Radiologic diagnosis and surgical treatment of urethral diverticulum in women. A reappraisal of voiding cystourethrography and positive pressure urethrography.
To reappraise the optimum radiologic procedure for the diagnosis of urethral diverticula in women and to assess the results of surgery. From January 1994 to December 1997, 132 urine-continent women with pelvic prolapse and the most characteristic symptoms of urethral diverticulum underwent pelvic repair. In addition to routine urologic evaluations and pelvic examinations, the women underwent voiding cystourethrography (VCUG) and positive pressure urethrography (PPUG) with a double-balloon catheter. The x-ray examination was scheduled as follows. One hundred thirty-two women initially underwent VCUG followed by a PPUG. Another VCUG was subsequently performed on women with a negative PPUG finding. Twelve patients were excluded because they were unable to urinate for the first VCUG; thus, the study group was composed of the remaining 120 patients. Subsequently those patients underwent various pelvic operations, including total abdominal/vaginal hysterectomy, abdominal colposacropexy, Manchester's operation, sacrospinous ligament suspension, diverticulectomy and colporrhaphy. Both VCUG and PPUG were able to demonstrate the diverticula in 20 of the 120 women. Another 13 women showed positive findings on PPUG. Ten of the 87 cases with a negative PPUG had a positive finding in the subsequent VCUG. Forty-two diverticula were detected in 39 patients during pelvic repair. The only complication of urethral diverticulectomy was urethrovaginal fistula, which occurred in 3 of the 39 patients. Though VCUG is not as sensitive as PPUG, it still has merits and can be used as a screening test. If VCUG is inconclusive but clinical suspicion persists, particularly when PPUG is doubtful, magnetic resonance imaging should be considered.


Four beams evanescent waves interference lithography for patterning of two dimensional features.
This work presents a theoretical study of using the interference of multiple counter-propagating evanescent waves as a lithography technique to print periodic two dimensional features. The formulation of the three dimensional Cartesian space expression of an evanescent wave is presented. In this work, the evanescent wave is generated by the total internal reflection of a plane wave at the interface between a incident dielectric material and a weakly absorbing transmission medium. The influences of polarization, incident angle and the phase shifting of the incident plane waves on the evanescent wave interference are studied. Numerical simulation results suggest that this technique enables fabrication of periodic two dimensional features with resolution less than one third the wavelength of the irradiation source.


Is Oral/Text Reading Fluency a "Bridge" to Reading Comprehension?
In the present study we investigated developmental relations among word reading fluency, listening comprehension, and text reading fluency to reading comprehension in a relatively transparent language, Korean. A total of 98 kindergartners and 170 first graders in Korea were assessed on a series of tasks involving listening comprehension, word reading fluency, text reading fluency, and reading comprehension. Results from multigroup structural equation models showed that text reading fluency was a dissociable construct for both kindergartners and first graders. In addition, a developmental pattern emerged: listening comprehension was not uniquely related to text reading fluency for first graders, but not for kindergartners, over and above word reading fluency. In addition, text reading fluency was uniquely related to reading comprehension for kindergartners, but not for first graders, after accounting for word reading fluency and listening comprehension. For first graders, listening comprehension dominated the relations. There were no differences in the pattern of relations for skilled and less skilled readers in first grade. Results are discussed from a developmental perspective for reading comprehension component skills including text reading fluency.


[The specific nature of the irritability to fenitrothion and malathion in blood-sucking mosquitoes].
Several populations of malaria mosquitos were previously discovered to have different irritability to two insecticides of the organophosphorous group, such as fenitrothion and malathion. Individual comparison of fenitrothion and malathion irritability levels in laboratory colonies of Anopheles stephensi, An. atroparvus, Culex pipiens, Aedes aegypti, and Ae. togoi and in the natural population of An. martinius has shown that irritability to the two chemicals is specific in all the six species. This is probably due to recognizing the insecticide molecules by means of a so-called "living group" which has different structure in fenitrothion and malathion.


Exploring the Genome and Phenotype of Multi-Drug Resistant Klebsiella pneumoniae of Clinical Origin.
Klebsiella pneumoniae is an important nosocomial pathogen with an extraordinary resistant phenotype due to a combination of acquired resistant-elements and efflux mechanisms. In this study a detailed molecular characterization of 11 K. pneumoniae isolates of clinical origin was carried out. Eleven clinical isolates were tested for their susceptibilities, by disk diffusion and broth microdilution and interpreted according to CLSI guidelines. Efflux activity was determined by measuring the extrusion of ethidium bromide and biofilm formation was assessed following static growth in Müeller-Hinton and minimal media M9 broths at two temperatures and time points. Template DNA from all 11 isolates was extracted and sequenced. The study collection was found to be resistant to several (extended-spectrum beta-lactam) ESBL-type compounds along with several (fluoro)quinolones (FQ). Resistance to tetracycline accounted for 55% of the study collection (n = 6) and three of the 11 isolates were resistance to carbapenems. Genotyping identified blaCTX-M-15 (82%), blaSHV-12 (55%), and blaTEM-1B (45%) ESBL encoding genes and FQ resistance was associated the presence of the oqxAB operon, identified in 10 of the 11 isolates and qnrB gene in one isolate. The polymorphisms detected in the quinolone resistance-determining regions (QRDRs) were associated with isolates of the clonal group CG15. Sequence types (ST) identified were representative of previously described clonal groups including CG258 (n = 7), CG15 (n = 3), and CG147 (n = 1). Plasmid replicon type databases were queried indicating the presence of IncFII and IncFIB replicon types in the majority of the isolates (91%), followed by IncFIA (45%), and IncR (45%). Two of the 11 isolates were found positive for yersiniabactin siderophore-encoding genes. No differences in the ability to efflux ethidium bromide were identified. Biofilm formation was stronger when the isolates were grown under stressed conditions at 37°C for a period up to 96 h. These data confirm the fact that well-recognized clonal groups of K. pneumoniae of importance to human health carries a diverse repertoire of antimicrobial resistance determinants, particularly related to critically important drugs in the ESBL and FQ classes. The capacity of most isolates to form strong biofilms, when stressed under laboratory-simulated conditions, supports the risk to human health associated with nosocomial infections deriving from indwelling medical devices.


High plasma TIMP-1 and serum CEA levels during combination chemotherapy for metastatic colorectal cancer are significantly associated with poor outcome.
To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival. Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy. Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment. Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.


Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide.
Second-order middle cerebral arteries (135.0 +/- 4.6 microns ID) from male, female, ovariectomized female (no endogenous estrogen), and estrogen-treated ovariectomized female Sprague-Dawley rats were harvested and mounted in a pressure myograph. Myogenic response was recorded over a pressure range of 10-100 mmHg and was repeated in the presence of N omega-nitro-L-arginine methyl ester (L-NAME; 2 x 10(-4) M, an inhibitor of nitric oxide (NO) synthase, and after endothelium removal, to examine the contribution of NO to net myogenic tone. With intact endothelium, there were no differences in myogenic tone between the groups, but in the presence of L-NAME and after endothelium removal, estrogen-exposed vessels developed significantly greater tone at-high transmural pressure. There were no differences in sensitivity to sodium nitroprusside, an NO donor, or A-23187, a calcium ionophore. These results suggest an increase in basal release of NO in cerebral arteries exposed to estrogen, without change in NO sensitivity or maximally stimulated NO release.


A Hierarchical Bayesian Mixture Model Approach for Analysis of Resting-State Functional Brain Connectivity: An Alternative to Thresholding.
This article proposes a Bayesian hierarchical mixture model to analyze functional brain connectivity where mixture components represent "positively connected" and "non-connected" brain regions. Such an approach provides a data-informed separation of reliable and spurious connections in contrast to arbitrary thresholding of a connectivity matrix. The hierarchical structure of the model allows simultaneous inferences for the entire population as well as for each individual subject. A new connectivity measure, the posterior probability of a given pair of brain regions of a specific subject to be connected given the observed correlation of regions' activity, can be computed from the model fit. The posterior probability reflects the connectivity of a pair of regions relative to the overall connectivity pattern of an individual, which is overlooked in traditional correlation analyses. This article demonstrates that using the posterior probability might diminish the effect of spurious connections on inferences, which is present when a correlation is used as a connectivity measure. In addition, simulation analyses reveal that the sparsification of the connectivity matrix using the posterior probabilities might outperform the absolute thresholding based on correlations. Therefore, we suggest that posterior probability might be a beneficial measure of connectivity compared with the correlation. The applicability of the introduced method is exemplified by a study of functional resting-state brain connectivity in older adults.


Effectiveness of practices for improving the diagnostic accuracy of Non ST Elevation Myocardial Infarction in the Emergency Department: A Laboratory Medicine Best Practices™ systematic review.
This article is a systematic review of the effectiveness of four practices (assay selection, decision point cardiac troponin (cTn) threshold selection, serial testing, and point of care testing) for improving the diagnostic accuracy Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) in the Emergency Department. The CDC-funded Laboratory Medicine Best Practices (LMBP) Initiative systematic review method for quality improvement practices was used. The current ACC/AHA guidelines recommend using cardiac troponin assays with a 99th percentile upper reference limit (URL) diagnostic threshold to diagnose NSTEMI. The evidence in this systematic review indicates that contemporary sensitive cTn assays meet the assay profile requirements (sensitivity, specificity, PPV, and NPV) to more accurately diagnose NSTEMI than alternate tests. Additional biomarkers did not increase diagnostic effectiveness of cTn assays. Sensitivity, specificity, and NPV were consistently high and low PPV improved with serial sampling. Evidence for use of point of care cTn testing was insufficient to make recommendation, though some evidence suggests that use may result in reduction to patient length of stay and costs. Based on the review of and the LMBP(TM) A-6 Method criteria, we recommend the use of cardiac troponin assays without additional biomarkers using the 99th percentile URL as the clinical diagnostic threshold for the diagnosis of NSTEMI. We recommend serial sampling with one sample at presentation and at least one additional second sample taken at least 6h later to identify a rise or fall in the troponin level. No recommendation is made either for or against the use of point of care tests. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry (CDC/ATSDR).


