Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma.
Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12-16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX. Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma. Fifty-four dogs with previously untreated lymphoma. Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days. The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis. Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations.


Utilization of Cofactor Binding Energy for Enzyme Catalysis: Formate Dehydrogenase-Catalyzed Reactions of the Whole NAD Cofactor and Cofactor Pieces.
The pressure to optimize enzymatic rate accelerations has driven the evolution of the induced-fit mechanism for enzyme catalysts where the binding interactions of nonreacting phosphodianion or adenosyl substrate pieces drive enzyme conformational changes to form protein substrate cages that are activated for catalysis. We report the results of experiments to test the hypothesis that utilization of the binding energy of the adenosine 5'-diphosphate ribose (ADP-ribose) fragment of the NAD cofactor to drive a protein conformational change activates Candida boidinii formate dehydrogenase (CbFDH) for catalysis of hydride transfer from formate to NAD+. The ADP-ribose fragment provides a >14 kcal/mol stabilization of the transition state for CbFDH-catalyzed hydride transfer from formate to NAD+. This is larger than the ca. 6 kcal/mol stabilization of the ground-state Michaelis complex between CbFDH and NAD+ (KNAD = 0.032 mM). The ADP, AMP, and ribose 5'-phosphate fragments of NAD+ activate CbFDH for catalysis of hydride transfer from formate to nicotinamide riboside (NR). At a 1.0 M standard state, these activators stabilize the hydride transfer transition states by ≈5.5 (ADP), 5.5 (AMP), and 4.4 (ribose 5'-phosphate) kcal/mol. We propose that activation by these cofactor fragments is partly or entirely due to the ion-pair interaction between the guanidino side chain cation of R174 and the activator phosphate anion. This substitutes for the interaction between the α-adenosyl pyrophosphate anion of the whole NAD+ cofactor that holds CbFDH in the catalytically active closed conformation.


Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats.
The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to-leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force-induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary, autonomic system functions. The research described here is rough and incomplete, but it is offered as a beginning, in the hope that researchers may find it of reference and carry the effort toward completion. The advances described here include (1) a finding that cerebral arterial perfusion pressure decreases to nearly zero under +5.0 Gz loads, (2) indications that G load may cause myocardial microinjuries, (3) detection of differences between cerebral regions in tissue-oxygen level under +3.0 Gz load, (4) discovery that hypotension is deeper under decreasing +Gz loads than increasing +Gz loads with use of an anti-G system, due in part to suppression of baroreceptor reflex, and (5) revelations and efforts investigating new measures to reduce cerebral hypotension, namely the "teeth-clenching pressor response" and preconditioning with slight but repeated G loads.


Advancing haematopoietic stem and progenitor cell biology through single-cell profiling.
Haematopoietic stem and progenitor cells (HSPCs) sit at the top of the haematopoietic hierarchy, and their fate choices need to be carefully controlled to ensure balanced production of all mature blood cell types. As cell fate decisions are made at the level of the individual cells, recent technological advances in measuring gene and protein expression in increasingly large numbers of single cells have been rapidly adopted to study both normal and pathological HSPC function. In this review we emphasise the importance of combining the correct computational models with single-cell experimental techniques, and illustrate how such integrated approaches have been used to resolve heterogeneities in populations, reconstruct lineage differentiation, identify regulatory relationships and link molecular profiling to cellular function.


Effect of nuclear protein HMG1 on in vitro slippage synthesis of the tandem repeat dTG x dCA.
Tandem repeats of simple doublet and triplet sequences occur with high frequency in the DNA of eucaryotes. Among the most frequent is the repeat of dTG, which has unusual structural properties. We show here that HMG1 (modeled by the second HMG box motif from HMG1 of the rat, HMGb) binds to complexes formed from annealing unequal lengths of dTG x dCA and inhibits the in vitro elongation of these complexes by the Klenow fragment of DNA polymerase I at 37 degrees C. At 46 degrees C, HMGb enhances the elongation. Polylysine inhibits elongation at both temperatures. These results show that the stability of this repeat in vivo can be influenced by the presence of basic proteins in general, and more selectively by the abundant nuclear protein HMG1.


Treatment of poststroke aphasia: current practice and new directions.
Aphasia is an acquired neurologic disorder that impairs an individual's ability to use and/or understand language. It commonly occurs after stroke or other injury to the brain's language network. The authors present the current methods of diagnosis and treatment of aphasia. They include a review of the evidence for the benefits of speech-language therapy, the most widespread approach to aphasia treatment, and a discussion of newer interventions such as medication and brain stimulation. These methods hold much promise for improving patient outcomes in aphasia; however, additional research regarding the best approaches to aphasia treatment will greatly improve our clinical approach.


Elderly people's quality of life in rural areas of Turkey and its relationship with loneliness and sociodemographic characteristics.
The aim of the present study was to examine the relationships between loneliness, quality of life and the factors that may be related to the quality of life in individuals ≥65 years old living in rural areas of Turkey. The World Health Organization Quality of Life Instrument Older Adults Module (WHOQOL OLD) and Loneliness Scale for the Elderly (LSE) was administered to 427 elderly participants. Multiple linear regression was used to determine the variables that affected QOL. The results of the multivariate linear regression analyses indicated that gender, marital status, education level, family income status, general health condition, living arrangement, and loneliness level for subdomains were within the predictors. Loneliness level had the strongest negative impact on the four WHOQOL OLD subdomains and total WHOQOL OLD score. It was the most important predictor for autonomy, past present future activities, social participation, death-and-dying, and intimacy subdomains and for the total QOL. Remarkably, a sense of loneliness in the elderly was determined to be the most important factor for predicting their QOL. Loneliness should be considered in attempts to improve QOL for the elderly, interventions to reduce loneliness should specifically target this group, and activities with the potential to increase QOL should be encouraged.


Barriers, challenges, and opportunities related to the provision of hospice care in assisted-living communities.
The purpose of this project was to clarify the barriers, challenges, and opportunities associated with providing care to older adults residing in assisted-living communities. Three focus groups (hospice team members, family members of individuals who received hospice care while in assisted living, and administrators of assisted-living communities) were convened to discuss hospice care. Thematic analysis of the transcribed focus group tapes was used by the authors to identify the common and unique barriers, challenges, and opportunities identified by each group. All three groups were overwhelmingly in support of the right of residents in assisted-living communities to live and die in place, without being transferred to nursing homes or other acute-care facilities, and of the role that hospice plays in enabling residents to achieve that goal. The three groups also agreed that trends in the development of assisted-living communities create difficulties for the industry, confusion for consumers, and the need for increased accountability by providers. Delivering hospice care to places where consumers want to live and die in place will be a complex task. Among other things, traditional hospice care is not easily transported into the social models of care characterized by assisted-living environments. Changes in hospice organization policies and procedures will be necessary, as will broader, industry-wide reforms in areas such as recruitment, retention of qualified staff and consistent quality-of-care standards.


Textured domains on tense surfaces and membranes: Effect of tilt and chirality.
We study the shape and texture of finite domains comprising chiral or achiral molecules carrying tilt, embedded in a two-dimensional surface or membrane, using a combination of simulations and exact variational calculations. We find a variety of shapes and textures including rectangular-shaped domains and a spontaneously broken chiral texture, when the molecules are achiral. We show that chiral tilt domains nucleating in a region of two-phase coexistence repel each other, thereby preventing coalescence and further growth. Our work principally addresses observations of domains in multicomponent giant unilamellar vesicles. It may also be relevant in the study of domains in phospholipid monolayers, nucleating domains of Sm-C* in Sm-A films, and chiral emulsions in Sm-A films, in situations where we can ignore dipolar interactions.


Comparison of sampling methods for hard-to-reach francophone populations: yield and adequacy of advertisement and respondent-driven sampling.
Francophones who live outside the primarily French-speaking province of Quebec, Canada, risk being excluded from research by lack of a sampling frame. We examined the adequacy of random sampling, advertising, and respondent-driven sampling for recruitment of francophones for survey research. We recruited francophones residing in the city of Calgary, Alberta, through advertising and respondentdriven sampling. These 2 samples were then compared with a random subsample of Calgary francophones derived from the 2006 Canadian Community Health Survey (CCHS). We assessed the effectiveness of advertising and respondent-driven sampling in relation to the CCHS sample by comparing demographic characteristics and selected items from the CCHS (specifically self-reported general health status, perceived weight, and having a family doctor). We recruited 120 francophones through advertising and 145 through respondent-driven sampling; the random sample from the CCHS consisted of 259 records. The samples derived from advertising and respondentdriven sampling differed from the CCHS in terms of age (mean ages 41.0, 37.6, and 42.5 years, respectively), sex (proportion of males 26.1%, 40.6%, and 56.6%, respectively), education (college or higher 86.7% , 77.9% , and 59.1%, respectively), place of birth (immigrants accounting for 45.8%, 55.2%, and 3.7%, respectively), and not having a regular medical doctor (16.7%, 34.5%, and 16.6%, respectively). Differences were not tested statistically because of limitations on the analysis of CCHS data imposed by Statistics Canada. The samples generated exclusively through advertising and respondent-driven sampling were not representative of the gold standard sample from the CCHS. Use of such biased samples for research studies could generate misleading results.


