Detection and disease diagnosis trends (2017-2022) for Streptococcus suis, Glaesserella parasuis, Mycoplasma hyorhinis, Actinobacillus suis and Mycoplasma hyosynoviae at Iowa State University Veterinary Diagnostic Laboratory.
Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis. S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs. Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.


A species of small antisense RNA in posttranscriptional gene silencing in plants.
Posttranscriptional gene silencing (PTGS) is a nucleotide sequence-specific defense mechanism that can target both cellular and viral mRNAs. Here, three types of transgene-induced PTGS and one example of virus-induced PTGS were analyzed in plants. In each case, antisense RNA complementary to the targeted mRNA was detected. These RNA molecules were of a uniform length, estimated at 25 nucleotides, and their accumulation required either transgene sense transcription or RNA virus replication. Thus, the 25-nucleotide antisense RNA is likely synthesized from an RNA template and may represent the specificity determinant of PTGS.


Cell differentiation mediated by co-culture of human umbilical cord blood stem cells with murine hepatic cells.
In the present study, purified human cord blood stem cells were co-cultivated with murine hepatic alpha mouse liver 12 (AML12) cells to compare the effect on endodermal stem cell differentiation by either direct cell-cell interaction or by soluble factors in conditioned hepatic cell medium. With that approach, we want to mimic in vitro the situation of preclinical transplantation experiments using human cells in mice. Cord blood stem cells, cultivated with hepatic conditioned medium, showed a low endodermal differentiation but an increased connexin 32 (Cx32) and Cx43, and cytokeratin 8 (CK8) and CK19 expression was monitored by reverse transcription polymerase chain reaction (RT-PCR). Microarray profiling indicated that in cultivated cord blood cells, 604 genes were upregulated 2-fold, with the highest expression for epithelial CK19 and epithelial cadherin (E-cadherin). On ultrastructural level, there were no major changes in the cellular morphology, except a higher presence of phago(ly)some-like structures observed. Direct co-culture of AML12 cells with cord blood cells led to less incisive differentiation with increased sex-determining region Y-box 17 (SOX17), Cx32 and Cx43, as well as epithelial CK8 and CK19 expressions. On ultrastructural level, tight cell contacts along the plasma membranes were revealed. FACS analysis in co-cultivated cells quantified dye exchange on low level, as also proved by time relapse video-imaging of labelled cells. Modulators of gap junction formation influenced dye transfer between the co-cultured cells, whereby retinoic acid increased and 3-heptanol reduced the dye transfer. The study indicated that the cell-co-cultured model of human umbilical cord blood cells and murine AML12 cells may be a suitable approach to study some aspects of endodermal/hepatic cell differentiation induction.


A randomized trial of an interim methadone maintenance clinic.
Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs. A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group. There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%). Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment.


The plant oncogene rolD stimulates flowering in transgenic tobacco plants.
The Agrobacterium rhizogenes T-DNA oncogene rolD under the control of its own 5' regulatory region was transferred to day-neutral tobacco plants. The main trait induced by rolD in transgenic plants is a striking precocity in flower setting and a strong enhancement of the flowering potential. In rolD plants, early flowering is followed by the very rapid growth of numerous lateral inflorescences. The analysis of several morphological and histological parameters suggests that some characteristic morphological abnormalities observed in rolD plants can be accounted for by their early reproductive phase transition and points to the involvement in the transition of a greater portion of the plant body than is the case for untransformed tobacco. The in vitro morphogenic potential of tissues from rolD plants was also tested. Superficial thin cell layer explants from rolD plants show an earlier and much enhanced flower organogenesis, compared to controls, both on flowering and on hormone-free medium.


Profiles of Adolescent Leisure Motivation and Substance Use in the HealthWise South Africa Research Trial: A Person-Centered Approach.
Engaging in intrinsically motivated behaviors, both within and outside of the leisure context, is associated with well-being. However, individuals can be driven by multiple types of motivation simultaneously, and the impact of constellations of leisure motivation is relatively unknown. The current study uses South African adolescents in the HealthWise South Africa efficacy trial (N=2,204; M age =14.0) to identify profiles of leisure motivation, examine the association between profiles and substance use, and evaluate the impact of HealthWise on changes in motivation profiles over time. Results indicate three distinct profiles: high consistent motivation, low consistent motivation, and high intrinsic motivation. Members of the high intrinsic profile had the lowest odds of substance use. Profiles were fairly stable across all time points except for females in a high-training intervention school. Results illustrate the importance of identifying and understanding typologies of leisure motivation and health across time, which can be used to promote positive development in adolescents.


Outpatient opiate detoxification treatment with buprenorphine. Preliminary investigation.
In an open study design, 50 opioid-dependent subjects (DSM-IV: 304. 0) were investigated in a gradual detoxification treatment with buprenorphine. The study was performed at the drug addiction outpatient clinic of the Department of General Psychiatry at the University of Vienna. Subjects had to contact the outpatient clinic on a daily basis and buprenorphine was administered according to their clinical status. Withdrawal symptoms were evaluated by applying the WANG scale. Urine samples were screened for drug toxicology to exclude additional consumption. In this investigation buprenorphine was applied sublingually in a free dosage scheme aimed at completing detoxification treatment within 10 days by reducing buprenorphine on a daily basis. A mean daily dosage of 2.3 mg buprenorphine was required by patients on day 1 of the treatment period. The highest mean daily buprenorphine dosage was given on day 2, followed by a daily reduction over the study period. The result of this open study design revealed that a gradual daily reduction of buprenorphine might be a successful alternative outpatient detoxification treatment in opioid-dependent subjects. Compliance was 70%, the reported and evaluated withdrawal symptoms during the study period were moderate.


Missing the Benefit of Metformin in Acute Myeloid Leukemia: A Problem of Contrast?
To evaluate whether metformin's cancer-related benefits reported in patients with solid tumors (ST) are also present in acute myeloid leukemia (AML) patients. Baseline demographic and clinical history for all diabetes mellitus patients newly diagnosed with AML or cancer of the breast, ovary, prostate, gastrointestinal tract, lung, or kidney at Roswell Park Cancer Institute in Buffalo, NY (January 2003-December 2010, n = 924) was collected. Overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier (KM) analysis and Cox proportional hazards regression (hazard ratio [HR]). Baseline metformin use provided significant OS and DFS benefit in ST but not in AML (KM: PST-OS= 0.003; PST-DFS= 0.002; PAML-OS= 0.961; PAML-DFS= 0.943). AML median survival was slightly better with metformin use, but users derived no relapse benefit. In ST, metformin nonusers had shorter median survival, 57.7 versus 86 months, and poorer outcomes (HRST-OS= 1.33; PST-OS= 0.002; HRST-DFS= 1.32; PST-DFS= 0.002). These findings remained significant in age-adjusted models (HRST-OS= 1.21; PST-OS= 0.039; HRST-DFS= 1.23; PST-DFS= 0.02) but not fully adjusted models (HRST-OS= 0.96; PST-OS= 0.688; HRST-DFS= 1.0; PST-DFS= 0.94). Higher mortality was noted in AML patients taking insulin versus oral diabetes pharmacotherapy at baseline (HRAML-OS= 2.03; PAML-OS= 0.04). Lack of metformin benefit in AML could be due to advanced age at cancer diagnosis. Metformin substitution with insulin before computed tomography scans with contrast - a frequent AML assessment practice - may also explain the lack of subsequent benefit despite taking metformin at baseline. A temporary metformin substitution is recommended by the package insert due to a possible drug interaction with the contrast dye. Our data suggest that metformin substitution was permanent in many patients. Nonetheless, the observed benefit in other malignancies warrants further investigation of metformin use in AML.


[Telemedicine and wireless devices in heart failure].
Telemedicine has the potential to constitute the central element of the future primary care and become an effective means of prevention and early warning of acute exacerbation of chronic diseases. Up to now, the application of telemedicine has found a variety of difficulties, regarding the types and methods of acquisition and transmission of biological signals, the acceptance and cooperation of the patient, etc. The latest technological developments involve the combined use of wireless technologies and smartphones, for the collection and the transmission of data, and specific softwares for their automatic analysis. This paper examines some of the critical aspects in the application of new technologies for heart failure remote management.


The MORPH-R web server and software tool for predicting missing genes in biological pathways.
A biological pathway is the set of molecular entities involved in a given biological process and the interrelations among them. Even though biological pathways have been studied extensively, discovering missing genes in pathways remains a fundamental challenge. Here, we present an easy-to-use tool that allows users to run MORPH (MOdule-guided Ranking of candidate PatHway genes), an algorithm for revealing missing genes in biological pathways, and demonstrate its capabilities. MORPH supports the analysis in tomato, Arabidopsis and the two new species: rice and the newly sequenced potato genome. The new tool, called MORPH-R, is available both as a web server (at http://bioinformatics.psb.ugent.be/webtools/morph/) and as standalone software that can be used locally. In the standalone version, the user can apply the tool to new organisms using any proprietary and public data sources.


