Health disparities research in global perspective: new insights and new directions.
This commentary introduces this volume's symposium on "Comparative Approaches to Reducing Health Disparities." Disparities in the health of socially and economically disadvantaged compared with more advantaged populations are observed worldwide. The lack of progress in addressing these disparities compels a continuing search for new ideas and evidence about potential solutions as well as efforts to understand when and where these solutions work and how they work. The symposium consists of five in-depth reviews led by established scholars who approach the topic from their different disciplinary and topical perspectives. Taken together, these reviews point out the conceptual and methodological opportunities for generating more effective disparities research within biomedical, public health, and health services approaches, the value of also applying theory and methods from disciplines such as political science and economics to health disparities research, and insights to be gained from comparisons of how disparities occur and are remedied in different societies.


Optimization of one-third harmonic generation in the presence of nonlinear phase modulations and power attenuation.
We investigate the one-third harmonic generation (OTHG) in optical microfibers with power attenuation considered by analytically analyzing and numerically solving the coupled mode equations (CMEs). Both the strength and effective length of signal power growing in nonlinear media, which are extremely sensitive to the relative phase between the interaction waves, contribute to the final conversion efficiency. The relative phase and its evolution along the propagating direction play crucial roles in highly efficient OTHG. In order to obtain high conversion efficiency, the general expressions of optical threshold conditions are derived and discussed for choosing proper initial parameters. Numerically simulations are performed with both partial and absolute phase matching, which are corresponding to the microfibers with uniform and non-uniform diameters, respectively. Optimizations of relative phase and phase compensation are suggested by the simulations and provide significant enhancement of conversion efficiencies.


Optical imaging of intrinsic signals in somatosensory cortex.
The methods of optical intrinsic signal (OIS) imaging and microelectrode mapping of single neuron receptive fields (RFs) were used in combination (in the same squirrel monkey or cat) to characterize the spatial and temporal attributes of the response of contralateral SI cortex to cutaneous flutter stimulation. A change in the location of the stimulated skin site was accompanied by a shift in the locus of the SI optical response. The spatial ordering of the optical responses to independent stimulation of each site in an array of skin sites was consistent with the features of SI topographical organization described in published RF mapping studies. While the single neuron RF mapping observations and the optical response obtained at a given time after onset of flutter stimulation always were positively correlated, the degree of correlation improved progressively with time after stimulus onset (the longest stimulus duration used was 10 s). Analysis of the temporal development of the optical response to cutaneous flutter stimulation revealed that not only does absorbance increase to attain a maximum in the SI region which receives its main input from the stimulated skin site, but at the same time absorbance declines to below-background values in an extensive region of surrounding cortex. The results are interpreted to indicate that the pattern of SI activity evoked by a cutaneous flutter stimulus exhibits increasing spatial contrast (becomes progressively more distinguishable from the activity of surrounding cortex) over periods of continuous stimulation at least as long as 10 s. This time-dependent 'funneling' of the SI spatial activity pattern is proposed to underlie the prominent enhancement of human spatial discriminative capacity which occurs (e.g. Physiol. Behav. 5 (1970) 1431) when oscillatory tactile stimuli are used.


Appraisal of the clinical value of serotoninergic drugs.
Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.


Negative bone scans of joints after aspiration or arthrography: experimental studies.
It has long been suspected anecdotally that needle aspiration or contrast arthrogram before bone scan may cause a false-positive bone scan. This dictum often directs the sequence of events in the clinical workup of joint disease, yet data to support or refute this are lacking. This study was undertaken to generate such data. Fifty-six joints in mature dogs were examined, including hips, knees, elbows, and shoulders. The joints were examined in pairs; one joint was injected with Conray 60 for an arthrogram, and the contralateral joint was injected with an equal volume of normal saline to simulate a joint aspiration. Confirmation of needle placement and injection into the joints was made with fluoroscopic and digital subtraction imaging. Numbers of attempts required for aspiration and quantity of contrast material extravasated were noted for each joint. Baseline 99mTc-HDP or 99mTc-MDP bone scans were done before the experimental joint aspirations, with follow-up scans at 24 and 96 hr. The scans showed no significant change from baseline after either needle aspiration or arthrogram. When the diagnostic workup suggests the need for such a procedure, it should be performed. In contradiction to popular belief, joint aspiration and/or arthrogram did not affect a subsequent bone scan.


What dimensions underlie patient responses to the General Practice Assessment Survey? A factor analytic study.
Patient self-report measures of primary care are being used increasingly for quality assessment and improvement. The General Practice Assessment Survey (GPAS) is a widely used measure. However, it is important that the measures used are valid and interpretable. Factor analysis is a useful method to assist in validation. The aim of this study was to determine the underlying structure of responses to the GPAS. Factor analysis of data from a number of patient surveys was carried out using the GPAS in primary care. Analysis indicated that three factors underlie responses to the GPAS. These were named "access", "patient-centredness" and "nursing". These factors were replicated in a second sample of GPAS survey data. Responses to the GPAS can best be summarized in terms of three underlying factors, which supports previous conceptual work. These factors may also have utility for reducing the overall length of the GPAS, and in reducing the need for multiple hypothesis testing associated with the use of the original scales.


A new ab initio potential energy surface for the collisional excitation of N2H(+) by H2.
We compute a new potential energy surface (PES) for the study of the inelastic collisions between N2H(+) and H2 molecules. A preliminary study of the reactivity of N2H(+) with H2 shows that neglecting reactive channels in collisional excitation studies is certainly valid at low temperatures. The four dimensional (4D) N2H(+)-H2 PES is obtained from electronic structure calculations using the coupled cluster with single, double, and perturbative triple excitation level of theory. The atoms are described by the augmented correlation consistent triple zeta basis set. Both molecules were treated as rigid rotors. The potential energy surface exhibits a well depth of ≃2530 cm(-1). Considering this very deep well, it appears that converged scattering calculations that take into account the rotational structure of both N2H(+) and H2 should be very difficult to carry out. To overcome this difficulty, the "adiabatic-hindered-rotor" treatment, which allows para-H2(j = 0) to be treated as if it were spherical, was used in order to reduce the scattering calculations to a 2D problem. The validity of this approach is checked and we find that cross sections and rate coefficients computed from the adiabatic reduced surface are in very good agreement with the full 4D calculations.


A new history and discussion of 180-day exclusivity.
Congress created 180-day exclusivity for generic drug applicants in the 1984 Hatch-Waxman amendments to the Federal Food, Drug, and Cosmetic Act (FDCA) and amended the provision substantially in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). The fundamental goal behind 180-day exclusivity was to provide an incentive for generic drug applicants to challenge innovator patents, and the core of the concept--as it has been applied by the Food and Drug Administration (FDA) and the courts--is that the first generic drug applicant to challenge an innovator's patent is entitled to six months of exclusivity against subsequent patent challengers for the same innovator drug. 180-day exclusivity is governed by sections 505(j)(5)(B)(iv) and 505(j)(5)(D) of the FDCA. In this article, the authors provide a comprehensive resource on 180-day exclusivity for old abbreviated new drug applications (ANDAs) (but less detail in some places where the 2007 article may be referenced) but focus more discussion on the new provisions as well as some policy and legal issues related to 180-day exclusivity that have not previously addressed.


2D Violet phosphorene with highly anisotropic mobility and its vdW heterojunction design for device applications.
Recently, the crystal structure of violet phosphorus and its monolayer violet phosphorene (VP) have been reconfirmed experimentally, and they were verified to be more thermally stable than their allotrope, black phosphorus. Here, we calculated the carrier mobility of monolayer VP using density functional theory. It is found that the carrier mobility is highly anisotropic and the hole mobility reaches 9.86 × 103 cm2 V-1 s-1 in the a-direction, endowing the potential application of VP in p-type semiconductor channel materials. Moreover, the Schottky barrier of the graphene/VP heterojunction turns into an ohmic contact when the electric field strength is >2 V nm-1. Therefore, VP and graphene/VP heterojunctions have potential prospects in electronic devices.


Automated regional myocardial displacement for facilitating the interpretation of dobutamine echocardiography.
Quantification of stress echocardiography may overcome the training requirements and subjective nature of visual wall motion score (WMS) assessment, but quantitative approaches may be difficult to apply and require significant time for image processing. The integral of long-axis myocardial velocity is displacement, which may be represented as a color map over the left ventricular myocardium. This study was designed to explore the feasibility and accuracy of measuring long-axis myocardial displacement, derived from tissue Doppler, for the detection of coronary artery disease (CAD) during dobutamine stress echocardiography (DBE). One hundred thirty patients underwent standard DBE, including 30 patients at low risk of CAD, 30 patients with normal coronary angiography (both groups studied to define normal ranges of displacement), and 70 patients who underwent coronary angiography in whom the accuracy of normal ranges was tested. Regional myocardial displacement was obtained by analysis of color tissue Doppler apical images acquired at peak stress. Displacement was compared with WMS, and with the presence of CAD by angiography. The analysis time was 3.2 +/- 1.5 minutes per patient. Segmental displacement was correlated with wall motion (normal 7.4 +/- 3.2 mm, ischemia 5.8 +/- 4.2 mm, viability 4.6 +/- 3.0 mm, scar 4.5 +/- 3.5 mm, p <0.001). Reversal of normal base-apex displacement was an insensitive (19%) but specific (90%) marker of CAD. The sum of displacements within each vascular territory had a sensitivity and specificity of 89% and 79%, respectively, for prediction of significant CAD, compared with 86% and 78%, respectively, for WMS (p = NS). The displacements in the basal segments had a sensitivity and specificity of 83% and 78%, respectively (p = NS). Regional myocardial displacement during DBE is feasible and offers a fast and accurate method for the diagnosis of CAD.


