A major chemotaxis gene cluster in Azospirillum brasilense and relationships between chemotaxis operons in alpha-proteobacteria.
Azospirillum brasilense shows chemotaxis to a variety of nutrients and oxygen. Genes encoding the central signal transduction pathway in chemotaxis were identified by phenotypic complementation of generally non-chemotactic mutants. Sequencing of a DNA fragment, which complemented two different mutants, revealed a region of five open reading frames translated in one direction and encoding homologs of known genes comprising excitation and adaptation pathways for chemotaxis in other bacterial species. The major chemotaxis gene cluster appears to be essential for all known behavioral responses that direct swimming motility in A. brasilense. Phylogenetic and genomic analysis revealed three groups of chemotaxis operons in alpha-proteobacterial species and assigned the A. brasilense operon to one of them. Interestingly, operons that are shown to be major regulators of behavior in several alpha-proteobacterial species are not orthologous.


Distinctive electrophoretic patterns of esterases from Klebsiella pneumoniae, K. oxytoca, Enterobacter aerogenes and E. gergoviae.
Esterases of 14 strains of Klebsiella pneumoniae, 14 strains of K. oxytoca, 16 strains of Enterobacter aerogenes and 16 strains of E. gergoviae were analysed by horizontal electrophoresis in polyacrylamide-agarose gel. Four principal esterase bands (designated E1 to E4) and nine minor bands differing in their activity towards synthetic substrates and in their sensitivity to heat and to di-isofluoropropyl phosphate were defined. The comparative distribution of bands showed that the four species analysed were characterized by distinct electrophoretic patterns of their esterases. Band E1 was found in all four species, bands E2 and E3 only in K. oxytoca and band E4 only in some strains of E. gergoviae. The apparent molecular weights of esterases E2 and E3, determined by electrophoresis in a 4 to 30% polyacrylamide gradient gel, were 58000 (+/- 1000) and 72000 (+/- 1800), respectively.


Partial breast reconstruction with mini superficial inferior epigastric artery and mini deep inferior epigastric perforator flaps.
In this study, partial breast reconstruction was undertaken after breast conservation therapy using mini abdominal free flaps on both an immediate and delayed basis.Patient demographics, oncologic status, reconstructive data, and complications were collected from medical records.Twelve patients (age range 39-60) were included in this study with a mean follow-up time of 5 years. Ten mini superficial inferior epigastric artery flaps and 2 mini deep inferior epigastric perforator flaps were used (7 immediate and 5 delayed reconstructions). No flap lost, 1 minor abdominal wound dehiscence, and no local or distant recurrences were noted. Good to excellent results were reported by 91% of the women.In properly selected patients with high motivation toward breast conservation, tailored abdominal mini-free flaps can safely and satisfactorily be implemented for the reconstruction of partial mastectomy defects. Patients should be comprehensively educated on the potential future implications of using the abdominal donor site for partial breast reconstruction.


Pregnancy in women with multiple sclerosis in France from 2010 to 2015: Incidence, outcomes, and exposure to disease-modifying therapies.
Multiple sclerosis (MS) is usually diagnosed between 20-40 years old, when women often plan to have children. Our objectives were to estimate pregnancy incidence rates in women with multiple sclerosis (MS), and to describe the use of disease-modifying therapies (DMTs) before conception and during pregnancy, and pregnancy outcomes. This retrospective cohort study included all 15- to 49-year-old women with MS in the French national health insurance database over 2010-2015. A pregnancy was exposed if a DMT reimbursement claim occurred during pregnancy or in the 14 preceding days. We used zero-inflated negative binomial (ZINB) regression models to estimate incidence rates and ordinal and multinomial regression models to estimate DMT exposure and pregnancy outcomes. The pregnancy incidence rate was 4.5 per 100 person-years. The probability of having a DMT-exposed pregnancy increased from 0.22 in 2010 to 0.30 in 2015. The probability of live birth was 0.72 (95% CI = 0.70-0.74) for exposed pregnancies (varied considerably among DMTs), 0.77 (95% CI = 0.76-0.79) without treatment, and 0.81 (95% CI = 0.79-0.83) if treatment was stopped within the previous year. In this population-based study, we showed an increase of exposed pregnancies over time, beta-interferon and glatiramer acetate being the most used DMTs and associated with the highest probabilities of live birth. Interrupted exposed pregnancies may reflect undesired pregnancies or fear of an adverse outcome, while recent DMT stop probably reflects pregnancy planning.


