The "fire stick farming" hypothesis: Australian Aboriginal foraging strategies, biodiversity, and anthropogenic fire mosaics.
Aboriginal burning in Australia has long been assumed to be a "resource management" strategy, but no quantitative tests of this hypothesis have ever been conducted. We combine ethnographic observations of contemporary Aboriginal hunting and burning with satellite image analysis of anthropogenic and natural landscape structure to demonstrate the processes through which Aboriginal burning shapes arid-zone vegetational diversity. Anthropogenic landscapes contain a greater diversity of successional stages than landscapes under a lightning fire regime, and differences are of scale, not of kind. Landscape scale is directly linked to foraging for small, burrowed prey (monitor lizards), which is a specialty of Aboriginal women. The maintenance of small-scale habitat mosaics increases small-animal hunting productivity. These results have implications for understanding the unique biodiversity of the Australian continent, through time and space. In particular, anthropogenic influences on the habitat structure of paleolandscapes are likely to be spatially localized and linked to less mobile, "broad-spectrum" foraging economies.


Socially induced inhibition of genetically determined maturation in the platyfish, Xiphophorus maculatus.
Maturation in Xiphophorus maculatus (Pisces; Poeciliidae) is under control of the sex-linked P gene. However, when two individuals are reared together the socially dominant individual delays the maturation of the subordinate. Nevertheless, it is not a requirement that a fish be socially dominant to become mature. The data suggest that inhibition of maturity takes place when an individual is not dominant at a time near the genetically determined age of maturation. Two hypotheses are offered to explain these results.


The Russian Aphasia Test: The first comprehensive, quantitative, standardized, and computerized aphasia language battery in Russian.
The lack of standardized language assessment tools in Russian impedes clinical work, evidence-based practice, and research in Russian-speaking clinical populations. To address this gap in assessment of neurogenic language disorders, we developed and standardized a new comprehensive assessment instrument-the Russian Aphasia Test (RAT). The principal novelty of the RAT is that each subtest corresponds to a specific level of linguistic processing (phonological, lexical-semantic, syntactic, and discourse) in different domains: auditory comprehension, repetition, and oral production. In designing the test, we took into consideration various (psycho)linguistic factors known to influence language performance, as well as specific properties of Russian. The current paper describes the development of the RAT and reports its psychometric properties. A tablet-based version of the RAT was administered to 85 patients with different types and severity of aphasia and to 106 age-matched neurologically healthy controls. We established cutoff values for each subtest indicating deficit in a given task and cutoff values for aphasia based on the Receiver Operating Characteristic curve analysis of the composite score. The RAT showed very high sensitivity (> .93) and specificity (> .96), substantiating its validity for determining presence of aphasia. The test's high construct validity was evidenced by strong correlations between subtests measuring similar linguistic processes. The concurrent validity of the test was also strong as demonstrated by a high correlation with an existing aphasia battery. Overall high internal, inter-rater, and test-retest reliability were obtained. The RAT is the first comprehensive aphasia language battery in Russian with properly established psychometric properties. It is sensitive to a wide range of language deficits in aphasia and can reliably characterize individual profiles of language impairments. Notably, the RAT is the first comprehensive aphasia test in any language to be fully automatized for administration on a tablet, maximizing further standardization of presentation and scoring procedures.


Demonstrating empathy when communicating with older people.
Empathy is an integral aspect of communication with older people and is central to person-centred care. As part of the provision of person-centred care, empathy supports effective communication, producing positive effects such as increased emotional well-being, increased adherence to treatment plans, reduced pain levels and improved wound healing. Empathy involves attempting to understand the other person's perspective and feelings and communicate that understanding back to them. Empathic communication can help older people feel that they are being listened to and valued as partners in healthcare relationships. This article focuses on why it is important to demonstrate empathy when communicating with older people and how this can be achieved. It explains the origin of the concept of empathy in nursing and provides different ways of characterising empathy. It explores barriers to empathic communication in older people nursing and identifies verbal and non-verbal communication skills that nurses can use to enhance their empathy. Finally, it explains the importance for nurses to develop self-awareness and undertake self-care to preserve their capacity to demonstrate empathy towards older people.


Dose-response characteristics of a ferrous-sulphate-doped gelatin system for determining radiation absorbed dose distributions by magnetic resonance imaging (Fe MRI).
The nuclear magnetic resonance (NMR) longitudinal relaxation rate R1 dose-response characteristics of a ferrous-sulphate-doped chemical dosimeter system (Fe MRI) immobilized in a gelatin matrix were explored. Samples containing various concentrations of the FeSO4 dosimeter were irradiated to absorbed doses of 0-150 Gy. R1 relaxation rates were determined by imaging the samples at a field strength of 1.5T(1H Lamor frequency of 63.8 MHz). The response of the system was found to be approximately linear up to doses of 50 Gy for all FeSO4 concentrations studied (0.1-2.0 mM). Changing concentrations in the range of 0.1-0.5 mM affected both the slope and intercept of the dose-response curve. For concentrations of 0.5-2.0 mM, the slope of the dose-response curves remained constant at approximately 0.0423 s-1 Gy-1 in the dose range of 0-50 Gy. However, the intercept of the curve continued to increase in that region, as expected, because of the additional paramagnetic ions. The reproducibility of the absorbed dose estimates for measurements made over a 22 cm field of view was found to be 5% in the range of 20-50 Gy (an uncertainty of 0.81 Gy on average), decreasing to approximately 10% in the dose range of 5-10 Gy.


A Long Preoperative Duration of Symptoms Is Associated With Worse Functional Outcomes After 1-Stage Arthroscopic Treatment of Rotator Cuff Tears With Shoulder Stiffness.
Rotator cuff tears with shoulder stiffness remain a difficult issue. Despite the reported satisfactory results of 1-stage surgery, little information is available regarding the factors that affect clinical outcomes. Purpose/Hypothesis: To evaluate the 1-stage arthroscopic treatment of rotator cuff tears with shoulder stiffness and to present the influence of duration of symptoms (DOS) on postoperative functional outcomes. The hypothesis was that a long preoperative DOS is related to worse functional outcomes. A long preoperative DOS is related to worse functional outcomes. Cohort study; Level of evidence, 2. A cohort study was performed with consecutive patients who underwent 1-stage surgery between January 2012 and July 2014. Forty-four patients were enrolled in the long DOS group (DOS ≥6 months or LDOS), and 38 were enrolled in the short DOS group (DOS <6 months or SDOS). There were no significant differences in the other variables between the groups. The patients were followed for a mean of 33.8 months, and the functional and radiographic outcomes were compared. Both groups achieved apparent functional postoperative improvements in terms of range of motion, pain, strength, and functional scores ( P < .001 for all). Despite the overall improvements, the patients in the SDOS group had significantly better outcomes according to all functional instruments. The mean postoperative abduction and external rotation at the side in the SDOS group were higher than in the LDOS group (abduction: 162.2° vs 152.8°, respectively [ P = .002]; external rotation: 64.7° vs 56.9°, respectively [ P = .004]). The mean postoperative functional scores in the SDOS group were all higher than in the LDOS group (American Shoulder and Elbow Surgeons [ASES] score: 91.1 vs 81.9, respectively; Constant-Murley score: 76.9 vs 71.8, respectively; Fudan University Shoulder Score [FUSS], 90.6 vs 81.1, respectively), and the mean postoperative visual analog scale (VAS) score for pain in the SDOS group was lower (0.7 vs 1.8, respectively) ( P < .001 for all). The difference in the retear rates was not significant, with 7 retears in the SDOS group and 4 in the LDOS group ( P = .216). One-stage surgery effectively achieved overall improvements. A preoperative DOS of ≥6 months led to poorer functional outcomes, which suggests that surgeons should propose a surgical treatment for this condition before symptoms persist for 6 months.


Effects of maternal exposure to di-(2-ethylhexyl) phthalate during fetal and/or neonatal periods on atopic dermatitis in male offspring.
Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and is ubiquitous in developed countries. Although maternal exposure to DEHP during fetal and/or neonatal periods reportedly affects reproductive and developmental systems, its effects on allergic diseases in offspring remain to be determined. In the present study, we examined whether maternal exposure to DEHP during fetal and/or neonatal periods in NC/Nga mice affects atopic dermatitis-like skin lesions related to mite allergen in offspring. We administered DEHP at a dose of 0, 0.8, 4, 20, or 100 microg/animal/week by intraperitoneal injection into dams during pregnancy (gestation days 0, 7, and 14) and/or lactation (postnatal days 1, 8, and 15). Eight-week-old male offspring of these treated females were injected intradermally with mite allergen into their right ears. We then evaluated clinical scores, ear thickening, histologic findings, and protein expression of eotaxin in the ear. Maternal exposure to a 100-microg dose of DEHP during neonatal periods, but not during fetal periods, enhanced atopic dermatitis-like skin lesions related to mite allergen in males. The results were concomitant with the enhancement of eosinophilic inflammation, mast cell degranulation, and protein expression of eotaxin in overall trend. Maternal exposure to DEHP during neonatal periods can accelerate atopic dermatitis-like skin lesions related to mite allergen in male offspring, possibly via T helper 2 (T(H)2)-dominant responses, which can be responsible, at least in part, for the recent increase in atopic dermatitis.


