Parent-Reported Personality and Weight Transitions across Adolescence.
Background: Adolescence is a critical transition point for body weight. Personality traits are associated consistently with weight and obesity risk in adulthood. We examined whether personality, particularly Conscientiousness (the tendency to be organized, disciplined, and responsible), is associated with weight outcomes between ages 13 and 17. Methods: Data are drawn from the Growing Up in Ireland suites of studies. Parents rated their child's personality at age 13, and trained staff measured weight and height at ages 13 and 17 (N = 4962). Logistic regression was used to predict risk of incident obesity and obesity remission between ages 13 and 17. Results: Among children who were not in the obesity category at age 13, higher Conscientiousness was associated with lower risk of moving into the obesity category by age 17, and, among children with obesity at age 13, Conscientiousness was associated with greater likelihood of moving to the nonobesity category by age 17. These associations were independent of sociodemographic characteristics, parent body mass index, and were similar across gender. The other five-factor model personality traits were unrelated to weight outcomes. Conclusions: Conscientiousness is one trait psychological factor implicated in weight transitions across a critical period during adolescence.


Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests.
An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens. PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined. Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ≤0.005% or ≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker's regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ≤250 parasites/μl (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046). In the present work, 10.7% of the isolates with a parasitaemia ≤0.005% (≤250 parasites/μl) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker'model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2.


Full-length L1CAM and not its Δ2Δ27 splice variant promotes metastasis through induction of gelatinase expression.
Tumour-specific splicing is known to contribute to cancer progression. In the case of the L1 cell adhesion molecule (L1CAM), which is expressed in many human tumours and often linked to bad prognosis, alternative splicing results in a full-length form (FL-L1CAM) and a splice variant lacking exons 2 and 27 (SV-L1CAM). It has not been elucidated so far whether SV-L1CAM, classically considered as tumour-associated, or whether FL-L1CAM is the metastasis-promoting isoform. Here, we show that both variants were expressed in human ovarian carcinoma and that exposure of tumour cells to pro-metastatic factors led to an exclusive increase of FL-L1CAM expression. Selective overexpression of one isoform in different tumour cells revealed that only FL-L1CAM promoted experimental lung and/or liver metastasis in mice. In addition, metastasis formation upon up-regulation of FL-L1CAM correlated with increased invasive potential and elevated Matrix metalloproteinase (MMP)-2 and -9 expression and activity in vitro as well as enhanced gelatinolytic activity in vivo. In conclusion, we identified FL-L1CAM as the metastasis-promoting isoform, thereby exemplifying that high expression of a so-called tumour-associated variant, here SV-L1CAM, is not per se equivalent to a decisive role of this isoform in tumour progression.


Papillomavirus common antigens. Papillomavirus antigen in verruca, benign papillomatous lesions, trichilemmoma, and bowenoid papulosis: an immunoperoxidase study.
We surveyed a variety of papillomatous lesions, trichilemmoma, and bowenoid papulosis for the presence of papillomavirus common antigen using an unlabeled antibody peroxidase-antiperoxidase technique and an antibody against papillomavirus common antigen. Papillomavirus common antigen was detected in four of six verruca vulgaris lesions overlying the nuclei of koilocytotic cells. The antigen was observed much less often in the granular zone of verrucous lesions that did not contain koilocytotic cells. Thirteen of 18 lesions of bowenoid papulosis had positive immunostaining overlying occasional nuclei in the granular zone but the antigen was not detected in the granular zone of squamous cell carcinoma in situ or of trichilemmoma. These data support the hypothesis that some lesions of bowenoid papulosis represent a form of cutaneous infection by papillomavirus.


The problem of pattern and scale in ecology: what have we learned in 20 years?
Over the past 20 years, major advances have clarified how ecological patterns inform theory, and how in turn theory informs applied ecology. Also, there has been an increased recognition that the problem of scale at which ecological processes should be considered is critical if we are to produce general predictions. Ecological dynamics is always stochastic at small scales, but variability is conditional on the scale of description. The radical changes in the scope and aims of ecology over the past decades reflect in part the need to address pressing societal issues of environmental change. Technological advances in molecular biology, global positioning, sensing instrumentation and computational power should not be overlooked as an explanation for these radical changes. However, I argue that conceptual unification across ecology, genetics, evolution and physiology has fostered even more fertile questions. We are moving away from the view that evolution is played in a fixed ecological theatre: the theatre is being rapidly and relentlessly redesigned by the players themselves. The maintenance of ecosystem functions depends on shifts in species assemblages and on cellular metabolism, not only on flows of energy and matter. These findings have far reaching implications for our understanding of how ecosystem function and biodiversity will withstand (or not) environmental changes in the 21st century.


Eye movements reveal impaired inhibitory control in adult male fragile X premutation carriers asymptomatic for FXTAS.
Fragile X premutation carriers (fXPCs) have an expansion of 55-200 CGG repeats in the FMR1 gene. Male fXPCs are at risk for developing a neurodegenerative motor disorder (FXTAS) often accompanied by inhibitory control impairments, even in fXPCs without motor symptoms. Inhibitory control impairments might precede, and thus indicate elevated risk for motor impairment associated with FXTAS. We tested whether inhibitory impairments are observable in fXPCs by assessing oculomotor performance. Participants were males aged 18-48 years asymptomatic for FXTAS. FXPCs (n = 21) and healthy age-matched controls (n = 22) performed four oculomotor tasks. In a Fixation task, participants fixated on a central cross and maintained gaze position when a peripheral stimulus appeared. In a Pursuit task, participants maintained gaze on a square moving at constant velocity. In a Prosaccade task, participants fixated on a central cross, then looked at a peripheral stimulus. An Antisaccade task was identical to the Prosaccade task, except participants looked in the direction opposite the stimulus. Inhibitory cost was the difference in saccade latency between the Antisaccade and Prosaccade tasks. Relative to controls, fXPCs had longer saccade latency in the Antisaccade task. In fXPCs, inhibitory cost was positively associated with vermis area in lobules VI-VII. Antisaccades require inhibitory control to inhibit reflexive eye movements. We found that eye movements are sensitive to impaired inhibitory control in fXPCs asymptomatic for FXTAS. Thus, eye movements may be useful in assessing FXTAS risk or disease progression.


Scientists' perspectives on consent in the context of biobanking research.
Most bioethics studies have focused on capturing the views of patients and the general public on research ethics issues related to informed consent for biobanking and only a handful of studies have examined the perceptions of scientists. Capturing the opinions of scientists is important because they are intimately involved with biobanks as collectors and users of samples and health information. In this study, we performed interviews with scientists followed by qualitative analysis to capture the diversity of perspectives on informed consent. We found that the majority of scientists in our study reported their preference for a general consent approach although they do not believe there to be a consensus on consent type. Despite their overall desire for a general consent model, many reported several concerns including donors needing some form of assurance that nothing unethical will be done with their samples and information. Finally, scientists reported mixed opinions about incorporating exclusion clauses in informed consent as a means of limiting some types of contentious research as a mechanism to assure donors that their samples and information are being handled appropriately. This study is one of the first to capture the views of scientists on informed consent in biobanking. Future studies should attempt to generalize findings on the perspectives of different scientists on informed consent for biobanking.


Symptoms and other factors associated with time to diagnosis and stage of lung cancer: a prospective cohort study.
This prospective cohort study aimed to identify symptom and patient factors that influence time to lung cancer diagnosis and stage at diagnosis. Data relating to symptoms were collected from patients upon referral with symptoms suspicious of lung cancer in two English regions; we also examined primary care and hospital records for diagnostic routes and diagnoses. Descriptive and regression analyses were used to investigate associations between symptoms and patient factors with diagnostic intervals and stage. Among 963 participants, 15.9% were diagnosed with primary lung cancer, 5.9% with other thoracic malignancies and 78.2% with non-malignant conditions. Only half the cohort had an isolated first symptom (475, 49.3%); synchronous first symptoms were common. Haemoptysis, reported by 21.6% of cases, was the only initial symptom associated with cancer. Diagnostic intervals were shorter for cancer than non-cancer diagnoses (91 vs 124 days, P=0.037) and for late-stage than early-stage cancer (106 vs 168 days, P=0.02). Chest/shoulder pain was the only first symptom with a shorter diagnostic interval for cancer compared with non-cancer diagnoses (P=0.003). Haemoptysis is the strongest symptom predictor of lung cancer but occurs in only a fifth of patients. Programmes for expediting earlier diagnosis need to focus on multiple symptoms and their evolution.


The use of a total bowel length measurement protocol may reduce reoperations and complications after single-anastomosis duodenal switch.
Most surgeons who perform single-anastomosis duodeno-ileal switches (SADI-S) use a pre-determined common channel length without measuring total bowel length (TBL). However, TBL varies between patients, and a standardized common channel length could contribute to malabsorptive complications and reoperations following SADI-S. The purpose of this study was to determine whether using a TBL measurement protocol to individualize common channel length would be associated with reduced reoperations and complications. A prospectively maintained data registry was retrospectively reviewed to identify all patients who underwent SADI-S between September 2017 and February 2022. In April 2021, we began using TBL measurements during SADI-S with 40% of the TBL used as the length for the common channel. Outcomes pre-TBL and post-TBL measurement protocol were compared. A total of 119 SADI-S recipients (59 pre-TBL; 60 post-TBL) were included. The pre-TBL group had a higher frequency of reoperations (23.7% vs 1.7%, p < 0.001) and late complications (29.3% vs 3.3%, p < 0.001). The mean time to reoperation was 13.7 months in the pre-TBL group and 6.7 months in the post-TBL group (p = 0.347). Patients in the post-TBL group had significantly higher serum albumin levels at 3 months (4.2 g/dL vs 3.5 g/dL, p < 0.001), 6 months (4.1 g/dL vs 3.6 g/dL, p < 0.001), and 12 months (4.2 g/dL vs 3.8 g/dL, p = 0.023) postoperatively when compared to the pre-TBL group. Using TBL measurements to individualize common channel length was associated with a significant reduction in reoperations and late complications following SADI-S.


