Bimanual coordination in chronic schizophrenia.
Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia, a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees ) and out-of-phase movements (hands separated by 180 degrees ) at both speeds with an external cue on or off. All participants performed the in-phase movements well, irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved.


Transcriptomics assisted proteomic analysis of Nicotiana occidentalis infected by Candidatus Phytoplasma mali strain AT.
Phytoplasmas are pathogenic bacteria within the class of Mollicutes, which are associated with more than 1000 plant diseases. In this study, we applied quantitative mass spectrometry to analyse affected pathways of the model plant tobacco (Nicotiana occidentalis) upon Candidatus Phytoplasma mali strain AT infection. Using tissue obtained from leaf midribs, 1466 plant-assigned proteins were identified. For 1019 of these proteins, we could reproducibly quantify the expression changes of infected versus noninfected plants, of which 157 proteins were up- and 173 proteins were downregulated. Differential expression took place in a number of pathways, among others strong downregulation of porphyrin and chlorophyll metabolism and upregulation of alpha-linolenic acid metabolism, which was consistent with observed increased levels of jasmonic acid, a key signal molecule of plant defence. Our data shed light on the molecular networks that are involved in defence of plants against phytoplasma infection and provide a resource for further studies.


Chernobyl the TV Series: On Suspending the Truth or What's the Benefit of Lies?
HBO's 2019 miniseries Chernobyl has catapulted the world's worst nuclear disaster back into public awareness with stunning cinematography and captivating dramaturgy. For historians of technology, however, its portrayal of Soviet reactor technology, as well as its baffling omission of the disaster mitigation's most successful feat-the construction of a gigantic concrete entombment-present challenges beyond simple claims to authenticity. Are historians doomed to "abandon even the hope of truth and content ourselves instead with stories?" This essay suggests that even inaccurate storytelling can generate genuine passion, and historians can utilize this passion to nurture curiosity and help our students to seek better answers.


12/15-Lipoxygenase Deficiency Impairs Neutrophil Granulopoiesis and Lung Proinflammatory Responses to Aspergillus fumigatus.
Development of invasive aspergillosis correlates with impairments in innate immunity. We and others have recently shown that arachidonic acid metabolism pathways, specifically the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) pathways, participate in the induction of protective innate immune responses during invasive aspergillosis. Based on the high degree of cooperation and interconnection within the eicosanoid network, we hypothesized that 12/15-LOX is also active during invasive aspergillosis. We report in this study that mice deficient in the gene encoding 12/15-LOX (Alox15) are profoundly susceptible to invasive aspergillosis. Decreased survival correlated with increased fungal burden and evidence of increased lung damage. These defects were associated with very early (6 and 12 h) 12/15-LOX-dependent inflammatory cytokine (IL-1α, IL-1β, and TNF-α) and chemokine (CCL3 and CCL4) production. Neutrophil levels in the lung were blunted in the absence of 12/15-LOX, although neutrophil antifungal activity was intact. However, lower neutrophil levels in the lungs of Alox15 -/- mice were not a result of impaired recruitment or survival; rather, Alox15 -/- mice demonstrated impaired neutrophil granulopoiesis in the bone marrow intrinsically and after fungal exposure. Employing a lower inoculum to allow for better survival allowed the identification of 12/15-LOX-dependent induction of IL-17A and IL-22. Impaired IL-17A and IL-22 production correlated with reduced invariant NKT cell numbers as well as lower IL-23 levels. Together, these data indicate that 12/15-LOX is a critical player in induction of the earliest aspects of the innate immune response to Aspergillus fumigatus.


Arthrocentesis and temporomandibular joint disorders: clinical and radiological results of a prospective study.
Purpose. We evaluated the efficacy of arthrocentesis in the treatment of temporomandibular joint (TMJ) disorders. Material and Methods. In this prospective clinical case series, 30 consecutive patients with TMJ disorders underwent arthrocentesis using saline and sodium hyaluronate injections. Outcome measures were TMJ pain, maximum mouth opening (MMO), joint noises, and anatomical changes in the TMJ architecture. Patients were evaluated using cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) at the beginning of treatment and 60 days after the last arthrocentesis. Pretreatment and posttreatment clinical parameters were compared using paired and unpaired t-tests, and McNemar's test was used to evaluate CBCT and MRI changes (P < 0.05). Results. At 1-year follow-up examinations, visual analogue scale scores indicated that pain was reduced significantly and mean postoperative MMO was increased significantly. CBCT findings showed no significant change, and MRI showed only slight reductions in inflammatory signs. Conclusions. Within the limitations of this study, we can conclude that arthrocentesis is a simple, minimally invasive procedure with a relatively low risk of complications and significant clinical benefits in patients with TMJ disorders. This trial is registered with NCT01903512.


Adapting the current mass mobilization approach in Ethiopia to enhance its impact on sustainable land management: Lessons from the Sago-kara watershed.
This paper analyses the effect of an adapted - more participatory and more integrated - mass mobilization training approach on Ethiopian farmers' motivation to practice integrated farming and invest in Sustainable Land Management (SLM). It is based on the results of an experiment carried-out in the Sago-kara watershed in the Central highlands of Ethiopia, in which a group of 26 farmers received an adapted training at the start of the mass mobilization campaign in 2016, which aimed to strengthen farmers' knowledge and awareness about natural resource management, drought mitigation and integrated farm planning. One year later, both qualitative and quantitative data were collected through group discussions, field observations and household surveys. For the before-after comparison we used descriptive statistics to analyze the data; the with-without comparison (with a control group) differences were statistically tested at 1% and 5% probability levels. The results show that the adapted training approach enhanced awareness of farmers, created motivation for integrated farm management and fostered implementation of SLM practices in the field. Most interesting is that farmers who followed the training better plan for drought mitigation and are more aware of the possible effects of drought on their farming activities. The study concludes that the current mass mobilization approach in Ethiopia can have more impact on SLM if it would pay serious attention to: 1) creating awareness on the causes and effects of erosion and drought focusing on sustainability issues, 2) fostering farmers' intrinsic motivation to be good stewards of their land; 3) training in integrated farm planning, and 4) developing farm plans based on farmers' visions for resilient farming. In order to make agricultural extension in Ethiopia more effective, one has to start with capacity building of the rural extension staff in participatory training methods, followed by empowering and motivating farmers for SLM. This will not only lay a foundation for sustainable agriculture and more food security on the farm, but is also crucial for the scaling-up of resilient farming to watershed and landscape levels in Ethiopia.


Avian coccidiosis. A review of acquired intestinal immunity and vaccination strategies.
The gut-associated lymphoid tissues contain B and T lymphocytes responsible for acquired immunity to avian coccidiosis. Intestinal B cells begin producing parasite-specific antibodies shortly after infection although their role in protecting against coccidiosis is debated. T-cell-mediated immunity, predominantly by intestinal intraepithelial lymphocytes and lamina propria lymphocytes, confers the main component of protective immunity to Eimeria. Many of these cells display the CD8 and gammadelta T-cell receptor surface antigens, phenotypic markers of cytotoxic T cells. Although their role in eliminating Eimeria infection remains to be completely elucidated, T cells have been implicated in parasite transport, and their activity is augmented by interferon-gamma and interleukin-2. Because of the importance of cell-mediated immunity, coccidiosis vaccines must be capable of stimulating intestinal T cells. Orally delivered, live parasite vaccines, either unattenuated or attenuated, are powerful stimulators of intestinal cell-mediated immunity, but antigenic variability between Eimeria species present in the vaccine and in the field may restrict their commercial application. The newer generations of recombinant DNA and subunit protein vaccines, particularly when used in conjunction with interferon-gamma and interleukin-2, have shown preliminary promise in controlling experimental infections but have yet to be commercially developed.


A comparison of the intracellular precursor polyproteins of simian sarcoma-associated virus [SiSV(SiAV)] and three human virus isolates: HL23V, HEL12V and A1476V.
The intracellular precursor polyproteins of simian sarcoma-simian-associated virus [SiSV(SiAV)] were compared to the intracellular proteins of the human retrovirus isolates. HL23V, HEL12V and A1476V, by radioimmunoprecipitation followed by SDS-polyacrylamide gel electrophoresis and tryptic peptide analysis. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200gag-pol, gPr80env, Pr80gag, Pr60gag and Pr40gag. Identical intracellular precursor polyprotein profiles were obtained from cells infected with HL23V, HEL12V and A1476V. Tryptic digest mapping of peptides containing [3H]leucine showed the structural composition of Pr60gag to be the virus core proteins, p28, p15/p12 and p10. The SiSV(SiAV) envelope precursor, gPr80env, contained the structural determinants of mature viral gp70 and a non-glycosylated protein termed p15E. The homology of the human isolate viruses, HL23V, HEL12V and A1476V, to the SiSV(SiAV)/GaLV (gibbon ape leukaemia virus) family of viruses was confirmed by mapping studies. Both gPr80env and Pr60gag of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retrovirus isolates examined. The potential significance of these results to considerations of the origins of SiAV and the SiAV-like human isolates is discussed.


