacin; sulfa medications; triamterene; indinavir; and ephedrine, alone or in combination with guaifenesin. When this situation occurs, discontinuation of the medication is usually necessary.


Effect of Motivational Interviewing on Weight Efficacy Lifestyle among Women with Overweight and Obesity: A Randomized Controlled Trial.
Obesity and overweight have become increasingly a major public health problem across the world. This study aimed at exploring the effects of motivational interviewing on weight efficacy lifestyle among women with obesity and overweight. A single-blind randomized clinical trial study was conducted on 100 overweight and obese women who attended a nutrition clinic. The samples were selected based on the clinical records and assigned into two groups, namely motivational interviewing arm (50 samples) and nutrition education arm (50 samples). Data were collected using a standard validated questionnaire entitled "weight efficacy lifestyle". The intervention was designed according to five motivation sessions and four nutrition education programs, such that the participants of the nutrition education arm were also provided with the nutrition pamphlets related to weight control. Data were finally analyzed using the SPSS statistical software by performing the independent t-test, chi-square, LSD and repeated measures ANOVA tests. P<0.05 were considered statistically significant. The mean age of women was 39.9±9.1 and 36.3±8.9 years in the control and motivational interviewing arms, respectively. Compared with the control group, the score of the motivational interviewing group was statistically significant in terms of weight efficacy lifestyle P=0.0001) and all subscales including social pressure (P=0.0001), physical discomfort (P=0.005), food accessibility (P=0.0001), positive and entertainment activities (P=0.0001), as well as negative emotions (P=0.003). Motivational interviewing appeared to be effective in increasing weight efficacy lifestyle among women with overweight and obesity. IRCT2014051817736N1.


ERG oncoprotein expression in prostatic acinar adenocarcinoma; clinicopathologic significance.
T/E fusion results in constitutive expression of ERG oncoprotein resulting in enhanced proliferation and invasive potential of prostatic cancer cells. In the present study we aimed to evaluate the ERG overexpression in 78 cases prostate acinar adenocarcinoma and its association with other prognostic parameters. ERG protein expression was noted in 39.7% (31 cases), out of which 3 cases (3.8%) showed low ERG expression, 10 cases (12.8%) showed intermediate expression and 18 cases (23.1%) revealed high ERG expression. Significant association of ERG expression was noted with gleason score (p = 0.009), WHO grade group (p = 0.008) and perineural invasion (p = 0.043). We found a significant proportion of our patients of prostatic acinar adenocarcinoma to over-express ERG protein which can help in devising therapeutic protocols. Significant association of ERG protein expression with gleason score and perineural invasion signifies its prognostic significance in prostatic carcinoma. Moreover, we also suggest that molecular studies should be performed in patients with prostatic carcinoma to look for T/E fusion gene and its correlation with ERG protein expression.


The Use of the Hamilton Rating Scale for Depression in Elderly Patients With Cognitive Impairment and Physical Illness.
The authors performed a prospective study to assess the impact of cognitive impairment and medical burden on the Hamilton Ratingh Scale for Depression (Ham-D) scores in older psychiatric inpatients. Over 1 year, all patients admitted to an acute-care geriatric psychiatry unit were assessed with an instrument that includes an anchored version of the 17-uten Ham-D. Ham-D scores of 72 patients who met DSM-III-R criteria for a major depressive episode were compared with the scores of 31 patients who did not. The scores of a depressed and nondepressed patients were significantly different on admission but not at discharge. By contrast, the Ham-D scores of 11 depressed patients with a primary dementia did not differ either on admission or at discharge from the scores of 61 depressed patients without dementia. Controlling for psychiatric diagnosis, cognitive impairment had no significant effect on Ham-D scores. Medical burden accounted for less than 6% of the variance in admission Ham-D yields valid ratings of the severity of depressive symptoms in elderly patients with a broad range of cognitive impairment and physical illness.


Automated detection of toxigenic Clostridium difficile in clinical samples: isothermal tcdB amplification coupled to array-based detection.
Clostridium difficile can carry a genetically variable pathogenicity locus (PaLoc), which encodes clostridial toxins A and B. In hospitals and in the community at large, this organism is increasingly identified as a pathogen. To develop a diagnostic test that combines the strengths of immunoassays (cost) and DNA amplification assays (sensitivity/specificity), we targeted a genetically stable PaLoc region, amplifying tcdB sequences and detecting them by hybridization capture. The assay employs a hot-start isothermal method coupled to a multiplexed chip-based readout, creating a manual assay that detects toxigenic C. difficile with high sensitivity and specificity within 1 h. Assay automation on an electromechanical instrument produced an analytical sensitivity of 10 CFU (95% probability of detection) of C. difficile in fecal samples, along with discrimination against other enteric bacteria. To verify automated assay function, 130 patient samples were tested: 31/32 positive samples (97% sensitive; 95% confidence interval [CI], 82 to 99%) and 98/98 negative samples (100% specific; 95% CI, 95 to 100%) were scored correctly. Large-scale clinical studies are now planned to determine clinical sensitivity and specificity.


An unusual complication of penile prosthesis following urethroplasty.
We report a case of an adult who had undergone transpubic urethroplasty for a 5-cm long posterior urethral stricture. A malleable penile prosthesis (AMS 600R) was implanted 19 months later for the trauma-related impotence. The patient was discovered to develop a complete obliteration of the urethra after removal of infected penile prosthesis 18 months later. Perineal urethroplasty cured his restricture. Suggestions are made to prevent urethral restricture if penile prosthesis is required after urethroplasty.


1,6-Conjugated Addition-Mediated [2+1] Annulation: Approach to Spiro[2.5]octa-4,7-dien-6-one.
A formal 1,6-conjugated addition-mediated [2+1] annulation to synthesize spiro[2.5]octa-4,7-dien-6-one with p-quinone methides and sulfur ylides has been described. This domino-type process was highly diastereoselective and exhibited good functional group tolerance and scalability without the use of metals and bases.


Oligonucleotide probes for the detection of TEM-1 and TEM-2 beta-lactamase genes and their transposons.
We describe the use of molecular probes to detect the TEM-type beta-lactamase genes. As a general probe, we prepared a 656 base pair restriction fragment, entirely within the TEM structural gene. This probe was specific for the TEM family, hybridizing only with TEM-1 and TEM-2. The TEM-1 and TEM-2 beta-lactamases differ by only one amino acid. We synthesized two oligonucleotides whose central bases correspond to this difference. The use of these oligonucleotides enables us to discriminate between TEM-1 and TEM-2 genes. Using oligonucleotides homologous to parts of Tn3, we also monitored the presence of TnA-like transposons in bacteria harboring different beta-lactamase genes. Only the TEM-1 and TEM-2 genes were found to be on transposons with terminal sequences identical to those of Tn3. All hybridization experiments were performed with both dot-blot and colony-hybridization techniques, and the suitability of these two methods for epidemiological studies is compared.


The high count rate performance of a two-dimensionally position-sensitive detector for positron emission tomography.
In positron tomographs using a small number of position-sensitive detectors, each detector must operate at high singles event rates, especially during dynamic studies. To enable the PENN-PET tomography to perform studies involving high data rates, the high count rate behaviour of the position-sensitive scintillation detector used in the tomograph was investigated at singles rates in excess of 2 million counts per second (MCPS). Detector dead-time, minimised through the use of pulse clipping (clipping time, 120 ns), is a maximum of 20% at the highest data rates. At 2 MCPS and 240 ns pulse integration time, the full width at half maximum of the point spread function (PSF) worsens by approximately 20% over its low count rate value of 5.2 mm. Furthermore, at high count rates, pulse pile-up produces long tails in the PSF along the detector's long axis. These tails were reduced or eliminated through the use of a shortened pulse integration time (160 ns instead of 240 ns), an upper level energy discriminator and a local centroid event positioning algorithm. Detector performance was characterised for different combinations of these event processing techniques, and the mechanisms by which pulse pile-up distorts the high count rate PSF were investigated using computer simulations. With the incorporation of the high count rate event processing techniques, the detector's count rate capability enables the PENN-PET tomograph to handle most current imaging protocols.


Spicular arrangement of amyloid in renal biopsy.
A spicular arrangement of amyloid on the epithelial aspect of the glomerular basement membrane has been seen to a variable degree in silver-stained sections of renal biopsies in eight of 38 patients with amyloidosis. Electron microscopical examination revealed a spectrum of appearances of the amyloid fibrils which would account for this finding. Only two of these eight patients had amyloidosis secondary to chronic infection, a much lower proportion than in the group as a whole. The possibility of confusion with membranous nephropathy is discussed with relevance to possible modes of treatment.