Monitoring of Chlamydia trachomatis infections after antibiotic treatment using RNA detection by nucleic acid sequence based amplification.
To investigate the value of RNA detection by nucleic acid sequence based amplification (NASBA) for the monitoring of Chlamydia trachomatis infections after antibiotic treatment. Cervical smears (n = 97) and urine specimens (n = 61) from 25 C trachomatis positive female patients were analysed for the presence of C trachomatis 16S ribosomal RNA (rRNA) by NASBA and C trachomatis plasmid DNA by the polymerase chain reaction (PCR) before and up to five weeks after antibiotic treatment. Chlamydia trachomatis RNA was found in all cervical smears taken before antibiotic treatment (n = 24) and in two smears taken one week after antibiotic treatment; no C trachomatis RNA was detected after two weeks or more. In contrast, C trachomatis DNA was found in all such specimens before treatment, and 21 of 25, six of 21, and five of 20 smears were found to be positive at one, two, and three weeks after treatment, respectively. After four weeks, only one of six smears was positive, and this smear had been negative in the two preceding weeks. Of the 61 urine samples investigated, C trachomatis DNA and C trachomatis RNA were found in all before treatment (n = 15), whereas one week after treatment four of 15 were C trachomatis DNA positive and C trachomatis RNA was detected in one sample only. These data show that RNA detection by NASBA can be used successfully to monitor C trachomatis infections after antibiotic treatment. Furthermore, it might be possible to use urine specimens as a test of cure because neither C. trachomatis DNA or RNA could be detected two weeks or more after treatment.


Distal appendicular skeletal involvement of diffuse large B-cell lymphoma on technetium-99m methylenediphosphonate bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: a case report.
We report a case of a patient with appendicular bone involvement of diffuse large B-cell lymphoma visualized by whole-body technetium-99m methylenediphosphonate bone scintigraphy (bone scan) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A 73-year-old Asian man who had gingival swelling of the labial area of the left maxillary lateral incisor presented to our institution. Positron emission tomography/computed tomography demonstrated hypermetabolic lesions with maximum standardized uptake values of 12.15 in the left testis, 1.92 in the skin of the right chest, and 2.88 in the left ulna and third metatarsal bone. A bone scan showed multiple uptakes in the left ulna, hand, both tibiae, and the left foot. We diagnosed the tumor as diffuse large B-cell lymphoma by excision. Magnetic resonance imaging showed enhanced signaling of lesions with soft tissue edema in the olecranon of the left ulna, the third metacarpal bone of the left hand, and the third metatarsal bone of the left foot. Magnetic resonance imaging findings prompted a diagnosis of lymphoma. Eight cycles of chemotherapy plus external radiotherapy targeted to the involved bone sites were given for 5 months. Follow-up positron emission tomography/computed tomography and bone scanning revealed the disappearance of hypermetabolism and decreased uptake in lesions compared with the previous images. Laboratory data were also all within the normal limits after chemotherapy. This report highlights that appendicular bone involvement of diffuse large B-cell lymphoma can be detected on whole-body bone scans and by positron emission tomography/computed tomography.


Pediatric Rhabdomyolysis.
Pediatric rhabdomyolysis is a common diagnosis that pediatricians need to be able to recognize because prompt treatment can prevent potential complications, such as acute kidney injury. The triggers for rhabdomyolysis are extensive, with viruses being the most common cause in pediatric patients. The pathophysiology behind rhabdomyolysis is complex and still being researched, but having a firm understanding of the cascade that results when muscle injury occurs is essential for proper management. Guidelines for managing pediatric rhabdomyolysis currently do not exist, but this article aims to review the available literature and give clinicians a general approach to aid in history taking, physical examination, diagnosis, acute management, follow-up, and prevention.


Mitochondrial Hyperactivation and Enhanced ROS Production are Involved in Toxicity Induced by Oncogenic Kinases Over-Signaling.
Targeted therapy is an effective, rational, and safe approach to solid and hematological tumors treatment. Unfortunately, a significant fraction of patients treated with tyrosine kinase inhibitors (TKI) relapses mainly because of gene amplification, mutations, or other bypass mechanisms. Recently a growing number of papers showed how, in some cases, resistance due to oncogene overexpression may be associated with drug addiction: cells able to proliferate in the presence of high TKI doses become also TKI dependent, undergoing cellular stress, and apoptosis/death upon drug withdrawal. Notably, if a sub-cellular population survives TKI discontinuation it is also partially re-sensitized to the same drug. Thus, it is possible that a subset of patients relapsing upon TKI treatment may benefit from a discontinuous therapeutic schedule. We focused on two different hematologic malignancies, chronic myeloid leukemia (CML) and anaplastic large cell lymphoma (ALCL), both successfully treatable with TKIs. The two models utilized (LAMA and SUP-M2) differed in having oncogene overexpression as the sole cause of drug resistance (CML), or additionally carrying kinase domain mutations (ALCL). In both cases drug withdrawal caused a sudden overload of oncogenic signal, enhanced mitochondria activity, induced the release of a high amount of reactive oxygen species (ROS), and caused genotoxic stress and massive cell death. In LAMA cells (CML) we could rescue the cells from death by partially blocking downstream oncogenic signaling or lowering ROS detrimental effect by adding reduced glutathione.


Upregulation of synoviocyte COX-2 through interactions with T lymphocytes: role of interleukin 17 and tumor necrosis factor-alpha.
T lymphocytes infiltrating rheumatoid synovium may alter the function of resident synoviocytes. We investigated the influence on synoviocyte cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production exerted by soluble factors released by T cells, with particular reference to interleukin 17 (IL-17). Human peripheral blood T cells were stimulated with antibodies directed against CD3 and CD28. Harvested T cell supernatants were applied to cultured human fibroblast-like synoviocytes in culture. The effects of IL-17 alone and in combination with tumor necrosis factor-a (TNF-a) were examined using recombinant cytokines and neutralizing antibodies. Synoviocyte COX-2 expression and PGE2 production were examined. Supernatants from stimulated T cells upregulated COX-2 expression and increased PGE2 production by synoviocytes. The T cell supernatants were found to contain IL-17 and TNF-a. Recombinant IL-17 upregulated synoviocyte COX-2 expression and enhanced TNF-a stimulated synoviocyte COX-2 expression. The upregulation of synoviocyte COX-2 expression by supernatants from stimulated T cells was partially inhibited by addition of neutralizing antibodies against IL-17 or TNF-a or by treatment of T cells with cyclosporin A prior to stimulation. Activated T cells are capable of paracrine upregulation of synoviocyte COX-2 expression and PGE2 production through release of soluble mediators. T cell derived IL-17, especially in combination with TNF-a, may contribute to ongoing inflammation through its effects on COX-2 expression and PGE2 production. These data provide additional evidence for the contribution of T cells in rheumatoid inflammation and highlight the potential of IL-17 as a therapeutic target.


Development and validation of an LC-MS/MS method for the detection of phomopsin A in lupin and lupin-containing retail food samples from the Netherlands.
Phomopsins (PHO) are mycotoxins produced by the fungus Diaporthe toxica (also referred to as Phomopsis leptostromiformis). Lupin is the most important host crop for this fungus and PHO are suspected as cause of lupinosis, a deadly liver disease, in sheep. Lupin is currently in use to replace genetically modified soy in many food products available on the European market. However, a validated method for analysis of PHO is not available until now. In this work, a dilute-and-shoot LC-MS/MS-based method was developed for the quantitative determination and identification of phomopsin A (PHO-A) in lupin and lupin-containing food. The method involved extraction by a mixture of acetonitrile/water/acetic acid (80/20/1 v/v), dilution of the sample in water, and direct injection of the crude extract after centrifugation. The method was validated at 5 and 25 µg PHO-A kg(-1) product. The average recovery and RSD obtained were 79% and 9%, respectively. The LOQ (the lowest level for which adequate recovery and RSD were demonstrated) was 5 µg PHO-A kg(-1). Identification of PHO-A was based on retention time and two transitions (789 > 226 and 789 > 323). Using the average of solvent standards from the sequence as a reference, retention times were all within ± 0.03 min and ion ratios were within ± 12%, which is compliant with European Union requirements. The LOD (S/N = 3 for the least sensitive transition) was 1 µg PHO-A kg(-1) product. Forty-two samples of lupin and lupin-containing food products were collected in 2011-2012 from grocery stores and internet shops in the Netherlands and analysed. In none of the samples was PHO-A detected.