Volume-Based F-18 FDG PET/CT Imaging Markers Provide Supplemental Prognostic Information to Histologic Grading in Patients With High-Grade Bone or Soft Tissue Sarcoma.
The aim of the study is to assess the prognostic value of different volume-based calculations of tumor metabolic activity in the initial assessment of patients with high-grade bone sarcomas (BS) and soft tissue sarcomas (STS) using F-18 FDG PET/CT.A single-site, retrospective study from 2002 to 2012 including 92 patients with histologically verified high-grade BS (N = 37) or STS (N = 55). All patients underwent a pretreatment F-18 FDG PET/CT scan. Clinical data were registered. Measurements of the accuracy of metabolic tumor volume with a preset threshold of 40% of the maximum standardized uptake value of primary tumor (MTV40%) and total lesion glycolysis (TLG) as prognostic variables and identification of optimal discriminating cut-off values were performed through ROC curve analysis. Patients were grouped according to the cut-off values. All deaths were considered an event in survival analysis. Kaplan-Meier survival estimates and log-rank test were used to compare the degree of equality of survival distributions. Prognostic variables with related hazard ratios (HR) were assessed using Cox proportional hazards regression analysis.Forty-one of 92 patients died during follow-up (45%; 12 BS and 29 STS). Average survival for included patients was 6.5 years (95% CI 5.8-7.3 years) and probability of 5-year survival was 52%. There was a high-significant accuracy of TLG and MTV40% as prognostic variables when looking on all patients and during subgroup analysis. AUCs were higher for TLG than for MTV40%. TLG above optimal cut-off value was the only variable which was independently prognostic for survival throughout multivariate regression analysis of all included patients (P = 0.01, HR 4.78 [95% CI 1.45-15.87]) and subgroup analysis (BS: P = 0.04, HR 11.11 [95% CI 1.09-111.11]; STS: P < 0.05, HR 3.37 [95% CI 1.02-11.11]). No significant results were demonstrated for MTV40%.Volume-based F-18 FDG PET/CT imaging markers in terms of pretreatment estimation of TLG provide supplemental prognostic information to histologic grading, with significant independent properties for prediction of overall survival in patients with high-grade BS or STS.


The relationship between occupational stress and dysmenorrhea in midwives employed at public and private hospitals and health care centers in Iran (Mashhad) in the years 2010 and 2011.
According to the biopsychosocial model, menstrual symptoms are caused not only by a combination of biological factors such as hormonal disorders and lifestyle, but also by psychological and social factors such as working environment. This study aimed to determine the relation between occupational stress and dysmenorrhea in Iranian midwives. This prospective correlational study was performed on 150 midwives at public and private hospitals and health care centers of Mashhad, Iran. The subjects were selected through two-stage cluster sampling during 2010-2011. At the beginning of the study, participants completed questionnaires containing demographic information, work circumstances, the 21-item Depression, Anxiety, and Stress Scale, and the Job Content Questionnaire. They then completed the short form of daily Menstrual Distress Questionnaire during three consecutive menstrual cycles. Independent Student's t-test, one-way analysis of variance, Kruskal-Wallis, Mann-Whitney, and chi-square tests, correlation coefficients, and linear regression analysis were used to analyze the data collected data in SPSS11.5. Dysmenorrhea was observed in 63.3% of the participants. Among these individuals, 15.7%, 45.2%, and 38.9% had mild, moderate, and severe symptoms, respectively. Moreover, 59.3% of the studied midwives had severe occupational stress. There was a significant positive correlation between occupational stress and severity of dysmenorrhea (P = 0.002, r = 0.82). Occupational stress is associated with increased risk of severe dysmenorrhea. This finding can be used to guide preventive measures to eliminate or decrease occupational stress and dysmenorrhea among Iranian midwives. However, identification of sources of occupational stress and related workloads is necessary.


Mimicking herpes simplex virus 1 and herpes simplex virus 2 mucosal behavior in a well-characterized human genital organ culture.
We developed and morphologically characterized a human genital mucosa explant model (endocervix and ectocervix/vagina) to mimic genital herpes infections caused by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequent analysis of HSV entry receptor expression throughout the menstrual cycle in genital tissues was performed, and the evolution of HSV-1/-2 mucosal spread over time was assessed. Nectin-1 and -2 were expressed in all tissues during the entire menstrual cycle. Herpesvirus entry mediator expression was limited mainly to some connective tissue cells. Both HSV-1 and HSV-2 exhibited a plaque-wise mucosal spread across the basement membrane and induced prominent epithelial syncytia.


The effect of age on medical decisions made by patients with chronic illness.
Patients are currently encouraged to appoint surrogates to make healthcare decisions for them in the event that they are not able to make those decisions for themselves. Many studies have suggested that in hypothetical situations, surrogates often make different decisions than the still-capacitated patients say they would make. Age difference between patient and appointed surrogate is one possible explanation because many surrogates are next-generation relatives. This study evaluated differences in end-of-life decision making between elderly and younger patients with chronic disease. Two age groups were interviewed: (1) geriatric patients aged 70 and older and; (2) acquired immunodeficiency syndrome (AIDS) patients aged 30-50. Subjects who demonstrated an understanding of cardiopulmonary resuscitation (CPR) and artificial nutrition and hydration (ANH) were asked to choose, on a five-point Likert scale, whether they would want these treatments for themselves in four hypothetical scenarios: (1) an older person in a coma after a car accident; (2) a younger person in a coma after a car accident; (3) an older person with Alzheimer's disease; (4) a younger person with AIDS dementia. One hundred seventy-six subjects were included: 84 geriatric patients and 92 AIDS patients. Differences in the two groups were significant only in the scenario of an older person in a coma after a car accident (p = 0.007), with the geriatric patients wanting more treatment. The lack of significant differences between healthcare decisions made by the two groups under the hypothetical scenarios utilized in this study may indicate that age differences will not prevent a next-generation healthcare agent from making substituted judgement that accurately reflects patient wishes.


Lipid degradation promotes prostate cancer cell survival.
Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.


[Outpatient surgery: an unstoppable evolution].
The trend is to definitely shorten hospital stays. It follows in the footsteps of a broader range of surgeries that can be managed in an ambulatory care setting. The expected benefits are: a reduction in costs, a shorter preoperative delay, a shorter absence for the work place and a lessened risk of hospital-borne infections. A multidisciplinary approach is essential for the success of such a program. Surgeons, anaesthetists and nursing staff must be prepared to modify and adapt their skills. The criterion of success for such an endeavour is a low level of readmissions and hospitalisations. If day surgery tends to keep the patient away for the hospital settings, it certainly places him in the centre of his medical management.


PER-CRISPR/Cas14a system-based electrochemical biosensor for the detection of ctDNA EGFR L858R.
The detection of epidermal growth factor receptor (EGFR) mutation L858R in circulating tumor DNA (ctDNA) is beneficial for the clinical diagnosis and personalized therapy of non-small cell lung cancer (NSCLC). Herein, for the first time, the combination of the primer exchange reaction (PER) and clustered regularly interspaced short palindromic repeats (CRISPR) and its associated nucleases (Cas) 14a was used in electrochemical biosensor construction for the detection of ctDNA EGFR L858R. EGFR L858R, as the target, induced the isothermal amplification of the PER reaction, and then the CRISPR/Cas14a system was activated; subsequently, the substrate ssDNA-MB was cleaved and the electron on the surface of the gold electrode transferred, resulting in the fluctuation of the electrochemical redox signal on the electrode surface, whereas the electrochemical signal will be stable when EGFR L858R is absent. Therefore, the concentration of EGFR L858R can be quantified by electrochemical signal analysis. The low detection limit is 0.34 fM and the dynamic detection range is from 1 fM to 1 μM in this work. The PER-CRISPR/Cas14a electrochemical biosensor greatly improved the analytical sensitivity. In addition, this platform also exhibited excellent specificity, reproducibility, stability and good recovery. This study provides an efficient and novel strategy for the detection of ctDNA EGFR L858R, which has great potential for application in the diagnosis and treatment of NSCLC.


The X-box binding protein 1 (XBP1) gene is not associated with methamphetamine dependence.
Bipolar disorder has known as a high risk factor for substance abuse and dependence such as alcohol and illegal drugs. Recently, Kakiuchi et al. reported that the -116C/G polymorphism in the promoter region of the X-box binding protein 1 (XBP-1) gene, which translates a transcription factor specific for endoplasmic reticulum stress caused by misfolded proteins, was associated with bipolar disorders and schizophrenia in a Japanese population. Abuse of methamphetamine often produces affective disorders such as manic state, depressive state, and psychosis resembling paranoid-type schizophrenia. To clarify a possible involvement of XBP-1 in the etiology of methamphetamine dependence, we examined the genetic association of the -116C/G polymorphism of the XBP-1 gene by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism either with methamphetamine dependence or any clinical phenotype of dependence. Because the polymorphism is located in the promoter region of the XBP-1 gene and affects transcription activity of the gene, it is unlikely that dysfunction of XBP-1 may induces susceptibility to methamphetamine dependence.


Hymenoptera of Afghanistan and the central command area of operations: assessing the threat to deployed U.S. service members with insect venom hypersensitivity.
Insect venom hypersensitivity can pose a threat to personnel deployed to a combat zone but the exposure risk in Afghanistan is currently unknown. This study was designed to assess the threat of Hymenoptera stings and associated allergic reactions in Afghanistan. Hymenoptera species were collected during a deployment to southern Afghanistan from June 2010 through January 2011. The literature was also reviewed to determine species of medically important Hymenoptera recorded in the region. The U.S. Army theater electronic medical data system was mined for ICD-9 codes associated with insect stings to determine the number of theater medical clinic encounters addressing insect sting reactions. Three species of flying hymenoptera were commonly encountered during the study period: Vespa orientalis L., Polistes wattii Cameron, and Vespula germanica (F.). A literature review also confirms the presence of honeybees (Apidae), numerous velvet ant (Mutillidae) species, and various ant (Formicidae) species all capable of stinging. No evidence was identified to suggest that fire ants (Solenopsis ssp.) are a threat in the region. Based on electronic medical records from the U.S. Central Command area of operations over a 2-year period, roughly 1 in 500 clinic visits involved a patient with a diagnosis of insect bite or sting. Cross-reactive members of all five flying Hymenoptera species commonly assessed for in Hymenoptera allergy evaluations are present in Afghanistan. The review of in-theater medical records confirms that insect stings pose an environmental threat to deployed service members.