Operating room management and strategies in Switzerland: results of a survey.
Operating room management structures and interrelationships both within the operating suite and with other departments in the hospital can be very complex. Several different professional and support groups are represented that often have infrastructures of their own that may compete or conflict with the management hierarchy in the operating room. Today, there is often little actual management of the operating suite as an entity. We surveyed current operating room management in Switzerland. A questionnaire was sent to the chief anaesthesiologists of all public hospitals in Switzerland. It asked for information about the structure, organization and management of operating rooms as well as respondents' opinions and expectations about management. Derived from both the literature and the results of the survey, a 'stages of excellence' model of best practice was developed. The overall response rate was 70%. Most anaesthesiologists were unsatisfied with current management policies and structures in their operating rooms. Of the hospitals questioned, 40% did not have an information system at all for the operating rooms. The remaining 60% had an information system that allowed rough scheduling in 71%, but only a few had more sophisticated systems that enabled dynamic scheduling (19%), user-defined conflict checking (5%), administration of a subsequent patient transfer station (postanaesthesia care units, intensive medical care, intensive care units) (10%) or other more advanced uses. All hospitals questioned offered some type of ambulatory surgery in a 'hospital-integrated' manner (i.e. use of the same operating room for both in- and outpatient surgery), but none had implemented a more efficient system where outpatient surgery was performed in separate facilities. Current management of the operating room in Switzerland is far from best-practice standards.


The individual blood cell telomere attrition rate is telomere length dependent.
Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at approximately 10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.


Checkpoint inhibition of origin firing prevents DNA topological stress.
A universal feature of DNA damage and replication stress in eukaryotes is the activation of a checkpoint-kinase response. In S-phase, the checkpoint inhibits replication initiation, yet the function of this global block to origin firing remains unknown. To establish the physiological roles of this arm of the checkpoint, we analyzed separation of function mutants in the budding yeast Saccharomyces cerevisiae that allow global origin firing upon replication stress, despite an otherwise normal checkpoint response. Using genetic screens, we show that lack of the checkpoint-block to origin firing results in a dependence on pathways required for the resolution of topological problems. Failure to inhibit replication initiation indeed causes increased DNA catenation, resulting in DNA damage and chromosome loss. We further show that such topological stress is not only a consequence of a failed checkpoint response but also occurs in an unperturbed S-phase when too many origins fire simultaneously. Together we reveal that the role of limiting the number of replication initiation events is to prevent DNA topological problems, which may be relevant for the treatment of cancer with both topoisomerase and checkpoint inhibitors.


Contact tracing versus facility-based screening for active TB case finding in rural South Africa: A pragmatic cluster-randomized trial (Kharitode TB).
There is a dearth of comparative effectiveness research examining the implementation of different strategies for active tuberculosis (TB) case finding, particularly in rural settings, which represent 60% of the population of sub-Saharan Africa. We conducted a pragmatic, cluster-randomized comparative effectiveness trial of two TB case finding strategies (facility-based screening and contact tracing) in 56 public primary care clinics in two largely rural districts of Limpopo Province, South Africa. In the facility-based screening arm, sputum Xpert MTB/RIF was performed on all patients presenting (for any reason) with TB symptoms to 28 study clinics, and no contact tracing was performed. In the contact-tracing arm, contacts of patients with active TB were identified (via household tracing in 14 clinics and using small monetary incentives in the other 14 clinics), screened for TB symptoms, and offered Xpert MTB/RIF testing. The primary outcome was the number of newly identified patients with TB started on treatment. The analysis used multivariable Poisson regression adjusted for historical clinic-level TB case volumes and district. The trial was registered with ClinicalTrials.gov (NCT02808507). From July 18, 2017, to January 17, 2019, a total of 3,755 individuals started TB treatment across 56 study clinics in the 18-month period. Clinic characteristics and clinic-level averages of patient characteristics were similar across the two arms: 40/56 (71%) clinics were in a rural location, 2,136/3,655 (58%) patients were male, and 2,243 (61%) were HIV positive. The treatment initiation ratio comparing the yield of TB patients started on treatment in the facility-based arm compared to that from the contact-tracing arm was 1.04 (95% confidence interval [CI] 0.83-1.30, p = 0. 73). In the contact-tracing arm, 1,677 contacts of 788 new TB index patients were screened, yielding 12 new patients with TB. Prespecified subgroup analyses resulted in similar results, with estimated treatment initiation ratios of 0.96 (95% CI 0.64-1.27; p = 0.78) and 1.23 (95% CI 0.87-1.59; p = 0.29) among historically smaller and historically larger clinics, respectively. This ratio was 1.02 (95% CI 0.66-1.37; p = 0.93) and 1.08 (95% CI 0.74-1.42; p = 0.68) in the Vhembe and Waterberg districts, respectively. The estimated treatment initiation ratio was unchanged in sensitivity analyses excluding 24 records whose TB registration numbers could not be verified (1.03, 95% CI 0.82-1.29; p = 0.78) and excluding transfers-in (1.02, 95% CI 0.80-1.29; p = 0.71). Study limitations include the possibility of imbalance on cluster size owing to changes in catchment population over time and the inability to distinguish the independent effects of the two contact investigation strategies. Contact tracing based on symptom screening and Xpert MTB/RIF testing did not increase the rate of treatment initiation for TB relative to the less resource-intensive approach of facility-based screening in this rural sub-Saharan setting. ClinicalTrials.gov NCT02808507.


A new paradigm for human stick balancing: a suspended not an inverted pendulum.
We studied 14 skilled subjects balancing a stick (a television antenna, 52 cm, 34 g) on their middle fingertip. Comprehensive three-dimensional analyses revealed that the movement of the finger was 1.75 times that of the stick tip, such that the balanced stick behaved more like a normal noninverted pendulum than the inverted pendulum common to engineering models for stick balancing using motors. The average relation between the torque applied to the stick and its angle of deviation from the vertical was highly linear, consistent with simple harmonic motion. We observed clearly greater rotational movement of the stick in the anteroposterior plane than the mediolateral plane. Despite this magnitude difference, the duration of stick oscillatory cycles was very similar in both planes, again consistent with simple harmonic motion. The control parameter in balancing was the ratio of active torque applied to the stick relative to gravitational torque. It determined both the pivot point and oscillatory cycle period of the pendulum. The pivot point was located at the radius of gyration (about the centre of mass) of the stick from its centre of mass, showing that the subjects attuned to the gravitational dynamics and mass distribution of the stick. Hence, the key to controlling instability here was mastery of the physics of the unstable object. The radius of gyration may--similar to centre of mass--contribute to the kinesthesis of rotating limb segments and control of their gravitational dynamics.


A site- and time-heterogeneous model of amino acid replacement.
We combined the category (CAT) mixture model (Lartillot N, Philippe H. 2004) and the nonstationary break point (BP) model (Blanquart S, Lartillot N. 2006) into a new model, CAT-BP, accounting for variations of the evolutionary process both along the sequence and across lineages. As in CAT, the model implements a mixture of distinct Markovian processes of substitution distributed among sites, thus accommodating site-specific selective constraints induced by protein structure and function. Furthermore, as in BP, these processes are nonstationary, and their equilibrium frequencies are allowed to change along lineages in a correlated way, through discrete shifts in global amino acid composition distributed along the phylogenetic tree. We implemented the CAT-BP model in a Bayesian Markov Chain Monte Carlo framework and compared its predictions with those of 3 simpler models, BP, CAT, and the site- and time-homogeneous general time-reversible (GTR) model, on a concatenation of 4 mitochondrial proteins of 20 arthropod species. In contrast to GTR, BP, and CAT, which all display a phylogenetic reconstruction artifact positioning the bees Apis mellifera and Melipona bicolor among chelicerates, the CAT-BP model is able to recover the monophyly of insects. Using posterior predictive tests, we further show that the CAT-BP combination yields better anticipations of site- and taxon-specific amino acid frequencies and that it better accounts for the homoplasies that are responsible for the artifact. Altogether, our results show that the joint modeling of heterogeneities across sites and along time results in a synergistic improvement of the phylogenetic inference, indicating that it is essential to disentangle the combined effects of both sources of heterogeneity, in order to overcome systematic errors in protein phylogenetic analyses.


Purification of viruses by centrifugation in gradients of inert substances.
By using a reorienting gradient centrifuge rotor cut from a block of Nylon and fitted with eight septae, it was possible to separate the components of the haemolymph of the mollusc Turbo sarmaticus into three fractions in a sucrose gradient held in the bowl of the rotor. The fractions were (108 and 98)S, 44S and 16-22S. The success of the experiment was due to the large differences in the sedimentation coefficients of the components. When the rotor was applied to the natural mixture of the five viruses of the caterpillars of Nudaurelia cytheria only the main component could be isolated in a pure state. The viruses were separated by isopycnic centrifugation in "self formed" caesium chloride gradients, using a Beckman Model E analytical centrifuge in which a separation cell fitted with a centerpiece with two perforated partitions was used.


