Cardiovascular responses to parathyroid hormone.
The synthetic amino terminal fragment of parathyroid hormone, PTH-(1-34), is a potent coronary artery vasodilator in the dog. In the present study, using instrumented open-chest dogs, we have performed the initial characterization of this effect and showed other dose-related cardiovascular effects of the hormone. A near-maximal flow response was obtained after intracoronary injection of 0.024 nmol X kg-1 PTH-(1-34) with minor, if any, concomitant changes in mean blood pressure, contractile force, or heart rate. At higher doses, mean blood pressure decreased while contractile force and heart rate increased in dose-dependent fashion. Infusion of PTH-(1-34) for 20 min showed that the vasodilatory effect could be sustained without a concomitant decrease in mean arterial pressure. Pharmacological characterization showed for the first time that the coronary response to PTH-(1-34) was unaltered in the presence of beta- or alpha-adrenergic, muscarinic, or histaminergic blockades. We conclude that PTH-(1-34), an endogenous circulating calcemic peptide, produces a large increase in coronary blood flow at doses sufficiently low to preclude complicating effects on blood pressure, contractile force, and heart rate. Furthermore, the results suggest that the vasodilatory effects may be specific.


Acquired Hemophilia A After Hepatic Yttrium-90 Radioembolization: A Case Report.
Acquired hemophilia is a rare but potentially life-threatening bleeding disorder caused by the development of autoantibodies (inhibitors) directed against plasma coagulation factors, most frequently factor VIII. We report a case of a 65-year-old man with hepatocellular carcinoma who bled massively after a hepatic Yttrium-90 radioembolization procedure (Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres [SIRTex]). An acquired deficiency of factor VIII was diagnosed and successfully treated with recombinant activated factor VII and immunosuppression.


Detection and characterization of the first North American mastrevirus in switchgrass.
Virus infections have the potential to reduce biomass yields in energy crops, including Panicum virgatum (switchgrass). As a first step towards managing virus-induced biomass reduction, deep sequencing was used to identify viruses associated with mosaic symptoms in switchgrass. Two sequences with homology to mastreviruses were identified. Total DNA extracted from switchgrass varieties 'Dewey Blue' and 'Cloud Nine' was used as template to amplify mastrevirus DNA by the rolling-circle method. Complete mastrevirus genome sequences were obtained from cloned amplicons. The two nucleotide sequences were 88 % identical to each other but only 56-57 % identical to the closest relatives in the genus Mastrevirus. Predicted amino acid sequences of the coat protein, replication-associated protein A, replication-associated protein, and putative movement protein encoded by the two mastrevirus-like sequences were 95 %, 79 %, 79 %, and 87 % identical to each other, respectively, and 46-48 %, 31 %, 31 %, and 42-48 % identical to those of the closest mastrevirus relatives. Based on a genome-wide identity threshold of 75 % set by the International Committee on Taxonomy of Viruses and phylogenetic analyses, the two virus sequences appear to represent a new mastrevirus species. The mastrevirus is tentatively named switchgrass mosaic-associated virus 1 (SgMaV-1) and is the first mastrevirus reported from North America.


Use of H2 as an inert gas during diving: pulmonary function during H2-O2 breathing at 7.06 ATA.
A review of the characteristics of hydrogen as an inert gas for use in diving is presented, with special emphasis on the extension of the respiratory limitation in diving by use of this least dense of all gases. Forced vital capacity, FEV1, FEV2, PEFR, PIFR, and MVV were measured on groups of subjects using the following gas mixtures, all at 7.06 ATA: four subjects breathing 97% H2-3% O2, two subjects breathing 97% He-3% O2, and two subjects using 97% N2-3% O2. The MVV while breathing H2-O2 at 7.06 ATA was 14% higher than with air at the surface, and was improved 40% compared with He-O2 and 171% when compared with N2-O2 at 7.06 ATA. Similar findings were obtained for FEV1, FEV2, PEFR, and PIFR. The values in this study for the relationship of relative gas density (rho) to flow are rho-0.41 for MVV, rho-0.44 for PEFR, and rho-0.45 for PIFR (method of Wood and Bryan).


Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function.
Peroxiredoxin-6 (PRDX6) is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2 (PLA2), which is involved in regulation of many cellular reactions. However, the function of PRDX6 during virus infection remains unknown. In this study, we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus (FMDV) infected cells. Overexpression of PRDX6 inhibited FMDV replication. In contrast, knockdown of PRDX6 expression promoted FMDV replication, suggesting an antiviral role of PRDX6. To explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function, a specific inhibitor of PLA2 (MJ33) and a specific inhibitor of peroxidase activity (mercaptosuccinate) were used to treat the cells before FMDV infection. The results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV replication. Meanwhile, overexpression of PRDX6 slightly enhanced type I interferon signaling. We further determined that the viral 3Cpro was responsible for degradation of PRDX6, and 3Cpro-induced reduction of PRDX6 was independent of the proteasome, lysosome, and caspase pathways. The protease activity of 3Cpro was required for induction of PRDX6 reduction. Besides, PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A (SVA), and the 3Cpro of SVA induced the reduction of PRDX6 through its proteolytic activity as well. Together, our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection, and the viral 3Cpro induces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.


[Progress in the field of medical devices for diabetes].
In the eighties major improvements were made in insulin injection and home blood glucose monitoring. However, in the nineties further improvements were rather disappointing. Despite considerable effort, non-invasive, continuous monitoring glucose sensors are still not ready for marketing. It will take 10-20 years before 'closed-loop systems' will appear, with the amount of insulin released by the pump adjusted automatically on the basis of the measuring results of a permanently implanted blood glucose sensor. Islet cell transplantation, if possible in a way that abolishes the need to take immunosuppressive medicines, is still under development. The number of people suffering from diabetes in the Netherlands is estimated to increase from about 285,400 in 1999 to about 400,000 in 2020. The costs of medical devices for diabetes will probably double in 2020. However, increased costs for devices may improve the quality of life and may result in decreased expenditure in other parts of health care by reducing the long-term complications.


Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects?
Two women developed significant neurologic dysfunction, consistent with subacute combined degeneration of the spinal cord, within eight weeks of being anesthetized with nitrous oxide. Investigation revealed that each had preclinical or masked vitamin B12 deficiency. The first patient had two previous ileal resections for Crohn's disease and the other had pernicious anemia. It is postulated that nitrous oxide anesthesia may precipitate neurologic disease in people with unrecognized deficiency of vitamin B12.


Centrally induced cardiovascular and sympathetic nerve responses to bradykinin in rats.
Central actions of bradykinin were studied by recording blood pressure and sympathetic nerve activity from the body of a recipient rat whose head was vascularly isolated and perfused by a donor rat. Intracarotid injections of bradykinin had biphasic effects consisting of initial inhibition followed by more prolonged stimulation. Initial vasodepression and sympathetic inhibition disappeared after intracerebroventricular injection of 6-hydroxydopamine. On the other hand, the secondary pressor response and its attendant sympathetic hyperactivity were reduced after inhibition of prostaglandin synthesis with indomethacin, and conversely, augmented after administration of the prostaglandin precursor, arachidonic acid. Pressor responses elicited by intracerebroventricular injection of bradykinin in awake rats were also inhibited by indomethacin. These results indicate that bradykinin has at least two centrally induced actions on blood pressure: an initial vasodepression caused by release of endogenous norepinephrine which activates alpha adrenergic vasodepressor mechanisms in supramedullary centers, and a secondary pressor effect that may be mediated via release of endogenous prostaglandins.


Drug-induced pemphigoid: a review of the literature.
Bullous pemphigoid is an acquired autoimmune disease that is characterized by subepidermal blistering and affects mainly the elderly. The pathogenesis of the condition has not yet been fully elucidated, but it is widely accepted that a strong correlation with various medications may exist. In reality, more than 50 different drugs have been associated with the appearance of bullous pemphigoid and as new therapies emerge, this number is very likely to increase. A number of pathogenetic mechanisms have been proposed in the past. It is true that a delicate immunological balance is disturbed in all patients with the disease. The variable effects that may be exhibited by the use of biological drugs could shed some light in this complex immunological behaviour. At the same time, drug-induced bullous pemphigoid is difficult to differentially diagnose from its idiopathic counterpart, as the clinical picture and histopathological findings in both conditions may only have subtle differences. Patients who present with bullous pemphigoid and receive multiple regimens should always be suspected of suffering from the drug-induced variant of the condition. This possibility must be considered, as after the withdrawal of the suspect medication most patients respond rapidly to treatment and do not experience relapses.


Decentralization and hospital pharmacy services: the case of Iranian university affilliated hospitals.
The aim of this study was to evaluate the satisfaction rate of hospital managerial/clinical teams (HMCTs) including principles (chief executives), managers, supervisor pharmacists and head nurses from services presented by private sectors directing 10 pharmacy departments in hospitals affiliated to Shahid Beheshti University of Medical Sciences. This study is an observational and descriptive study in which a questionnaire containing 16 questions evaluating the satisfaction of the HMCTs from private sectors, and questions about demography of the responders was used for data collection. Collected data was applied to assign a satisfaction score (maximum 64) for each respondent. SPSS 17.0 and Microsoft Office Excel 2007 were used for statistical description and analysis of these information (where applicable). Overall, 97 people in charge of the hospitals (HMCTs) entered the study. The average satisfaction score was 26.38 ± 6.81 with the lowest satisfaction rate observed in Mofid children specialty hospital (19.5%) and the highest rate obtained for Imam Hussein (p.b.u.h) general hospital (65.3%). Generally, 59% of the HMCTs believed that the function of the private sector in the pharmacy of hospitals is satisfactory. Assuming that the satisfaction scores under 75% of the total obtainable score (i.e. 48 out of 64) could not be considered as an indicator of desired pharmacy services, our results revealed that the status of the services offered by private sectors are far behind the desired satisfactory level.