Coronary response to large decreases of hemoglobin-O2 affinity in isolated rat heart.
In this study, the consequences of large increases of P50 (O2 partial pressure at 50% oxyhemoglobin saturation) on coronary blood flow (CBF) were investigated in isolated Wistar rat heart. Rightward shifts of the O2 dissociation curve (ODC), obtained by lysing and resealing erythrocytes to encapsulate inositol hexaphosphate (IHP), led to a very large increase in P50 without side effects. Each heart was perfused alternatively with control stored human blood [P50 = 18.8 +/- 0.3 (SE) mmHg] and IHP-treated human blood (P50 = 47.1 +/- 1.7 mmHg), according to the technique of Langendorff (mean perfusion pressure 80 mmHg; hematocrit 25%). Arterial PO2 of 180 mmHg was maintained to keep arterial O2 content identical for both types of blood. When hemoglobin affinity was lowered, CBF decreased from 5.32 +/- 0.20 to 3.40 +/- 0.14 ml X min-1 X g-1, coronary sinus PO2 (PcsO2) rose from 39.9 +/- 0.9 to 69.9 +/- 4.2 mmHg, and myocardial O2 consumption (MVO2) rose slightly from 0.125 +/- 0.005 to 0.149 +/- 0.010 ml O2 X min-1 X g-1 (P less than 0.05). A significant negative correlation was found between CBF and P50 (r = -0.90; n = 32) and a significant positive correlation between PcsO2 and P50 (r = +0.84; n = 28). The coronary blood flow response to high P50 values was not abolished when maximal dilation was induced by adenosine, so this response seems independent of metabolic needs. These experiments have demonstrated that if O2 uptake by erythrocytes remains constant, in the presence of a high P50, sufficient O2 supply may be achieved with substantially less blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of pemphigus and systemic corticosteroid use with comorbid health disorders: A case-control study.
Pemphigus is a group of debilitating autoimmune blistering disorders associated with painful blisters of the skin and/or mucous membranes. Identification and management of the comorbiditiesof pemphigus is critically important to minimize morbidity and decrease mortality. To identify the comorbid health conditions of pemphigus vulgaris. This was a case-control study of 130 cases of pemphigus verified by a clinical and laboratory diagnosis and 390 age and sex-matched controls with complete follow-up at a large metropolitanquaternary care medical center. Pemphigus vulgaris and its treatments were significantly associated with type 2 diabetes mellitus (adjusted odds ratio [95% confidence interval]: 5.68 [2.93-11.02]), hypertension (2.15 [1.25-3.71]), osteopenia (10.07 [3.72-27.25]), osteoporosis (4.19 [1.50-11.73]), cataracts (7.00 [1.81-27.07]), insomnia (15.00 [1.75-128.39]), and benign prostatic hyperplasia (6.84 [1.79-26.18]). A history of taking systemic corticosteroids was found in 76% of pemphigus vulgaris patients. There were significant statistical interactions between pemphigus vulgaris and a history of using systemic corticosteroids as predictors of diabetes mellitus type 2, hypertension, osteoporosis, and insomnia. Safer and more effective systemic treatment options are needed for pemphigus to minimize iatrogenic complications of disease.


Aggregation of beta-lactoglobulin regulated by glucosylation.
A large number of proteins are glycosylated, either in vivo or as a result of industrial processing. Even though the effect of glycosylation on the aggregation of proteins has been studied extensively in the past, some reports show that the aggregation process is accelerated, whereas others found that the process is inhibited by glycosylation. This paper investigates the reasons behind these controversial results as well as the potential mechanism of the effect of glucosylation on aggregation using bovine beta-lactoglobulin as a model. Glucosylation was found to inhibit denaturant-induced aggregation, whereas heat-induced aggregation was accelerated. It was also found that the kinetic partitioning from an unfolded state was driven toward refolding for glucosylated protein, whereas aggregation was the preferred route for the nonglucosylated protein.


Impact of gait speed and instrumental activities of daily living on all-cause mortality in adults ≥65 years with heart failure.
Mobility and function are important predictors of survival. However, their combined impact on mortality in adults ≥65 years with heart failure (HF) is not well understood. This study examined the role of gait speed and instrumental activities of daily living (IADL) in all-cause mortality in a cohort of 1,119 community-dwelling Cardiovascular Health Study participants ≥65 years with incident HF. Data on HF and mortality were collected through annual examinations or contact during the 10-year follow-up period. Slower gait speed (<0.8 m/s vs ≥0.8 m/s) and IADL impairment (≥1 vs 0 areas of dependence) were determined from baseline and follow-up assessments. A total of 740 (66%) of the 1,119 participants died during the follow-up period. Multivariate Cox proportional hazards models showed that impairments in either gait speed (hazard ratio 1.37, 95% confidence interval 1.10 to 1.70; p = 0.004) or IADL (hazard ratio 1.56, 95% confidence interval 1.29-1.89; p <0.001), measured within 1 year before the diagnosis of incident HF, were independently associated with mortality, adjusting for sociodemographic and clinical characteristics. The combined presence of slower gait speed and IADL impairment was associated with a greater risk of mortality and suggested an additive relation between gait speed and IADL. In conclusion, gait speed and IADL are important risk factors for mortality in adults ≥65 years with HF, but the combined impairments of both gait speed and IADL can have an especially important impact on mortality.


From sagittal distance to area. A study of transverse, vocal tract cross-sectional area.
In speech articulation studies, data on the pharynx are scarce. Still, the pharynx is an important part of the vocal tract. The present paper reports on an attempt to use computed tomography for investigating the pharynx. Axial computed tomograms were taken at four levels in the pharynx of a male and a female subject sustaining the vowels [u:, i:, a:, oe:]. From the tomograms the lateral width and the cross-sectional area were measured and their relations to the sagittal distance from the back pharynx wall to the midline of the tongue examined and compared with previously published data. In addition, some previous results derived from plaster casts are presented showing the corresponding distance-to-area relationship in the mouth region of some male and female subjects.


A Retrospective Study on Possible Predictive Factors for Long-term Temporomandibular Joint Degeneration and Impaired Mobility in Juvenile Arthritis Patients.
To determine possible predictive factors for long-term temporomandibular joint (TMJ) degeneration and dysfunction in juvenile idiopathic arthritis (JIA) patients. A total of 94 patients (77% female) who had received a JIA diagnosis in an outpatient rheumatology clinic from 1993 to 1994 at a mean ± standard deviation age of 8.3 ± 4.53 years were included in the study. At inclusion, TMJ status regarding condylar degeneration was assessed orthopantomographically and given a Rohlin and Petersson score of 0 or ≥ 1. The maximal mouth opening (MMO) was also measured. Data on possible predictors were gathered retrospectively from the consultation at intake: gender, age at JIA onset, JIA subtype, physical limitations (ie, a Steinbrocker classification score of 0 or ≥ 1), human leukocyte antigen-B27, and antinuclear and rheumatoid factors. Disease duration and medication type were also considered. Associations between all of these factors and long-term condylar degeneration and MMO were assessed by using single and multiple regression analyses. Long-term TMJ degeneration and smaller MMO were both associated with younger age at JIA onset (P = .01; P = .03) and longer disease duration (P = .05; P = .002). Moreover, MMO was negatively associated with physical limitations at intake (P = .04). Within the limitations of this retrospective study design, these results suggest that young JIA patients with early physical limitations and prolonged disease are at risk of long-term TMJ degeneration and impaired mobility.


Linear rheology of water-soluble reversible neodymium(III) coordination polymers.
The rheology of reversible coordination polymer networks in aqueous solution is studied. The polymers are formed by neodymium(III) ions and bifunctional ligands, consisting of two pyridine-2,6-dicarboxylate groups connected at the 4-positions by an ethylene oxide spacer. Neodymium(III) ions can bind three of these terdendate ligand groups. At high concentrations, the polymer networks yield viscoelastic materials, which can be described with the Maxwell model. The scaling of the elastic modulus, relaxation time, and zero-shear viscosity with concentration are in good agreement with the predictions of Cates' model that describes the dynamics of linear equilibrium polymers. This indicates that the networks have only few cross-links and can be described as linear equilibrium polymers. The gels are also thermo-reversible. At high temperatures, fast relaxation was found, resulting in liquidlike behavior. Upon cooling, the viscoelastic properties returned immediately. From the temperature dependence of the relaxation time, an activation energy of 49 kJ/mol was determined for the breaking and reptation of the polymers.


Status epilepticus in pregnancy. A case report.
Status epilepticus is a serious emergency that rarely complicates the management of the pregnant patient with seizure disorders. Because of concerns regarding the safety of anticonvulsion medications, this condition may appear with increasing frequency. Our management of such a case resulted in a healthy mother and infant.


The large millimeter telescope/el Gran Telescopio Milimétrico: a new instrument for astrobiology.
The Instituto Nacional de Astrofísica, Optica y Electrónica in Mexico and the University of Massachusetts in the U.S.A. are collaborating to build the world's largest radio telescope that operates at short millimeter wavelengths. This facility, known as the Large Millimeter Telescope (LMT) or el Gran Telescopio Milimétrico (GTM), is being sited at an altitude of 4600 m on Volcan Sierra Negra in the Mexican state of Puebla. The telescope will be a fully steerable dish with a diameter of 50 m and a surface consisting of 180 panels that are actively adjusted under computer control to correct for deformations due to gravity and temperature gradients. Instruments will include focal plane arrays to image both continuum and spectral line emission from celestial sources. The LMT/GTM will be an extremely powerful facility for studies encompassing almost all areas of astronomy, including astrobiology. In particular, the high sensitivity, angular resolution, and mapping speed will enable detailed investigations of the organic chemistry of interstellar molecular clouds, protoplanetary disks, and comets.