Pancreas transplants from donors aged 45 years or older.
Since donor age of 45 years or more is considered a relative contraindication for pancreas transplantation (PTx), we herein report our experience with these donors. Pancreases from donors aged 45 years or older were used in 16 of 147 PTx procedures (11%). The final decision to accept a graft for PTx was based mainly on the quality of visceral perfusion and the gross appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging in age from 45 to 55 years (average, 48.9 years) who were donors, due to cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac arrest (12.5%). Pancreases were transplanted either simultaneously with a cadaveric kidney (n = 6) or as solitary grafts (n = 10). After a mean period of cold preservation of 616 minutes (range, 475 to 844 min), delayed endocrine function occurred in 1 recipient (6%), who subsequently achieved insulin independence. Two recipients died suddenly, with functioning grafts. Two further grafts were lost due to portal vein thrombosis (6%) or late arterial thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively. Meticulous donor selection and short preservation times allow the safe use of pancreases procured from donors aged 45 years or older, thus expanding the donor pool for PTx procedures.


[Changes in the physical development of Kiev schoolchildren over a ten-year period (1996-2008)].
Physical development and morphofunctional state were assessed in 2452 urban schoolchildren, by using the Ukrainian standards (intergroup regression scales). During their schooling, the Kiev schoolchildren of both sexes were shown to have significant qualitative and quantitative physical and morphofunctional worsening that was more obvious in boys. Not more than 57-59% of the Kiev children aged 6 to 17 years had normal physical development and harmonic morphofunctional state. Every six Kiev boys and every five girls had overweight and reduced chest circumference. In the period 1996-2008, there was significant weight gain without respective changes in chest circumference and height, which indicated an imbalance in growth processes and physical development in the present-day Kiev schoolchildren. Evaluation standards for schoolchildren's physical development were developed and put into practice of the state sanitary-and-epidemiological service of Ukraine.


Supplemental corn grain for steers grazing native rangeland during summer.
Effects of supplemental corn grain on forage OM intake (FOMI), digesta kinetics, ruminal fermentation patterns, in vitro OM digestibility (IVOMD), and in situ OM digestion were examined in steers grazing summer blue grama rangeland in northeastern New Mexico during July and August 1988. Sixteen ruminally cannulated steers (average BW 507 kg) were allotted to four treatments and individually fed whole-shelled corn at 0, .2, .4, and .6% of BW in a complete random design with repeated measurements over time. Forage OMI decreased linearly (P = .02) with increasing levels of supplemental corn; however, a tendency toward greater FOMI, as well as faster particulate and fluid passage, was observed when corn was fed at .2% of BW compared with 0, .4, or .6% of BW. Molar proportions of butyrate increased (P less than .10) but molar proportions of acetate and propionate, ruminal pH, and total VFA concentration did not change (P greater than .10) with added corn. Added corn linearly decreased (P less than .10) ruminal ammonia N concentrations in July, but patterns were inconsistent in August. A cubic response (P less than .05) for in situ OM disappearance with added corn was noted after 24, 72, and 96 h of incubation. Supplemental whole corn fed at .2% of BW had no detrimental effects and tended to increase FOMI. However, supplemental corn fed at .4 or .6% of BW decreased FOMI compared with 0 or .2% of BW.


Resolvase-catalysed reactions between res sites differing in the central dinucleotide of subsite I.
The resolvase-catalysed reaction between two res sites in a circular DNA substrate normally gives two circular recombination products linked in a two-noded catenane. Homology between the two res sites at the central overlap dinucleotide of subsite I is important for recombination. Reactions between res sites differing at one position in the central dinucleotide (AC X AT) gave a low yield of recombinants containing mismatched base-pairs, but gave large amounts of a non-recombinant four-noded knot. This result was predicted by a 'simple rotation' model for strand exchange. The mismatch is evidently recognized only after commitment to an initial 180 degrees rotation of the resolvase-linked DNA ends, and it induces a second 180 degrees rotation which restores correct base-pairing at the overlap, giving the four-noded product. Correct base-pairing is not essential for religation, but may be important for release of the products. Characteristic patterns of 4, 6, 8 and 10 node knots, or 4, 8, 12 and 16 node knots were obtained, depending on the reaction conditions and the resolvase. Two pathways for multiple rounds of rotation in 360 degrees steps are inferred. The results support a model for strand exchange by supercoil-directed subunit rotation within a resolvase tetramer.


Too Deep or Not Too Deep?: A Propensity-Matched Comparison of the Analgesic Effects of a Superficial Versus Deep Serratus Fascial Plane Block for Ambulatory Breast Cancer Surgery.
Serratus fascial plane block can reduce pain following breast surgery, but the question of whether to inject the local anesthetic superficial or deep to the serratus muscle has not been answered. This cohort study compares the analgesic benefits of superficial versus deep serratus plane blocks in ambulatory breast cancer surgery patients at Women's College Hospital between February 2014 and December 2016. We tested the joint hypothesis that deep serratus block is noninferior to superficial serratus block for postoperative in-hospital (pre-discharge) opioid consumption and pain severity. One hundred sixty-six patients were propensity matched among 2 groups (83/group): superficial and deep serratus blocks. The cohort was used to evaluate the effect of blocks on postoperative oral morphine equivalent consumption and area under the curve for rest pain scores. We considered deep serratus block to be noninferior to superficial serratus block if it were noninferior for both outcomes, within 15 mg morphine and 4 cm·h units margins. Other outcomes included intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and incidence of postoperative nausea and vomiting. Deep serratus block was associated with postoperative morphine consumption and pain scores area under the curve that were noninferior to those of the superficial serratus block. Intraoperative fentanyl requirements, time to first analgesic request, recovery room stay, and postoperative nausea and vomiting were not different between blocks. The postoperative in-hospital analgesia associated with deep serratus block is as effective (within an acceptable margin) as superficial serratus block following ambulatory breast cancer surgery. These new findings are important to inform both current clinical practices and future prospective studies.


Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from baseline relative to placebo (p<0·0001). Our results suggest that inhibition of PCSK9 synthesis by RNA interference (RNAi) provides a potentially safe mechanism to reduce LDL cholesterol concentration in healthy individuals with raised cholesterol. These results support the further assessment of ALN-PCS in patients with hypercholesterolaemia, including those being treated with statins. This study is the first to show an RNAi drug being used to affect a clinically validated endpoint (ie, LDL cholesterol) in human beings. Alnylam Pharmaceuticals.


Secretagogue-specific effects of interleukin-1 on gastric acid secretion.
Interleukin-1 beta (IL-1 beta) has recently been shown to reduce the severity of experimental gastroduodenal damage and to inhibit acid secretion in the pylorus-ligated rat. In the present study, the effects of IL-1 beta on pentagastrin-stimulated acid secretion were compared with those of two other cytokines, namely IL-1 alpha and tumor necrosis factor (TNF) alpha. Also, the effects of IL-1 beta on gastric acid secretion stimulated by bethanechol or histamine were assessed. Anesthetized rats were pretreated intravenously with one of the cytokines, at doses in the 0.1-5 micrograms/kg range, 30 min before starting an intravenous infusion of pentagastrin. TNF alpha failed to significantly affect acid secretion, whereas IL-1 alpha and IL-1 beta exhibited significant inhibitory effects. For example, at a dose of 5 micrograms/kg, IL-1 alpha and IL-1 beta reduced acid secretion by 33 and 80%, respectively. The inhibitory effects of IL-1 beta on acid secretion could be completely inhibited by preincubation with an antibody directed against IL-1 beta but not by pretreatment with indomethacin (5 mg/kg sc) or by bilateral vagotomy. If acid secretion was stimulated by intravenous infusions of histamine or bethanechol, neither IL-1 beta nor TNF alpha produced significant inhibitory effects. Inhibition of acid secretion by IL-1 was also observed when the IL-1 was administered subsequent to stimulation by pentagastrin administration. These results demonstrate that IL-1 beta is an extremely potent inhibitor of acid secretion stimulated by pentagastrin but not that stimulated by histamine or bethanechol, through a mechanism that is at least in part independent of the vagus nerve and of prostaglandin synthesis. IL-1 alpha is less potent as an inhibitor of gastric acid secretion, whereas TNF appears to be inactive. Because pentagastrin-stimulated acid secretion could be completely inhibited by a histamine H2-receptor antagonist (cimetidine) and because IL-1 had no effect on histamine-stimulated acid secretion, it is possible that IL-1 exerts its antisecretory actions by inhibiting pentagastrin-stimulated histamine release.


Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B.
Elevated alanine transaminase (ALT) levels and low serum hepatitis B virus (HBV) DNA predict a higher likelihood of hepatitis B e antigen (HBeAg) loss in patients with chronic hepatitis B treated with interferon. Predictors of HBeAg loss in patients treated with lamivudine are not known. The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss. Predictors of HBeAg loss in patients treated with interferon, lamivudine plus interferon, or placebo are also described. A total of 805 adults with chronic hepatitis B were treated either with lamivudine (n = 406), matching placebo (n = 196), interferon (n = 68), or the combination of lamivudine plus interferon (n = 135). Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss. HBeAg loss correlated with increased pretreatment ALT levels in all groups. The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the lamivudine group (56%). Multivariate modeling indicated that elevated baseline ALT levels (P <.001) and histologic activity index (HAI) score (P <.001) were important predictors of HBeAg loss in response to lamivudine. The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians. In conclusion, elevated pretreatment ALT levels and/or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss. Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels.