[A Case of Severe Bradycardia Associated with Bladder Perforation during Spinal Anesthesia].
Here we report a case of severe bradycardia associated with bladder perforation during transurethral resection of the bladder. The patient was diagnosed with bladder cancer eight months ago and underwent transurethral resection of the bladder tumor. After balloon-occluded arterial infusion chemotherapy, she was scheduled for a bladder biopsy under spinal anesthesia. Spinal anesthesia was induced with 2.5 ml of 0.5% bupivacaine hydrochloride at L3-4, and sensory loss (T9) was confirmed. The operation started uneventfully 20 minutes after bupivacaine administration. However, ten minutes into the operation, bladder perforation occurred and was followed by severe bradycardia (20-30 beats x min(-1)). While preparing for transcutaneous pacing, bradycardia improved with intravenous atropine and ephedrine. The level of spinal anesthesia remained unchanged. General anesthesia was induced with propofol, rocuronium and fentanyl. The patient was extubated uneventfully after the operation and was discharged 14 days later.


Consumers' opinions on warning labels on food packages: A qualitative study in Brazil.
This study aimed to assess consumers' uses of and opinions on the current Brazilian food label and their reaction to the introduction of a front-of-package warning label. We conducted 12 focus groups among a diverse sample of adult consumers, to broadly assess: (1) uses of and perceptions about the current food label, and (2) opinions about implementing a front-of-package warning label to guide food purchases. Data was analyzed with a triangulation of researchers using an exploratory content analysis, which allowed codes to emerge from the data. The frequency of codes across focus groups was compared by gender and socioeconomic status to explore differences by these sociodemographic factors. Codes were divided into six main themes: (1) "Reasons for using food labels"; (2) "Barriers to using food labels"; (3) "Requirements for a new label"; (4) "Perceived influence on consumption behaviors"; (5) "Perceived influence on child behaviors"; and (6) "Perceptions of the food manufacturers using of warning labels". Participants used food labels to check nutrient content and ingredient information but the format of these labels and the technicality of the content displayed often made the information inaccessible, particularly for those with low socioeconomic status. Most participants were supportive of the display of front-of-package warning labels on products and considered them useful to inform purchases. Women believed that they and their children would reduce the consumption of foods with front-of-package warning labels, while men reported more polarity in their intentions. For men and their children, front-of-package warning labels would result in either stopping food intake entirely or continued consumption without changes to the amount. The study results highlight the potential of front-of-package warning labels to support healthier behaviors in both consumers and their children.


The Association between Diabetes and Herpes Simplex Eye Disease.
To evaluate the association between diabetes mellitus (DM) and presence and severity of Herpes simplex eye disease (HSED). We conducted two sub-studies. We included the patients seen on the Cornea Service of the Wills Eye Hospital from January 2008 to August 2012. Study 1 included 541 patients with HSED and 3226 controls. Study 2 involved 40 diabetic and 120 non-diabetic ocular surface HSED patients. Severity of ocular surface HSED was graded as mild, moderate, or severe, based on best-corrected visual acuity (BCVA). Patients were excluded if they had fewer than two office visits or had non-Herpes simplex-related vision-threatening conditions. Diabetes was graded as: diet group (DM controlled with diet), oral group (DM controlled with oral medications), and insulin group (DM control required insulin). Five of 541 (0.93%) HSED patients had type 1 DM, similar to 19/3246 (0.59%) controls (p = 0.375); 48 of 541 (8.88%) HSED patients had type 2 DM, similar to 287/3246 (8.84%) controls (p = 0.981). Using multinomial logistic regression analyses, the probability/risk of being in the severe ocular surface HSED group as opposed to the mild ocular surface HSED group were not statistically significantly different between DM patients and those without DM (p = 0.120; OR, 1.900; 95% CI, 0.846-4.266). There may not be a positive association between type 2 DM and HSED.


Methoprene affects the rotation of the male terminalia of Aedes aegypti mosquitoes.
The rotation of the male terminalia of Aedes aegypti mosquitoes was investigated with chemical surgical, and mechanical methods. Neither decapitation nor ventral nerve cord transection affected the postemergence rotation, but methoprene administered to 4th-instar larvae and early instar pupae slowed rotation significantly and, in the case of pupal treatment, also interfered with successful insemination. Methoprene appeared to interfere with the developmental maturation of the cross muscles located between the 7th and 8th abdominal segment and postemergence nervous or humoral signals did not appear to affect this rotation.


Tribology of Si/SiO2 in humid air: transition from severe chemical wear to wearless behavior at nanoscale.
Wear at sliding interfaces of silicon is a main cause for material loss in nanomanufacturing and device failure in microelectromechanical system (MEMS) applications. However, a comprehensive understanding of the nanoscale wear mechanisms of silicon in ambient conditions is still lacking. Here, we report the chemical wear of single crystalline silicon, a material used for micro/nanoscale devices, in humid air under the contact pressure lower than the material hardness. A transmission electron microscopy (TEM) analysis of the wear track confirmed that the wear of silicon in humid conditions originates from surface reactions without significant subsurface damages such as plastic deformation or fracture. When rubbed with a SiO2 ball, the single crystalline silicon surface exhibited transitions from severe wear in intermediate humidity to nearly wearless states at two opposite extremes: (a) low humidity and high sliding speed conditions and (b) high humidity and low speed conditions. These transitions suggested that at the sliding interfaces of Si/SiO2 at least two different tribochemical reactions play important roles. One would be the formation of a strong "hydrogen bonding bridge" between hydroxyl groups of two sliding interfaces and the other the removal of hydroxyl groups from the SiO2 surface. The experimental data indicated that the dominance of each reaction varies with the ambient humidity and sliding speed.


Phenotype and genotype correlation of inherited epidermolysis bullosa in Indonesia.
Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran-Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling.


Identification of erythrocyte biomarkers in amyotrophic lateral sclerosis.
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. It has been hypothesised that red blood cells (RBCs) may be involved in the disease process by the release of damaging molecules. The aim of this ex vivo study is to compare RBCs biochemical and hemorheological parameters between ALS patients and healthy donors to identify novel biomarkers of the ALS disease. We included 82 ALS patients and 40 gender age-matched healthy donors. We performed quantification of erythrocyte aggregation and deformability, nitric oxide (NO) efflux from RBCs, acetylcholinesterase (AChE) enzyme activity and intraerythrocytic concentration of nitrite, nitrate and S-nitrosogluthatione (GSNO). Erythrocyte deformability and AChE activity were increased in patients with ALS in comparison to healthy donors. NO efflux from RBCs and concentration of intraerythrocytic nitrite were lower in ALS patients. In patients, we found that for higher NO range of values the respiratory function is worse and that for higher AChE range of values the RBCs nitrite content increase. The results of the present study indicate that NO efflux from RBCs and RBCs AChE should be further explored as potential biomarkers for ALS.


Prioritizing Clinically Relevant Copy Number Variation from Genetic Interactions and Gene Function Data.
It is becoming increasingly necessary to develop computerized methods for identifying the few disease-causing variants from hundreds discovered in each individual patient. This problem is especially relevant for Copy Number Variants (CNVs), which can be cheaply interrogated via low-cost hybridization arrays commonly used in clinical practice. We present a method to predict the disease relevance of CNVs that combines functional context and clinical phenotype to discover clinically harmful CNVs (and likely causative genes) in patients with a variety of phenotypes. We compare several feature and gene weighing systems for classifying both genes and CNVs. We combined the best performing methodologies and parameters on over 2,500 Agilent CGH 180k Microarray CNVs derived from 140 patients. Our method achieved an F-score of 91.59%, with 87.08% precision and 97.00% recall. Our methods are freely available at https://github.com/compbio-UofT/cnv-prioritization. Our dataset is included with the supplementary information.


Delay-asymmetric nonlinear loop mirror for DPSK demodulation.
We demonstrate the use of a delay-asymmetric nonlinear loop mirror (DANLM) for tunable differential phase shift keying (DPSK) demodulation. The DANLM introduces tunable differential delay between two counterpropagating signals while maintaining their phase information. The device is demonstrated using degenerate four-wave mixing wavelength-conversion and wavelength-dependent group delay. The DANLM can support the demodulation of DPSK signals over a wide range of continuously tunable bit rates and delays. We experimentally achieve the demodulation of return-to-zero DPSK signals at 10 and 20 Gbits/s using the same DANLM. Demodulation of nonreturn-to-zero DPSK signal at 10 Gbits/s with one-, half-, and quarter-bit delays has also been demonstrated. Widely opened eye diagrams and error-free detection have been obtained.


Structural mechanisms of human RecQ helicases WRN and BLM.
The RecQ family DNA helicases Werner syndrome protein (WRN) and Bloom syndrome protein (BLM) play a key role in protecting the genome against deleterious changes. In humans, mutations in these proteins lead to rare genetic diseases associated with cancer predisposition and accelerated aging. WRN and BLM are distinguished from other helicases by possessing signature tandem domains toward the C terminus, referred to as the RecQ C-terminal (RQC) and helicase-and-ribonuclease D-C-terminal (HRDC) domains. Although the precise function of the HRDC domain remains unclear, the previous crystal structure of a WRN RQC-DNA complex visualized a central role for the RQC domain in recognizing, binding and unwinding DNA at branch points. In particular, a prominent hairpin structure (the β-wing) within the RQC winged-helix motif acts as a scalpel to induce the unpairing of a Watson-Crick base pair at the DNA duplex terminus. A similar RQC-DNA interaction was also observed in the recent crystal structure of a BLM-DNA complex. I review the latest structures of WRN and BLM, and then provide a docking simulation of BLM with a Holliday junction. The model offers an explanation for the efficient branch migration activity of the RecQ family toward recombination and repair intermediates.