Aortic aneurysms and consumptive coagulopathy.
We describe three cases of consumptive coagulopathy caused by extensive thrombus formation in otherwise 'uncomplicated' aortic aneurysms. These cases demonstrate the importance of performing a coagulation screen in any patient presenting with thrombocytopenia who may have an aortic aneurysm. Effective therapy with low-dose heparin was demonstrated with subsequent haemostasis being maintained with warfarin.


Interrelated modification of excitatory and inhibitory synapses in three-layer olivary-cerebellar neural network.
The model of three-layer olivary-cerebellar neural network with modifiable excitatory and inhibitory connections between diverse elements is suggested. The same Hebbian modification rules are proposed for Purkinje cells, granule (input) cells, and deep cerebellar nuclei (output) cells. The inverse calcium-dependent modification rules for these cells and hippocampal/neocortical neurones or Golgi cells are conceivably the result of the involvement of cGMP and cAMP in postsynaptic processes. The sign of simultaneous modification of excitatory and inhibitory inputs to a cell is opposite and determined by the variations in pre- and/or postsynaptic cell activity. Modification of excitatory transmission between parallel fibers and Purkinje cells, mossy fibers and granule cells, and mossy fibers and deep cerebellar nuclei cells essentially depends on inhibition effected by stellate/basket cells, Golgi cells and Purkinje cells, respectively. The character of interrelated modifications of diverse synapses in all three layers of the network is influenced by olivary cell activity. In the absence (presence) of a signal from inferior olive, the long-term potentiation (depression) in the efficacy of a synapse between input mossy fiber and output cell can be induced. The results of the suggested model are in accordance with known experimental data.


Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases.
Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised children. Invasive aspergillosis has been well characterized in adults; however, the incidence and analysis of risk factors, diagnostic tools, treatments, and outcomes have not been well described for a large cohort of pediatric patients. We conducted the largest retrospective review of contemporary cases of proven and probable pediatric invasive aspergillosis diagnosed at 6 major medical centers (January 1, 2000, to July 1, 2005). Aspergillus fumigatus was the species most frequently recovered (52.8%) for the 139 patients analyzed. The majority of the children had a malignancy with or without hematopoietic stem cell transplant. Significant risk factors that impacted survival were immunosuppressive therapies and allogeneic stem cell transplant. The most common clinical site of invasive aspergillosis was the lungs (59%), and the most frequent diagnostic radiologic finding was nodules (34.6%). Only 2.2% of children showed the air crescent sign, 11% demonstrated the halo sign, and cavitation was seen in 24.5% of patients. Before the diagnosis of invasive aspergillosis, 43.1% of patients received fluconazole, and 39.2% received liposomal amphotericin B. After the diagnosis of invasive aspergillosis, 57% were treated with a lipid formulation of amphotericin B; however, 45.8% received > or = 3 concomitant antifungal agents. Analysis did not show superiority of any 1 antifungal related to overall mortality. A total of 52.5% (73 of 139) died during treatment for invasive aspergillosis. Of all the interventions implemented, surgery was the only independent predictor of survival. Our analyses revealed common findings between adult and pediatric invasive aspergillosis. However, one key difference is diagnostic radiologic findings. Unlike adults, children frequently do not manifest cavitation or the air crescent or halo signs, and this can significantly impact diagnosis. Immune reconstitution, rather than specific antifungal therapy, was found to be the best predictor of survival.