[Low-magnitude vibration promotes osteogenesis of osteoblasts in ovariectomized osteoporotic rats via the estrogen receptor α].
The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s2). Then we loaded the optimal vibration parameter on the osteoblasts of ovariectomized rats with osteoporosis. The protein expression of osteogenic markers and ERα were detected with Western blot; the distribution of ERα was examined with immunofluorescence technique. Finally, through inhibiting the expression of ERα with estrogen receptor inhibitor ICI182780, the protein and mRNA expression of osteogenic markers were examined. First, the results showed that low-magnitude vibration could promote the expression of osteogenic markers and ERα in osteoblasts of ovariectomized rats with osteoporosis (P < 0.05), and make ERα transfer to the nucleus. On the other hand, the results also showed that after inhibiting the expression of ERα in osteoblasts of ovariectomized rats with osteoporosis, the protein and mRNA expression of osteogenic marker were decreased (P < 0.05). In our study, low-magnitude vibration played an important role in the osteogenesis of osteoblasts in ovariectomized rats with osteoporosis through increasing the expression and causing translocation of ERα. Furthermore, it provides a theoretical basis for the application of low-magnitude vibration in the prevention and treatment of postmenopausal osteoporosis.


Controlling synchrony in oscillatory networks via an act-and-wait algorithm.
The act-and-wait control algorithm is proposed to suppress synchrony in globally coupled oscillatory networks in the situation when the simultaneous registration and stimulation of the system is not possible. The algorithm involves the periodic repetition of the registration (wait) and stimulation (act) stages, such that in the first stage the mean field of the free system is recorded in a memory and in the second stage the system is stimulated with the recorded signal. A modified version of the algorithm that takes into account the charge-balanced requirement is considered as well. The efficiency of our algorithm is demonstrated analytically and numerically for globally coupled Landau-Stuart oscillators and synaptically all-to-all coupled FitzHugh-Nagumo as well as Hodgkin-Huxley neurons.


Evaluating Diuretics in Normal Care (EVIDENCE): a feasibility report of a pilot cluster randomised trial of prescribing policy in primary care to compare the effectiveness of thiazide-type diuretics in hypertension.
Obtaining evidence on comparative effectiveness and safety of widely prescribed drugs in a timely and cost-effective way is a major challenge for healthcare systems. Here, we describe the feasibility of the Evaluating Diuretics in Normal Care (EVIDENCE) study that compares a thiazide and thiazide-like diuretics for hypertension as an exemplar of a more general framework for efficient generation of such evidence. In 2011, the UK NICE hypertension guideline included a recommendation that thiazide-like diuretics (such as indapamide) be used in preference to thiazide diuretics (such as bendroflumethiazide) for hypertension. There is sparse evidence backing this recommendation, and bendroflumethiazide remains widely used in the UK. Patients prescribed indapamide or bendroflumethiazide regularly for hypertension were identified in participating general practices. Allocation of a prescribing policy favouring one of these drugs was then randomly applied to the practice and, where required to comply with the policy, repeat prescriptions switched by pharmacy staff. Patients were informed of the potential switch by letter and given the opportunity to opt out. Practice adherence to the randomised policy was assessed by measuring the amount of policy drug prescribed as a proportion of total combined indapamide and bendroflumethiazide. Routinely collected hospitalisation and death data in the NHS will be used to compare cardiovascular event rates between the two policies. This pilot recruited 30 primary care practices in five Scottish National Health Service (NHS) Boards. Fifteen practices were randomised to indapamide (2682 patients) and 15 to bendroflumethiazide (3437 patients), a study population of 6119 patients. Prior to randomisation, bendroflumethiazide was prescribed to 78% of patients prescribed either of these drugs. Only 1.6% of patients opted out of the proposed medication switch. The pilot and subsequent recruitment confirms the methodology is scalable within NHS Scotland for a fully powered larger study; currently, 102 GP practices (> 12,700 patients) are participating in this study. It has the potential to efficiently produce externally valid comparative effectiveness data with minimal disruption to practice staff or patients. Streamlining this pragmatic trial approach has demonstrated the feasibility of a random prescribing policy design framework that can be adapted to other therapeutic areas. ISRCTN Registry, ISRCTN46635087 . Registered on 11 August 2017.


Family history and age at initiation of colorectal cancer screening.
To review and combine the best available epidemiological evidence, by sex and age, that may help decision and policy makers form recommendations as to how much earlier colorectal cancer (CRC) screening should be initiated among people with a family history of CRC than among average-risk people. Combining population-based cancer registry and health interview survey data from the United States and results of a recent meta-analysis of epidemiological studies, we estimated cumulative incidence of CRC within subsequent 10 yr (CI(10)) at various ages among men and women with and without a family history of CRC. We estimated both the CI(10) levels reached in average-risk 45-, 50-, 55-, and 60-yr-old men and women and the age at which the same CI(10) levels are reached in men and women with a history of CRC in a first-degree relative. Despite major differences in CRC risk by sex, and despite the strong age gradient in relative risk associated with a positive family history, "risk advancement periods" for those with a family history were consistently found to be between 9 and 11 yr for both sexes and at all four ages assessed. Advancement of first CRC screening by 10 yr among both men and women with a family history of CRC compared to the average-risk population (e.g., from 50 to 40 yr of age) appears to be a reasonable, evidence-based recommendation.


The tripartite basal enhancer of the gonadotropin-releasing hormone (GnRH) receptor gene promoter regulates cell-specific expression through a novel GnRH receptor activating sequence.
The molecular mechanisms regulating restricted expression of GnRH receptor and gonadotropin subunit genes to gonadotrope cells have been the focus of intense interest. Using deletion and mutational analysis we have identified a tripartite enhancer that regulates cell-specific expression of the GnRH receptor gene in the gonadotrope-derived alphaT3-1 cell line. Individual elements of this enhancer include binding sites for steroidogenic factor-1; activator protein 1 (AP-1); and a novel element referred to as the GnRH receptor activating sequence (GRAS). Mutation of each element alone results in loss of approximately 60% of promoter activity. Combinatorial mutations of any two elements decreases promoter activity by approximately 80%. Finally, mutation of all three elements reduces promoter activity to a level not different from promoterless vector. Using 2-bp mutations, we have defined the functional requirements for transcriptional activation by GRAS. The core motif of GRAS is at -391 to -380 bp relative to the start site of translation and has the sequence 5'-CTAGTCACAACA-3'. Three copies of GRAS or GRAS with a 2-bp mutation (muGRAS) were cloned into a luciferase expression vector immediately upstream of the thymidine kinase minimal promoter (TK) and tested for expression in alphaT3-1 cells. When compared with TK promoter alone, activity of 3xGRAS-TKLUC was increased by more than 5-fold while activity of 3xmuGRAS-TKLUC was unchanged. When 3xGRAS-TKLUC was transfected into a variety of nongo-nadotrope cell lines, it did not increase activity of the TK promoter. We propose that basal activity of the GnRH receptor gene is regulated by a tripartite enhancer, and the key component of this enhancer is an element, GRAS, that activates transcription in a cell-specific fashion.


Characterization of an insertion sequence element associated with genetically diverse plant pathogenic Streptomyces spp.
Streptomycetes are common soil inhabitants, yet few described species are plant pathogens. While the pathogenicity mechanisms remain unclear, previous work identified a gene, nec1, which encodes a putative pathogenicity or virulence factor. nec1 and a neighboring transposase pseudogene, ORFtnp, are conserved among unrelated plant pathogens and absent from nonpathogens. The atypical GC content of nec1 suggests that it was acquired through horizontal transfer events. Our investigation of the genetic organization of regions adjacent to the 3' end of nec1 in Streptomyces scabies 84.34 identified a new insertion sequence (IS) element, IS1629, with homology to other IS elements from prokaryotic animal pathogens. IS1629 is 1,462 bp with 26-bp terminal inverted repeats and encodes a putative 431-amino-acid (aa) transposase. Transposition of IS1629 generates a 10-bp target site duplication. A 77-nucleotide (nt) sequence encompassing the start codon and upstream region of the transposase was identified which could function in the posttranscritpional regulation of transposase synthesis. A functional copy of IS1629 from S. turgidiscabies 94.09 (Hi-C-13) was selected in the transposon trap pCZA126, through its insertion into the lambda cI857 repressor. IS1629 is present in multiple copies in some S. scabies strains and is present in all S. acidiscabies and S. turgidiscabies strains examined. A second copy of IS1629 was identified between ORFtnp and nec1 in S. acidiscabies strains. The diversity of IS1629 hybridization profiles was greatest within S. scabies. IS1629 was absent from the 27 nonpathogenic Streptomyces strains tested. The genetic organization and nucleotide sequence of the nec1-IS1629 region was conserved and identical among representatives of S. acidiscabies and S. turgidiscabies. These findings support our current model for the unidirectional transfer of the ORFtnp-nec1-IS1629 locus from IS1629-containing S. scabies (type II) to S. acidiscabies and S. turgidiscabies.


Suppressive effect of dietary raffinose on T-helper 2 cell-mediated immunity.
The effects of the dietary oligosaccharide raffinose on immune responses, with special reference to its anti-allergic functions, were examined in vivo. First, feeding a diet supplemented with 50 g raffinose/kg to BALB/c mice significantly (P<0.05) increased interleukin (IL) 12 secretion from isolated Peyer's patch (PP) cells in vitro compared with feeding control diet. When isolated PP cells were used as antigen-presenting cells (APC) for CD4+ T-splenocytes isolated from ovalbumin (OVA)-specific T-cell receptor transgenic (Tg) mice in the presence of OVA as antigen, significantly (P<0.05) higher levels of interferon-gamma were observed in the cultures using APC from raffinose-fed mice than those cultures using APC from control mice. Second, the diet containing 50 g raffinose/kg or control diet was fed to OVA Tg mice, and subsequently, OVA was added to each diet to prime T cells in vivo. CD4+ T-cells from the mesenteric lymph nodes of the raffinose-fed mice secreted significantly (P<0.05) higher levels of IL-2 and significantly (P<0.05) lower levels of IL-4 following in vitro antigenic stimulation compared with those of the control mice. These present results suggest that feeding raffinose may suppress differentiation of naïve T-helper (Th) cells into Th2 cells in the mesenteric lymphoid nodes. Last, feeding raffinose suppressed rises of serum immunoglobulin E levels in the Tg mice treated with long-term ingestion of OVA. In conclusion, it is suggested that dietary raffinose suppresses serum immunoglobulin E response through suppression of Th2-type immune response against oral antigen in the lymphoid organs located in or near the intestine.