BCL6 confers KRAS-mutant non-small-cell lung cancer resistance to BET inhibitors.
The bromodomain and extra-terminal domain (BET) proteins are promising therapeutic targets to treat refractory solid tumors; however, inherent resistance remains a major challenge in the clinic. Recently, the emerging role of the oncoprotein B cell lymphoma 6 (BCL6) in tumorigenesis and stress response has been unveiled. Here, we demonstrate that BCL6 was upregulated upon BET inhibition in KRAS-mutant cancers, including non-small-cell lung cancer (NSCLC). We further found that BRD3, not BRD2 or BRD4, directly interacted with BCL6 and maintained the negative autoregulatory circuit of BCL6. Disrupting this negative autoregulation by BET inhibitors (BETi) resulted in a striking increase in BCL6 transcription, which further activated the mTOR signaling pathway through repression of the tumor suppressor death-associated protein kinase 2. Importantly, pharmacological inhibition of either BCL6 or mTOR improved the tumor response and enhanced the sensitivity of KRAS-mutant NSCLC to BETi in both in vitro and in vivo settings. Overall, our findings identify a mechanism of BRD3-mediated BCL6 autoregulation and further develop an effective combinatorial strategy to circumvent BETi resistance in KRAS-driven NSCLC.


Assessing Hospital Adaptive Resource Allocation Strategies in Responding to Mass Casualty Incidents.
Hospitals are expected to operate at a high-performance level even under exceptional conditions of peak demand and resource disruptions. This understanding is not mature yet, and there are wide areas of possible improvement. In particular, the fast mobilization and reconfiguration of resources frequently result into the severe disruption of elective activities, worsening the quality of care. More resilient resource allocation strategies, ie, which adapt to the dynamics of the prevailing circumstance, are needed to maximize the effectiveness of health-care delivery. In this study, a simulation approach was adopted to assess and compare different hospital's adaptive resource allocation strategies in responding to a mass casualty incident (MCI). A specific set of performance metrics was developed to take into consideration multiple objectives and priorities and holistically assess the effectiveness of health-care delivery when coping with an MCI event. Discrete event simulation (DES) and system dynamics (SD) were used to model the key hospital processes and the MCI plan. In the daytime scenario, during the recovery phase of the emergency, a gradual disengagement of resources from the emergency department (ED) to restart ordinary activities in operating rooms and wards, returned the best performance. In the night scenario, the absorption capacity of the ED was evaluated by identifying the current bottleneck and assessment of the benefit of different resource mobilization strategies. The present study offers a robust approach, effective strategies, and new insights to design more resilient plans to cope with MCIs. Future research is needed to widen the scope of the analysis and take into consideration additional resilience capacities, such as operational coordination mechanisms, among multiple hospitals in the same geographic area.


The centriolar satellite protein Cep131 is important for genome stability.
The centrosome acts as a centre for microtubule organisation and plays crucial roles in cell polarity, migration, growth and division. Cep131 has recently been described as a basal body component essential for cilium formation, but its function in non-ciliogenic cells is unknown. We identified human Cep131 (also known as AZI1) in a screen for regulators of genome stability. We show that centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Cep131 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Depletion of Cep131 results in a reduction in proliferation rate, centriole amplification, an increased frequency of multipolar mitosis, chromosomal instability and an increase in post-mitotic DNA damage. These data therefore highlight the importance of human Cep131 for maintaining genomic integrity.


Changing the dehydrogenation pathway of LiBH4-MgH2via nanosized lithiated TiO2.
Nanosized lithiated titanium oxide (LixTiO2) noticeably improves the kinetic behaviour of 2LiBH4 + MgH2. The presence of LixTiO2 reduces the time required for the first dehydrogenation by suppressing the intermediate reaction to Li2B12H12, leading to direct MgB2 formation.


Electron temperatures and densities in the venus ionosphere: pioneer venus orbiter electron temperature probe results.
Altitude profiles of electron temperature and density in the ionosphere of Venus have been obtained by the Pioneer Venus orbiter electron temperatutre probe. Elevated temperatutres observed at times of low solar wind flux exhibit height profiles that are consistent with a model in which less than 5 percent of the solar wind energy is deposited at the ionopause and is conducted downward through an unmagnetized ionosphere to the region below 200 kilomneters where electron cooling to the neutral atmosphere proceeds rapidly. When solar wind fluxes are higher, the electron temperatures and densities are highly structured and the ionopause moves to lower altitudes. The ionopause height in the late afternoon sector observed thus far varies so widely from day to (day that any height variation with solar zenith angle is not apparent in the observations. In the neighborhood of the ionopause, measuremnents of plasma temperatures and densities and magnetic field strength indicate that an induced magnetic barrier plays an important role in the pressure transfer between the solar wind and the ionosphere. The bow, shock is marked by a distinct increase in electron current collected by the instrument, a featutre that provides a convenient identification of the bow shock location.


Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.
Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process. Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings. Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories. Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.


Mechanism by which shock wave lithotripsy can promote formation of human calcium phosphate stones.
Human stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS, resulting in CaP nucleation and tubular plugging. The left kidney (T) of nine farm pigs was treated with SWL, and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3 (-) delivery. Histopathological studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3 (-) delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3 (-), water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is the thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH.


Effectiveness of Thermal Annular Procedures in Treating Discogenic Low Back Pain.
Discogenic low back is a distinct clinic entity characterized by pain arising from a damaged disc. The diagnosis is clouded by the controversy surrounding discography. The treatment options are limited, with unsatisfactory results from both conservative treatment and surgery. Multiple interventional therapies have been developed to treat discogenic pain, but most have not yet been validated by high quality studies.The best studied treatment for discogenic pain is the use of heat, which has been labeled as thermal intradiscal procedures (TIPs) by the Centers for Medicare and Medicaid Services (CMS). As the pathology is located in the annulus, we use the term thermal annular procedures (TAPs). The aim of this study is to evaluate and update the efficacy of TAPs to treat chronic refractory discogenic pain. The design of this study is a systematic review. The available literature on TAPs in treating chronic refractory discogenic pain was reviewed. The quality of each article used in this analysis was assessed.The level of evidence was classified on a 5-point scale from strong, based upon multiple randomized controlled trials (RCTs) to weak, based upon consensus, as developed by the US Preventive Services Task Force (USPSTF) and modified by the American Society of Interventional Pain Physicians (ASIPP).Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2015 and manual searches of the bibliographies of known primary and review articles.The primary outcome measures were pain relief and functional improvement of at least 40%. Short-term efficacy was defined as improvement for less than 6 months; long-term efficacy was defined as improvement for 6 months or more. For this systematic review, 49 studies were identified. Of these, there were 4 RCTs and no observational studies which met the inclusion criteria. Based upon 2 RCTs showing efficacy, with no negative trials, there is Level I, or strong, evidence of the efficacy of biacuplasty in the treatment of chronic, refractory discogenic pain.Based upon one high-quality RCT showing efficacy and one moderate-quality RCT interpreted as showing no benefit, there is Level III, or moderate, evidence supporting the use of intradiscal electrothermal therapy (IDET) in treating chronic, refractory discogenic pain.The evidence supporting the use of discTRODE is level V, or limited. The evidence is Level I, or strong, that percutaneous biacuplasty is efficacious in the treatment of chronic, refractory discogenic pain. Biacuplasty may be considered as a first-line treatment for chronic, refractory discogenic pain.The evidence is Level III, or moderate, that IDET is efficacious in the treatment of chronic, refractory discogenic pain.The evidence is Level V, or limited, that discTRODE is efficacious in the treatment of chronic, refractory discogenic pain.Key words: Spinal pain, chronic low back pain, intradiscal disorder, IDET, biacuplasty, discTRODE, thermal intradiscal disorders, thermal annular disorders.


Photosynthetic redox control of nuclear gene expression.
Chloroplasts contain 3000-4000 different proteins but only a small subset of them is encoded in the plastid genome while the majority is encoded in the nucleus. Expression of these genes therefore requires a high degree of co-ordination between nucleus and chloroplast. This is achieved by a bilateral information exchange between both compartments including nucleus-to-plastid (anterograde) and plastid-to-nucleus (retrograde) signals. The latter represent a functional feedback control which couples the expression of nuclear encoded plastid proteins to the actual functional state of the organelle. The efficiency of photosynthesis is a very important parameter in this context since it is influenced by many environmental conditions and therefore represents a sensor for the residing environment. Components of the photosynthetic electron transport chain exhibit significant changes in their reduction/oxidation (redox) state depending on the photosynthetic electron flow and therefore serve as signalling parameters which report environmental influences on photosynthesis. Such redox signals control chloroplast and nuclear gene expression events and play an important role in the co-ordination of both genetic compartments. It is discussed here which photosynthetic parameters are known to control nuclear gene expression, how these signals are transduced toward the nucleus, and how they interact with other plastid retrograde signals and cytosolic light perception systems.