Smoke-free schools? Results of a secondary school smoking policies survey 2002.
To describe the cigarette-smoking policies of a sample of New Zealand secondary schools. Schools randomly selected from six geographical regions for participation in the Health Sponsorship Council's 2002 Youth Lifestyle Study (YLS) were invited to also participate in the School Smoking Policies Survey (SSPS). Eighty one of 82 schools responded (response rate 98.8%); 64 schools (79.0%) provided copies of smoking policies. Of the schools that provided policies, only 31 (50.8%) were totally smoke free, ie, banned smoking 24 hours a day, seven days a week. Five schools (8.2%) were both smoke free and fully compliant with existing legislation. Seventy eight schools (96.3%) provided education about smoking and imposed sanctions on students caught smoking. Most respondents (74.1%) considered school staff would support proposed changes to the Smoke-free Environments Act that would make all school buildings and grounds totally smoke free. Most secondary schools are not smoke free, but most staff are likely to support smoke-free status. Existing inconsistency among educational messages, school practice and staff actions may undermine tobacco-smoking-prevention efforts. Proposed strengthening of smoke-free legislation is both timely and necessary to ensure that all New Zealand students are provided with totally smoke-free school environments, consistent with health education messages.


Studies with a reconstituted muscle glycolytic system. The rate and extent of creatine phosphorylation by anaerobic glycolysis.
A mixture of purified muscle glycolytic enzymes was reconstituted and the mixture shown to behave in a fashion analogous to that occurring in vivo. Glycolysis leads to ATP production in muscle and results in the phosphorylation of creatine. The extent of this phosphorylation by anaerobic glycolysis was shown to depend to a small extent on the relative proportions of available P(i) and creatine initially, but more importantly on the first step in glycolysis, in this case the enzyme phosphorylase. With less than 0.1% of the phosphorylase in the a form, only about one-third of the creatine was phosphorylated in 30min, whereas with 4% or more of phosphorylase a, 90% of the creatine was phosphorylated within this time. Inclusion of an adenosine triphosphatase decreased the steady-state concentration of phosphocreatine in the system. Calculations of the theoretical concentrations of ADP and AMP showed that phosphorylase b was almost inactive even in the presence of 9mum-AMP, because of ATP inhibition. With phosphorylase a present, glycolysis was able to continue at least until the calculated concentration of MgADP(-) was only 7mum, and AMP in the sub-mumolar range. The relation of these values to measured concentrations of nucleotides and to phosphorylase a percentages in intact muscle is discussed.


Do organisational and ward-level factors explain the variance in multi-site musculoskeletal pain in eldercare workers? A multi-level cross-sectional study.
Multi-site musculoskeletal pain (MSP) is highly prevalent among eldercare workers, leading to increased incidence of sickness absence and early retirement. Most research on MSP in eldercare workers has focused on individual-level factors reported by the employees, with limited focus at the organisation and ward level. To address this gap, the aim of this study was to investigate whether organisation and ward-level factors explain the variance in MSP among Danish eldercare workers. A multi-level cross-sectional study was conducted among 20 Danish nursing homes, containing 126 wards, and 418 workers who participated in measurements of organisational factors, working environment factors, and MSP (classified as reporting pain in 2 or more body regions). Data were collected at the level of the organisation, ward, and individual. The proportion of variance in MSP explained by each level was estimated using variance components analysis. The association between factors at each level of the organisation and MSP was investigated using generalised linear mixed-effects regression. Sixty seven percent of participants reported having MSP. The organisational and ward-level factors explained 0% of the variance in MSP, while the individual-level factors explained 100% of the variance in MSP. Moreover, no factors at the organisational and ward levels showed statistically significant associations with MSP. Individual-level perceived physical exertion and quantitative demands had a statistically significant association with a higher prevalence of MSP. The organisation and ward levels did not contribute to explaining any of the variance in MSP. All variance in MSP was explained at the individual level.


An ex vivo characterization of Paclitaxel loaded chitosan films after implantation in mice.
The objective of present investigation was the characterization of chitosan films after in vivo implantation. Chitosan films were prepared at three dose loadings of paclitaxel by classical casting method. They were implanted subcutaneously in Swiss mice in the neck region and were removed at 7, 15, 21 and 30 days post implantation for characterization. In vitro release studies on explanted films were done to observe the influence of the time of implantation and loading on paclitaxel release, which were correlated with amount of paclitaxel remaining in films. Residual amount of paclitaxel remaining in explanted films decreased with increase in loading i.e. after 30 days, the % residual content of drug at 25, 20 and 15 mg loadings (per film) were 13, 20 and 45 % of the initial loading. The in vivo release of paclitaxel from films with higher loadings was higher, indicating that paclitaxel, per se, altered biodegradation of chitosan. Light microscopy and SEM studies of films removed from mice provided qualitative information on the loss of integrity and biodegradation of films with time. Further, FTIR and ATR-FTIR spectra revealed the changes in the film matrix that occur after implantation.


Human cell transfection with skin cancer DNAs.
Spectacular progress towards understanding the molecular changes in DNA of many human tumors has been gained using NIH 3T3s as cellular recipients of transfecting DNA (1). Similar advances in analyzing human skin cancers have not been possible, as DNAs of most skin cancers or skin cancer cell lines--including most malignant melanomas--do not transform 3T3s (2). We have developed a DNA transfection system using human cells as recipients (3): normal human cells are transformed to anchorage-independent growth by transfection with a variety of skin cancer DNAs. This method may allow identification of the genes and specific sequences altered in sunlight-induced human skin cancers.


The influence of digital elevation model resolution on overland flow networks for modelling urban pluvial flooding.
This paper presents the developments towards the next generation of overland flow modelling of urban pluvial flooding. Using a detailed analysis of the Digital Elevation Model (DEM) the developed GIS tools can automatically generate surface drainage networks which consist of temporary ponds (floodable areas) and flow paths and link them with the underground network through inlets. For different commercially-available Rainfall-Runoff simulation models, the tool will generate the overland flow network needed to model the surface runoff and pluvial flooding accurately. In this paper the emphasis is placed on a sensitivity analysis of ponds and preferential overland flow paths creation. Different DEMs for three areas were considered in order to compare the results obtained. The DEMs considered were generated using different acquisition techniques and hence represent terrain with varying levels of resolution and accuracy. The results show that DEMs can be used to generate surface flow networks reliably. As expected, the quality of the surface network generated is highly dependent on the quality and resolution of the DEMs and successful representation of buildings and streets.


Epidermolysis bullosa acquisita.
Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal bullous disease with clinical features similar to the genetic form of dystrophic epidermolysis bullosa. EBA is characterized by the presence of autoantibodies against type VII collagen which is a major component of the anchoring fibrils at the dermal-epidermal junction. EBA can be divided into two main clinical types; mechanobullous and inflammatory EBA. Mechanobullous EBA, referred to as classic EBA, presents with skin fragility, blisters and dystrophic changes on trauma-prone areas. Inflammatory EBA resembles other autoimmune subepidermal bullous diseases. Compelling evidence from mouse models supports a pathogenic role of autoantibodies against type VII collagen in EBA. Treatment of EBA is often unsatisfactory. The most widely used systemic treatment is corticosteroids. Colchicine and dapsone have been reported to be good treatment modalities when combined with corticosteroids. Some intractable cases of EBA have successfully been treated with intravenous immunoglobulin or rituximab.


HECTD2 is associated with susceptibility to mouse and human prion disease.
Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods.


Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.
Dendritic cells (DCs) are a heterogeneous group of professional antigen-presenting cells functioning as sentinels of the immune system and playing a key role in the initiation and amplification of innate and adaptive immune responses. DC development and functions are acquired during a complex differentiation and maturation process influenced by several factors present in the local milieu. A common feature at pathologic sites is represented by hypoxia, a condition of low pO(2), which creates a unique microenvironment affecting cell phenotype and behavior. Little is known about the impact of hypoxia on the generation of mature DCs (mDCs). In this study, we identified by gene expression profiling a significant cluster of genes coding for immune-related cell surface receptors strongly up-regulated by hypoxia in monocyte-derived mDCs and characterized one of such receptors, TREM-1, as a new hypoxia-inducible gene in mDCs. TREM-1 associated with DAP12 in hypoxic mDCs, and its engagement elicited DAP12-linked signaling, resulting in ERK-1, Akt, and IκBα phosphorylation and proinflammatory cytokine and chemokine secretion. Finally, we provided the first evidence that TREM-1 is expressed on mDCs infiltrating the inflamed hypoxic joints of children affected by juvenile idiopathic arthritis, representing a new in vivo marker of hypoxic mDCs endowed with proinflammatory properties.


CaeNDR, the Caenorhabditis Natural Diversity Resource.
Studies of model organisms have provided important insights into how natural genetic differences shape trait variation. These discoveries are driven by the growing availability of genomes and the expansive experimental toolkits afforded to researchers using these species. For example, Caenorhabditis elegans is increasingly being used to identify and measure the effects of natural genetic variants on traits using quantitative genetics. Since 2016, the C. elegans Natural Diversity Resource (CeNDR) has facilitated many of these studies by providing an archive of wild strains, genome-wide sequence and variant data for each strain, and a genome-wide association (GWA) mapping portal for the C. elegans community. Here, we present an updated platform, the Caenorhabditis Natural Diversity Resource (CaeNDR), that enables quantitative genetics and genomics studies across the three Caenorhabditis species: C. elegans, C. briggsae and C. tropicalis. The CaeNDR platform hosts several databases that are continually updated by the addition of new strains, whole-genome sequence data and annotated variants. Additionally, CaeNDR provides new interactive tools to explore natural variation and enable GWA mappings. All CaeNDR data and tools are accessible through a freely available web portal located at caendr.org.


HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes.
Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization of ischemic tissue. Ex vivo expansion of EPCs might be useful for potential clinical cell therapy of myocardial ischemia. However, cultivation of primary cells leads to cellular aging (senescence), thereby severely limiting the proliferative capacity. Therefore, we investigated whether statins might be able to prevent senescence of EPCs. EPCs were isolated from peripheral blood and characterized. After ex vivo cultivation, EPCs became senescent as determined by acidic beta-galactosidase staining. Atorvastatin or mevastatin dose-dependently inhibited the onset of EPC senescence in culture. Moreover, atorvastatin increased proliferation of EPCs as assessed by BrdU incorporation and colony-forming capacity. Whereas geranylgeranylpyrophosphate or farnesylpyrophosphate reduced the senescence inhibitory effect of atorvastatin, NO synthase inhibition, antioxidants, or Rho kinase inhibitors had no effect. To get further insights into the underlying downstream effects of statins, we measured telomerase activity and determined the expression of various cell cycle regulatory genes by using a microarray assay. Whereas telomerase activity did not change, atorvastatin modulated expression of cell cycle genes including upregulation of cyclins and downregulation of the cell cycle inhibitor p27Kip1. Taken together, statins inhibited senescence of EPCs independent of NO, reactive oxygen species, and Rho kinase, but dependent on geranylgeranylpyrophosphate. Atorvastatin-mediated prevention of EPC senescence appears to be mediated by the regulation of various cell cycle proteins. The inhibition of EPC senescence and induction of EPC proliferation by statins in vitro may importantly improve the functional activity of EPCs for potential cell therapy.


The FATHER Model of Loss and Grief After Child's Life-Limiting Illness.
Loss of a child to a life-limiting condition (LLC) is 1 of the most traumatic life events for parents. Research focusing on fathers' experiences is in its infancy. Using a meta-ethnographic approach, we systematically reviewed the literature around fathers' predeath and postdeath experiences of loss and grief. We searched Medline, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Science Direct, and used the meta-ethnography reporting guidelines; the Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and sampling strategy, type of study, approaches, range of years, limits, inclusion and exclusions, terms used, and electronic sources recommendations. We used the Guide to Children's Palliative Care and the directory of LLCs to select qualitative articles published up until the end of March 2023 that described fathers' predeath and postdeath experiences of loss and grief after their child's LLC. We excluded studies that failed to differentiate outcomes between mothers and fathers. Extracted data included study details, participants' characteristics, response rate, source of participants, method and time of data collection, children's characteristics, and quality assessment. First-order and second-order data were also extracted. Forty studies informed a FATHER model of loss and grief. This highlights both similarities (ambivalence, trauma responses, fatigue, anxiety, unresolved grief, guilt) and distinct features defining the predeath and postdeath experiences of loss and grief. There was a bias toward greater mother participation in research. Specific categories of fathers remain underrepresented in palliative care literature. Many fathers experience disenfranchised grief and deterioration in mental health after a child's diagnosis and postdeath. Our model opens possibilities for personalized clinical support in the palliative care system for fathers.


[Cholesterol ester transfer protein. A major player in cholesterol metabolism].
Plasma cholesterol transfer protein (P-CETP) plays a central role in cholesterol metabolism by pronroting transfer of cholesteryl esters from high density lipoprotein (HDL) to very low density lipoproteins in exchange for triglycerides. The CETP-reaction may hereby be a critical factor in reverse cholesterol transport, i.e., the transfer of cholesterol from peripheral tissues to the river for catabolism. Human genetic CETP deficiency is associated with increased P-HDL-cholesterol, whereas CEPT transgenic mice display decreased P-HDL-cholesterol. The effects of CETP on atherogenesis are currently unpredictable, and they are likely to depend on the metabolic context. However, the presence of specific polymorphisms in the CETP gene may be of clinical importance, and CETP should be considered among the factors relevant for differentiation of dyslipidemic syndromes associated with susceptibility to and protection from atherosclerotic disease.


Microenvironmental determinants of adult neural stem cell proliferation and lineage commitment in the healthy and injured central nervous system.
The discovery of neural stem cells (NSC) which ensure continuous neurogenesis in the adult mammalian brain, has led to a conceptual revolution in basic neuroscience and to high hopes for clinical nervous tissue repair. However, several research issues remain to address before neural stem cells can be harnessed for regenerative therapies. The presence of NSC in a nervous structure is demonstrated in vitro by primary culture of dissociated adult nervous tissue in the presence of the specific mitogens EGF and bFGF. This leads to spherical masses of proliferating cells endowed with capacities for self-renewal and, after growth factor removal, differentiation into the three characteristic cell types of nervous tissue (neurons, astrocytes, oligodendrocytes). In vivo, neurogenesis per se, i.e. production of new neurons, occurs only in a small subset of NSC-endowed structures. The production of oligodendrocytes, i.e. myelinating glial cells, is similarly restricted. Such in vivo restrictions were formally demonstrated to arise from the tissular microenvironnement, which led to the emerging concept of "neurogenic niche". In this context, major challenges now consist in identifying the nature of tissue-specific extracellular signals that determine lineage commitment of NSC progeny, understanding why NSCs display weak in vivo reactivity to lesions compared to other stem cell types in adults, and identifying the factors behind the very high resistance to tumorigenesis displayed by NSCs. Altogether, the current data offer hope for the future use of adult NSCs in regenerative therapies, provided that tissue-specific signals are identified in view of counteracting the intrinsic repression of new cell genesis and/or stimulating endogenous NSC recruitment to lesion sites.


A Zika virus from America is more efficiently transmitted than an Asian virus by Aedes aegypti mosquitoes from Asia.
Zika is a mosquito-borne disease associated with neurological disorders that causes an on-going pandemic. The first outbreak was recorded in Micronesia in 2007, then in French Polynesia in 2014 from which it spread to South America in 2015 and ignited a widespread epidemic. Interestingly, Zika outbreaks in Asia remained of moderate intensity although the virus is circulating. To understand these epidemiological variations, we investigated the entomological determinants of ZIKV transmission in Asia. We used oral infection of mosquitoes collected in Singapore to identify the vector species, to quantify the blood infection threshold and to compare transmissibility between an Asian ZIKV strain (H/PF13) and an American strain collected in Brazil (BE H 815744). We have confirmed the vector status of Aedes aegypti and determined that 103 pfu/ml of blood is sufficient to infect mosquitoes. We showed that only the American strain was present in the saliva 3 days post-infection, and that this strain had a 30-40% higher rate of saliva infection in Ae. aegypti from 3 to 14 days post-infection than the Asian strain. Our data suggests that American strains are more efficiently transmitted than Asian strains, which raises concerns about the introduction of American strains in Asia.


Effects of vitrification on nuclear maturation, ultrastructural changes and gene expression of canine oocytes.
Cryopreservation of oocytes, which is an interesting procedure to conserve female gametes, is an essential part of reproductive biotechnology. The objective of the present study was to investigate the effects of vitrification on nuclear maturation, ultrastructural changes and gene expression of canine oocytes. Immature oocytes (germinal vesicles) isolated from ovaries of normal bitches (> 6 months of age) were either vitrified in open pulled straw (OPS) using 20% ethylene glycol (EG) and 20% dimethyl sulfoxide (DMSO) as vitrification solution or exposed to vitrification solution without subjected to liquid nitrogen. After warming, oocytes were investigated for nuclear maturation following in vitro maturation (IVM), ultrastructural changes using transmission electron microscopy (TEM) and gene expression using RT-PCR. Fresh immature oocytes were used as the control group. The rate of resumption of meiosis in vitrified-warmed oocytes (53.4%) was significantly (P < 0.05) lower than those of control (93.8%) and exposure (91.4%) groups. However, there were no statistically significant differences among groups in the rates of GV oocytes reaching the maturation stage (metaphase II, MII). The ultrastructural alterations revealed by TEM showed that cortical granules, mitochondria, lipid droplets and smooth endoplasmic reticulum (SER) were affected by vitrification procedures. RT-PCR analysis for gene expression revealed no differences in HSP70, Dnmt1, SOD1 and BAX genes among groups, whereas Bcl2 was strongly expressed in vitrified-warmed group when compared to the control. Immature canine oocytes were successfully cryopreserved, resumed meiosis and developed to the MII stage. The information obtained in this study is crucial for the development of an effective method to cryopreserve canine oocytes for establishment of genetic banks of endangered canid species.


Phylogeny and generic limits in the sister tribes Psychotrieae and Palicoureeae (Rubiaceae): Evolution of schizocarps in Psychotria and origins of bacterial leaf nodules of the Malagasy species.
• Premise of the study: The pantropical, species-rich Psychotrieae and Palicoureeae are sister tribes of mostly drupe-bearing and nonbacterial leaf-nodulating species with problematic generic limits. This problem is more complicated in Psychotrieae due to the paraphyly of the genus Psychotria, the lack of diagnostic characters for some major lineages, and the poor sampling from some biodiversity hotspots. Schizocarps and bacterial leaf nodules have been used for recognizing formal groups in Psychotrieae, but their evolution and taxonomic value have not been studied using a robust phylogeny of the tribe.• Methods: We analyzed 287 samples from the entire ranges of the tribes, with particular emphasis on the Western Indian Ocean region, with the Bayesian Markov chain Monte Carlo method.• Key results: All allied Psychotria genera investigated are nested within a paraphyletic Psychotria. Schizocarps evolved independently two times within Psychotria, and one reversal back to the drupaceous condition is inferred. The Malagasy leaf-nodulated Psychotrieae (except Apomuria bullata) and the Comorian non-leaf-nodulated Psychotria conocarpa are nested within the (African) leaf-nodulated clade. Within Palicoureeae, Chassalia is paraphyletic with respect to Geophila sensu stricto, and the Malagasy Geophila gerrardii and the African Hymenocoleus are closely related.• Conclusions: A widely circumscribed Psychotria encompassing the entire Psychotrieae is supported. Within Psychotria, two separate origins of schizocarps from drupes, one reversal back to the drupaceous condition, and two independent origins of the Malagasy leaf-nodulated species are inferred. A new genus Puffia is described to accommodate Geophila gerrardii, and a narrow circumscription of Chassalia is adopted. Thirty-two new combinations, two lectotypifications, and 25 new names are presented.