Study of type a and B behavior patterns in patients with multiple sclerosis in an Iranian population.
In adults, throughout life, uniqueness maintains the equivalent; but, it might be tailored in the track of neurological disarrays. As in the partition of cognitive function associated with multiple sclerosis (MS), numerous studies have been performed, but there are very few reports in this area of behavior. The aim of this study was to investigate the prevalence of personality types A and B in relation to individuals' behaviors with MS and type A behavior with demographic characteristics and the level of disability. A cross-sectional descriptive study was performed between September 2010 and March 2011 on 50 patients who were referred to MS clinic (located at the Kashani hospital), Isfahan Neurosciences Research Centre (INRC). The subjects were evaluated using Friedman and Rosenman questioner and the Expanded Disability Status Scale (EDSS). The data were analyzed by SPSS software (version 17) based on Chi-square test and independent T-test. Of the subjects, 65% were of personality type A and 35% were of personality type B (X2: 3.5, P < 0.05). There were no significant differences in individuals with type A behavior in relation to gender and marital status. In connection to EDSS (EDSS < 4.5 or EDSS > 4.5), patients with higher EDSS score, i.e., individuals with EDSS > 4.5 mostly had type A behavior pattern. People with type A behavior pattern are reported to have more stress, nervousness, and anxiety. In this study, MS patients had more characteristics of type A than type B behavior. This behavior was increased in individuals with EDSS score > 4.5.


Sustained effects of transdermal nitroglycerin in patients with angina pectoris.
The antianginal efficacy of a transdermal therapeutic delivery system for nitroglycerin (TNG) was compared with that of placebo in a double-blind crossover study. Twenty-five patients with stable angina pectoris were evaluated. The transdermal system delivered 5 mg of nitroglycerin over a 24-hour period and was applied once every 48 hours. Treadmill exercise testing (Bruce protocol) was done 48 hours after the patch was applied in the first phase of the crossover and at the conclusion of the second phase of the crossover, 48 hours after the final dose of the second treatment. Exercise performance was significantly improved (P less than 0.05, analysis of covariance) with TNG as compared with placebo, as were frequency of episodes of angina and nitroglycerin consumption (P less than 0.05, analysis of variance). The incidence of mild-to-moderate headache in patients was greater during treatment with TNG (20%) than during placebo treatment (6.7%). Four cases of mild transient dermatitis and occasional reports of dizziness, lightheadedness, and nausea were noted.


Primary and Chronic HIV Infection Differently Modulates Mucosal Vδ1 and Vδ2 T-Cells Differentiation Profile and Effector Functions.
Gut-associated immune system has been identified as a major battlefield during the early phases of HIV infection. γδ T-cells, deeply affected in number and function after HIV infection, are able to act as a first line of defence against invading pathogens by producing antiviral soluble factors and by killing infected cells. Despite the relevant role in mucosal immunity, few data are available on gut-associated γδ T-cells during HIV infection. Aim of this work was to evaluate how primary (P-HIV) and chronic (C-HIV) HIV infection affects differentiation profile and functionality of circulating and gut-associated Vδ1 and Vδ2 T-cells. In particular, circulating and mucosal cells were isolated from respectively whole blood and residual gut samples from HIV-infected subjects with primary and chronic infection and from healthy donors (HD). Differentiation profile and functionality were analyzed by multiparametric flow cytometry. P-HIV and C-HIV were characterized by an increase in the frequency of effector Vδ1-T cells both in circulating and mucosal compartments. Moreover, during P-HIV mucosal Vδ1 T-cells expressed high levels of CD107a, suggesting a good effector cytotoxic capability of these cells in the early phase of infection that was lost in C-HIV. P-HIV induced an increase in circulating effector Vδ2 T-cells in comparison to C-HIV and HD. Notably, P-HIV as well as HD were characterized by the ability of mucosal Vδ2 T-cells to spontaneously produce IFN-γ that was lost in C-HIV. Altogether, our data showed for the first time a functional capability of mucosal Vδ1 and Vδ2 T-cells during P-HIV that was lost in C-HIV, suggesting exhaustion mechanisms induced by persistent stimulation.


Five-year report on partial ossicular replacement prostheses and total ossicular replacement prostheses.
Although much progress has been achieved in the functional restoration of ears damaged by chronic suppurative otitis media since the introduction of tympanoplasty 30 years ago, adequate hearing improvements in ears with loss of the stapedial arch have been the most elusive. It is now recognized that such ears present the surgeon with numerous associated problems that require control for a satisfactory outcome; the problem of establishing an efficient link between the tympanic membrane and oval window has proved the most difficult. The introduction of biocompatible materials was heralded as a possible solution. In order to evaluate the claims for these new materials, the five-year results obtained with one of these, porous polyethylene, were evaluated. The one-year success rate with partial ossicular replacement prostheses was 64%; the five-year success rate was 43%. With total ossicular replacement prostheses the success rate was 59% at one year and 22% at five years. These poor results, coupled with evidence of digestion of porous polyethylene, give little justification for the continued use of this material in tympanoplasty.


Surgical and medical treatment options for urge incontinence.
As the population ages, urinary incontinence is becoming an important health issue. In the United States, urinary incontinence had an estimated annual cost of $26 billion in 1995. The author presents a literature review to inform primary care physicians about the most current medical and surgical treatment of urge incontinence. Developments in medical research have produced oral medications that are increasingly effective in controlling the symptoms of urge incontinence. This advance has resulted in a decreasing need for surgical intervention. Although surgical therapy has not been proven to be as effective as oral medications in the treatment of urge incontinence, it is still considered to be a viable therapy in select patient populations.


Failure of ipratropium bromide to modify the diurnal variation of asthma in asthmatic children.
Thirty one children with asthma were given 40 micrograms of ipratropium bromide and identical placebo by inhalation three times a day in a double blind, randomised crossover study to test the ability of an anticholinergic drug to modify the diurnal variation in airway calibre and bronchial reactivity. Subjects measured peak expiratory flow rate approximately eight hourly, before and after inhaled salbutamol, for four week periods. Paired t tests and cosinor analysis were used to assess the diurnal variation in airway calibre from the peak expiratory flow rate recorded before salbutamol and to assess the diurnal variation in bronchodilator responsiveness from the increase in peak expiratory flow rate after salbutamol. Maintenance treatment with ipratropium bromide 40 micrograms three times daily reduced the provocative dose of histamine which caused a 20% fall in FEV1 (geometric mean PD20 = 0.78 v 0.49 mg/ml, p less than 0.05), despite an eight to 12 hour gap between the last dose of ipratropium and histamine challenge. It did not, however, diminish the diurnal variation in airway calibre (mean amplitude = 12.7 v 10.1) or in bronchodilator responsiveness (mean amplitude = 62.4 v 63.5). There was no improvement in the clinical state of subjects while they were taking ipratropium bromide.


Social relationships, leisure activity, and health in older adults.
Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modeling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults.


Importance of peers and dating in the development of romantic relationships and sexual activity of young adults with cerebral palsy.
The aim of this study was to describe the peer group activities, romantic relationships, and sexual activity and their interrelations of young adults with cerebral palsy (CP). A cross-sectional study was performed in 87 participants (51 males, 36 females; mean age 20 y 4 mo, SD 1 y 3 mo range age 18-22 y) without cognitive disabilities. Ninety-four per cent had spastic CP and 49% unilateral CP, while 78% were classified at Gross Motor Function Classification System level I and 84% at Manual Ability Classification System level I. Peer group activities, dating, romantic relationships, and sexual activity were assessed with an interview and questionnaire. Associations were analysed using logistic regression analyses. The study cohort reported having friends and participating in activities with peers; 71% had experience of dating, 23% had a current romantic relationship, and 38% had experience of intercourse. Young adults with CP had less experience in romantic and sexual relationships than an age-appropriate Dutch reference population. Peer group activities and dating favoured development of romantic relationships and sexual activity. Older age was associated with greater sexual activity. Motor functioning, education level, and gender did not correlate with romantic relationships or sexual activity. Being involved in peer group activities and creating a context to arrange dates seems relevant for young adults with CP to develop romantic relationships and sexual activity.