Immunological measurement of aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation.
Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation. A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation. METAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation. ALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.


PQ, a new program for phylogeny reconstruction.
Many algorithms and programs are available for phylogenetic reconstruction of families of proteins. Methods used widely at present use either a number of distance-based principles or character-based principles of maximum parsimony or maximum likelihood. We developed a novel program, named PQ, for reconstructing protein and nucleic acid phylogenies following a new character-based principle. Being tested on natural sequences PQ improves upon the results of maximum parsimony and maximum likelihood. Working with alignments of 10 and 15 sequences, it also outperforms the FastME program, which is based on one of the distance-based principles. Among all tested programs PQ is proved to be the least susceptible to long branch attraction. FastME outperforms PQ when processing alignments of 45 sequences, however. We confirm a recent result that on natural sequences FastME outperforms maximum parsimony and maximum likelihood. At the same time, both PQ and FastME are inferior to maximum parsimony and maximum likelihood on simulated sequences. PQ is open source and available to the public via an online interface. The software we developed offers an open-source alternative for phylogenetic reconstruction for relatively small sets of proteins and nucleic acids, with up to a few tens of sequences.


A Comparative Case Study: Does the Organization of Primary Health Care in Brazil and Turkey Contribute to Reducing Disparities in Access to Care?
Brazil and Turkey are among the few high-middle-income countries that explicitly chose to strengthen their primary health care (PHC) systems as the centerpiece of much broader health system reforms aiming to narrow inequities in access to care. This comparative case study reviews the organization of Brazil and Turkey's PHC systems to derive lessons that can apply to other countries that may consider reforming the organization of PHC systems as a way to address health inequities. The analysis uses the Flagship Framework to investigate how the organization of PHC delivery in Brazil and Turkey can lead to measurable improvements in access to care. It compares (1) the degree of decentralization in PHC service delivery responsibilities, (2) the use of multi-professional PHC teams, and (3) patient impanelment strategies. The comparative analysis offers three important lessons. First, changes in the organization of PHC systems can contribute to observable improvements in the level and distribution of health outcomes, but organizational strategies do not guarantee eliminating disparities in access. Second, PHC systems can operate in health systems with varying degrees of decentralization, but the level of decentralization may influence implementation. Third, relying on multi-professional PHC teams that serve geographically empaneled populations can improve equitable access to care, but course corrections may be needed to address evolving health demands.


Transglutaminase facilitates the formation of polymers of the beta-amyloid peptide.
One of the major pathological characteristics of Alzheimer's disease is the increased number of amyloid-containing senile plaques within the brain. The dense cores of these plaques are composed primarily of highly insoluble aggregates of a 39-43-residue peptide referred to as the beta-amyloid peptide (beta A). The mechanisms by which these insoluble extracellular deposits of beta A are formed remain unknown. In this study, the cross-linking of beta A by the calcium-dependent enzyme, transglutaminase was examined. Transglutaminases are a family of enzymes which are found in brain, and catalyse the cross-linking of specific proteins into insoluble polymers. Synthetic beta A (1-40) was readily cross-linked by transglutaminase, forming multimers in a time-dependent fashion. Furthermore, a second peptide with a substitution similar to that in the Dutch-type hereditary amyloidosis mutation (Glu22 to Gln) was also found to be a substrate for transglutaminase. Since transglutaminase covalently cross-links proteins through glutamine residues, it is suggested that transglutaminase contributes to amyloid deposition in Dutch-type hereditary amyloidosis, and possibly Alzheimer's disease.


Rapidly-deposited polydopamine coating via high temperature and vigorous stirring: formation, characterization and biofunctional evaluation.
Polydopamine (PDA) coating provides a promising approach for immobilization of biomolecules onto almost all kinds of solid substrates. However, the deposition kinetics of PDA coating as a function of temperature and reaction method is not well elucidated. Since dopamine self-polymerization usually takes a long time, therefore, rapid-formation of PDA film becomes imperative for surface modification of biomaterials and medical devices. In the present study, a practical method for preparation of rapidly-deposited PDA coating was developed using a uniquely designed device, and the kinetics of dopamine self-polymerization was investigated by QCM sensor system. It was found that high temperature and vigorous stirring could dramatically speed up the formation of PDA film on QCM chip surface. Surface characterization, BSA binding study, cell viability assay and antibacterial test demonstrates that the polydopamine coating after polymerization for 30 min by our approach exhibits similar properties to those of 24 h counterpart. The method has a great potential for rapid-deposition of polydopamine films to modify biomaterial surfaces.


Draft Whole-Genome Sequence of Xenorhabdus sp. Strain GDc328, Isolated from the Indigenous South African Nematode Host Steinernema khoisanae.
Here, we describe the draft genome sequence of Xenorhabdus sp. GDc328, an endosymbiont of the native South African entomopathogenic nematode host, Steinernema khoisanae. The total genome size of the bacteria is 4.09 Mb. The genome comprises a total of 3,608 genes with a molecular G+C content of 44.64%.


Trends in fetal and perinatal mortality in the United States, 2006-2012.
Total, early, and late fetal mortality rates were generally flat in the United States from 2006 through 2012. Over this same period, fetal mortality rates were also essentially unchanged among each of the three largest race and Hispanic origin groups: non-Hispanic white, non-Hispanic black, and Hispanic women. The perinatal mortality rate declined 4% from 2006 through 2011, a result of a decrease in early neonatal mortality. The perinatal mortality rate fell 8% for non- Hispanic black women; declines among non-Hispanic white and Hispanic women were not statistically significant. The continued decline in the perinatal mortality rate is noteworthy. The rate is down 10% since 2000 (4), and the pace of decline for the most current period, 2006–2011, is consistent with that for 2000–2005. The U.S. fetal mortality rate, however, did not improve during 2006–2012.


RAS pathway biomarkers for breast cancer prognosis.
Metastatic breast cancer is a highly heterogeneous, rapidly evolving and devastating disease that challenges our ability to find curative therapies. RAS pathway activation is an understudied research area in breast cancer. EGFR/RAS pathway activation is prevalent in breast cancer with poor prognosis. The prognostic RAS pathway biomarkers can be used to identify resistant tumour clones, stratify patients and guide therapies.


Development of pattern recognition based on nanosheet-DNA probes and an extendable DNA library.
Pattern recognition, also called "array sensing," is a recognition strategy with a wide and expandable analysis range, based on high-throughput analysis data. In this work, we constructed a sensor array for the identification of targets including bacterial pathogens and proteins by using FAM-labeled DNA probes and 2D nanosheet materials. We designed an ordered and extendible DNA library for the collection of recognition probes. Unlike traditional DNA probes with random and massive sequences, our DNA library was constructed following a 5-digit binary number (00000-11111, 0 = CCC, and 1 = TTT), and especially, 8 special symmetry sequences were chosen from the library. Two different nanosheet materials were used as the quencher. When targets were added, the interaction between DNA and the nanosheets was competitively affected, and as a result, the fluorescence signal changed accordingly. Finally, by using our fluorescent sensor array, 17 bacteria and 8 proteins were precisely recognized. We believe that our work has provided a simple and valuable strategy for the improvement of the recognition range and discrimination precision for the development of pattern recognition.


Maternal smoking during pregnancy and multiple sclerosis amongst offspring.
An association between parental smoking and multiple sclerosis (MS) in offspring has been reported. This study examined whether maternal smoking during pregnancy is associated with MS in offspring. Swedish general population registers provided prospectively recorded information on maternal smoking during pregnancy. The study identified 143 cases with MS diagnosed by 2006 and 1730 matched controls. Subjects were born since 1982 and individually matched by year of birth, age, sex and region of residence. Conditional logistic regression assessed the association of maternal smoking with MS in offspring with adjustment for socioeconomic index. Maternal smoking during pregnancy was not associated with MS in offspring, with an odds ratio (and 95% confidence interval) of 0.96 (0.65-1.44). When stratified by paediatric or later MS onset there was no association with maternal smoking in either stratum. It is unlikely that smoking during pregnancy represents a risk for early-onset MS amongst offspring.