Prevalence of refractive error and attitude to spectacle use among drivers of public institutions in Ibadan, Nigeria.
High rate of motor vehicle accidents' have been associated with poor vision. Studies on drivers from elsewhere other than health institutions have found abnormal visual acuities. The aim of this study is to determine prevalence of refractive errors and the attitude to spectacle wear among drivers of public institutions studied. A cross sectional population study of all 99 motor vehicle drivers from the College of Medicine, University of Ibadan and University College Hospital (UCH) Ibadan between December 2003 and January 2004. The ninety-nine motor vehicle drivers in the study comprised of 67 (67.7%) from the College of Medicine, and 32 (32.3%) from the UCH. All were males, aged 38 to 60 years, mean 50.1 +/- (SD= 4.8 years). Proportion of drivers with refractive errors was 16.7% (95% CI, 16.6-16.8) but only 56.3% of these wear glasses while driving (others did not including 3 out 4 who were bilaterally visually impaired without glasses). Relative frequency of RTA among drivers was 16.2%, the risk was marginally higher among drivers with refractive error (OR 1.2, 95% CI: 0.4-3.7). The commonest refractive error was simple hypermetropia present in 15 eyes. Hypermetropia was associated with increasing age of drivers (p<0.05). Majority (97.7%) of the drivers were presbyopic but only 32 (32.3%) were current wearers of spectacles. Refractive errors were present in 16.7% of drivers studied. But 43.8% of these (3 out 4 of whom were bilaterally visually impaired without glasses) do not wear corrective lenses while driving. There is need for periodic visual screening exercise and eye health education on drivers.


Monitoring the three-dimensional distribution of endogenous species in the lungs by matrix-assisted laser desorption/ionization mass spectrometry imaging.
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is routinely employed to monitor the distribution of compounds in tissue sections and generate two-dimensional (2D) images. Whilst informative the images do not represent the distribution of the analyte of interest through the entire organ. The generation of 3D images is an exciting field that can provide a deeper view of the analyte of interest throughout an entire organ. Serial sections of mouse and rat lung tissue were obtained at 120 μm depth intervals and imaged individually. Homogenate registration markers were incorporated in order to aid the final 3D image construction. Using freely available software packages, the images were stacked together to generate a 3D image that showed the distribution of endogenous species throughout the lungs. Preliminary tests were performed on 16 serial tissue sections of mouse lungs. A 3D model showing the distribution of phosphocholine at m/z 184.09 was constructed, which defined the external structure of the lungs and trachea. Later, a second experiment was performed using 24 serial tissue sections of the left lung of a rat. Two molecular markers, identified as [PC (32:1) + K]+ at m/z 770.51 and [PC (36:4) + K]+ at m/z 820.52, were used to generate 3D models of the parenchyma and airways, respectively. A straightforward method to generate 3D MALDI-MS images of selected molecules in lung tissue has been presented. Using freely available imaging software, the 3D distributions of molecules related to different anatomical features were determined.


Early detection and response to meningococcal disease epidemics in sub-Saharan Africa: appraisal of the WHO strategy.
To assess the sensitivity, specificity and predictive value positive of the WHO threshold strategy for detecting meningococcal disease epidemics in sub-Saharan Africa and to estimate the impact of the strategy on an epidemic at district level. Data on meningitis cases at the district level were collected weekly from health ministries, WHO country and regional offices, and nongovernmental organizations in countries where there were epidemics of meningococcal disease in 1997. An epidemic was defined as a cumulative district attack rate of at least 100 cases per 100,000 population from January to May, the period of epidemic risk. The sensitivity, specificity and predictive value positive of the WHO threshold rate were calculated, and curves of sensitivity against (1 - specificity) were compared with alternatively defined threshold rates and epidemic sizes. The impact of the WHO strategy on a district epidemic was estimated by comparing the numbers of epidemic cases with cases estimated to have been prevented by vaccination. An analysis was made of 48 198 cases reported in 174 districts in Benin, Burkina Faso, the Gambia, Ghana, Mali, Niger, and Togo. These cases were 80.3% of those reported from Africa to WHO during the 1997 epidemic period. District populations ranged from 10,298 to 573,908. The threshold rate was crossed during two consecutive weeks in 69 districts (39.7%) and there were epidemics in 66 districts (37.9%). Overall, the sensitivity of the threshold rate for predicting epidemics was 97%, the specificity was 95%, and the predictive value positive was 93%. Taken together, these values were equivalent or better than the sensitivity, specificity and predictive value positive of alternatively defined threshold rates and epidemics, and remained high regardless of district size. The estimated number of potential epidemic cases decreased by nearly 60% in the age group targeted for vaccination in one district where the guidelines were followed in a timely manner. The use of the WHO strategy was sensitive and specific for the early detection of meningococcal disease epidemics in countries of sub-Saharan Africa during 1997 and had a substantial impact on a district epidemic. Nevertheless, the burden of meningococcal disease in these countries remains formidable and additional control measures are needed.


Analysis of Annotated and Unannotated Long Noncoding RNAs from Exosome Subtypes Using Next-Generation RNA Sequencing.
Long noncoding RNAs (lncRNAs) contain >200 nucleotides and act as regulatory molecules in transcription and translation processes in both normal and pathological conditions. LncRNAs have been reported to localize in nuclei, cytoplasm, and, more recently, extracellular vesicles such as exosomes. Exosomal lncRNAs have gained much attention as exosomes secreted from one cell type can transfer their cargo (e.g., protein, RNA species, and lipids) to recipient cells and mediate phenotypic changes in the recipient cell. In recent years, many exosomal lncRNAs have been discovered and annotated and are attracting much attention as potential markers for disease diagnosis and prognosis. It is expected that many exosomal lncRNAs are yet to be identified. However, characterization of unannotated exosomal RNAs with non-protein-coding sequences from massive RNA sequencing data is technically challenging. Here, we describe a method for the discovery of annotated and unannotated exosomal lncRNA. This method includes a large-scale isolation and purification strategy for exosome subtypes, using the human colorectal cancer cell line (LIM1863) as a model. The method inputs RNA sequencing clean reads and performs transcript assembly to identify annotated and unannotated exosomal lncRNAs. Cutoffs (length, number of exon, classification code, and human protein-coding probability) are used to identify potentially novel exosomal lncRNAs. Raw read count calculation and differential expression analysis are also introduced for downstream analysis and candidate selection. Exosomal lncRNA candidates are validated using RT-qPCR. This method provides a template for exosomal lncRNA discovery and analysis from next-generation RNA sequencing.


Escherichia coli 5'-nucleotidase: purification, properties and its release by osmotic shock.
Escherichia coli 5'-nucleotidase was purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis. Its molecular weight was estimated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, by gel exclusion chromatography, and by membrane filtration; values of 66 000, 48 500, and 15 000 to 30 000, respectively, were obtained. The enzyme was completely released from bacteria by osmotic shock treatment. The apparently anomalous behaviour of 5'-nucleotidase in terms of the molecular sieving hypothesis for the release of enzymes by osmotic shock proposed by Smith & Wyatt (1974) and extended by Broad & Smith (1979) is discussed.


Cell culture and animal studies for intracerebral delivery of borocaptate in liposomal formulation.
The efficacy of a liposomal formulation for intracerebral delivery of borocaptate (BSH) to brain tumor cells has been investigated using cell culture to study BSH uptake and persistence and using tumor-bearing rats to determine BSH distribution in the brain. During a 16-hr incubation, cellular uptake of BSH solution or BSH liposomal formulation was similar. However, the cellular persistence of BSH greatly increased when BSH was present in liposome. The differences in cellular persistence for BSH solution and BSH-loaded liposomes were significant both in 12-hr and 24-hr incubation experiments (p < 0.05 and p < 0.01, respectively). For the studies involving tumor-bearing rats, BSH level in tumor tissue was significantly higher than that in normal brain tissue at 2 hr and 6 hr after intracerebral injection of BSH-loaded liposomes (p < 0.01). Our study indicated that the liposomal formulation enhanced cellular persistence of BSH in tumor cells and therefore favored the boron accumulation in the cells. With the prolonged physical retention of liposomes at the local injection site and the cellular retention of BSH enhanced by the liposomes, the intracerebral delivery of BSH using liposomal formulation may provide an effective boron delivery approach for boron neutron capture therapy of brain tumors.


Targeted mutagenesis by homologous recombination in D. melanogaster.
We used a recently developed method to produce mutant alleles of five endogenous Drosophila genes, including the homolog of the p53 tumor suppressor. Transgenic expression of the FLP site-specific recombinase and the I-SceI endonuclease generates extrachromosomal linear DNA molecules in vivo. These molecules undergo homologous recombination with the corresponding chromosomal locus to generate targeted alterations of the host genome. The results address several questions about the general utility of this technique. We show that genes not near telomeres can be efficiently targeted; that no knowledge of the mutant phenotype is needed for targeting; and that insertional mutations and allelic substitutions can be easily produced.


Dominance and overdominance of mildly deleterious induced mutations for fitness traits in Caenorhabditis elegans.
We estimated the average dominance coefficient of mildly deleterious mutations (h, the proportion by which mutations in the heterozygous state reduce fitness components relative to those in the homozygous state) in the nematode Caenorhabditis elegans. From 56 worm lines that carry mutations induced by the point mutagen ethyl methanesulfonate (EMS), we selected 19 lines that are relatively high in fitness and estimated the viabilities, productivities, and relative fitnesses of heterozygotes and homozygotes compared to the ancestral wild type. There was very little effect of homozygous or heterozygous mutations on egg-to-adult viability. For productivity and relative fitness, we found that the average dominance coefficient, h, was approximately 0.1, suggesting that mildly deleterious mutations are on average partially recessive. These estimates were not significantly different from zero (complete recessivity) but were significantly different from 0.5 (additivity). In addition, there was a significant amount of variation in h among lines, and analysis of average dominance coefficients of individual lines suggested that several lines showed overdominance for fitness. Further investigation of two of these lines partially confirmed this finding.