Internal dosimetry: enhancements in application, update on the IDEA project.
Efforts in many internal dosimetry laboratories to increase the accuracy and speed of measurements, to improve detection limits and to reduce uncertainties have resulted in improved or new internal monitoring techniques, both in in vivo measurement and in bioassay analysis. The EC-funded IDEA project (internal dosimetry--enhancements in application) aims to investigate why most of these techniques have not yet entered routine monitoring programmes (a summary of these new techniques is given here, showing their potential improvements compared with the currently employed monitoring routines). The project further aims at a comprehensive assessment of these techniques and the enhancements necessary to bring them to broader acceptance with those performing routine monitoring.


Analysis of temperature-dependent abnormal bursting patterns of neurons in Aplysia.
Temperature affects the firing pattern and electrical activity of neurons in animals, eliciting diverse responses depending on neuronal cell type. However, the mechanisms underlying such diverse responses are not well understood. In the present study, we performed in vitro recording of abdominal ganglia cells of Aplysia juliana, and analyzed their burst firing patterns. We identified atypical bursting patterns dependent on temperature that were totally different from classical bursting patterns observed in R15 neurons of A. juliana. We classified these abnormal bursting patterns into type 1 and type 2; type 1 abnormal single bursts are composed of two kinds of spikes with a long interspike interval (ISI) followed by short ISI regular firing, while type 2 abnormal single bursts are composed of complex multiplets. To investigate the mechanism underlying the temperature dependence of abnormal bursting, we employed simulations using a modified Plant model and determined that the temperature dependence of type 2 abnormal bursting is related to temperaturedependent scaling factors and activation or inactivation of potassium or sodium channels.


Low Potassium Dialysate as a Protective Factor of Sudden Cardiac Death in Hemodialysis Patients with Hyperkalemia.
Hyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD. We conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed. There were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13-0.85). Using low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.


Effect of disulfiram on the platelet function and fibrinolysis in healthy volunteers.
Disulfiram was studied for platelet and fibrinolytic activity in 12 healthy volunteers of both sexes (age 23-75 years). Placebo was given for 7 days, followed by disulfiram, 800 mg for 2 days and 400 mg for an additional 12 days. Finally, there was another placebo period of 14 days. With the exception of an initial platelet activation on day 2, no significant effects were found on the platelet variables studied: platelet aggregation with collagen, ADP and adrenaline, beta-thromboglobulin and platelet factor 4. Treatment for 14 days with disulfiram resulted in a decreased euglobulin clot lysis time: from 421 +/- 82 to 246 +/- 41 min (p less than 0.01). After an initial increase, plasminogen activator inhibitor activity was slightly decreased on disulfiram, from 8.4 +/- 1.6 on placebo to 6.0 +/- 1.2 U/ml (p less than 0.05) after 14 days of treatment. Plasminogen, fibrinogen and alpha 2-antiplasmin were unchanged. It is concluded that disulfiram can increase fibrinolytic activity in healthy subjects.


Mitochondrial DNA sequence and gene order of the Sri Lankan Schistosoma nasale is affiliated to the African/Indian group.
A 1.9 kb nucleotide sequence of part of the mitochondrial (mt) genome covering the cox1-trnT-rrnL-trnC-rrnS region, and the order of the remaining mitochondrial protein-coding genes for S. nasale of Sri Lankan origin, has been determined for analysis of the possible placement of this species in the genus Schistosoma. The gene order of this species is similar to that of the African and Indian Schistosoma species, but strikingly different from the East Asian species. Analysis of an alignment of the 1.9 kb sequence with available sequences from other schistosomes indicated affinities with S. spindale (found in Sri Lanka) and African species (in particular S. intercalatum and S. haematobium). Phylogenetic trees inferred from the alignment including 1 kb of RNA (transfer RNA and ribosomal RNA) sequence for 8 other Schistosoma spp. and Fasciola hepatica as an out-group revealed that S. nasale is placed proximally to S. spindale, S. intercalatum, S. haematobium and S. mansoni in the African sub-group while the East Asian species are more distant. S. incognitum lies basal to the combined African/Indian clade. The mtDNA analysis strongly supports the hypothesis that S. nasale is closely affiliated with the African/Indian schistosome group rather than the East Asian Schistosoma species.


Arterial oxygen partial pressure and cardiovascular surgery in elderly patients.
Arterial blood gas assessment is still routinely performed in candidates for a cardiovascular surgery. Whether sampling arterial blood is useful in an elderly patient with a near normal lung function and who meets all other criteria for operability, is unknown. Therefore, it was our purpose to provide reference values for arterial blood gases in these patients and to examine how the level of arterial oxygen partial pressure (PaO(2)) might influence postoperative outcome. We retrospectively studied arterial blood gases in 201 patients, aged 70-92 years with normal or near normal ventilatory function awaiting a planned cardiovascular surgery. PaO(2) averaged 81.6+/-7.6 mmHg and PaCO(2) averaged 37.7+/-3.2 mmHg. Both were independent of age. Factors associated with mortality according to bivariate analysis were: gender (female), type of surgery (valve replacement), and a low PaO(2) with strictly no ventilatory abnormality. In conclusion, PaO(2) values in elderly patients with cardiac disease and normal ventilatory function are greater than those obtained by extrapolation from healthy younger subjects. PaO(2) measurement should be recommended prior to cardiovascular surgery in elderly patients since a low PaO(2) with strictly normal ventilatory function is significantly associated with an increased risk for postoperative mortality.


[Rectal administration of drugs. Fundamentals and applications in anesthesia].
Rectal administration of drugs has become a standard procedure in clinical anesthesia, most notably for anorectal induction in children. Limitations of this method include low bioavailability, a wide scatter of pharmacokinetic and pharmacological results, and poor predictability of the clinical effect in any particular patient. Historically, the rectal route has been used for the administration of smoke ("fumigation") for resuscitation and various other purposes. An ether boiler for rectal application was developed by Pirogoff as early as 1847. The pharmacokinetics of rectally administered drugs are determined by the anatomical properties of the rectum and, owing to interindividual variance, this adds to the inconsistency of absorption. Aspects that can be better controlled include the drug preparation and the vehicle, with hydrophilic solutions resulting in improved absorption. Larger volumes such as are associated with lower concentrations increase the bioavailability by enlarging the mucosal surface in contact with the drug. In contrast to the hypothetical assumption that hepatic circulation may be circumvented--thus avoiding first-pass metabolism--by direct venous drainage from the rectum into the systemic circulation via the vena cava, it has been shown that hepatic clearance is the main factor affecting bioavailability. This may be due to blood flow through anastomoses interconnecting the superior, medium and inferior rectal venous systems. Resorption from the rectum is also determined by physicochemical properties of drugs. According to the pH-partition hypothesis, only the non-ionized moiety of a compound will be available for transmucosal diffusion. The degree of ionization is a function of the local (or microclimate) milieu pH and pKa of the drug; the former is close to neutral in adults but alkaline in most children. Adsorption of feces, intraluminal degradation by microorganisms, metabolism within the mucosal cell, and lymphatic drainage do not significantly affect the fate of rectally administered drugs. In clinical practice, the rectal administration of methohexital and midazolam is an established method of premedication or induction of anesthesia in children; so far, midazolam appears to be associated with fewer complications. Ketamine has been shown to be as effective and as quick-acting as methohexital, but at least in one study its use as sole induction agent was associated with respiratory distress in some cases. However, painful diagnostic or therapeutic procedures in children may be indications for the rectal administration of ketamine. Early trials with rectally administered etomidate have been abandoned since its implication in suppression of cortisol synthesis. Narcotic analgesics in a hydrogel vehicle are effective in adult pain management.(ABSTRACT TRUNCATED AT 400 WORDS)


Retention of Different Attachment Systems for Digitally Designed Mandibular Implant Overdenture.
Primary retention and gradual loss of retention of different attachment systems are important key factors in proper attachment selection; however, studies on attachment retention show a wide range of retention values concerning the same attachment system. This in vitro study uses a novel approach that utilizes a digitally designed and 3D-printed reinforced overdenture, which has a digitally determined geometric center, in order to standardize results for future research and clinical work. This study aims to evaluate initial retention along with the gradual loss of retention at different time intervals between three types of stud attachments, retaining a digitally designed, reinforced mandibular overdenture after 5475 cycles simulating 5 years of attachment usage. An epoxy model of an ACP Class I (American College of Prosthodontists) edentulous mandible was constructed. A fully computer-designed surgical guide was employed after virtual denture design to place two implants according to prosthetically driven implant placement protocol. A metal meshwork with tissue stops was designed digitally to reinforce the denture and to carry the geometric center. The meshwork was incorporated into the denture-intaglio surface, which was planned for attachment pickup. Forty-eight digitally designed and metal-reinforced 3D-printed dentures were divided into four groups (12 dentures for each group). Loss of retention was measured to compare two novel Locator attachments (12 pairs of Locator R-TX, 12 pairs of Locator F-TX medium and low retention, with 12 pairs of ball and socket). Each group was subjected to an insertion and removal fatigue test resembling 5 years of patient usage. Retention values were recorded using a universal testing machine. Locator F-TX medium and low retention showed loss of retention by 91.93% and 92.91%, after fatigue testing equivalent to 2 and 3 years of use, respectively. Ball and socket and Locator R-TX showed loss of retention by 19.87% and 26.31%, respectively, after fatigue testing equivalent to 5 years of use. Locator R-TX attachment systems showed promising retention for implant overdentures compared to ball and socket attachments. The proposed digital technique of denture reinforcement is capable of standardizing results for research and clinical work.