Na+ and K+ cell concentrations in collagenase-treated rat kidney tubules incubated at various temperatures.
Na+ and K+ cell contents were measured in single pieces of tubule (0.4-0.8 mm/sample) micro-dissected from the outer medulla of collagenase-treated rat kidney tissue. Extracellular cations were washed out by rinsing the tubules in ice-cold choline-chloride solution. Na+ and K+ cell contents were measured by emission flame microphotometry after appropriate treatment of the samples. Tubular volumes were calculated from photographic pictures taken before (at 4 degrees C) and after incubation of the samples. Medullary collecting tubules (MCT) and medullary thick ascending limbs of Henle (MAL) were used in this study. When kept at 4 degrees C for 2 h or more, Na+ and K+ concentrations (meq/l cell volume) were 86.3 and 30.6, respectively, in MCT and 16.2 and 94.3, respectively, in MAL. After about 5 min of incubation at 30 degrees C, MCT samples inverted their cation contents up to new steady-state concentrations (Na+ 17.4 and K+ 97.5). During incubation, the volume of MCT samples decreased slowly and in an exponential way, the rate of which was highly temperature dependent. Na+ and K+ cell concentrations in such incubated MCT samples, however, remained fairly constant between 20 and 37 degrees C. In contrast, when MAL samples were incubated at 30 degrees C, Na+ and K+ concentrations (15.9 and 90.4, respectively) remained equal to those measured at 4 degrees C and no change in volume was observed in MAL samples.


Accumbal Adenosine A2A Receptors Enhance Cognitive Flexibility by Facilitating Strategy Shifting.
The deficits of cognitive flexibility (including attentional set-shifting and reversal learning) concomitant with dysfunction of the striatum are observed in several neuropsychiatric disorders. Rodent and human studies have identified the striatum [particularly the dorsomedial striatum (DMS) and nucleus accumbens (NAc)] as the critical locus for control of cognitive flexibility, but the effective neuromodulator and pharmacological control of cognitive flexibility remains to be determined. The adenosine A2A receptors (A2ARs) are highly enriched in the striatopallidal neurons where they integrate dopamine and glutamate signals to modulate several cognitive behaviors, but their contribution to cognitive flexibility control is unclear. In this study, by coupling an automated operant cognitive flexibility task with striatal subregional knockdown (KD) of the A2AR via the Cre-loxP strategy, we demonstrated that NAc A2AR KD improved cognitive flexibility with enhanced attentional set-shifting and reversal learning by decreasing regressive and perseverative errors, respectively. This facilitation was not attributed to mnemonic process or motor activity as NAc A2AR KD did not affect the visual discrimination, lever-pressing acquisition, and locomotor activity, but was associated with increased attention and motivation as evident by the progressive ratio test (PRT). In contrast to NAc A2ARs, DMS A2ARs KD neither affected visual discrimination nor improved set-shifting nor reversal learning, but promoted the effort-related motivation. Thus, NAc and DMS A2ARs exert dissociable controls of cognitive flexibility with NAc A2ARs KD selectively enhancing cognitive flexibility by facilitating strategy shifting with increased motivation/attention.


Hemolytic anemia and thrombocytopenia associated with penicillamine ingestion.
A case of a 52-year-old white woman who developed hemolytic anemia and thrombocytopenia after receiving D-penicillamine is presented. Although there appears to be a causative relationship, it cannot be documented at this time. No other case of hemolysis has been suggested in patients treated with penicillamine. Since penicillamine is being used more frequently and in an ever-growing list of conditions, it is advisable to be alert to the possibility of hemolytic anemia as another of the complications of therapy.


Risk of lymphadenopathy from SARS-CoV-2 vaccination: a self-controlled case series analysis.
To assess the risk of lymphadenopathy following SARS-CoV-2 vaccination. A self-controlled case series design was used to determine whether the risk of lymphadenopathy was higher in the 1- to 42-day risk interval after COVID-19 vaccination compared to the control period. In addition, subgroup analyses were conducted according to baseline characteristics, time since vaccination, and sensitivity analyses adjusted for the length of the risk interval. The risk of developing lymphadenopathy in the risk interval (1-42 days) after COVID-19 vaccination compared to the control period was significantly increased, with a relative incidence (RI) of 1.17 (95% CI, 1.17-1.18) when the first, second, and third doses were combined. The RI was greater on the day of vaccination (1.47; 95% CI, 1.44-1.50). In subgroup analyses by baseline characteristics, a significantly increased risk or trend toward increased risk was observed in most subgroups except for those aged 70 years and older, with a significant increase in risk in younger individuals, those with a Charlson's comorbidity index <5, and those who received mRNA vaccines (mRNA-1273 > BNT162b2). Within the 1- to 42-day post-dose risk period, the relative risk was highest during the 1- to 7-day post-dose period (1.59; 95% CI, 1.57-1.60) compared to the control period, and then the risk declined. In the sensitivity analysis, we found that the longer the risk window, the smaller the RI. SARS-CoV-2 vaccination is associated with a statistically significant increase in the risk of lymphadenopathy, and this risk was observed only with mRNA vaccines.


Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons.
We have performed a screen combining subtractive hybridization with PCR to isolate genes that are regulated when neuroepithelial (NE) cells differentiate into neurons. From this screen, we have isolated a number of known genes that have not previously been associated with neurogenesis, together with several novel genes. Here we report that one of these genes, encoding a guanine nucleotide exchange factor (GEF), is regulated during the differentiation of distinct neuronal populations. We have cloned both rat and mouse GEF genes and shown that they are orthologs of the human gene, MR-GEF, which encodes a GEF that specifically activates the small GTPase, Rap1. We have therefore named the rat gene rat mr-gef (rmr-gef) and the mouse gene mouse mr-gef (mmr-gef). Here, we will collectively refer to these two rodent genes as mr-gef. Expression studies show that mr-gef is expressed by young neurons of the developing rodent CNS but not by progenitor cells in the ventricular zone (VZ). The expression pattern of mr-gef during early telencephalic neurogenesis is strikingly similar to that of GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by GABAergic interneurons generated in the ventral telencephalon, some of which migrate into the cortex during development. These observations suggest that mr-gef encodes a protein that is part of a signaling pathway involved in telencephalic neurogenesis; particularly in the development of GABAergic interneurons.


The billion cell construct: will three-dimensional printing get us there?
How structure relates to function--across spatial scales, from the single molecule to the whole organism--is a central theme in biology. Bioengineers, however, wrestle with the converse question: will function follow form? That is, we struggle to approximate the architecture of living tissues experimentally, hoping that the structure we create will lead to the function we desire. A new means to explore the relationship between form and function in living tissue has arrived with three-dimensional printing, but the technology is not without limitations.


Integrated circuits and logic operations based on single-layer MoS2.
Logic circuits and the ability to amplify electrical signals form the functional backbone of electronics along with the possibility to integrate multiple elements on the same chip. The miniaturization of electronic circuits is expected to reach fundamental limits in the near future. Two-dimensional materials such as single-layer MoS(2) represent the ultimate limit of miniaturization in the vertical dimension, are interesting as building blocks of low-power nanoelectronic devices, and are suitable for integration due to their planar geometry. Because they are less than 1 nm thin, 2D materials in transistors could also lead to reduced short channel effects and result in fabrication of smaller and more power-efficient transistors. Here, we report on the first integrated circuit based on a two-dimensional semiconductor MoS(2). Our integrated circuits are capable of operating as inverters, converting logical "1" into logical "0", with room-temperature voltage gain higher than 1, making them suitable for incorporation into digital circuits. We also show that electrical circuits composed of single-layer MoS(2) transistors are capable of performing the NOR logic operation, the basis from which all logical operations and full digital functionality can be deduced.


Giant cell tumour in the diaphysis of radius - a report.
We present a case of a 35 yrs old female who presented with swelling over her forearm. This is a rare case of a giant cell tumour in a nonepiphyseal region. Case report and presentation of clinical, radiological and histological data on single case of giant cell tumour of diaphysis of radius. Although age, clinical features and radiological features are helpful, it is still the histology that helps to clinch the diagnosis. A thorough literature search and an exhaustive online search using various search engines revealed seven reported cases of giant cell tumours in the diaphysis of long bones. We reiterate the fact that irrespective of the location, a giant cell tumour should be diagnosed based on its histology.


Antimicrobial resistance in humans, livestock and the wider environment.
Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem.


A reciprocal-space formulation of surface hopping.
Surface hopping has seen great success in describing molecular phenomena where electronic excitations tend to be localized, but its application to materials with band-like electronic properties has remained limited. Here, we derive a formulation of fewest-switches surface hopping where both the quantum and classical equations of motion are solved entirely in terms of reciprocal-space coordinates. The resulting method is directly compatible with band structure calculations and allows for the efficient description of band-like phenomena by means of a truncation of the Brillouin zone. Using the Holstein and Peierls models as examples, we demonstrate the formal equivalence between real-space and reciprocal-space surface hopping and assess their accuracy against mean-field mixed quantum-classical dynamics and numerically exact results. Having very similar equations of motion, reciprocal-space surface hopping can be straightforwardly incorporated in existing (real-space) surface hopping implementations.