Uptake of homologous single-stranded fragments by superhelical DNA: a possible mechanism for initiation of genetic recombination.
Superhelical [3-H]DNA (replicative form I, RFI) of bacteriophage phiX174 slowly but spontaneously took up 32-P-labeled homologous single-stranded fragments at 4 degrees. Uptake was accelerated by heating to 75 degrees. RFI did not take up single-stranded fragments derived from DNA of Escherichia coli or from separated strands of phage lambda. Uptake was inhibited by low concentrations of ethidium bromide. Relaxed circular phiX174 DNA did not take up homologous fragments. Per molecule of RFI, the complexes contained as much as 90 nucleotide residues of homologous fragment. The 32-P-lebeled fragments were largely resistant to digestion by exonuclease I, and were not displaced by heating complexes at 60 degrees for 1 min in 16 mM or 100 mM NaCl. Under comparable conditions of temperature and salt all of the fragments were displaced from complexes in which at least one phosphodiester bond was cleaved by pancreatic DNase, but a significant fraction of the fragments was retained in complexes that were relaxed by digestion with S1 nuclease. These observations are interpreted to mean that S1 nuclease digested the plus (viral) strand of the recipient RF at the site of uptake in some instances. Transfection of E. coli by heterozygous complexes produced recombinant progeny, thereby showing that genetic information can be transferred from the fragment of plus strand to progeny plus strands. We propose that both uptake of a third strand by superhelical DNA and the action of nucleases on the resulting complex may simulate early steps in genetic recombination.


Secretory expression of the human serum albumin gene in the yeast, Saccharomyces cerevisiae.
We have fused a cDNA gene encoding mature human serum albumin (HSA) to several secretory leader-encoding sequences. The hybrid genes were cloned into an episomal vector under the control of several yeast promoters and then introduced into yeast cells. The GAL1 promoter in combination with either the native HSA pre-sequence or a modified HSA pre-sequence gave the highest production of immunoreactive HSA, 90 mg/liter being reached in a shake flask culture. The invertase pre-sequence, the mating factor alpha 1 prepro-sequence, and the modified HSA pre-sequence directed accurate processing. In contrast, the chicken lysozyme pre-sequence and the native HSA pre-sequence directed incorrect processing. Episomal vectors were unstable within the host cells under non-selective culture conditions. To improve the plasmid stability, the hybrid genes were incorporated into an integrative vector. Transformants carrying multicopies of the plasmid integrated at the LEU2 locus stably secreted HSA. The highest yield of 65 mg/liter in a shake flask culture was obtained with the combination of the yeast glyceraldehyde-3-phosphate dehydrogenase promoter and the modified HSA pre-sequence. By constructing transformed strains containing multicopies of plasmids integrated at both the chromosome LEU2 and HIS4 loci, we have obtained a stable strain that continuously secretes as much as 85 mg HSA per liter of culture medium.


[Recurrence after intestinal resection for Crohn's disease].
Although recurrence is one of the major problems in the surgical management of a patient with Crohn disease, the factors that influence recurrence rate remain controversial. To elucidate some of this controversy, the records of a consecutive series of 100 patients, who underwent resectional surgery for Crohn's disease, were analyzed to evaluate the effect of several clinical and histologic features on the recurrence rate. In this study, recurrence was defined as clinical and or laboratory findings of re-emergent disease confirmed by objective means after resection of all lesions. Recurrence rate seems lower in colitis than ileitis or ileocolitis, but this data did not reach statistic significance; the site of recurrence was conditioned by the initial location of the disease and the extent of resection into healthy tissue above and below the lesions and the histological findings of section lines did not modify the risk of recurrence. In conclusion the recurrence is almost inevitable. The multifactorial aspect of the recurrence cannot be ignored, however some clinical factors were more closely related to the recurrence. A part from Crohn's colitis, type of surgery (radical vs limited resection) had little chance of minimizing the risk of recurrence.


[Social contact and depression in geriatric patients: is there an influence of gender?].
Depression is one of the most common affective illnesses. The investigation of changeable factors that are associated with depression is an important condition for the establishment of preventive measures. In a cross-sectional study, data on social factors were recorded from 580 geriatric patients of the municipal hospital in Munich. Ordinal logistic regression was used to analyse their association with depression (clinical diagnoses by ICD-10) and depressive symptoms (GDS). The results indicate that the occurrence of depressive symptoms and of depression was associated with less social contacts and less support, even after adjustment for other risk factors (for example, physical and cognitive impairment). This association was more distinct for women (for example, depressive symptoms: moderate versus much contact: OR=2.7; 95% CI: 1.8-4.1) than for men (OR=1.3; 95% CI: 0.7-2.4). Further research is needed to investigate whether women could benefit more than men from programmes promoting social support.


Yeast wall protein 1 of Candida albicans.
Yeast wall protein 1 (Ywp1, also called Pga24) of Candida albicans is predicted to be a 533 aa polypeptide with an N-terminal secretion signal, a C-terminal glycosylphosphatidylinositol anchor signal and a central region rich in serine and threonine. In yeast cultures, Ywp1p appeared to be linked covalently to glucans of the wall matrix, but, as cultures approached stationary phase, Ywp1p accumulated in the medium and was extractable from cells with disulfide-reducing agents. An 11 kDa propeptide of Ywp1p was also present in these soluble fractions; it possessed the sole N-glycan of Ywp1p and served as a useful marker for Ywp1p. DNA vaccines encoding all or part of Ywp1p generated analytically useful antisera in mice, but did not increase survival times for disseminated candidiasis. Replacement of the coding sequence of YWP1 with the fluorescent reporter GFP revealed that expression of YWP1 is greatest during yeast exponential-phase growth, but downregulated in stationary phase and upon filamentation. Expression was upregulated when the extracellular phosphate concentration was low. Disruption by homologous recombination of both YWP1 alleles resulted in no obvious change in growth, morphology or virulence, but the Ywp1p-deficient blastoconidia exhibited increased adhesiveness and biofilm formation, suggesting that Ywp1p may promote dispersal of yeast forms of C. albicans.


Neonatal Cholestasis: A Pandora's Box.
Neonatal cholestasis (NC) is a diagnostic dilemma frequently countered in a neonatal care unit. Early diagnosis is vital for achieving an optimal patient outcome as many causes of cholestasis such as biliary atresia are time-sensitive and amenable to treatment if analyzed and treated early. Nonetheless, it is not generally simple to analyze these cases right on time as some of them are regularly missed due to the presence of pigmented stools, lack of newborn metabolic screening, and named as instances of prolonged jaundice. In this manner, we prescribe to explore all reasons for prolonged jaundice stretching out past 14 days in neonates. Besides, we suggest that stool card ought to be a piece of release rundown for all newborn children being released from the nursery. This is of most extreme significance in the nation like India where guaranteeing customary follow-up is as yet a tough assignment. These stool cards will help in the early determination of patients with NC particularly biliary atresia and guarantee their auspicious cure. Another reason which needs exceptional say is parenteral nutrition-associated liver illness, as the proportion of preterm babies is getting greater and greater with better neonatal care. These extreme preterm infants are in the requirement for prolonged (>14 days) total parenteral nourishment because of which they are at high hazard for NC contrasted with their more developed peers. In this survey, we will give an understanding of clinical approach, differential diagnosis, and clinical review of NC.


Primary cardiac amyloidosis: A review of the literature.
A review of the literature on primary cardiac amyloidosis is presented. Its differentiation from constrictive pericarditis, both on clinical and haemodynamic grounds, is outlined. The importance of antemortem endomyocardial biopsy in establishing a definitive diagnosis of this relatively rare condition is stressed. Finally, an updated overview of the classification and immunological pathogenesis of this disease is given.


Green light powered molecular state motor enabling eight-shaped unidirectional rotation.
Molecular motors convert external energy into directional motions at the nano-scales. To date unidirectional circular rotations and linear motions have been realized but more complex directional trajectories remain unexplored on the molecular level. In this work we present a molecular motor powered by green light allowing to produce an eight-shaped geometry change during its unidirectional rotation around the central molecular axis. Motor motion proceeds in four different steps, which alternate between light powered double bond isomerizations and thermal hula-twist isomerizations. The result is a fixed sequence of populating four different isomers in a fully unidirectional trajectory possessing one crossing point. This motor system opens up unexplored avenues for the construction and mechanisms of molecular machines and will therefore not only significantly expand the toolbox of responsive molecular devices but also enable very different applications in the field of miniaturized technology than currently possible.


Revision total hip and knee arthroplasty implant identification: implications for use of Unique Device Identification 2012 AAHKS member survey results.
FDA's Unique Device Identification (UDI) Rule will mandate manufacturers to assign unique identifiers to their marketed devices. UDI use is expected to improve implant documentation and identification. A 2012 American Association of Hip and Knee Surgeons membership survey explored revision total hip and knee arthroplasty implant identification processes. 87% of surgeons reported regularly using at least 3 methods to identify failed implants pre-operatively. Median surgeon identification time was 20 min; median staff time was 30 min. 10% of implants could not be identified pre-operatively. 2% could not be identified intra-operatively. UDI in TJA registry and UDI in EMR were indicated practices to best support implant identification and save time. FDA's UDI rule sets the foundation for UDI use in patient care settings as standard practice for implant documentation.