Prevalence of dyslipidemia and risk factors in Campos dos Goytacazes, in the Brazilian state of Rio de Janeiro.
To determine the prevalence of dyslipidemias in adults in the city of Campos dos Goytacazes, in the Brazilian state of Rio de Janeiro, and to identify its relation to risk factors. Cross-sectional, population-based, observational study with sampling through conglomerates and stratified according to socioeconomic levels, sex, and age, with 1,039 individuals. Risk factors, familial history, blood pressure, anthropometric measurements, glucose, triglycerides and cholesterol were determined. The following prevalences were observed: of dyslipidemias 24.2%; of hypercholesterolemia, 4.2%; of elevated LDL-C, 3.5%; of low HDL-C, 18.3%; and of hypertriglyceridemia, 17.1%. The following mean levels were observed: cholesterol, 187.6 +/- 33.7 mg/dL; LDL-C, 108.7 +/- 26.8 mg/dL; HDL-C, 48.5 +/- 7.7 mg/dL; and triglycerides, 150.1 +/- 109.8 mg/dL. The following variables showed a positive correlation with dyslipidemia: increased age (P<0.001), male sex (P<0.001), low familial income (P<0.001), familial history (P<0.01), overweight/obesity (P<0.001), waist measure (P<0.001), high blood pressure (P<0.001), and diabetes mellitus (P<0.001). The following variables had no influence on dyslipidemias: ethnicity, educational level, smoking habits, and sedentary lifestyle. The frequency of lipid changes in the population studied was high, suggesting that measures for the early diagnosis should be taken, in association with implementation of programs for primary and secondary prevention of atherosclerosis.


Is there a role for bowel rest in nutrition management of Crohn's disease?
In 1988, Greenberg and colleagues published a large randomized controlled trial to address whether bowel rest could lead to improved disease activity in patients with active Crohn's disease. The results of this study provide substantial evidence that bowel rest is not necessary to achieve remission in patients with active Crohn's disease receiving nutrition support. Before this study, great controversy existed about the use of nutrition support and bowel rest in the treatment of active Crohn's disease because of a limited number of conflicting studies providing evidence for and against its application. The results of the publication by Greenberg et al are fundamental because they helped to settle this important argument. Furthermore, this pivotal paper changed the clinical guidelines for the use of nutrition support in the management of active Crohn's disease. Since the publication of this pivotal article, many developments in the field of nutrition and in the treatment of Crohn's disease have helped validate and further its results. Subsequent studies and debate center on the use of enteral nutrition as primary treatment in patients with active Crohn's disease. Data regarding the efficacy, composition, and overall role of adult enteral nutrition in the management of Crohn's disease are presented. This article revisits the Greenberg paper and discusses some of these innovations in nutrition.


MR cholangiopancreatography findings of biliary tract complications after liver transplantation
Background/aim: We aimed to present the magnetic resonance cholangiopancreatography (MRCP) findings of biliary tract complications after liver transplantation. Materials and methods: Seventy-five patients who underwent MRCP in our department between July 2011 and July 2015 after liver transplantation were retrospectively evaluated. The MRCP images were reevaluated by three radiologists in consensus. Diagnostic confirmation of MRCP findings was obtained with direct cholangiographic examinations or with clinical, radiological, and laboratory findings and concordance between MRCP findings and the final diagnosis was investigated. Results: Twenty-seven of the 75 patients had normal MRCP findings and at least one type of biliary tract complication was detected on the MR images of 48 patients. These complications included anastomotic stricture, dilatation of the biliary tract, nonanastomotic stricture, biliary leakage, cholangitis, biloma, abscess due to cholangitis, biliary stone-sludge, and donor-to-recipient bile duct disproportion. Thirty of the 75 patients were followed only by clinical and laboratory findings without further imaging. Forty-five patients underwent direct cholangiographic examinations. At the end of the follow-up period, 28 of the 75 patients were considered free of biliary tract complications, and at least one bile duct complication was diagnosed in 47 patients. Conclusion: With its high sensitivity and specificity, MRCP should be the first choice of method in the diagnosis and follow-up of biliary complications after liver transplantation.


Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.
The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs with shortened life span and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here, we studied ageing in the presence and absence of ERCs, and unexpectedly found no evidence of gene expression differences that might indicate stress responses or metabolic feedback caused by ERCs. Neither did we observe any global change in the widespread disruption of gene expression that accompanies yeast ageing, altogether suggesting that ERCs are largely inert. Much of the differential gene expression that accompanies ageing in yeast was actually associated with markers of the senescence entry point (SEP), showing that senescence, rather than age, underlies these changes. Cells passed the SEP irrespective of ERCs, but we found the SEP to be associated with copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) forming linear fragments up to approximately 1.8 Mb size, which arise in aged cells due to rDNA instability but through a different mechanism to ERCs. Therefore, although rDNA copy number increases dramatically with age due to ERC accumulation, our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing.


Professional identity and emerging occupational therapy practice: An autoethnography.
Research about occupational therapy practice in the community with people who have been imprisoned remains limited and may be considered an emerging area of practice. This paper provides a critical, first-person account about emerging occupational therapy practice with men transitioning to the community post-imprisonment. The practice context is described and reflected on from the lens of a new graduate. Autoethnography draws meaning from reciprocal interactions between an individual and a culture. Data was collected by the primary author through reflective journal entries and process notes pertaining to a Photovoice project. Iterative application of established evaluative criteria served as a framework in an analytical writing process. Autethnography promoted self-reflection and professional development while Photovoice provided an evidence-based framework in an emerging setting. Current occupational therapy theories and models have limited applicability to inform practice with marginalized populations potentially benefitting from participatory research (e.g., Photovoice) and autoethnography.


The regulation of hepatic carbon flux by pyruvate dehydrogenase and pyruvate dehydrogenase kinase during long-term food restriction.
The present study investigated the effects of chronic food restriction (achieved by limiting access to food to 2 h daily for up to 8 weeks) on the activity of the active form of pyruvate dehydrogenase (PDHa) in liver. Accelerated and exaggerated activation of hepatic PDH in response to a meal, previously demonstrated to occur within 10 days of food restriction, was demonstrated to persist for 4 and 8 weeks of food restriction, despite a food intake of only 50-60% of controls. Activation of hepatic PDH during feeding in rats subjected to food restriction for 4 weeks was dependent on continued food intake. As a consequence, hepatic PDHa activities in food-restricted rats were suppressed relative to controls for 19 h of the 24 h daily cycle. Curve-fitting by second-order polynomial regression analysis demonstrated a significant positive correlation between hepatic PDHa activity and lipogenic rate over the range of PDHa activities observed during the 2 h feeding period. Increased lipogenesis during feeding in food-restricted rats was not at the expense of hepatic glycogen synthesis or deposition; measurement of concurrent rates of glycogenesis and lipogenesis revealed simultaneous flux through both pathways, but specific activation of lipogenesis. The accelerated re-activation of hepatic PDH observed within 1 h of feeding in rats subjected to 4 weeks of food restriction was facilitated by a failure of the 22 h interprandial fasting period to induce a stable increase in hepatic PDH kinase activity. The present study indicates differential regulation of hepatic PDH kinase activity during periods of food withdrawal between food-restricted rats and starved/re-fed control rats. Such regulation occupies a critical role in determining the rate of activation of hepatic PDH during feeding. In turn, increased activity of hepatic PDHa during feeding in food-restricted rats bears a close positive relationship with hepatic lipogenic rate.


Low serum citrulline concentration correlates with catheter-related bloodstream infections in children with intestinal failure.
Serum citrulline concentration is used as a biomarker of enterocyte mass and enteral tolerance, and low serum concentrations are correlated with bacteremia in immunosuppressed adults undergoing hematopoietic stem cell transplant. The authors sought to determine if citrulline was associated with the development of catheter-related bloodstream infections (CRBSIs) in children with intestinal failure. Data were reviewed from 66 children treated in a multidisciplinary intestinal rehabilitation program, who had serum concentration citrulline measured between January 2007 and August 2009. All patients had a diagnosis of intestinal failure requiring parenteral nutrition (PN) support. Exclusion criteria included central venous catheter in situ <30 days, creatinine clearance <20 mL/minute, or a history of organ transplant/immunosuppression. A total of 15 patients were excluded because of the above criteria. In this cohort of 51 patients, 26 (51%) developed CRBSIs. Both groups were similar in terms of gestational age, diagnosis, nutrition status, and biochemical liver function tests. The mean (± standard deviation [SD]) minimum serum citrulline concentration was significantly lower in patients who developed CRBSIs (6.7 ± 4.6 µmol/L) than in those who did not (11.3 ± 6.4 µmol/L, P = .004). Multivariate logistic regression analysis identified lower minimum serum citrulline concentration and longer central venous catheter duration as independently associated with CRBSI (P = .003 and P = .038, respectively). Low serum citrulline concentration and longer central venous catheter time are independently associated with CRBSI in children with intestinal failure. Serum citrulline concentration may be a useful biomarker to identify patients with intestinal failure who are at high risk of developing a CRBSI.


Implications of amyloidosis on prostatic biopsy.
Transrectal ultrasound-guided biopsy of the prostate is an integral step in the investigation of patients at risk of prostate adenocarcinoma. With an increasing number of biopsies being performed, uncommon forms of prostatic pathology will be identified more frequently. Amyloidosis of the prostate and/or the seminal vesicles may be noted on transrectal ultrasound-guided biopsy of the prostate and the implications of this histological diagnosis must be understood. We present our experience of two such cases of amyloidosis and review the literature regarding their management.