Selective effects of typical antipsychotic drugs on SNAP-25 and synaptophysin in the hippocampal trisynaptic pathway.
Recent studies indicate that levels of presynaptic proteins are altered in the post-mortem brain in schizophrenia. In particular, the hippocampus exhibits reduced levels of synaptophysin and the SNARE protein SNAP-25. The effects of treatment with antipsychotic drugs on levels of SNAP-25 in the hippocampus remains unknown. To determine the effects of typical antipsychotic drugs on levels of synaptophysin and SNAP-25 in the hippocampus, rats were treated with chlorpromazine, haloperidol or trifluoperazine for 21 d. Quantitative immunohistochemistry was used to measure immunoreactivity within the trisynaptic circuit of the hippocampus. Trifluoperazine decreased synaptophysin within the Schaffer collateral region of the radiatum lacunosum in CA1, while haloperidol and chlorpromazine increased SNAP-25 throughout the trisynaptic pathway of the hippocampus, with strongest effects in the mossy fibre region of CA3. These results indicate that presynaptic proteins represent a potential molecular substrate for the effects of antipsychotic drugs on hippocampal synaptic connectivity.


Developing brain and in utero cocaine exposure: effects on neural ontogeny.
Within the last decade, many investigators have focused on the physical, neurodevelopmental, and neuropsychological effects of prenatal cocaine exposure on infants and young children. Although inconclusive on many crucial issues, published studies reveal the beginnings of a profile of possible cocaine-related effects on neuropsychological functions subserving arousal and attention regulation. That profile is informed by preclinical studies in which important factors such as duration and type of exposure as well as environmental conditions may be more adequately controlled. In the developing brain, there are a number of candidate mechanisms that account for how prenatal cocaine exposure may interfere with neural ontogeny. This review focuses on the monoamine system, one of the primary sites of action of cocaine in the adult. In the developing organism, monoamines play critical trophic roles through all phases of central nervous system (CNS) ontogeny--cell proliferation, neural migration, growth, maturation, and synaptogenesis. Because of their trophic role in CNS ontogeny, cocaine effects on developing nervous system may be mediated in part through effects on monoamine system ontogeny. In turn, these effects may be expressed behaviorally in disrupted patterns of arousal and attention regulation given that these domains are connected intimately to monoaminergic systems.


Beyond restructuring. Futuristic rapid-cycle change to improve patient care.
Rapid changes in the healthcare environment provide an impetus to look closely at the way patient care is delivered. It is increasingly important to be both patient focused and cost effective in the delivery of care. No longer can tradition, organizational structures, or poor communication impede effective and efficient patient care. A rapid-cycle change process is one method that involves staff members in identifying and implementing needed change to improve patient care and to remove waste from the system.


The role of education in developing specialist practice.
It really is a great pleasure for me to write this paper. Before EDTNA was born, when it was a only a glimmer in its Mother's eye, I fell in love with renal nursing. And it was through renal nursing that I became involved with the Royal College of Nursing of the United Kingdom, which has played such an important role in advancing the art and science of nursing, and in encouraging the development of clinical nursing expertise, and the role of specialist practice.


Enterochromaffin-like cells in rat stomach respond to short-term infusion of high doses of cholecystokinin but not to long-term, sustained, moderate hyperCCKemia caused by continuous cholecystokinin infusion or pancreaticobiliary diversion.
The histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa are controlled by gastrin. An acute gastrin challenge induces release and accelerated resynthesis of ECL cell histamine. Long-term stimulation with gastrin causes ECL cell hyperplasia. We set out to study whether the ECL cells respond not only to gastrin but also to cholecystokinin (CCK). A wide dose range of gastrin-14 sulfated and -17 non-sulfated and CCK-8 sulfated (CCK-8s) and non-sulfated (CCK-8) was infused intravenously to rats for 3 h. The activity of the histamine-forming enzyme was measured at termination of infusion. Gastrins and CCK-8s were equally effective in activating the enzyme, whereas sulfated CCK-8 was notably less potent than the other three peptides. Clearly, the receptor responsible for activation of the ECL cells distinguishes poorly between gastrin-17 and CCK-8s, which is in line with the characteristics of the CCK-B receptor. Moreover, neither the response to gastrin-17 nor that to CCK-8s was affected by concomitant infusion of devazepide (200 micrograms/kg/h), a selective CCK-A-receptor antagonist. One group of rats received CCK-8s continuously via a minipump. Another group of rats was subjected to pancreaticobiliary diversion (PBD), which increases the plasma CCK concentration 10- to 20-fold. The rats were killed 7 or 10 weeks later, respectively, and the stomachs were analyzed with regard to mucosal growth and ECL cell hyperplasia. HyperCCKemic rats had increased pancreatic weights but showed no signs of growth stimulation in the stomach and no ECL cell hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuropsychological deficits following head injury in children.
Children who had sustained head injuries were divided into three groups on the basis of severity of injury defined according to neurological criteria, and their performance on a battery of neuropsychological tests was compared. The groups were matched for age and sex. Performance IQ and timed tests of motor speed, fine-motor coordination, tactual-spatial functions, and verbal fluency showed significantly greater deficits for severely injured patients than for those who were mildly or moderately injured. Relations between neurologic indices of severity of injury and psychological outcome measures were investigated. Glasgow Coma Scale severity scores and the duration of altered consciousness were related to performance on several major neuropsychological functions. Acute intracranial pressure measures were unrelated to outcome. Comparisons of neuropsychological profiles indicated that the pattern of deficit after severe head injury is more distinctive than are those after mild and moderate injuries. Deficit patterns were least similar for the mild and severe groups, and were most similar for the mild and moderate groups. Results were discussed in terms of their prognostic utility, and suggestions were made for the future study of neurologic-psychologic relations after head injury.


Solitary Trichoepithelioma of the Eyelid: A Clinico-Pathological Correlation.
Solitary trichoepithelioma of the eyelid is a very rare tumor, which needs to be differentiated from basaloid epithelioma and basal cell carcinoma. Diagnosis is based on clinical and histopathological examination. We present a case of an eyelid trichoepithelioma presenting as a long standing nodule with associated dermatochalasis. Although rare, this entity should be kept in the differential diagnosis of chronic, firm, nodular eyelid lesions.


Polymer monolithic capillary microextraction combined on-line with inductively coupled plasma MS for the determination of trace rare earth elements in biological samples.
A rapid and sensitive method based on polymer monolithic capillary microextraction combined on-line with microconcentric nebulization inductively coupled plasma MS has been developed for the determination of trace/ultratrace rare earth elements in biological samples. For this purpose, the iminodiacetic acid modified poly(glycidyl methacrylate-trimethylolpropane trimethacrylate) monolithic capillary was prepared and characterized by SEM and FTIR spectroscopy. Factors affecting the extraction efficiency, such as sample pH, sample flow rate, sample/eluent volume, and coexisting ions were investigated in detail. Under the optimal conditions, the LODs for rare earth elements were in the range of 0.08 (Er) to 0.97 ng/L (Nd) with a sampling frequency of 8.5 h(-1), and the RSDs were between 1.5% (Sm) and 7.4% (Nd) (c = 20 ng/L, n = 7). The proposed method was successfully applied to the analysis of trace/ultratrace rare earth elements in human urine and serum samples, and the recoveries for the spiked samples were in the range of 82-105%. The developed method was simple, rapid, sensitive, and favorable for the analysis of trace/ultratrace rare earth elements in biological samples with limited sample volume.


An opportunity not to be missed--how do we improve postpartum screening rates for women with gestational diabetes?
The ability to detect postpartum dysglycaemia, intervene and prevent type 2 diabetes in this high-risk population may be the most compelling reason to diagnose gestational diabetes. However, most studies show that less than 50% of women receive any glucose screening in the postpartum period and are thus denied this opportunity. Although many have advocated for simpler testing, the 75-g oral glucose tolerance test remains the gold standard as fasting glucose level will miss 30-40% of cases of type 2 diabetes and will not detect isolated impaired glucose tolerance. Haemoglobin A(1c) as a screening test has not been adequately studied. To improve postpartum screening rates, we need to increase awareness of the very high risk of type 2 diabetes, improve communication between providers, reduce fragmentation of care and introduce system factors that facilitate screening adherence.


Influence of five different priming solutions on platelet function in patients undergoing cardiac surgery.
The ideal choice of a priming solution of the cardiopulmonary bypass (CPB) and its influence on the hemostatic system are not clear. Addition of albumin was reported to inhibit platelet damaging by blood-surface interactions ("coating"). To explore this possibility in 60 consecutive male patients undergoing elective aortocoronary bypass grafting, five different priming solutions were randomly used: (1) 1000 mL of 5% dextrose + 1000 mL of Ringer's solution (RS) + 250 mL of 5% human albumin (HA); (2) 1850 mL of RS + 400 mL of 20% HA; (3) 1750 mL of RS + 500 mL of 10% low molecular weight hydroxyethyl starch (molecular weight average: 200,000; molar substitution ratio: 0.5); (4) 1750 mL of RS + 500 mL of 3.5% gelatin; (5) 2250 mL of RS. Platelet function was studied by aggregometry (= turbidometric technique; 1.0 and 2.0 mumol/L of adenosine diphosphate (ADP), 4 microL/mL of collagen, 25 mumol/L of epinephrine) before, during, and after CPB until the first postoperative day. Blood loss and need for homologous blood was not different between the groups. During CPB, maximum platelet aggregation induced by ADP was least compromised in group 1 and group 4. At the end of the operation ADP-induced aggregation increased in group 1 (+27%), whereas aggregation was decreased in the other priming solution groups. A significant increase in maximum aggregation was found in group 1 even on the first postoperative day (+132% +/- 16%). Collagen-induced aggregation was also least compromised in group 1. Epinephrine-induced platelet aggregation did not change and was similar for all groups. Maximum gradient of aggregation was influenced in an identical way as maximum aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)


High NaCl diet increases anterior hypothalamic alpha 2-adrenoceptors in SHR.
Previous studies carried out in our laboratories demonstrated that dietary NaCl supplementation induced an increase in blood pressure associated with a reduction in noradrenaline release in the anterior hypothalamic region of NaCl-sensitive spontaneously hypertensive rats (SHR). The present study tested the hypothesis that this reduction in noradrenaline release induces a compensatory increase in alpha 2-adrenoceptor number in the anterior hypothalamic region of SHR. Low affinity p-[3H]aminoclonidine (alpha 2-adrenoceptor agonist) binding in the anterior hypothalamic region was increased significantly in SHR, but not in normotensive Wistar-Kyoto (WKY) rats on a high (compared to a basal) NaCl diet. Increased p-[3H]aminoclonidine binding was present at 1 and 2 weeks following initiation of the diets. In contrast, in the posterior hypothalamic region of SHR, alpha 2-adrenoceptors were significantly reduced following 1 week on the high (compared to basal) NaCl diet, and no difference between groups was observed following 2 weeks on the diets. The high NaCl diet did not alter alpha 2-adrenoceptors in the medulla, nor did it affect alpha 1- or beta-adrenoceptors in any brain region studied in either SHR or WKY. In SHR, dietary Ca2+ supplementation diminished the blood pressure elevation associated with high NaCl diets, and simultaneously prevented the NaCl induced increase in alpha 2-adrenoceptors in the anterior hypothalamic region. These data support the hypothesis that, in susceptible individuals, changes in noradrenergic transmission in the anterior hypothalamic region contribute to the cardiovascular effects of dietary NaCl loading and Ca2+ supplementation.


Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology.
The increasing trend of carbapenem resistance in Acinetobacter baumannii worldwide is a concern since it limits drastically the range of therapeutic alternatives. Metallo-beta-lactamases (VIM, IMP, SIM) have been reported worldwide, especially in Asia and western Europe, and confer resistance to all beta-lactams except aztreonam. The most widespread beta-lactamases with carbapenemase activity in A. baumannii are carbapenem-hydrolysing class D beta-lactamases (CHDLs) that are mostly specific for this species. These enzymes belong to three unrelated groups of clavulanic acid-resistant beta-lactamases, represented by OXA-23, OXA-24 and OXA-58, that can be either plasmid- or chromosomally-encoded. A. baumannii also possesses an intrinsic carbapenem-hydrolysing oxacillinase, the expression of which may vary, that may play a role in carbapenem resistance. In addition to beta-lactamases, carbapenem resistance in A. baumannii may also result from porin or penicillin-binding protein modifications. Several porins, including the 33-kDa CarO protein, that constitute a pore channel for influx of carbapenems, might be involved in carbapenem resistance.


Decentralization of the DOTS programme within a Russian penitentiary system. How to ensure the continuity of tuberculosis treatment in pre-trial detention centres.
In Kemerovo region (Siberia), three pre-trial detention centres (SIZO; Ministry of Justice) serve as the gateway to the penitentiary system, comprised of 23 prisons and 30,000 detainees. The follow-up for tuberculosis (TB) patients released into civil society is unreliable. Due to varying detention times and frequent transfers to temporary detention centres (IVS; Ministry of Internal Affairs) for investigation and trial, and concerns about continuity of treatment, SIZOs were not included in the revised TB control programme initiated during 1996. To investigate the feasibility of DOTS (Directly Observed Therapy, Short-Course) expansion into SIZOs, general detainee release was studied by examining 10% of files from detainees admitted during 1998 (SIZOs 1,2,3). Then, 5% of general files from SIZO 1 were examined to determine SIZO-IVS flow; 224 TB patient files from SIZO 3 were evaluated to determine the pattern of release/transfer. TB patients in SIZO 3 have less chance of release before six months of detention than non-TB detainees (14/224, 6.3% versus 774/2276, 34%; p < 0.001). Among detainees not released, 60% are not moved during the first six months of detention. For those who move, the mean stay in IVS was 9.5 (+/- 6) days. The incidence of active disease detected upon entry to SIZO 3 was 4,560/100,000, the subsequent rate during the same year of detention 880/100,000. Despite frequent detainee movements between institutions, DOTS should be introduced into the earliest stages of detention to prevent case mismanagement, and links to the civilian programme should be developed.


Secondhand Smoke Enhances Lung Cancer Risk in Male Smokers: An Interaction.
Previous studies revealed that some indoor air pollutants and fine particle matter can interact with active smoking, enhancing lung cancer risk in smokers. Secondhand smoke (SHS), with remarkable differences from active smoking, contributes significantly to indoor air pollution and generates a considerable amount of fine particle matter, may cause a similar interaction with active smoking. Information on lifetime SHS along with active smoking and other confirmed or suspected risk factors for lung cancer was collected in this case-referent study. Odds ratios and the 95% confidence intervals (95% CIs) of smoking status in different levels of SHS were evaluated. Potential multiplicative and additive interactions were explored. Compared with never-smokers without SHS, current smokers who were exposed to a high level of SHS demonstrated the highest odds ratio (15.13, 95% CI: 8.60, 26.65), almost doubles the effect in the current smokers without SHS. Significant additive interactions between current smoking and high level of SHS were observed for all lung cancers (synergy index = 1.80, 95% CI: 1.02, 3.24) and the squamous carcinoma subgroup. High level of SHS exposure greatly enhanced lung cancer risk among current smokers, consistent with an additive interaction; while this interaction was predominant for the squamous carcinoma. The results provide new evidence to the rationale of promoting global smoking cessation. Some indoor air pollutants can interact with active smoking, yielding a synergistic effect on inducing lung cancer. SHS, with noticeable differences from active smoking, is a major source of indoor air pollution. However, little has been known about the effect of SHS in smokers and whether there is a similar interaction between SHS and active smoking. In this study, we evaluated their separate and joint effects and indeed found a more than additive interaction between them. This finding suggests a potential problem of gathering smoking aggravating by venue restriction policies and re-advocates policy efforts on smoking cessation.


Intra-observer and inter-observer agreement of the manual examination of the lumbar spine in chronic low-back pain.
Examination is a cornerstone in the manual procedures leading to mobilisation/manipulation of the low back. The observer variation of the more specific segmental tests remains to be investigated. Two skilled specialists in manual medicine examined the segmental changes in the lumbar spine. The patients were unknown to the examiners and no information of the case history was given. All test results were recorded by an observer present in the room who ensured that no conversation was allowed during the examination. The primary outcome measures were the kappa values for each test. The matching was defined as acceptable (acc) within two neighbouring levels and perfect (per) on the same level. Intra-observer variation (tested in 33 patients and 10 subjects without low-back pain): The agreement between first and second segmental diagnosis examination was 70% (per) and 82% (per + acc). Kappa values were: segmental diagnosis 0.60 (per) and 0.70 (per + acc), multifidus test 0.51 (per) and 0.60 (per + acc), sideflexion 0.57 (per) and 0.69 (per + acc), and ventral flexion 0.31 (per) and 0.45 (per + acc). Inter-observer variation (tested in 60 patients): The agreement for segmental diagnosis between the examiner A and B was 42% (per) and 75% (per + acc). Kappa values were: segmental diagnosis 0.21 (per) and 0.57 (acc), multifidus test 0.12 (per) and 0.48 (acc), sideflexion 0.22 (per) and 0.45 (acc), and ventralflexion 0.22 (per) and 0.44 (acc). By manual tests, skilled examiners seem to be able to diagnose segmental dysfunctions in the low back. The clinical implication of these dysfunctions remains to be clarified.


Preventive effect of taurine on experimental type II diabetic nephropathy.
It has been verified that taurine has some preventive effects on diabetes and its complications when used alone or together with other drugs, but there are few reports about taurine on the prevention of diabetic nephropathy, the mechanisms of which are still unknown. Taurine was administered to type diabetic rats induced by high fat high sugar diet combined with STZ injection. The preventive effect of taurine on diabetic nephropathy was investigated by detecting blood glucose, lipid metabolism, kidney function and glomerular basement membrane metabolism. Taurine could lower blood glucose, TG, TC, BUN, Scr, NAG, U-PRO, the expression of laminin B1(LBN1) mRNA, and increase HDL-C of diabetic rats. The results indicated that taurine could prevent the occurrence and development of diabetic nephropathy by decreasing blood glucose, improving lipid metabolism, glomerular basement membrane metabolism, and kidney function.


Association between excessive BMI increase during puberty and risk of cardiovascular mortality in adult men: a population-based cohort study.
Being overweight during childhood and adolescence is associated with increased risk of cardiovascular disease in adulthood, but the relative contribution of prepubertal childhood BMI and BMI change during puberty to adult mortality due to cardiovascular disease is unknown. We assessed the contribution of these two distinct developmental BMI parameters for cardiovascular mortality in adult men. As a part of the ongoing population-based BMI Epidemiology Study (BEST) in Gothenburg, Sweden, men born between 1945 and 1961 with information on both their childhood BMI at age 8 years and BMI change during puberty were included in the study and followed up until December, 2013. Participants who died or emigrated before age 20 years were excluded from the analysis. BMI was collected from paediatric growth charts and mandatory military conscription tests. Childhood overweight (BMI of ≥17·9 kg/m2) was defined according to the Centers for Disease Control and Prevention's cutoff at 8 years of age, and BMI change during puberty was defined as the difference between young adult BMI and childhood BMI (BMI at age 20 years minus BMI at age 8 years). Information on mortality was retrieved from high quality national registers with the participants' ten-digit personal identity number. We used Cox proportional hazard regression to analyse the association between exposures and mortality. The ethics committee of the University of Gothenburg, Sweden, approved the study and waived the requirement for written informed consent. We followed 37 672 Swedish men from age 20 years for a mean of 37·8 years (1 422 185 person-years follow-up). 3188 all-cause deaths and 710 cardiovascular deaths occurred during follow-up. The correlation between childhood BMI and BMI change during puberty was marginal (r=0·06). BMI change during puberty, but not childhood BMI, was independently associated with adult all-cause and cardiovascular mortality in men. Boys that became overweight during puberty (HR 2·39; 95% CI 1·86-3·09) and boys who were overweight consistently throughout childhood and puberty (1·85; 1·28-2·67), but not boys overweight in childhood that normalised during puberty (0·99, 0·65-1·50), had increased risk of cardiovascular mortality compared with participants who were not overweight in childhood or as young adults. The association between BMI change during puberty and cardiovascular mortality was non-linear with a substantial association above a threshold of 6·7 units increase in BMI. Excessive BMI increase during puberty is a risk marker of adult cardiovascular mortality. These results indicate that BMI should be monitored during puberty to identify boys with increased risk of adult cardiovascular mortality. Swedish Research Council, the Swedish Government (under the Avtal om Läkarutbildning och Medicinsk Forskning [Agreement for Medical Education and Research]), the Lundberg Foundation, the Torsten Söderberg Foundation, the Novo Nordisk Foundation, the Knut and Alice Wallenberg Foundation, and the Anna Ahrenberg Foundation.