BRG-1 is required for RB-mediated cell cycle arrest.
The antiproliferative action of the retinoblastoma tumor suppressor protein, RB, is disrupted in the majority of human cancers. Disruption of RB activity occurs through several disparate mechanisms, including viral oncoprotein binding, deregulated RB phosphorylation, and mutation of the RB gene. Here we report disruption of RB-signaling in tumor cells through loss of a critical cooperating factor. We have previously reported that C33A cells fail to undergo cell cycle inhibition in the presence of constitutively active RB (PSM-RB). To determine how C33A cells evade RB-mediated arrest, cell fusion experiments were performed with RB-sensitive cells. The resulting fusions were arrested by PSM-RB, indicating that C33A cells lack a factor required for RB-mediated cell cycle inhibition. C33A cells are deficient in BRG-1, a SWI/SNF family member known to stimulate RB activity. Consistent with BRG-1 deficiency underlying resistance to RB-mediated arrest, we identified two other BRG-1-deficient cell lines (SW13 and PANC-1) and demonstrate that these tumor lines are also resistant to cell cycle inhibition by PSM-RB and p16ink4a, which activates endogenous RB. In cell lines lacking BRG-1, we noted a profound defect in RB-mediated repression of the cyclin A promoter. This deficiency in RB-mediated transcriptional repression and cell cycle inhibition was rescued through ectopic coexpression of BRG-1. We also demonstrate that 3T3-derived cells, which inducibly express a dominant-negative BRG-1, arrest by PSM-RB and p16ink4a in the absence of dominant-negative BRG-1 expression; however, cell cycle arrest was abrogated on induction of dominant-negative BRG-1. These findings demonstrate that BRG-1 loss renders cells resistant to RB-mediated cell cycle progression, and that disruption of RB signaling through loss of cooperating factors occurs in cancer cells.


Estimates for the temporal response characteristics of chromatic pathways.
When equiluminous red and green fields are temporally alternated, it is generally accepted that the hue of the field fuses to yellow at a slower flicker rate than the critical flicker frequency (cff). However, when sufficient precautions are taken to avoid optically created achromatic artifacts and the illumination of the test field is kept fairly low (70 trolands), the modulation threshold for color fusion and that for flicker fusion are equivalent. The purely chromatic, artifact-free stimulus shows a much lower cff than has been reported in the literature under comparable conditions. It seems likely that many studies of the chromatic pathways have overestimated the ability of these pathways to follow rapid temporal alternation, presumably because the more sensitive achromatic pathways were detecting achromatic artifacts. A simple means for detecting achromatic artifacts in a temporal alternation will be demonstrated by the finding that an equiluminous surrounding field enhances modulation sensitivity only for achromatic flicker and not for chromatic flicker.


Apical hypertrophic cardiomyopathy: bedside diagnosis by intravenous contrast echocardiography.
Apical cardiomyopathy is rare in the West. The characteristic appearance on left ventriculography has been used to confirm the diagnosis of this condition; transthoracic echocardiography can also be useful in this regard. However, apical artifacts may obscure the typical appearance during echocardiography, and although the advent of tissue harmonic echocardiography has resulted in improved image quality, the technique still may be inadequate in the establishment of a diagnosis. We hypothesized that contrast echocardiography, which improves endocardial border delineation, may be the technique of choice for the diagnosis of apical hypertrophic cardiomyopathy. We report the case of a 40-year-old woman with Down syndrome who had chest pain. The electrocardiogram showed T-wave changes in the lateral precordial leads, but cardiac enzymes were normal. Tissue harmonic echocardiography showed apical akinesia. Intravenous contrast echocardiography, however, revealed typical features of hypertrophic apical cardiomyopathy. Thus contrast echocardiography may be used to establish the diagnosis of this condition.


The onion skin-like organization of the septum arises from multiple embryonic origins to form multiple adult neuronal fates.
In the past several decades, tremendous progress has been achieved through developmental studies of the central nervous system structures such as the cerebral cortex. The septum, which receives reciprocal connections from a variety of brain structures, contains diverse projection neurons but few interneurons. However, the mechanisms underlying its development remain poorly understood. Here we show that the septum is organized into an onion skin-like structure composed of five groups of neurons. These neurons are parvalbumin, choline acetyltransferase, neuronal nitric oxide synthase, calretinin and calbindin immunoreactive. Using the BrdU birth-dating method, we found that these five groups of neurons in the septum are grossly generated following an outside-in pattern. Interestingly, the distinct molecular identities of these neuronal subtypes correspond to their heterogeneous subpallial origins. Using three specific transgenic mouse lines and focal in utero electroporation of Cre-reporter plasmid, we showed that septal neurons originate from not only local progenitor regions but also neighboring progenitor regions including the medial ganglionic eminence and preoptic area. Thus, the neuronal diversity of the septum is achieved through both temporal and spatial control. Our results also suggest that multiple neuronal subtypes arrive to the septum through both radial and tangential migration. Based on these findings, we proposed a novel developmental model involving multiple spatial-temporal origins of septal neurons. This study presents new perspectives for comprehensively exploring septal functions in brain circuits.


Analysis of Sn-Bi Solders: X-ray Micro Computed Tomography Imaging and Microstructure Characterization in Relation to Properties and Liquid Phase Healing Potential.
This work provides an analysis of X-ray micro computed tomography data of Sn-xBi solders with x = 20, 30, 35, 47, 58 wt.% Bi. The eutectic thickness, fraction of eutectic and primary phase are analyzed. Furthermore, the 3D data is evaluated by means of morphology parameters, such as, shape complexity, flatness, elongation and mean intercept length tensor. The investigated alloys are categorized in three groups based on their morphology, which are described as "complex dominant", "complex- equiaxed" and "mixed". The mechanical behavior of Sn-Bi alloys in the semi-solid configuration and the correlation with microstructural parameters are discussed. A varying degree of geometric anisotropy of the investigated alloys is found through the mean intercept length tensor. Representative volume element models for finite element simulations (RVE-FEM) are created from tomography data of each alloy to analyze a correlation of geometric and elastic anisotropy. The simulations reveal an elastic isotropic behavior due to the small difference of elastic constants of primary and eutectic phase. A discussion of properties in the semi-solid state and liquid phase healing is provided.


Motivational deficits in major depressive disorder: Cross-sectional and longitudinal relationships with functional impairment and subjective well-being.
Many individuals with major depressive disorder present with prominent motivational deficits; however, the effect of these symptoms on functional outcomes in the illness remains unclear. Individuals with major depression who participated in the Sequenced Treatment Alternatives to Relieve Depression study were included in the present investigation (N=1563). Motivational deficits were evaluated using a derived measure from the Hamilton Depression Rating Scale, while functioning was assessed using the Work and Social Adjustment Scale. Subjective outcomes were also evaluated using the Quality of Life Enjoyment and Satisfaction Questionnaire. After treatment with citalopram, over 70% of participants continued to experience some degree of motivational deficits. These deficits were significantly associated with greater functional impairments both globally and in each domain of functioning evaluated. These symptoms were also linked to worse subjective outcomes such as overall life satisfaction and quality of life. Change in the severity of motivational deficits over time was significantly linked with changes in outcome. Motivational deficits continued to demonstrate a significant association with outcomes, even after controlling for potentially confounding variables such as duration of depressive episode and severity of other depressive symptoms. Motivational deficits are significantly linked to the functional impairment present in many people with major depression, just as they are in other psychiatric illnesses such as schizophrenia. A greater understanding of the underlying mechanisms of these motivational deficits in particular, beyond other depressive symptoms, is critical to the development of strategies aimed at enhancing functional recovery and improved subjective well-being.


Relationships between feed efficiency, scrotal circumference, and semen quality traits in yearling bulls.
A meta-analysis was conducted to examine phenotypic relationships between feed efficiency, scrotal circumference, and semen quality traits in yearling bulls. Data evaluated were obtained from 5 postweaning trials involving Angus (n = 92), Bonsmara (n = 62), and Santa Gertrudis (n = 50) bulls fed diets that ranged from 1.70 to 2.85 Mcal ME/kg DM. After an adaptation period of 24 to 28 d, feed intake was measured daily, and BW was measured at 7- or 14-d intervals during the 70- to 77-d trials. Ultrasound carcass traits (12th-rib back fat thickness, BF; LM area, LMA) and scrotal circumference (SC) were measured at the start and end of each trial. Semen samples were collected by electroejaculation within 51 d of the end of the trials when the age of bulls averaged from 365 to 444 d and were evaluated for progressive sperm motility and morphology. Residual feed intake (RFI) was calculated as the difference between actual DMI and expected DMI from linear regression of DMI on ADG and midtest BW(0.75), with trial, trial by ADG, and trial by midtest BW(0.75) as random effects. Across all studies, bulls with low RFI phenotypes (<0.5 SD below the mean RFI of 0) consumed 20% less DM and had 10% less BF but had similar ADG, SC, and semen quality traits compared with high-RFI bulls (>0.5 SD above the mean RFI of 0). Gain to feed ratio was strongly correlated with ADG (0.60) and weakly correlated with initial BW (-0.17) and DMI (-0.26). Residual feed intake was not correlated with ADG, initial age, or BW but was correlated with DMI (0.71), G:F (-0.70), and BF (0.20). Initial SC (-0.20), gain in SC (-0.28), and percent normal sperm (-0.17) were correlated with G:F, but only sperm morphology was found to be weakly associated with RFI (0.13). These data suggest that RFI is not phenotypically associated with SC or sperm motility but is weakly associated with sperm morphology.