[The conservative therapy of chronic colostasis].
In 1972-1988 487 (5.35%) of patients were hospitalized in a Ukrainian SSR Proctological Center for chronic colostasis; 243 (49.8%) were operated on due to developing decompensation of the large intestine and failed multicomponent conservative treatment and invalidism. 244 patients admitted to the clinic were conservatively treated. A scheme of conservative treatment used in the clinic is described.


Enzymatic characterization of soluble organic phosphorus in lake water.
Although the concentration of soluble organic phosphorus in lake water often exceeds that of orthophosphate severalfold, little is known of its composition. By using enzyme assays it was determined that up to 50 percent of the organic fraction is hydrolyzable by phytase. The enzymatically degradable material consists of both low and high molecular weight fractions.


Do End-of-Rotation Evaluations Adequately Assess Readiness to Operate?
Medical educators have developed no standard way to assess the operative performance of surgical residents. Most residency programs use end-of-rotation (EOR) evaluations for this purpose. Recently, some programs have implemented workplace-based "microassessment" tools that faculty use to immediately rate observed operative performance. The authors sought to determine (1) the degree to which EOR evaluations correspond to workplace-based microassessments and (2) which factors most influence EOR evaluations and directly observed workplace-based performance ratings and how the influence of those factors differs for each assessment method. In 2017, the authors retrospectively analyzed EOR evaluations and immediate postoperative assessment ratings of surgical trainees from a university-based training program from the 2015-2016 academic year. A Bayesian multivariate mixed model was constructed to predict operative performance ratings for each type of assessment. Ratings of operative performance from EOR evaluations vs workplace-based microassessment ratings had a Pearson correlation of 0.55. Postgraduate year (PGY) of training was the most important predictor of operative performance ratings on EOR evaluations: Model estimates ranged from 0.62 to 1.75 and increased with PGY. For workplace-based assessment, operative autonomy rating was the most important predictor of operative performance (coefficient = 0.74). EOR evaluations are perhaps most useful in assessing the ability of a resident to become a surgeon compared with other trainees in the same PGY of training. Workplace-based microassessments may be better for assessing a trainee's ability to perform specific procedures autonomously, thus perhaps providing more insight into a trainee's true readiness for operative independence.


Lipid processing and lipoprotein synthesis by the developing human fetal colon.
Despite significant progress in the elucidation of the ontogeny of gastrointestinal function, little attention has been given to colonic lipid processing during development. The major purpose of this study was to explore the intracellular phase of fat absorption, lipid synthesis, and secretion in the human fetal colon compared with the jejunum originating from the same fetuses. The synthesis of lipids and major apolipoproteins was examined using cultured fetal colonic explants incubated with [14C]oleic acid and [36S]methionine, respectively. Fetal colonic explants demonstrated substantial ability to incorporate [14C]oleic acid (dpm/mg protein) into phospholipids (48,743 +/- 4,783), triglycerides (25,687 +/- 2,469), and cholesteryl esters (6,751 +/- 1,227). The total amount of radiolabeled lipids was much higher within the tissue (87,472 +/- 9,142) than in the medium (51,916 +/- 4,970), indicating a limited capacity of the fetal colon to export newly synthesized lipids. The limited colonic lipid secretory process was even more evident when compared with homologous fetal jejunal de novo synthesized lipids in tissue (133,975 +/- 13,836) and medium (279,858 +/- 1,610), respectively. Similar to the jejunum, the colon was able to elaborate all the phospholipid classes, with phosphatidylcholine accounting for > 70% of tissue phospholipids. However, their individual levels were present in lesser amounts in the colon (P < 0.001). Colonic explants elaborated most of the major lipoprotein classes but were less efficient than jejunal explants in exporting chylomicrons (33-fold), very low density lipoprotein (1.5-fold), and high-density lipoprotein (9-fold) into the medium. Apolipoprotein (apo) B synthesis and apo B mRNA editing were comparable in colonic and jejunal explants; thus they are not responsible for the defective lipoprotein secretion in the fetal large bowel. These results establish for the first time te capability of the human fetal colon to form, but not to efficiently transport, lipids, lipoproteins, and apoproteins.


The Usefulness of Argon Plasma Coagulation Compared with Endoscopic Submucosal Dissection to Treat Gastric Adenoma.
To date, the best therapeutic modality for gastric adenoma, especially low-grade adenoma, has not been established. The aim of this study was to assess the usefulness of argon plasma coagulation (APC) in treating gastric adenoma compared with endoscopic submucosal dissection (ESD). We included 210 patients with gastric adenoma, who underwent treatment with either APC (97 patients) or ESD (113 patients). The clinical and pathologic characteristics, mean duration of hospital stay, complications, and recurrence rates between the two groups were compared. The mean adenoma size was 0.9 cm and 1.1 cm in the APC group and ESD group, respectively (p<0.001). The mean duration of hospital stay was significantly shorter in the APC group than in the ESD group (1.6 days vs. 5.8 days, p<0.001). Complications did not occur in the APC group. However, one case of perforation (0.9%) and 6 cases of bleeding (5.3%) occurred in the ESD group. The recurrence rates were 15.3% (15/97 patients) in the APC group and 3.5% (4/113 patients) in the ESD group (p=0.003). The proportion of hospitalization was less in the APC group (43.3%, 42/97) than in the ESD group (100.0%, 113/113) (p<0.001). Medical expense was less in the APC group (377,172 won) than in the ESD group (1,430,610 won) (p<0.001). The findings of this study suggest that APC is a safe treatment method for gastric adenoma without serious complications. However, regular endoscopic follow-up is necessary to detect any residual or recurrent lesions due to the relatively high rate of local recurrence after APC.


Treatment-Free Remission in Chronic Myeloid Leukemia: Can We Identify Prognostic Factors?
Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKI became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon retreatment, indicating TKI discontinuation is safe. However, there is still a gap in understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it examines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.


Ecological impacts of genotypic diversity in the clonal seagrass Zostera marina.
Genetic diversity, like species diversity, can have important consequences for communities and ecosystems. However, little is known about whether the effects of genetic diversity demonstrated in experimental assemblages are of sufficient strength to generate patterns in natural systems. We conducted a survey of eelgrass (Zostera marina) to examine the correlation between eelgrass clonal diversity and two metrics of community structure across two seasons: shoot density (reflective of habitat quality) and biomass of epiphytic algae (as a measure of food resource availability). Eelgrass clonal diversity was not related to epiphyte biomass in either winter or summer. Interestingly, there was a positive relationship between eelgrass clonal diversity and shoot density only in the winter, when eelgrass experiences stress from abiotic and biotic factors. The magnitude of this correlation was similar to that of other factors known to affect shoot density such as tidal elevation or position in the bed. In contrast, summer shoot density and diversity were uncorrelated. This natural pattern is consistent with previous experimental results in which diversity positively affected shoot density only during periods of abiotic or biotic stress, suggesting that the effects of clonal diversity are sufficiently strong to influence shoot density in the field, despite the presence of potentially confounding environmental gradients.


Generation of Streptomyces globisporus SMY622 strain with increased landomycin E production and it's initial characterization.
Landomycin E (LaE) overproducing strain Streptomyces globisporus SMY6222 has been developed using UV induced mutagenesis and selection for streptomycin resistance. SMY622 has been shown by HPLC to produce 200-fold higher amounts of LaE when comparing with parental strain. The levels of transcription of regulatory gene lndI and oxygenase gene lndE are two times higher in the mutant than in the wild type. Gene rpsL for ribosomal protein S12 from SMY622 was shown to contain point mutation K43R. Possible reasons for increased LaE synthesis in SMY622 are discussed.


Oral lactic acid bacteria related to the occurrence and/or progression of dental caries in Japanese preschool children.
Previous studies have demonstrated that the presence of lactic acid bacteria (LAB), especially those classified into the genus Lactobacillus, is associated with the progression of dental caries in preschool children. Nevertheless, the kinds of species of LAB and the characteristics that are important for dental caries have been unclear. The aims of this study were: (1) to investigate the distribution of oral LAB among Japanese preschool children with various prevalence levels of caries; and (2) to reveal the characteristics of these isolated LAB species. Seventy-four Japanese preschool children were examined for caries scores and caries progression, and their dental cavity samples were collected for LAB isolation and identification. The saliva-induced agglutination rate and the resistance to acidic environments of the identified strains were measured. Statistical analysis showed that preschool children carrying Lactobacillus (L.) salivarius or Streptococcus mutans have a significantly higher prevalence of dental caries, the growth ability in acidic environments correlates with the caries scores of individuals with L. salivarius, and the caries scores exhibit positive correlation with saliva-induced agglutination in L. salivarius. These results show that specific Lactobacillus species are associated with dental caries based on the level of carious lesion severity. The present study suggests that these specific Lactobacillus species, especially those with easily agglutinated properties and acid resistance, affect the dental caries scores of preschool children, and that these properties may provide useful information for research into the prevention of dental caries.