Pre-Descemetic Placement of Intracorneal Ring Segments for Keratoconus after Mechanical Implantation.
We report the case of a 23-year-old male who was referred to our clinic for a routine follow-up examination. The patient was treated for keratoconus 3 years ago in Colombia, where intracorneal ring segments were implanted mechanically in both eyes to improve his visual acuity. Surprisingly, we discovered a pre-descemetic placement of intracorneal ring segments, which could lead to potential complications, under circumstances. We illustrate this impressive finding with slit-lamp photography and high-resolution anterior segment OCT and advocate for the use of femtosecond laser as the method of choice for intracorneal ring segment insertion in order to provide maximal precision and safety.


Role of microRNAs in leukemia stem cells.
Leukemia cells can carry a small subset of poorly differentiated cells, which are considered to be precursors of lymphoblasts, myeloblasts, or monoblasts. Thus these cells are also called leukemia stem cells (LSCs) because they are capable of instigating, maintaining and serially propagating leukemia in vivo, while retaining the ability to differentiate into committed progeny that lack these properties. Like hematopoietic stem cells (HSCs), LSCs possess the ability of self-renewal under a complex regulatory system. The recent discovery of microRNAs may shed new light on regulation of LSCs and leukemogenesis. As master gene regulators, microRNAs participate in these processes through coordinated work with key transcription factors required for hematopoiesis. Therefore, microRNAs could play a critical role in normal HSCs as well as LSCs. The purpose of this review is to provide updates on the role of microRNAs in HSCs and LSCs and to highlight their potential in differentiation therapy of leukemias.


Lack of matrix metalloproteinase (MMP)-1 and -3 expression in Ewing sarcoma may be due to loss of accessibility of the MMP regulatory element to the specific fusion protein in vivo.
Ewing sarcoma is a malignant bone and soft tissue tumor of children and young adults, which is known to be highly aggressive and invasive. It expresses specific chimeric genes (EWS-FLI-1, EWS-ERG, EWS-ETV1, and EWS-E1AF), the 3' portions of which are all members of the ETS family. ETS-related proteins, such as FLI-1, ERG, and E1AF, transactivate the promoters of matrix metalloproteinase (MMP) genes, which play important roles in the processes of invasion and metastasis. Therefore, we hypothesize that the Ewing sarcoma-specific chimeric genes also transactivate the MMP genes, contributing to the tumor's invasiveness and propensity for metastasis. To verify this hypothesis, we investigated the expression of MMPs in eight Ewing sarcoma cell lines. Surprisingly, MMP-1 and MMP-3 were not expressed at all in any of the cell lines. MMP-9 was expressed in four out of the eight cell lines, and MMP-2 and MT1-MMP in all of the cell lines. Ewing sarcoma-specific chimeric genes have been shown to transactivate the promoter of the MMP-1 gene by the reporter assay, and bind to the putative recognition sites in the MMP regulatory elements by the gel shift assay. However, an in vivo formaldehyde cross-linking study revealed that the chimeric protein did not bind to the predicted ETS recognition sites in the regulatory elements of the MMPs. These results indicate that the absence of the MMP expression in the tumor cells is at least in part due to the loss of accessibility of the ETS recognition sites in the regulatory elements of the MMP genes. Therefore, we should be careful before theorizing simply that a putative binding site is essential for the transcription of critical genes, since the binding of this fusion protein was found to be modulated in tumor cells in this study.


Differential effects of activity and climate on onset of subarachnoid hemorrhage.
Conflicting findings of the effect of climate on onset of subarachnoid hemorrhage (SAH) may result from the influence of strenuous activities which can trigger aneurysmal rupture independent of climatological factors. The effect of climate and patient activities on onset of SAH were analyzed. The clinical records of 786 consecutive patients with aneurysmal SAH admitted to our hospital for 10 years were reviewed. Activities at onset were categorized according to the intensity of strain at onset. Seasonal variation, circannual cyclic trend, and association with 90 meteorological factors were examined in each category and the results were compared between categories. Bimonthly occurrence in the light strain group showed a significant seasonal variation and cyclic trend with two peaks in early spring and fall, whereas no significant trend was detected in the overall patients and in the heavy strain group. The significant meteorological factors were global solar radiation, sunshine hours, changes in mean and minimum temperature and mean vapor pressure from the previous day, and minimum pressure in the previous 7 days. Lower global solar radiation in the light strain group was associated with onset with the lowest p value (p = 0.0046). No factors were significant in the heavy strain group. There is some evidence of the possible influence of climatological factors on onset of SAH without strenuous activity. Strenuous activity seems to affect onset more strongly, which masks any effect of climate.


Collagens of articular cartilage: structure, function, and importance in tissue engineering.
Collagen is a crucial matrix component of articular cartilage. Because articular cartilage is a load bearing tissue, developing mechanical integrity is a central goal of tissue engineering. The significant role of collagen in cartilage biomechanics necessitates creating a collagen network in tissue engineered constructs. An extensive network of collagen fibrils provides cartilage with mechanical integrity, but developing strategies to replicate this collagen network remains a challenge for articular cartilage tissue engineering efforts. To study the structure and biomechanics of the collagen network, many experimental and computational methodologies have been developed. However, despite extensive cartilage tissue engineering research, few studies have assessed collagen type, crosslinks, or fibril orientation. Further study of the collagen network, both within native tissue and engineered neotissue, will enable more robust constructs to be developed. This review focuses on the biology and biomechanics of the collagen network, relevant experimental methods for assessing the collagen network, and articular cartilage tissue engineering studies that have examined collagen.


Description of a new syndrome: auricular abnormalities and cleft lip in two sibs, in association with cleft palate and unusual opthalmological findings.
We describe the association of auricular abnormalities and cleft lip with or without cleft palate in two siblings. One sibling has postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus of 23 weeks gestation with severe cleft lip, cleft palate and external ear abnormalities. As this constellation of features has not been described together before, we believe this is a new syndrome.


Reduction mammaplasty in patients with bulimia nervosa.
Women with eating disorders have been disqualified as candidates for plastic surgery. We present a group of 6 young women with bulimia nervosa who presented with clinically symptomatic evidence of macromastia. All patients reported that dysfunctional eating habits, at least in part, where due to breast enlargement. Five patients underwent bilateral reduction mammaplasty. Patients were interviewed postoperatively and reported relief of physical symptoms and improvement in psychological well-being. Symptoms of eating disorders were completely eliminated or greatly reduced. This series has supported the contention that macromastia can produce a distortion of body image and become a secondary cause of eating disorders. Surgical correction of large breasts has improved body image, leads to the amelioration of associated eating disorders, and may in part represent a surgical treatment for a psychological abnormality. The presence of an eating disorder should not, therefore, automatically exclude a patient from surgical consideration. Routine preoperative evaluation of young women seeking plastic surgery should include a set of standard questions regarding eating behaviors.


Time to talk: counselling for people with dysphasia.
In this small-scale qualitative study, 20 dysphasic people, including some with severe language impairments, were offered up to 20 sessions of individual counselling. The trained counsellors were a speech and language therapist and a teacher who had personal experience of dysphasia. The paper describes how the service was set up, and how it was evaluated through the use of interviews before, during and after the process of counselling. In general, participants valued the service and a number of positive outcomes were described. Negative reactions were largely due to problems with the setting, timing and organization of the counselling and to the presence of social problems which could not be addressed through counselling. A number of recommendations for setting up a counselling service for people with dysphasia can be drawn from this study. These are discussed in this paper, together with the issues arising from the collaboration between dysphasic and non-dysphasic researchers.


Bronchoalveolar lavage and transbronchial biopsy in children following heart-lung and lung transplantation.
Between July 1985 and March 1992, 20 children received either heart-lung (11), double lung (8), or single lung (1) transplants at our center. Since 1988, flexible fiberoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy have been carried out to monitor for rejection or infection in these patients. As of March 31, 1992, we have performed a total of 112 transbronchial biopsies in our patients, who ranged from 6.8 to 18 years of age and 19.3 to 67.3 kg in weight. All but two of these procedures were carried out using conscious sedation and a transnasal approach. Four to seven biopsy samples were obtained at each procedure. One patient had hemorrhage (< 100 ml) and no patient had pneumothorax as a complication. Of the biopsy samples, 72.4 percent had a surface area of greater than 2 mm2, and 89.5 percent of the biopsy samples were deemed adequate for pathologic interpretation. We believe that for the majority of pediatric lung or heart-lung recipients, flexible bronchoscopy and transbronchial biopsy using conscious sedation and a transnasal approach is safe and permits the recovery of adequate tissue for pathologic evaluation. The avoidance of general anesthesia, endotracheal intubation, and mechanical ventilation at the time of bronchoscopy and transbronchial biopsy probably decreases the likelihood of pneumothorax as a complication of the procedure.