Preliminary design of the internal geometry in a minimally invasive left ventricular assist device under pulsatile-flow conditions.
A minimally invasive, partial-assist, intra-atrial blood pump has been proposed, which would unload the left ventricle with a flow path from the left atrium to the arterial system. Flow modulation is a common strategy for ensuring washout in the pump, but it can increase power consumption because it is typically achieved through motor-speed variation. However, if a pump's performance curve had the proper gradient, flow modulation could be realized passively. To achieve this goal, we propose a pump performance operating curve as an alternative to the more standard operating point. Mean-line theory was employed to generate an initial set of geometries that were then tested on a hydraulic test rig at ~20,000 r/min. Experimental results show that the intra-atrial blood pump performed below the operating region; however, it was determined that smaller hub diameter and longer chord length bring the performance of the intra-atrial blood pump device closer to the operating curve. We found that it is possible to shape the pump performance curve for specifically targeted gradients over the operating region through geometric variations inside the pump.


Conflicts between expected and actually performed behavior lead to verbal report of incidentally acquired sequential knowledge.
According to the Unexpected-Event Hypothesis (UEH) (Frensch, Haider, Rünger, Neugebauer, Voigt & Werg, 2002), conflicts between expected and actually performed behaviors trigger attribution processes and ultimately lead to the ability to verbally report an incidentally experienced sequential regularity. In two experiments, we manipulated the likelihood that a specific conflict, a premature response, occurred in a sequential version of the Number Reduction Task (NRT). Experiment 1 demonstrated that a longer RSI leads to a larger number of premature responses and to more verbal report than a shorter RSI. However, this effect of the RSI on verbal report was removed when participants were discouraged from emitting premature responses. Experiment 2 revealed that artificially inducing premature responses leads to an increase in verbal report, but only when premature responses are introduced late in training. Overall, the findings strongly support the assumptions of the UEH.


The impact of social conditions on patient adherence to pulmonary tuberculosis treatment.
Tuberculosis (TB) remains one of the main concerns in global health. One of the main threats to treatment success is patient non-adherence to anti-tuberculosis treatment. To identify the relation between social conditions and treatment adherence in a prospective cohort setting in an intermediate TB burden country. To identify associations between poor adherence and social conditions, including educational level, type of residence and occupation, we constructed hierarchical logistic regression models. A total of 551 participants were included in the study. Low educational levels, poor housing and occupations in the construction and manufacturing industries and service sectors were associated with poor adherence; this association was likely to be differentiated by previous history of anti-tuberculosis treatment. Policy making should focus on improving the social conditions of patients by working towards better housing conditions and providing health promoting working conditions to enable treatment adherence.


A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes.
Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK and RYK, both targets of the same micro RNA miR-1271, exhibit significant and consistent functional down-regulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor. Here we show that Grb2 and NOX4 play critical roles in reducing the severity of both the diseases. The study demonstrates that the abundance of Grb2 in degenerative conditions, in conjunction with NOX4, reverse cytoskeletal degradation by counterbalancing the network of small GTPases. PAX4, a transcription factor for both Grb2 and NOX4, emerges as the key link between the common pathways of AD and T2D. Down-regulation of both ALK and RYK through miR-1271, elevates the PAX4 level by reducing its suppressor ARX via Wnt/β-Catenin signaling. For the first time, this study brings together RTKs beyond Insulin Receptor (IR) family, transcription factor PAX4 and both AD and T2D pathologies on a common regulatory platform.


FUNDC1 Regulates Autophagy by Inhibiting ROS-NLRP3 Signaling to Avoid Apoptosis in the Lung in a Lipopolysaccharide-Induced Mouse Model.
The incidence and mortality of acute respiratory distress syndrome (ARDS) are high, but the relevant mechanism for this disorder remains unclear. Autophagy plays an important role in the development of ARDS. The mitochondrial outer membrane protein FUNDC1 is involved in hypoxia-mediated mitochondrial autophagy, which may contribute to ARDS development. This study explored whether FUNDC1 regulates autophagy by inhibiting ROS-NLRP3 signaling to avoid apoptosis in the lung in a lipopolysaccharide-induced mouse model. In this study, FUNDC1 knockout mice were constructed, and a lipopolysaccharide-induced mouse model was generated. HE staining of pathological sections from the lung, wet/dry lung measurements, myeloperoxidase concentration/neutrophil counts in BALF and survival time of mice were examined to determine the effect of modeling. The release of cytokines (TNF-α, IL-1β, IL-6, and IL-10) in response to LPS in the BALF and plasma was assessed using ELISA. The effects of oxidative stress (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase) in lung tissue in response to LPS were detected by biochemical analysis. Oxidative stress damage was validated by iNOS staining, and apoptosis was assessed by TUNEL staining after LPS. Finally, the expression of autophagy-associated proteins and inflammasome-associated proteins in lung tissue after LPS intervention was analyzed by western blot. We found that wild-type control, FUNDC1 knockout control, lipopolysaccharide-induced wild-type, and FUNDC1 knockout mouse models were used to investigate whether FUNDC1-mediated autophagy is involved in lung injury and its possible molecular mechanisms. Compared with the normal control group, lung tissue FUNDC1 and LC3 II increased and p62/SQSTM1 decreased after LPS intervention, and increased ROS levels led to a decrease in corresponding antioxidant enzymes along with an increased inflammatory response and apoptosis. Levels of autophagy in lipopolysaccharide-induced mice deficient in FUNDC1 were significantly decreased, but the expression of ROS and inflammatory factors in lung tissue was more severe than in lipopolysaccharide-induced wild-type mice, and the survival rate was significantly decreased. Western blot analysis showed that autophagy was significantly inhibited in the FUNDC1 KO+LPS group, and there was a significant increase in NLRP3, caspase-1, IL-1β, and ASC compared with the lipopolysaccharide-induced wild-type group. In summary, lipopolysaccharide-induced wild-type mice exhibit ROS-dependent activation of autophagy, and knocking out FUNDC1 promotes inflammasome activation and exacerbates lung injury.


Formation and use of biogenic jarosite carrier for high-rate iron oxidising biofilms.
Jarosite precipitates formed in iron oxidising bioreactors have been shown to harbour iron-oxidisers. The aim of this study was to develop an iron oxidising bioprocess where microorganisms are retained solely on biogenic jarosite particles. Based on preliminary experiments using a fluidised-bed bioreactor (FBR), the formed jarosite particles started to disintegrate and wash out at upflow velocities of ≥0.21 cm/s. Therefore, the generation and use of biogenic jarosite carrier was studied in an expanded-bed bioreactor (J-EBR) with an upflow velocity of 0.19 cm/s. Inside J-EBR, the jarosite particles formed granules of 0.5-3 mm containing 200-460 mg/g of attached biomass. The performance of J-EBR was compared with an activated carbon biofilm FBR at 0.82 cm/s upflow velocity (AC-FBR). At 35 ± 2 °C with a feed ferrous iron concentration of 10 g/l, the highest obtained iron oxidation rate of J-EBR (6.8 g/l/h) was 33% lower than that of AC-FBR (10.1 g/l/h). This was likely due to the 80% lower recirculation rate and subsequently higher oxygen mass transfer limitation in J-EBR compared to AC-FBR. The present study demonstrates that biogenic jarosite can be used for retainment of iron oxidising biofilms in expanded-bed bioreactors that oxidise iron at high rates.


Regeneration of plantlets from mature embryo calli of Western Ghats land race cultivar of rice, Oryza sativa L.
The Malnad region located in the Western Ghats of Karnataka is known for the cultivation of indigenous rain fed land race cultivar of rice. The present study was to investigate the callogenic and caulogenic potentialities of the two indigenous rice cultivar namely Karimundaga and Kanadatumba using dehusked mature embryo explants. For callus and shoot bud differentiation, the explants were cultured on Murashige and Skoog (MS) medium supplemented with 2,4-D (1-3 mg/L), IAA (1-2 mg/L), Kn (1-4 mg/L) and BAP (1-4 mg/L). The morphogenic potentialities of the two rice cultivar differed in texture of callus. In both the cultivar callogenic frequency was optimized at 1 mg/L 2,4-D concentration, it was 94% in Karimundaga and 58% in Kanadatumba. Supplementation of IAA either alone (1-2 mg/L) or in combination with Kn or BAP at 1 to 4 mg/L concentration of each induces shoot bud differentiation from the calli. In the cultivar Karimundaga caulogenic frequency was highest (10.60 +/- 2.55) at 1.0 mg/L IAA and 4.0 mg/L BAP concentration. While in the cultivar Kanadatumba highest number of shoot buds (7.90 +/- 2.69) was differentiated at 1.0 mg/L IAA and 4.0 mg/L Kn concentration. The calli derived regenerants were successfully acclimatized in the greenhouse and agro-morphological variations were evaluated. The growth characteristics and yield related parameters exhibited by in vitro plants were lower than the in vivo plants.


Manipulating ZmEXPA4 expression ameliorates the drought-induced prolonged anthesis and silking interval in maize.
Drought poses a major environmental threat to maize (Zea mays) production worldwide. Since maize is a monoecious plant, maize grain yield is dependent on the synchronous development of male and female inflorescences. When a drought episode occurs during flowering, however, an asynchronism occurs in the anthesis and silking interval (ASI) that results in significant yield losses. The underlying mechanism responsible for this asynchronism is still unclear. Here, we obtained a comprehensive development-drought transcriptome atlas of maize ears. Genes that function in cell expansion and growth were highly repressed by drought in 50 mm ears. Notably, an association study using a natural-variation population of maize revealed a significant relationship between the level of α-expansin4 (ZmEXPA4) expression and drought-induced increases in ASI. Furthermore, genetic manipulation of ZmEXPA4 expression using a drought-inducible promoter in developing maize ears reduced the ASI under drought conditions. These findings provide important insights into the molecular mechanism underlying the increase in ASI in maize ears subjected to drought and provide a promising strategy that can be used for trait improvement.