The effect of local application of 1,25-dihydroxycholecalciferol on osteoclast numbers in orthodontically treated rats.
Orthodontic tooth movement requires remodeling of periodontal tissues, especially alveolar bone. 1,25-(OH)2D3, the active form of vitamin D3, is known to be a potent stimulator of osteoclastic bone resorption. The purpose of this study was to investigate the effect of local application of 1,25-(OH)2D3 on osteoclast numbers induced by experimental tooth movement. A piece of orthodontic elastic band was inserted between the first and second upper molars of male Wistar rats weighing about 200 g each. Twenty microL of 1,25-(OH)2D3 (10(-12)-10(-7) mol/L) was injected locally into the submucosal palatal area of the root bifurcation of the right first molar. The left side was injected with phosphate-buffered saline (PBS). The number of osteoclasts was counted in a 700 x 1050 microns 2 area of the interradicular septum. The local injection of 1,25-(OH)2D3 caused a dose-dependent increase in osteoclast number. The effect of 1,25-(OH)2D3 reached a response plateau at 10(-10) mol/L when greater than a three-fold rise in osteoclast number was attained compared with the PBS-treated controls. While the insertion of a piece of elastic band for three days induced a significant increase in osteoclasts in the alveolar bone, daily injections of 20 microL of 10(-10) mol/M 1,25-(OH)2D3 for three days markedly stimulated the numbers of osteoclasts induced by the insertion of an elastic band. 1,25-(OH)2D3 was apparently synergistic with mechanical stimuli, resulting in enhancement of the numbers of osteoclasts induced by mechanical stimuli alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-term effect of topical brinzolamide on human central corneal thickness.
To investigate the effect of short-term brinzolamide application on human central corneal thickness (CCT). Seventeen eyes of 16 patients who underwent neodymium:YAG laser posterior capsulotomy were included in the study group. Twenty-two subjects served as controls. Brinzolamide twice daily and fluorometholone four times daily were initiated after the procedure. Corneal thickness was evaluated with an ultrasound pachymetry from the central region. CCT measurements were performed before the procedure, at first day, and at the end of first week. The mean baseline CCT value was 535.1+/-37.8 micronm. In comparison to the control group (546.4+/-22.2 micronm), there was no statistically significant difference (p=0.248). After brinzolamide instillation, the mean CCT values at first day and at first week was measured as 545.1+/-40.1 micronm and 538.8+/-39.4 micronm, respectively. The difference at first day was statistically significant when compared to the baseline values (p=0.00017). When compared to the control group, no statistically significant difference was observed for the mean CCT values of the first day and first week (p=0.906 and p=0.484, respectively). In the fellow eyes, mean CCT values increased following the dorzolamide instillation (529.3+/-42.6 micronm, 534+/-41.7 micronm, and 533+/-41.9 micronm, respectively). No statistically significant difference was observed between the control group and fellow eye group when compared (p=0.162, p=0.247, p=0.270, respectively). Brinzolamide may cause a short-term increase in the human CCT, particularly on the first day.


In vivo evidence of mitochondrial dysfunction and altered redox homeostasis in a genetic mouse model of propionic acidemia: Implications for the pathophysiology of this disorder.
Accumulation of toxic metabolites has been described to inhibit mitochondrial enzymes, thereby inducing oxidative stress in propionic acidemia (PA), an autosomal recessive metabolic disorder caused by the deficiency of mitochondrial propionyl-CoA carboxylase. PA patients exhibit neurological deficits and multiorgan complications including cardiomyopathy. To investigate the role of mitochondrial dysfunction in the development of these alterations we have used a hypomorphic mouse model of PA that mimics the biochemical and clinical hallmarks of the disease. We have studied the tissue-specific bioenergetic signature by Reverse Phase Protein Microarrays and analysed OXPHOS complex activities, mtDNA copy number, oxidative damage, superoxide anion and hydrogen peroxide levels. The results show decreased levels and/or activity of several OXPHOS complexes in different tissues of PA mice. An increase in mitochondrial mass and OXPHOS complexes was observed in brain, possibly reflecting a compensatory mechanism including metabolic reprogramming. mtDNA depletion was present in most tissues analysed. Antioxidant enzymes were also found altered. Lipid peroxidation was present along with an increase in hydrogen peroxide and superoxide anion production. These data support the hypothesis that oxidative damage may contribute to the pathophysiology of PA, opening new avenues in the identification of therapeutic targets and paving the way for in vivo evaluation of compounds targeting mitochondrial biogenesis or reactive oxygen species production.


Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.
Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Of 40 trial patients, 39 entered the extension period, and 38 completed 18 months. Absolute values and percent change over time were determined for spleen and liver volume, hemoglobin concentration, platelet count, bone mineral density, bone marrow burden, and Gaucher disease biomarkers. For patients randomized to eliglustat in the double-blind period, continuing treatment with eliglustat for 9 more months resulted in incremental improvement of all disease parameters. For patients randomized to placebo in the double-blind period, eliglustat treatment during the 9-month, open-label period resulted in significant decrease of spleen and liver volumes and significant increase of hemoglobin and platelets, with a similar rate of change to patients who had received eliglustat in the double-blind period. Eliglustat treatment was also associated with improvement in bone marrow burden score, bone mineral density, and established biomarkers of Gaucher disease, including reduction of the bioactive lipid, glucosylsphingosine. These findings underscore the efficacy of eliglustat in treatment-naïve patients. Eliglustat was well-tolerated, and there were no new safety concerns with longer-term exposure.


Computed tomography of the thymus gland in myasthenia gravis.
Sixteen consecutive patients with myasthenia gravis were examined by computed tomography (CT) before thymectomy. Surgical and histologic findings were compared with those obtained at CT. The results, like those of most other recent studies, indicate that CT is a reliable method for identifying thymoma. In all three patients with thymoma, and in five out of eight patients with hyperplasia, the lesion was observed at CT, giving an overall accuracy of 80 per cent. Although thymic hyperplasia is a basically histologic diagnosis an enlarged gland may give a correct diagnosis of this abnormality.


The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases.
The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.


Reproductive patterns among mothers of males diagnosed with Duchenne or Becker muscular dystrophy.
Diagnosis of a child with Duchenne or Becker muscular dystrophy (DBMD) may impact future maternal reproductive choice; however, little is known about the reproductive patterns of mothers with a male child diagnosed with DBMD. Using population-based surveillance data collected by the muscular dystrophy surveillance, tracking, and research network, the proportion of mothers who conceived and delivered a live birth following the diagnosis of DBMD in an affected male child and factors associated with such reproductive choice were identified. To accomplish this, maternal demographic data were linked to birth certificate data to construct the reproductive history for 239 mothers. Univariable and bivariable analyses were conducted to determine the proportion of mothers delivering a live birth and associated factors. By the time of the current study, 96 (40.2%) of the 239 mothers had at least one live birth following delivery of their oldest affected male child; 53 (22.2%) of these mothers had a live birth before and 43 (18.0%) had a live birth after DBMD diagnosis of a male child. Mothers with a live birth after diagnosis were significantly younger at diagnosis of the oldest affected male child (26.2 ± 4.2 years vs. 31.5 ± 5.5 years), and were less likely to be white non-Hispanic compared to those with no live birth after diagnosis. These results suggest that about one in five mothers deliver a live birth subsequent to DBMD diagnosis in a male child. Maternal age and race/ethnicity were associated with this reproductive choice.


Addressing the Social Determinants of Mental Health: If Not Now, When? If Not Us, Who?
In public health, recognition of the importance of the social determinants of health has led to significant shifts in practice and research. Psychiatry is making great progress in developing evidence-based, high-fidelity treatments that improve outcomes for patients who have access to high-quality mental health care. But for the less fortunate, acting further upstream, long before these mental health problems occur, is just as important as advancing new treatments. "Treating" the social determinants of mental health involves focusing more on policies than on medication, therapy, and neurobiological innovation. It entails creating public policies that improve these issues and changing social norms to place greater value on giving everyone an equal chance at living a fulfilling and healthy life. Local, state, and federal governments set policies, and the psychiatric field has considerable power in influencing those policies and shaping the social norms that inform them. This new column offers a forum to discuss these issues.


Application of a homogenous membrane potential assay to assess mitochondrial function.
Decreases in mitochondrial membrane potential (MMP) have been associated with mitochondrial dysfunction that could lead to cell death. The MMP is generated by an electrochemical gradient via the mitochondrial electron transport chain coupled to a series of redox reactions. Measuring the MMP in living cells is commonly used to assess the effect of chemicals on mitochondrial function; decreases in MMP can be detected using lipophilic cationic fluorescent dyes. To identify an optimal dye for use in a high-throughput screening (HTS) format, we compared the ability of mitochondrial membrane potential sensor (Mito-MPS), 5,5',6,6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolylcarbocyanine iodide, rhodamine 123, and tetramethylrhodamine to quantify a decrease in MMP in chemically exposed HepG2 cells cultured in 1,536-well plates. Under the conditions used, the optimal dye for this purpose is Mito-MPS. Next, we developed and optimized a homogenous cell-based Mito-MPS assay for use in 1,536-well plate format and demonstrated the utility of this assay by screening 1,280 compounds in the library of pharmacologically active compounds in HepG2 cells using a quantitative high-throughput screening platform. From the screening, we identified 14 compounds that disrupted the MMP, with half-maximal potencies ranging from 0.15 to 18 μM; among these, compound clusters that contained tyrphostin and 3'-substituted indolone analogs exhibited a structure-activity relationship. Our results demonstrate that this homogenous cell-based Mito-MPS assay can be used to evaluate the ability of large numbers of chemicals to decrease mitochondrial function.