A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: applications in detecting the activity of phagocyte NADPH oxidase and other oxidases.
The enzymatic determination of hydrogen peroxide can be accomplished with high sensitivity and specificity using N-acetyl-3, 7-dihydroxyphenoxazine (Amplex Red), a highly sensitive and chemically stable fluorogenic probe for the enzymatic determination of H2O2. Enzyme-catalyzed oxidation of Amplex Red, which is a colorless and nonfluorescent derivative of dihydroresorufin, produces highly fluorescent resorufin, which has an excitation maximum at 563 nm and emission maximum at 587 nm. The reaction stoichiometry of Amplex Red and H2O2 was determined to be 1:1. This probe allows detection of 5 pmol H2O2 in a 96-well fluorescence microplate assay. When applied to the measurement of NADPH oxidase activation, the Amplex Red assay can detect H2O2 release from as few as 2000 phorbol myristate acetate-stimulated neutrophils with a sensitivity 5- to 20-fold greater than that attained in the scopoletin assay under the same experimental conditions. Furthermore, the oxidase-catalyzed assay using Amplex Red results in an increase in fluorescence on oxidation rather than a decrease in fluorescence as in the scopoletin assay. In comparison with other fluorometric and spectrophotometric assays for the detection of monoamine oxidase and glucose oxidase, this probe is also found to be more sensitive. Given its high sensitivity and specificity, Amplex Red should have a broad application for the measurement of H2O2 in a variety of oxidase-mediated reactions and very low levels of H2O2 in food, environmental waters, and consumer products.


Retinal telangiectasis in facioscapulohumeral muscular dystrophy with deafness.
A 22-year-old patient with newly diagnosed facioscapulohumeral (FSH) muscular dystrophy had a macular lesion in her right eye and poor central vision, which had been present since early childhood. Fluorescein angiographic examination revealed bilateral peripheral vessel closure, peripheral retinal telangiectasis, and hyperfluorescence in both foveae. This widespread vascular abnormality was deemed responsible for her macular disease. Her mother, brother, and sister, all of whom are affected by varying degrees of FSH muscular dystrophy and clinical deafness, also have abnormal retinal vasculature, as determined by fluorescein angiography. However, none had related visual symptoms and two showed no ophthalmoscopic evidence of vascular abnormalities. In young patients with unexplained retinal vascular lesions, the diagnosis of FSH muscular dystrophy should be considered. Similarly, young patients with FSH muscular dystrophy should be examined for sight-threatening and potentially treatable vascular retinopathy.


Breaking down barriers: multidisciplinary education model.
A pilot project was implemented involving students from three disciplines: dental hygiene, physical therapy, and physician assistant. The purpose was to prepare students to work together in multidiscipline teams utilizing concepts of problem-based learning (PBL) on both simulated and real patients. The project was divided into three phases. Phase I introduced discipline specific information, team concepts, and PBL concepts. Phase II involved students working in multidisciplinary teams solving a simulated patient case in the PBL format. Phase III consisted of students working in small groups and on real patients, performing an extraoral/intraoral and periodontal examination, a problem oriented physical examination, and a neuromuscular assessment. Pre and posttest evaluation of Phase I revealed no difference in knowledge among the three disciplines. Of those students evaluating Phase II and III, 100% felt PBL was an effective means of presenting multidisciplinary material; 93% reported enhanced problem-solving; 98% indicated improvements in working in groups; and 98% felt they had learned more about each other's discipline. This model may provide a viable means to prepare interdisciplinary teams to work effectively together.


Effects of food restriction across stages of juvenile and early adult development on body weight, survival and adult life history.
Organisms have to allocate limited resources among multiple life-history traits, which can result in physiological trade-offs, and variation in environmental conditions experienced during ontogeny can influence reproduction later in life. Food restriction may lead to an adaptive reallocation of the limited resources among traits as a phenotypically plastic adjustment, or it can act as an overall constraint with detrimental effects throughout reproductive life. In this study, we investigated experimentally the effects of food restriction during different stages of the juvenile and early adult development on body weight, survival and reproductive success in females and males of the European earwig Forficula auricularia. Individuals either received limited or unlimited access to food across three different stages of development (fully crossed) allowing us to identify sensitive periods during development and to test both additive and interactive effects of food limitation across stages on development and reproduction. Food restriction during the early and late juvenile stage had additive negative effects on juvenile survival and adult body weight. With regard to reproductive success of females which produce up to two clutches in their lifetime, restriction specifically in the late juvenile stage led to smaller first and second clutch size, lower probability of second clutch production and reduced hatching success in the second clutch. Reproductive success of females was not significantly affected when their male mates experienced food restriction during their development. Our findings in general support the 'silver-spoon' hypothesis in that food restriction during juvenile development poses constraints on development and reproduction throughout life.


[Testing of polyurethane as an implant for its biological compatibility].
A simple biological method is described for testing the biological compatibility of plastics without histological investigation. This is the implantation into the anterior chamber of the rabbit eye. The test material is polyurethane soft foam (SYSpur). It can be observed as biologically compatible. This result agreed with expert opinions on toxicity and histocompatibility.


Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.
Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.


Aluminum tolerance in transgenic plants by alteration of citrate synthesis.
Aluminum when in soluble form, as found in acidic soils that comprise about 40 percent of the world's arable land, is toxic to many crops. Organic acid excretion has been correlated with aluminum tolerance in higher plants. Overproduction of citrate was shown to result in aluminum tolerance in transgenic tobacco (Nicotiana tabacum) and papaya (Carica papaya) plants.


Tail docking in pigs: acute physiological and behavioural responses.
Tail docking of piglets is a routine procedure on farms to control tail-biting behaviour; however, docking can cause an acute stress response. The objectives of this research were to determine the stress responses to tail docking in piglets and to compare two methods of tail docking; cautery iron (CAUT) and the more commonly used blunt trauma cutters (BT). At approximately 6 days of age, piglets were tail docked using CAUT (n = 20), BT (n = 20) or sham tail docked with their tails remaining intact (CON; n = 40). Blood samples were taken prior to tail docking and at 30, 60 and 90 min after tail docking to evaluate the effect of tail docking on white blood cell (WBC) measures and cortisol concentrations. The above experiment was repeated to observe behaviour without the periodic blood sampling, so as not to confound the effects of blood sampling on piglet behaviour. Piglet behaviour was recorded in the farrowing crate using 1 min scan-samples via live observations for 60 min prior to and 90 min after tail docking. Total WBC counts were reduced (P > 0.05) among BT and CAUT compared with CON piglets 30 min after tail docking. Cortisol concentrations were higher (P < 0.01) among BT compared with CON and CAUT piglets 60 min after tail docking. Cautery and BT-docked piglets spent more (P < 0.05) time posterior scooting compared with CON piglets between 0 and 15 min, and 31 and 45 min after tail docking. Piglets tail docked using CAUT and BT tended to spend more (P < 0.07) time sitting than CON piglets between 0 and 15 min post tail docking. Elevated blood cortisol can be reduced by the use of the CAUT rather than the BT method of tail docking. Although the tail docking-induced rise in cortisol was prevented by using CAUT, the behavioural response to BT and CAUT docking methods was similar.


[Tissue Doppler imaging of physiological asynchrony in intracardiac myocardium].
Tissue Doppler imaging (TDI) is one of the most widely used methods of quantitative assessment of asynchrony of ventricular myocardium movements. To study the parameters physiological asynchrony using TDI, we examined 32 healthy subjects (18 male, 14 female, mean age of 35.8 +/- 11.0) with no history and signs of cardiovascular disease. The putative relative parameters of systolic and diastolic asynchrony (intra- and interventricular heterogeneity at basal and mid level of 8 myocardial segments) and traditional absolute values (septolateral S-L delay, QE, TsSD, TESD intervals) were measured and compared. We have established the range of normal values of the relative physiological myocardium asynchrony factors in healthy persons, and found that systolic and diastolic asynchrony is more evident at the midventricular level compared to basal level, and diastolic asynchrony is more apparent than systolic; this fact is discussed in terms of single-layer spiral myocardium theory.


Full-length messenger RNA sequences greatly improve genome annotation.
Annotation of eukaryotic genomes is a complex endeavor that requires the integration of evidence from multiple, often contradictory, sources. With the ever-increasing amount of genome sequence data now available, methods for accurate identification of large numbers of genes have become urgently needed. In an effort to create a set of very high-quality gene models, we used the sequence of 5,000 full-length gene transcripts from Arabidopsis to re-annotate its genome. We have mapped these transcripts to their exact chromosomal locations and, using alignment programs, have created gene models that provide a reference set for this organism. Approximately 35% of the transcripts indicated that previously annotated genes needed modification, and 5% of the transcripts represented newly discovered genes. We also discovered that multiple transcription initiation sites appear to be much more common than previously known, and we report numerous cases of alternative mRNA splicing. We include a comparison of different alignment software and an analysis of how the transcript data improved the previously published annotation. Our results demonstrate that sequencing of large numbers of full-length transcripts followed by computational mapping greatly improves identification of the complete exon structures of eukaryotic genes. In addition, we are able to find numerous introns in the untranslated regions of the genes.