Dialytic interval and the timing of electrocardiographic screening for subcutaneous cardioverter-defibrillator placement in chronic hemodialysis patients.
Hemodialysis (HD) patients have a high risk of sudden death but limited vascular access and high complication rates from transvenous implantable cardioverter-defibrillators (ICDs). Subcutaneous ICDs (S-ICD) may be an alternative, but dynamic ECG changes may result in inappropriate shocks. This study aims to define the screen failure rate for S-ICD in patients pre- and post-HD. ECG waveforms were obtained using electrodes mimicking the S-ICD sensing vectors in an unselected test group of chronic HD patients and a control group of ICD-eligible non-dialysis patients. Participants passed screening if their QRS and T-waves fit within the screening template in supine and standing positions in any lead. Test group participants were screened before and after HD and control group patients were screened at two separate time points. HD patients were stratified into the four following groups: (A) passed screening before and after HD, (B) failed screening before but passed after HD, (C) passed screening before but failed after HD, and (D) failed screening before and after HD. Patients in group A passed the screening for ICD implantation, and patients in groups B, C, and D failed the screening for ICD implantation. Control patients were similarly classified by pass/fail status at the two assessment points. Of the 76 patients enrolled, 51 were HD patients and 25 were controls. Of the 51 HD patients, 43 (84%) were in group A, four participants (8%) were in group B, one (2%) was in group C, and three participants (6%) were in group D. There were no differences in any of the clinical or demographic variables between the pass and fail test HD groups. None of the 25 controls failed the screening at either time point (p = 0.047 vs HD patients). Overall, HD patients were more likely to fail S-ICD screening compared to non-HD patients (16 v 0%, p = 0.047) and are more likely to do so prior to HD. Patients on HD should be screened at multiple time points around the dialytic interval to reduce the risk of inappropriate shocks.


Phenotypic factor analysis of psychopathology reveals a new body-related transdiagnostic factor.
Comorbidity challenges the notion of mental disorders as discrete categories. An increasing body of literature shows that symptoms cut across traditional diagnostic boundaries and interact in shaping the latent structure of psychopathology. Using exploratory and confirmatory factor analysis, we reveal the latent sources of covariation among nine measures of psychopathological functioning in a population-based sample of 13024 Finnish twins and their siblings. By implementing unidimensional, multidimensional, second-order, and bifactor models, we illustrate the relationships between observed variables, specific, and general latent factors. We also provide the first investigation to date of measurement invariance of the bifactor model of psychopathology across gender and age groups. Our main result is the identification of a distinct "Body" factor, alongside the previously identified Internalizing and Externalizing factors. We also report relevant cross-disorder associations, especially between body-related psychopathology and trait anger, as well as substantial sex and age differences in observed and latent means. The findings expand the meta-structure of psychopathology, with implications for empirical and clinical practice, and demonstrate shared mechanisms underlying attitudes towards nutrition, self-image, sexuality and anger, with gender- and age-specific features.


Maintaining a high physical activity level over 20 years and weight gain.
Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs. To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-1986 to 2005-2006. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multicenter cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline. Average annual changes in BMI and waist circumference. Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (0.15 BMI units per year; 95% confidence interval [CI], 0.11-0.18 vs 0.20 in the lower activity group; 95% CI, 0.17-0.23), and women maintaining higher activity gained 6.1 fewer kilograms (0.17 BMI units per year; 95% CI, 0.12-0.21 vs 0.30 in the lower activity group; 95% CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (0.52 cm per year; 95% CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95% CI,0.60-0.75 cm) and women maintaining higher activity gained 3.8 fewer centimeters(0.49 cm per year; 95% CI, 0.39-0.58 cm vs 0.67 cm in the lower activity group; 95% CI, 0.60-0.75 cm) [corrected]. Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.


Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures.
Aging has less effect on adipose-derived mesenchymal stem cells (ADSCs) than on bone marrow-derived mesenchymal stem cells (BMSCs), but whether the fact holds true in stem cells from elderly patients with osteoporotic fractures is unknown. In this study, ADSCs and BMSCs of the same donor were harvested and divided into two age groups. Group A consisted of 14 young patients (36.4 ± 11.8 years old), and group B consisted of eight elderly patients (71.4 ± 3.6 years old) with osteoporotic fractures. We found that the doubling time of ADSCs from both age groups was maintained below 70 hrs, while that of BMSCs increased significantly with the number of passage. When ADSCs and BMSCs from the same patient were compared, there was a significant increase in the doubling time of BMSCs in each individual from passages 3 to 6. On osteogenic induction, the level of matrix mineralization of ADSCs from group B was comparable to that of ADSCs from group A, whereas BMSCs from group B produced least amount of mineral deposits and had a lower expression level of osteogenic genes. The p21 gene expression and senescence-associated β-galactosidase activity were lower in ADSCs compared to BMSCs, which may be partly responsible for the greater proliferation and differentiation potential of ADSCs. It is concluded that the proliferation and osteogenic differentiation of ADSCs were less affected by age and multiple passage than BMSCs, suggesting that ADSCs may become a potentially effective therapeutic option for cell-based therapy, especially in elderly patients with osteoporosis.


Effect of hyaluronic acid on intraocular pressure in rats.
To study the effect of acute or chronic intracameral injection of hyaluronic acid on intraocular pressure (IOP) in rats. Acute or chronic injections of hyaluronic acid were performed unilaterally in the rat eye's anterior chamber, whereas the contralateral eye was injected with saline solution. IOP was assessed daily or weekly by a tonometer in conscious rats. IOP was also assessed in both experimental groups at several intervals during the light-dark cycle. A single injection of hyaluronic acid induced an increase of IOP that lasted for 8 days (P < 0.01), whereas its chronic administration during 9 weeks induced a significant and sustained increase in IOP, compared with the eye injected with vehicle (P < 0.01). This hyaluronic acid-induced hypertension was significantly decreased by the application of 1 drop of brimonidine (0.2%), latanoprost (0.005%), or timolol (0.5%). Significant daily variations of IOP were observed in both control and hyaluronic acid-injected eyes, peaking during the dark phase (P < 0.001, ANOVA). These results suggest that the intracameral administration of hyaluronic acid could be a model of ocular hypertension in rats.


The effect of prosthetic mass properties on the gait of transtibial amputees--a mathematical model.
Present models in the literature, predicting that prostheses should not be too lightweight, are not supported by empirical evidence. Recent studies suggest that these models are incorrectly based on the assumption that the swing phase is uninfluenced by muscle activity. The purpose of the present study was to introduce a new mathematical model to predict the effect of mass properties on the gait of transtibial amputees, based on experimental findings that subjects adapt to mass perturbations by maintaining the same joint kinematics. Effect of mass perturbations on the lower leg was evaluated in terms of muscular cost and forces between stump and socket, using a linked-segment model of the swing phase. Gait analysis and anthropometric data from 10 transtibial amputees were used as model input. Location of perturbation strongly influenced the muscular cost. Cost generally increased after distally adding mass but decreased after proximally adding mass to the lower leg. Stump-socket interface forces always increased after mass addition. A new model was introduced, predicting that the weight of distally located components (e.g. foot, ankle, shoe) strongly influence the estimated muscular cost, in contrast to proximal components. A comparison with experimental literature suggests this new model better describes the experimental data than existing models.


CT urography: definition, indications and techniques. A guideline for clinical practice.
The aim was to develop clinical guidelines for multidetector computed tomography urography (CTU) by a group of experts from the European Society of Urogenital Radiology (ESUR). Peer-reviewed papers and reviews were systematically scrutinized. A summary document was produced and discussed at the ESUR 2006 and ECR 2007 meetings with the goal to reach consensus. True evidence-based guidelines could not be formulated, but expert guidelines on indications and CTU examination technique were produced. CTU is justified as a first-line test for patients with macroscopic haematuria, at high-risk for urothelial cancer. Otherwise, CTU may be used as a problem-solving examination. A differential approach using a one-, two- or three-phase protocol is proposed, whereby the clinical indication and the patient population will determine which CTU protocol is employed. Either a combined nephrographic-excretory phase following a split-bolus intravenous injection of contrast medium, or separate nephrographic and excretory phases following a single-bolus injection can be used. Lower dose (CTDIvol 5-6 mGy) is used for benign conditions and normal dose (CTDIvol 9-12 mGy) for potential malignant disease. A low-dose (CTDIvol 2-3 mGy) unenhanced series can be added on indication. The expert-based CTU guidelines provide recommendations to optimize techniques and to unify the radiologist's approach to CTU.


Uncoupling histone turnover from transcription-associated histone H3 modifications.
Transcription in eukaryotes is associated with two major changes in chromatin organization. Firstly, nucleosomal histones are continuously replaced by new histones, an event that in yeast occurs predominantly at transcriptionally active promoters. Secondly, histones become modified post-translationally at specific lysine residues. Some modifications, including histone H3 trimethylation at lysine 4 (H3K4me3) and acetylation at lysines 9 (H3K9ac) and 14 (H3K14ac), are specifically enriched at active promoters where histones exchange, suggesting a possible causal relationship. Other modifications accumulate within transcribed regions and one of them, H3K36me3, is thought to prevent histone exchange. Here we explored the relationship between these four H3 modifications and histone turnover at a few selected genes. Using lysine-to-arginine mutants and a histone exchange assay, we found that none of these modifications plays a major role in either promoting or preventing histone turnover. Unexpectedly, mutation of H3K56, whose acetylation occurs prior to chromatin incorporation, had an effect only when introduced into the nucleosomal histone. Furthermore, we used various genetic approaches to show that histone turnover can be experimentally altered with no major consequence on the H3 modifications tested. Together, these results suggest that transcription-associated histone turnover and H3 modification are two correlating but largely independent events.