Lattice energies of apatites and the estimation of DeltaH f degrees (PO 4 3-, g).
Experimentally based lattice energies are calculated for the apatite family of double salts M(5)(PO(4))(3)X, where M is a divalent metal cation (Ca, Sr, Ba) and X is hydroxide or a halide. These values are also shown to be estimable, generally to within 4%, using the recently derived Glasser-Jenkins equation, U(POT) = AI(2I/V(m))(1/3), where A = 121.39 kJ mol(-)(1). The apatites exhibiting greater covalent character (e.g., M = Pb, Cd, etc.) are less well reproduced but are within 8% of the experimentally based value. The lattice energy for ionic apatites (having identical lattice ionic strengths, I) takes the particularly simple form U(POT)/kJ mol(-)(1) = 26680/(V(m)/nm(3))(1/3), reproducing cycle values of U(POT) well when V(m) is estimated by ion volume summation and employing a volume for the PO(4)(3)(-) ion (not previously quantified with an associated error) of 0.063 +/- 0.003 nm(3). A value for the enthalpy of formation of the gaseous phosphate ion, DeltaH(f)( ) degrees (PO(4)(3)(-), g), is absent from current thermochemical tabulations. Examination of solution and solid state thermochemical cycles for apatites, however, leads us to a remarkably consistent value of 321.8 +/- 1.2 kJ mol(-)(1). Experimental and estimated lattice energies were used along with other thermodynamic data to determine enthalpies, entropies, and free energies of dissolution for apatites of uncertain stabilities. These dissolution values are compared with the corresponding values for stable apatites and are used to rationalize the relative instability of certain derivatives.


The ICF comprehensively covers the spectrum of health problems encountered by health professionals in patients with musculoskeletal conditions.
The objective of this study was to investigate, whether the International Classification of Functioning, Disablity and Health (ICF) comprehensively covers the spectrum of health problems encountered by medical doctors and physiotherapists in patients with musculoskeletal conditions. A worldwide e-mail survey with questionnaires that requested lists of relevant areas in the ICF components-body functions, body structures, activities and participation, and environmental factors-in patients with rheumatoid arthritis, osteoarthritis, low back pain and osteoporosis was conducted. The suitability of linking the named concepts to the ICF as well as the precision of the linking was characterized by assigning the concepts to six groups. All concepts that were named by the experts could be linked to the ICF, with the exception of personal factors. Between 32% (environmental factors) and 51% (activities and participation) of the named concepts were linked to an ICF category with an identical meaning and the same grade of precision. All other named concepts were linked to ICF categories with a lower level of precision, or encompassed more than one ICF category, or were linked to an ICF category with a related, but not identical meaning. The ICF covers comprehensively the spectrum of problems encountered in patients with musculoskeletal conditions by clinical experts throughout the world. This strengthens the validity of the ICF in the view of the users and will encourage the use of ICF-based applications such as the ICF checklist and the now-developed ICF Core Sets.


The detection of genotoxin-induced DNA adducts in the common mussel Mytilus edulis.
In order to establish the capacity of Mytilus spp. to form genotoxin-DNA adducts, a series of in vitro and in vivo studies were conducted in which tissue samples and animals were exposed to five model genotoxins. Following the in vitro characterization of the major adducts induced by the compounds, a series of in vivo studies were conducted to determine if the levels of genotoxin-DNA adduct formation followed a dose response. The results of these studies suggested that under appropriate conditions, DNA adducts in the hepatopancreas could be used as molecular dosimeters of exposure to genotoxic compounds in the species. However, these studies also revealed that the successful detection of such genotoxin-DNA adducts depends largely upon their chromatographic properties and thus the vigour of the characterization undertaken.