Implant-supported welded titanium frameworks in the edentulous maxilla: a 5-year prospective multicenter study.
This study evaluated the 5-year clinical and radiographic performance of fixed implant-supported maxillary prostheses with either welded titanium or conventional cast-gold alloy frameworks. Fifty-eight consecutive patients were provided with 349 osseointegrated Brånemark system implants in the edentulous maxilla at six different implant centers. Twenty-eight of the patients received, at random, prostheses with laser-welded titanium frameworks, and the remaining 30 patients had prostheses with conventional cast-gold alloy frameworks. Clinical and radiographic data were collected for 5 years after prosthesis placement. The titanium and cast-gold framework groups exhibited similar cumulative survival and success rates (CSR). The 5-year implant CSR from time of placement was 91.4% and 94.0%, respectively, and from prosthesis delivery the rate was 94.9% and 95.6%, respectively. The corresponding 5-year prosthesis CSRs were 96.4% and 93.3%. One patient from each group lost all the implants and turned to complete dentures within the first year of function. Another patient with a cast-gold framework had the prosthesis replaced after 4 years, basically because of problems with the veneering material. No fractures of implant components were observed during the follow-up period. Bone loss was on average 0.59 mm (SD 0.97 mm) during 5 years, with no statistical difference between the two groups. Welded titanium frameworks presented a similar favorable clinical performance as conventional cast-gold alloy frameworks in fixed implant-supported prostheses in the edentulous maxilla after 5 years in function. Implant failures were concentrated in only a few patients in each study group.


[Effects of platelet-rich plasma on hemostasis and transfusion requirement in vascular surgery].
To assess the effect of intraoperative autologous platelet-rich plasma (PRP) transfusion on haemostasis, blood loss and blood requirements during vascular surgery. Randomized clinical trial. Twenty patients undergoing elective abdominal infrarenal aortic aneurysmectomy, using autologous transfusion techniques (predonation programme and/or preoperative normovolaemic haemodilution and/or intraoperative use of a cell-saver), were randomly allocated either into the PRP group (n = 10) or the Control group (n = 10). In patients of PRP group, 10 mL.kg-1 of PRP were obtained over 40 to 50 min, prior to induction of anaesthesia, and compensated simultaneously with an equivalent amount of hydroxyethyl starch. Each PRP unit was transfused to its donor after aortic declamping. Blood samples were obtained before induction, before incision, at wound closing and at the end of PRP unit transfusion for determination of biological variables. The PRP units transfused in the patients of PRP group contained 755 +/- 117 mL of plasma with a platelet count of 62 +/- 31 G.L-1. The intra and postoperative blood losses were similar in both groups (1622 +/- 758 and 233 +/- 322 mL respectively in PRP group vs 1890 +/- 1331 and 291 +/- 303 mL respectively in Control group). In both groups, three patients required an additional transfusion of homologous blood. The results of biological tests (haematocrit, platelet and white cell counts, prothrombin time, aPTT, thrombin time, fibrinogen, D-dimers, proteins, calcium) were also similar between groups at the various times of sampling. The reinfusion of the PRP unit did not increase the platelet count. This study demonstrates that intraoperative infusion of autologous PRP does not decrease blood loss and homologous transfusion requirements in patients undergoing elective abdominal infrarenal aortic aneurysmectomy. This result can be related to the relatively moderate enrichment in platelets obtained with the centrifugation speed used in this study.


No bone tunnel enlargement in patients with open growth plates after transphyseal ACL reconstruction.
Bone tunnel enlargement after ACL reconstruction has been described extensively in adults. However, little is known about this phenomenon in patients with open growth plates. Thus, the goals of the current study were to evaluate changes in bone tunnel size in patients with open growth plates after transphyseal ACL reconstruction with suspensory fixation and to correlate tunnel size with clinical outcome after medium-term follow-up. Fourteen patients with open growth plates were included that underwent primary transphyseal ACL reconstruction using hamstrings autografts and suspensory fixation. Mean follow-up time was 7 years. At the time of follow-up, MRIs of the operated knee were performed, and outcome was assessed using KOS-ADLS, Lysholm score, IKDC Subjective Knee Form score, Knee Examination Form score, and KT-1000 measurements. On MRI, the cross-sectional area of the bone tunnels was assessed using special axial cuts perpendicular to the axes of the tunnels. Two orthopaedic surgeons and two radiologists analysed the MRIs. Change in bone tunnel size from surgery to follow-up was calculated. No significant changes in bone tunnel size from surgery to follow-up were found. Regarding outcome measures, KOS-ADLS averaged 95%, Lysholm Score averaged 96 points, IKDC Subjective Knee Form averaged 95%, IKDC Knee Examination Form scores were 8A, 5B, 1C, and KT-1000 measurements averaged 1.8 ± 1.4 mm. No significant correlations were found between tunnel size at follow-up and outcome measures. Based on our study, bone tunnel enlargement does not occur in patients who have open growth plates and undergo ACL reconstruction using suspensory fixation.


[Energy policy rather than climate policy].
Energy policy and climate policy are two different issues and should not be treated as if they were the same. Whether the climate gets warmer or colder, saving energy and developing sustainable forms of energy production remain of paramount importance because fossil hydrocarbons are likely to be exhausted soon. But climate policy is a fallacy: it is human arrogance to think we can control the climate by reducing emissions and by storing CO2 underground. In spite of rising CO2 levels, the climate has cooled down slightly over the past decade. Since the International Panel on Climate Change (IPCC) did not predict this, it is questionable whether they can reliably predict warming. Other factors such as solar activity are probably more important for climate than greenhouse gases. The danger of coupling energy policy to climate policy is evident: if the climate cools down, people will lose belief in the greenhouse effect and therefore also lose interest in saving energy.


Targeted Metabolomic Pathway Analysis and Validation Revealed Glutamatergic Disorder in the Prefrontal Cortex among the Chronic Social Defeat Stress Mice Model of Depression.
Major depressive disorder (MDD) is a severe psychiatric disease that has critically affected life quality for millions of people. Chronic stress is gradually recognized as a primary pathogenesis risk factor of MDD. Despite the remarkable progress in mechanism research, the pathogenesis mechanism of MDD is still not well understood. Therefore, we conducted a liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection of 25 major metabolites of tryptophanic, GABAergic, and catecholaminergic pathways in the prefontal cortex (PFC) of mice in chronic social defeat stress (CSDS). The depressed mice exhibit significant reduction of glutamate in the GABAergic pathway and an increase of L-DOPA and vanillylmandelic acid in catecholaminergic pathways. The data of real-time-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis revealed an altered level of glutamatergic circuitry. The metabolomic and molecular data reveal that the glutamatergic disorder in mice shed lights to reveal a mechanism on depression-like and stress resilient phenotype.


The Maracaibo Aging Study: population and methodological issues.
The Maracaibo Aging Study is a longitudinal, population-based, one-step multidisciplinary study of age-related diseases, with a particular focus on memory-related disorders, among subjects over 55 years living in a neighborhood of the city of Maracaibo, Venezuela. Three phases were scheduled for this study. First, a door-to-door survey was conducted in order to build a registry and to obtain general and sociodemographic characteristics. During the second phase, information regarding changes in the abilities of the subjects was collected. The third phase consisted of a full neuropsychiatric examination, cardiovascular evaluation, nutritional assessment, neuropsychological testing, routine laboratory tests and genetic analysis. 3,657 subjects were surveyed between January and August, 1998. There were more women than men, and the average number of years of formal education was low, particularly among women. The limitations and strengths of the study are discussed.


A non-invasive technique for cell volume determination in perfused rat liver.
1) In isolated perfused rat liver, the intracellular ([14C]urea-accessible minus [3H]inulin accessible) water space was determined from the washout profiles of simultaneously infused [3H]inulin and [14C]urea. The washout profile of infused [14C]urea was indistinguishable from that of infused tritiated water. During normotonic perfusions and without hormones or amino acids in influent, the intracellular water space was 548 +/- 10 microliters/g liver wet weight (n = 44). Use of [3H]raffinose instead of [3H]inulin as marker for the extracellular space yielded almost identical values for the intracellular water space (i.e. 98.9 +/- 0.2% of that found with [3H]inulin/[14C]urea). When volume-regulatory K+ fluxes were completed following hypo- and hypertonic exposure of perfused rat livers and a steady state was reached, the intracellular water space was found to be increased and decreased, respectively. The extent of anisotonic exposure was linearly related to the change of intracellular water space. 2) Anisotonicity-, glutamine- and glycine-induced liver mass changes were almost fully explained by the simultaneously occurring alterations of the intracellular water space, indicating that cell volume changes in perfused rat liver under these conditions are not accompanied by significant changes of the extracellular space. Volume-regulatory K+ (plus accompanying anion) efflux following hypotonic perfusion accounted for about 70-85% of regulatory cell volume decrease, which occurred during the first 10 min of hypotonic exposure. 3) Cell volume of isolated hepatocytes was determined as the "hepatocrit" after gentle centrifugation of the cell suspension.(ABSTRACT TRUNCATED AT 250 WORDS)


Shape-specific detection based on fluorescence resonance energy transfer using a flexible water-soluble conjugated polymer.
We present the detection of the shape-specific conformation of DNA based on the fluorescence resonance energy transfer (FRET) by using a novel flexible water-soluble cationic conjugated polymer (CCP). The flexible backbone of CCP has more conformational freedom with the potential to be responsive to analyte shape by electrostatic interaction between flexible CCP and negatively charged DNA. The analyte shape dependent recognition is accomplished by structural changes that compressed or extended the flexible CCP. The morphology-dependent spectral properties of the novel flexible polymer related to the analyte shapes are investigated in detail, where two types of chromophores, referred to as "isolated" segment and "packed" segment aggregates, within the flexible polymer are identified by means of ensemble and single molecule measurements upon binding with different geometric DNA. The change in fluorescence intensity upon binding with shape-specific DNA without obvious color shifts makes this novel flexible polymer a suitable CCP donor for FRET measurements. The results provide insights for understanding the spectral properties of flexible water-soluble CCP and CCP/DNA interaction related to the geometry of target analyte.