CRISPR/Cas9-mediated genome editing of Epstein-Barr virus in human cells.
The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a highly efficient and powerful tool for RNA-guided editing of the cellular genome. Whether CRISPR/Cas9 can also cleave the genome of DNA viruses such as Epstein-Barr virus (EBV), which undergo episomal replication in human cells, remains to be established. Here, we reported on CRISPR/Cas9-mediated editing of the EBV genome in human cells. Two guide RNAs (gRNAs) were used to direct a targeted deletion of 558 bp in the promoter region of BART (BamHI A rightward transcript) which encodes viral microRNAs (miRNAs). Targeted editing was achieved in several human epithelial cell lines latently infected with EBV, including nasopharyngeal carcinoma C666-1 cells. CRISPR/Cas9-mediated editing of the EBV genome was efficient. A recombinant virus with the desired deletion was obtained after puromycin selection of cells expressing Cas9 and gRNAs. No off-target cleavage was found by deep sequencing. The loss of BART miRNA expression and activity was verified, supporting the BART promoter as the major promoter of BART RNA. Although CRISPR/Cas9-mediated editing of the multicopy episome of EBV in infected HEK293 cells was mostly incomplete, viruses could be recovered and introduced into other cells at low m.o.i. Recombinant viruses with an edited genome could be further isolated through single-cell sorting. Finally, a DsRed selectable marker was successfully introduced into the EBV genome during the course of CRISPR/Cas9-mediated editing. Taken together, our work provided not only the first genetic evidence that the BART promoter drives the expression of the BART transcript, but also a new and efficient method for targeted editing of EBV genome in human cells.


Probing site-specific 13C/15N-isotope enrichment of spider silk with liquid-state NMR spectroscopy.
Solid-state nuclear magnetic resonance (NMR) has been extensively used to elucidate spider silk protein structure and dynamics. In many of these studies, site-specific isotope enrichment is critical for designing particular NMR methods for silk structure determination. The commonly used isotope analysis techniques, isotope-ratio mass spectroscopy and liquid/gas chromatography-mass spectroscopy, are typically not capable of providing the site-specific isotope information for many systems because an appropriate sample derivatization method is not available. In contrast, NMR does not require any sample derivatization or separation prior to analysis. In this article, conventional liquid-state (1)H NMR was implemented to evaluate incorporation of (13)C/(15)N-labeled amino acids in hydrolyzed spider dragline silk. To determine site-specific (13)C and (15)N isotope enrichments, an analysis method was developed to fit the (1)H-(13)C and (1)H-(15)N J-splitting (J CH and J NH) (1)H NMR peak patterns of hydrolyzed silk fiber. This is demonstrated for Nephila clavipes spiders, where [U-(13)C3,(15)N]-Ala and [1-(13)C,(15)N]-Gly were dissolved in their water supplies. Overall, contents for Ala and Gly isotopomers are extracted for these silk samples. The current methodology can be applied to many fields where site-specific tracking of isotopes is of interest.


Histologic effects of external ultrasound-assisted lipectomy on adipose tissue.
This study aimed to observe the effects of ultrasound waves at different frequencies on abdominal fat tissue. External ultrasound-assisted lipectomy (XUAL) via both histologic and immunohistochemic examinations was used to assess adipose tissue alterations, including cells and collagenic fibers. The results, at the immunofluorescence level, show that ultrasound used at 1 MHz with a potency of 3 W resulted in no alterations or only limited cell destruction with collagen fibers intact. In contrast, when the ultrasound was 2 and especially 3 MHz, adipocyte alterations usually were evident. Massive adipose tissue destruction, confirmed using Oil red-O staining, was observed. In addition, at the immunofluorescence level, diffuse collagen fiber retraction was detected. This was particularly evident in comparisons with biopsies of intact control samples, which showed normal adipose tissue and intact collagen fibers. The results obtained using morphologic techniques, which do not allow fixation artifacts and include collagen observations, demonstrate that with the XUAL technique, ultrasound at 1 MHz does not induce cellular alterations. In contrast, both 2- and 3-MHz frequencies are capable of causing complete fat tissue disruption, including destruction of adipose cells and collagenic fibers.


Novel aortic arch reconstruction using a modified Norwood procedure based on hypoplastic left heart syndrome-specific anatomical malformations.
Postoperative left pulmonary artery (PA) or bronchus compression occasionally follows narrowing of the retroaortic space after the Norwood procedure. We examined hypoplastic left heart syndrome (HLHS)-specific anatomical malformations and hypothesized that a long main pulmonary arterial trunk might contribute to a larger retroaortic space. In this study, we introduced a modified Norwood procedure [pulmonary artery trunk-saving method (PATS)] and evaluated the results. HLHS-specific anatomical malformations were examined using computed tomographic data from 23 consecutive patients who underwent bilateral pulmonary banding. Fourteen patients had HLHS or associated conditions (Group H), and 9 patients had other complex cardiac defects and underwent biventricular repair (Group B). Five consecutive HLHS patients underwent PATS as a modified Norwood operation, and 6 controls underwent a conventional Norwood procedure. We used computed tomography to measure the lengths of the aorta and PA and the angle of both pulmonary branches to evaluate the effect of PATS. Preoperative examination confirmed HLHS-specific right PA branching adjacent to the pulmonary valve and a trend towards a shorter main pulmonary arterial trunk with the conventional Norwood procedure. Also, both right and left pulmonary arterial branching from the dorsal aspect of the main pulmonary arterial trunk and the PA branch angle were minimal in HLHS patients. Postoperative data showed the retroaortic space behind the reconstructed neoaorta was significantly wider in PATS patients than in conventional Norwood patients. Longitudinal measurements (between the aortic arch and pulmonary valve) and sagittal measurements (ascending aorta to descending aorta) were larger in PATS patients, and no left PA or airway obstruction was observed following PATS. PATS resulted in a wider aortopulmonary space without left pulmonary arterial stenosis or bronchus obstruction. HLHS-specific anatomical malformations suggested that PATS may avoid extrinsic compression of the left PA and bronchus by the neoaorta and can be an alternative for HLHS patients.


Alberta Stroke Program Early CT Scoring of CT perfusion in early stroke visualization and assessment.
Qualitative CT perfusion (CTP) assessment by using the Alberta Stroke Program Early CT Score (ASPECTS) allows rapid calculation of infarct extent for middle cerebral artery infarcts. Published thresholds exist for noncontrast CT (NCCT) ASPECTS, which may distinguish outcome/complication risk, but early ischemic signs are difficult to detect. We hypothesized that different ASPECTS thresholds exist for CTP parameters versus NCCT and that these may be superior at predicting clinical and radiologic outcome in the acute setting. Thirty-six baseline acute stroke NCCT and CTP studies within 3 hours of symptoms were blindly reviewed by 3 neuroradiologists, and ASPECTS were assigned. Treatment response was defined as major neurologic improvement when a > or =8-point National Institutes of Health Stroke Scale improvement at 24 hours occurred. Follow-up NCCT ASPECTS and 90-day modified Rankin score (mRS) were radiologic and clinical reference standards. Receiver operating characteristic curves derived optimal thresholds for outcome. Cerebral blood volume and NCCT ASPECTS had similar radiologic correlations (0.6 and 0.5, respectively) and best predicted infarct size in the absence of major neurologic improvement. A NCCT ASPECT threshold of 7 and a cerebral blood volume threshold of 8 discriminated patients with poor follow-up scans (P < .0002 and P = .0001) and mRS < or =2 (P = .001 and P < .001). Only cerebral blood volume predicted major neurologic improvement (P = .02). Interobserver agreement was substantial (intraclass correlation coefficient, 0.69). Cerebral blood volume ASPECTS sensitivity, specificity, positive predictive value, and negative predictive value for clinical outcome were 60%, 100%, 100%, and 45%, respectively. No patients with cerebral blood volume ASPECTS <8 achieved good clinical outcome. Cerebral blood volume ASPECTS is equivalent to NCCT for predicting radiologic outcome but may have an additional benefit in predicting patients with major neurologic improvement.


Elevated serum acylated (biologically active) ghrelin and resistin levels associate with pregnancy-induced weight gain and insulin resistance.
To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg). Cross-sectional case control study. Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups. Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.


Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses.
In Southeast Asia, dengue viruses often co-circulate with other flaviviruses such as Japanese encephalitis virus, and due to the presence of shared antigenic epitopes it is often difficult to use serological methods to distinguish between previous infections by these flaviviruses. Convalescent sera from 69 individuals who were known to have had dengue or Japanese encephalitis virus infection were tested by western blotting against dengue, Japanese encephalitis and West Nile virus antigens. We determined that individuals who had been infected with dengue viruses had IgG responses against the premembrane protein of dengue viruses but not Japanese encephalitis, whereas individuals who had been infected with Japanese encephalitis had IgG specific for the premembrane protein of Japanese encephalitis virus but not the dengue viruses. None reacted with the premembrane protein of West Nile virus. Using the Pearson Chi Square test, it was determined that the difference between the two groups was highly significant with a p value of <0.001. The use of flavivirus premembrane protein in seroepidemiological studies will be useful in determining what flaviviruses have circulated in a community.