The importance of recognizing Buffer Zones to lands being developed, restored, or remediated: on planning for protection of ecological resources.
Environmental management relies on many types of information before making decisions regarding remediation, restoration, or other land use decisions, including ecological data, such as risks to species, populations, communities, and ecosystems. The aim of this investigation was to describe the ecological information required within the context of making environmental decisions and providing visual communication tools for regulators, conservationists, and the public to understand the risk to ecological resources on- and off-site. It is suggested that ecological information used in environmental decisions is required to be transparent throughout the planning and execution of a project, which needs to include: 1) ecological information and evaluations within development areas or units (in this case, watersheds), and 2) resources in adjacent areas (Buffer Zones) that might be affected. The Melton Valley administrative watershed (Oak Ridge Reservation, TN) is used as a case study because this site still has active facility development and environmental remediation, and there are important ecological resources on and off-site. Data indicate that although there are important resources on Melton Valley administrative watershed, there are also significant resources in the Buffer Zone around the watershed. Compared to the Melton Valley administrative watershed, the Buffer Zone contains more Interior (and Buffer) Forest and greater value resources. The point is made that when remediation, restoration, or development occurs, it is equally important to consider resources that are adjacent to the site in a Buffer Zone, particularly when remediation and development might continue for many years or decades.


Quality of care and in-hospital outcomes in patients with coronary heart disease in rural and urban hospitals (from Get With the Guidelines-Coronary Artery Disease Program).
Previous studies have suggested that patients with coronary artery disease (CAD) in rural areas may have worse outcomes due to limited availability of specialists, fewer resources, and less institutional funding. Data were collected from hospitals participating in the Get With the Guidelines-Coronary Artery Disease Program (GWTG-CAD) from January 2000 to December 2008. In-hospital outcomes and quality of care were stratified by care at rural versus urban hospitals. Multivariate logistic regression analysis was used to determine the association of rural locale with in-hospital mortality, length of stay, and compliance with the GWTG-CAD performance measurements including (1) early aspirin use, (2) smoking cessation counseling and discharge prescriptions of (3) aspirin, (4) angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers for left ventricular systolic dysfunction, (5) beta-blockers, and (6) lipid-lowering therapy and a composite of all 6 measurements. Data were collected from 22,096 patients at 71 rural centers and 329,938 patients at 477 urban centers. Unadjusted rates of compliance with performance measurements were lower in rural (range 82.4% to 90.5%) compared to urban (range 81.3% to 95.0%) hospitals including the composite (74.7% vs 80.6%, p <0.0001). In multivariate analysis, rural status was not independently associated with lower compliance with any of the performance measurements. Unadjusted mortality rates were higher in rural versus urban hospitals (5.7% vs 4.4%, p <0.0001), but this was not significant in multivariate analysis (odds ratio 1.05, 95% confidence interval 0.87 to 1.26). In conclusion, within the GWTG-CAD quality improvement initiative, patients with CAD treated at rural hospitals receive similar quality of care and have similar outcomes as those at urban centers.


Effects of replacing fish meal with soy protein concentrate and of DL-methionine supplementation in high-energy, extruded diets on the growth and nutrient utilization of rainbow trout, Oncorhynchus mykiss.
Our objectives were to test the potential replacement of fish meal by soy protein concentrate (SPC) in high-energy, extruded diets fed to rainbow trout (Oncorhynchus mykiss) and to evaluate the efficiency of DL-methionine supplementation of soy-based diets. Groups of trout (initial BW 103 to 106 g) were fed to visual satiety with isonitrogenous (6.6% DM) high-energy (22.8 MJ/kg DM gross energy), extruded diets, in which fish meal was progressively replaced with SPC (0, 50, 75, and 100%). Three 100% SPC diets were formulated to be either unsupplemented or supplemented with DL-methionine, so that total methionine content was .8 or 1.0% of DM. The quality of the SPC source used was assessed by measuring the antitryptic and antigenic activities and the concentrations of the isoflavones daidzein and genistein. Apparent digestibility of the diets was determined using the indirect method. A growth trial was conducted over 90 d at a water temperature of 18 degrees C. In addition to body composition analysis, plasma amino acid concentrations, anti-soy protein antibodies in the serum, and isoflavone concentrations in the bile were measured. The SPC source tested exhibited low antitryptic and antigenic activities, but it contained high concentrations of isoflavones (1,990 and 5,903 ppm for daidzein and genistein, respectively). Protein digestibility was high (92%) and was unaffected either the proportion of SPC in the diet or by DL-methionine supplementation. This was also true for the availability of amino acids, except phenylalanine. Digestibility of lipid and energy was reduced by 19% when SPC totally replaced fish meal. Growth rate was reduced when more than 50% of the dietary protein was of soy origin (daily growth coefficient of 3.2 and 2.1% for the control and the unsupplemented 100% SPC diet, respectively). The effect on growth was mainly explained by a general decline in feed intake (13.7 and 12.0 g DM x kg BW(-1) x d(-1) for the control and the unsupplemented 100% SPC diet, respectively) and in lipid and, thus, in energy digestibility. The DL-methionine supplementation partially reversed the depressive effects of high dietary SPC incorporation (+13% growth), mainly by enhancing intake. The negative effect of SPC incorporation either may be due to the high isoflavone concentration or to an interaction between the soy protein component and the dietary lipids.