Direct writing electrodes using a ball pen for paper-based point-of-care testing.
The integration of paper with an electrochemical device has attracted growing attention for point-of-care testing, where it is of great importance to fabricate electrodes on paper in a low-cost, easy and versatile way. In this work, we report a simple strategy for directly writing electrodes on paper using a pressure-assisted ball pen to form a paper-based electrochemical device (PED). This method is demonstrated to be capable of fabricating electrodes on paper with good electrical conductivity and electrochemical performance, holding great potential to be employed in point-of-care applications, such as in human health diagnostics and food safety detection. As examples, the PEDs fabricated using the developed method are applied for detection of glucose in artificial urine and melamine in sample solutions. Furthermore, our developed strategy is also extended to fabricate PEDs with multi-electrode arrays and write electrodes on non-planar surfaces (e.g., paper cup, human skin), indicating the potential application of our method in other fields, such as fabricating biosensors, paper electronics etc.


Mallory-Denk body pathogenesis revisited.
This editorial reviews the recent evidence showing that Mallory-Denk bodies (MDBs) form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation. The shift is the result of changes in gene expression induced in promoter activation, which is induced by the IFNγ and TNFα signaling pathway. This activates TLR 2 and 4 receptors. The TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth factors. The MDB- forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDB- forming cells, which selectively proliferate in response to drug toxicity. All of these mechanisms are induced by drug toxicity, and are prevented by feeding the methyl donors SAMe and betaine, supporting the epigenetic response of MDB formation.


Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells.
The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs. adherent conditions. In the present study, an ES cell line derived from an Atoh1-green fluorescent protein (GFP) transgenic mouse was used to track the generation of otic progenitors, initial HCs and to compare these two differentiation systems. We used a two-step short-term differentiation method involving an induction period of 5 days during which ES cells were cultured in the presence of Wnt/transforming growth factor TGF-β inhibitors and insulin-like growth factor IGF-1 to suppress mesoderm and reinforce presumptive ectoderm and otic lineages. The generated embryoid bodies were then differentiated in medium containing basic fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture methods. Upon completion of differentiation, quantitative polymerase chain reaction analysis and immunostaining monitored the expression of otic/HC progenitor lineage markers. The results indicate that cells differentiated in suspension cultures produced cells expressing otic progenitor/HC markers at a higher efficiency compared with the production of these cell types within adherent cultures. Furthermore, we demonstrated that a fraction of these cells can incorporate into ototoxin-injured mouse postnatal cochlea explants and express MYO7A after transplantation. Copyright © 2016 John Wiley & Sons, Ltd.


[What is the cerebral amygdaloid complex?].
The amygdaloid complex (AC) is considered to be one the basal nuclei of the telencephalon. However, a combination of two principals of the grey substance organizations--nuclear and shielded--in its territory, distinguished AC from the group of the subcortical nuclei defines its specific position among other structures of the telencephalon. A peculiar structure of AC is a consequence of certain evolutionary rearrangements of the brain in the process of histological development of organisms; principally important among them is appearance of the ancient cortex formations (++semi-separated) from elements of the ganglionic tubercle. The latter explains existence of tight anatomical and functional connections between typical nuclei and the ancient cortex structures. The new notion of the AC substrate as a specific nucleolar-paleocortical integrative center of the telencephalon gives a clue for understanding a number of specific, still remaining enigmatic functional phenomena in this formation. They evidently reflect a close interaction of its nuclei and paleocortical structures, that makes the base of its activity.


Time Trend and Demographic and Geographic Disparities in Childhood Obesity Prevalence in China-Evidence from Twenty Years of Longitudinal Data.
Childhood overweight and obesity (ow/ob) has become a serious threat to many countries, including China. However, limited evidence was obtained from longitudinal data in China. This study examined the secular trends and geographic variation in the prevalence of ow/ob and obesity only, and age, gender, and urban-rural disparities among school-aged children across China. Data from children aged 6-17 surveyed in China Health and Nutrition Survey (CHNS) from 1991 (n = 2712) to 2011 (n = 1054) were used. Overweight and obesity were defined based on the International Obesity Task Force (IOTF) recommended Asian age-sex-specific BMI cut-off-points. We found that: (1) childhood ow/ob and obesity prevalence increased from 11.7% to 25.2% and from 2.8% to 10.1% during 1991-2011, respectively; (2) children aged 6-12 experienced a 1.3 and 1.6 times increase in ow/ob and obesity prevalence than children aged 13-17, respectively; (3) the urban-rural gap in ow/ob prevalence widened; (4) ow/ob prevalence in boys was higher and increased faster than in girls, especially in an urban setting; and (5) geographic variation was observed with faster increases in more economically developed east, central and northeast regions than in the less developed west. The findings added more nuances to the picture of temporal changes in ow/ob prevalence among Chinese children.


Acupressure at the Meridian Acupoint Xiyangguan (GB33) Influences Near-Infrared Spectroscopic Parameters (Regional Oxygen Saturation) in Deeper Tissue of the Knee in Healthy Volunteers.
Up to now, it is still unknown whether microcirculation of deeper peripheral tissue (knee) can be modulated by acupuncture or acupressure on a meridian acupoint. The goal of this pilot study was to investigate possible effects of acupressure at the Xiyangguan acupoint (GB33) on the regional oxygen saturation of the deeper knee tissues by near-infrared spectroscopy (NIRS). Twelve healthy volunteers with a mean age of 23.8 ± 1.6 years were investigated. Acupressure stimulation was performed for 5 minutes at the Xiyangguan acupoint. The results of the controlled study showed a significant increase of the values of regional oxygen saturation on the stimulated side of the knee (P = 0.033), whereas the opposite side on the same knee showed insignificant changes. These results may serve as a valuable basis for monitoring a possible therapeutic effect (e.g., after Khalifa therapy) in patients with knee problems.


A quarter century of reaping what we SOE.
Gene Splicing by Overlap Extension (SOE), described in a BioTechniques Research Report 23 years ago, is still widely used today in spite of changes in technology and scientific fashion. The history of SOE offers practical lessons for those who seek the best techniques, and for those who strive to develop them.


Model based on COVID-19 evidence to predict and improve pandemic control.
Based on the extensive data accumulated during the COVID-19 pandemic, we put forward simple to implement indicators, that should alert authorities and provide early warnings of an impending sanitary crisis. In fact, Testing, Tracing, and Isolation (TTI) in conjunction with disciplined social distancing and vaccination were expected to achieve negligible COVID-19 contagion levels; however, they proved to be insufficient, and their implementation has led to controversial social, economic and ethical challenges. This paper focuses on the development of simple indicators, based on the experience gained by COVID-19 data, which provide a sort of yellow light as to when an epidemic might expand, despite some short term decrements. We show that if case growth is not stopped during the 7 to 14 days after onset, the growth risk increases considerably, and warrants immediate attention. Our model examines not only the COVID contagion propagation speed, but also how it accelerates as a function of time. We identify trends that emerge under the various policies that were applied, as well as their differences among countries. The data for all countries was obtained from ourworldindata.org. Our main conclusion is that if the reduction spread is lost during one, or at most two weeks, urgent measures should be implemented to avoid scenarios in which the epidemic gains strong impetus.


Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder.
The synthesis and structure-activity relationship of a novel series of compounds with combined effects on 5-HT(3A) and 5-HT(1A) receptors and on the serotonin (5-HT) transporter (SERT) are described. Compound 5m (Lu AA21004) was the lead compound, displaying high affinity for recombinant human 5-HT(1A) (K(i) = 15 nM), 5-HT(1B) (K(i) = 33 nM), 5-HT(3A) (K(i) = 3.7 nM), 5-HT(7) (K(i) = 19 nM), and noradrenergic β(1) (K(i) = 46 nM) receptors, and SERT (K(i) = 1.6 nM). Compound 5m displayed antagonistic properties at 5-HT(3A) and 5-HT(7) receptors, partial agonist properties at 5-HT(1B) receptors, agonistic properties at 5-HT(1A) receptors, and potent inhibition of SERT. In conscious rats, 5m significantly increased extracellular 5-HT levels in the brain after acute and 3 days of treatment. Following the 3-day treatment (5 or 10 (mg/kg)/day) SERT occupancies were only 43% and 57%, respectively. These characteristics indicate that 5m is a novel multimodal serotonergic compound, and 5m is currently in clinical development for major depressive disorder.


Single-Cell Approaches to Profile the Response to Immune Checkpoint Inhibitors.
Novel treatments based upon the use of immune checkpoint inhibitors have an impressive efficacy in different types of cancer. Unfortunately, most patients do not derive benefit or lasting responses, and the reasons for the lack of therapeutic success are not known. Over the past two decades, a pressing need to deeply profile either the tumor microenvironment or cells responsible for the immune response has led investigators to integrate data obtained from traditional approaches with those obtained with new, more sophisticated, single-cell technologies, including high parameter flow cytometry, single-cell sequencing and high resolution imaging. The introduction and use of these technologies had, and still have a prominent impact in the field of cancer immunotherapy, allowing delving deeper into the molecular and cellular crosstalk between cancer and immune system, and fostering the identification of predictive biomarkers of response. In this review, besides the molecular and cellular cancer-immune system interactions, we are discussing how cutting-edge single-cell approaches are helping to point out the heterogeneity of immune cells in the tumor microenvironment and in blood.