Factors influencing why nursing care is missed.
This study explores the reasons nurses identify missed care and what factors account for this variance in nursing practice. Second, the study seeks to understand if the identified reasons behind missed care interact with one another and form a multidimensional construct. This study draws on the results of previous research conducted by Kalisch in developing the MISSCARE research survey tool and now applies it to an Australian context. This study engages a nonexperimental exploratory approach where 16 latent variables are identified and estimated using structural equation modelling to determine the capacity each of these factors has in predicting the reasons for reported missed nursing care. Data were obtained from an electronic survey sent to nursing members of the Australian Nursing and Midwifery Federation of South Australia. A self-report, Likert-type instrument was used to capture the strength and direction of consensus derived from a sample of 289 nurses and midwives. Eight variables were identified as having direct predictor effects as to why nursing care was being missed, and included shift type, nursing resource allocation, health professional communication, workload intensity, workload predictability, the nurses' satisfaction with their current job and their intention to remain working. Additional indirect effects of other variables explained 34% of the variance of the total scores for why nursing care was reported as being missed. Historically, the MISSCARE survey has identified and quantified what types of nursing care is missed. This paper takes this concept further by producing an interactional model identifying the effects different variables have on why nursing care is missed. These Australian findings not only contribute to other international studies that identify why nursing care is omitted, it provides a framework for why reported episodes of missed care can be predicted and subsequently addressed.


Effects of NADH on dopamine release in rat striatum.
Nicotinamide adenine dinucleotide (NADH) may be utilized for the synthesis and regeneration of tetrahydrobiopterin (BH(4)), which in turn is an essential cofactor for tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of dopamine (DA). NADH has been reported to relieve some of the symptoms of Parkinson's disease, presumably by altering dopaminergic function. The present study examines the efficacy of NADH in influencing DA activity in the rat striatum. In striatal slices, NADH (350 microM) significantly increased basal DA and DOPAC efflux and caused a 2-fold increase in the DA overflow evoked by high KCl (25 mM). Tissue levels of BH(4), basal BH(4) efflux, and KCl-evoked BH(4) overflow were unaffected by NADH, as was [(3)H]DA uptake into striatal synaptosomes. In contrast to the effects of NADH on DA function in vitro, no effects were observed when NADH was administered systemically. NADH (10 or 100 mg/kg, s.c.) did not influence the tissue content of DA, 5-HT, or their metabolites in the midbrain or striatum, nor did it alter DA extracellular concentrations. These results indicate that NADH can increase DA release from striatal slices, although we are as yet unable to detect this effect in vivo.


[Effect of leucomisine on cell and humoral immunity indices].
The influence of the sesquiterpene lactone leucomisine on the cell and humoral immunity indices has been studied. It is established that the administration of leucomisine in a dose of 10 mg/kg dose stimulates IgM and IgG antibody production.


Intrinsic structure and dynamics of monolayer ring polymer melts.
We present the general structural and dynamical characteristics of flexible ring polymers in narrowly confined two-dimensional (2D) melt systems using atomistic molecular dynamics simulations. The results are further analyzed via direct comparison with the 2D linear analogue as well as the three-dimensional (3D) ring and linear melt systems. It is observed that dimensional restriction in 2D confined systems results in an increase in the intrinsic chain stiffness of the ring polymer. Fundamentally, this arises from an entropic penalty on polymer chains along with a reduction in the available chain configuration states in phase space and spatial choices for individual segmental walks. This feature in combination with the intermolecular interactions between neighboring ring chains leads to an overall extended interpenetrated chain configuration for the 2D ring melt. In contrast to the generally large differences in structural and dynamical properties between ring and linear polymers in 3D melt systems, relatively similar local-to-global chain structures and dynamics are observed for the 2D ring and linear melts. This is attributed to the general structural similarity (i.e., extended double-stranded chain conformations), the less effective role of the chain ends, and the absence of complex topological constraints between chains (i.e., interchain entanglement and mutual ring threading) in the 2D confined systems compared with the corresponding 3D bulk systems.


Rapid visualization of hydrogen positions in protein neutron crystallographic structures.
Neutron crystallography is a powerful technique for experimental visualization of the positions of light atoms, including hydrogen and its isotope deuterium. In recent years, structural biologists have shown increasing interest in the technique as it uniquely complements X-ray crystallographic data by revealing the positions of D atoms in macromolecules. With this regained interest, access to macromolecular neutron crystallography beamlines is becoming a limiting step. In this report, it is shown that a rapid data-collection strategy can be a valuable alternative to longer data-collection times in appropriate cases. Comparison of perdeuterated rubredoxin structures refined against neutron data sets collected over hours and up to 5 d shows that rapid neutron data collection in just 14 h is sufficient to provide the positions of 269 D atoms without ambiguity.


MOSAIC_SSD: a new web tool for species sensitivity distribution to include censored data by maximum likelihood.
Censored data are seldom taken into account in species sensitivity distribution (SSD) analysis. However, they are found in virtually every dataset and sometimes represent the better part of the data. Stringent recommendations on data quality often entail discarding a lot of these meaningful data, resulting in datasets of reduced size which lack representativeness of any realistic community. However, it is reasonably simple to include censored data in SSD by using an extension of the standard maximum likelihood method. The authors detail this approach based on the use of the R-package fitdistrplus, dedicated to the fit of parametric probability distributions. The authors present the new Web tool MOSAIC_SSD, that can fit an SSD on datasets containing any type of data, censored or not. The MOSAIC_SSD Web tool predicts any hazardous concentration and provides bootstrap confidence intervals on the predictions. Finally, the authors illustrate the added value of including censored data in SSD, taking examples from published data.


Complete or partial loss of the Y chromosome in an unselected cohort of 865 non-vasectomized, azoospermic men.
Structural abnormalities as well as minor variations of the Y chromosome may cause disorders of sex differentiation or, more frequently, azoospermia. This study aimed to determine the prevalence of loss of Y chromosome material within the spectrum ranging from small microdeletions in the azoospermia factor region (AZF) to complete loss of the Y chromosome in azoospermic men. Eleven of 865 azoospermic men (1.3%) collected from 1997 to 2022 were found to have a karyotype including a 45,X cell line. Two had a pure 45,X karyotype and nine had a 45,X/46,XY mosaic karyotype. The AZF region, or part of it, was deleted in eight of the nine men with a structural abnormal Y-chromosome. Seven men had a karyotype with a structural abnormal Y chromosome in a non-mosaic form. In addition, Y chromosome microdeletions were found in 34 men with a structural normal Y chromosome. No congenital malformations were detected by echocardiography and ultrasonography of the kidneys of the 11 men with a 45,X mosaic or non-mosaic cell line. In men with azoospermia, Y chromosome loss ranging from small microdeletions to complete loss of the Y chromosome was found in 6.1% (53/865). Partial AZFb microdeletions may give a milder testicular phenotype compared to complete AZFb microdeletions.


DEXA analysis on the bones of rats exposed in utero and neonatally to static and 50 Hz electric fields.
Effects of the electromagnetic fields on living bodies, bones in particular, are among the relevant issues of contemporary life. In this study, we report the influences of 50 Hz and 0 Hz (static) electric fields (EF), on intact rat bones, as evaluated by dual energy X-ray absorbtion (DEXA) measurements on bone content and density when these animals (n = 27) are continuously exposed in utero and neonatally to EFs (10 kV/m) 14 days before and 14 days after their birth, for 28 days in total. Differences between 50 Hz EF and static EF groups are found to be significant (95% confidence level) for total bone mineral content (BMC), TBMC (P = .002). Differences between 50 Hz and control groups are found to be significant for total bone mineral density (BMD), TBMD (P = .002), lumbar BMC, LBMC (P = .023), and TBMC (P = .001). Differences between static EF and control groups are found to be significant for femoral BMD, FBMD (P = .009), TBMD (P = .002), LBMC (P = .001), and TBMC (P = .001). Note that TBMC parameters are jointly significant for all differences between the three groups of test animals. These results have shown that both static and 50 Hz EFs influence the early development of rat bones. However, the influence of static EFs is more pronounced than that of the 50 Hz field.


Coats' Disease: Very Long-Term Outcome After Early Stage Conventional Treatment.
To report on the outcome of conventional therapy in patients with Coats' disease. Retrospective analysis of the charts of thirteen patients with Coats' disease. Mean age of 9 male (70%) and 4 female (30%) patients was 17.7 (range, 5-33) years; one female had bilateral disease. Eleven eyes with retinal telangiectasia and exudation were treated with argon laser photocoagulation alone or photocoagulation associated with cryotherapy; the mean follow up was 32.5 (range,17-41) years. In four eyes without foveal involvement (stage 2a) the mean presenting visual acuity (VA) remained at 0.8 or improved, whereas poor VA in seven stage 2b eyes deteriorated minimally over time. In one and two of the three eyes with total retinal detachment, phthisis or neovascular glaucoma ensued. About three decades after conventional treatment of Coats' disease stage 2a, treated eyes maintained good VA, and stage 2b eyes did not progress to advanced stages.