Editorial Commentary: Those Who Don't Know History Are Condemned to Repeat It-What Are the Next Steps to Improve Posterolateral Knee Outcomes?
Two decades ago, it was not uncommon to call the posterolateral corner of the knee the "dark side of the knee." This was because there were few quantitative anatomic data, no anatomic-based reconstructions, and a high rate of clinical outcome failures. Most nonanatomic posterolateral reconstruction procedures at the time commonly resulted in significant recurrent increases in varus gapping and significant overconstraint in external rotation. Postoperative protocols for treating these injuries were designed to often either cast or immobilize the operative knee for 2 to 6 weeks, which resulted in a higher incidence of arthrofibrosis. In addition, missed or neglected posterolateral corner injuries were frequently the cause of failed anterior and posterior cruciate ligament reconstruction graft failures. Anatomic-based posterolateral corner reconstructions have now been validated clinically to significantly improve patient outcomes. The next steps in improving patient outcomes would be to further refine these anatomic-based techniques, improve postoperative rehabilitation protocols, and ensure that future outcome studies have both patient-reported outcomes and objective data with stress radiographs to confirm that we are building a better mousetrap to treat this pathology.


Regulation of type II luteinizing hormone-releasing hormone (LHRH-II) gene expression by the processed peptide of LHRH-I, LHRH-(1-5) in endometrial cells.
Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary gonadotropin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on LHRH-I, LHRH-II, and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 18.104.22.168 (EP24.15) that cleaves the hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1-5). Given its importance in the brain, we have investigated the role of the specific processed peptide of LHRH-I, LHRH-(1-5), within Ishikawa cells, a human endometrial cell line. Using real-time polymerase chain reaction, we observed that LHRH-(1-5) upregulates LHRH-II mRNA expression in Ishikawa cells but does not exert any influence on LHRH-I mRNA levels. This is in contrast to the effects of LHRH-I, which affects the expression of LHRH-I mRNA. Our findings support a potential role for LHRH-(1-5) as a processed metabolite in the endometrium. Further investigations are needed to determine the role of this processed metabolite and to identify specific pathways involved in LHRH-(1-5) signaling.


Induction and cross-species activity of rat fibroblast-derived interferon.
Interferon derived from rat fibroblasts (RFA-1) was pH 2 stable and heat labile. Denaturants such as SDS and urea inactivated this interferon but beta-mercaptoethanol alone did not. IFN yield after Newcastle disease virus was multiplicity of infection (moi) dependent. Optimal induction was obtained with an moi of 10. RFA-1 cells produced small amounts of IFN (less than or equal to 10(1.5) U/ml) when exposed to varying amounts of poly(rI): poly(rC). Addition of DEAE-dextran and/or pretreatment with IFN did not change this response. Pretreatment resulted in increased interferon production, priming, but on the average it was only about a 2-fold increase. However, the kinetics of interferon production were altered by pretreatment with IFN whether there was an increase in production or not. Both IFN synthesis and production peaks were detected 2-4 h earlier in IFN-pretreated RFA-1 cells. Rat IFN exhibited a great deal of cross-species activity. It is 100-300% cross-reactive on mouse (L929B and 3T3) cells, and 5-10% active on guinea pig fibroblasts, human (GM 2767) and bovine (MDBK) cells. These cells were more sensitive to rat IFN than Jensen sarcoma cells (a rat tumour cell line). Neither chicken embryo fibroblasts nor monkey (Vero) cells developed an antiviral state when exposed to rat IFN.


Renal ultrastructural findings in Anderson-Fabry disease.
Anderson-Fabry disease (AFd) is caused by an X-linked inborn error in the glycosphingoLipid metabolic pathway due to an enzymatic defect in a lysosomal hydrolase: alpha-galactosidase A. The defect results in the progressive accumulation of neutral glycosphingolipids in most body fluids and several tissues. The clinical manifestations of AFd are related to organ damage and, obviously, are more severe in hemizygous males than in heterozygous females. In the third decade of life, the course of the disease involves severe deterioration of kidney function progressing to end-stage renal failure. All kind of cells of renal structures are filled with glycosphingolipid deposits. Electron microscopic studies document typical intracytoplasmic osmiophilic bodies with a characteristic "zebra" or "onion-skin" appearance due to concentric lamellation of alternating clear and dark layers. Clinical interest in Fabry patients is related to recent advances in treatment with an intravenous specific enzyme to modify the biochemical error of the glycosphingolipid catabolic pathway.


Arterial injuries during inguinal herniorrhaphy.
In all common forms of inguinal herniorrhaphy, stitches pass either just superficial to the internal iliac artery and vein or through their sheath. Despite the potential for arterial injury, documented cases seem to exist only in the foreign-language literature. We report four cases of arterial injury following inguinal herniorrhaphy in adults. The artery is placed in jeopardy when the transversalis fascia is incorporated in the stitches used to close the medial aspect of the internal inguinal ring. The depth of penetration of the needle and the proximity of the external iliac artery must be accurately judged. Injury can result from direct puncture of the artery or avulsion of one of its branches. Immediate repair of any arterial injury is paramount, and newly subnormal pulses below the inguinal injury are unacceptable. Exposure must be adequate, and division of the floor of the inguinal canal may be necessary for this purpose. Repair may require a simple hemostatic suture, a patch graft, or an interposition graft.


Development of sensitive immunoassays for free and total human glandular kallikrein 2.
Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 microg/L. The median total hK2 concentration was 0.022 microg/L (range, 0.0015-0.37 microg/L). hK2 concentrations were 0.1-58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41-50 and 51-60 years of age. The ratio of hK2 to PSA steadily decreased from 5-30% at PSA <1 microg/L to 1-2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 microg/L (range, 0.0015-16.2 microg/L). The median free hK2 concentration was 0.070 (range, 0.005-12.2) microg/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.


[Risk factor for residual deep vein thrombosis after fondaparinux administration in patients with postoperative replacement arthroplasty].
Deep venous thrombosis (DVT) is a life-threatening postoperative complication and occurs frequently after total-knee-replacement arthroplasty (TKA) and total-hip-replacement arthroplasty (THA). Fondaparinux (FPX) has been used to treat and prevent DVT, however interindividual difference of the drug efficacy exists. Therefore, this chart review was retrospectively conducted to research risk factors for a residual DVT after FPX treatment. Total of 112 patients undergone TKA or THA were treated with 2.5 mg FPX once a day between postoperative day (POD) 1 and 14 from July 2007 through December 2008. Among these patients, 30 patients who were detected DVT on POD 4 were enrolled in this study. Thirty patients were divided into two groups according to the presence (n=11) or absence (n=19) of DVT on POD14. The DVT (-) group had a significantly longer activated partial thromboplastin time (APTT, median 31.4 s) on POD 1 than the DVT (+) group (28.5 s) (p<0.02). Multivariate logistic regression analysis revealed that APTT lower than 28.5 seconds on POD1 was considered to be independent risk factor significantly contributing to residual DVT (odds ratio 17.5, 95% confidential interval 2.0-295.4, p=0.02). These findings should provide useful information for understanding the interindividual difference of the efficacy of FPX after TKA or THA.


Evaluation, identification and impact assessment of abnormal internal standard response variability in regulated LC-MS bioanalysis.
Internal standard (IS) plays an important role in LC-MS bioanalysis by compensating for the variability of the analyte of interest in bioanalytical workflow. Due to the complexity of biological sample compositions and bioanalytical processes, a certain level of IS response variability across a run or a study is anticipated. However, an extensive variability may raise doubts to the accuracy of the measured results and also suggest nonoptimal analytical method. In this current paper, recent publications and guidelines regarding IS response in LC-MS bioanalysis were thoroughly reviewed with focus on the evaluation, identification and impact assessment of 'abnormal' IS response variability. A systematic decision tree was proposed to facilitate investigation into abnormal IS response variability after each run.


Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes.
Leakage of lysosomal enzymes is associated with irreversible cellular damage. To determine the effect of prostaglandin I2 analogue and propranolol on the ischaemic myocardium in relation to changes in lysosomal integrity 26 anaesthetised mongrel dogs were divided into three treatment groups and subjected to 2 h coronary occlusion. In the control group (n = 12) physiological saline was infused throughout the experiment. In the prostaglandin I2 analogue group (n = 7) the prostaglandin I2 analogue, OP-41483-alpha-CD;5(E)-6-Deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PGI2. alpha-cyclodextrin clathrate (5 ng.kg-1.min-1) was infused from 25 min before occlusion until the end of the experiment. In the propranolol group (n = 7) propranolol (0.3 mg.kg-1) was injected for 10 min 25 min before occlusion. Two hours after occlusion mitochondria were prepared from both ischaemic and non-ischaemic areas in each group and their function measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischaemic and ischaemic areas was performed and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase; beta-glucuronidase) were measured. In the control group, mitochondrial function in the ischaemic area was reduced compared with that from the non-ischaemic area. The activities of both lysosomal enzymes were increased significantly in the supernatant fraction obtained from the ischaemic area compared with those for the supernatant from the non-ischaemic area. The administration of prostaglandin I2 analogue or propranolol not only prevented the leakage of lysosomal enzymes but also maintained mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgically-induced deformation in biodegradable orthopaedic implant devices.
The biocompatibility and mechanical performance of biodegradable metals (e.g. magnesium, iron, and zinc-based alloys) in orthopaedic-targeted applications are contingent on limiting the rate of corrosion in vivo throughout the bone healing. Concurrently, the surgical procedure for the implantation of internal bone fixation devices may impart plastic deformation to the device, potentially altering the corrosion rate of the device. However, the potential effect of the surgical implantation procedure on the mechanochemical performance of metallic degradable orthopaedic devices in vivo remains largely unresolved. The objective of the present study is to develop a robust technique that permits the quantification of the strain introduced due to surgical implantation of degradable orthopaedic devices. Specifically, a novel combined experimental-modelling approach based on 3D laser scanning in situ and the finite element method is utilised to quantify the plastic strain introduced to a bone fixation plate following surgical implantation in a cadaveric porcine model where the plate is based on a ternary magnesium-zinc-calcium alloy (ZX10). The magnitude of plastic strains determined by the above approach for the Mg craniofacial miniplate confirms that the surgical procedure itself has the potential to enhance the corrosion rate of the Mg alloy in an accelerated and potentially localised manner. STATEMENT OF SIGNIFICANCE: Biodegradable metallic orthopaedic implant devices have emerged as a potential alternative to permanent implants, although successful adoption is contingent on achieving an acceptable degradation profile. Plastic strain that is introduced to the device during surgical implantation may influence the resulting degradation behaviour of the implant. In the present work, 3D laser scanning is combined with computer simulation to estimate the level and distribution of surgically-induced plastic strain in a magnesium alloy (ZX10). Subsequently, clinically-relevant pre-strain is shown to influence the rate of corrosion of ZX10 in vitro, indicating the value of such an approach in the design of biodegradable metallic devices under multiaxial loading.


Fatal mastitis of dairy cows: a retrospective study.
The necropsy records of dairy cows with mastitis were reviewed from the provincial veterinary laboratory in Guelph (44 cases of mastitis in nine years) and from the Ontario Veterinary College (168 cases in 14 years). Mastitis was considered to be the primary cause of death in 167 of 212 cows (79%). Of these 167 cases of mastitis, Escherichia coli was involved in 107 (64%), Klebsiella sp. in 12 (7%) and Staphylococcus aureus in 11 (7%). Bacteriology was not reported in 22 cases. Coliform mastitis, the most commonly identified type of fatal mastitis, was characterized histologically by the presence of infarcted areas in affected glands and by the lack of demonstrable bacteria, and was thus easily identified from fatal mastitis caused by S. aureus.


A yeast-based screening assay identifies repurposed drugs that suppress mitochondrial fusion and mtDNA maintenance defects.
Mitochondria continually move, fuse and divide, and these dynamics are essential for the proper function of the organelles. Indeed, the dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs as well as preserving their integrity. As a consequence, mitochondrial fusion and fission dynamics and the proteins that control these processes, which are conserved from yeast to human, are essential, and their disturbances are associated with severe human disorders, including neurodegenerative diseases. For example, mutations in OPA1, which encodes a conserved factor essential for mitochondrial fusion, lead to optic atrophy 1, a neurodegeneration that affects the optic nerve, eventually leading to blindness. Here, by screening a collection of ∼1600 repurposed drugs on a fission yeast model, we identified five compounds able to efficiently prevent the lethality associated with the loss of Msp1p, the fission yeast ortholog of OPA1. One compound, hexestrol, was able to rescue both the mitochondrial fragmentation and mitochondrial DNA (mtDNA) depletion induced by the loss of Msp1p, whereas the second, clomifene, only suppressed the mtDNA defect. Yeast has already been successfully used to identify candidate drugs to treat inherited mitochondrial diseases; this work may therefore provide useful leads for the treatment of optic atrophies such as optic atrophy 1 or Leber hereditary optic neuropathy.


The management trail.
The author discussed various advanced roles for the perioperative RN; commitment and passion for the OR professional; the need for education, education, education; and how to plan your career.


[Gene therapy of heart transplantation].
Somatic gene therapy involves the delivery and expression of a protective gene into a somatic organ. Cardiovascular gene therapy currently includes more than twenty clinical trials carried out worldwide. These trials evaluate gene delivery of vascular growth factors to the ischemic heart and legs in patients with coronary and peripheral artery disease, respectively. In contrast, no clinical trials have been carried out in gene therapy of heart transplantation. However, there is increasing experimental evidence for a therapeutic potential of this approach. Using a rat model of heart transplantation, we have shown that gene delivery of an inhibitor of interleukine-1, a pro-inflammatory molecule involved in allograft rejection, results in prolonged allograft survival. Another experimental study (5) has shown that gene transfer of a chimeric molecule comprising the cytotoxic T lymphocytic antigen-4 fused to an immunoglobulin (CTLA-4 Ig), which acts as a suppressor of T lymphocyte co-stimulation, induces an immune tolerance that is selective for the allograft. The recent development of gene transfer vectors that are capable of expressing a transgene for extended periods of time and in a regulatable manner represents an important step towards clinical applications in gene therapy of heart transplantation.


PSMA-ligand uptake can serve as a novel biomarker in primary prostate cancer to predict outcome after radical prostatectomy.
The prostate-specific membrane antigen (PSMA) is a relevant target in prostate cancer, and immunohistochemistry studies showed associations with outcome. PSMA-ligand positron emission tomography (PET) is increasingly used for primary prostate cancer staging, and the molecular imaging TNM classification (miTNM) standardizes its reporting. We aimed to investigate the potential of PET-imaging to serve as a noninvasive imaging biomarker to predict disease outcome in primary prostate cancer after radical prostatectomy (RP). In this retrospective analysis, 186 primary prostate cancer patients treated with RP who had undergone a 68Ga-PSMA-11 PET up to three months prior to the surgery were included. Maximum standardized uptake value (SUVmax), SUVmean, tumor volume (TV) and total lesion (TL) were collected from PET-imaging. Moreover, clinicopathological information, including age, serum prostate-specific antigen (PSA) level, and pathological characteristics, was assessed for disease outcome prediction. A stage group system for PET-imaging findings based on the miTNM framework was developed. At a median follow-up after RP of 38 months (interquartile range (IQR) 22-53), biochemical recurrence (BCR) was observed in 58 patients during the follow-up period. A significant association between a positive surgical margin and miN status (miN1 vs. miN0, odds ratio (OR): 5.428, p = 0.004) was detected. miT status (miT ≥ 3a vs. miT < 3, OR: 2.696, p = 0.003) was identified as an independent predictor for Gleason score (GS) ≥ 8. Multivariate Cox regression analysis indicated that PSA level (hazard ratio (HR): 1.024, p = 0.014), advanced GS (GS ≥ 8 vs. GS < 8, HR: 3.253, p < 0.001) and miT status (miT ≥ 3a vs. miT < 3, HR: 1.941, p = 0.035) were independent predictors for BCR. For stage I disease as determined by PET-imaging, a shorter BCR-free survival was observed in the patients with higher SUVmax (IA vs. IB stage, log-rank, p = 0.022). Preoperative miTNM classification from 68Ga-PSMA-11 PET correlates with postoperative GS, surgical margin status and time to BCR. The association between miTNM staging and outcome proposes 68Ga-PSMA-11 PET as a novel non-invasive imaging biomarker and potentially serves for ancillary pre-treatment stratification.


Validating a model: the expert systems research approach.
The nursing profession is invariably resorting to the use of models to depict the key facets and relationships that are being uncovered through research. The expert systems approach to model validation incorporates into research methods a process authenticated by the disciplines of engineering and information systems. The seven-step process developed for a computer expert systems approach has been transformed into a Nine-Stage Schematic of the Process for Validating System Models. This article proposes the expert systems research approach to model validation as a means of clarifying and defining models within the discipline of nursing. This process was used to validate Boswell's Model of the Structure of Knowledge for Nursing, and the process conducted for this model will be discussed as a case study of the use of the expert systems approach for model validation.


Surprising sequential effects on MMN.
The mismatch negativity (MMN) is conceptualized as a confidence-weighted error signal elicited when a deviation violates the predicted next-state based on regularity. The mechanisms underpinning its generation remain contentious. Smaller MMN response is a robust finding in schizophrenia and reduced amplitude may implicate impairment in prediction-error signalling. An enriched understanding of factors that influence MMN size in healthy people is a prerequisite for translating the relevance of reduced MMN in schizophrenia. This paper features two studies designed to explore factors that impact MMN in healthy individuals. Study 1 confirms that MMN amplitude does not faithfully reflect transition statistics and is susceptible to order-driven bias. In study 2, we demonstrate that an order-driven bias remains despite repeated encounters with sound sequences. These data demonstrate that factors that impact on MMN size in non-clinical groups are not fully understood and that some mechanisms driving relevance filtering are likely influenced by 'top-down' expectations.