Structure, dynamics, and Hck interaction of full-length HIV-1 Nef.
Nef is an HIV accessory protein that plays an important role in the progression of disease after viral infection. It interferes with numerous signaling pathways, one of which involves serine/threonine kinases. Here, we report the results of an NMR structural investigation on full-length Nef and its interaction with the entire regulatory domain of Hck (residues 72-256; Hck32L). A helical conformation was found at the N-terminus for residues 14-22, preceding the folded core domain. In contrast to the previously studied truncated Nef (Nef Δ1-39), the full-length Nef did not show any interactions of Trp57/Leu58 with the hydrophobic patch formed by helices α1 and α2. Upon Hck32L binding, the N-terminal anchor domain as well as the well-known SH3-binding site of Nef exhibited significant chemical shift changes. Upon Nef binding, resonance changes in the Hck spectrum were confined mostly to the SH3 domain, with additional effects seen for the connector between SH3 and SH2, the N-terminal region of SH2 and the linker region that contains the regulatory polyproline motif. The binding data suggest that in full-length Nef more than the core domain partakes in the interaction. The solution conformation of Hck32L was modeled using RDC data and compared with the crystal structure of the equivalent region in the inactivated, full-length Hck, revealing a notable difference in the relative orientations of the SH3 and SH2 domains. The RDC-based model combined with (15)N backbone dynamics data suggest that Hck32L adopts an open conformation without binding of the polyproline motif in the linker to the SH3 domain.


Lymphocyte subpopulations in homozygous sickle cell anaemia.
Patients with sickle cell disease have an increased tendency to develop frequent and severe pyogenic infections. Lymphocyte subpopulations were studied in 14 patients with homozygous sickle cell anaemia (SCA) using the OKT monoclonal antibody. The mean absolute lymphocyte counts observed in patients with SCA were similar to that of controls. The OKT8+ lymphocytes were significantly higher in SCA patients than in controls. The mean OKT3+ and OKT4+ lymphocytes were significantly lower in SCA patients than in controls, and there is a reversal of the normal OKT4+: OKT8+ ratio. The number of B cells present, as detected by surface membrane immunoglobulin, was significantly higher in SCA patients when compared with control values. These preliminary findings suggest an important mechanism to further explain the increased tendency to infection in SCA patients, in addition to the previously described immunological disorders and the asplenic state.


[Endoprosthetic repair with stent grafts in coronary artery restenosis].
Timely performed reconstructive operations on carotid arteries considerably decrease the incidence rate of ischaemic-type acute impairments of cerebral circulation. Nevertheless, restenoses developing in the zone of reconstruction of carotid arteries level the positive result of the primary operation in remote terms of follow up. In such cases it is more preferable to perform stenting of the damaged portions. The article deals with cases of successful use of self-expandable stent grafts in restenoses of carotid arteries after carotid endarterectomy and operations of prosthetic repair of carotid arteries. The analysis was carried out by international publications concerning this problem.


Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours.
The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.