Chronic myeloid leukemia stem cells require cell-autonomous pleiotrophin signaling.
Tyrosine kinase inhibitors (TKIs) induce molecular remission in the majority of patients with chronic myelogenous leukemia (CML), but the persistence of CML stem cells hinders cure and necessitates indefinite TKI therapy. We report that CML stem cells upregulate the expression of pleiotrophin (PTN) and require cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL+ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. Hematopoietic cell-specific deletion of PTN suppressed CML development in BCR/ABL+ mice, suggesting that cell-autonomous PTN signaling was necessary for CML disease evolution. Mechanistically, PTN promoted CML stem cell survival and TKI resistance via induction of Jun and the unfolded protein response. Human CML cells were also dependent on cell-autonomous PTN signaling, and anti-PTN antibody suppressed human CML colony formation and CML repopulation in vivo. Our results suggest that targeted inhibition of PTN has therapeutic potential to eradicate CML stem cells.


Protein phosphatase-mediated regulation of protein kinase C during long-term depression in the adult hippocampus in vivo.
The neural substrates of learning and memory are thought to involve use-dependent long-term changes in synaptic function, including long-term depression (LTD) of synaptic strength. One biochemical event hypothesized to contribute to the maintenance and expression of LTD is decreased protein phosphorylation, caused by a decrease in protein kinase activity and/or an increase in protein phosphatase activity. We tested whether the activity of protein kinase C (PKC) decreases after the induction of LTD in area CA1 of the adult hippocampus in vivo, and then investigated the mechanism responsible for the LTD-associated alteration in PKC activity. We found that LTD was associated with a significant decrease in both autonomous and cofactor-dependent PKC activity. The decrease in PKC activity was prevented by NMDA receptor blockade and was not accompanied by a decrease in the level of either PKCalpha, beta, gamma, or zeta. Western blot analysis with phosphospecific antibodies revealed that phosphorylation of Ser-657 on the catalytic domain of PKCalpha (Ser-660 on PKCbetaII) was decreased significantly after the induction of LTD, and that this dephosphorylation was prevented by the protein phosphatase inhibitor okadaic acid. The decrease in autonomous and cofactor-dependent PKC activity likewise was prevented by okadaic acid. These findings suggest that LTD in the adult hippocampus in vivo involves a decrease in PKC activity that is mediated, at least in part, by dephosphorylation of the catalytic domain of PKC by protein phosphatases activated after LTD-inducing stimulation. Our findings are consistent with the idea that protein dephosphorylation contributes to the expression of LTD.


Comparing the effects of acupuncture and electroacupuncture at Zusanli and Baihui on cell proliferation and neuroblast differentiation in the rat hippocampus.
We compared the effects of acupuncture and electroacupuncture on cell proliferation and neuroblast differentiation using specific markers, Ki67 and doublecortin (DCX), in the subgranular zone of the dentate gyrus (SZDG) in 13-week old Wistar rats. Acupuncture and electroacupuncture were applied simultaneously in the acu-points, ST36 (Zusanli) and GV20 (Baihui), once a day for 3 weeks. Acupuncture and electroacupuncture at these acu-points significantly increased the number of Ki67-positive cells and DCX-immunoreactive neuroblasts compared to the control or sham acupuncture group. Electroacupuncture treatment significantly increased the number of well-developed (tertiary) dendrites in the SZDG compared to acupuncture treatment. These results suggest that both acupuncture and electroacupuncture increase neurogenesis in the normal, but that electroacupuncture has greater effects on neuroblast plasticity than acupuncture in the dentate gyrus.


Danshen attenuates cartilage injuries in osteoarthritis in vivo and in vitro by activating JAK2/STAT3 and AKT pathways.
Articular cartilage degradation is a main feature of osteoarthritis (OA). The effects of Danshen, a traditional Chinese herb, in mitigating cartilage damage have been reported before. This study was conducted to investigate the effects of Danshen on cartilage injuries in OA. Rabbit OA models were established by surgical destabilization of the medial meniscus and the anterior and posterior cruciate ligaments in the left knee joint. Injection of Danshen into the articular cavity attenuated OA cartilage destruction in vivo. The levels of phosphorylated Janus kinase 2 (JAK2) and phosphorylated signal transducer and activator of transcription 3 (STAT3) were decreased in osteoarthritic cartilage, while they were rescued upon Danshen treatment. Furthermore, chondrocytes isolated from normal rabbit cartilage were exposed to 2 mM sodium nitroprusside (SNP) to establish an OA model in vitro. We found that the oxidative stress and chondrocyte apoptosis induced by SNP were suppressed by Danshen. The phosphorylation levels of JAK2 and STAT3 were decreased in response to SNP treatment, whereas they were rescued by Danshen. Additionally, AG490, a specific JAK2 inhibitor, counteracted the anti-apoptotic effect of Danshen. The phosphorylation level of protein kinase B (AKT) was also altered in response to SNP and reversed by Danshen. The anti-apoptotic effect of Danshen was counteracted by AKT pathway inhibitor LY194002. Taken together, Danshen attenuates OA cartilage destruction by regulating the JAK2/STAT3 and AKT signaling pathways.


[Clinical study of perinatal hysterectomy between 2000-2011 in the clinic of obstetrics, gynecological diseases and oncological gynecology in Bydgoszcz].
Perinatal hysterectomy (PH) is usually a life-saving procedure, which is performed after all conservative treatment options fail. The PH frequency rate ranges from 0.04 to 0.23%. The most frequent indications for this procedure include: abnormal placental implantation, placenta previa, uterine rupture and uterine atony Clinical study of perinatal hysterectomy cases taking into consideration the frequency indications, complications and risk factors related to this procedure. The study included 16 women who underwent perinatal hysterectomy at the Department and Clinic of Obstetrics and Gynecological Diseases between 2000-2011. The following data were collected from medical records: course of pregnancy labor and puerperium. The profile of the study group was conducted in terms of: maternal age, parity gestation length, history of caesarean sections and gynecological operations. The following factors were studied: the termination of pregnancy, indications for caesarean section, hysterectomy-related complications and indications, neonatal birth weight and Apgar score. The statistical analysis was performed using Statistica 9.1 by StatSoft. Data are expressed as the arithmetic mean and standard deviation (SD). Sixteen perinatal hysterectomy procedures were performed, accounting for 0.066% of the overall number of labors. Average maternal age and pregnancy length were 31.6 years [SD+/-6.3] and 36.1 weeks of gestation [SD+/-3.4], respectively PH was more frequently performed among multiparous women (81.25%) and after caesarean sections (87.5%). Fetal asphyxia was the most frequent indication for caesarean section (35.7%). Fourteen percent of all indications accounted for the lack of consent from a pregnant woman to make an attempt at spontaneous vaginal delivery after previous c-section. Fifty percent of the women from the study group had a previous caesarean section, whereas 25% had more than one prior c-section. Between 2009-2011, as compared to previous years, the highest percentage of hysterectomies (80%) was reported in pregnant women after a previous caesarean section. The most frequent indication for hysterectomy included abnormal placental implantation (43.75%) diagnosed more often in patients with a history of caesarean section (57%). Among PH complications, a hemorrhagic shock was reported in 37.4% and bladder injury in 18.7% of the women. Every patient required a transfusion of erythrocyte concentrate, 4.7 units [SD+/-3.5] on average. Twenty-five percent of the neonates were born in poor condition with an Apgar score of 1-3. In case of all women, the therapy required cooperation of different specialists including obstetricians, anesthesiologists, urologists, surgeons and general practitioners. 1. Current and previous caesarean section constitutes a risk factor for perinatal hysterectomy 2. Placental pathology is the most frequent indication for perinatal hysterectomy 3. The growing number of caesarean sections should encourage obstetricians to conduct a more careful analysis of indications.


Circulating activated platelets assist THP-1 monocytoid/endothelial cell interaction under shear stress.
Circulating complexes of leukocytes and activated platelets are markers for atherosclerosis, but their interaction with the arterial endothelial lining has not been studied. Therefore, the effect of activated platelets on rolling and adhesion of labeled human THP-1 monocytoid cells to human umbilical vein endothelial cell (HUVEC) monolayers was studied by epifluorescence microscopy in a parallel plate flow chamber. In the absence of activated platelets, THP-1 rolling on resting HUVEC was negligible at shear rates greater than 300 s(-1). Activation of HUVEC with 100 nmol/L phorbol myristate acetate (PMA) increased THP-1 cell adhesion at shear rates less than 400 s(-1). Therefore, a shear rate of 400 s(-1) was identified as a threshold for THP-1 adhesion. THP-1 rolling on activated HUVEC was reduced by 64% after L-selectin inhibition but was not affected by P-selectin inhibition. The addition of 1 to 50 thrombin receptor-activating peptide (TRAP)-activated platelets per THP-1 cell enhanced interactions between THP-1 cells and HUVEC, resulting in a steep bell-shaped dose-response curve, with a peak of 10 +/- 3 rolling cells/50 seconds at 3 platelets per THP-1 cell (P <.01 v control) with a concomitant 2- to 3-fold increase of firmly adhering cells (P <.01 v control). In reconstituted blood, low numbers of activated platelets had the same effect on THP-1 rolling and adhesion. P-selectin inhibition reduced platelet/THP-1 cell interaction in suspension and deposition of the complexes on the endothelial monolayer. Inhibition of both P- and L-selectin reduced THP-1/HUVEC interactions to 14% (P <.01, n = 4). Sialidase digestion and removal of terminal sialic acid residues from HUVEC or THP-1 cells but not from platelets abolished the platelet mediated augmentation of THP-1 cell adhesion. Thus, THP-1 rolling on HUVEC is shear-dependent and largely mediated by L-selectin. P-selectin expressed on activated platelets increases monocytoid cell adhesion to endothelial cells at shear rates found in coronary arteries through interactions with both endothelial and monocytoid cells and may facilitate macrophage accumulation in the vessel wall.