Risk Factors for Severe Infection, Hospitalization, and Prolonged Antimicrobial Therapy in Patients with Babesiosis.
Babesiosis is an emerging tick-borne disease transmitted by the hard tick Ixodes scapularis, which also transmits Lyme disease. Better gradation of prognostic indicators are needed to determine which patients may develop serious complications requiring hospitalization, and to provide early guidance on appropriate therapy. In this study, we evaluated 128 patients with smear or real time polymerase chain reaction-confirmed Babesia microti infections over a period of 16 years. Patients with asplenia or immunocompromising conditions were more likely to have severe infection (P < 0.01), require hospitalization (P < 0.01), or receive prolonged courses of antimicrobials (P < 0.01). Nausea or vomiting (P < 0.01) and diarrhea (P < 0.01) along with hyperbilirubinemia (P < 0.01) were predictive of severe infection, hospitalization, and prolonged antimicrobial therapy. Patients with concurrent Lyme disease were less likely to require hospitalization and had similar severity of disease and length of antibiotic treatment compared with those without Lyme disease.


Study of the diagnostic value of interleukin-6 and interleukin-8 in children with acute gastroenteritis.
Gastroenteritis in children is responsible for high morbidity and mortality. Our aim was to determine the serum and fecal levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in children with acute gastroenteritis of viral and bacterial etiology to assess their utility as diagnostic biomarkers for these infections. In this case-control study, the children were classified according to the pathogen recovered from the stool by bacterial culture or by direct viral antigen detection by enzyme immunoassay (EIA) into 50 children with acute bacterial gastroenteritis and 50 children with acute viral gastroenteritis. In addition, 50 apparently healthy children were included as a control group. Blood and stool samples were subjected to detection of IL-6 and IL-8. There were statistically significant elevations of total leucocytes counts, absolute neutrophils count, C-reactive protein, serum IL-6 and serum IL-8 in children with gastroenteritis compared to healthy children (p<0.001). CRP, serum IL-6 and IL-8 had significantly elevated levels in children with bacterial gastroenteritis compared to viral gastroenteritis. Fecal IL-6 and IL-8 had significantly elevated levels in children with acute gastroenteritis than in healthy control (p<0.001). The area under the curve (AUC) showed that CRP and serum IL-6 could be used as discriminative markers for acute bacterial gastroenteritis in children, in comparison to serum IL-8. Elevated serum IL-6 and CRP can aid in differentiation between viral and bacterial gastroenteritis. Serum IL-8 had limited discrimination ability between viral and bacterial gastroenteritis. Stool levels of IL-6 and IL-8 were elevated in children with viral and bacterial gastroenteritis, however, their assessment by enzyme linked immunosorbent assay had technical limitations to be used as differentiation biomarkers.


An Update on Novel Taxa and Revised Taxonomic Status of Bacteria Isolated from Domestic Animals Described in 2018 to 2021.
Novel bacterial taxonomy and nomenclature revisions can have significant impacts on clinical practice, disease epidemiology, and veterinary microbiology laboratory operations. Expansion of research on the microbiota of humans, animals, and insects has significant potential impacts on the taxonomy of organisms of clinical interest. Implications of taxonomic changes may be especially important when considering zoonotic diseases. Here, we address novel taxonomy and nomenclature revisions of veterinary significance. Noteworthy discussion centers around descriptions of novel mastitis pathogens in Streptococcaceae, Staphylococcaceae, and Actinomycetaceae; bovine reproductive tract pathogens in Corynebacteriaceae; novel members of Mannheimia spp., Leptospira spp., and Mycobacterium spp.; the transfer of Ochrobactrum spp. to Brucella spp.; and revisions to the genus Mycoplasma.


Analysis of Cervical Angiograms in Cervical Spine Trauma Patients, Does it Make a Difference?
Retrospective review. To evaluate computed tomography angiogram (CTA) use for diagnosing blunt vertebral artery injury (BVAI) at a single institution, to assess the incidence of BVAI in the studied population, and determine if diagnosis affected care. We also wanted to evaluate if testing and treatment resulted in complications. BVAI is an example of a previously underdiagnosed injury. Ease of CTA has simplified vertebral artery evaluation. Injury to the vertebral or carotid arteries is diagnosed in approximately 0.1% of blunt trauma patients when there is high clinical suspicion, or when symptoms of central nervous system damage are apparent on initial examination. Routine screening of asymptomatic patients increases the incidence to approximately 1%. After IRB approval, the hospital trauma registry identified patients aged 18-89 presenting with cervical spine fracture from 2006 to 2011. A retrospective review of charts was completed. Data collection included demographic data, fracture pattern, and neurological findings. The indications for and the results of CTA was also reviewed. The type of treatment and any complications were recorded. A total of 637 charts reviewed. A total of 108 subjects underwent CTA/magnetic resonance angiography; 15 diagnosed with VAI injury. Four received treatment. There were no complications from imaging or treatment of BVAI. Eight subjects without CTA evaluation presented with symptoms potentially related to injury on arrival. Three had neurological decline, although none were eligible for treatment. No routine diagnostic/treatment protocol for vertebral arteries was found at our institution. Although neurological sequelae after VAI can be devastating, routine screening after cervical spine fracture may not be warranted. Beside cost, our study suggests it is rarely associated with symptoms, and the asymptomatic patient rarely receives treatment due to concomitant injuries. Our study reinforces the need for further research to establish protocols so that patient-appropriate, cost-effective evaluation and treatment can be provided.


[Healthcare challenges for people with diabetes during the national state of emergency due to COVID-19 in Lima, Peru: primary healthcare recommendations].
Patients diagnosed with type 2 diabetes mellitus, who then become infected with SARS-CoV-2, are at greater risk of developing complications from COVID-19, which may even lead to death. Diabetes is a chronic condition that requires continuous contact with healthcare facilities; therefore, this type of patients should have regular access to medicines, tests and appointments with healthcare personnel. In Peru, care and treatment continuity have been affected since the national state of emergency due to COVID-19 began; because many healthcare facilities suspended outpatient consultations. The strategies presented in this study were developed by different Peruvian health providers in the pandemic context to ensure care continuity for people with diabetes. This article provides recommendations to strengthen primary healthcare, because it is the first level of healthcare contact for patients with diabetes.


Domestic abuse on women in China before, during, and after pregnancy.
Some researchers found that partner-perpetrated physical violence increased in frequency and severity during the postpartum period compared with the antenatal period, however, limited data exists describing abuse of women in China. The purpose of this study was to examine patterns of abuse in China before, during, and after pregnancy, and explore possible factors related to abuse. A community-based face-to-face survey of a representative group of women who had a child aged 6 to 18 months in 32 communities of Tianjin, Liaoning, Henan, and Shaanxi provinces was carried out between November 1, 2001 and February 28, 2002. The prevalence of domestic abuse (emotional, sexual, or physical) occurring in any period (before, during, or after pregnancy) was 12.6%. The prevalence of abuse during the approximate 9 months of pregnancy (4.3%) was relatively lower compared with the prevalence of abuse during the 12 months before pregnancy (9.1%) and after delivery (8.3%) during the mean 11-month postpartum period studied. Abuse before pregnancy was a strong risk factor for abuse during pregnancy and abuse after pregnancy, and abuse during any previous period was a strong risk factor for subsequent abuse. Many women who suffered abuse of any kind generally experienced multiple acts over time and most acts were not severe. The results of logistic regression analysis showed that the factors associated with abuse during pregnancy included women previously witnessing domestic violence, a poor relationship with the partner, socioeconomic level, alcohol consumption, and smoking. It is necessary to do in-depth training and to raise awareness of partner abuse among all health professionals. Routine screening of abuse in maternity clinics is advocated to decrease the adverse impact of abuse on women and fetuses.


Slow-light-enhanced gain in active photonic crystal waveguides.
Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experimentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers.


An erythroid specific enhancer upstream to the gene encoding the cell-type specific transcription factor GATA-1.
The transcription factor GATA-1 is expressed in a subset of hemopoietic cells, where it mediates the cell-type specific expression of several genes. We have cloned the mouse and human GATA-1 genes. A region upstream to the first exon, and highly conserved between mouse and man, acts as an erythroid specific enhancer in transient assays, if linked to the GATA-1 or to the SV40 promoter. The activity of the enhancer is almost completely dependent on the integrity of a dimeric GATA-1 binding site.


X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution.
The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r = 0.239). Results confirm that the heme is covalently attached to the protein via two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and modified methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has been identified at the amino terminus of the helix containing the proximal His(336). Determination of the x-ray crystal structure of a myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this chloride ion can be replaced by bromide. Bromide is also seen to bind, at partial occupancy, in the distal heme cavity, in close proximity to the distal His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The bromide-binding site in the distal cavity appears to be the halide-binding site responsible for shifts in the Soret band of the absorption spectrum of myeloperoxidase. It is proposed that halide binding to this site inhibits the enzyme by effectively competing with H(2)O(2) for access to the distal histidine, whereas in compound I, the same site may be the halide substrate-binding site.


A dynamic model of tomato fruit growth integrating cell division, cell growth and endoreduplication.
In this study, we developed a model of tomato (Solanum lycopersicum L.) fruit growth integrating cell division, cell growth and endoreduplication. The fruit was considered as a population of cells grouped in cell classes differing in their initial cell age and cell mass. The model describes fruit growth from anthesis until maturation and covers the stages of cell division, endoreduplication and cell growth. The transition from one stage to the next was determined by predefined cell ages expressed in thermal time. Cell growth is the consequence of sugar import from a common pool of assimilates according to the source-sink concept. During most parts of fruit growth, potential cell growth rate increases with increasing cell ploidy and follows the Richards growth function. Cell division or endoreduplication occurs when cells exceed a critical threshold cell mass:ploidy ratio. The model was parameterised and calibrated for low fruit load conditions and was validated for high fruit load and various temperature conditions. Model sensitivity analysis showed that variations in final fruit size are associated with variations in parameters involved in the dynamics of cell growth and cell division. The model was able to accurately predict final cell number, cell mass and pericarp mass under various contrasting fruit load and most of the temperature conditions. The framework developed in this model opens the perspective to integrate information on molecular control of fruit cellular processes into the fruit model and to analyse gene-by-environment interaction effects on fruit growth.