The endocannabinoid anandamide causes endothelium-dependent vasorelaxation in human mesenteric arteries.
The endocannabinoid anandamide (AEA) causes vasorelaxation in animal studies. Although circulating AEA levels are increased in many pathologies, little is known about its vascular effects in humans. The aim of this work was to characterise the effects of AEA in human arteries. Ethical approval was granted to obtain mesenteric arteries from patients (n=31) undergoing bowel resection. Wire myography was used to probe the effects and mechanisms of action of AEA. RT-PCR was used to confirm the presence of receptor mRNA in human aortic endothelial cells (HAECs) and intracellular signalling proteins were measured using multiplex technology. AEA caused vasorelaxation of precontracted human mesenteric arteries with an Rmax of ∼30%. A synthetic CB1 agonist (CP55940) caused greater vasorelaxation (Rmax ∼60%) while a CB2 receptor agonist (HU308) had no effect on vascular tone. AEA-induced vasorelaxation was inhibited by removing the endothelium, inhibition of nitric oxide (NO) synthase, antagonising the CB1 receptor and antagonising the proposed novel endothelial cannabinoid receptor (CBe). AEA-induced vasorelaxation was not affected by CB2 antagonism, by depleting sensory neurotransmitters, or inhibiting cyclooxygenase activity. RT-PCR showed CB1 but not CB2 receptors were present in HAECs, and AEA and CP55940 had similar profiles in HAECs (increased phosphorylation of JNK, NFκB, ERK, Akt, p70s6K, STAT3 and STAT5). Post hoc analysis of the data set showed that overweight patients and those taking paracetamol had reduced vasorelaxant responses to AEA. These data show that AEA causes moderate endothelium-dependent, NO-dependent vasorelaxation in human mesenteric arteries via activation of CB1 receptors.


Ethanol potently and competitively inhibits binding of the alcohol antagonist Ro15-4513 to alpha4/6beta3delta GABAA receptors.
Although GABA(A) receptors have long been implicated in mediating ethanol (EtOH) actions, receptors containing the "nonsynaptic" delta subunit only recently have been shown to be uniquely sensitive to EtOH. Here, we show that delta subunit-containing receptors bind the imidazo-benzodiazepines (BZs) flumazenil and Ro15-4513 with high affinity (K(d) < 10 nM), contrary to the widely held belief that these receptors are insensitive to BZs. In immunopurified native cerebellar and recombinant delta subunit-containing receptors, binding of the alcohol antagonist [(3)H]Ro15-4513 is inhibited by low concentrations of EtOH (K(i) approximately 8 mM). Also, Ro15-4513 binding is inhibited by BZ-site ligands that have been shown to reverse the behavioral alcohol antagonism of Ro15-4513 (i.e., flumazenil, beta-carbolinecarboxylate ethyl ester (beta-CCE), and N-methyl-beta-carboline-3-carboxamide (FG7142), but not including any classical BZ agonists like diazepam). Experiments that were designed to distinguish between a competitive and allosteric mechanism suggest that EtOH and Ro15-4513 occupy a mutually exclusive binding site. The fact that only Ro15-4513, but not flumazenil, can inhibit the EtOH effect, and that Ro15-4513 differs from flumazenil by only a single group in the molecule (an azido group at the C7 position of the BZ ring) suggest that this azido group in Ro15-4513 might be the area that overlaps with the alcohol-binding site. Our findings, combined with previous observations that Ro15-4513 is a behavioral alcohol antagonist, suggest that many of the behavioral effects of EtOH at relevant physiological concentrations are mediated by EtOH/Ro15-4513-sensitive GABA(A) receptors.


Case file coding of child maltreatment: Methods, challenges, and innovations in a longitudinal project of youth in foster care.
State social service agency case files are a common mechanism for obtaining information about a child's maltreatment history, yet these documents are often challenging for researchers to access, and then to process in a manner consistent with the requirements of social science research designs. Specifically, accessing and navigating case files is an extensive undertaking, and a task that many researchers have had to maneuver with little guidance. Even after the files are in hand and the research questions and relevant variables have been clarified, case file information about a child's maltreatment exposure can be idiosyncratic, vague, inconsistent, and incomplete, making coding such information into useful variables for statistical analyses difficult. The Modified Maltreatment Classification System (MMCS) is a popular tool used to guide the process, and though comprehensive, this coding system cannot cover all idiosyncrasies found in case files. It is not clear from the literature how researchers implement this system while accounting for issues outside of the purview of the MMCS or that arise during MMCS use. Finally, a large yet reliable file coding team is essential to the process, however, the literature lacks training guidelines and methods for establishing reliability between coders. In an effort to move the field toward a common approach, the purpose of the present discussion is to detail the process used by one large-scale study of child maltreatment, the Studying Pathways to Adjustment and Resilience in Kids (SPARK) project, a longitudinal study of resilience in youth in foster care. The article addresses each phase of case file coding, from accessing case files, to identifying how to measure constructs of interest, to dealing with exceptions to the coding system, to coding variables reliably, to training large teams of coders and monitoring for fidelity. Implications for a comprehensive and efficient approach to case file coding are discussed.


Study on the Autonomous Non-contact Measurement of Biometric Signals.
In this study, we developed a robot that can recognize and track a person, and autonomously measure two biological signals, respiration rate and heart rate, in a non-contact manner. Through experiments, we confirmed that both signals can be measured with high accuracy and that the robot can perform the measurement under conditions similar to those in actual workplaces. We also investigated factors that can affect the accuracy of the non-contact measurement and studied a method to evaluate the reliability of the measured signals.


Factors responsible for increased excitability of dentate gyrus granule cells during exposure to lindane.
Rats were anesthetized with urethane, implanted with stimulating and recording electrodes in the perforant path and dentate gyrus, and exposed to different doses of lindane. Analysis of evoked field potential responses indicated that lindane exposure resulted in consistent, dose-dependent changes. Two separable effects were observed. First, lindane produced a small increase in the field excitatory postsynaptic potential (EPSP). Second, lindane produced much more significant effects upon granule cell excitability as evidenced by decreased threshold for evoking the field population spike (PS), increased amplitude of the PS and decreased latencies to PS onset and to peak. An analysis of these data suggests that presynaptic actions, e.g., increased transmitter release from perforant path terminals, do not appear to play an important role in the increased responsivity of granule cells. The most important factor appears to be a dose-dependent increase in the excitability of the granule cell due to other causes. In comparable studies, other subjects were prepared similarly and tested with other convulsive agents. Comparison of lindane to other convulsants revealed that lindane mimicked the changes produced in dentate gyrus responses by GABA antagonist drugs including picrotoxin, pentylenetetrazol and bicuculline. The glycine antagonist, strychnine, produced a different spectrum of effects. The data lend support to the hypothesis that an interaction of lindane with the GABA receptor-chloride channel complex is an important mechanism underlying both subconvulsant and convulsant actions. A reduction in tonic, GABA-mediated inhibition may be the basis for the increase in intrinsic granule cell excitability.


Genomic profiling reveals mutational landscape in parathyroid carcinomas.
Parathyroid carcinoma (PC) is an extremely rare malignancy lacking effective therapeutic intervention. We generated and analyzed whole-exome sequencing data from 17 patients to identify somatic and germline genetic alterations. A panel of selected genes was sequenced in a 7-tumor expansion cohort. We show that 47% (8 of 17) of the tumors harbor somatic mutations in the CDC73 tumor suppressor, with germline inactivating variants in 4 of the 8 patients. The PI3K/AKT/mTOR pathway was altered in 21% of the 24 cases, revealing a major oncogenic pathway in PC. We observed CCND1 amplification in 29% of the 17 patients, and a previously unreported recurrent mutation in putative kinase ADCK1. We identified the first sporadic PCs with somatic mutations in the Wnt canonical pathway, complementing previously described epigenetic mechanisms mediating Wnt activation. This is the largest genomic sequencing study of PC, and represents major progress toward a full molecular characterization of this rare malignancy to inform improved and individualized treatments.


Investigation of human papillomavirus in transitional cell carcinomas of the urinary bladder in South Africa.
To investigate the prevalence of human papillomavirus in transitional cell carcinoma of the urinary bladder in South Africa. Ninety-one archival samples of bladder transitional cell carcinoma were subjected to polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. HPV was detected in only one case with PCR. HPV was not detected in any of the cases subjected to the NISH system. This study shows that although HPV has been shown to be associated with uterine cervical and esophageal squamous cell carcinomas in South Africa, this virus is not present in the transitional cell carcinoma of the urinary bladder in this geographical location. It is suggested that other factors, including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events, may play a role in the carcinogenesis of this neoplasm in the bladder.


Prediction of severe complications and death in superobese patients undergoing open gastric bypass with the Recife Score.
Superobese patients who undergo gastric bypass have a greater incidence of complications. The greater incidence of comorbidity in this group leads to a higher surgical risk, and a need for special care. By analyzing the risk factors identified in the preoperative period, scoring them, constructing a score and assessing the occurrence of serious complications and death, we will have elements to identify which patients are at greater risk. To determine the accuracy of the Recife Score for predicting serious postoperative complications and death in superobese patients who undergo Roux-en-Y gastric bypass surgery by the conventional method. An ambidirectional study was conducted to validate the diagnostic test on 203 severely obese patients submitted to Roux-en-Y gastric bypass at the Hospital das Clínicas of the Federal University of Pernambuco, Recife, PE, Brazil, from September 1997 to May 2007. The dependent variables were major postoperative complications and death. The independent variable was the Recife Score. The data were analyzed using the Epi-Info 3.5.1 program. The accuracy of the Recife Score was analyzed considering the following parameters: sensitivity, specificity, positive predictive value, negative predictive value, positive verisimilitude ratio and negative verisimilitude ratio. The accuracy of the Recife Score with cut-off points higher than 3 and higher than 5 to predict serious postoperative complications was, respectively, a frequency of complications of 12.3%, with a risk ratio of 2.83, sensitivity of 57.1% and specificity of 69.8%, and 12.5%, with a risk ratio of 1.88, sensitivity of 7.1% and specificity of 96.3%. The accuracy of the Recife Score with cut-off points higher than 3 and higher than 5 to predict death was, respectively, a frequency of death of 7.7%, with a risk ratio of 10.62, sensitivity of 83.3% and specificity of 69.5%, and 12.5%, with a risk ratio of 4.88, sensitivity of 16.7% and specificity of 96.5%. A Recife Score >3 prior to conventional gastric bypass presents a high level of accuracy in the prediction of serious postoperative complications and death.