Versatile transformations of hydrocarbons in anaerobic bacteria: substrate ranges and regio- and stereo-chemistry of activation reactions.
Anaerobic metabolism of hydrocarbons proceeds either via addition to fumarate or by hydroxylation in various microorganisms, e.g., sulfate-reducing or denitrifying bacteria, which are specialized in utilizing n-alkanes or alkylbenzenes as growth substrates. General pathways for carbon assimilation and energy gain have been elucidated for a limited number of possible substrates. In this work the metabolic activity of 11 bacterial strains during anaerobic growth with crude oil was investigated and compared with the metabolite patterns appearing during anaerobic growth with more than 40 different hydrocarbons supplied as binary mixtures. We show that the range of co-metabolically formed alkyl- and arylalkyl-succinates is much broader in n-alkane than in alkylbenzene utilizers. The structures and stereochemistry of these products are resolved. Furthermore, we demonstrate that anaerobic hydroxylation of alkylbenzenes does not only occur in denitrifiers but also in sulfate reducers. We propose that these processes play a role in detoxification under conditions of solvent stress. The thermophilic sulfate-reducing strain TD3 is shown to produce n-alkylsuccinates, which are suggested not to derive from terminal activation of n-alkanes, but rather to represent intermediates of a metabolic pathway short-cutting fumarate regeneration by reverse action of succinate synthase. The outcomes of this study provide a basis for geochemically tracing such processes in natural habitats and contribute to an improved understanding of microbial activity in hydrocarbon-rich anoxic environments.


Cross-cultural adaptation and validation of the Chinese version of the short-form of the Central Sensitization Inventory (CSI-9) in patients with chronic pain: A single-center study.
Chronic pain affects more than 30% of the general population. The 9-item Central Sensitization Inventory (CSI-9) is a shortened version of the CSI-25, which is a patient-reported instrument used to screen people at risk of central sensitization (CS). The aim of this study was to cross-culturally adapt and validate a Chinese version of the CSI-9. The Chinese CSI-9 was generated by translation of the original English version, back-translation, cultural adaptation, and revision using the Delphi method. The Chinese CSI-9 was administered to 235 patients with chronic pain and 55 healthy controls. Structural validity (confirmatory factor analysis), construct validity (correlations with other scales), test-retest reliability (intraclass correlation coefficient, ICC), and internal consistency (Cronbach's α) were evaluated. Confirmatory factor analysis was performed using one factor. The Chinese CSI-9 score was positively correlated with the Pain Catastrophic Scale (PCS) total score (r = 0.463), PCS subscale scores (r = 0.347-0.463), Brief Pain Inventory (BPI) mean item score (r = 0.524), BPI total score (r = 0.773), and the number of painful sites (r = 0.451). The Chinese CSI-9 had excellent test-retest reliability (ICC = 0.958) and excellent internal consistency (Cronbach's α = 0.902 in the overall sample and 0.828 in the chronic pain population). The optimal cut-off value for the Chinese CSI-9 was 18 points. The Chinese CSI-9 had excellent test-retest reliability and satisfactory structural validity and construct validity. The CSI-9 could potentially be utilized in China as a self-report questionnaire in both clinical practice and research settings.


Implementation of hazard analysis critical control point in jameed production.
The average of standard plate count and coliforms, Staphylococcus aureus and Salmonella counts for three home-made jameed samples, a traditional fermented dairy product, before applying hazard analysis critical control point system were 2.1 × 10(3), 8.9 × 10(1), 4 × 10(1) and less than 10 cfu/g, respectively. The developed hazard analysis critical control point plan resulted in identifying ten critical control points in the flow chart of jameed production. The critical control points included fresh milk receiving, pasteurization, addition of starter, water and salt, straining, personnel hygiene, drying and packaging. After applying hazard analysis critical control point system, there was significant improvement in the microbiological quality of the home-made jameed. The standard plate count was reduced to 3.1 × 10(2) cfu/g whereas coliform and Staphylococcus aureus counts were less than 10 cfu/g and Salmonella was not detected. Sensory evaluation results of color and flavor of sauce prepared from jameed showed a significant increase in the average scores given after hazard analysis critical control point application.


Surgical-site infection surveillance in general surgery: a critical issue.
This prospective study assessed the Surgical Site Infection (SSI) rates in General Surgery and the microorganisms isolated. From January 2000 to October 2000, 898 patients were enrolled and electively operated in a General Surgery Clinic in Athens, Greece. Pre-coded questionnaires were used. The diagnosis and surveillance of SSIs was made by the surgeon-investigator who interviewed the patients. Patients were monitored during hospitalization and post-discharge for 30 days. Overall, 402 patients underwent a clean and 496 patients underwent a clean-contaminated operation. A total of 17 SSIs (4.2%) were observed in clean and 64 SSIs (12.9%) in clean-contaminated operations. Microorganisms were isolated in 36 of 65 (55%) of cases that microbiological evaluation was performed. Staphylococcus aureus was the commonest microorganism isolated, followed by Escherichia coli and Pseudomonas aeruginosa. SSI rates were higher than expected and most SSIs, 43 of 81 (53.1%), were diagnosed post-operatively. Post-discharge surveillance of SSIs remains a critical issue. Health care professionals, especially surgeons, should participate in surveillance networks and be aware of the results so to take appropriate action.


Divergence of Rho residue 43 impacts GEF activity.
RhoA, RhoB and RhoC GTPases are over 85% identical at the amino acid level, with RhoA and RhoC differing at only one residue (43) across the initial two-thirds of their sequences. A putative regulatory distinction between the molecules is their capacity to be uniquely activated by guanine nucleotide exchange factors (GEFs). We hypothesize that variation of amino acid residue 43 between RhoA/B (valine) and RhoC (isoleucine) impacts GEF activity. Direct participation of residue 43 in GEF-catalyzed exchange was confirmed by the observation that mutation of this position to a threonine reduced GEF-catalyzed nucleotide exchange activity in vitro (Vav2, XPLN, GEFT, Dbl and Dbs) and greatly depressed RhoA and RhoC GTP-loading profiles in cell lysates. Using a residue swap approach, substitution of RhoA Val 43 with an Ile was found to significantly promote basal nucleotide exchange activity and enhance GTP-loading in cells. Substitution of Val 43 with an Ile in RhoB negatively affected nucleotide exchange in vitro. Substitution of RhoC Ile 43 with a Val increased GEF-catalyzed exchange in vitro. In addition, RhoC-I43V was more efficacious at driving ovarian cancer cell invasion through matrigrel than wild-type RhoC, RhoC-I43T, wild-type RhoA, RhoA-V43I or RhoA-V43T GTPases. These findings suggest that a divergence between RhoA/B and RhoC at residue 43 impacts basal and GEF-stimulated nucleotide exchange activity.


Synthesis and use of probes to investigate the cryptoregiochemistry of the first animal acetylenase.
Thaumetopoea pityocampa pheromone glands contain an unusual Delta(11) acetylenase that produces an alkynoic fatty acid intermediate in the sex pheromone biosynthetic pathway of this species. In this article, we describe the synthesis and use of the deuterated (Z)-11-hexadecenoic acid probes required to decipher the cryptoregiochemistry of this enzyme. The label in the olefinic bonds was introduced by Wittig reaction between the appropriate deuterated reagents. Besides the vinyl deuterium atoms, for reliable GC-MS analyses these compounds bear a tetradeuterium tag, which was introduced by deuteration of an alkyne intermediate in the presence of the Wilkinson catalyst. Pheromone gland metabolization studies of these probes provided experimental evidence that the transformation of (Z)-11-hexadecenoic acid into 11-hexadecynoic acid by the Delta(11) acetylenase takes place by a stepwise mechanism, in which a significant perturbation of the strong vinyl C11-H bond occurs prior to a fast elimination of the vinyl hydrogen at C-12.


Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response.
Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments. Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts.


[Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines].
To study the cancer stem cell populations in esophageal cancer cell lines KYSE150 and TE1 and identify whether resulting stem-like cell spheres display radiation resistance characteristics. Serum-free medium (SFM) suspension was used to culture the esophageal cancer stem cell lines and enrich the esophageal stem-like cell spheres. RT-PCR assay was used to detect the stem cell gene expression in the sphere cells. Radiosensitivity of the sphere cells and parental cells were evaluated by clone formation assay. Different cells after irradiation at different doses were tested to evaluate the changes of sphere formation, and cell cycle and CD44(+)CD271(+) expression of the sphere cells were also analyzed by flow cytometry before and after irradiation. Cancer stem-like cell spheres were generated from KYSE150 and TE1 cells and enriched by culture in serum-free medium, and the number of spheres was increasing alone with the increase of cell passages. The numbers of spheres formed from the 1st, 2nd and 3rd generations of KYSE150 cells were 25 ± 2, 37 ± 2 and 47 ± 3, respectively. The numbers of spheres formed from the 1st, 2nd and 3rd generations of TE1 cells were 15 ± 3, 24 ± 3 and 36 ± 4, respectively. Certain doses of radiation increased the sphere formation rate. The average survival fraction (SF2) of the suspension-cultured KYSE150 stem-like cell spheres after 2 Gy irradiation were 0.81 ± 0.03 and 0.69 ± 0.04, while that of TE1 parental cells were 0.87 ± 0.01 and 0.80 ± 0.03 (P < 0.05 for all). In the esophageal parental KYSE150 and TE1 cells, arrest at G2 phase was induced after irradiation. After the same dose of irradiation, the inhibition of proliferation of the cancer stem cells was lower than that of the parent cells (P < 0.05). After 0, 4 and 8 Gy irradiation, the CD44(+)CD271(+) cell percentage of KYSE150 parental cells were (1.08 ± 0.03)%, (1.29 ± 0.07)% and (1.11 ± 0.09)%; the CD44(+)CD271(+) cell percentage of TE1 parental cells were (1.16 ± 0.11)%, (0.97 ± 0.08)% and (1.45 ± 0.35)% (P > 0.05 for all). After 0, 4 and 8 Gy irradiation, the percentage of CD44(+)CD271(+) cells of KYSE150 stem cell-like spheres were (35.83 ± 1.23)%, (44.90 ± 1.67)% and (57.77 ± 1.88)%, and that of TE1 stem cell-like spheres were (16.07 ± 0.91)%, (22.67 ± 1.12)% and (33.27 ± 1.07)%. Compared the 4 Gy and 8 Gy irradiated KYSE150 and TE1 stem-like cell spheres with the 0 Gy irradiated spheres, the differences were statistically significant (P < 0.05 for all). The cancer stem cells in KYSE150 and TE1 spheres are more radio-resistant than their parental cells. It may suggest that cancer stem cell populations in the esophageal cancer cells are related to the mechanism of occurrence of radioresistance.


Influence of transition metal electronegativity on the oxygen storage capacity of perovskite oxides.
The selection of highly efficient oxygen carriers (OCs) is a key step necessary for the practical development of chemical looping combustion (CLC). In this study, a series of ABO3 perovskites, where A = La, Ba, Sr, Ca and B = Cr, Mn, Fe, Co, Ni, Cu, are synthesized and tested in a fixed bed reactor for reactivity and stability as OCs with CH4 as the fuel. We find that the electronegativity of the transition metal on the B-site (λB), is a convenient descriptor for oxygen storage capacity (OSC) of our perovskite samples. By plotting OSC for total methane oxidation against λB, we observe an inverted volcano plot relationship. These results could provide useful guidelines for perovskite OC design and their other energy related applications.


The Behavioral Intervention with Technology for E-Weight Loss Study (BITES): Incorporating Energy Balance Models and the Bite Counter into an Online Behavioral Weight Loss Program.
This study evaluated feasibility and acceptability of adding energy balance modeling displayed on weight graphs combined with a wrist-worn bite counting sensor against a traditional online behavioral weight loss program. Adults with a BMI of 27-45 kg/m2 (83.3% women) were randomized to receive a 12-week online behavioral weight loss program with 12 weeks of continued contact (n = 9; base program), the base program plus a graph of their actual and predicted weight change based on individualized physiological parameters (n = 7), or the base program, graph, and a Bite Counter device for monitoring and limiting eating (n = 8). Participants attended weekly clinic weigh-ins plus baseline, midway (12 weeks), and study culmination (24 weeks) assessments of feasibility, acceptability, weight, and behavioral outcomes. In terms of feasibility, participants completed online lessons (M = 7.04 of 12 possible lessons, SD = 4.02) and attended weigh-ins (M = 16.81 visits, SD = 7.24). Six-month retention appears highest among nomogram participants, and weigh-in attendance and lesson completion appear highest in Bite Counter participants. Acceptability was sufficient across groups. Bite Counter use (days with ≥ 2 eating episodes) was moderate (47.8%) and comparable to other studies. Participants lost 4.6% ± 4.5 of their initial body weight at 12 weeks and 4.5% ± 5.8 at 24 weeks. All conditions increased their total physical activity minutes and use of weight control strategies (behavioral outcomes). Although all groups lost weight and the study procedures were feasible, acceptability can be improved with advances in the technology. Participants were satisfied with the online program and nomograms, and future research on engagement, adherence, and integration with other owned devices is needed. ClinicalTrials.gov Identifier: NCT02857595.


Prognostic significance of hematoma thickness to midline shift ratio in patients with acute intracranial subdural hematoma: a retrospective study.
Acute intracranial subdural hematoma (ASDH) is commonly associated with a grave prognosis citing a high incidence of morbidity and mortality. The parameters to decide on surgical evacuation of the hematoma are sometimes controversial. In this study, we theorized that the ratio between maximal hematoma thickness and midline shift would be varied by associated intrinsic brain pathology emanating from the trauma and would thus objectively evaluates the prognosis in ASDH. The records of patients diagnosed with ASDH who were submitted to surgical evacuation through a craniotomy were revised. Data collected included basic demographic data, preoperative general and neurological examinations, and radiological findings. The maximal thickness of the hematoma (H) on the preoperative CT brain was divided by the midline shift at the same level (MS) formulating the H/MS ratio. Postoperative data obtained included Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), and follow-up period. Sixty-seven eligible patients were included in the study, of which 53 (79.1%) patients were males. Mean age was 34 years. The H/MS ratio ranged from 0.69 to 1.8 with a mean of 0.93. Age above 50 years (P = 0.0218), admission GCS of less than 6 (0.0482), and H/MS ratio of 0.79 or less (P = 0.00435) were negative prognostic factors and correlated with a low postoperative GCS and GOS. H/MS ratio is a useful prognostic tool in patients diagnosed with ASDH and can be added to the armamentarium of data to improve the management decision in this cohort of patients.


Mammalian wound repair environment does not permit skeletal muscle regeneration.
Repair and regeneration are mutually exclusive responses to injury. Previous studies have shown that wound fluids promote proliferation, but not differentiation, of myoblasts in vitro. This study explored the ability of the repair environment within polyvinyl alcohol sponges to support cellular events of skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to express beta-galactosidase then inoculated into plain sponges or sponges containing minced muscle. Labeled myoblasts were found in myotubes within minced muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained mononucleate. Occurrence of labeled myoblasts within myotubes, which required fusion, represents differentiation of inoculated myoblasts to participate in regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle suggests that this wound repair environment cannot support morphologic differentiation of myoblasts. Although this repair environment can support the survival of myoblasts, it did not support myogenesis, an event necessary to complete skeletal muscle regeneration. Data from this study reinforce earlier studies in vitro and suggest that the properties attributed to wound fluids are inherent in the wound environment. Whether the inability of this environment to support myogenesis is the consequence of the absence of essential factors or the presence of inhibitors remains to be determined.


Methods for Detection of Protein Interactions with Plasmodesmata-Localized Reticulons.
Plant reticulon family proteins (RTN) tubulate the ER by dimerization and oligomerization, creating localized ER membrane tensions that result in membrane curvature. Two RTN ER-shaping proteins have been found in the plasmodesmata (PD) proteome which could potentially contribute to the formation of the desmotubule, an ER-derived structure that crosses primary PD and physically connects the ER of two cells. Here we describe two methods used to identify partners of two PD-resident reticulon proteins, RTN3 and RTN6 that are located in primary PD at cytokinesis in tobacco (Nicotiana tabacum): immunoprecipitations using GFP-Trap®_A beads to find novel interaction partners and FRET-FLIM to test for and quantify direct protein-protein interactions in planta.


Two new species of lace bugs from Dominican amber and a new species from Colombian copal (Hemiptera: Heteroptera: Tingidae).
Two new fossil species (Phatnoma pulchra sp. nov., Leptopharsa antica sp. nov.) of the family Tingidae (Hemiptera: Heteroptera) from Dominican amber (Dominican Republic) and one new species (Leptopharsa colombiana sp. nov.) from Colombian copal (Colombia) are described and illustrated with photos. Features of similarities and differences from closely related fossil and recent species are given.


A Microflow Cytometer Based on a Disposable Microfluidic Chip With Side Scatter and Fluorescence Detection Capability.
In this paper, we present a microflow cytometer based on a polydimethylsiloxane (PDMS) microfluidic chip. The PDMS chip has a smooth sidewall because of the proposed double molding process. Thus, the side scatter (SSC) detection can be used for the cytometer. The coincidence error using the sheathless focus mechanism is less than 0.069%. Using Flow-Check alignment beads for the counting experiment, the coefficient of variation (CV) of the SSC and the fluorescein isothiocyanate (FITC) channel can reach 8.37% and 2.46%, respectively. The gating of the lymphocytes according to CD45/SSC was also demonstrated successfully. It proves that the chip is a promising solution for point of care (POC) microflow cytometers.


A collaborative approach to improving representation in viral genomic surveillance.
The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic. Over subsequent months, poor surveillance enabled variants to emerge unnoticed. Against this backdrop, long-standing social and racial inequities have contributed to a greater burden of cases and deaths among minority groups. To begin to address these problems, we developed a new variant surveillance model geared toward building 'next generation' genome sequencing capacity at universities in or near rural areas and engaging the participation of their local communities. The resulting genomic surveillance network has generated more than 1,000 SARS-CoV-2 genomes to date, including the first confirmed case in northeast Louisiana of Omicron, and the first and sixth confirmed cases in Georgia of the emergent BA.2.75 and BQ.1.1 variants, respectively. In agreement with other studies, significantly higher viral gene copy numbers were observed in Delta variant samples compared to those from Omicron BA.1 variant infections, and lower copy numbers were seen in asymptomatic infections relative to symptomatic ones. Collectively, the results and outcomes from our collaborative work demonstrate that establishing genomic surveillance capacity at smaller academic institutions in rural areas and fostering relationships between academic teams and local health clinics represent a robust pathway to improve pandemic readiness.