[Zoledronate inhibits TRPV5 and NFATc1 expression during differentiation of osteoclasts].
To explore the effect of zoledronate (ZOL) on osteoclast differentiation and expressions of transient receptor potential vanilloid 5 channel (TRPV5) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). RAW264.7 cells were divided into two groups for treatment with RANKL for 5 days (group A) or with additional ZOL treatment in the last 2 days of RANKL treatment (group B). Osteoclastogenesis of the cells and the mRNA and protein expressions of TRPV5 and NFATc1 after the treatments were examined. In group B, the number of newly generated osteoclasts (≥ 3 nuclei), number and size of dentin resorption lacunaes were 29.0 ± 2.4, 24.8 ± 1.1, and 2 030.0 ± 165.7 µm², respectively, which were significantly lower than those in group A (56.5 ± 4.5, 49.3 ± 0.9, and 3 946.7 ± 367.5 µm², respectively, P<0.01). Fluorescent intensity of TRPV5 and NFATc1 were also significantly decreased in group B (P<0.01). Compared with those in group A, TRPV5 mRNA and protein expressions in group B were down-regulated by 50.4% and 37.8%, and those of NFATc1 by 68.0% and 48.4%, respectively (P<0.01). ZOL can significantly inhibit osteoclastogenesis and bone resorption, which may be attributed, at least partly, to ZOL-induced inhibition of TRPV5 and NFATc1 expressions.


Assessing organisational development in European primary care using a group-based method: a feasibility study of the Maturity Matrix.
The Maturity Matrix is a tool designed in the U.K. to assess family practice organisational development and to stimulate quality improvement. It is practice-led, formative and undertaken by a practice team with the help of trained facilitators. The aim of this study is to assess the Maturity Matrix as a tool and an organisational development measure in European family practice settings. Using a convenience sample of 153 practices and 11 facilitators based in the U.K., Germany, The Netherlands, Switzerland and Slovenia, feasibility was assessed against six criteria: completion; coverage; distribution; scaling; translation; and missing data. Information sources were responses to evaluation questionnaires by facilitators and completed Maturity Matrix profiles. All practices taking part completed the Maturity Matrix sessions successfully. The Netherlands, the U.K. and Germany site staff suggested including additional dimensions: interface between primary and secondary care; access; and management of expendable materials. Maturity Matrix scores were normally distributed in each country. Scaling properties, translation and missing data suggested that the following dimensions are most robust across the participating countries: clinical performance audit; prescribing; meetings; and continuing professional development. Practice size did not make a significant difference to the Maturity Matrix profile scores. The study suggests that the Maturity Matrix is a feasible and valuable tool, helping practices to review organisational development as it relates to healthcare quality. Future research should focus on developing dimensions that are generic across European primary care settings.


Central venous catheter dressing durability: an evaluation.
Skin organisms at the insertion site are frequently implicated in central venous catheter blood stream infections (CVC BSIs) yet few studies have compared the durability of CVC dressings in critically ill patients. To undertake an evaluation of the durability and associated costs of different CVC dressings. Dressing duration was captured prospectively using a pro forma on four different dressings on five critical care units over a 12-month period. Staff received training on CVC dressing evidence-based practices and a 'how to guide' was implemented. A total of 1229 CVC dressings were observed from 590 CVCs. One dressing had a median (IQR) duration of 68.5 h (range, 32-105 h) compared to a median duration of 43.5, 46.0 and 40.5 h for the other dressings (P <0.001). The mean time to change a CVC dressing was 13.5 min and the cost of a dressing change was in the range of £1.97-4.97. During the 12-month study period we observed a downward trend in CVC BSIs. Despite few dressings remaining adherent for 7 days, the low rates of CVC BSI observed suggests good dressing practices. One dressing appeared more durable than the others, although it was still below the recommended standard and more expensive.


Fibroblasts From Longer-Lived Species of Primates, Rodents, Bats, Carnivores, and Birds Resist Protein Damage.
Species differ greatly in their rates of aging. Among mammalian species life span ranges from 2 to over 60 years. Here, we test the hypothesis that skin-derived fibroblasts from long-lived species of animals differ from those of short-lived animals in their defenses against protein damage. In parallel studies of rodents, nonhuman primates, birds, and species from the Laurasiatheria superorder (bats, carnivores, shrews, and ungulates), we find associations between species longevity and resistance of proteins to oxidative stress after exposure to H(2)O(2) or paraquat. In addition, baseline levels of protein carbonyl appear to be higher in cells from shorter-lived mammals compared with longer-lived mammals. Thus, resistance to protein oxidation is associated with species maximal life span in independent clades of mammals, suggesting that this cellular property may be required for evolution of longevity. Evaluation of the properties of primary fibroblast cell lines can provide insights into the factors that regulate the pace of aging across species of mammals.


Role of interleukin-6 in mortality from and physiologic response to sepsis.
Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker and a mediator for the severity of sepsis. We tested whether interleukin 6 knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to increasing degrees of sepsis severity. Physiologic support was given with fluids and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the onset of sepsis, and a complete hematologic profile was performed on day 2. As expected, increasing sepsis severity resulted in greater and more rapid mortality. However, the mortality was nearly identical in the IL-6KO and WT mice. All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis, while IL-6KO were near or below the lower limit of detection. Among the WT mice, mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL-6KO and WT mice destined to die in the early stages of sepsis had substantial and nearly identical weight gain in the first 24 h. However, at later stages the WT mice had significantly greater weight loss than the KO mice. The KO mice failed to develop the characteristic hypothermia within the first 24 h of severe sepsis routinely observed in the WT mice. These data demonstrate that IL-6 serves as a marker of disease severity in sepsis and does modulate some physiologic responses, but complete lack of IL-6 does not does not alter mortality due to sepsis.


Stimuli-Responsive Soft Untethered Grippers for Drug Delivery and Robotic Surgery.
Untethered microtools that can be precisely navigated into deep in vivo locations are important for clinical procedures pertinent to minimally invasive surgery and targeted drug delivery. In this mini-review, untethered soft grippers are discussed, with an emphasis on a class of autonomous stimuli-responsive gripping soft tools that can be used to excise tissues and release drugs in a controlled manner. The grippers are composed of polymers and hydrogels and are thus compliant to soft tissues. They can be navigated using magnetic fields and controlled by robotic path-planning strategies to carry out tasks like pick-and-place of microspheres and biological materials either with user assistance, or in a fully autonomous manner. It is envisioned that the use of these untethered soft grippers will translate from laboratory experiments to clinical scenarios and the challenges that need to be overcome to make this transition are discussed.


Carcinogenic and Non-carcinogenic Risk Assessment of Heavy Metals in Groundwater Wells in Neyshabur Plain, Iran.
The present work reports the As, Cr, Cu, Pb, Zn, and Fe concentrations of drinking water samples in Neyshabur Plain, Iran. This study aimed also to ascertain the potential consumers' health risk of heavy metal intake. Heavy metal concentrations were analyzed by inductively coupled plasma optical emission spectrometry. The highest and lowest average values in the analyzed water samples were observed for Fe (9.78 ± 5.61 μg/L) and As (1.30 ± 2.99 μg/L), respectively. These values were well below the limits recommended by the World Health Organization and the Iranian national standard. Heavy metal pollution index and heavy metal evaluation index were used to evaluate drinking water quality. The risk index was calculated by chronic daily intake and hazard quotient according to the United States Environmental Protection Agency approach. Heavy metal pollution index in all the samples was less than 100, indicating that it is a low-level heavy metal. The total risk of all heavy metals in the urban environment varied from 40.164 × 10-7 to 174.8 × 10-7. In this research, the maximum average of risk belonged to lead and copper with the respective values of 60.10 × 10-7and 33.99 × 10-7 from the selected wells. However, considering the toxic effect of some elements, including Pb and As, in the chronic exposure of consumers, we suggest a continuous evaluation and monitoring of drinking water resources.