[Clinical Observation of Erlotinib as the First-line Treatment for Patients with Advanced Non-small Cell Lung Cancer.].
To evaluate the efficacy and toxicity of erlotinib as the first-line therapy for advanced non-small cell lung cancer (NSCLC). A total of 28 pathologically-confirmed NSCLC patients who could not receive willingly or tolerate traditional cytotoxic drugs chemotherapy were enrolled. Erlotinib was orally administered 150 mg daily until disease progression or the occurrence of intolerable toxicity. Among a total of 28 patients, the objective response rate (ORR) of erlotinib was 28.6%. The disease control rate (DCR) was 60.7%. The rate of symptom relief was 53.6%. The median progression free survival (PFS) was 3.2 (95%CI: 0.851-5.585) months. The median overall survival (OS) was 9.6 (95%CI: 7.179-12.021) months. One-year survival rate was 32.1%. The therapeutic effect was better in patients with rash. Most of the toxicities were grade I and grade II toxicity. The most common adverse events were rash (46.4%), diarrhea (32.1%), skin dry (25.0%), anorexia(17.9%), fatigue (10.7%) and increased transaminase (7.1%). Erlotinib provided another choice for the patients who could not willingly receive or tolerate chemotherapy.


On the Role of Mitochondrial Oxidative Phosphorylation in Photosynthesis Metabolism as Studied by the Effect of Oligomycin on Photosynthesis in Protoplasts and Leaves of Barley (Hordeum vulgare).
Low concentrations of oligomycin, which strongly inhibit mitochondrial oxidative phosphorylation but do not affect chloroplast photophosphorylation, caused an inhibition of photosynthesis by 30 to 40% in barley (Hordeum vulgare L.) leaf protoplasts. This inhibition is reversed and the full rate of photosynthesis is regained when the protoplasts are ruptured so as to leave the chloroplasts intact. Oligomycin fed into barley leaves by the transpiration stream inhibited photosynthesis in these leaves by up to 60%. The measurement of metabolites in protoplast and leaf extracts showed that oligomycin caused a decrease in the ATP/ADP ratio and an increase in the content of glucose- and fructose 6-phosphate. Subcellular analysis of protoplasts revealed that the decrease in ATP/ADP ratio in the cytosol was larger than in the stroma and that the increase in hexose monophosphates was restricted to the cytosol, whereas the stromal hexosemonophosphates decreased upon the addition of oligomycin. Moreover, oligomycin caused an increase in the triosephosphate-3-phosphoglycerate ratio. It is concluded from these results that during photosynthesis of a plant leaf cell mitochondrial oxidative phosphorylation contributes to the ATP supply of the cell and prevents overreduction of the chloroplast redox carriers by oxidizing reductive equivalents generated by photosynthetic electron transport.


Founder effect of a pathogenic MSH2 mutation identified in Spanish families with Lynch syndrome.
Lynch syndrome is caused by germline mutations in the mismatch repair genes MLH1, MSH2, MSH6 or PMS2. The novel MSH2 c.[2635-3T>C; 2635-5C>T] mutation was identified in 4 Lynch families, cosegregating with the disease. This mutation, located in intron 15, was predicted to alter the correct mRNA processing by in silico analysis. Our aim was to perform the c.[2635-3T>C; 2635-5C>T] mutation screening in high risk CRC cases and control populations, to evaluate the founder effect in our population by haplotype analysis and to confirm the pathogenic effect of the mutation by MSH2 expression studies. Mutation screening was performed by SSCP and CSCE in genomic DNA from 323 high risk CRC cases and 289 controls. Haplotyping was performed analysing 4 MSH2 extragenic microsatellite markers (D2S288, D2S2227, D2S1247 and D2S1248) in 50 controls and mutation carriers by using the PHASE program. We analysed the effect of the mutation in mRNA processing by RT-PCR and in MSH2 expression by qRT-PCR using RNA from 5 mutation carriers and 18 controls. None of the remaining high risk CRC cases or controls analysed harboured the mutation. We identified a common telomeric haplotype and two centromeric haplotypes, both rare in our population. Although we were not able to identify any abnormal transcript by RT-PCR with the design used, we observed a significant reduction of mRNA MSH2 expression in carriers when compared with controls. Haplotype analyses suggest a founder effect of the c.[2635-3T>C; 2635-5C>T] MSH2 mutation and expression studies support a pathogenic role of this mutation.


Pandemic influenza planning in nursing homes: are we prepared?
Avian influenza or Influenza A (H5N1) is caused by a viral strain that occurs naturally in wild birds, but to which humans are immunologically naïve. If an influenza pandemic occurs, it is expected to have dire consequences, including millions of deaths, social disruption, and enormous economic consequences. The Department of Health and Human Resources plan, released in November 2005, clearly affirms the threat of a pandemic. Anticipating a disruption in many factions of society, every segment of the healthcare industry, including nursing homes, will be affected and will need to be self-sufficient. Disruption of vaccine distribution during the seasonal influenza vaccine shortage during the 2004/05 influenza season is but one example of erratic emergency planning. Nursing homes will have to make vital decisions and provide care to older adults who will not be on the initial priority list for vaccine. At the same time, nursing homes will face an anticipated shortage of antiviral medications and be expected to provide surge capacity for overwhelmed hospitals. This article provides an overview of current recommendations for pandemic preparedness and the potential effect of a pandemic on the nursing home industry. It highlights the need for collaborative planning and dialogue between nursing homes and various stakeholders already heavily invested in pandemic preparedness.


Comparative study of the Triton X-100-sodium deoxycholate method and detergent-enzymatic digestion method for decellularization of porcine aortic valves.
Valve replacement is the primary surgical treatment for heart valve disease. However, the clinical benefit of biological valve substitutes is limited by their potential immunogenicity. To seek a better method of preparing biological scaffolds for tissue engineering heart valves, we compared the ability of different decellularization procedures to remove cells and maintain the scaffold structure. Specimens of fresh porcine aortic valve leaflets were randomly divided into group I (n = 16), group II (n = 16) and group III (n = 16). The valve leaflets in group I were not decellularized; group II were treated with Triton X-100 and sodium deoxycholate; and group III were treated by a detergent-enzymatic digestion method. The valve leaflets were investigated by gross examination, hematoxylin-eosin staining, Masson's trichrome staining, and scanning electron microscopy to observe the valve structure and the integrity of collagen and elastin. The DNA content was measured to confirm the removal of cells. The detergent-enzymatic digestion method completely removed cells and led to valve fiber structural alterations in group III. The Triton X-100-sodium deoxycholate method achieved both complete decellularization and preservation of the valve fiber structure in group II. The detergent-enzymatic digestion method is a better technique for decellularization than the Triton X-100-sodium deoxycholate method, as it enables both complete decellularization and preservation of the valve scaffold structure.


Temporary Rise in Blood Thrombogenicity in Patients with Acute Myocardial Infarction.
Objective Although blood thrombogenicity seems to be one of the determinant factors for the development of acute myocardial infarction (MI), it has not been dealt with in-depth. This study aimed to investigate blood thrombogenicity and its change in acute MI patients. Methods and Results We designed a prospective, observational study that included 51 acute MI patients and 83 stable coronary artery disease (CAD) patients who underwent cardiac catheterization, comparing thrombogenicity of the whole blood between: (1) acute MI patients and stable CAD patients; and (2) acute and chronic phase in MI patients. Blood thrombogenicity was evaluated by the Total Thrombus-Formation Analysis System (T-TAS) using the area under the flow pressure curve (AUC 30 ) for the AR-chip. Acute MI patients had significantly higher AUC 30 than stable CAD patients (median [interquartile range], 1,771 [1,585-1,884] vs. 1,677 [1,527-1,756], p = 0.010). Multivariate regression analysis identified acute MI with initial TIMI flow grade 0/1 as an independent determinant of high AUC 30 ( β = 0.211, p = 0.013). In acute MI patients, AUC 30 decreased significantly from acute to chronic phase (1,859 [1,550-2,008] to 1,521 [1,328-1,745], p = 0.001). Conclusion Blood thrombogenicity was significantly higher in acute MI patients than in stable CAD patients. Acute MI with initial TIMI flow grade 0/1 was significantly associated with high blood thrombogenicity by multivariate analysis. In acute MI patients, blood thrombogenicity was temporarily higher in acute phase than in chronic phase.


Ca(2+)-dependent and thapsigargin-inhibited phosphorylation of Na+,K(+)-ATPase catalytic domain following chimeric recombination with Ca(2+)-ATPase.
Two chimeric proteins comprising the Na,K-ATPase catalytic domain (large cytosolic loop) and the two flanking regions of the Ca-ATPase were obtained by transient or stable expression in mammalian cells transfected with recombinant DNA. In the first chimera (CpNC), a large portion (containing the nucleotide-binding site) of the cytosolic loop between putative membrane spans M4 and M5 of the sarcoendoplasmic reticulum Ca2+ (SERCA) 1 (fast muscle) ATPase was replaced by the corresponding portion of the Na,K-ATPase alpha 1 subunit. In the second chimera (CNpC), an even larger portion (containing the nucleotide-binding site and the phosphorylation site) of the analogous cytosolic loop of the SERCA2 (cardiac muscle) ATPase was replaced by the corresponding portion of the Na,K-ATPase alpha 1 subunit. Steady state Ca2+ transport and coupled ATP hydrolysis by the chimeric proteins were negligible as compared to those obtained with SERCA enzymes. Nevertheless, the chimeric proteins were able to utilize ATP to form phosphoenzyme levels equal to those formed by SERCA ATPases. Chimeric and SERCA enzymes exhibited an identical Ca2+ requirement for ATP utilization and sensitivity to thapsigargin (TG) which is a specific inhibitor of SERCA ATPase and not of Na,K-ATPase. Furthermore, both SERCA and chimeric enzymes could be phosphorylated with P(i), and this reaction required removal of Ca2+. In comparative experiments, the functional pattern of seemingly unaffected phosphoenzyme formation and inhibited Ca2+ transport was produced in the SERCA ATPase even by single mutation of Pro337 to Ala, evidently due to defective protein conformation. Retention of Ca2+ and TG sensitivity by the chimeric proteins demonstrates that the Ca(2+)- and TG-binding domains do not reside within the cytosolic loop replaced by chimeric substitution and strongly support previous studies suggesting that binding of calcium required for enzyme activation occurs within the membrane-bound region of the SERCA ATPases (Clarke et al., 1989a; Sumbilla et al., 1991).