Triggering mechanism of B lymphocytes. II. Induction of ornithine decarboxylase in B cells by anti-immunoglobulin and enhancing soluble factor.
In vitro stimulation of rabbit lymphocytes with anti-immunoglobulin antibody (anti-Ig) induced ornithine decarboxylase (ODC) (EC126.96.36.199) in the cells. The enzyme activity reached the maximum at 8 hr after stimulation of the cell with antibody and returned to the unstimulated level after 20 hr. The optimum concentration of antibody to produce the maximum activity of ODC was 25 mug/ml, which was in the same range that required for the maximum production of IgG and the highest rate of DNA synthesis. ODC was again induced with soluble factor (SF) in the cells that had been previously treated with anti-Ig antibody for 24 hr. The treatment of the cells with anti-thymocyte serum and complement did not affect the activity of the enzyme induced by anti-Ig or by SF, indicating that enzyme induction was an event occurring in B cells and not in T cells. The addition of mitotic inhibitors, such as hydroxy-urea (HU) or cytosine arabinoside (Ara-C), to the culture with anti-Ig did not inhibit the production of ODC. The presence of cytochalasin-B with anti-Ig did not inhibit, but rather enhanced, the synthesis of ODC. On the other hand, the presence of HU or cytochalasin-B with soluble factor completely suppressed the induction ODC. These results suggested that intracellular events that trigger the induction of ODC by the interaction of Ig receptor with anti-Ig may be different from the events that induce the same enzyme triggered by SF.


Effects of shock wave lithotripsy on plasma and urinary levels of nitrite and adrenomedullin.
In this prospective clinical study, we aimed to determine whether shockwave lithotripsy (SWL) has any specific effect on plasma as well as urinary nitrite, a stabile metabolite of nitric oxide (NO) and adrenomedullin (AM) concentrations, and to investigate whether these variables can be used as a marker for detecting shockwave-induced impairment of renal tubular and glomerular cells. A total of 20 patients with renal pelvic or caliceal stones < or =2 cm undergoing anesthesia-free SWL without auxiliary measures and a control group of ten patients without any urological symptoms were included in this study. The plasma and urinary concentrations of nitrite and AM were measured before, 24 h, and 7 days after SWL. Nitrite levels were measured by Griess reaction. Reverse-phase high-performance liquid chromatography (HPLC) was used to determine AM levels. Application of high-energy shock waves (HESW) in our study caused a statistically significant increase in plasma levels of both NO and AM, which reflected an organized response of the kidney to this type of trauma in an attempt to maintain normal renal hemodynamics. Mean plasma nitrite concentration before SWL application was 29.9+/-7.6 micromol/l and this value was found to be 39.02+/-8.45 micromol/l at 24-h follow-up. Comparative evaluation of the plasma concentrations of AM revealed a significant increase at the 24-h examination: 20.51+/-3.0 pmol/ml and 32.54+/-4.3 pmol/l, respectively. On the other hand, comparative evaluation of urinary levels of both nitrite and AM levels before as well as 24 h after SWL application revealed a statistically significant increase related to markers. This first clinical study on plasma-urinary nitrite and AM levels in patients undergoing the SWL procedure indicated that plasma and urine levels of both peptides were increased. Our findings in turn suggested that SWL application to kidney can stimulate the NO-cGMP signalling pathway to increase NO production in the kidney. Our findings also indicated that the increased levels of NO and AM secretion during renal parenchymal ischemia may be protective enough for renal pathological alterations resulting from SWL-induced renal trauma. We suggest that this increase may be a compensatory response to SWL induced injury.


The effects of disease dispersal and host clustering on the epidemic threshold in plants.
For an epidemic to occur in a closed population, the transmission rate must be above a threshold level. In plant populations, the threshold depends not only on host density, but on the distribution of hosts in space. This paper presents an alternative analysis of a previously presented stochastic model for an epidemic in continuous space (Bolker, 1999, Bull. Math. Biol. 61, 849-874). A variety of moment closures are investigated to determine the dependence of the epidemic threshold on host spatial distribution and pathogen dispersal. Local correlations that arise during the early phase of the outbreak determine whether a true global epidemic will occur.


Expression patterns of Pax6 and Pax7 in the adult brain of a urodele amphibian, Pleurodeles waltl.
Expression patterns of Pax6, Pax7, and, to a lesser extent, Pax3 genes were analyzed by a combination of immunohistochemical techniques in the central nervous system of adult specimens of the urodele amphibian Pleurodeles waltl. Only Pax6 was found in the telencephalon, specifically the olfactory bulbs, striatum, septum, and lateral and central parts of the amygdala. In the diencephalon, Pax6 and Pax7 were distinct in the alar and basal parts, respectively, of prosomere 3. The distribution of Pax6, Pax7, and Pax3 cells correlated with the three pretectal domains. Pax7 specifically labeled cells in the dorsal mesencephalon, mainly in the optic tectum, and Pax6 cells were the only cells found in the tegmentum. Large populations of Pax7 cells occupied the rostral rhombencephalon, along with lower numbers of Pax6 and Pax3 cells. Pax6 was found in most granule cells of the cerebellum. Pax6 cells also formed a column of scattered neurons in the reticular formation and were found in the octavolateral area. The rhombencephalic ventricular zone of the alar plate expressed Pax7. Dorsal Pax7 cells and ventral Pax6 cells were found along the spinal cord. Our results show that the expression of Pax6 and Pax7 is widely maintained in the brains of adult urodeles, in contrast to the situation in other tetrapods. This discrepancy could be due to the generally pedomorphic features of urodele brains. Although the precise role of these transcription factors in adult brains remains to be determined, our findings support the idea that they may also function in adult urodeles.


Leishmaniasis: new insights from an old and neglected disease.
Leishmaniases are a clinically heterogeneous group of diseases caused by protozoa of the genus Leishmania. There is growing evidence that the true incidence of the disease is underestimated, especially in hyperendemic regions. Moreover, climate changes together with the increasing movement of humans and animals raise concerns about the possible introduction of Leishmania infection in previously spared areas. The disease is emerging in immunocompromised patients undergoing bone marrow or solid organ transplantation or treatment with biologic drugs. Furthermore, the deployment of military troops and travel to endemic areas are associated with the observation of a growing number of patients with cutaneous disease. Improvement in diagnostic methods, both in the field and in specialized laboratories, has been obtained through the implementation of molecular amplification methods and using the rK39 antigen as the substrate. Finally, new therapeutic approaches are gaining attention, such as the use of miltefosine for cutaneous leishmaniasis and paromomycin for visceral leishmaniasis, as well as the use of various antileishmanial drugs in combination.


Breath-holding during the Calibration Scan Improves the Reproducibility of Parallel Transmission at 7T for Human Brain.
The B0 and B1+ maps required for calculation of the radiofrequency (RF) pulse of parallel transmission (pTx) are obtained in calibration scans; however, they may be affected by respiratory motion. We aimed to compare the reproducibility of B0 and B1+ maps and gradient echo (GRE) images of the brain scanned with pTx at 7T between free-breathing (FB) and breath-holding (BH) conditions during the calibration scan. Nine healthy volunteers were scanned by 7T MRI using a two-channel quadrature head coil. In the pTx calibration scans performed with FB and BH, the B0 map was obtained from two different TE images and the B1+ map was calculated by the Bloch-Siegert method. A GRE image (gradient-recalled-acquisition in steady state) was also obtained with RF shimming and RF design of pTx with spoke method, as well as quadrature transmission (qTx). All the scans were repeated over five sessions. The reproducibility of the B0 and B1+ maps and GRE image was evaluated with region-of-interest measurements using inter-session standard deviation (SD) and coefficient of variation (CV) values. Intensity homogeneity of GRE images was also assessed with in-plane CV. Inter-session SDs of B0 and B1+ maps were significantly smaller in BH (P < 0.01). Inter-session CVs of GRE images were significantly smaller in qTx than BH and FB (P < 0.01, both); however, the CVs of BH were significantly smaller (P < 0.01). In-plane CVs of FB and BH with RF shimming were not significantly different with qTx; however, CVs of FB and BH with RF design were significantly smaller than those of qTx (P < 0.05 and P < 0.01, respectively). BH could improve the reproducibility of B0 and B1+ maps in pTx calibration scans and GRE images. These results might facilitate the development of pTx in human brain at 7T.


Post-traumatic osteochondritis of the lateral sesamoid in active adolescents.
Many authors believe that osteochondritis occurs more frequently in the medial sesamoid than in the lateral. The authors of this paper discuss three cases of fibular sesamoid fracture in adolescents that they believe have progressed secondarily to osteochondritis.


Population-based analysis of POT1 variants in a cutaneous melanoma case-control cohort.
Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein-telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies.