Pfaffian state generation by strong three-body dissipation.
We propose a scheme for preparing and stabilizing the Pfaffian state with high fidelity in rapidly rotating 2D traps containing a small number of bosons. The goal is achieved by strongly increasing three-body loss processes, which suppress superpositions of three particles while permitting pairing. This filtering mechanism gives rise to reasonably small losses if the system is initialized with the right angular momentum. We discuss some methods for tuning independently two- and three-body interactions.


Human pressures predict species' geographic range size better than biological traits.
Geographic range size is the manifestation of complex interactions between intrinsic species traits and extrinsic environmental conditions. It is also a fundamental ecological attribute of species and a key extinction risk correlate. Past research has primarily focused on the role of biological and environmental predictors of range size, but macroecological patterns can also be distorted by human activities. Here, we analyse the role of extrinsic (biogeography, habitat state, climate, human pressure) and intrinsic (biology) variables in predicting range size of the world's terrestrial mammals. In particular, our aim is to compare the predictive ability of human pressure vs. species biology. We evaluated the ability of 19 intrinsic and extrinsic variables in predicting range size for 4867 terrestrial mammals. We repeated the analyses after excluding restricted-range species and performed separate analyses for species in different biogeographic realms and taxonomic groups. Our model had high predictive ability and showed that climatic variables and human pressures are the most influential predictors of range size. Interestingly, human pressures predict current geographic range size better than biological traits. These findings were confirmed when repeating the analyses on large-ranged species, individual biogeographic regions and individual taxonomic groups. Climatic and human impacts have determined the extinction of mammal species in the past and are the main factors shaping the present distribution of mammals. These factors also affect other vertebrate groups globally, and their influence on range size may be similar as well. Measuring climatic and human variables can allow to obtain approximate range size estimations for data-deficient and newly discovered species (e.g. hundreds of mammal species worldwide). Our results support the need for a more careful consideration of the role of climate change and human impact - as opposed to species biological characteristics - in shaping species distribution ranges.


The Association between Coffee Consumption and Bone Status in Young Adult Males according to Calcium Intake Level.
The purpose of this study was to investigate the association between coffee consumption and bone status (bone mineral density and bone metabolism-related markers) according to calcium intake level in Korean young adult males. Healthy and nonsmoking males (19-26 years, n = 330) participated in this study. Anthropometric measurements, dietary habits, and nutrient intakes were surveyed. Bone status of the calcaneus was measured by using quantitative ultrasound (QUS). Bone metabolism-related markers including serum total alkaline phosphatase activity (TALP), N-mid osteocalcin (OC), and type 1 collagen C-terminal telopeptide (1CTP) were analyzed. The subjects were divided into two groups based on daily calcium intake level: a calcium-sufficient group (calcium intake ≥ 75% RI, n = 171) and a calcium-deficient group (calcium intake < 75% RI, n = 159). Each group was then further divided into three subgroups based on daily average coffee consumption: no-coffee, less than one serving of coffee per day, and one or more servings of coffee per day. There were no significant differences in height, body weight, body mass index, energy intake, or calcium intake among the three coffee consumption subgroups. QUS parameters and serum 1CTP, TALP, and OC were not significantly different among either the two calcium-intake groups or the three coffee consumption subgroups. Our results may show that current coffee consumption level in Korean young men is not significantly associated with their bone status and metabolism according to the calcium intake level.


Gene transfer to human placenta ex vivo: a novel application of dual perfusion of human placental cotyledon.
The purpose of this study was to determine whether the transfer of a marker gene in dual recirculating human placental perfusion is feasible and whether the transgene production is detectable by X-Gal histochemistry. Four term human placentas were perfused for 9 to 16 hours in a dual perfusion chamber. At the beginning of each experiment, an adenoviral vector that carried beta-galactosidase gene was added to the maternal perfusate that was entering the intervillous space; at the end, the placental tissues were analyzed for beta-galactosidase activity by X-Gal staining. Adenovirus-mediated gene transfer resulted in a 0.5% to 1% gene transfer efficiency in placental trophoblastic cells after 9 hours of perfusion, whereas the gene transfer efficiency was much higher, to 5% after 16 hours of perfusion. When postperfusion tissue explant cultures were analyzed for beta-galactosidase expression 56 hours after the perfusion, the transfection rate was as high as 11%. Perfused human placenta can be efficiently transfected with adenoviral vectors, and the expression of the transgene can be detected in the trophoblastic cells. This system can be used for the optimization and analysis of gene transfer conditions to human placenta without any risk to the fetus.


A Personalized Spring Network Representation of Emphysematous Lungs From CT Images.
Emphysema is a progressive disease characterized by irreversible tissue destruction and airspace enlargement, which manifest as low attenuation area (LAA) on CT images. Previous studies have shown that inflammation, protease imbalance, extracellular matrix remodeling and mechanical forces collectively influence the progression of emphysema. Elastic spring network models incorporating force-based mechanical failure have been applied to investigate the pathogenesis and progression of emphysema. However, these models were general without considering the patient-specific information on lung structure available in CT images. The aim of this work was to develop a novel approach that provides an optimal spring network representation of emphysematous lungs based on the apparent density in CT images, allowing the construction of personalized networks. The proposed method takes into account the size and curvature of LAA clusters on the CT images that correspond to a pre-stressed condition of the lung as opposed to a naïve method that excludes the effects of pre-stress. The main findings of this study are that networks constructed by the new method 1) better preserve LAA cluster sizes and their distribution than the naïve method; and 2) predict different course of emphysema progression compared to the naïve method. We conclude that our new method has the potential to predict patient-specific emphysema progression which needs verification using clinical data.


Benefit of β-blocker treatment for patients with acute myocardial infarction and preserved systolic function after percutaneous coronary intervention.
β-blockers are the standard treatment for myocardial infarction (MI) based on evidence from the pre-thrombolytic era. The aim of this study was to examine the effect of β-blocker treatment in patients with acute MI and preserved systolic function in the era of percutaneous coronary intervention (PCI). We analysed a multicentre registry and identified 3019 patients who presented with acute MI between 2004 and 2009. Patients were treated with PCI, had left ventricular EFs ≥50% according to echocardiograms that were performed during the index PCI, and were alive at the time of discharge. The association between β-blocker use after discharge and mortality (all-cause death and cardiac death) within 3 years was examined. Patients who were not treated with β-blockers (n=595) showed higher rates of all-cause death and cardiac death compared to patients treated with β-blockers (10.8% vs 5.7%, p<0.001, 7.6% vs 2.6%, p<0001). The multivariate Cox proportional hazards model showed that β-blocker treatment was associated with a significant reduction in all-cause death (adjusted HR 0.633, 95% CI 0.464 to 0.863; p=0.004) and cardiac death (adjusted HR 0.47, 95% CI 0.32 to 0.70; p<0.001). Comparable results were obtained after propensity score matching. β-blocker treatment was associated with reduced long term mortality in patients with acute MI and preserved systolic function who received PCI.


Toward a consilient science of psychology.
From its inception, psychology has been characterized by conceptual fragmentation and slow scientific progress (Henriques, 2004; Meehl, 1978). In contrast, the natural sciences have achieved in recent decades a remarkable degree of consilience--the linking of fact, theory, and method across disciplines (and subdisciplines) and across nested levels of informational complexity (Wilson, 1998). Although such consilience serves as a potent catalyst of scientific discovery, there exists several barriers to the emergence of a consilient science of psychology (e.g., the persistent influence of dualism, longstanding internecine discord, resistance to perceived reductionism, etc.). We discuss the manner in which the development of metatheoretical frameworks (including Henriques' Tree of Knowledge model) may play an important role in addressing such barriers. Likewise, we describe the hybrid interdisciplinary domain of cognitive neuroscience, which provides an empirically testable metatheory and a promising consilient bridge between psychology and the natural sciences.


Expression of transforming growth factor beta (TGFbeta) type III receptor restores autocrine TGFbeta1 activity in human breast cancer MCF-7 cells.
While transforming growth factor beta (TGFbeta) type III receptor (RIII) is known to increase TGFbeta1 binding to its type II receptor (RII), the significance of this phenomenon is not known. We used human breast cancer MCF-7 cells to study the role of RIII in regulating autocrine TGFbeta1 activity because they express very little RIII and no detectable autocrine TGFbeta activity. A tetracycline-repressible RIII expression vector was stably transfected into this cell line. Expression of RIII increased TGFbeta1 binding to TGFbeta type I receptor (RI) as well as RII. Treatment with tetracycline suppressed RIII expression and abolished TGFbeta1 binding to RI and RII. Growth of RIII-transfected cells was reduced by 40% when plated at low density on plastic. This reduction was reversed by tetracycline treatment and was partially reversed by treatment with a TGFbeta1 neutralizing antibody. The activity of a TGFbeta-responsive promoter construct when transiently transfected was more than 3-fold higher in the RIII-transfected cells than in the control cells. Treating the cells with tetracycline or the TGFbeta1 neutralizing antibody also significantly attenuated the increased promoter activity. These results suggest that expression of RIII restored autocrine TGFbeta1 activity in MCF-7 cells. The RIII-transfected cells were also much less clonogenic in soft agarose than the control cells indicating a reversion of progression. Thus, RIII may be essential for an optimal level of the autocrine TGFbeta activity in some cells, especially in the transformed cells with reduced RII expression.