Systematic comparison of conventional oesophageal manometry with oesophageal motility while eating bread.
Conventional oesophageal manometry is seldom accompanied by symptoms and may indeed be normal in patients with a history of dysphagia. We have recently shown that oesophageal manometry during eating may be helpful in the evaluation of patients with dysphagia but there has been little systematic comparison of fed oesophageal motor patterns with conventional clinical manometry. Oesophageal manometry in response to water swallows and during eating was therefore examined in 58 consecutive patients who had been referred for clinical oesophageal function studies. The patients were divided into three groups according to the percentage of peristaltic activity during conventional manometry: group 1 (n = 21) had 100% peristalsis; group 2 (n = 29) had 1-99% peristalsis and group 3 (n = 8) were aperistaltic. All the patients in group 3 had achalasia and remained aperistaltic during eating, however, was less than with water swallows in both group 1 (53% compared with 100%) and group 2 (49% compared with 82.3%) patients. Synchronous contractions and non-conducted swallows were correspondingly increased during eating. Although there was a significant correlation between the amplitude of peristaltic contractions with water and bread in groups 1 and 2, mean peristaltic amplitudes were less with bread than with water swallows. The data show that there are substantial differences in the distal oesophageal motility patterns produced by water swallows and by eating. Conventional manometry with water swallows does not allow prediction of the fed oesophageal motility pattern, except in patients with achalasia.


Targeting Hsp90 in Non-Cancerous Maladies.
Heat shock protein-90 (Hsp90) is a molecular chaperone critical to the folding, stability and activity of over 200 client proteins including many responsible for tumor initiation, progression and metastasis. Hsp90 chaperone function is linked to its ATPase activity and Hsp90 inhibitors interfere with this activity, thereby making Hsp90 an attractive target for cancer therapy. Also post-translational modification (PTM) and co-chaperone proteins modulate Hsp90 function, providing additional targets for secondary inhibition. Recent reports have shown that pathogens utilize both their own Hsp90 and that of their host for the propagation of infectious elements. In this review we will summarize our current knowledge of Hsp90 structure and function in both the pathogen and the host. We will focus on the role of Hsp90 in viral and parasitic diseases and the potential beneficial application of Hsp90 inhibitors alone and in combination with disease-specific inhibitors.


1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model.
Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT.


Lactulose Suppresses Osteoclastogenesis and Ameliorates Estrogen Deficiency-Induced Bone Loss in Mice.
Postmenopausal osteoporosis is characterized by excess osteoclastogenesis which leads to net bone loss and brittle fractures. Studies have demonstrated that estrogen deficiency-associated bone loss is microbiota-dependent and could be prevented by probiotics and prebiotics. In this study, we report that orally administered lactulose (20 g/kg, 6 weeks) orally administered significantly inhibited osteoclastogenesis, bone resorption, and prevented ovariectomy (OVX)-induced bone loss in mice. Lactulose increased intestinal Claudin 2, 3 and 15, compared to the OVX group, and lowered pro-osteoclastogenic cytokines levels including tumor necrosis factor-α, interleukin(IL)-6, receptor activator of nuclear factor kappa-Β ligand (RANKL), and IL-17 as well as increased the anti-inflammatory cytokine IL-10 in the intestine, peripheral blood, and bone marrow. Lactulose significantly preserved the number of Foxp3+ Treg cells in the intestines compared with that in OVX mice. Lactulose altered the composition of intestinal microbiota measured by 16s rDNA sequencing and increased intestinal and serum short-chain fatty acids (SCFAs) levels including acetate, propionate and butyrate which were decreased in OVX mice as measured by gas chromatography. Oral administration of lactulose for 2 weeks significantly lowered the level of bone resorption marker C-telopeptide of type 1 collagen-1 in healthy male young volunteers (aging 20-25 years). In conclusion, lactulose inhibited osteoclastogenesis and bone resorption by altering the intestinal microbiota and increasing SCFAs. Lactulose could serve as an ideal therapeutic agent for postmenopausal osteoporosis.


Validation of Chinese version of the Modified Pulmonary Functional Status and Dyspnea Questionnaire with heart failure patients in Taiwan.
Dyspnea is a distressing and functionally limiting symptom that patients with heart failure commonly experience. A valid instrument to quantify dyspnea for comparison of groups and for illness management is important. To validate the Chinese version of the Modified Pulmonary Functional Status and Dyspnea Questionnaire. The Chinese version was developed by using translation and back translation and was tested in Taiwan in 88 patients who had heart failure but no pulmonary disease or comorbid conditions limiting physical function. Data on a Taiwanese subsample (n=30) were compared with data on 30 patients in the United States matched by sex, age, and severity of disease to determine the equivalence of the Chinese and English versions. Construct validity was assessed by testing the hypothesis that health-related quality of life measured by using the Minnesota Living With Heart Failure Questionnaire is associated with the score on the dyspnea questionnaire. Reliability was assessed by using the Cronbach alpha and item-total correlations. Equivalence between the US and Taiwanese samples was high, from 0.67 to 0.91 for each item of the questionnaire and for the total score. Satisfactory correlations between the Chinese dyspnea and the Minnesota questionnaires, especially in the physical dimension (r=0.71, P<.001), provided support for the construct validity of the Chinese questionnaire. Reliability of the Chinese questionnaire was adequate (alpha=0.94). The Chinese Modified Pulmonary Functional Status and Dyspnea Questionnaire is a reliable and valid measure for dyspnea that can be used in Taiwanese patients with heart failure.


A brief review of diagnostic properties of point-of-care ultrasound for adult bowel intussusception: Making the case for ultrasound.
Undifferentiated abdominal pain in adults is a common chief complaint in acute care clinics and emergency departments worldwide, representing up to 10% of visits to emergency departments. Many patients have a non-specific presentation and an initial workup with labwork, urine analysis or X-ray might not reveal a specific diagnosis. Although bowel intussusception is a primarily pediatric disease, adult intussusception is a recognized but rare cause of bowel obstruction often requiring surgical intervention. However, recent data from advanced multi-detector computed tomography imaging shows that milder or recurring cases in adults have been underrecognized. Multi-detector computed tomography is still the imaging gold standard for detecting intussusception in adults, but new data showed that sonographers with basic training using the point-of-care ultrasound approach have a reasonable accuracy in detecting this pathology. As the point-of-care ultrasound for undifferentiated abdominal pain is an emerging core skill in the acute care setting, knowledge of sonographic signs of intestinal intussusception should be included in the skill set of physicians. Sonographic findings in adults mimic pediatric cases, but different location patterns and higher malignancy rates exist in adults. In this manuscript, we will review the current literature on adult intussusception and summarize key knowledge of intestinal intussusception in adults. We will present four adult patients diagnosed with different types of adult acute bowel intussusception using the point-of-care ultrasound and describe a focused scanning approach with typical sonographic findings.


The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.
Rapid reperfusion of an infarct-related artery reduces the extent of myocardial damage and improves survival in acute myocardial infarction (AMI). Currently, anticoagulant treatment with unfractionated heparin (UFH) is used as adjuvant therapy to fibrinolytic treatment. The low-molecular-weight heparin (LMWH) dalteparin is at least as effective as UFH in unstable coronary artery disease. The ASSENT PLUS trial was carried out to evaluate whether dalteparin is as effective as UFH as an adjunct to recombinant tissue-plasminogen activator (rt-PA) and aspirin in obtaining patency and Thrombolysis in Myocardial Infarction (TIMI)-3 flow in patients with AMI. The primary assessment of this phase II trial was TIMI flow, determined by coronary angiography. Patients with ST-elevation MI were randomized to receive aspirin and either rt-PA and UFH for 48 h, or rt-PA and dalteparin for 4 to 7 days. Evaluation was by TIMI flow after 4 to 7 days and clinical events (death, reinfarction, or revascularization) up to 30 days. There was a clear trend toward greater TIMI 3 flow with dalteparin compared with UFH. There was significantly less TIMI 0-1 flow or thrombus in the dalteparin group. Bleeding rates were similar. The occurrence of reinfarction was reduced during dalteparin treatment. These findings suggest that dalteparin could be substituted for UFH as an adjunct to rt-PA/aspirin in the management of patients with AMI.


Lack of effect of 4 weeks of oral H1 antagonist on bronchial responsiveness.
Ten patients with stable chronic asthma completed a randomized double-blind placebo controlled crossover study examining the effect of 120mg terfenadine twice daily for 4 weeks on bronchial responsiveness. Bronchial responsiveness was measured by methacholine inhalation tests performed by the tidal breathing technique at 0, 2 and 4 weeks of active and placebo treatment periods separated by a one week washout period. There were no significant differences in mean baseline forced expired volume in 1 sec (FEV1) for placebo and terfenadine treatments (p greater than 0.05) and there were no differences between geometric mean provocative concentrations of methacholine to cause a 20% fall in FEV1 (PC20M) at 2 and 4 weeks of terfenadine (0.89 and 0.99 mg.ml.1) from placebo (0.94 and 0.84 mg.ml.1) (p greater than 0.05). Examination of individual PC20M values during terfenadine treatment showed that 5 patients had PC20M's outside their 95% confidence interval; 2 increased both 2 and 4 week values, 1 increased one value and 2 decreased one value each. It is concluded that terfenadine does not produce clinically significant changes in stable asthmatics.