[Ethical considerations in the evolution of organised cancer screening programs].
Ethical considerations in the evolution of organised cancer screening programs Since 2009, the French National Cancer Institute has set up a working group on the ethics of screening programs for breast, colon and cervical cancer. Collective and individual interest, equity and respect for autonomy are the values addressed in the respective reports. Ethical analysis has highlighted issues that are specific to each programme: the importance of the information provided by health professionals in a context of uncertainty for breast cancer screening; health professionals as a relay of information, access to test and support in the colorectal cancer screening process and, for cervical cancer screening, the implementation of an organisation adapted to women populations concerned. A public health policy whose efficiency depends on the public's adhesion of screening proposals must respect a fundamental ethical principle, namely the assessment of the benefit/risk balance.


Prostate cancer: psychosocial implications and management.
This review summarizes some of the key psychosocial issues related to prostate cancer, both generally and for an older adult population. It focuses on three main areas: quality-of-life issues, psychosocial implications and management of these psychosocial issues. Broadly, the article presents information on the general background, screening guidelines, common side effects of treatment and current psychiatric and psychological management strategies in prostate cancer. The article addresses the clinical approaches, as well as the complexities that surface when deciding the treatment for patients with prostate cancer. Clinical and future implications are also discussed.


Genome-wide patterns of segregation and linkage disequilibrium: the construction of a linkage genetic map of the poplar rust fungus Melampsora larici-populina.
The poplar rust fungus Melampsora larici-populina causes significant yield reduction and severe economic losses in commercial poplar plantations. After several decades of breeding for qualitative resistance and subsequent breakdown of the released resistance genes, breeders now focus on quantitative resistance, perceived to be more durable. But quantitative resistance also can be challenged by an increase of aggressiveness in the pathogen. Thus, it is of primary importance to better understand the genetic architecture of aggressiveness traits. To this aim, our goal is to build a genetic linkage map for M. larici-populina in order to map quantitative trait loci related to aggressiveness. First, a large progeny of M. larici-populina was generated through selfing of the reference strain 98AG31 (which genome sequence is available) on larch plants, the alternate host of the poplar rust fungus. The progeny's meiotic origin was validated through a segregation analysis of 115 offspring with 14 polymorphic microsatellite markers, of which 12 segregated in the expected 1:2:1 Mendelian ratio. A microsatellite-based linkage disequilibrium analysis allowed us to identify one potential linkage group comprising two scaffolds. The whole genome of a subset of 47 offspring was resequenced using the Illumina HiSeq 2000 technology at a mean sequencing depth of 6X. The reads were mapped onto the reference genome of the parental strain and 144,566 SNPs were identified across the genome. Analysis of distribution and polymorphism of the SNPs along the genome led to the identification of 2580 recombination blocks. A second linkage disequilibrium analysis, using the recombination blocks as markers, allowed us to group 81 scaffolds into 23 potential linkage groups. These preliminary results showed that a high-density linkage map could be constructed by using high-quality SNPs based on low-coverage resequencing of a larger number of M. larici-populina offspring.


The effects of Pilates on health-related outcomes in individuals with increased risk of fracture: a systematic review.
This systematic review examined the effect of Pilates on health-related outcomes in individuals with increased fracture risk to inform the 2021 Clinical Practice Guidelines for Management of Osteoporosis and Fracture Prevention in Canada. Seven electronic databases were searched to December 2020. Studies of Pilates in men and postmenopausal women aged ≥50 years with low bone mineral density (BMD), history of fragility fracture, or moderate-high risk of fragility fracture were included. Two reviewers independently screened studies and performed risk of bias assessment. Of 7286 records and 504 full-text articles, 5 studies were included, encompassing data from 143 participants (99% female). Data were insufficient for meta-analyses. There is low-certainty evidence that Pilates improved physical functioning and health-related quality of life. The effect of Pilates on falls and BMD is uncertain. No evidence was available for the effect of Pilates on mortality, fractures, or adverse events. Overall, Pilates may improve physical functioning and quality of life. Evidence of benefits relative to harms of Pilates in people with increased fracture risk, particularly males, is limited. PROSPERO registration: CRD42019122685. Novelty: Pilates may improve physical functioning and quality of life in women with osteoporosis. Evidence of the effect of Pilates on BMD, falls, fractures, or adverse events is limited.


Severe congenital rickets secondary to maternal hypovitaminosis D: a case report.
We report a full-term baby boy who presented soon after birth with severe congenital rickets. Maternal and neonatal vitamin D levels were very low and the infant responded well to oral vitamin D. Transient secondary hyperparathyroidism normalised on treatment. The mother's vitamin D deficiency was attributed to the region's cultural dress code which prevents exposure to sunlight. There has not been a previous report of severe congenital rickets from this region.


A Rare Case of Benign Pneumatosis Intestinalis with Portal Venous Gas and Pneumoperitoneum Induced by Acarbose.
Alpha glucosidase inhibitors have been shown to be associated with pneumatosis intestinalis (PI) in recent reports. We herein report the case of a 73-year old man who received treatment with an alpha glucosidase inhibitor (acarbose) and presented with acute abdomen. A computed tomography scan demonstrated PI in addition to intrahepatic portal air and pneumoperitoneum. During exploratory laparotomy, we found no evidence of hollow organ perforation or bowel necrosis. The patient recovered after conservative treatment with cessation of the alpha glucosidase inhibitor. This is the first report to describe the combination of PI with portal venous gas and pneumoperitoneum caused by an alpha-glucosidase inhibitor.


Draft Genome Sequence of an Attenuated Streptococcus agalactiae Strain Isolated from the Gut of a Nile Tilapia (Oreochromis niloticus).
Streptococcus agalactiae is a pathogen that causes severe anthropozoonosis within a broad range of hosts from aquatic animals to mammals, including human beings. Here, we describe the draft genome of S. agalactiae HZAUSC001, a low-virulent strain isolated from the gut of a moribund tilapia (Oreochromis niloticus) in China.


ET-1 stimulates ERK signaling pathway through sequential activation of PKC and Src in rat myometrial cells.
In this study, we analyzed in rat myometrial cells the signaling pathways involved in the endothelin (ET)-1-induced extracellular signal-regulated kinase (ERK) activation required for the induction of DNA synthesis. We found that inhibition of protein kinase C (PKC) by Ro-31-8220 abolished ERK activation. Inhibition of phospholipase C (PLC) by U-73122 or of phosphoinositide (PI) 3-kinase by wortmannin partially reduced ERK activation. A similar partial inhibition was observed after treatment with pertussis toxin or PKC downregulation by phorbol ester treatment. The effect of wortmannin was additive with that produced by PKC downregulation but not with that due to pertussis toxin. These results suggest that both diacylglycerol-sensitive PKC, activated by PLC products, and diacylglycerol-insensitive PKC, possibly activated by a G(i)-PI 3-kinase-dependent process, are involved in ET-1-induced ERK activation. These two pathways were found to be activated mainly through the ET(A) receptor subtype. ET-1 and phorbol ester stimulated Src activity in a PKC-dependent manner, both responses being abolished in the presence of Ro-31-8220. Inhibition of Src kinases by PP1 abrogated phorbol ester- and ET-1-induced ERK activation. Finally, ET-1 activated Ras in a PP1- and Ro-31-8220-sensitive manner. Altogether, our results indicate that ET-1 induces ERK activation in rat myometrial cells through the sequential stimulation of PKC, Src, and Ras.


Seroprevalence of SARS-CoV-2 antibodies in social housing areas in Denmark.
COVID-19 is thought to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas. We conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning risk factors associated with COVID-19. As a proxy for the general Danish population we accessed data on seroprevalence from Danish blood donors (total Ig ELISA assay) in same time period. Of the 13,279 included participants, 2296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p > 0.001). Seropositivity was higher among males (RR 1.1, 95% CI 1.05-1.22%, p = 0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p = 0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among household members (OR 5.0, 95% CI 4.1-6.2 p < 0,001). Living at least four people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.0-1.6, p = 0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.6, p = 0.003). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Danish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased slightly with age. Living in multiple generations households or in households of more than four persons was a strong risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.


The effect of laser in situ keratomileusis on low contrast vision.
To determine the effects of laser in situ keratomileusis (LASIK) on low contrast visual acuity. Thirty eyes of 15 LASIK patients with myopia and astigmatism were evaluated preoperatively, and 1 and 3 months postoperatively. High contrast visual acuity (HCVA), low contrast visual acuity (LCVA), and contrast threshold were determined. Mean spherical correction (SE) was -3.24 +/- 1.90 D; 16 eyes had a mean SE between -1.00 and -3.00 D, and 14 eyes were between -3.25 and -6.50 D. There was no significant change in HCVA observed at 1 and 3 months in any eye. There was a decrease in LCVA in eyes with a correction >3 D SE at 1 month (P=.04), which returned to normal at 3 months (P=.13). There was an increase in the contrast threshold at 1 month (P=.016). When eyes were divided into groups, those with >3D SE correction had an increase in contrast threshold at 1 month (P=.002); no change was seen in eyes with <3D SE correction (P=.15). At 3 months, contrast threshold was similar to baseline values in all eyes (P=.226). LASIK transiently decreased low contrast visual function in patients with greater than 3.00 D of myopic correction.


[Conditions associated with impaired social skills in a convenience sample of crack users].
The article analyzes conditions associated with low scores on the Social Skills Inventory (SSI) among crack users in Greater Metropolitan Porto Alegre, Rio Grande do Sul State, Brazil, based on a cross-sectional study in a convenience sample of 519 individuals interviewed in 2011. Low SSI scores occurred in 52.8% of the sample, and there were no differences according to currently active use of crack (yes/no) or current addiction treatment. Higher likelihood of low SSI was associated with crack users in pre-contemplation or contemplation in University of Rhode Island Change Assessment - URICA (p = 0.031), high Beck Depression Inventory - BDI scores (p = 0.037), mourning a deceased child (p = 0.001), and having committed armed robbery to obtain crack (p = 0/020). Lower likelihood of low SSI was associated with 9 or more years of schooling (p = 0.001), high social support (p < 0.001), high resilience (p < 0.001), having lost contact with parents (p = 0.032), history of hospitalization due to crack (p = 0.009), and history of sex to obtain crack (p = 0.009). The findings are clinically useful and highlight the issue's importance.