A survey of antenatal and peripartum provision of information on analgesia and anaesthesia.
Pregnant women should receive information about what they might expect to experience during their delivery. Despite this, research shows many women are inadequately prepared for anaesthetic interventions during labour. We surveyed 903 postnatal women across 28 Greater London hospitals about: the analgesic and anaesthetic information that they recalled receiving during pregnancy and delivery; their confidence to make decisions on analgesia; and their satisfaction with the analgesia used. Wide variation was observed between hospitals. Overall, 67 of 749 (9.0%) women recalled receiving antenatal information covering all aspects of labour analgesia, and 108 of 889 (12.1%) covering anaesthesia for caesarean section. Regarding intrapartum information, 256 of 415 (61.7%) respondents recalled receiving thorough information before epidural insertion for labour analgesia, and 102 of 370 (27.6%) before anaesthesia for caesarean section. We found that 620 of 903 (68.7%) women felt well enough informed to be confident in their analgesic choices, and 675 of 903 (74.8%) stated that their analgesia was as expected or better. Receiving information verbally, regardless of provider, was the factor most strongly associated with respondents recalling receiving full information: odds ratio (95%CI) for labour analgesia 20.66 (8.98-47.53; p < 0.0001); epidural top-up for caesarean section 5.93 (1.57-22.35; p = 0.01); and general anaesthesia for caesarean section 12.39 (2.18-70.42; p = 0.01). A large proportion of respondents did not recall being fully informed before an anaesthetic intervention. Collaboration with current antenatal service providers, both in promoting information delivery and providing resources to assist with delivery, could improve the quality of information offered and women's retention of that information.


Intensity of trematode metacercariae in cyprinoid fish in Chiang Mal Province, northern Thailand.
The intensity of infection of trematode metacercariae was determined in five species of cyprinoid fish collected from Mae Ngud reservoir, Chiang Mai Province. These species were Thynnichthys thynnoides, Puntioplites proctozysron, Hampala macrolepidota, Puntius leiacanthus and Puntius gonionotus. T. thynnoides contained the highest number (83.0%) of metacercariae, whereas P. gonionotus had the fewest (0.19%). The caudal fin was the area of highest infection of metacercariae (49.39%), with the anal fin having the fewest (5.93%). Most metacercariae was isolated from Haplorchis taichui (63.27%), with an intensity variation of 0.3-165.2 metacercariae/fish.


Nonparametric estimation of stage occupation probabilities in a multistage model with current status data.
Multistage models are used to describe individuals (or experimental units) moving through a succession of "stages" corresponding to distinct states (e.g., healthy, diseased, diseased with complications, dead). The resulting data can be considered to be a form of multivariate survival data containing information about the transition times and the stages occupied. Traditional survival analysis is the simplest example of a multistage model, where individuals begin in an initial stage (say, alive) and move irreversibly to a second stage (death). In this article, we consider general multistage models with a directed tree structure (progressive models) in which individuals traverse through stages in a possibly non-Markovian manner. We construct nonparametric estimators of stage occupation probabilities and marginal cumulative transition hazards. Empirical calculations of these quantities are not possible due to the lack of complete data. We consider current status information which represents a more severe form of censoring than the commonly used right censoring. Asymptotic validity of our estimators can be justified using consistency results for nonparametric regression estimators. Finite-sample behavior of our estimators is studied by simulation, in which we show that our estimators based on these limited data compare well with those based on complete data. We also apply our method to a real-life data set arising from a cardiovascular diseases study in Taiwan.


beta 2-Microglobulin instability in pathological urine.
Urinary excretion of beta 2-microglobulin (beta 2M) is a widely used test of renal proximal tubular function. beta 2M is known to be unstable in normal urine with a pH less than 5.5. The results of a study of beta 2M excretion in patients receiving gentamicin suggested that beta 2M might be more unstable in pathological urine. A series of experiments was designed to define the extent, variability, and mechanism of its instability in pathological urine. It was unstable in pathological urine with a pH of 6.0 at 37 degrees C and pH 5.5 at room temperature, but this varied in urines from different patients. The instability was abolished by heating the urine to 80 degrees C. These results suggest that the most likely explanation for the instability is enzymic degradation. Because enzymuria will vary among patients, investigators should test the stability of beta 2M in urine from the patients they wish to study before trying to define conditions for urine collection.


Engineering independent electrostatic control of atomic-scale (∼4 nm) silicon double quantum dots.
Scalable quantum computing architectures with electronic spin qubits hosted by arrays of single phosphorus donors in silicon require local electric and magnetic field control of individual qubits separated by ∼10 nm. This daunting task not only requires atomic-scale accuracy of single P donor positioning to control interqubit exchange interaction but also demands precision alignment of control electrodes with careful device design at these small length scales to minimize cross capacitive coupling. Here we demonstrate independent electrostatic control of two Si:P quantum dots, each consisting of ∼15 P donors, in an optimized device design fabricated by scanning tunneling microscope (STM)-based lithography. Despite the atomic-scale dimensions of the quantum dots and control electrodes reducing overall capacitive coupling, the electrostatic behavior of the device shows an excellent match to results of a priori capacitance calculations. These calculations highlight the importance of the interdot angle in achieving independent control at these length-scales. This combination of predictive electrostatic modeling and the atomic-scale fabrication accuracy of STM-lithography, provides a powerful tool for scaling multidonor dots to the single donor limit.


RNA-Seq analysis of the toxicant-induced transcriptome of the marine diatom, Ceratoneis closterium.
Diatoms are of enormous ecological importance as they account for as much as 20% of global primary production, yet they are still understudied from a genomic perspective. The benthic diatom Ceratoneis closterium is well-characterized from an ecotoxicological perspective including its use in ecotoxicological risk assessments and investigating the mode-of-action of metal toxicity. However, this organism has little sequence information available. In this study, 454 pyrosequencing of the stressor-responsive transcriptome was undertaken. These transcripts could be used to characterize general physiological processes such as photosynthesis and respiration, as well as to enable a description of the ecotoxicogenomic responses of this organism. After a 96 h exposure to the concentration of toxicant that inhibited growth rate by 10% (IC10) for the following common coastal contaminants: ammonia, copper, crude oil and simazine (a photosystem II inhibiting herbicide), diatom cells were harvested for RNA extraction and their transcriptomes characterized via 454 pyrosequencing. This resulted in 1.25 million reads, which were assembled into 4768 contigs, when contigs encoding rRNA were removed. More than 80% of the remaining contigs had an ortholog in the BLASTx protein databases. These contigs represented 1660 unique transcripts. The role of these transcripts in stress response, as well as photosynthesis and respiration is discussed. Overall, this study greatly enhances the genomic information available for this important taxonomic group.


Is the present cut-point to define type 2 diabetes appropriate in Latin-Americans?
The diagnosis of diabetes mellitus type 2 (DM2) is based either on increased plasma glucose or Glycated hemoglobin levels. Since these measures are the only means for diagnosis of DM2, they must be well adapted to each population according to their metabolic characteristics, given that these may vary in each population. The World Health Organization (WHO) determined the cut-points of plasma glucose levels for the diagnosis of DM2 by associating hyperglycemia with the risk of a specific microvascular complication-retinopathy. Cardiovascular diseases are however the principal causes of mortality in patients with DM2 and we reported that in the Colombo-Ecuadorian population impaired fasting glucose and impaired glucose tolerance are both risk markers for myocardial infarction. We propose that the current cut-points accepted by the WHO need to be revaluated in populations such as Latin America and that there should be lower cut points for glycaemia in this population, to reduce the prevalence of cardiovascular complications associated with DM2.


Nuclear translocation of telomerase reverse transcriptase: a critical process in chemical induced hepatocellular carcinogenesis.
Telomerase, a ribonuclearprotein complex, functions not only in cancer development but also in apoptosis, and senescence. As a catalytic subunit of telomerase, telomerase reverse transcriptase (TERT) has been confirmed to regulate telomerase activity in a rate-limiting manner. Although a lot of work has been done, the dynamic state of TERT protein and the relationship with telomerase have not been delineated systematically in cancer development. The purpose of this study was to do such an exploration. To investigate the role of TERT in the in vivo carcinogenesis, we performed immunofluorescence and Western blot analysis, respectively, to detect the alteration of TERT status as well as telomeric repeat amplification protocol (TRAP) assay to detect telomerase activity in diethyl nitrosoamine (DENA) induced rat hepatocellular carcinoma (HCC). The course of cancer development was divided into three main stages, which were inflammation ( <12 weeks), hepatocirrhosis (15 weeks), and hepatocarcinoma (18-21 weeks). In normal liver and its early inflammatory stage, concomitant with a weak positive TERT signal, which was detected exclusively in the cytoplasm, telomerase activity was very low at this stage. However, in late hepatocirrhosis and particularly cancer stage, high levels of TERT expression (P = 0.044 and P = 0.001, respectively) and telomerase activity (P = 0.02 and P = 0.01, respectively) were observed following TERT nuclear translocation. Our data suggest that TERT protein might regulate telomerase activity. TERT translocation from cytoplasm to the nucleus might be a turning point in cancer development. Therefore, TERT translocation might be more useful than TERT expression level and telomerase activity in predicting the progression of HCC.