Coping Strategies and Factors Related to Problematic Substance Use and Behavioral Addictions Among Adolescents and Young Adults with Cancer.
Purpose: This study aimed to explore and identify the factors associated with problematic substance use (alcohol, tobacco, and cannabis) and behavioral addictions (internet and eating disorders) over time in adolescents and young adults (AYAs) treated for cancer. Methods: AYAs newly diagnosed with cancer, 15-25 years of age, completed a questionnaire during their hospitalization (T1), assessing their consumption of alcohol, tobacco, and cannabis (The Alcohol Use Disorders Identification Test; The Smoking Behavior Questionnaire; and The Cannabis Abuse Screening Test), their internet use (The Internet Addiction Test), their body preoccupations (The Eating Attitudes Test), as well as their coping strategies (Brief COPE) and emotional adjustment (The Hospital Anxiety and Depression Scale). Questionnaires were completed again 6 months later (T2). Results: Seventy-three AYAs were included at T1 and 21 AYAs at T2. Nearly one out of two (46.58%) AYAs had a problematic substance use or behavioral addiction after cancer diagnosis (T1). Problematic use of internet was frequently reported (23.29%), as well as harmful alcohol consumption or addiction (16.44%) and cannabis dependence (12.33%). The main factor related to problematic substance use was being older, while the main factor related to behavioral addiction was having a higher anxiety score. Substance use as a coping strategy was used more frequently by AYAs with problematic substance use and emotional support as a coping strategy was used more frequently by AYAs with a behavioral addiction. Conclusions: High rates of problematic substance use and behavioral addiction were reported in our sample. AYAs surveyed had high problematic use of cannabis and high internet use. Attention to substance use and addictive behaviors is recommended to ensure optimal care.


Combining wet etching and real-time damage event imaging to reveal the most dangerous laser damage initiator in fused silica.
A reliable method, combining a wet etch process and real-time damage event imaging during a raster scan laser damage test, has been developed to directly determine the most dangerous precursor inducing low-density laser damage at 355 nm in fused silica. It is revealed that ~16% of laser damage sites were initiated at the place of the scratches, ~49% initiated at the digs, and ~35% initiated at invisible defects. The morphologies of dangerous scratches and digs were compared with those of moderate ones. It is found that local sharp variation at the edge, twist, or inside of a subsurface defect is the most dangerous laser damage precursor.


Appropriateness of the revised Japanese guidelines' risk classification for the prognosis of papillary thyroid carcinoma: a retrospective analysis of 5,845 papillary thyroid carcinoma patients.
The revised Japan Association of Endocrine Surgeons (JAES)/Japanese Society of Thyroid Surgery (JSTS) guidelines for patients with papillary thyroid carcinoma (PTC) describe four risk classes: very-low-risk, low-risk, intermediate-risk, and high-risk. Here we conducted a retrospective analysis to evaluate the appropriateness of these guidelines' risk classification of PTCs. Lymph node recurrence-free, distant recurrence-free and cause-specific survivals at 15-year of high-risk group were significantly poorer than those at 15-year of intermediate-group and these survivals of intermediate-group were poorer than of low- or very-low-risk patients. In the subset analyses based on patient age (≥55 years and <55 years), we obtained the same results in both subsets. Age significantly worsen the whole prognosis of high-risk patients and cause-specific survival of intermediate-risk patients, but not the prognosis of low- or very-low-risk patients. Therefore, the risk classification of the revised JAES/JSTS guidelines is appropriate, and therapeutic strategies should be decided based on the risk class together with the patients' age.


Bovine milk proteome in the first 9 days: protein interactions in maturation of the immune and digestive system of the newborn.
In order to better understand the milk proteome and its changes from colostrum to mature milk, samples taken at seven time points in the first 9 days from 4 individual cows were analyzed using proteomic techniques. Both the similarity in changes from day 0 to day 9 in the quantitative milk proteome, and the differences in specific protein abundance, were observed among four cows. One third of the quantified proteins showed a significant decrease in concentration over the first 9 days after calving, especially in the immune proteins (as much as 40 fold). Three relative high abundant enzymes (XDH, LPL, and RNASE1) and cell division and proliferation protein (CREG1) may be involved in the maturation of the gastro-intestinal tract. In addition, high correlations between proteins involved in complement and blood coagulation cascades illustrates the complex nature of biological interrelationships between milk proteins. The linear decrease of protease inhibitors and proteins involved in innate and adaptive immune system implies a protective role for protease inhibitor against degradation. In conclusion, the results found in this study not only improve our understanding of the role of colostrum in both host defense and development of the newborn calf but also provides guidance for the improvement of infant formula through better understanding of the complex interactions between milk proteins.


[Diverticuli of duodenal papillar region and their role in development of choledocholithiasis and strictures of bile and pancreatic ducts].
Up to present time there is no common view on the role of diverticuli of the papillar region of the duodenum (DPRD) in development of the strictures of terminal parts of the common bile duct and major pancreatic duct. The main method for the diagnosis of DPRD is fibroduodenoscopy (FDS). Relaxational FDS is the most informative method for detailed examination of diverticulum and for assessment of its interrelations with longitudinal crease and the major duodenal papilla (MDP). During the last 2 years all patients with DPRD underwent ERCPG, which helped to obtain more complete information of the presence and the character of the strictures of terminal parts of the common bile duct and the pancreatic duct. DPR has been revealed in 5% of patients with calculous cholecystitis and in 9.5% of patients with choledocholithiasis. Of the patients, admitted to the Institute for postcholecystectomy syndrome from 1994 to 1999, DPRD were revealed in 30% of cases. The patients with DPR and chronic pancreatitis of nonalcoholic and nonlithogenic etiology, made up 9% of all patients with DPR and chronic pancreatitis. In 87 patients with DPR, suffering from various surgical diseases, following changes of bile and pancreatic ducts were revealed: choledocholithiasis (47%), stenosis of the large bile duct (15%), strictures of terminal parts of the large bile duct and major pancreatic duct (10%). There is evidence, that para- and peripapillary diverticuli deteriorate evacuatory function of the bile and pancreatic tracts due to compression of terminal parts of the choledochus and the pancreatic ducts with strictures formation, which promote disturbances of the bile and pancreatic juice passage. Biliary stasis and pancreatic juice passage disturbances create favorable conditions for lithogenesis and promote development of cholangitis, mechanical jaundice and chronic pancreatitis. Patients with choledochal and major pancreatic duct strictures and stenoses of the papilla in DPR underwent EPST with favorable initial and long-term results. The authors suggest, that DPR are an important etiopathogenetic link in the development of many diseases of the organs of hepatobiliary region, associated with biliary and pancreatic hypertension.


Properties and applications of new monoclonal antibodies raised against calf DNA polymerase alpha.
A panel of 12 hybridoma cell lines secreting monoclonal antibodies against alpha-polymerase were prepared by fusion of mouse myeloma cells and spleen cells of a rat immunized with homogeneous calf thymus alpha-polymerase. Hybridomas were selected and cloned on the basis of immunobinding to pure alpha-polymerase in solid phase radioimmunoassay. Antibodies secreted by these cells eventually were purified in milligram quantities from ascites fluids. These antibodies, all of the rat immunoglobulin M class, cross-reacted with alpha-polymerases from calf and monkey cells as revealed by immunobinding in radioimmunoassay and by immunoprecipitation of DNA polymerase activity. The antibodies were not capable of neutralizing the enzyme activity. With the methods described these antibodies may be used to immunoprecipitate alpha-polymerase from crude extracts of mammalian cells and to measure levels of the enzyme protein.


Analysis of postoperative radiotherapy effects within risk groups in patients with FIGO I, II, and III endometrial cancer.
To define indications for adjuvant radiotherapy in patients with endometrial cancer, the risk groups have been established according to clinical and pathological prognostic factors. The purpose was to determine precise criteria for adjuvant radiotherapy and identify patients with increased risk for disease relapse who may benefit from postoperative radiotherapy, with an acceptable level of toxicity. A retrospective study was conducted at the Department of Oncology and Radiology, Kragujevac, during a 5-year period. A group of 80 patients with endometrial cancer treated with adjuvant radiotherapy were included in the study. Patients were divided into four risk groups according to ESMO-ESGO-ESTRO Consensus Conference classification. The Kaplan-Meier method was used for overall and progression-free survival. A statistical analysis was performed using SPSS 20.0 statistical software. The 5-year survival rate was 80%, and 66.3% patients were progression-free during this period. Fatal outcome occurred in 20% of patients. The results showed survival was shortest in patients from the high-risk group. Factors that had impact on the 5-year survival were comorbidities, FIGO stage, postoperative radiotherapy, organ site of late toxicity, and localization of metastases. The analysis of postoperative radiotherapy effects showed that 72.5% of patients had no complications. The most common symptoms of late irradiation toxicity arose from the gastrointestinal tract. Toxicity was usually moderate. Adjuvant radiotherapy can potentially prolong survival and prevent recurrence, with acceptable level of toxicity, to preserve patient's quality of life. Patient classification into appropriate risk groups allows for adjuvant treatment individualization.