A viral movement protein as a nuclear shuttle. The geminivirus BR1 movement protein contains domains essential for interaction with BL1 and nuclear localization.
For the nuclear replicating bipartite geminiviruses such as squash leaf curl to systemically infect the host requires the active participation of two virus-encoded movement proteins, BR1 and BL1. These act in a cooperative manner to transport the viral single-stranded DNA genome from its site of replication in the nucleus to the cell periphery (A.A. Sanderfoot, S.G. Lazarowitz [1995] Plant Cell 7: 1185-1194). We have proposed that BR1 functions as a nuclear shuttle protein, transporting the viral single-stranded DNA to and from the nucleus as a complex that is recognized by BL1 for movement to adjacent cells. To further investigate this, we expressed BR1 mutants known to affect viral infectivity in Spodoptera frugiperda insect cells and Nicotiana tabacum L. cv Xanthi protoplasts and found these to be defective in either their nuclear targeting or their ability to be redirected to the cell periphery when co-expressed with BL1. Translational fusions to beta-glucuronidase and alanine-scanning mutagenesis further demonstrated that the C-terminal 86 amino acids of BR1 contains a domain(s) essential for its interaction with BL1 and identified two nuclear localization signals within the N-terminal 113 residues of BR1. These nuclear localization signals were precisely located within distinct 16- and 22-peptide segments of BR1. These studies support and extend our model for squash leaf curl virus movement, showing that BR1 has a domain structure, with an N-terminal region required for nuclear targeting and a C-terminal region required for its interaction with BL1.


Feasibility and behavioral effects of an at-home multi-night sleep restriction protocol for adolescents.
Sleep deprivation is common among adolescents and has been associated with adverse behavioral and educational outcomes. However, it is difficult to draw strong causal conclusions because of a dearth of experimental sleep research. In part, this appears related to methodological challenges when working with this population. This study tested the feasibility and behavioral effects of a multi-night, at-home experimental sleep restriction protocol in a sample of adolescents. Twenty healthy adolescents aged 13.9-16.9 years were enrolled in a three-week sleep manipulation protocol using a counterbalanced cross-over experimental design. The protocol included a baseline week, followed in random order by a short sleep week (Monday-Friday nights limited to 6.5 hours time in bed) and an extended sleep week (10 hours lights-out time in bed Monday-Friday nights). Sleep was monitored via self-report and objective actigraphy. These were reviewed with participants and parents on the Saturdays at the end of each week, when parents and participants also completed behavior rating questionnaires. One participant dropped out of the study, but each of the remaining 19 displayed markedly less sleep in the short sleep condition than the extended sleep condition (average nightly gap approximately 2.5 hours). Data also reflected indirect effects of sleep deprivation that are consistent with an increase in homeostatic sleep drive. Compared to the extended sleep week, parents during the short sleep week reported that the participants displayed significantly greater problems with sleepiness, attention, oppositionality/irritability, behavior regulation, and metacognition. Participant self-report results were similar, though less robust. A multi-night, at-home sleep manipulation protocol for use with adolescents is indeed feasible. This study also provided the first experimental evidence that chronic sleep restriction during adolescence is causally related to a wide range of behavioral deficits.


Hardness Alternation in α,ω-Alkanedicarboxylic Acids.
The variation of hardness as a function of the number of carbon atoms in α,ω-alkanedicarboxylic acids, C(N)H(2N-2)O4 (4≤N≤9), was examined by recourse to nanoindentation on the major faces of single crystals. Hardness exhibits odd-even alternation, with the odd acids being softer and the even ones harder; the differences decrease with increasing chain length. These variations are similar to those seen for other mechanical, physical, and thermal properties of these diacids. The softness of odd acids is rationalized due to strained molecular conformations in them, which facilitate easier plastic deformation. Relationships between structural features, such as interplanar spacing, interlayer separation distance, molecular chain length, and signatures of the nanoindentation responses, namely, discrete displacement bursts, were also examined. Shear sliding of molecular layers past each other during indentation is key to the mechanism for plastic deformation in these organic crystals.


Lymphocyte subpopulations, oxidative burst and apoptosis in peripheral blood cells of patients with multiple sclerosis-effect of interferon-beta.
At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-beta. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-beta acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-alpha (CD25) on CD3+ T cells, CD19+ B cells, foetal-type gamma(delta)+CD3+ T cells and foetal-type CD5+CD19+ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-beta1b (BETAFERON, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n = 8) with application of 8 Mill. units IFN-beta1 b every other day, and (2) placebo group (n = 4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-beta has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-beta therapy is warranted.


Intracranial hematomas at a glance: advanced visualization for fast and easy detection.
To retrospectively assess the detection rate for intracranial hematomas achieved with use of curved maximum intensity projections (MIPs) that parallel the inner table of the skull compared with the rate achieved by reading transverse sections of computed tomography (CT) only. This retrospective study was approved by the institutional review board, which waived informed consent. A total of 314 consecutive patients who underwent CT for cranial trauma (155 male, 159 female; mean age ± standard deviation, 58 years ± 24 [range, 2-98 years]) were included. The algorithm unfolded the meningeal spaces into four images per patient. Four radiologists independently evaluated all cases. Hematomas less than 3 mm thick were considered thin. Radiologists were blinded to patient names, and patient and group orders were randomly assigned. The results were compared with a reference standard built by two experts. Logistic regression with repeated measurements was used for statistical analysis. Use of the reference standard helped confirm 121 intracranial hematomas in 39 patients. For all readers, reading time for hematoma detection was significantly shorter (3-5 times shorter, P < .001) for curved MIPs. Mean lesion-based detection rate for all readers was 80% (193 of 242) for transverse sections and 83% (200 of 242) for curved MIPs. For thin hematomas, the mean detection rate increased from 20% (eight of 40) with transverse sections to 83% (33 of 40) with curved MIPs. Curved MIPs of the meningeal spaces may shorten detection time for epidural and subdural hematomas, increase sensitivity (especially for thin hematomas), and reduce the required operator experience for detection.


Clinical utility of microarray-based gene expression profiling in the diagnosis and subclassification of leukemia: report from the International Microarray Innovations in Leukemia Study Group.
The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias.


Effects of dietary essential fatty acids on murine mammary gland development.
Removal of unsaturated fatty acids from the diet of female C3H mice resulted in the gradual onset of essential fatty acid deficiency. Upon reaching the deficient state, alveolar components of the mammary gland began to regress as did the ovarian corpora lutea. An increase in the viscosity of microsomal membranes and a decrease in the number of prolactin binding sites also occurred concomitantly as the deficient state increased in severity. Modification of fats with the diet changes the fluidity of cellular membranes. This appears to alter the functionality of the membrane-associated receptors and their subsequent ability to respond to circulating hormones.


Superinfection as a driver of genomic diversification in antigenically variant pathogens.
A new pathogen strain can penetrate an immune host population only if it can escape immunity generated against the original strain. This model is best understood with influenza viruses, in which genetic drift creates antigenically distinct strains that can spread through host populations despite the presence of immunity against previous strains. Whether this selection model for new strains applies to complex pathogens responsible for endemic persistent infections, such as anaplasmosis, relapsing fever, and sleeping sickness, remains untested. These complex pathogens undergo rapid within-host antigenic variation by using sets of chromosomally encoded variants. Consequently, immunity is developed against a large repertoire of variants, dramatically changing the scope of genetic change needed for a new strain to evade existing immunity and establish coexisting infection, termed strain superinfection. Here, we show that the diversity in the alleles encoding antigenic variants between strains of a highly antigenically variant pathogen was equal to the diversity within strains, reflecting equivalent selection for variants to overcome immunity at the host population level as within an individual host. This diversity among strains resulted in expression of nonoverlapping variants that allowed a new strain to evade immunity and establish superinfection. Furthermore, we demonstrated that a single distinct allele allows strain superinfection. These results indicate that there is strong selective pressure to increase the diversity of the variant repertoire beyond what is needed for persistence within an individual host and provide an explanation, competition at the host population level, for the large genomic commitment to variant gene families in persistent pathogens.


Chromosome Dynamics during Mitosis.
The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to "resolve" sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors.


QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen Elderly Study.
Prolongation of heart rate-adjusted QT length (corrected QT interval [QTc]) is associated with elevated risk of coronary heart disease and sudden death. This may have to do with autonomic cardiac control. Because insulin is known to stimulate sympathetic activity, we studied the association of insulin level and glucose tolerance with QTc. In 1990, 383 elderly men 70-89 years of age without previous myocardial infarctions or known diabetes had a 12-lead electrocardiogram recorded and glucose tolerance determined in the frame of an ongoing follow-up study. QTc was significantly associated with fasting glucose, insulin, and C-peptide and glucose levels 60 and 120 min after an oral glucose load. For fasting C-peptide and the area under the glucose curve (AUGC), this association could not be explained by the concomitant occurrence of other risk factors of coronary heart disease. Furthermore, fasting C-peptide and the AUGC were independently additive predictors of QTc duration. The difference in QTc between men in the extreme quintiles of both variables was 22 ms. QTc prolongation seems to be part of the insulin resistance syndrome. The association may be explained by increased sympathetic activity induced by high insulin levels. An additional explanation could be an effect of high insulin, impaired glucose utilization, or both on membrane activity of myocardial cells.