Cross-sectional survey of patients, caregivers, and physicians on diagnosis and treatment of brain metastases.
The development of brain metastases (BM) is one of the most feared complications of cancer due to the substantial neurocognitive morbidity and a grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have demonstrated promising intracranial response rates for tumors of multiple histologies. As overall survival for these patients improves, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been an adequate study to specifically explore these questions of survivorship and practice standardization for patients with advanced cancer and BM. Here, we present results from a cross-sectional survey in which we analyze responses from 237 patients, 209 caregivers, and 239 physicians to identify areas of improvement in the clinical care of BM. In comparing physician and patient/caregiver responses, we found a disparity in the perceived discussion of topics pertaining to important aspects of BM clinical care. We identified variability in practice patterns for this patient population between private practice and academic physicians. Many physicians continue to have patients with BM excluded from clinical trials. Finally, we obtained patient/physician recommendations on high-yield areas for federal funding to improve patient quality of life. By identifying potential areas of unmet need, we anticipate this wealth of actionable information will translate into tangible benefits for both patients and caregivers. Future studies are needed to validate our findings.


[Between being born "alive" and being born "alive and vital": the clinical evaluation of viability].
This paper reviews the definition of stillbirth and its clinical implications in assessing survivability outside the womb. The World Health Organization's definition of stillbirth and its epidemiological purposes are taken into account, together with a brief review of the international opinions regarding the medical assessment of the presence of life signs at birth.


Antibiotics in the agricultural soils from the Yangtze River Delta, China.
This study focused on the occurrence and spatial distribution of 13 common antibiotics in the agricultural soils of the Yangtze River Delta (YRD), China. Antibiotics were detected in all the 241 soil samples (i.e., 100% detection rate) with the total concentrations ranging from 4.55 to 2,010 ng/g dry weight. The concentrations of three antibiotic classes decreased in the order: quinolones (mean 48.8 ng/g) > tetracyclines (mean 34.9 ng/g) > sulfonamides (mean 2.35 ng/g). Ciprofloxacin was the prevalent compound with a mean concentration of 27.7 ng/g, followed by oxytetracycline (mean of 18.9 ng/g). A distinct spatial distribution was observed, where high concentrations of antibiotics were detected in the sites adjacent to the livestock and poultry farms. The potential sources of antibiotics in the agricultural soils were the application of manure and wastewater irrigation in this region. Risk assessment for single antibiotic compound indicated that tetracyclines and quinolones could pose a potential risk, in which doxycycline and ciprofloxacin had the most severe ecological effect in the agricultural soils. Antibiotic resistance genes (ARGs), such as tetA, sulI, and qnrS, were detected in 15 analyzed soil samples, and sulI showed significant correlations with quinolones, tetracyclines, copper, and zinc. Further studies on the distribution of other ARGs in agricultural soil at a region-scale are needed for the risk management of extensively used antibiotics and major ARGs.


Identification of Novel and Early Biomarkers for Cisplatin-induced Nephrotoxicity and the Nephroprotective Role of Cimetidine using a Pharmacometabolomic-based Approach Coupled with In Vitro Toxicodynamic Modeling and Simulation.
Cisplatin is widely used for the treatment of various types of cancer. However, cisplatin-induced nephrotoxicity (CIN) is frequently observed in patients receiving cisplatin therapy which poses a challenge in its clinical utility. Currently used clinical biomarkers for CIN are not adequate for early detection of nephrotoxicity, hence there is a need to identify potential early biomarkers in predicting CIN. In the current study, a combination of in vitro toxicodynamic (TD) modeling and untargeted global metabolomics approach was used to identify novel potential metabolite biomarkers for early detection of CIN. In addition, we investigated the protective role of cimetidine (CIM), an inhibitor of the organic cation transporter 2 (OCT2), in suppressing CIN. We first characterized the time-course of nephrotoxic effects of cisplatin (CIS) and the protective effects of CIM in a human pseudo-immortalized renal proximal tubule epithelial cell line (RPTEC), SA7K cell line. Secondly, we used a mathematical cell-level, in vitro TD modeling approach to quantitatively characterize the time-course effects of CIS and CIM as single agents and combination in SA7K cells. Based on the experimental and modeling results, we selected relevant concentrations of CIS and CIM for our metabolomics study. With the help of PCA (Principal Component Analysis) and PLS-DA (Projection to Latent Structure - Discriminate Analysis) analyses, we confirmed global metabolome changes for different groups (CIS, CIM, CIS+CIM vs control) in SA7K cells. Based on the criterion of a p-value ≤ 0.05 and a fold change ≥ 2 or ≤ 0.5, we identified 20 top metabolites that were significantly changed during the early phase i.e. within first 12 h of CIS treatment. Finally, pathway analysis was conducted that revealed the key metabolic pathways that were most impacted in CIN.


Use of angiotensin receptor blockers and the risk of cancer.
A recent meta-analysis of randomized trials suggested that use of angiotensin receptor blockers (ARBs) may be associated with a modestly increased risk of incident cancer, particularly lung cancer. We linked individual-level data from Danish registries on filled drug prescriptions, diagnostic information, and covariates. In a nationwide cohort of new users of ARBs and angiotensin-converting enzyme inhibitors ≥35 years of age during 1998 to 2006, we compared incidence rates of all cancer, cancer subgroups by anatomic site, and cancer mortality. Among 107 466 ARB users, 3954 cases of cancer were detected during 312 753 person-years of follow-up compared with 6214 cases during 435 207 person-years of follow-up in 209 692 angiotensin-converting enzyme inhibitor users (adjusted rate ratio, 0.99; 95% confidence interval, 0.95 to 1.03). Cancer risk did not increase with increasing duration of ARB exposure (increase in rate ratio per year, 0.99; 95% confidence interval, 0.99 to 1.00,) and was similar across individual ARBs. In subgroup analyses, there was a significant association between ARB use and cancer of male genital organs (rate ratio, 1.15; 95% confidence interval, 1.02 to 1.28), but no significantly increased risk of any of the other 15 cancer subgroups, including lung cancer (rate ratio, 0.92; 95% confidence interval, 0.82 to 1.02). For cancer mortality, the rate ratio was 0.77 (95% confidence interval, 0.72 to 0.82). In this large nationwide cohort, use of ARBs was not significantly associated with increased risk of incident cancer overall or of lung cancer.


Regularly scheduled voluntary exercise synchronizes the mouse circadian clock.
Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism.


Outcomes of primary total hip arthroplasty following septic arthritis of the hip : a case-control study.
Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA. We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m2 (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39). The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both). There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J 2022;104-B(2):227-234.


Variability of palmprint ridge density in a North Indian population and its use in inference of sex in forensic examinations.
Fingerprints and palmprints are unique to an individual, and these biometric characters are used in the identification of individuals. In the recent past, ridge density (ridge count in a defined area) has been explored for its applicability in inference of sex from the fingerprints and palmprints recovered at the crime scene. The present research aims to study the variability of palmprint ridge density in a North Indian population, and its significance in inference of sex in forensic examinations. The sample consisted of 157 healthy young adults (110 females and 47 males) from Shimla city in North India. Bilateral palmprints were taken from all the participants following standard methods. The palmprints were manually analyzed in four defined areas of each palmprint that included the central prominent part of the thenar eminence (P1), the mount distal to the axial triradius on the hypothenar region (P2), the mount proximal to the triradius of the second digit (P3) and the mount proximal to the triradius of the fifth digit (P4). The ridge density was calculated diagonally using a square measuring 5 mm × 5 mm. The sex differences in palmprint ridge densities were statistically analyzed for each of the designated areas using statistical considerations. Receiver operating characteristic (ROC) curve analysis was done to test the overall ability of the palmprint ridge densities obtained from each area in inference of sex. The mean palmprint ridge density was found to be significantly greater in females than in males in all the four defined areas of the palmprint. Ridge densities in P3 and P4 areas of the palmprint showed statistically significant bilateral differences in both males and females. The study observed variations in the ridge density between the four designated areas of the palmprint. Based on the area under the ROC curve (AUC), maximum sexing potential for the palmprint ridge density was observed in the P4 area, followed by P3 area on both right and left sides. ROC analysis of the total palmprint ridge density indicated that the sexing accuracy from the right and left palmprint ridge densities was 70.2% and 71.8% respectively. The study shows variability of palmprint ridge density among sexes and in different regions of the palm on both sides. In view of the considerable overlapping in male and female values and lower levels of accuracy obtained in ROC analysis, the present research concludes that the palmprint ridge density cannot be used as an effective tool in inference of sex. However, in absence of other more reliable means/evidence, it still can be considered as a supportive trait in sex inference.


Non-random length distribution of individual telomeres in immunodeficiency, centromeric instability and facial anomalies syndrome, type I.
Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. While it was demonstrated that the mean telomere length is significantly shorter in ICF type I cells, it is unknown whether all telomeres are equally vulnerable to shortening. To study this question we determined by combined telomere-FISH and spectral karyotyping the relative length of each individual telomere in lymphoblastoid cell lines (LCLs) generated from multiple ICF syndrome patients and control individuals. Here we confirm the short telomere lengths, and demonstrate that telomere length variance in the ICF patient group is much larger than in the control group, suggesting that not all telomeres shorten in a uniform manner. We identified a subgroup of telomeres whose relatively short lengths can distinguish with a high degree of certainty between a control and an ICF metaphase, proposing that in ICF syndrome cells, certain individual telomeres are consistently at greater risk to shorten than others. The majority of these telomeres display high sequence identity at the distal 2 kb of their subtelomeres, suggesting that the attenuation in DNMT3B methylation capacity affects individual telomeres to different degrees based, at least in part, on the adjacent subtelomeric sequence composition.