Ultrathin Rh Nanosheets with Rich Grain Boundaries for Efficient Hydrogen Oxidation Electrocatalysis.
Two-dimensional (2D) Pt-group ultrathin nanosheets (NSs) are promising advanced electrocatalysts for energy-related catalytic reactions. However, improving the electrocatalytic activity of 2D Pt-group NSs through the addition of abundant grain boundaries (GBs) and understanding the underlying formation mechanism remain significant challenges. Herein, we report the controllable synthesis of a series of Rh-based nanocrystals (e.g., Rh nanoparticles, Rh NSs, and Rh NSs with GBs) through a CO-mediated kinetic control synthesis route. In light of the 2D NSs' structural advantages and GB modification, the Rh NSs with rich GBs exhibit an enhanced electrocatalytic activity compared to pure Rh NSs and commercial Pt/C toward the hydrogen oxidation reaction (HOR) in alkaline media. Both experimental results and theoretical computations corroborate that the GBs in the Rh NSs have the capacity to ameliorate the adsorption free energy of reaction intermediates during the HOR, thus resulting in outstanding HOR catalytic performance. Our work offers novel perspectives in the realm of developing sophisticated 2D Pt-group metal electrocatalysts with rich GBs for the energy conversion field.


An ultrastructural analysis of breast carcinoma presenting as isolated axillary adenopathy.
Metastatic adenocarcinoma in the axillary lymph nodes of a female patient often originates from a primary tumor in the ipsilateral breast. Mastectomy may be recommended if adenocarcinoma is found in the axillary nodes even when the primary tumor is not clinically detectable. In these circumstances, the recommendation for mastectomy should be based on the firm histologic diagnosis of adenocarcinoma. In the present report, five female patients are discussed who presented with axillary lymphadenopathy without clinically evident breast masses or mammographic evidence of malignancy. Axillary lymph node biopsies, performed in each patient, were inconclusive after conventional light microscopic examination. Electron microscopy established the diagnosis of adenocarcinoma. These findings were complemented by sex steroid analyses of the tumors where possible. Each patient underwent ipsilateral mastectomy, and in each specimen an occult breast carcinoma was found. The necessity of making a precise tissue diagnosis in all cases of metastatic cancer from an unknown primary is stressed, and special techniques to accomplish this must be considered preoperatively. This is particularly important in the female patient with metastatic breast carcinoma in an isolated axillary lymph node, since ipsilateral mastectomy may be curative.


[The parameters of clearance of industrially significant alpha-emitters from the lungs of mammals].
Results of assessment of biokinetic parameters of change in the burden of significant alpha-emitters in the lungs of mammals in various times after inhalation intake (Qt(lung)) were generalized. 1740 Wistar rats of both sex with the initial age of 2-2.5 months and 143 mature mongrel dogs used in 23 and 3 animal tests, respectively, were involved in this work. The analysis of experimental data resulted in selection of three groups of chemically soluble compounds of alpha-emitters that differ in the rate of radionuclide clearance from the lung as well as in integral doses. Stable complex compounds of quadrivalent and of hexavalent nuclides and non-complex salts of quinquivalent and of hexavalent 237Np were assigned to the group of soluble compounds of 239Pu and 237Np. A three-component exponential model of change in Qt(lung) with the prevalence of fast and of intermediate phases (55%, T(eff) = 0.41 days and 35%, T(eff) = 18.1 days respectively) and the presence of a slow clearance phase (10%, T(eff) = 206 days) was developed for these compounds. Complex compounds of quadrivalent 239Pu and 237Np unstable in the environment of pH and of body temperature, their non-complex salts of mineral acids in ionic or polymer form, and submicron plutonium dioxide (SMD = 0.07 mkm) were assigned to the group of relatively soluble compounds includes. An exponential model with 2-3 components with the prevalence of intermediate and of slow clearance phases (71%, T(eff) = 19.3 days and 22%, T(eff) = 169 days respectively) was developed for compounds of this group. The third group of the compounds is presented based on the soluble 241Am compounds that could be typical for stable trivalent compounds of rare-earth and transuranium radionuclides. Their biokinetics is described by a 3-4-component exponential model with the fast phase prevailing (96.7%, T(eff) < or = 6.8 days), and with intermediate (2.6%, T(eff) = 69 days) and with slow (0.7%, T(eff) = 1040 days) phases being negligible. Physical chemicas and biological processes determining nuclides biokinetics in lungs are discussed.


Reliability and validity of a linear position transducer for measuring jump performance.
This study determined the reliability and validity of a linear position transducer to measure jump performance by comparing the mean force, peak force, and time-to-peak force measurements with data obtained simultaneously with a force platform. Twenty-five men performed squat, countermovement, and drop jumps with the linear transducer connected from a waist belt and base, which were placed upon a force platform. The Pearson correlation coefficients across the 3 jumps for the mean force (r = 0.952-0.962), peak force (r = 0.861-0.934), and time-to-peak force (r = 0.924-0.995) were high, providing evidence that the linear-transducer and force-platform measurements were similar. The trial-to-trial reliability of the jumps measured by the linear position transducer gave an intraclass correlation coefficient of 0.924-0.975 for mean force, 0.977-0.982 for peak force, and 0.721-0.964 for time-to-peak force. The coefficients of variation were 2.1-4.5% for mean force, 2.5-8.4% for peak force, and 4.1-11.8% for time-to-peak force. Our findings showed that the calculations derived from the linear transducer were very similar to those of the force platform and hence provided evidence of the validity of this method. The data from the linear transducer were also shown to be reliable. Therefore, this method of calculating force may provide a cost-effective alternative to the force platform for measuring this variable.


Unveiling the Microfiber Release Footprint: Guiding Control Strategies in the Textile Production Industry.
Microplastic fibers from textiles have been known to significantly contribute to marine microplastic pollution. However, little is known about the microfiber formation and discharge during textile production. In this study, we have quantified microfiber emissions from one large and representative textile factory during different stages, spanning seven different materials, including cotton, polyester, and blended fabrics, to further guide control strategies. Wet-processing steps released up to 25 times more microfibers than home laundering, with dyeing contributing to 95.0% of the total emissions. Microfiber release could be reduced by using white coloring, a lower dyeing temperature, and a shorter dyeing duration. Thinner, denser yarns increased microfiber pollution, whereas using tightly twisted fibers mitigated release. Globally, wet textile processing potentially produced 6.4 kt of microfibers in 2020, with China, India, and the US as significant contributors. The study underlined the environmental impact of textile production and the need for mitigation strategies, particularly in dyeing processes and fiber choice. In addition, no significant difference was observed between the virgin polyesters and the used ones. Replacing virgin fibers with recycled fibers in polyester fabrics, due to their increasing consumption, might offer another potential solution. The findings highlighted the substantial impact of textile production on microfiber released into the environment, and optimization of material selection, knitting technologies, production processing, and recycled materials could be effective mitigation strategies.


Rachis morphology cannot accurately predict the mechanical performance of primary feathers in extant (and therefore fossil) feathered flyers.
It was previously suggested that the flight ability of feathered fossils could be hypothesized from the diameter of their feather rachises. Central to the idea is the unvalidated assumption that the strength of a primary flight feather (i.e. its material and structural properties) may be consistently calculated from the external diameter of the feather rachis, which is the only dimension that is likely to relate to structural properties available from fossils. Here, using three-point bending tests, the relationship between feather structural properties (maximum bending moment, Mmax and Young's modulus, Ebend) and external morphological parameters (primary feather rachis length, diameter and second moment of area at the calamus) in 180 primary feathers from four species of bird of differing flight style was investigated. Intraspecifically, both Ebend and Mmax were strongly correlated with morphology, decreasing and increasing, respectively, with all three morphological measures. Without accounting for species, however, external morphology was a poor predictor of rachis structural properties, meaning that precise determination of aerial performance in extinct, feathered species from external rachis dimensions alone is not possible. Even if it were possible to calculate the second moment of area of the rachis, our data suggest that feather strength could still not be reliably estimated.


[Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells].
Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.


The Impact of Hypernatremia in Preterm Infants on Neurodevelopmental Outcome at 18 Months of Corrected Age.
The study objective was to assess the correlation between hypernatremia during the first week of life and neurodevelopmental outcomes at 18 months of corrected age in premature infants. A retrospective observational study of preterm infants born at less than 32 weeks of gestation who had a neurodevelopmental assessment with the Bayley scales of infant and toddler development III at 18 ± 6 months of corrected age. Serum sodium levels from birth through 7 days of life were collected. The study cohort was divided into two groups: infants with a peak serum sodium of >145 mmol/L (hypernatremia group) and infants with a peak serum sodium level of <145 mmol/L (no hypernatremia group). Prenatal, intrapartum, and postnatal hospital course and neurodevelopmental data at 18 ± 6 months were collected. Logistic regression analysis was used to assess the correlation between neonatal hypernatremia and neurodevelopment with adjustment for selected population characteristics. Eighty-eight preterm infants with complete neurodevelopmental outcome data at 18 ± 6 months of corrected gestational age were included in the study. Thirty-five neonates were in the hypernatremia group and 53 were in the no hypernatremia group. Maternal and neonatal characteristics were similar between the two groups except that the hypernatremia group had a significantly lower average birth weight and gestational age. Comparison of the mean neurodevelopmental scores between the two groups showed that patients in the hypernatremia group as compared with those in the no hypernatremia group had significantly lower neurodevelopmental scaled scores in the fine motor domain (p = 0.01). This difference remained significant (p = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6-0.97) when adjusted for birth weight and gestational age. Preterm infants born at less than 32 weeks of gestation with hypernatremia in the first week of life have lower fine motor scores at 18 months of corrected age. · Hypernatremia is a common electrolyte disturbance in preterm neonates.. · Hypernatremia may be associated with long-term neurodevelopmental outcomes in preterm infants.. · Hypernatremia is a potentially modifiable risk factor..