[Subarachnoidal anesthesia: the limits of its potentials].
A total of 250 subarachnoidal anesthesias (SA) have been performed in patients operated on the lower limbs, perineum, external genitals, pelvic organs, and anterior abdominal wall at department for plastic and reconstructive surgery. The efficacy and safety of SA in everyday practice has been evaluated. A total of simultaneous 228 SA with three hyperbaric solutions were carried out: 5% ultracaine, 0.75% bupivacaine, 0.5% marcaine, and one isobaric solution 0.5% bupivacaine. Prolonged SA was administered to 10 patients and combined spinal-epidural anesthesia (CSEA) to 19. The sensory block was assessed by the pin prick test and the motor blocking by Bromage score. Of the central segmentary blockades, SA has been preferred for the above-listed interventions in recent years. Hyperbaric and isobaric solutions caused analgesia of different duration, latent period, and dissemination of the anesthetic under different clinical situations. Prolonged SA is justified in patients with limited hemodynamic reserves, and CSEA should be preferred when the expected duration of the intervention is longer than the estimated duration of SA effects. SA is an effective and safe method for surgical anesthesia on condition of proper choice of the local anesthetic, use of high-quality kits, and strict adherence to the protocol of subarachnoidal puncture and injection.


Interaction between temperature and sublethal infection with the amphibian chytrid fungus impacts a susceptible frog species.
The amphibian chytrid fungus Batrachochytrium dendrobatidis is an emerging infectious pathogen present on every continent except Antarctica. It causes the disease chytridiomycosis in a subset of species but does not always result in disease or death for every host. Ambient temperature influences both amphibian metabolism and chytrid pathogenicity, however the interactive effects on host physiology is not well understood. We investigated the sublethal effect of B. dendrobatidis infection on a susceptible host, Litoria aurea to test (1) whether the infection load, metabolic activity, body fat and gonad size differed in L. aurea at either 24 °C or 12 °C ambient temperatures and (2) whether previous Bd infection caused long-term changes to body fat and gonad size. Litoria aurea in 12 °C treatments had higher infection loads of B. dendrobatidis and lower survivorship. Metabolic rate was higher and fat mass was lower in infected individuals and in animals in 24 °C treatments. Male L. aurea previously infected with B. dendrobatidis had smaller testes 5 months-post clearance of infection, an effect likely to translate to fitness costs in wild populations. These experiments demonstrate a physiological cost to sublethal B. dendrobatidis infection, which suggests a reduction in host fitness mediated by temperature in the host's environment regardless of whether infection leads to mortality.


White matter hyperintensity shape is associated with long-term dementia risk.
We aimed to investigate the association between white matter hyperintensity (WMH) shape and volume and the long-term dementia risk in community-dwelling older adults. Three thousand seventy-seven participants (mean age: 75.6 ± 5.2 years) of the Age Gene/Environment Susceptibility (AGES)-Reykjavik study underwent baseline 1.5T brain magnetic resonance imaging and were followed up for dementia (mean follow-up: 9.9 ± 2.6 years). More irregular shape of periventricular/confluent WMH (lower solidity (hazard ratio (95% confidence interval) 1.34 (1.17 to 1.52), p < .001) and convexity 1.38 (1.28 to 1.49), p < .001); higher concavity index 1.43 (1.32 to 1.54), p < .001) and fractal dimension 1.45 (1.32 to 1.58), p < .001)), higher total WMH volume (1.68 (1.54 to 1.87), p < .001), higher periventricular/confluent WMH volume (1.71 (1.55 to 1.89), p < .001), and higher deep WMH volume (1.17 (1.08 to 1.27), p < .001) were associated with an increased long-term dementia risk. WMH shape markers may in the future be useful in determining patient prognosis and may aid in patient selection for future preventive treatments in community-dwelling older adults.


Outcome of resonant voice therapy for female teachers with voice disorders: perceptual, physiological, acoustic, aerodynamic, and functional measurements.
Teachers have a high percentage of voice problems. For voice disordered teachers, resonant voice therapy is hypothesized to reduce voice problems. No research has been done on the physiological, acoustic, and aerodynamic effects of resonant voice therapy for school teachers. The purpose of this study is to investigate resonant voice therapy outcome from perceptual, physiological, acoustic, aerodynamic, and functional aspects for female teachers with voice disorders. A prospective study was designed for this research. The research subjects were 24 female teachers in Taipei. All subjects received resonant voice therapy in groups of 4 subjects, 90 minutes per session, and 1 session per week for 8 weeks. The outcome of resonant voice therapy was assessed from auditory perceptual judgment, videostroboscopic examination, acoustic measurements, aerodynamic measurements, and functional measurements before and after therapy. After therapy the severity of roughness, strain, monotone, resonance, hard attack, and glottal fry in auditory perceptual judgments, the severity of vocal fold pathology, mucosal wave, amplitude, and vocal fold closure in videostroboscopic examinations, phonation threshold pressure, and the score of physical scale in the Voice Handicap Index were significantly reduced. The speaking Fo, maximum range of speaking Fo, and maximum range of speaking intensity were significantly increased after therapy. No significant change was found in perturbation and breathiness measurements after therapy. Resonant voice therapy is effective for school teachers and is suggested as one of the therapy approaches in clinics for this population.


Integrated analysis of transcriptomic data reveals the platelet response in COVID-19 disease.
COVID-19 is associated with an increased risk of thrombotic events. However, the pathogenesis of these complications is unclear and reports on platelet infection and activation by the virus are conflicting. Here, we integrated single-cell transcriptomic data to elucidate whether platelet activation is a specific response to SARS-CoV-2 infection or a consequence of a generalized inflammatory state. Although platelets from patients infected with SARS-CoV-2 over expressed genes involved in activation and aggregation when compared to healthy controls; those differences disappeared when the comparison was made with patients with generalized inflammatory conditions of other etiology than COVID-19. The membrane receptor for the virus, ACE-2, was not expressed by infected or control platelets. Our results suggest that platelet activation in patients with severe COVID-19 is mainly a consequence of a systemic inflammatory state than direct invasion and activation.


In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development.
In humans, sexual differentiation of the external genitalia is established at 7-12 weeks post conception (wpc). During this period, maintaining the appropriate intrauterine hormone environment is critical. In contrast to other species, this regulation extends to the human fetal adrenal cortex, as evidenced by the virilization that is associated with various forms of congenital adrenal hyperplasia. The mechanism underlying these clinical findings has remained elusive. Here we show that the human fetal adrenal cortex synthesized cortisol much earlier than previously documented, an effect associated with transient expression of the orphan nuclear receptor nerve growth factor IB-like (NGFI-B) and its regulatory target, the steroidogenic enzyme type 2 3beta-hydroxysteroid dehydrogenase (HSD3B2). This cortisol biosynthesis was maximal at 8-9 wpc under the regulation of ACTH. Negative feedback was apparent at the anterior pituitary corticotrophs. ACTH also stimulated the adrenal gland to secrete androstenedione and testosterone. In concert, these data promote a distinctive mechanism for normal human development whereby cortisol production, determined by transient NGFI-B and HSD3B2 expression, provides feedback at the anterior pituitary to modulate androgen biosynthesis and safeguard normal female sexual differentiation.


Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands.
In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces a selective enhancement of adherens junction or focal contact assembly, respectively, throughout the cell. N-cadherin transfected CHO cells (CHO-Ncad) were incubated with different ligands including N-cadherin extracellular domain (NEC), anti-N-cadherin antibodies, fibronectin and concanavalin A (ConA), conjugated to synthetic beads. Electron microscopic examination indicated that both cadherin- and integrin-reactive beads bound tightly to the cell surface and were apparently endocytosed after several hours of incubation. The ConA-beads remained largely at the cell surface. Immunofluorescence labeling of the cells with antibodies to different adhesion-associated molecules indicated that both NEC- and anti-N-cadherin-conjugated beads induced a major increase in the level of junction-associated cadherin and beta-catenin labeling and a modest increase in junctional vinculin labeling, compared to untreated cells or cells bound to ConA-beads. FN-conjugated beads, on the other hand, significantly enhanced vinculin labeling at focal contacts and suppressed cadherin and beta-catenin staining in cell-cell junctions. The cadherin-reactive beads specifically stimulated tyrosine phosphorylation at cell-cell junctions, while the FN-beads increased the levels of focal contact-associated phosphotyrosine, as shown by immunofluorescence labeling of the cells for phosphotyrosine. Inhibition of this phosphorylation by genistein resulted in a complete suppression of the effects of both types of beads. These findings indicate that specific cadherin- and integrin-mediated surface interactions can trigger positively cooperative long-range signaling events which lead to the selective assembly of cell-cell or cell-matrix adhesions, and that these signals involve tyrosine phosphorylation.


Rate dynamics of ectotherm responses to thermal stress.
Critical thermal limits (CTLs) show much variation associated with the experimental rate of temperature change used in their estimation. Understanding the full range of variation in rate effects on CTLs and their underlying basis is thus essential if methodological noise is not to overwhelm or bias the ecological signal. We consider the effects of rate variation from multiple intraspecific assessments and provide a comprehensive empirical analysis of the rate effects on both the critical thermal maximum (CTmax) and critical thermal minimum (CTmin) for 47 species of ectotherms, exploring which of the available theoretical models best explains this variation. We find substantial interspecific variation in rate effects, which takes four different forms (increase, decline, no change, mixed), with phylogenetic signal in effects on CTmax, but not CTmin. Exponential and zero exponential failure rate models best explain the rate effects on CTmax. The majority of the empirical rate variation in CTmin could not be explained by the failure rate models. Our work demonstrates that rate effects cannot be ignored in comparative analyses, and suggests that incorporation of the failure rate models into such analyses is a useful further avenue for exploration of the fundamental basis and implications of such variation.