A preliminary examination of treatment for posttraumatic stress disorder in chronic pain patients: a case study.
Manualized treatments have become popular, despite concern about their use when comorbid diagnoses are present. In this report, the efficacy of manualized posttraumatic stress disorder (PTSD) treatment was examined in the presence of chronic pain. Additionally, the effect of PTSD treatment on chronic pain and additional psychiatric diagnoses was explored. Six female patients with both PTSD and chronic pain following motor vehicle accidents were treated for PTSD using a multiple baseline design. The results indicate that manualized treatment for PTSD was effective in reducing PTSD symptoms in these patients. Although there were no changes in subjective pain, there were pain-related functional improvements and reductions in other psychiatric diagnoses for the majority of patients.


Correlation between TM joint disease and rheumatic diseases detected on bone scintigraphy and clinical factors.
The aim of this study was to evaluate the effect of rheumatic disease as a risk factor for temporomandibular disease (TMD). A total of 143 outpatients reporting symptoms indicating rheumatic disease at their first visit to the rheumatology clinic were included. We evaluated the temporomandibular joint (TMJ) with scintigraphic images, and standard questionnaires were administered for the symptomatic assessment for all patients. The patients were classified into 'healthy controls' or as per their diagnosis into 'osteoarthritis', 'axial spondyloarthritis', 'peripheral spondyloarthritis', 'rheumatoid arthritis', or 'other rheumatic diseases' groups. The patients were also differentiated depending on the presence or absence of axial involvement. The relation between the rheumatic disease type and findings at the TMJ were evaluated using statistical analyses. Axial spondyloarthritis, peripheral spondyloarthritis, and rheumatic arthritis patients showed significantly higher scintigraphic uptake at the TMJ compared with those in the control and osteoarthritis groups (axial spondyloarthritis: 4.5, peripheral spondyloarthritis: 4.5, rheumatoid arthritis: 4.09, control: 3.5, osteoarthritis: 3.4, p < 0.0001). Compared with patients without axial involvement, patients with axial involvement also showed significantly higher TMJ scintigraphic uptake (axial involvement: 4.24, without axial involvement: 3.50, p < 0.0001) with elevated symptomatic rates in TMD (axial involvement: 17.82, without axial involvement: 9.97, p < 0.005).


Adjusting Acute Kidney Injury Kidney Disease: Improving Global Outcomes Urine Output Criterion for Predicted Body Weight Improves Prediction of Hospital Mortality.
Based on the Kidney Disease: Improving Global Outcomes (KDIGO) definitions, urine output, serum creatinine, and need for kidney replacement therapy are used for staging acute kidney injury (AKI). Currently, AKI staging correlates strongly with mortality and can be used as a predictive tool. However, factors associated with the development of AKI may affect its predictive ability. We tested whether adjustment for predicted (versus actual) body weight improved the ability of AKI staging to predict hospital mortality. A total of 3279 patients who had undergone cardiac surgery in a university hospital were retrospectively analyzed. AKI was staged according to KDIGO criteria (standard staging) and after adjustment for hourly urine output adjusted by predicted body weight for each patient and each day of their hospital stay. The incidence of AKI (all stages) was 43% (predicted body weight adjusted) and 50% (standard staging), respectively (P < .001). In sensitivity-specificity analyses for predicting hospital mortality, the area under the curve was significantly higher after adjustment for predicted body weight than with standard staging (P = .002). Compared to standard staging, adjustment of urine output for predicted body weight increases the specificity and improves prediction of hospital mortality in patients undergoing cardiac surgery.


Efficacy of platelet-rich plasma and platelet-rich fibrin in arthroscopic rotator cuff repair: A systematic review and meta-analysis.
Basic scientific studies have demonstrated positive effects of platelet-rich therapies, such as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), on tendon repair. However, clinical evidence indicating improved prognosis is controversial. In this study, we aimed to determine whether augmentation of arthroscopic rotator cuff repair with PRP and PRF improves outcomes compared to arthroscopic repair alone. PubMed, Embase, and Cochrane library databases were comprehensively searched for randomized controlled trials (RCTs) published until June 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. No language restriction was applied. The primary outcomes were the rate of repeat tears after arthroscopic rotator cuff repair (retear rate) and clinical function scores (Constant-Murley Score, University of California, Los Angeles Score), and the extracted data were assessed for quality. Statistical analyses were performed using Review manager 5.3, and p < .05 was considered statistically significant. Ten RCTs with 628 patients were included. The results showed that augmenting surgery with PRP reduces retear rates compared to surgery alone (risk ratio [RR] = 0.40, 95% confidence interval [CI] 0.23-0.69, p = .001), whereas PRF has no effect on retear rates (p = .92). Regarding clinical function, PRP improves Constant-Murley scores (mean difference [MD] = 2.03, 95% CI 0.13-3.93, p = .04) and University of California, Los Angeles scores (MD = 1.30, 95% CI 0.36-2.24, p = .007), whereas PRF improves only Constant-Murley scores (MD = 3.93, 95% CI 1.50-6.36, p = .002). However, these differences were small and below the minimum clinically important difference threshold. This study showed that compared to arthroscopic rotator cuff repair alone, the application of PRP in arthroscopic rotator cuff repair reduces retear rate and improves clinical function scores, whereas the application of PRF has no clinically meaningful benefit. The small number and heterogeneity of studies as well as methodological limitations and risk of bias limit confidence in the true effect.


Prevalence and risk factors of pre-hypertension and hypertension among adults in Southeastern Iran: Findings from the baseline survey of the Zahedan adult cohort study.
Hypertension (HTN) stands as the leading modifiable risk factor for cardiovascular disease(CVD) and premature death globally. Understanding its prevalence and risk factors is essential for effective prevention and management of HTN. This study aimed to investigate the prevalence of Pre-hypertension (pre-HTN), HTN, and its risk factors in adults participating in the Zahedan adult cohort study (ZACS). This cross-sectional study used the baseline data of the ZACS. Ordinal logistic regression analysis was used to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for potential risk factors. Among the 10,016 participants in this study, 60.89% were women, with an average age of 50.44 ± 9.18 years. The prevalence of pre-HTN and HTN was 42.03% (men 45.44%, women 39.84%) and 18.47% (men 21.09%, women 16.79%), respectively. Being male, older age, having higher socioeconomic status (SES), being overweight and obese, having a family history of HTN, comorbidities such as diabetes and CVD, as well as abnormal blood lipid levels (triglycerides and HDL cholesterol) were the most significant predictors of pre-HTN and HTN. These findings highlight that more than half of the participants in this study exhibit pre-HTN or HTN, placing them at risk for CVD and stroke. Implementing comprehensive preventive strategies tailored to these identified risk factors is imperative to alleviate the disease burden, enhance disease management, and improve HTN treatment and control.


KINATEST-ID: a pipeline to develop phosphorylation-dependent terbium sensitizing kinase assays.
Nonreceptor protein tyrosine kinases (NRTKs) are essential for cellular homeostasis and thus are a major focus of current drug discovery efforts. Peptide substrates that can enhance lanthanide ion luminescence upon tyrosine phosphorylation enable rapid, sensitive screening of kinase activity, however design of suitable substrates that can distinguish between tyrosine kinase families is a huge challenge. Despite their different substrate preferences, many NRTKs are structurally similar even between families. Furthermore, the development of lanthanide-based kinase assays is hampered by incomplete understanding of how to integrate sequence selectivity with metal ion binding, necessitating laborious iterative substrate optimization. We used curated proteomic data from endogenous kinase substrates and known Tb(3+)-binding sequences to build a generalizable in silico pipeline with tools to generate, screen, align, and select potential phosphorylation-dependent Tb(3+)-sensitizing substrates that are most likely to be kinase specific. We demonstrated the approach by developing several substrates that are selective within kinase families and amenable to high-throughput screening (HTS) applications. Overall, this strategy represents a pipeline for developing efficient and specific assays for virtually any tyrosine kinase that use HTS-compatible lanthanide-based detection. The tools provided in the pipeline also have the potential to be adapted to identify peptides for other purposes, including other enzyme assays or protein-binding ligands.


Hyperbaric oxygen treatment for the management of radiation-induced xerostomia.
Hyperbaric oxygen therapy (HBOT) is widely used for the treatment of the late effects of radiation therapy. We report a prospective observational cohort study of 51 patients designed to examine the effectiveness of hyperbaric oxygen treatment (HBOT) for xerostomia following radiotherapy. Objective (saliva volume) and subjective (quality of life scoring and visual analogue scale (VAS) of discomfort) measurements associated with xerostomia were compared prior to commencement of HBOT, after 30 sessions (over 6 weeks) of HBOT at 243 kPa for 90 minutes daily for five days per week and at 6-week review (12 weeks from commencement). One hundred and one courses of treatment in 99 patients were examined. For 53 (53%) courses in 51 patients, data were recorded before and after HBOT and so could be included in the analysis. Thirty-four (34%) of these patients had complete data for all three time points. The unit of study was per treatment course, not per person. There were no major complications to HBOT. There was a statistically significant difference in saliva volume following HBOT (P = 0.016). The mean saliva volume increase was 0.9 mL over a 5-min collection period (95% CI 0.2-1.5). There was also a statistically significant improvement in discomfort after HBOT (P < 0.001) and QOL (P < 0.001). The mean visual analogue scale for discomfort (VAS on a 0-10 scale) score decreased by 1.4 units (95% CI 0.7-2.1), whilst the mean QOL score was 10 points lower after treatment (95% CI 5.9-14.4). Hyperbaric oxygen therapy may be a safe and effective treatment for symptoms of xerostomia after radiation therapy and should be considered when available.