[DNA immobilization on modified inorganic sorbents].
Fragments of denaturated DNA having the length of about 500 nucleotides were immobilized, using silica carriers modified by organic polymers. It was shown that the organic coating allows to obtain sorbents, which practically exclude non-specific sorption with respect to DNA. The immobilization was carried out on hydroxyl-containing sorbents and on their phrosphorylated derivatives by means of water-soluble carbodiimide. The resulting preparations contained up to 60 units at A260 of DNA per 1 g of carrier. The effects of endonuclease A236, exonuclease A5 and pancreatic DNAse on the immobilized RNA were studied.


Promoting Community Awareness of Lung Cancer Screening Among Disparate Populations: Results of the cancer-Community Awareness Access Research and Education Project.
Lung cancer is the no. 1 cause of cancer death in the United States. Racial/ethnic minority and medically underserved populations suffer higher mortality than whites. Early detection through uptake of low-dose computed tomography (LDCT) among screening-eligible adults may mitigate high mortality. However, nearly 5 years since the publication of the US Preventive Services Task Force lung cancer screening guideline, population awareness of LDCT is low, and only 4% of screening-eligible adults have undergone screening. This project used an education intervention to change participants' knowledge, attitudes, and beliefs about cancer risk factors and lung cancer and to connect eligible individuals to LDCT screening and tobacco cessation services. Community-engaged strategies were used to deliver a 4-week educational program in 13 community sites. Trained community health workers delivered the intervention. The intervention was guided by the Health Belief Model. Data were collected by survey to 481 participants; 93% were African American, the majority was female (73.1%), mean age was 58.3 (SD, 10.9) years. There were knowledge increase regarding lung cancer screening (P = .001), a significant decrease in Perceived Severity and Perceived Barriers subscales (P = .001), and an overall increase in response to Perceived Benefits of lung cancer screening and Self-efficacy (P = .001). Fifty-four percent of tobacco users engaged in cessation; 38% of screening-eligible participants underwent LDCT screening. Community health workers are effective in increasing awareness of lung cancer screening and affecting behavior change among disparate populations. Community health workers may have a clinical role in LDCT shared decision making.


Increased Heart Rate Variability Response Among Infants with Reported Rhinorrhea and Watery Eyes: A Pilot Study.
Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheeze, emergency department visits, and hospitalizations. These findings were independent of allergic sensitization, and we theorized that increased parasympathetic tone underlay the association. We also reported that increased heart-rate variability (HRV) in infants predicted wheeze in 2-3 year-olds. In a convenience sample of children participating in a birth cohort study, we tested the hypothesis that infants with RWWC would have elevated HRV, indicating increased parasympathetic tone. RWWC symptoms since birth were queried for 3-month-old children. At 4-months, HRV was assessed (root mean square of successive differences [RMSSD]) during a standardized infant-mother still-face paradigm, which included 2 minutes of mother/child play immediately followed by 2 minutes of the mother maintaining a still-face. Among participants (n=38), RWWC was common for girls (32%) and boys (21%). The children with the greatest decrease in RMSSD between play and still-face challenge (lowest tertile) had a higher prevalence of RWWC as compared with children in the higher tertiles (50% vs 16%, P=0.045). In a logistic regression model controlling for sex, age and time between HRV and RWWC assessment, children with greater decrease in HRV between play and still-face (lowest tertile) had greater odds of having RWWC (odds ratio=6.0, P=0.029). In this relatively small study, we demonstrated greater decreases in HRV in response to a stressor among children with reported RWWC, suggesting that these children might have increased parasympathetic tone and/or overall greater vagal reactivity.


Cardiovascular effects of environmental noise: research in Serbia.
Research on the cardiovascular effects of noise in Serbia started in the year 2002, including experimental studies on humans and epidemiological studies on the adult and children population of Belgrade and Pancevo. Experimental exposure to noise [L eq = 89 dB (A)] had a hypodynamic effect, significantly lowering the cardiac index, cardiac work, and pump performance (P < 0.01). The vasoconstrictive effect of noise was shown through the significant elevation of after-load (P < 0.01). In a cross-sectional population study that was carried out on 2874 residents [1243 males and 1631 females] in Pancevo City, a significant odds ratio (adjusted for age, body mass index (BMI), and smoking habits) was found for self-reported hypertension (OR = 1.8, 95% CI = 1.0 - 2.4, P < 0.01) in men with a high level of noise annoyance compared to those with a low level of noise annoyance. In another study on 2503 residents (995 men and 1508 women) residents of Belgrade, the proportions of men with hypertension in the noisy [(L night , 8h > 45 dB (A)] and quiet areas [(L night , 8h ≤ 45 dB (A)] were 23.6% and 17.5%, respectively. The adjusted odds ratio (OR) for hypertension of the exposed group was 1.58 (95% CI = 1.03 - 2.42, P = 0.038), where men living in quiet streets were taken as a reference category. Associations between road traffic noise and blood pressure were also investigated in 328 preschool children in Belgrade. The systolic blood pressure was significantly higher among children from noisy residences and kindergartens, compared to children from both quiet environments (97.30 ± 8.15 and 92.33 ± 8.64 mmHg, respectively, P < 0.01). As a continuation of the study on preschool children, investigations were also carried out on 856 school children, aged between seven and eleven years, in Belgrade. It was found that systolic pressure was significantly higher among children from noisy schools and quiet residences, compared to children from both quiet environments (102.1 ± 9,3 and 100.4 ± 10.4 mmHg, respectively, P < 0.01).


Development of a simplified counterflow centrifugation elutriation procedure for depletion of lymphocytes from human bone marrow.
Graft-versus-host disease (GVHD) remains a major complication of allogeneic bone marrow (BM) transplantation. Techniques that effectively purge BM of mature T lymphocytes should reduce the incidence of GVHD and improve survival. We have developed a simplified, two-flow rate, fixed rotor speed counterflow centrifugation-elutriation (CCE) procedure that reproducibly depletes 99% of lymphocytes from Ficoll-Hypaque(F/H)-separated BM or BM buffy-coat. Two predetermined flow rates (24 and 28 ml/min) were used to purge small and intermediate-to-large lymphocytes, respectively, whereas faster sedimenting cells were recovered at the termination of the run. Lymphocyte depletion was substantiated by pan-T monoclonal antibody analysis as well as by complete loss of responsiveness to alloantigens and mitogens. Despite the lack of mature T cells, the depleted marrow fraction retained lymphoid colony-forming ability. Lymphocyte-purged marrow was obtained in high yield (72%), and retained high viability (greater than 97%) and hematopoietic colony-forming ability (greater than 99%). The ratio of total myeloid/erythroid colony-forming cells to T lymphocytes was 73-fold higher in the lymphocyte-depleted fraction than in unseparated BM. We concluded that a two-step CCE procedure can be used to rapidly deplete lymphocytes from both F/H-separated and buffy-coat BM inocula without altering hematopoietic capacity as measured by the in vitro clonogenic assays. It may be possible to adapt this procedure to the separation of the large number of marrow cells required for human BM transplantation.


Phytoestrogens/flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance.
Breast cancer resistance protein (BCRP), also called ABCG2, confers resistance to anticancer agents such as 7-ethyl-10-hydroxycamptothecin (SN-38), mitoxantrone, and topotecan. We found previously that sulfated estrogens are physiologic substrates of BCRP. Flavonoids with weak estrogenic activities are called phytoestrogens. In this study, we show that phytoestrogens/flavonoids, such as genistein, naringenin, acacetin, and kaempferol, potentiated the cytotoxicity of SN-38 and mitoxantrone in BCRP-transduced K562 (K562/BCRP) cells. Some glycosylated flavonoids, such as naringenin-7-glucoside, also effectively inhibited BCRP. These flavonoids showed marginal effect on the drug sensitivity of K562 cells. Genistein and naringenin reversed neither P-glycoprotein-mediated vincristine resistance nor multidrug resistance-related protein 1-mediated VP-16 resistance. Genistein and naringenin increased cellular accumulation of topotecan in K562/BCRP cells. K562/BCRP cells also accumulated less [(3)H]genistein than K562 cells. [(3)H]genistein transport in the basal-to-apical direction was greater in BCRP-transduced LLC-PK1 (LLC/BCRP) cells, which express exogenous BCRP in the apical membrane, than in parental cells. Fumitremorgin C abolished the increased transport of [(3)H]genistein in LLC/BCRP cells compared with parental cells. TLC analysis revealed that genistein was transported in its native form but not in its metabolized form. These results suggest that genistein is among the natural substrates of BCRP and competitively inhibits BCRP-mediated drug efflux. The results have two important clinical implications: (a) flavonoids and glycosylated flavonoids may be useful in overcoming BCRP-mediated drug resistance in tumor cells; and (b) coadministration of flavonoids with BCRP-substrate antitumor agents may alter the pharmacokinetics and consequently increase the toxicity of specific antitumor agents in cancer patients.