Comparison of R1 and R2 gastrectomy for gastric cancer in patients over 80 years of age.
To evaluate the benefit of R2 gastrectomy for gastric cancer in Japanese patients over 80 years of age, data on 93 patients who underwent gastrectomy between 1967 and 1989 were collected retrospectively from charts filed in the Kyushu University Hospital and two affiliated national hospitals. Of 93 patients, 62 had a localized tumor without evidence of metastatic spread. These 62 patients were classified into two groups according to the procedures performed: 35 underwent R1 gastrectomy and 27, R2 gastrectomy. The clinical and pathological characteristics of the patients in the two groups were comparable at the time of surgery, except that the group who underwent R1 gastrectomy was older. R2 gastrectomy involved a significantly longer operation time (P less than 0.01) and greater intraoperative blood loss (P less than 0.05) when compared to R1 gastrectomy, but no patient undergoing this extensive surgery died. The difference in the morbidity rate between the two groups was not statistically significant. The 5-year survival rate was 55.8% in the R1 group and 65.4% in the R2 group. When gastric cancer invaded the serosa and/or secondary nodes, a substantial increase in survival time was gained with R2 gastrectomy when compared to an R1 operation. These findings suggest that an R2 gastrectomy is feasible, even for patients over 80 years, but is indicated mainly when the carcinoma had invaded the serosa and/or secondary nodes and the patients are at good risk for major surgery.


Anion binding in covalent and self-assembled molecular capsules.
This critical review describes selected examples extracted from the extensive literature generated during the past 42 years on the topic of anion binding in molecular capsules. The goal of including anions in molecular capsules emerges from the idea of incorporating the traits exhibited by biological receptors into synthetic ones. At the outset of this research area the capsules were unimolecular. The scaffold of the receptor was designed to covalently link a series of functional groups that could converge into a cavity and to avoid its collapse. The initial examples involved the encapsulation of one monoatomic spherical anion. With time, the cavity size of the receptor was increased and encapsulation of polyatomic anions and co-encapsulation became a reality. Synthetic economy fueled the use of aggregates of self-complementary molecules rather than one large molecule as capsules. The main purpose of this review is to give a general overview of the topic which might be of interest to supramolecular or non supramolecular chemists alike (149 references).


Mild Behavioral Impairment in Psychogeriatric Patients: Clinical Features and Psychopathology Severity.
The Mild Behavioral Impairment (MBI) concept was developed to determine whether late-onset persistent neuropsychiatric symptoms (NPSs) may be early manifestations of cognitive decline. Our study aims to investigate the prevalence and differentiating features of MBI with respect to major neurocognitive disorders (MNDs) and primary psychiatric disorders (PPDs). A total of 144 elderly patients who were referred to our psychogeriatric outpatient service were recruited. The severity of mental illness was evaluated by means of the Clinical Global Impression Severity scale, the severity of psychopathology was evaluated by means of the Brief Psychiatric Rating Scale (BPRS), and overall functioning was evaluated by means of the Global Assessment of Functioning scale. The sample included 73 (50.6%) patients with PPDs, 40 (27.8%) patients with MBI, and 31 (21.5%) patients with MNDs. Patients with MNDs reported the greatest severity of mental illness, the highest BPRS Total, Psychosis, Activation, and Negative Symptom scores, and the lowest functioning. Patients with MBI and PPDs had comparable levels of severity of mental illness and overall functioning, but MBI patients reported higher BPRS Total and Negative Symptom scores than PPD patients. Patients with MBI frequently reported specific clinical features, including a higher severity of apathy and motor retardation. These features merit further investigation since they may help the differential diagnosis between MBI and PPDs.


Dissecting pathways to thrombocytopenia in a mouse model of visceral leishmaniasis.
Visceral leishmaniasis is an important yet neglected parasitic disease caused by infection with Leishmania donovani or L infantum. Disease manifestations include fever, weight loss, hepatosplenomegaly, immune dysregulation, and extensive hematological complications. Thrombocytopenia is a dominant hematological feature seen in both humans and experimental models, but the mechanisms behind this infection-driven thrombocytopenia remain poorly understood. Using a murine model of experimental visceral leishmaniasis (EVL), we demonstrated a progressive decrease in platelets from day 14 after infection, culminating in severe thrombocytopenia by day 28. Plasma thrombopoietin (TPO) levels were reduced in infected mice, at least in part because of the alterations in the liver microenvironment associated with granulomatous inflammation. Bone marrow (BM) megakaryocyte cytoplasmic maturation was significantly reduced. In addition to a production deficit, we identified significant increases in platelet clearance. L donovani-infected splenectomized mice were protected from thrombocytopenia compared with sham operated infected mice and had a greater response to exogenous TPO. Furthermore, infection led to higher levels of platelet opsonization and desialylation, both associated with platelet clearance in spleen and liver, respectively. Critically, these changes could be reversed rapidly by drug treatment to reduce parasite load or by administration of TPO agonists. In summary, our findings demonstrate that the mechanisms underpinning thrombocytopenia in EVL are multifactorial and reversible, with no obvious residual damage to the BM microenvironment.


Long-term clarithromycin in cystic fibrosis: effects on inflammatory markers in BAL and clinical status.
Macrolides have antiinflammatory effects that are potentially useful in cystic fibrosis (CF). In this placebo-controlled, randomized, double-blind crossover study, 18 CF patients were randomized to receive either clarithromycin (CM) (Group 1) or placebo (Group 2) for three months. After 15 days, the treatments were crossed over. Bronchoalveolar lavage (BAL) was obtained in the beginning and at the end of each treatment period. There was no significant difference in median cell counts and median cytokine levels at baseline, after CM use and after placebo use between the two groups. In Group 2, the median neutrophil elastase (NE) level decreased with CM. Patients had less acute pulmonary exacerbations and median clinical score decreased with CM in both groups. Median z-scores for weight increased with CM in Group 2. We could not demonstrate a fall in proinflammatory cytokines in BAL; however, some improvement in clinical status could be shown with three-month CM.


Body size and hip fracture risk. Swedish Hip Fracture Study Group.
The objective of this population-based case-control study was to determine the independent association between height, weight at different ages and adult weight change on hip fracture risk, and the joint effects of these factors. The study base comprised postmenopausal women 50-81 years of age who resided in six counties in Sweden during the period October 1993 to February 1995. The study included 1,327 cases with an incident hip fracture and 3,262 randomly selected controls. We obtained information on body measures and other factors possibly related to hip fracture through mailed questionnaires and telephone interviews. Height and weight change were dominant risk factors. Tall women (> or = 169 cm) had an odds ratio of 3.16 (95% confidence interval = 2.47-4.05) compared with women shorter than 159 cm. Weight gain during adult life was strongly protective: compared with those with moderate weight change (-3 to 3 kg), those with substantial weight gain (> or =12 kg) had a markedly decreased risk of hip fracture (odds ratio = 0.35; 95% confidence interval = 0.27-0.45), whereas weight loss was associated with an increased risk. Weight change retained important effects among all subjects, even after controlling for current weight and weight at age 18. In contrast, among women who gained weight, the separate effects of current weight and weight at age 18 were small or absent. Among women who lost weight, both current weight and weight at age 18 had effects that remained after controlling for weight change. Adult weight change and height are dominant body size risk factors for hip fracture. Weight loss vs weight changes demarcates different patterns of hip fracture risk.


[Cystic fibrosis, a paradigm for modern medicine].
Cystic fibrosis is the most frequent and severe genetic disorder in caucasian children. It is a multisystemic disease progressively involving many organs. Patients' survival was poor most of them dying as children. There has been now however an important improvement of prognosis. The median survival is 38 years today. Such a progress is related to comprehensive care based not only on scientific research but multidisciplinary clinical approach implying physicians and paramedics. Moreover pediatricians stimulated already in the 1960s patient autonomy by supporting national and international patients organisations. This approach has greatly contributed to increase the visibility of this disease and its support in our society. Cystic fibrosis is a paradigm for improving care of chronic diseases in medicine.


Cryopreserving whole blood for functional assays using viable lymphocytes in molecular epidemiology studies.
There is an increasing need for viable lymphocytes in performing phenotypic assays for biomarker studies. Both fresh and cryopreserved lymphocytes have been used for cell culture-based functional assays. However, fresh lymphocytes do not allow assays to be done in batches and cryopreservation of isolated lymphocytes results in a considerable loss of viable cells. To investigate the feasibility of using cryopreserved whole blood as a source of viable lymphocytes in molecular epidemiology studies, two well-established biomarkers, the host-cell reactivation (HCR) and mutagen sensitivity assays, were used to compare the method of cryopreserving whole blood with the traditional methods. In 25 paired blood samples assayed for DNA repair capacity (DRC) by the HCR assay, the DRC values of frozen whole blood (mean +/- SD, 11.59 +/- 3.07) were similar to those of frozen isolated lymphocytes (11.08 +/- 3.50). The correlation between the paired DRC values was 0.77 (P < 0.001). In 31 paired blood samples assayed for the gamma-radiation-induced chromatid breaks by the mutagen sensitivity assay, there was no significant difference between the baseline level of chromatid breaks in lymphocytes from frozen blood (0.05 +/- 0.03) and fresh blood (0.06 +/- 0.03). The blastogenic rate and mitotic index of the cells used for the two assays were compared between the different processing methods. The lymphocytes from frozen whole blood were more sensitive to gamma-radiation, with a higher mean level of chromatid breaks (0.68 +/- 0.21) than that in fresh blood (0.42 +/- 0.12, P < 0.01), and the correlation between the numbers of chromatid breaks in the paired samples was statistically significant (r = 0.61, P < 0.001). These data suggest that within the limits of the parameters investigated here, cryopreserved whole blood is a good source of viable lymphocytes for biomarker assays in molecular epidemiological studies.