Drugs from the new world: the contribution of the pre-Columbian to the European medical matter.
The discovery of America still goes on through the analysis of its medical matter. From the exploitation of the resources made by Columbus, to the comprehension of local civilizations and to the reception of their therapeutic means, is a path that winds, supported by different reasons: the economic return, the therapeutic efficacy, the cultural exchanges between peoples. Unfortunately, with the passing of time, many traditions, fruit of the experience of mysterious centuries, are lost. It is through the examination of American medical matter that we try - with the advantage of acquiring new curative means - to find a new key for the comprehension of its peoples.


Potential novel biomarkers of cardiovascular dysfunction and disease: cardiotrophin-1, adipokines and galectin-3.
Cardiovascular disease is one of the main burdens of healthcare systems worldwide. Nevertheless, assessing cardiovascular risk in both apparently healthy individuals and low/high-risk patients remains a difficult issue. Already established biomarkers (e.g. brain natriuretic peptide, troponin) have significantly improved the assessment of major cardiovascular events and diseases but cannot be applied to all patients and in some cases do not provide sufficiently accurate information. In this context, new potential biomarkers that reflect various underlying pathophysiological cardiac and vascular modifications are needed. Also, a multiple biomarker evaluation that shows changes in the cardiovascular state is of interest. This review describes the role of selected markers of vascular inflammation, atherosclerosis, atherothrombosis, endothelial dysfunction and cardiovascular fibrosis in the pathogenesis and prognosis of cardiovascular disease: the potential use of cardiotrophin-1, leptin, adiponectin, resistin and galectin-3 as biomarkers for various cardiovascular conditions is discussed.


Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore.
We have previously found marine n-3 fatty acids to be inversely related to post-menopausal breast cancer in Chinese women from Singapore. Post-menopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87]. Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is a suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial by-products. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis, nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71, 95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1 positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer relationships were observed in either pre-menopausal or post-menopausal women at baseline. However, post-menopausal women possessing the combined GSTM1 null and GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar relationship was observed among women with the combined GSTT1 null and GSTP1 AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).


Understanding and Managing Cognitive Distortions in Individuals With Schizophrenia.
Schizophrenia is characterized by psychotic symptoms such as delusions, hallucinations, and disorganized thinking and speech. Patients suffering from schizophrenia incited by these delusions react violently in response to real or imagined threats; this engages them in violent behaviours and thus poses a threat. Sparse data are available for patients from India with regard to schizophrenia patients acting on their delusions. The aim of this study was to assess the prevalence of delusional action in patients suffering from schizophrenia and to identify the phenomenological characteristics of those delusions which are associated with action. This study was conducted on patients with a diagnosis of schizophrenia admitted to the indoor patient department (IPD) of the Department of Psychiatry, K.D. Medical College, Hospital & Research Centre, Mathura, India, during the period of February 2022 to July 2022. A semi-structured, semi-open-ended questionnaire was used for interviewing patients regarding demographics, the course of illness, past medical illness, the family history of psychiatric disturbances, and substance use. The study tool used for delusion was the Maudsley Assessment of Delusions Schedule (MADS). Out of 56 selected subjects, 34 acted on delusion and out of these, 19 were male and 15 female. In our study gender did not play any significant role in acting on delusion. Literacy and nuclear living households played a significant role in influencing delusion-driven behaviours, while the distinction between urban and rural living, though noteworthy, fell just short of achieving statistical significance. An emotional state like anger was significantly important to the patient's acting on delusion, which led to violent behaviour or self-harm. Positive responses are more likely to be associated with leading action on delusion as compared to negative responses, which were also associated with action on delusion; for example, anger was significantly important in the patient's acting on delusion, which led to violent behaviour or self-harm.


Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine-7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts.
Purine DNA represents an alternative pairing system formed by two purines in the base pair with the recognition elements of Watson-Crick DNA. Base functionalization of 7-deaza-2'-deoxyxanthosine with ethynyl and octadiynyl residues led to clickable side chain derivatives with short and long linker arms. As complementary bases, purine-2,6-diamine or 7-deazapurine-2,6-diamine 2'-deoxyribonucleosides were used. 7-Deaza-7-iodo-2'-deoxyxanthosine served as a starting material for Sonogashira cross-coupling and the p-nitrophenylethyl group for base protection. Phosphoramidite building blocks for DNA synthesis were prepared. Oligonucleotides containing single modifications or runs of three purine base pairs embedded in 12-mer Watson-Crick DNA were synthesized and hybridized with complementary strands with purine- or 7-deazapurine-2,6-diamine located opposite to the xanthine derivatives. The stability of base pairs was evaluated in a comparative study on the basis of DNA melting experiments and Tm values. As 7-deazaxanthine and xanthine nucleosides form anionic forms at neutral pH, duplex stability became pK-dependent, and the system with 7-deazapurine displayed a significant higher stability as that containing xanthine. Alkynyl side chains are well accommodated in the purine-purine helix. Click adducts with pyrene showed that short linker arms destabilize duplexes, whereas long linkers increase duplex stability. CD and fluorescence measurements provide further insights into purine-purine base pairing.


Neighborhood matters: racial socialization of African American children.
Differences in racial socialization practices and their effects were examined in a sample of 241 African American 1st graders (average age 6.59 years) living in an urban area. Child outcomes included cognitive development, receptive language skills, and child problem behavior. The cultural environment of the home was associated with higher cognitive scores for boys living in high negative social climate and low social capital neighborhoods and for girls living in high social capital neighborhoods. The positive association of promotion of mistrust and child behavior problems was magnified in neighborhoods that had low levels of social capital. A high negative social climate in the neighborhood attenuated the positive association between preparation for bias/promotion of mistrust and externalizing problems.


Motor function domains in alternating hemiplegia of childhood.
To characterize motor function profiles in alternating hemiplegia of childhood, and to investigate interrelationships between these domains and with age. We studied a cohort of 23 patients (9 males, 14 females; mean age 9y 4mo, range 4mo-43y) who underwent standardized tests to assess gross motor, upper extremity motor control, motor speech, and dysphagia functions. Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure-88 (GMFM-88), Manual Ability Classification System (MACS), and Revised Melbourne Assessment (MA2) scales manifested predominantly mild impairments; motor speech, moderate to severe; Modified Dysphagia Outcome and Severity Scale (M-DOSS), mild-to moderate deficits. GMFCS correlated with GMFM-88 scores (Pearson's correlation, p=0.002), MACS (p=0.038), and MA2 fluency (p=0.005) and accuracy (p=0.038) scores. GMFCS did not correlate with motor speech (p=0.399), MA2 dexterity (p=0.247), range of motion (p=0.063), or M-DOSS (p=0.856). Motor speech was more severely impaired than the GMFCS (p<0.013). There was no correlation between any of the assessment tools and age (p=0.210-0.798). Our data establish a detailed profile of motor function in alternating hemiplegia of childhood, argue against the presence of worse motor function in older patients, identify tools helpful in evaluating this population, and identify oropharyngeal function as the more severely affected domain, suggesting that brain areas controlling this function are more affected than others.


Noncanonical Amino Acids for Hypoxia-Responsive Peptide Self-Assembly and Fluorescence.
Design of endogenous stimuli-responsive amino acids allows for precisely modulating proteins or peptides under a biological microenvironment and thereby regulating their performance. Herein we report a noncanonical amino acid 2-nitroimidazol-1-yl alanine and explore its functions in creation of the nitroreductase (NTR)-responsive peptide-based supramolecular probes for efficient hypoxia imaging. On the basis of the reduction potential of the nitroimidazole unit, the amino acid was synthesized via the Mitsunobu reaction between 2-nitroimidazole and a serine derivate. We elucidated the relationship between the NTR-responsiveness of the amino acid and the structural feature of peptides involving a series of peptides. This eventually facilitates development of aromatic peptides undergoing NTR-responsive self-assembly by rationally optimizing the sequences. Due to the intrinsic role of 2-nitroimidazole in the fluorescence quench, we created a morphology-transformable supramolecular probe for imaging hypoxic tumor cells based on NTR reduction. We found that the resulting supramolecular probes penetrated into solid tumors, thus allowing for efficient fluorescence imaging of tumor cells in hypoxic regions. Our findings demonstrate development of a readily synthesized and versatile amino acid with exemplified properties in creating fluorescent peptide nanostructures responsive to a biological microenvironment, thus providing a powerful toolkit for synthetic biology and development of novel biomaterials.