The psychosocial experience of individuals living with osteogenesis imperfecta: a mixed-methods systematic review.
Osteogenesis imperfecta (OI) is a genetic disorder (prevalence: 1:10,000), leading to bone fragility, frequent fractures, and varying degrees of physical limitations. Despite a substantial amount of research on the genetics, pathophysiology, and treatments related to OI, there remains a paucity of knowledge concerning the lived psychosocial experience of the OI population. This mixed-methods systematic review aimed to review, appraise, and synthesize the literature on the psychosocial experience of children and adults with OI with the goal of identifying implications for research, practice, and policy-making. Using a systematic methodology, quantitative, qualitative, and mixed-methods studies were accessed through database searching, screened, assessed for eligibility, and appraised. Data from the selected studies fulfilling the eligibility and quality criteria were extracted and synthesized using thematic analysis with an inductive approach. A total of four qualitative and 20 quantitative studies, with various study designs and methodologies ranging in quality, were included in the review (n = 800; comprising 610 children and 175 adults with OI types I, III, IV, and V, ten parents and five healthcare professionals). Six themes were identified: intellectual feats, isolation and feeling different, fear of fractures, coping with challenges, adapting by learning new skills, and social relationships. These findings highlighted key aspects of the experiences of children and adults with OI and will be essential for improving the quality and direction of research, tailoring clinical interventions addressing the psychosocial needs and quality of life of individuals with OI, and raising awareness among caregivers, healthcare professionals, administrators, and policy-makers associated with the OI population.


Soil erosion and deposition in the new shorelines of the Three Gorges Reservoir.
During the last few decades, the construction of storage reservoirs worldwide has led to the formation of many new shorelines in former upland areas. After the formation of such shorelines, a dynamic phase of soil erosion and deposition follows. We explored the factors regulating soil dynamics in the shorelines of the Three Gorges Reservoir (TGR) on the Yangtze River in China. We selected four study sites on the main stem and three on the tributaries in the upstream parts of the reservoir, and evaluated whether the sites close to the backwater tail (the point at which the river meets the reservoir) had more soil deposition than the sites far from the backwater tail. We also tested whether soil erosion differed between the main stem and the tributaries and across shorelines. We found that soil deposition in the new shorelines was higher close to the backwater tail and decreased downstream. Soil erosion was higher in the main stem than in the tributaries and higher at lower compared to higher shoreline altitudes. In the tributaries, erosion did not differ between higher and lower shoreline levels. Erosion increased with increasing fetch length, inundation duration and distance from the backwater tail, and decreased with increasing soil particle fineness. Our results provide a basis for identifying shorelines in need of restorative or protective measures.


Association between family history of alcohol use disorder and catamenial epilepsy.
The purpose of this investigation was to determine whether a family history of alcohol use disorder (AUD) might be a risk factor and possible clinical biomarker for catamenial epilepsy. The retrospective case-control data came from 119 women, aged 13-48 years, with intractable seizures. We report the relative risk for positive family history of AUD among women with catamenial epilepsy (Group 1) relative to women with noncatamenial epilepsy (Group 2). The risk ratio (RR) for positive AUD history for Group 1 (n = 59) relative to Group 2 (n = 60) was 3.46 (95% confidence interval = 1.36-8.76, p = .009). The RRs were significant for women who had the (C1) perimenstrual (p = .009) and (C3) entire luteal phase (p = .003) patterns but not the (C2) preovulatory pattern. AUD history had a high specificity of 91.7% (55/60) but relatively low sensitivity of 28.8% (17/59) for the prediction of catamenial epilepsy. The positive predictive value was 77.3% (17/22), whereas the negative predictive value was 56.7% (55/97). AUD history is a highly specific biomarker for catamenial epilepsy but has relatively low sensitivity for its detection. Further investigation may identify additional biomarkers that are more efficient than seizure-menses calendars.


Inflammatory back pain: a concept, not a diagnosis.
The concept of inflammatory back pain (IBP) describes a cohort of patients with chronic back pain (CBP) who have distinct clinical characteristics, rather than being a diagnosis in and of itself. IBP is a common and important feature of axial spondyloarthritis (axSpA) but this is not the only differential. This review examines the utility of IBP in both primary and secondary care settings. There are a number of suggested referral strategies for patients with suspected axSpA that include IBP. These strategies attempt to strike a balance between ensuring potential axSpA patients are not overlooked, whilst simultaneously not overwhelming secondary care services. Their success relies on the clinicians who first encounter these patients being familiar with IBP as a concept; however, it is still poorly recognized by many healthcare professionals. IBP may be helpful as part of a referral strategy; however, other clinical features, laboratory investigations and radiology must be incorporated for the final diagnostic outcome in axSpA. Delayed diagnosis is a major clinical problem in axSpA and is associated with worse clinical outcomes. When recognized and utilized correctly, IBP can be a useful tool to promote prompt referral to rheumatology services.


Intellectual engagement and cognitive ability in later life (the "use it or lose it" conjecture): longitudinal, prospective study.
To examine the association between intellectual engagement and cognitive ability in later life, and determine whether the maintenance of intellectual engagement will offset age related cognitive decline. Longitudinal, prospective, observational study. Non-clinical volunteers in late middle age (all born in 1936) living independently in northeast Scotland. Sample of 498 volunteers who had taken part in the Scottish Mental Health Survey of 1947, from one birth year (1936). Cognitive ability and trajectory of cognitive decline in later life. Typical intellectual engagement was measured by a questionnaire, and repeated cognitive measurements of information processing speed and verbal memory were obtained over a 15 year period (recording more than 1200 longitudinal data points for each cognitive test). Intellectual engagement was significantly associated with level of cognitive performance in later life, with each point on a 24 point scale accounting for 0.97 standardised cognitive performance (IQ-like) score, for processing speed and 0.71 points for memory (both P<0.05). Engagement in problem solving activities had the largest association with life course cognitive gains, with each point accounting for 0.43 standardised cognitive performance score, for processing speed and 0.36 points for memory (both P<0.05). However, engagement did not influence the trajectory of age related decline in cognitive performance. Engagement in intellectual stimulating activities was associated with early life ability, with correlations between engagement and childhood ability and education being 0.35 and 0.22, respectively (both P<0.01). These results show that self reported engagement is not associated with the trajectory of cognitive decline in late life, but is associated with the acquisition of ability during the life course. Overall, findings suggest that high performing adults engage and those that engage more being protected from relative decline.


Tuberculosis among health care workers in KwaZulu-Natal, South Africa: a retrospective cohort analysis.
Tuberculosis (TB) is an occupational hazard for health care workers (HCWs) who are at greater risk of developing TB than the general population. The objective of this study was to compare the difference in TB incidence among HCWs with versus without a history of working in TB wards, to estimate the incidence of TB among HCWs, and to identify risk factors for TB disease in HCWs. A retrospective cohort study (January 2006 to December 2010) was conducted in three district hospitals in KwaZulu-Natal, South Africa. Data were abstracted via chart review from occupational health medical records. Bivariate and multivariate analyses were performed using a Poisson multilevel mixed model. Of 1,313 (92%) medical charts reviewed with data on location of work documented, 112 (9%) cases of TB were identified. Among HCWs with TB 14 (13%) had multidrug-resistant TB. Thirty-six (32%) were cured, 33 (29%) completed treatment, and 13 (12%) died. An increased incidence of TB was reported for HCWs with a history of working in TB wards (incidence rate ratio [IRR] 2.03, 95% CI 1.11-3.71), pediatric wards (IRR 1.82 95% CI 1.07-3.10), outpatient departments (IRR 2.08 95% CI 1.23-3.52), and stores/workshop (IRR 2.38 95% CI 1.06-5.34) compared with those without such a history. HCWs living with HIV had a greater incidence of TB (IRR 3.2, 95% CI 1.54-6.66) than HIV-negative HCWs. TB incidence among HCWs was approximately two-fold greater than that of the general population over the study period. HCWs working in a TB ward had an increased incidence of TB. However, a greater incidence of TB was also found in HCWs working in other wards including pediatric wards, outpatient departments and stores. We also identified a greater incidence of TB among HCWs than the general population. These findings further support the need for improved infection control measures not only in TB or drug-resistant TB wards or areas perceived to be at high-risk but also throughout hospitals to protect HCWs. Additionally, it is recommended for occupational health services to routinely screen HCWs for TB and provide HCWs with access to care for TB and HIV.


Evaluation of a Simplified Risk Stratification Twice-Daily Aspirin Protocol for Venous Thromboembolism Prophylaxis After Total Joint Replacement.
To determine using a simplified risk-stratified protocol to select candidates for aspirin therapy have similar death and postoperative complications as universal warfarin therapy in patients undergoing total joint replacement (TJR). Retrospective cohort study comparing 30-day postoperative outcomes 6 months before and after the implementation of the aspirin protocol (January 1, 2015) in patients undergoing TJR. The control group was comprised of patients using warfarin for VTE prophylaxis. The protocol group included patients who used aspirin 325 mg twice-daily or warfarin if deemed high thrombotic risk or aspirin intolerant by the criteria set forth by the aspirin protocol. This study included 449 patients. No difference was found in the rates of 30-day postoperative bleeding, VTE, death, composite end point of VTE and death, and length of stay between the control and the protocol groups (all P > .05). Thirty-day postoperative surgical site infections (SSIs; 5.8% vs 1.2%; P = .02) and return to operative room (OR; 3.9% vs 0.4%; P = .03) were less frequent in the protocol group. A simplified risk-stratified protocol used to choose patients for aspirin 325 mg twice-daily therapy is safe and effective in patients undergoing TJR, and SSI and return to OR rates may be lower when compared to universal warfarin therapy.