[Histologic classification of breast cancer and its precancerous stages].
A proliferating mastopathy with severe epithelial atypia as well as with so-called radial scars, intraductal papillomatosis, and findings of so-called lobular cancerisation are regarded as possible precursors of mammary carcinoma. The histological differential diagnosis can be difficult between atypical epithelial proliferations in mastopathy and noninvasive intraductal carcinoma, between tubular formations in radial scars and tubular carcinoma, papilloma and papillary carcinoma as well as between primary and secondary lobular cancerisation. Noninvasive and invasive breast carcinomas can be diagnosed according to the WHO classification (12) with a relatively good reproduceability. Besides the histological type, other macroscopic (tumour size, number of metastatically involved lymph nodes, distant metastases), microscopic (tumour grading) as well as biochemical findings (receptor status) are also important for treatment and prognosis of breast carcinoma.


A 13-year-old female with Turner syndrome and achalasia.
The most common gastrointestinal problems associated with Turner syndrome are intestinal telangiectasia, colon carcinomas, inflammatory bowel, and liver diseases. In this paper we present for the first time a 13-year-old female with 45,X karyotype associated with achalasia. As far as we know, achalasia associated with Turner syndrome has not been reported previously. The aim of this report was to point out the association of Turner syndrome and achalasia. It could be a coincidental or Turner syndrome-associated finding.


Taking a history of childhood trauma in psychotherapy : achieving an optimal approach.
The authors examine the process of taking an initial history of childhood abuse and trauma in psychodynamic psychotherapy. In exploring the advantages, complexities, and potential complications of this practice, they hope to heighten the sensitivities of clinicians taking trauma histories. Emphasis on the need to be active in eliciting important historical material is balanced with discussion of concepts that can help therapists avoid interpersonal dynamics that reenact and perpetuate the traumas the therapy seeks to treat. Ensuring optimal psychotherapeutic treatment for patients who have experienced childhood trauma requires attention to the following concepts: a safe holding environment, destabilization, compliance, the repetition compulsion, and projective identification.


Accuracy of apex locator.
An evaluation of the accuracy of the "Root ZX" apex locator was conducted on 20 single-rooted teeth that had been extracted because of severe disease or orthodontic treatment. After the pulp chamber had been accessed and the tooth length determined using the Root ZX apparatus, the file was fixed to the tooth with light-cured composite resin. After extraction, the tooth was longitudinally ground with a diamond bur until the file was visible. The distance between the file tip and the apical foramen was measured under a microscope (x 100). The results showed that the tip of the instrument reached the apical foramen in all teeth.


A Novel Self-Microemulsifying System for the Simultaneous Delivery and Enhanced Oral Absorption of Curcumin and Resveratrol.
The use of curcumin and resveratrol in combination has now become increasingly of interest because of their synergistic effects as therapeutic agents for various diseases, especially cancer. To overcome the poor oral bioavailability of both compounds and improve patient compliance, a novel self-microemulsifying formulation containing curcumin together with resveratrol was developed. Capryol 90, Cremophor EL, and Labrasol were selected as the oil, surfactant, and co-surfactant in the formulation, respectively, based on the solubility study of both compounds. More than 70 % and 80 % of curcumin and resveratrol, respectively, were released in 20 min. The formulation formed a fine oil in water microemulsion with droplet sizes in aqueous media of 15-20 nm. In addition, the formulation containing curcumin and resveratrol showed greater antioxidant activity than that of the formulations with individual compounds, while the cytotoxic activity against HT-29 of the co-formulation (IC50 = 18.25 µM; curcumin and resveratrol in the ratio 1 : 1) was less than the formulation with only curcumin (IC50 = 30.1 µM) and only resveratrol (IC50 = 25.4 µM). After oral administration to rabbits, the self-microemulsifying formulation containing curcumin together with resveratrol increased the total plasma concentrations of curcumin and resveratrol by 10-fold and 6-fold, respectively, compared to the unformulated combination. This study clearly demonstrated the potential use of the self-microemulsifying formulation for co-delivery, and enhanced oral absorption of poorly water-soluble natural compounds. In addition, the combination was found to produce synergistic antioxidant activity and cytotoxicity against HT-29 cells.


A Case Series of Nephrotic Syndrome: A Harbinger of Catastrophic Oncologic Diseases.
A cancer patient can have numerous complications involving the kidneys, ranging from acute kidney injury, chronic kidney disease, glomerulopathies, electrolyte, and acid-base disorders. It can be due to the malignancy itself or due to chemotherapeutic agents. Paraneoplastic glomerulopathy is a rare presentation of neoplastic disease. We present a case series of two patients presenting with nephrotic syndrome as a paraneoplastic syndrome associated with a gynecologic tumor. Both patients responded only partially to steroids and immunosuppressive therapy. Complete remission was only achieved after treatment of primary malignancy. It is critical to recognize this entity as immunosuppression may induce a flare in the tumor course and worsen outcomes. So, age-appropriate screening of malignancy should ideally be performed in any adult patient with nephrotic syndrome.


NHC-catalyzed C-O or C-N bond formation: efficient approaches to α,β-unsaturated esters and amides.
Simple and efficient NHC-catalyzed transformations of bromoenal or α,β-dibromoenal into α,β-unsaturated esters or amides with high stereoselectivity through C-O or C-N bond formation have been demonstrated. The NHC-catalyzed processes occur under mild conditions. The ready availability of the starting materials, avoidance of external oxidants and the usefulness of the products all make the strategy attractive.


Quantitative proteomic analysis for radiation-induced cell cycle suspension in 92-1 melanoma cell line.
Melanoma is a malignant tumor with high invasive and metastatic properties. Though radiation is the major therapy for melanoma, its radio-resistance has been shown to severely influence the clinical outcome. So it is imperative to enhance the sensitivity of uveal melanoma cells to radiotherapy. Previously, we found that the cell cycle of 92-1 uveal melanoma cells was suspended and remained unchanged for up to 5 days after exposure to 10 Gy of X-rays, which might be relevant to the high radio-sensitivity of 92-1 cells. To further investigate the cell cycle suspension-associated proteins, we employed two analyses with stable isotope labeling with amino acids in cell culture technology and two-dimensional liquid chromatography tandem mass spectrometry. Cells were incubated for 15 h or 48 h after irradiation with 10 Gy of X-rays. We identified a total of 737 proteins at 15 h (Group A) and 530 proteins at 48 h post-irradiation (Group B). The gene ontology biological pathway was used to obtain a systems level view of proteome changes in 92-1cells under cell cycle suspension. We further selected the significantly changed proteins for investigation of their potential contribution to cell cycle suspension, growth arrest and cell senescence. These proteins are involved in the cell cycle, stress response, glycolysis and the tricarboxylic acid cycle, etc. Our study expected to reveal potential marker proteins associated with cell suspension induced by irradiation, which might contribute to understanding the mechanism beyond the cell cycle suspension.


Long-term mild exercise training enhances hippocampus-dependent memory in rats.
Although exercise training improves hippocampus-related cognition, the optimum exercise intensity is still disputed. Based on the lactate threshold (LT, approximately 20 m/min on treadmill) of rats, we have shown that 2 weeks of training with stress-free mild exercise (ME, <LT), but not intense exercise (IE, >LT), comprising exercise stress, promotes adult hippocampal neurogenesis (Okamoto et al., PNAS, 2012), a potential substrate for memory improvement. These results led us to postulate that long-term ME, but not IE, training leads to improved hippocampal function as assessed with a Morris water maze (MWM) task. To test this hypothesis, we investigated the changes in physiological stress levels and MWM task performance in rats assigned to 6 weeks of sedentary control (CONT), ME-training or IE-training conditions. Results showed that, compared to the other conditions, only IE causes general adaptive syndrome (GAS), including adrenal hypertrophy, thymic atrophy and hypercorticosteronemia. In the MWM, ME led to enhanced memory, but not learning, compared with CONT, while IE produced no change in either capacity, probably due to GAS. These findings support the hypothesis that 6 weeks of continuous ME training leads to enhanced hippocampus-related memory, which may have implications for both healthy adults and subjects with low physical capacity.


Optimization of aqueous-based film coating of tablets performed by a side-vented pan-coating system.
The purpose of this research was to characterize the aqueous-based hydroxypropylmethylcellulose (HPMC) film coating of tablets utilizing a laboratory-scale side-vented pan-coating apparatus (Thai coater). The process and apparatus parameters of potential importance with respect to the final film quality were evaluated by using fractional factorial design (2(6-2)IV) and the process was optimized using response surface methodology (central composite design). Rotating speed of the pan was identified as a major parameter with respect to film thickness (weight increase; p < 0.05) and breaking strength (p < 0.05) of the aqueous HPMC film-coated tablets. Increasing the rotating speed from 5 rpm to 10 rpm resulted in a mean relative change of -43.9% and 2.4% of film thickness (weight increase) and breaking strength, respectively. As expected, inlet air temperature significantly affected the moisture content of the final film-coated tablets (p < 0.01) and the film thickness (weight increase; p < 0.05), but the effects on the other responses studied were minimal or negligible. Pneumatic spraying pressure and position of the spray gun (excluding angle of the gun) did not affect the responses studied. The process parameters relevant to a side-vented pan-coating process can be identified (by fractional factorial design) and, consequently, optimized (by central composite design) by using the factorial design approach.