Innate immune responses against Epstein Barr virus infection.
EBV persists life-long in >95% of the human adult population. Whereas it is perfectly immune-controlled in most infected individuals, a minority develops EBV-associated diseases, primarily malignancies of B cell and epithelial cell origin. In recent years, it has become apparent that the course of primary infection determines part of the risk to develop EBV-associated diseases. Particularly, the primary symptomatic EBV infection or IM, which is caused by exaggerated T cell responses, resulting in EBV-induced lymphocytosis, predisposes for EBV-associated diseases. The role of innate immunity in the development of IM remains unknown. Therefore, it is important to understand how the innate immune response to this virus differs between symptomatic and asymptomatic primary EBV infection. Furthermore, the efficiency of innate immune compartments might determine the outcome of primary infection and could explain why some individuals are susceptible to IM. We will discuss these aspects in this review with a focus on intrinsic immunity in EBV-infected B cells, as well as innate immune responses by DCs and NK cells, which constitute promising immune compartments for the understanding of early immune control against EBV and potential targets for EBV-specific immunotherapies.


[Cyclic AMP-dependent pig brain protein kinase: subunit structure, mechanism of autophosphorylation and holoenzyme dissociation under cyclic AMP action].
Some properties of cyclic AMP-dependent pig brain protein kinase were studied. The holoenzyme was shown to exist in solution in the form of a tetramer complex R2C2 with mol. weight of 180 000. The limited proteolysis of the regulatory subunit caused the formation of a fragment with mol. weight of 35 000, capable of independent binding of 3H-cyclic AMP and containing a site, which can be phosphorylated in the autophosphorylation reaction. Autophosphorylation of the holoenzyme led to an increase in the degree of dissociation of the former into individual subunits under the effect of cyclic AMP. The ability of the phosphoform of the catalytic subunit was demonstrated. The autophosphorylation process and the phosphotransferase reaction involve the same active site of the catalytic subunit.


Prevalence of Extended-Spectrum β-Lactamase-Producing Bacteria on Fresh Vegetables in Japan.
Extended-spectrum β-lactamase (ESBL)-producing bacteria are spreading rapidly, posing a threat to human and animal health. Contamination of vegetables with antimicrobial-resistant bacteria or those harboring antimicrobial resistance genes or a combination of both presents a potential route of transmission to humans. Therefore, the aim of this study was to determine the prevalence of these bacteria in fresh vegetables in Japan. A total of 130 samples of fresh vegetables were collected from seven supermarkets in Japan. The predominant genus detected was Pseudomonas spp., including 10 ESBL-producing strains, isolated from 10 (7.7%) of the vegetable samples. Two ESBL genes were detected, blaTEM-116 (n = 7) and blaSHV-12 (n = 3), and some of these strains were resistant to multiple antibiotics. Because vegetables are often consumed raw, those contaminated with ESBL producers could represent an important route of transmission to humans in Japan. Thus, more stringent hygiene measures and monitoring are required to prevent transmission via this source.


Effect of bovine colostrum, cheese whey, and spray-dried porcine plasma on the in vitro growth of probiotic bacteria and Escherichia coli.
The aim of this study is to evaluate the effects of defatted colostrum (Col), defatted decaseinated colostrum whey, cheese whey, and spray-dried porcine plasma (SDPP) as supplements of a growth medium (de Man - Rogosa - Sharpe (MRS) broth) on the multiplication of lactic acid bacteria, probiotic bacteria, and potentially pathogenic Escherichia coli. Using automated spectrophotometry (in vitro system), we evaluated the effect of the 4 supplements on maximum growth rate (μ(max)), lag time (LagT), and biomass (OD(max)) of 12 lactic acid bacteria and probiotic bacteria and of an E. coli culture. Enrichment of MRS broth with a Col concentration of 10 g/L increased the μ(max) of 5 of the 12 strains by up to 55%. Negative effects of Col or SDPP on growth rates were also observed with 3 probiotic strains; in one instance μ(max) was reduced by 40%. The most effective inhibitor of E. coli growth was SDPP, and this effect was not linked to its lysozyme content. The positive effect of enrichment with the dairy-based ingredient might be linked to enrichment in sugars and increased buffering power of the medium. These in vitro data suggest that both Col and SDPP could be considered as supplements to animal feeds to improve intestinal health because of their potential to promote growth of probiotic bacteria and to inhibit growth of pathogenic bacteria such as E. coli.


Association of poly(ADP-ribose) polymerase with the nuclear matrix: the role of intermolecular disulfide bond formation, RNA retention, and cell type.
The recovery of the enzyme poly(ADP-ribose) polymerase (pADPRp) in the nuclease- and 1.6 M NaCl-resistant nuclear subfraction prepared from a number of different sources was assessed by Western blotting. When rat liver nuclei were treated with DNase I and RNase A followed by 1.6 M NaCl, approximately 10% of the nuclear pADPRp was recovered in the sedimentable fraction. The proportion of pADPRp recovered with the residual fraction decreased to less than 5% of the total nuclear polymerase when nuclei were prepared in the presence of the sulfhydryl blocking reagent iodoacetamide and increased to approximately 50% of the total nuclear pADPRp when nuclei were treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) prior to fractionation. To determine whether this effect of disulfide bond formation was unique to rat liver nuclei, nuclear matrix/cytoskeleton structures were prepared in situ by sequentially treating monolayers of tissue culture cells with Nonidet-P40, DNase I and RNase A, and 1.6 M NaCl (S.H. Kaufmann and J.H. Shaper (1991) Exp. Cell Res. 192, 511-523). When nuclear monolayers were prepared from HTC rat hepatoma cells, CaLu-1 human lung carcinoma cells, and CHO hamster ovary cells in the absence of NaTT, pADPRp was undetectable in the nuclease- and 1.6 M NaCl-resistant fraction. In contrast, when nuclear monolayers were isolated in the presence of NaTT, from 5% (CaLu-1) to 26% (HTC cells) of the total nuclear pADPRp was recovered with the nuclease- and salt-resistant fraction. Examination of these residual structures by SDS-polyacrylamide gel electrophoresis under nonreducing conditions suggested that pADPRp was present as a component of disulfide cross-linked complexes. Further analysis by immunofluorescence revealed that the pADPRp was diffusely distributed throughout the CaLu-1 or CHO nuclear matrix. In addition, when matrices were prepared in the absence of RNase A, pADPRp was also observed in the residual nucleoli. These observations reveal that the recovery of pADPRp with a nuclease- and salt-resistant nuclear subfraction is dependent on the source of the nuclei and on the conditions used to fractionate those nuclei. In addition, these observations raise the possibility that there might be different functional classes of pADPRp molecules within the nucleus.


Cross-face grafting in facial paralysis.
I report the two-year follow-up results obtained by cross-face grafting in seven patients. The advantages of the method, ie, reduction of innervation of the healthy side of the face and restoration of emotional movements of the paralyzed side, are counterbalanced by the long delay in reinnervation and the limited number of motor fibers available for matched contralateral diversion. For this reason, cross-face grafting should still be considered as an experimental stage and should not be used in an indiscriminate way to achieve symmetry of emotional movements in irreversible unilateral facial palsy.


Low back pain in pregnancy.
The aim of this case report is to discuss the subject of acupuncture in pregnancy and which acupuncture points, or areas, are safe to needle. Low back pain in a 21-year-old Caucasian primigravida at 24 weeks gestation was incapacitating and acupuncture was offered. Prior to pregnancy investigations had excluded a serious organic cause and acupuncture was employed successfully to control pain and improve function. Acupuncture can be offered to sufferers of low back pain in pregnancy after risk / benefit analysis is undertaken and informed patient consent is obtained.


Wood production response to climate change will depend critically on forest composition and structure.
Established forests currently function as a major carbon sink, sequestering as woody biomass about 26% of global fossil fuel emissions. Whether forests continue to act as a global sink will depend on many factors, including the response of aboveground wood production (AWP; MgC ha(-1 ) yr(-1) ) to climate change. Here, we explore how AWP in New Zealand's natural forests is likely to change. We start by statistically modelling the present-day growth of 97 199 individual trees within 1070 permanently marked inventory plots as a function of tree size, competitive neighbourhood and climate. We then use these growth models to identify the factors that most influence present-day AWP and to predict responses to medium-term climate change under different assumptions. We find that if the composition and structure of New Zealand's forests were to remain unchanged over the next 30 years, then AWP would increase by 6-23%, primarily as a result of physiological responses to warmer temperatures (with no appreciable effect of changing rainfall). However, if warmth-requiring trees were able to migrate into currently cooler areas and if denser canopies were able to form, then a different AWP response is likely: forests growing in the cool mountain environments would show a 30% increase in AWP, while those in the lowland would hardly respond (on average, -3% when mean annual temperature exceeds 8.0 °C). We conclude that response of wood production to anthropogenic climate change is not only dependent on the physiological responses of individual trees, but is highly contingent on whether forests adjust in composition and structure.