A Generic multi-dimensional feature extraction method using multiobjective genetic programming.
In this paper, we present a generic feature extraction method for pattern classification using multiobjective genetic programming. This not only evolves the (near-)optimal set of mappings from a pattern space to a multi-dimensional decision space, but also simultaneously optimizes the dimensionality of that decision space. The presented framework evolves vector-to-vector feature extractors that maximize class separability. We demonstrate the efficacy of our approach by making statistically-founded comparisons with a wide variety of established classifier paradigms over a range of datasets and find that for most of the pairwise comparisons, our evolutionary method delivers statistically smaller misclassification errors. At very worst, our method displays no statistical difference in a few pairwise comparisons with established classifier/dataset combinations; crucially, none of the misclassification results produced by our method is worse than any comparator classifier. Although principally focused on feature extraction, feature selection is also performed as an implicit side effect; we show that both feature extraction and selection are important to the success of our technique. The presented method has the practical consequence of obviating the need to exhaustively evaluate a large family of conventional classifiers when faced with a new pattern recognition problem in order to attain a good classification accuracy.


Cone visual pigments of monotremes: filling the phylogenetic gap.
We have determined the sequence and genomic organization of the genes encoding the cone visual pigment of the platypus (Ornithorhynchus anatinus) and the echidna (Tachyglossus aculeatus), and inferred their spectral properties and evolutionary pathways. We prepared platypus and echidna retinal RNA and used primers of the middle-wave-sensitive (MWS), long-wave-sensitive (LWS), and short-wave sensitive (SWS1) pigments corresponding to coding sequences that are highly conserved among mammals; to PCR amplify the corresponding pigment sequences. Amplification from the retinal RNA revealed the expression of LWS pigment mRNA that is homologous in sequence and spectral properties to the primate LWS visual pigments. However, we were unable to amplify the mammalian SWS1 pigment from these two species, indicating this gene was lost prior to the echidna-platypus divergence (21 MYA). Subsequently, when the platypus genome sequence became available, we found an LWS pigment gene in a conserved genomic arrangement that resembles the primate pigment, but, surprisingly we found an adjacent (20 kb) SWS2 pigment gene within this conserved genomic arrangement. We obtained the same result after sequencing the echidna genes. The encoded SWS2 pigment is predicted to have a wavelength of maximal absorption of about 440 nm, and is paralogous to SWS pigments typically found in reptiles, birds, and fish but not in mammals. This study suggests the locus control region (LCR) has played an important role in the conservation of photo receptor gene arrays and the control of their spatial and temporal expression in the retina in all mammals. In conclusion, a duplication event of an ancestral cone visual pigment gene, followed by sequence divergence and selection gave rise to the LWS and SWS2 visual pigments. So far, the echidna and platypus are the only mammals that share the gene structure of the LWS-SWS2 pigment gene complex with reptiles, birds and fishes.


Acid-Catalyzed Liquefaction of Biomasses from Poplar Clones for Short Rotation Coppice Cultivations.
Liquefaction of biomass delivers a liquid bio-oil with relevant chemical and energetic applications. In this study we coupled it with short rotation coppice (SRC) intensively managed poplar cultivations aimed at biomass production while safeguarding environmental principles of soil quality and biodiversity. We carried out acid-catalyzed liquefaction, at 160 °C and atmospheric pressure, with eight poplar clones from SRC cultivations. The bio-oil yields were high, ranging between 70.7 and 81.5%. Average gains of bio-oil, by comparison of raw biomasses, in elementary carbon and hydrogen and high heating, were 25.6, 67, and 74%, respectively. Loss of oxygen and O/C ratios averaged 38 and 51%, respectively. Amounts of elementary carbon, oxygen, and hydrogen in bio-oil were 65, 26, and 8.7%, and HHV averaged 30.5 MJkg-1. Correlation analysis showed the interrelation between elementary carbon with HHV in bio-oil or with oxygen loss. Overall, from 55 correlations, 21 significant and high correlations among a set of 11 variables were found. Among the most relevant ones, the percentage of elementary carbon presented five significant correlations with the percentage of O (-0.980), percentage of C gain (0.902), percentage of O loss (0.973), HHV gain (0.917), and O/C loss (0.943). The amount of carbon is directly correlated with the amount of oxygen, conversely, the decrease in oxygen content increases the elementary carbon and hydrogen concentration, which leads to an improvement in HHV. HHV gain showed a strong positive dependence on the percentage of C (0.917) and percentage of C gain (0.943), while the elementary oxygen (-0.885) and its percentage of O loss (0.978) adversely affect the HHV gain. Consequently, the O/C loss (0.970) increases the HHV positively. van Krevelen's analysis indicated that bio-oils are chemically compatible with liquid fossil fuels. FTIR-ATR evidenced the presence of derivatives of depolymerization of lignin and cellulose in raw biomasses in bio-oil. TGA/DTG confirmed the bio-oil burning aptitude by the high average 53% mass loss of volatiles associated with lowered peaking decomposition temperatures by 100 °C than raw biomasses. Overall, this research shows the potential of bio-oil from liquefaction of SRC biomasses for the contribution of renewable energy and chemical deliverables, and thereby, to a greener global economy.


In vitro and in vivo angiogenic capacity of BM-MSCs/HUVECs and AT-MSCs/HUVECs cocultures.
The aim of this study was to comparatively evaluate the angiogenic capacity of cocultures using either human bone marrow- or human adipose tissue-derived mesenchymal stem cells (MSCs) (BM- or AT-MSCs) with human umbilical vein endothelial cells (HUVECs) both in vitro and in vivo at early time points (i.e. days 3 and 7). In vitro, cells were either monocultured (i.e. BM-MSCs, AT-MSCs or HUVECs) or cocultured (i.e. BM-MSCs/HUVECs and AT-MSCs/HUVECs) on Thermanox® (2-dimensional, 2D) or in collagen gels (3-dimensional, 3D). For the in vivo experiment, cells (cocultures) were embedded in collagen gels and implanted subcutaneously in nude mice. For both in vitro and in vivo experiments, samples were collected on days 3 and 7 and histologically processed for hematoxylin-eosin and platelet endothelial cell adhesion molecule (PECAM-1; CD31) staining. For in vivo samples, quantitative parameters for evaluating angiogenesis included CD31-positive staining percentage, total vessel-like structure (VLS) area percentage, VLS density, and average VLS area (i.e. the size of per VLS). In vitro results showed the formation of VLS in both cocultures, while none of the monocultures showed VLS formation, irrespective of 2D or 3D culture condition. Although VLS formation occurred after in vivo implantation, no significant difference in angiogenic capacity was observed between the two cocultures, either on day 3 or on day 7. Further, VLS density decreased and anastomosis of the new human vessels with the murine host vasculature occurred over time. In conclusion, this study demonstrated that AT-MSCs/HUVECs and BM-MSCs/HUVECs have equal angiogenic capacity both in vitro and in vivo, and that vessels from donor origin can anastomose with the host vasculature within seven days of implantation.


Case Study: The Use of Massage Therapy to Relieve Chronic Low-Back Pain.
To study the effects of massage on chronic low-back pain in a patient with four different diagnoses: osteoarthritis, scoliosis, spinal stenosis, and degenerative disc disease. The patient's goal was to cut down on the amount of pain medication he takes. A 63-year-old man with chronic back pain received four massages across a twenty-day period. Progress was recorded using the Oswestry Low Back Pain Scale, as he self-reported on levels of pain and interference with his activities of daily living. Improvement was noted in 9 out of 10 measurements of self-reported pain and activities of daily living, with the only exception being his ability to lift heavy objects, which remained unchanged. The most dramatic differences were improvements in his ability to walk, and in the changing degrees of pain. The client also self-reported being able to decrease his pain medication and the ability to ride his bicycle for the first time in years. Massage therapy is a promising treatment for chronic low-back pain for patients who may have multiple pathologies, any one of which could be responsible for the condition. Further study is encouraged to determine the efficacy of massage therapy as a readily accessible, lower-cost alternative to more invasive therapies and as an adjunct to regular medical care, when appropriate.


Characteristics and Complete Genome Analysis of a Pathogenic Aeromonas Veronii SJ4 from Diseased Siniperca Chuatsi.
As an opportunistic pathogen, Aeromonas veronii can cause hemorrhagic septicemia of various aquatic animals. In our present study, a dominant strain SJ4, isolated from naturally infected mandarin fish (Siniperca chuatsi), was identified as A. veronii according to the morphological, physiological, and biochemical features, as well as molecular identification. Intraperitoneal injection of A. veronii SJ4 into S. chuatsi revealed clinical signs similar to the natural infection, and the median lethal dosage (LD50) of the SJ4 to S. chuatsi in a week was 3.8 × 105 CFU/mL. Histopathological analysis revealed that the isolate SJ4 could cause cell enlargement, obvious hemorrhage, and inflammatory responses in S. chuatsi. Detection of virulence genes showed the isolate SJ4 carried act, fim, flgM, ompA, lip, hly, aer, and eprCAL, and the isolate SJ4 also produce caseinase, dnase, gelatinase, and hemolysin. In addition, the complete genome of A. veronii SJ4 was sequenced, and the size of the genome of A. veronii SJ4 was 4,562,694 bp, within a G + C content of 58.95%, containing 4079 coding genes. Nine hundred ten genes encoding for several virulence factors, such as type III and VI secretion systems, flagella, motility, etc., were determined based on the VFDB database. Besides, 148 antibiotic resistance-related genes in 27 categories related to tetracyclines, fluoroquinolones, aminoglycosides, macrolides, chloramphenicol, and cephalosporins were also annotated. The present results suggested that A. veronii was etiological agent causing the bacterial septicemia of S. chuatsi in this time, as well as provided a valuable base for revealing pathogenesis and resistance mechanism of A. veronii.