The oxidation of glucose by Acinetobacter calcoaceticus: interaction of the quinoprotein glucose dehydrogenase with the electron transport chain.
The coupling of the quinoprotein glucose dehydrogenase to the electron transport chain has been investigated in Acinetobacter calcoaceticus. No evidence was obtained to support a previous suggestion that the soluble form of the dehydrogenase and the soluble cytochrome b associated with it are involved in the oxidation of glucose. Analysis of cytochrome content, and of reduction of cytochromes in membranes by substrates, and of sensitivity to cyanide indicated that glucose, succinate and NADH are all oxidized by way of the same b-type cytochrome(s) and cytochrome oxidases (cytochrome o and cytochrome d). Mixed inhibition studies [with KCN and hydroxyquinoline N-oxide (HQNO)] showed that the b-type cytochrome(s) formed a binary complex with the o-type oxidase and that there was thus no communication between the electron transport chains at the cytochrome level. Measurements of the reduction of ubiquinone-9 by glucose and NADH, and inhibitor studies using HQNO, indicated that the ubiquinone mediates electron transport from both the glucose and NADH dehydrogenases. In some conditions the quinone pool facilitated communication between the 'glucose oxidase' and 'NADH oxidase' electron transport chains, but in normal conditions these chains were kinetically distinct.


Late-Life Physical Activities Moderate the Relationship of Amyloid-β Pathology with Neurodegeneration in Individuals Without Dementia.
Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited. We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia. This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire. This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect. The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults.


Toxicokinetics of toluene in the rat.
Toxicokinetic experiments with toluene that rely on data pooled from several animals have typically provided estimates of rate constants based on single exponential functions; in the present study a within-subject design was used to describe the time course of toluene in the blood to see if additional exponential terms could be resolved. Each rat was exposed for 2 h to either 1 000, 1 780, or 3 000 ppm of toluene. Blood samples were drawn at different times from indwelling jugular cannulae, and blood toluene concentrations were determined by vapor phase equilibrium chromatography. There was substantial variability between the peak blood values of the animals at each exposure concentration. Nonlinear regression was used to determine regression parameters for data drawn from individual animals. A bi-exponential function was found to minimize significantly the residual sum of squares observed during elimination. However, only a single exponential function could be resolved reliably during uptake. The mean half-time during uptake was approximately 34 min; the two half-times for elimination averaged approximately 6 and 90 min. Because of between-subject variability, a more accurate description of the time course of toluene uptake and elimination can be provided by kinetic studies that use a within-subject design.


Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease: The EUCLID Trial.
Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management. The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone. In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA1c) that might affect risk for major cardiovascular and limb outcomes. A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).


[Characteristics of peritoneal exudate microflora in children with appendicular peritonitis].
Bacteriological investigation of peritoneal exudate was conducted in 131 children with peritonitis. The greatest quantity of pathogenic and conventionally pathogenic Escherichias and bacteroids was revealed in March, April and September. In summer peritonitis was caused by pathogenic and conventionally pathogenic Escherichias in association with enterobacterias, staphylococci and other microorganisms.


Measuring Attitude toward Chemistry, Biology, and Math at a Hispanic-Serving Institution.
This work describes the evaluation of the Attitude toward the Subject of Chemistry Inventory (ASCI), as well as two modifications (one for measuring attitude toward math and one for measuring attitude toward biology), for college students at a Hispanic Serving Institution. Instrument reliability was tested via multiple administrations of the instruments, and confirmatory factor analysis supported a two-factor structure similar to an existing model of a revised version of the ASCI for all three instruments. The similar factor structure of the three instruments, coupled with interviews with students, provide validity evidence for the instruments and support an interpretation that one of the subscales aligns with a cognitive aspect of attitude while the other subscale aligns with an affective aspect. The results of these instruments indicate that students have a more positive attitude toward biology than either chemistry or math, and more positive affective attitude than cognitive attitude for all three subjects, although student attitudes show little change with respect to biology, chemistry, or math during a typical semester. However, major perturbations, such as switching to remote instruction midsemester, can lead to small but significant increases and decreases in attitude.


Quantification of micropolarity and microviscosity of aggregation and salt-induced gelation of sodium deoxycholate (NaDC) using Nile red fluorescence.
This study reports the utility of the hydrophobic probe Nile Red (NR) to understand the concentration induced microenvironmental changes of sodium deoxycholate (NaDC) bile salt from the premicellar to postmicellar range. The spectroscopic properties like absorbance value, fluorescence intensity and fluorescence lifetime of NR are significantly sensitive towards different states of aggregation of NaDC bile salt. The critical aggregation concentrations of different states (dimer to primary micellar aggregates (1.0 mM), secondary micellar aggregates (7.0 mM), and higher micellar aggregates (14 mM)) have been determined from the absorbance value and fluorescence intensity measurements. The ET(30) polarity parameter values suggest a considerable decrease in the micropolarity with an increase in NaDC concentrations. Furthermore, the spectroscopic properties of NR are also sensitive towards the NaCl induced gelation process of NaDC bile salt. Changes in the micropolarity and microviscosity of the NaDC + NaCl mixed system have been estimated using the emission maximum value (cm-1) and fluorescence lifetime values of NR with an increase in the NaCl concentration. Microviscosity of the medium increases from ∼19 mPa s to ∼26 mPa s from the sol phase to the gel phase. Temperature dependence of both size and phase changes of the NaDC + NaCl (30 mM + 1 M) gel network has been studied using differential scanning calorimetry and dynamic light scattering studies. Temperature induced polarity and microviscosity changes of the NaDC + NaCl (30 mM + 1 M) gel network have also been studied using the fluorescence properties of NR.


Arrested coalescence behaviour of giant Pickering droplets and colloidosomes stabilised by poly(tert-butylaminoethyl methacrylate) latexes.
The coalescence of two oil droplets grown at pH 10 in the presence of lightly cross-linked 260 nm diameter charge-stabilised poly(tert-butylamino)ethyl methacrylate (PTBAEMA) latexes was monitored using a high-speed video camera. Three model oils (n-dodecane, isopropyl myristate and sunflower oil) were investigated, each in the absence and presence of an oil-soluble cross-linker [tolylene 2,4-diisocyanate-terminated poly(propylene glycol), PPG-TDI]. In the absence of PPG-TDI, rapid coalescence was observed for giant PTBAEMA-stabilised Pickering oil droplets, which exhibited faster coalescence times compared to bare oil droplets. However, an increase in the damping coefficients for coalescing Pickering droplets (compared to those of bare oil droplets) indicated PTBAEMA latex particle adsorption. Addition of PPG-TDI cross-linker to oil droplets in the absence of latex particles led to a reduction in the interfacial tension confirming its surface-active nature. The oil-soluble PPG-TDI reacts with the secondary amine groups on the PTBAEMA latex, producing giant colloidosomes that remain stable to coalescence when brought into contact. This stability to coalescence was not observed for bare oil droplets in the presence of PPG-TDI, confirming that the cross-linked latex particles at the interface provide the additional stability. Finally, interactions between asymmetric n-dodecane droplets were examined. Adding oil-soluble cross-linker to only one droplet resulted in "arrested coalescence" behaviour in the presence of PTBAEMA latex particles. In this context, the droplet ageing time was found to be critical and is attributed to the relatively slow particle adsorption kinetics. Ageing times of less than 60 s led to catastrophic droplet coalescence, whereas ageing times longer than 60 s indicated cross-linker diffusion from one droplet to the other, which produced inter-cross-linked colloidosomes. Arrested coalescence was only observed for ageing times of approximately 60 s.


Exercise thallium 201 imaging. Clinical implications of normal exercise images.
To determine whether normal exercise images can reduce the need for coronary arteriography, we analyzed our data on 102 patients with normal thallium 201 exercise images who underwent coronary arteriographic studies. Eight-two patients had normal or insignificant coronary artery disease; 20 patients had significant coronary artery disease. Eight patients had disease limited to one of the secondary branches of the left system; seven patients had disease limited to one of the major coronary arteries; two patients had disease involving the right coronary artery and a secondary branch; two patients had disease involving two secondary branches; and one patient had disease involving the three major vessels. Seven of the 20 patients had abnormal exercise ECGs, and the remaining 13 patients had normal or inconclusive exercise ECGs. Our findings indicate that significant coronary artery disease is rare in patients with normal exercise images, especially if patients with abnormal exercise ECGs are excluded. Thus, normal exercise images could possibly reduce the need for coronary arteriography, since in these patients coronary artery disease rarely requires bypass surgery.


Differentiating Cerebellar Impact on Thalamic Nuclei.
The cerebellum plays a role in coordination of movements and non-motor functions. Cerebellar nuclei (CN) axons connect to various parts of the thalamo-cortical network, but detailed information on the characteristics of cerebello-thalamic connections is lacking. Here, we assessed the cerebellar input to the ventrolateral (VL), ventromedial (VM), and centrolateral (CL) thalamus. Confocal and electron microscopy showed an increased density and size of CN axon terminals in VL compared to VM or CL. Electrophysiological recordings in vitro revealed that optogenetic CN stimulation resulted in enhanced charge transfer and action potential firing in VL neurons compared to VM or CL neurons, despite that the paired-pulse ratio was not significantly different. Together, these findings indicate that the impact of CN input onto neurons of different thalamic nuclei varies substantially, which highlights the possibility that cerebellar output differentially controls various parts of the thalamo-cortical network.