Infant and childhood growth patterns, insulin sensitivity, and blood pressure in prematurely born young adults.
Preterm infants are at increased risk to develop insulin resistance and high blood pressure. The influence of growth during childhood is not well established. We investigated childhood growth patterns in relation to blood pressure and insulin sensitivity, measured by the hyperinsulinemic euglycemic clamp, in young adults. We compared 29 subjects born preterm appropriate for gestational age, 28 subjects born preterm small for gestational age, and 30 subjects born at term with a normal birth weight. Insulin sensitivity expressed as Mi value (glucose disposal mg/kg/min (insulin levels pmol/l) x 100) was lower in infants in the POPS-AGA (18.2) and POPS-SGA (15.2) groups than in the CON group (24.7). Systolic and diastolic blood pressure (mmHg) were higher in infants in the POPS-AGA (132/72) and POPS-SGA (127/71) groups than in the CON group (118/65). The preterm-born subjects, in lowest insulin sensitivity quartile had a higher height standard deviation score at ages 1, 2, and 5 years and a higher weight SD score at ages 2, 5, 10, 19, and 21 years than did those in the lowest insulin sensitivity quartile. The infants in the highest systolic blood pressure quartile had a higher height SD score at 3 months of age and at ages 2, 5, 10, 19, and 21 years and a higher weight SD score at ages 1, 2, 5, 10, 19, and 21 years than those in the lowest systolic blood pressure quartile. Young adults born preterm have lower insulin sensitivity and higher blood pressure than controls. Increments in height and weight during childhood are associated with lower insulin sensitivity and higher blood pressure in adulthood.


IMMUNOLOGICAL AND BIOCHEMICAL STUDIES ON SERUM HAPTOGLOBIN.
Antibody to purified type 1-1 human serum haptoglobin was obtained in rabbits. Using this antiserum it was demonstrated that the antigenic determinants of the haptoglobin molecule reside in both alpha- and beta-chains. No immunological difference between the normal alpha(1F)- and alpha(1S)-chains of haptoglobin could be detected. A number of healthy individuals whose haptoglobin pattern appeared normal by starch gel electrophoresis were shown to possess a haptoglobin which could be distinguished immunologically from the common haptoglobin types. These immunological atypical haptoglobins have been observed in individuals of types 1-1, 2-1, and 2-2. Combined immunological and chemical studies of purified haptoglobin have enabled the construction of a tentative model for the structure of human type 1-1 haptoglobin.


Postsplenectomy type-1 hypersensitivity response: a correlation between IL-4 and IgE serum levels.
Authors demonstrated the presence of allergic manifestations in splenectomized patients following traumatic rupture of this organ. In particular, allergic diathesis, as supported by serum IgE increase, was exclusively found in patients with preserved T helper (h)-2 lymphocyte function. Th-2 function was monitored by measuring serum levels of interleukin (IL)-4, a cytokine involved in IgE synthesis. On the opposite, in splenectomized individuals with a reduced Th-2 function as supported by lower IL-4 serum levels, no IgE increase and allergic manifestations were detectable. On these grounds, authors hypothesize that allergic manifestations may be correlated to splenectomy since its exeresis may favor the persistence of antigens in the blood. Consequentially, in patients with a preserved Th-2 function, antigenic overload may lead to IgE increase and allergy onset.


RAFT polymer cross-coupling with boronic acids.
The ability to modify the thiocarbonylthio end-groups of RAFT polymers is important for applications where an inert or highly functionalised material is required. Here we report a copper promoted cross-coupling reaction between RAFT polymer end-groups and aryl boronic acids. This method gives high conversion to the modified polymers, and is compatible with a wide variety of functional molecules.


More than measurement: practice team experiences of screening for type 2 diabetes.
The feasibility, cost-effectiveness and best means to implement population screening for type 2 diabetes remain to be established. To learn from the experiences of practice staff undertaking a diabetes screening programme in order to inform future screening initiatives. Qualitative analysis of interviews with staff in six general practices in the 'ADDITION-Cambridge' trial; three randomly allocated to intensively manage screen-detected patients and three providing usual care. We conducted semi-structured interviews with seven nurses, four doctors, three health care assistants and four managers. Four researchers analysed the transcripts practice by practice, preparing vignettes and comparing interpretations. Participants commented on a summary report. Each practice team implemented the screening and intervention programme differently, depending on numbers at risk and decisions about staff contributions. Several emphasized the importance of administrative support. As they screened, they extended the reach of the programme, testing patients outside the target group if requested, checking other risk factors, providing health information and following up people with impaired glucose tolerance. Staff felt that patients accepted the screening and subsequent management as any other clinical activity. Although those developing screening programmes attempt to standardize them, primary care teams need to adapt the work to fit local circumstances. Staff need a sense of ownership, training, well-designed information technology systems and protected time. Furthermore, screening is more than measurement; at the individual level, it is a complete health care interaction, requiring individual explanations, advice on health-related behaviour and appropriate follow-up. The UK 'NHS Health Checks' programme should embrace these findings.


Exact simulation of conditioned Wright-Fisher models.
Forward and backward simulations play an increasing role in population genetics, in particular when inferring the relative importance of evolutionary forces. It is therefore important to develop fast and accurate simulation methods for general population genetics models. Here we present an exact simulation method that generates trajectories of an allele׳s frequency in a finite population, as described by a general Wright-Fisher model. The method generates conditioned trajectories that start from a known frequency at a known time, and which achieve a specific final frequency at a known final time. The simulation method applies irrespective of the smallness of the probability of the transition between the initial and final states, because it is not based on rejection of trajectories. We illustrate the method on several different populations where a Wright-Fisher model (or related) applies, namely (i) a locus with 2 alleles, that is subject to selection and mutation; (ii) a locus with 3 alleles, that is subject to selection; (iii) a locus in a metapopulation consisting of two subpopulations of finite size, that are subject to selection and migration. The simulation method allows the generation of conditioned trajectories that can be used for the purposes of visualisation, the estimation of summary statistics, and the development/testing of new inferential methods. The simulated trajectories provide a very simple approach to estimating quantities that cannot easily be expressed in terms of the transition matrix, and can be applied to finite Markov chains other than the Wright-Fisher model.


The relation of chronic diseases to all-cause mortality risk--the Seven Countries Study.
The relation of chronic conditions on all-cause mortality in population samples was studied based on observations from the Seven Countries Study. The objective of this work was to study the risk of death during a 15-year follow-up of middle-aged men in relation to six chronic diseases. Fifteen cohorts of men aged 50-69, totalling 8122 subjects, were examined around 1970 in seven countries: Finland, The Netherlands, Italy, Croatia (former Yugoslavia), Serbia (former Yugoslavia), Greece and Japan. Clinical diagnoses findings were made for coronary heart disease (CHD), 'other heart diseases' (OTH), peripheral arterial disease (PAD), stroke (STR), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DIAB). All-cause mortality was assessed in the subsequent 15 years. Death rates and relative risks were estimated from crude data, and in proportional hazards models after adjustment for age, systolic blood pressure and serum cholesterol level, cigarette smoking and body mass index. Large regional differences were found in the prevalence of the six conditions. Weak relations were found between population prevalence of each disease and population death rates for that disease. Among cohorts the relative risk of death in 15 years from any cause, adjusted for other risk factors, showed little variation among countries. Pooled relative risks, adjusted by the inverse of variance (with 95% CI) were: for CHD, 1.81 (1.60-2.06); for OTH, 1.47 (1.28-1.69); for PAD, 1.64 (1.39-1.93); for STR, 1.56 (1.23-1.98); for COPD, 1.67 (1.48-1.88); and for DIAB, 1.75 (1.43-2.15). The smallest variability of prognosis among countries was found for CHD, OTH and DIAB; the largest for PAD, STR and COPD. Despite simple clinical diagnostic procedures and large differences in prevalence, the relation of established prevalent conditions to subsequent all-cause mortality is relatively uniform among countries and across these conditions, with a relative risk of dying in 15 years usually ranging between 1.5 and 2.0.


Single Nucleotides Moving through Nanoslits Composed of Self-Assembled Monolayers via Equilibrium and Nonequilibrium Molecular Dynamics.
Nonequilibrium molecular dynamics (MD) simulations were used to study the effect of three chemical surface groups on the separation of DNA mononucleotide velocity (or time-of-flight) distributions as they pass through nanoslits. We used nanoslits functionalize with self-assembled monolayers (SAMs) since they have relatively smooth surfaces. The SAM molecules were terminated with either a methyl, methylformyl, or phenoxy group, and the nucleotides were driven electrophoretically with an electric field intensity of 0.1 V/nm in slits about 3 nm wide. Although these large driving forces are physically difficult to achieve experimentally, the simulations are still of great value as they provide molecular level insight into nucleotide translocation events and allow comparison of different surfaces. Nucleotides adsorbed and desorbed from the slit surface multiple times during the simulations. The required slit length for 99% accuracy in identifying the deoxynucleotide monophosphates (dNMPs), based on the separation of the distributions of time of flight, was used to compare the surfaces with shorter lengths indicating more efficient separation. The lengths were 6.5 μm for phenoxy-terminated SAMs, 270 μm for methylformyl-terminated SAMs, and 2400 μm for methyl-terminated SAMs. Our study showed that a slit with a section with methyl termination and the second section with methylformyl termination lead to a required length of 120 μm, which was significantly lower than for only a methylformyl- or methyl-terminated surface.