Seasonal expressions of SPAG11A and androgen receptor in the epididymis of the wild ground squirrels (Citellus dauricus Brandt).
Sperm-associated antigen 11A (SPAG11A) is expressed exclusively in the epididymis, which can specifically regulate sperm maturation. The aim of this study was to investigate the seasonal expressions of beta-defensin (SPAG11A) and androgen receptor (AR) in the epididymis of the wild ground squirrels (Citellus dauricus Brandt). Morphologically, the results showed that epididymis length and weight in the breeding season were significantly higher than those of the non-breeding season. Histologically, the results revealed that enlarged lumen diameters, thickened epithelial and abundant sperm in the breeding season while reduced lumen diameters and epithelial with no sperm in the non-breeding season. SPAG11A was intensely expressed in cytoplasm and nucleus of epithelial cells in the breeding season, and weaker staining in the non-breeding season. The immunostaining of AR was only presented in nucleus of smooth muscle cells and epithelial cells in the whole epididymis with stronger staining in the breeding season. The results of real-time quantitative PCR also showed that the mRNA levels of SPAG11A and AR in the epididymis during the breeding season were significantly higher than those of the non-breeding season. In addition, the levels of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum were higher during the breeding season. Taken together, these results suggested that SPAG11A might play an important role to regulate seasonal changes in epididymal function of the wild ground squirrels.


Recent data on magnesium and osteoporosis.
Larger and more perfect bone mineral crystals and decreased bone magnesium concentration were found in postmenopausal osteoporosis, senile osteoporosis, alcoholic osteoporosis and osteoporosis associated with thalassaemia. The decreased bone magnesium concentration and the increased retention of magnesium in the magnesium load test suggest magnesium deficiency in post-menoposal osteoporosis, probably caused by magnesium malabsorption.


Turbulent burning velocity and thermodiffusive instability of premixed flames.
Reported in the paper are results of unsteady three-dimensional direct numerical simulations of laminar and turbulent, lean hydrogen-air, complex-chemistry flames propagating in forced turbulence in a box. To explore the eventual influence of thermodiffusive instability of laminar flames on turbulent burning velocity, (i) a critical length scale Λ_{n} that bounds regimes of unstable and stable laminar combustion is numerically determined by gradually decreasing the width Λ of computational domain until a stable laminar flame is obtained, and (ii) simulations of turbulent flames are performed by varying the width from Λ<Λ_{n} (in this case, the instability is suppressed) to Λ>Λ_{n} (in this case, the instability may grow). Moreover, simulations are performed either using mixture-averaged transport properties (low Lewis number flames) or setting diffusivities of all species equal to heat diffusivity of the mixture (equidiffusive flames), with all other things being equal. Obtained results show a significant increase in turbulent burning velocity U_{T} when the boundary Λ=Λ_{n} is crossed in weak turbulence, but almost equal values of U_{T} are computed at Λ<Λ_{n} and Λ>Λ_{n} in moderately turbulent flames characterized by a Karlovitz number equal to 3.4 or larger. These results imply that thermodiffusive instability of laminar premixed flames substantially affects burning velocity in weak turbulence only, in line with a simple criterion proposed by Chomiak and Lipatnikov (Phys. Rev. E 107, 015102, (2023)10.1103/PhysRevE.107.015102).


Adherence to federal guidelines for reporting of sex and race/ethnicity in clinical trials.
The National Institutes of Health Revitalization Act of 1993 requires that NIH-funded clinical trials include women and minorities as subjects; other federal agencies have adopted similar guidelines. The objective of this study was to determine the current level of compliance with these guidelines in federally funded randomized controlled trials. Randomized controlled trials published in nine influential medical journals in 2004 were identified by PubMed search. Studies where individuals were not the unit of analysis, those begun before 1994, and those not receiving federal funding were excluded. Included studies were examined to determine sample characteristics and presence of subgroup reporting. PubMed located 589 published papers. After exclusion of ineligible papers, 69 remained for analysis. Among 46 clinical studies enrolling both men and women, women were generally underrepresented, comprising on average 37% of the sample and only 24% of the sample when analysis was restricted to drug trials. Eighty-seven percent of the studies did not report any outcomes by sex or include sex as a covariate in modeling. Among all 69 studies, 18% did not break down sample sizes by racial and ethnic groups, and 87% did not provide any analysis by racial or ethnic groups. Only 5 studies indicated that the generalizability of their results may be limited by lack of diversity among those studied. These findings illustrate inadequate compliance with the NIH guidelines. Researchers, editors, and journal audiences share the responsibility of ensuring compliance with our country's policies regarding federally funded research to effect healthcare improvements for all.


Adjuvant and immunogenic activities of the 73kDa N-terminal alpha-domain of BrkA autotransporter and Cpn60/60kDa chaperonin of Bordetella pertussis.
A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge. IgG1 and IgG2a were stimulated suggesting that the immune response could be modulated to produce Th1 or Th2.


Retention Models on Core-Shell Columns.
A thin, active shell layer on core-shell columns provides high efficiency in HPLC at moderately high pressures. We revisited three models of mobile phase effects on retention for core-shell columns in mixed aqueous-organic mobile phases: linear solvent strength and Snyder-Soczewiński two-parameter models and a three-parameter model. For some compounds, two-parameter models show minor deviations from linearity due to neglect of possible minor retention in pure weak solvent, which is compensated for in the three-parameter model, which does not explicitly assume either the adsorption or the partition retention mechanism in normal- or reversed-phase systems. The model retention equation can be formulated as a function of solute retention factors of nonionic compounds in pure organic solvent and in pure water (or aqueous buffer) and of the volume fraction of an either aqueous or organic solvent component in a two-component mobile phase. With core-shell columns, the impervious solid core does not participate in the retention process. Hence, the thermodynamic retention factors, defined as the ratio of the mass of the analyte mass contained in the stationary phase to its mass in the mobile phase in the column, should not include the particle core volume. The values of the thermodynamic factors are lower than the retention factors determined using a convention including the inert core in the stationary phase. However, both conventions produce correct results if consistently used to predict the effects of changing mobile phase composition on retention. We compared three types of core-shell columns with C18-, phenyl-hexyl-, and biphenyl-bonded phases. The core-shell columns with phenyl-hexyl- and biphenyl-bonded ligands provided lower errors in two-parameter model predictions for alkylbenzenes, phenolic acids, and flavonoid compounds in comparison with C18-bonded ligands.


Comparative reproductive performance and early lactation productivity of Jersey x Holstein cows in predominantly Holstein herds in a pasture-based dairying system.
The aim of this study was to compare the reproductive performance, milk production, live weight, and body condition loss during early lactation of purebred Holstein (H) cows to Jersey x H (J x H) crossbred cows in 4 Victorian herds. Cows of H and J x H breeding were managed together within each herd, and all herds had a seasonally concentrated calving pattern that commenced in early spring (July). All crossbred cows included in the study were 25, 50, or 75% H and were considered collectively as J x H regardless of the sire and dam breeds used to reach those percentages. Each herd owner provided records of reproductive performance and milk production. Compared with H cows, J x H cows had higher first-service conception rates (52 vs. 42%), higher percentages confirmed pregnant by 6 (68 vs. 54%) and 14 wk (86 vs. 78%) after the first day of inseminating, and lower final not-in-calf rates (11 vs. 16%); however, these differences were not observed in all herds. A random selection of H and J x H cows had body condition assessed on 3 occasions between the start of calving and the first day of the artificial insemination program. The selected cows were also weighed on the final occasion. Overall, body condition scores were slightly higher for J x H cows than for H cows, but changes in body condition score between calving and the start of inseminating were similar between breed groups. The H cows were 40 kg heavier than J x H cows and had daily milk yields in early lactation that were 2.2 kg higher. Daily yields of milk fat and protein did not differ between H and J x H cows during the study period. The improved reproductive performance of J x H cows compared with H cows may render them more suitable for use in dairy herds with seasonally concentrated calving patterns. Their improved reproductive performance was not associated with differences in condition loss in early lactation.


Biomechanical analysis of the thoracolumbar spine under physiological loadings: Experimental motion data corridors for validation of finite element models.
Biomechanical studies that involve normal, injured or stabilized human spines are sometimes difficult to perform on large samples due to limited access to cadaveric human spines and biological variability. Finite element models alleviate these limitations due to the possibility of reusing the same model, whereas cadaveric spines can be damaged during testing, or have their mechanicals behaviour modified by fatigue, permanent deformation or structural failure. Finite element models need to be validated with experimental data to make sure that they represent the complex mechanical and physiological behaviour of normal, injured and stabilized spinal segments. The purpose of this study is to characterize the mechanical response of thoracolumbar spine segments with an analytical approach drawn from experimental measurements. A total of 24 normal and fresh cadaveric thoracolumbar spine segments (T11-L3), aged between 53 and 91 years, were tested in pure flexion/extension, lateral bending and axial torsion using a specific experimental setup. Measurements of global and intervertebral angle variations were performed using three-dimensional mark tracking methods. Load/angle curves for each loading were fitted by a logarithmic approach with two coefficients. The coefficients for the functions describing the response of the spinal segments are given and constitute predictive models from experimental data. This work provides data corridors of human thoracolumbar spine motion segments subjected to pure bending in the three physiological planes. These data could be very useful to validate finite element models of the human spine.