Group A Streptococcus induces apoptosis in human epithelial cells.
Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to examine the fate of GAS-infected epithelial cells. GAS has the ability to invade A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infection with GAS. Epithelial cell death mediated by GAS was at least in part through apoptosis, as shown by changes in cellular morphology, DNA fragmentation laddering, and propidium iodide staining for hypodiploid cells. A total of 20% of A-549 cells and 11 to 13% of HEp-2 cells underwent apoptosis after 20 h of GAS infection, whereas only 1 to 2% of these cells exhibited spontaneous apoptosis. We further examined whether streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease produced by GAS, was involved in the apoptosis of epithelial cells. The speB isogenic mutants had less ability to induce cell death than wild-type strains. When A-549 cells were cocultured with the mutant and SPE B for 2 h, the percentage of apoptotic cells did not increase although the number of intracellular bacteria increased to the level of wild-type strains. In addition, apoptosis was blocked by cytochalasin D treatment, which interfered with cytoskeleton function. The caspase inhibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apoptosis. These results demonstrate for the first time that GAS induces apoptosis of epithelial cells and internalization is required for apoptosis. The caspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.


Morphine glucuronidation and glucosidation represent complementary metabolic pathways that are both catalyzed by UDP-glucuronosyltransferase 2B7: kinetic, inhibition, and molecular modeling studies.
Morphine 3-β-D-glucuronide (M3G) and morphine 6-β-D-glucuronide (M6G) are the major metabolites of morphine in humans. More recently, morphine-3-β-d-glucoside (M-3-glucoside) was identified in the urine of patients treated with morphine. Kinetic and inhibition studies using human liver microsomes (HLM) and recombinant UGTs as enzyme sources along with molecular modeling were used here to characterize the relationship between morphine glucuronidation and glucosidation. The M3G to M6G intrinsic clearance (C(Lint)) ratio (∼5.5) from HLM supplemented with UDP-glucuronic acid (UDP-GlcUA) alone was consistent with the relative formation of these metabolites in humans. The mean C(Lint) values observed for M-3-glucoside by incubations of HLM with UDP-glucose (UDP-Glc) as cofactor were approximately twice those for M6G formation. However, although the M3G-to-M6G C(Lint) ratio remained close to 5.5 when human liver microsomal kinetic studies were performed in the presence of a 1:1 mixture of cofactors, the mean C(Lint) value for M-3-glucoside formation was less than that of M6G. Studies with UGT enzyme-selective inhibitors and recombinant UGT enzymes, along with effects of BSA on morphine glycosidation kinetics, were consistent with a major role of UGT2B7 in both morphine glucuronidation and glucosidation. Molecular modeling identified key amino acids involved in the binding of UDP-GlcUA and UDP-Glc to UGT2B7. Mutagenesis of these residues abolished morphine glucuronidation and glucosidation. Overall, the data indicate that morphine glucuronidation and glucosidation occur as complementary metabolic pathways catalyzed by a common enzyme (UGT2B7). Glucuronidation is the dominant metabolic pathway because the binding affinity of UDP-GlcUA to UGT2B7 is higher than that of UDP-Glc.


Theorising women's health and health inequalities: shaping processes of the 'gender-biology nexus'.
Since the theoretical frameworks and conceptual tools we employ shape research outcomes by guiding research pathways, it is important that we subject them to ongoing critical reflection. A thoroughgoing analysis of the global production of women's health inequality calls for a comprehensive theorization of how social relations of gender and the biological body mutually interact in local contexts in a nexus with women's health. However, to date, the predominant concern of research has been to identify the biological effects of social relations of gender on the body, to the relative neglect of the co-constitutive role that these biological changes themselves may play in ongoing cycles of gendered health oppressions. Drawing on feminist and gender theoretical approaches, and with the health of women and girls as our focus, we seek to extend our understanding of this recursive process by discussing what we call the 'shaping processes' of the 'gender-biology nexus' which call attention to not only the 'gender-shaping of biology' but also the 'biologic-shaping of gender'. We consider female genital mutilation/cutting as an illustration of this process and conclude by proposing that a framework which attends to both the 'gender-shaping of biology' and the 'biologic-shaping of gender' as interweaving processes provides a fruitful approach to theorising the wider health inequalities experienced by women and girls.


Perceived Threat of Disaster, Efficacy, and Psychological Distress Among Individuals with a Physical Disability: A Longitudinal Model.
Individuals with physical disabilities experience distress when faced with the threat of human-made and natural disasters, yet little is known about how to reduce that distress. This study used Protection Motivation Theory to longitudinally test the relationships between psychological distress and disaster-related cognitive appraisals, including perceived threat, emergency preparedness self-efficacy, and response efficacy, in a sample of individuals with physical disabilities. A nationwide convenience sample of 106 adults completed 2 surveys approximately 5 years apart. Structural equation modeling was used to assess effects of perceived threat, self-efficacy, and response efficacy on psychological distress across the 2 waves. Our results suggest that the associations of proximal perceived threat and self-efficacy with psychological distress remain stable across time, while the effect of response efficacy is variable and may be more context-specific. Importantly, individuals who reported an increase in self-efficacy over time also reported (on average) a decrease in psychological distress. In addition to broadening our understanding of factors related to psychological distress, these results have potentially important intervention implications; for example, to the extent that self-efficacy is a malleable construct, one way of reducing disaster-related psychological distress may be to increase an individual's self-efficacy.


Complete evidence regarding major vascular injuries during laparoscopic access.
Recent reports by the Australian Safety and Efficacy Register for New interventions and Procedures (ASERNIP-S) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) concluded that insufficient evidence is available to assess the safety of the open versus closed laparoscopy in regard to major vascular and visceral injuries. The aim of this study was to assess the relative safety of open and closed laparoscopy with respect to rates of major vascular and visceral injuries. A combined prospective/retrospective review of a single-surgeon series of 5900 open laparoscopies was performed. A meta-analysis of all reported series of open and closed laparoscopy was conducted using PubMed and MEDLINE search engines to compare major vascular and visceral injury rates. Medicolegal and manufacturer device reports were also reviewed. The case series of 5900 open laparoscopies reported a single visceral injury and no major vascular injuries. The meta-analysis revealed 336 major vascular injuries in 760,890 closed laparoscopies, a mean rate of 0.044%, 1 injury per 2272 cases, compared with 0 injuries in 22,465 open laparoscopies (P = 0.003). Visceral injuries occurred more frequently, 515 injuries in 760,890 closed laparoscopies (mean rate, 0.07) and 11 injuries in 22,465 open laparoscopies (mean rate, 0.05; P = 0.18). Medicolegal and device reports revealed a further 647 major vascular injuries and 500 major visceral injuries. In contrast to the conclusion formed by the RANZCOG and ASERNIP-S, the available evidence shows that open laparoscopy eliminates the risk of major vascular injury and reduces the rate of major visceral injuries. Open laparoscopy using the Hasson cannula should be the preferred method of peritoneal access.


Maternal-fetal cellular trafficking: clinical implications and consequences.
Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells between mother and fetus during pregnancy. This results in the presence of fetal cells in the maternal circulation, known as fetal microchimerism, and maternal cells in the fetal circulation, known as maternal microchimerism. The biologic role of this transplacental cellular trafficking during pregnancy is not known, although it has been implicated in development of the fetal immune system, tolerance mechanisms during pregnancy, tissue repair in autoimmune disease and cancer, and immune surveillance. Clinical utility of MFCT has been identified in prenatal testing for aneuploidies and prediction of pregnancy complications. Additionally, this transplacental passage of cells has been implicated in the delicate balance between immunologic priming and tolerance, which can influence the occurrence of autoimmune disease and transplantation outcomes. Ongoing studies are evaluating the utility of microchimerism in predicting the risk of graft rejection in transplantation. In this review, we will discuss the clinical implications of MFCT in pregnancy, fetal surgery, autoimmune disease, transplantation, and cancer.


Febrile seizures in young children: role of fluid intake and conservation.
Febrile seizures are a common occurrence in young children with incidence rates varying from 3-14%, depending on the geographic region. Studies have suggested that an elevated temperature is a factor in their development, though other factors may synergistically lower the seizure threshold. While it is recognized that excessive or rapid dilute fluid intake can cause seizures in young children, and in adults during strenuous physical activity, less focus has been paid to its involvement during febrile illnesses. Young children are more vulnerable to the development of febrile seizures due to their small skull size relative to brain volume. In animals, reduced serum sodium levels have been shown to lower the threshold to convulsive stimuli, while hypertonic saline has been shown to rapidly reverse these effects. Similarly vasopressin, frequently elevated during acute infections, enhances fluid retention and may also be a precipitating factor for febrile seizures. Although an elevated temperature may augment seizure risk, antipyretics have not been shown to prevent them. In fact, some may increase seizure risk through a reduction in urine output. It has long been observed that fluid retention occurs during febrile infections, followed by diuresis during convalescence. This characteristic observation led to recommendations for restricted fluid intake during acute infections dating back more than 2,000 years. Only recently has there been a return to restricted fluid intake for patients with potentially reduced free water excretion. Further studies are required to determine the role of the overall fluid balance in the etiology of childhood febrile seizures.