Cholinesterase inhibitors associated with lower rate of mortality in dementia patients with heart failure: a nationwide propensity weighting study.
This study investigates the potential impact of cholinesterase inhibitors (ChEIs) on patients with heart failure (HF) and dementia. ChEIs are known to boost acetylcholine levels and benefit cognition in patients with dementia; however, their effect on patients with HF is uncertain. This study aimed to assess whether cardiovascular events and mortality among patients with HF and dementia are altered by ChEI therapy. Data from the National Health Insurance Research Database in Taiwan were retrospectively analyzed. Dementia patients diagnosed with HF were followed for 5 years until all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, or the end of the study. Multivariable Cox models and inverse probability of treatment weighting (IPTW) were employed. Out of 20,848 patients with dementia, 5138 had HF. Among them, 726 were ChEI users and 4412 were non-users. Based on IPTW, the ChEI users had significantly lower estimated risks of all-cause mortality [hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.38-0.49, p < 0.001] and cardiovascular mortality (HR 0.41; 95% CI 0.33-0.53, p < 0.001) compared with the non-users, but there was no significant difference in hospitalization for worsening HF (HR 0.73; 95% CI 0.51-1.05, p = 0.091) after 5 years. The survival benefits of ChEIs were consistent across subgroups. The results of this retrospective cohort study suggest that ChEIs may be beneficial in reducing all-cause and cardiovascular mortality in patients with dementia with HF. Further research is needed to validate these findings and explore the potential benefits of ChEIs in all patients with HF, including those without dementia.


Hypertension after Kidney Transplantation: Clinical Significance and Therapeutical Aspects.
Most of the kidney transplanted patients develop arterial hypertension after renal transplantation. Together with very well-known and usual risk factors, post-transplant hypertension contributes to the whole cardiovascular morbidity and mortality in the kidney transplant population. The reasons of post-transplant hypertension are factors related to donors and recipients, immunosuppressive therapy like Calcineurin Inhibitors (CNI) and surgery procedures (stenosis and kinking of the renal artery and ureteral obstruction). According to Eighth National Committee (JNC 8) recommendations, blood pressure > 140/90 mmHg is considered as hypertension. The usual antihypertensive drugs used for the control of hypertension are Calcium channel blockers (CCB), Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin -II receptor blockers (ARB), B- blockers and diuretics. Follow the KDIGO guidelines the target blood pressure < 140/90 mmHg for patients without proteinuria and < 125/75 mmHg in patients with proteinuria is recommended. Better control of post-transplant hypertension improves the long-term graft and patient's survival.


Peritumoral Hyperintensity at Hepatobiliary Phase Gadoxetic Acid-enhanced MRI in Hepatic Neuroendocrine Tumors.
To identify the imaging and clinical features of hepatic neuroendocrine tumors (NETs) associated with peritumoral hyperintensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance (MR) imaging. Fifty-seven patients with hepatic NETs were enrolled. Based on the degree of peritumoral hyperintensity, patients were divided into three groups: group 0 (no peritumoral hyperintensity), group 1 (lower peritumoral hyperintensity), and group 2 (higher peritumoral hyperintensity). The imaging and clinical findings were compared among the three groups. Apparent diffusion coefficient (ADC) values of group 2 were significantly lower than those of group 0 and group 1. Atypical (cholangiocarcinoma-like) enhancement pattern in the arterial phase was significantly more frequently observed in group 2 as compared to that in group 0 and group 1. Group 2 patients showed significantly poorer progression-free survival than group 0 patients. Hepatic NETs with greater peritumoral hyperintensity exhibit greater malignant potential.


Autoimmune encephalitis associated with Ma2 antibodies and immune checkpoint inhibitor therapy.
Immune checkpoint inhibitors have transformed the treatment of advanced malignancy, while increasing the risk of immune-related adverse events. A 56-year-old woman who had received nivolumab for stage 4 renal cell carcinoma subsequently developed altered behaviour, memory deficits and worsening of previously stable epilepsy. MR scan of the brain showed bilateral FLAIR (fluid-attenuated inversion recovery) hyperintensity of the mesial temporal lobes, and there were anti-Ma2 antibodies in both serum and cerebrospinal fluid. She was treated with corticosteroids but developed further clinical relapses requiring immunoglobulin and rituximab. The immune-related adverse events relating to immune checkpoint inhibitors are an emerging challenge for the neurologist. Some cases are refractory and require serial immunosuppression.


Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis.
Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.


[First experience with gel plasty of the anal canal in children with fecal incontinence].
Fecal incontinence in children after surgical correction of anorectal defects and trauma of the holding apparatus of the rectum in certain cases can be dependent on low basal pressure in the anal canal at the expense of incompetence of the interior sphincter muscle of the anus. In order to eliminate low pressure in the anal canal we introduced polyacrylamide gel "DAM +" into its submucous layer. The introduction of this volume-forming substance into the anal canal was an effective procedure. Fecal incontinence became less in all cases, and completely regressed in 50% of the patients.


Absorption of selenium from milk protein and isolated soy protein formulas in preschool children: studies using stable isotope tracer 74Se.
Absorption of selenium as the stable isotopic tracer [74Se]selenite was measured in four preschool children who were receiving liquid formula diets based on casein, isolated soy protein, and a 50:50 combination of the two protein sources. The children were in continuous ambulatory balance studies within the Clinical Research Center during three consecutive 11-day collection periods. The enrichment of the 74Se/76Se ratio in feces was measured by radiochemical neutron activation analysis, with fractional absorption estimated therefrom. Mean fractional absorption of selenium (+/- SD) from the formulas based on milk, isolated soy protein, and milk-soy were 64.2 +/- 14.6, 73.4 +/- 19.0, and 45.0 +/- 10.9%, respectively, with the combined formula having a significantly lower intestinal uptake for added selenite than the casein formula. Stable isotopes of selenium are safe and potentially useful tools for examining its bioavailability in the diets of young children.


A 12-week, randomized, double-masked study of fixed combination latanoprost/timolol versus latanoprost or timolol monotherapy.
To evaluate the efficacy and safety of fixed combination latanoprost/timolol versus latanoprost or timolol monotherapy. This 12-week, randomized, double-masked study was designed to overcome potential shortcomings of previous trials. We enrolled 788 subjects with open-angle glaucoma or ocular hypertension treated with a beta-blocker for > or = 4 weeks before screening. After washout, 500 subjects with a baseline mean intraocular pressure (IOP) > or = 26 and < 37 mmHg were randomized to fixed combination latanoprost-timolol in the evening (n = 170), latanoprost monotherapy in the evening (n = 165), or timolol monotherapy in the morning (n = 165). At weeks 2, 6, and 12, each subject's IOP level was measured in triplicate at 8 AM (predose), 10 AM, and 4 PM in each eye. Adverse events were monitored throughout. The statistical superiority of the fixed combination for the 18 pairwise comparisons with the 2 monotherapies was evaluated (analysis of variance). RESULTS. The statistical superiority of the fixed combination was demonstrated at 7/9 time points versus latanoprost and 9/9 time points versus timolol. Mean diurnal IOP levels were similar at baseline but significantly lower with the fixed combination than with either monotherapy at weeks 6 and 12 (each p < 0.05). Patients treated with the fixed combination were significantly more likely than those treated with either monotherapy to reach prespecified percent IOP reductions at the upper thresholds and to achieve very low target diurnal IOP levels. All therapies were well tolerated. CONCLUSIONS. Fixed combination latanoprost/timolol safely reduces IOP levels in patients with glaucoma or ocular hypertension, though only slightly more than does latanoprost monotherapy.


Evaluation of an evidence based quality improvement innovation for patients with musculoskeletal low back pain in an accident and emergency setting.
We conducted a five stage pilot study which initially consisted of a review of 75 case notes of people attending an emergency department (ED) in an inner London Teaching Hospital with musculoskeletal (MSK) low back pain (LBP). This review highlighted inconsistencies in how they were assessed and managed across and within different staff groups. We found patient documentation was often incomplete and that a biomedical model approach to the management of these patients was common. As a result, four further stages in the project were conducted. Our primary aim was to evaluate the impact of implementing a locally developed quality improvement intervention for the assessment and treatment of MSK LBP in this ED. Secondary aims were to explore the user experience of the new pathway, measured by the patient experience questionnaire (PEQ), and any associated health economic costs of changes in practice. The quality improvement intervention consisted of an evidence based low back pain pathway (EBLBPP), a staff educational program, and a patient education booklet. We undertook a retrospective baseline audit of 100 clinical records of patients was undertaken prior to the instigation of the quality improvement intervention, and four months post implementation. The pre-defined variables of interest were: documentation of the case history, examination, classification of back pain (and if correct), prescribed management and if the documentation was compliant with medico-legal standards. All patients in the study were sent a PEQ to complete and return in a self-addressed envelope. Estimated health costs associated with each patient episode of care were calculated including re-attendance episodes for any people presenting with MSK LBP within a four week period. There was a significant improvement in all areas evaluated post implementation in all groups (simple, referred and simple, referred and serious spinal pathology combined). In particular; screening for red flags (22%) and biopsychosocial factors (29%), as well as noting the prevalence of previous symptoms (44%), observation of the painful area (57%), and analysis classification (59%) at a at 95% confidence interval (CI). In terms of management, an increase in adherence to the analgesic ladder, patients receiving reassurance and appropriate referral back to their GP's increased 45%, 23% and 44% at 95% CI respectively. Unfortunately, there was insufficient data to draw any meaningful conclusions from the patient experience data due to a low response rate. In conclusion, the introduction of the EBLBPP, patient education leaflet and teaching training for staff involved in the treatment of MSK LBP patients has improved the quality and consistency of the documented assessment and subsequent management of MSK LBP patients.


Further evidence concerning the autoantigenic status of the trophoblast.
Heterologous antisera were raised by inoculation of rabbits with fairly pure suspensions of trophoblast, lymphoid, fetal (excluding placental components), epidermal, decidual, and renal cells from Fischer rats. After absorption of hemagglutinins, these antisera were assayed for abortifacient activity by intramuscular inoculation into time-mated Fischer females. The anti-trophoblast serum aborted all the recipients, but had some nonspecific activity in that it caused the deaths of 12% of them. Anti-lymphocyte serum was more toxic and less potent as an abortifacient. None of the other sera harmed either the mothers or their fetuses. However, the anti-kidney cell serum caused kidney lesions. Absorption of the anti-trophoblast serum with lymphoid cells completely removed its toxicity for the pregnant females without perceptible impairment of its abortifacient activity. However, the latter could be removed by absorption with trophoblast cells. (a) The lymphocyte-absorbed anti-trophoblast serum was equally effective in aborting rats over the range 7-18 days postconception; (b) a single injection of 1 ml was sufficient in most cases, and (c) it was equally efficacious in terminating gestation in rats irrespective of their genetic constitution, and (d) its effect was highly species-specific. These findings support the premise that a unique antigen (or antigens), of possible clinical significance, is associated with trophoblast cells.


Circadian rhythms in the Limulus visual system.
A circadian clock in the Limulus brain generates efferent optic nerve activity at night. The endogenous activity begins near dusk, continues during the night, and stops near dawn. Approximately 10 to 20 efferent fibers in each lateral optic nerve trunk fire in close synchrony with one another and with the efferent fibers in the opposite nerve trunk producing bursts of nerve impulses at night. The synchronous bursting activity indicates extensive coupling in the brain among the efferent neurons or among the circadian pacemakers that drive them. The efferent optic nerve activity mediates circadian rhythms in retinal responses. Electroretinograms (ERGs) from both the lateral eyes and median ocelli exhibit circadian rhythms of equal phase. Sectioning the optic nerves abolishes the rhythms. When the animal is kept in darkness, the phase of the rhythm can be shifted by illuminating the lateral eyes but not the median ocelli. The endogenous rhythm persists for at least 1 year in darkness without attenuation and without substantial changes in the circadian period. Across a large population of animals the duration of the circadian period ranges from 22.2 to 25.5 hr, with a mean value of 23.9 +/- 0.7 hr (n = 75). The nighttime increase in ERG amplitude represents a 20- to 100-fold increase in retinal sensitivity. Most of the increased sensitivity results from an increase in the number of photons absorbed by the photoreceptors at night. A small component may be due to an increase in gain. Pulses of current delivered to the lateral optic nerve during the day mimic the effects of endogenous efferent activity and transform the eye to the nighttime state. The Limulus visual system has evolved numerous mechanisms for adapting visual sensitivity to daily fluctuations in the photic environment. A key to understanding the organization of the visual system is the circadian clock and its associated neural circuitry.


The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients with Helicobacter pylori infection and eradication.
H. pylori persists for the virtual life of its host. Recent studies suggested that CD4+ CD25+ regulatory T cells may be involved in this process. However, the alteration of CD4+ CD25+ regulatory T cells after eradication of H. pylori remains a question. By using biopsies from 45 H. pylori-positive patients and the ones after eradication of H. pylori and 35 H. pylori-negative adults, real-time PCR and general PCR were used to quantify the expression of Foxp3 mRNA. IHC was used to semi-quantify the number of CD4+ CD25+ T cells in gastric mucosa. We found that proportion of CD25+ T cell in CD4+ T cells accounted for 0.739% in H. pylori-negative individuals, while it was accounted for 5.012% in H. pylori-positive patients. After eradication of H. pylori, proportion of CD25+ T cell in CD4+ T cells declined (p < 0.01) and it accounted for 0.551%. The level of Foxp3 mRNA significantly decreased (p < 0.01) in gastric mucosa of patients after eradication of H. pylori. CD4+ CD25+ regulatory T cells decreased in gastric mucosa when patients received eradication of H. pylori. Eradication of H. pylori results in the significant descrease of Foxp3 mRNA in gastric mucosal, or using the drugs of anti-H. pylori induce the reduction of gastric mucosal Foxp3 mRNA expression, which is the a key regulatory gene for the development and function of CD4+ CD25+ regulatory T cells, thus contributing to the eradication of H. pylori. All the data offer new possibilities that Foxp3 gene may be the new target of immunization intervention strategies for eradication of H. pylori.


Pullulan and dextran: uncommon composition dependent Flory-Huggins interaction parameters of their aqueous solutions.
Vapor pressure measurements were performed for aqueous solutions of pullulan ( M w 280 kg/mol) and dextran ( M w 60 and 2100 kg/mol, respectively) at 25, 37.5, and 50 degrees C. The Flory-Huggins interaction parameters obtained from these measurements, plus information on dilute solutions taken from the literature, show that water is a better solvent for pullulan than for dextran. Furthermore, they evince uncommon composition dependencies, including the concurrent appearance of two extrema, a minimum at moderate polymer concentration and a maximum at high polymer concentration. To model these findings, a previously established approach, subdividing the mixing process into two clearly separable steps, was generalized to account for specific interactions between water and polysaccharide segments. Three adjustable parameters suffice to describe the results quantitatively; according to their numerical values, the reasons for the solubility of polysaccharides in water, as compared with that of synthetic polymers in organic solvents, differ in a principal manner. In the former case, the main driving force comes from the first step (contact formation between the components), whereas it is the second step (conformational relaxation) that is advantageous in the latter case.


Risk indicators of periodontal disease in older Thai adults.
The aim of this study was to identify risk indicators for periodontitis using cross-sectional data from a group of older Thai adults. The study group consisted of 2,005 individuals, aged 50 to 73 years old. They received detailed medical examinations and periodontal examinations including plaque score, probing depth, and clinical attachment level. These individuals were categorized into mild, moderate, or severe periodontitis if mean clinical attachment level was <2.5 mm, 2.5 to 3.9 mm, or > or = 4.0 mm, respectively. The degree of association between the severity of periodontitis and various independent variables was investigated using multinomial logistic regression analysis. The percentage of subjects classified as mild, moderate, and severe periodontitis was 30.5, 53.6, and 15.9, respectively. The prevalence of severe periodontitis was higher in males and increased with age. In univariate analysis, older subjects, males, less educated persons, persons with lower income, persons with higher plaque score, smokers, drinkers, and diabetics were more likely to have both moderate and severe periodontitis. In multivariate analysis, males, less educated persons, persons with higher plaque score, and current smokers were more likely to have moderate periodontitis. Three additional factors including older age, former smokers, and diabetes significantly increased the odds for having severe periodontitis. Income, alcohol consumption, body mass index, and waist circumference had no significant effects on periodontal disease severity in the multivariate model. Our data suggest that age, gender, education, oral hygiene status, smoking, and diabetes are significantly associated with periodontal disease severity in this study group. Longitudinal studies will establish whether these variables are true risk factors.


Relationship of primary mitochondrial respiratory chain dysfunction to fiber type abnormalities in skeletal muscle.
Variation in the size and relative proportion of type 1 and type 2 muscle fibers can occur in a number of conditions, including structural myopathies, neuropathies, and various syndromes. In most cases, the pathogenesis of such fiber type changes is unknown and the etiology is heterogeneous. Skeletal muscle mitochondrial respiratory chain analysis was performed in 10 children aged 3 weeks to 5 years with abnormalities in muscle fiber type, size, and proportion. Five children were classified as having definite, four as probable, and one as possible mitochondrial disease. Type 1 fiber predominance was the most common histological finding (six of 10). On light microscopy, four cases had subtle concomitants of a mitochondriopathy, including mildly increased glycogen, lipid, and/or succinate dehydrogenase staining, and one case had more prominent evidence of underlying mitochondrial disease with marked subsarcolemmal staining. Most cases (nine of 10) had abnormal mitochondrial morphology on electron microscopy. All were found to have mitochondrial electron transport chain (ETC) abnormalities and met diagnostic criteria for mitochondrial disease. We did not ascertain any patients who had isolated fiber type abnormalities and normal respiratory chain analysis during the period of study. We conclude that mitochondrial ETC disorders may represent an etiology of at least a subset of muscle fiber type abnormalities. To establish an etiologic diagnosis and to determine the frequency of such changes in mitochondrial disease, we suggest analysis of ETC function in individuals with fiber type changes in skeletal muscle, even in the absence of light histological features suggestive of mitochondrial disorders.