Keratometric changes after cataract extraction.
One hundred cases of uncomplicated cataract with clear corneae had cataract extraction and were examined at 20 days and six weeks after operation. Keratometry was done preoperatively and keratometry and retinoscopy at each of the follow-up visits. The study was undertaken to evaluate the type (whether pre- or postplaced) and the number of sutures (one, three, or five) that produce the least postoperative astigmatism. We found that the type of suture was immaterial but that three sutures produced the least astigmatism.


Assessing the potential impact of immunity waning on the dynamics of COVID-19 in South Africa: an endemic model of COVID-19.
We developed an endemic model of COVID-19 to assess the impact of vaccination and immunity waning on the dynamics of the disease. Our model exhibits the phenomenon of backward bifurcation and bi-stability, where a stable disease-free equilibrium coexists with a stable endemic equilibrium. The epidemiological implication of this is that the control reproduction number being less than unity is no longer sufficient to guarantee disease eradication. We showed that this phenomenon could be eliminated by either increasing the vaccine efficacy or by reducing the disease transmission rate (adhering to non-pharmaceutical interventions). Furthermore, we numerically investigated the impacts of vaccination and waning of both vaccine-induced immunity and post-recovery immunity on the disease dynamics. Our simulation results show that the waning of vaccine-induced immunity has more effect on the disease dynamics relative to post-recovery immunity waning and suggests that more emphasis should be on reducing the waning of vaccine-induced immunity to eradicate COVID-19.


[The organization of the microcirculatory bed of the vascular plexus of the lateral cerebral ventricles in rabbits].
Electron microscopic studies of the choroid plexus' microvessels in the rabbit brain revealed diaphragm-covered caveolae and fenestrae in them. Some endotheliocytes possess outgrowths and sprouts on the abluminal surface that penetrate through the basal membrane of the capillaries into the brain and make contacts with its neurosecretory cells. The choroid capillaries were shown to be innervated by nerve fibers and terminals adjoining the basal membrane of the endothelium. Fever induced by i.v. pyrogenal was accompanied by changes in the organisation and permeability of the capillaries. These changes seem to be due to the action of interleukin-I released from activated blood and endothelial cells under the influence of pyrogenal.


The preparation of calmodulins from barley (Hordeum sp.) and basidiomycete fungi.
1. Calmodulin-like proteins were purified from the fruiting bodies of higher (basidiomycete) fungi and barley (Hordeum sp.) shoots. 2. These calmodulins have electrophoretic mobilities on 10% (w/v) polyacrylamide gels at pH 8.3 in the presence of 6 M-urea and at pH 8.3 in the presence of 0.1% sodium dodecyl sulphate similar to that of bovine brain calmodulin. They interacted with rabbit skeletal-muscle troponin I in the presence of Ca2+. 3. Barley and fungal calmodulins activated myosin light-chain kinase and phosphodiesterase in the presence of Ca2+, although the amounts needed were at least an order of magnitude greater than is required to produce the same effect with mammalian calmodulin. 4. Amino acid analyses indicated a number of differences from the mammalian protein, most notably the absence of trimethyl-lysine. 5. By using 125I-labelled calmodulin, a small amount of calmodulin-binding protein was detected in homogenates of barley and fungi. 6. No protein corresponding to calmodulin could be found in Escherichia coli or yeast, although a relatively high concentration of a protein that bound calmodulin was detected in E. coli by this technique.


Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals.
Holoprosencephaly (HPE), the most common malformation of the human forebrain, may be due to mutations in genes associated with non-syndromic HPE. Mutations in ZIC2, located on chromosome 13q32, are a common cause of non-syndromic, non-chromosomal HPE. To characterise genetic and clinical findings in patients with ZIC2 mutations. Through the National Institutes of Health and collaborating centres, DNA from approximately 1200 individuals with HPE spectrum disorders was analysed for sequence variations in ZIC2. Clinical details were examined and all other known cases of mutations in ZIC2 were included through a literature search. By direct sequencing of DNA samples of an unselected group of unrelated patients with HPE in our NIH laboratory, ZIC2 mutations were found in 8.4% (49/582) of probands. A total of 157 individuals from 119 unrelated kindreds are described, including 141 patients with intragenic sequence determined mutations in ZIC2. Only 39/157 patients have previously been clinically described. Unlike HPE due to mutations in other genes, most mutations occur de novo and the distribution of HPE types differs significantly from that of non-ZIC2 related HPE. Evidence is presented for the presence of a novel facial phenotype which includes bitemporal narrowing, upslanting palpebral fissures, a short nose with anteverted nares, a broad and well demarcated philtrum, and large ears. HPE due to ZIC2 mutations is distinct from that due to mutations in other genes. This may shed light on the mechanisms involved in formation of the forebrain and face and will help direct genetic counselling and diagnostic strategies.


Longitudinal outcomes in spinal cord injury: aging, secondary conditions, and well-being.
To specify the degree to which current age, duration of injury, and neurologic status affect the frequency of secondary health and psychosocial conditions in persons with long-term spinal cord injury (SCI), using both longitudinal and cross-sectional analysis techniques. Prospective longitudinal examination and data collection involving individuals with SCI studied initially at their 5th, 10th, and 15th anniversaries postinjury, and subsequently 5 years later at their 10th, 15th, and 20th anniversaries postinjury. Five Regional Model Spinal Cord Injury Systems. The 439 individuals who meet the inclusion criteria for the National SCI Database and who are enrolled in a longitudinal study of secondary conditions and SCI. Physical and psychosocial status at various times postinjury. There are different reports of various conditions when analyzing by neurologic groups, duration of injury, and age. Cross-sectional and longitudinal analyses also demonstrate different patterns of complications. The longitudinal method, like cross-sectional research, allows for identification of physical and psychosocial changes soon after they occur. Longitudinal research, however, also makes possible the development of predictive models for various long-term outcomes.


Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.
Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches.


Escalation from intra-aortic balloon pump to axillary impella 5.5 support: Staged removal of the femoral access.
Background: With the growing population of advanced heart failure, the use of Impella 5.5 has been increasing. Here, we report an effective strategy of removing the intra-aortic balloon pump (IABP) in the setting of escalation of support to Impella 5.5.Results: From January 1, 2022 to June 30, 2022, a total of 6 patients have undergone IABP removal during Impella 5.5 insertion. The IABP was subsequently removed over the long wire with manual compression on the femoral artery to control bleeding. An 8 or 9 Fr short sheath is inserted over the wire. Staged hemostasis was successfully performed in 4 patients, and the remaining two patients required escalation of support to veno-arterial membrane oxygenation as EC-PELLA utilizing the femoral arterial sheath.Conclusion: This does not only achieve secured hemostasis but also enables a smooth transition to further escalate support such as extracorporeal membrane oxygenation support, if necessary.


Bergmann's rule and the thrifty genotype.
One of Roberts' key contributions was his work demonstrating the applicability of several ecological rules to human populations (Roberts [1953] Am. J. Phys. Anthropol. 11:533-558; [1978] Climate and Human Variability, 2nd ed., Menlo Park, CA: Cummings). His finding that average body weight systematically covaries with mean annual temperature was widely taken as confirmation of Bergmann's rule for humans. More recently his findings on weight and temperature have been extended and confirmed (Ruff [1994] Yrbk. Phys. Anthropol. 37:65-407; Katzmarzyk and Leonard [1995] Hum Biol Council Program Abstracts 132) although the strength of the association may be decreasing when considering more recent surveys (Katzmarzyk and Leonard [1995]). Roberts noted in 1953 that Oceanic populations may be somewhat of an exception to Bergmann's rule, and we propose that Neel's ([1962] Am. J. Hum. Genet. 14:353-362) thrifty genotype model may account for some of the deviation from predicted weights among these populations. We provide an updated version of the thrifty genotype model, suggesting that selection for energetic efficiency may have occurred for some Oceanic populations during the voyaging to and settlement of their island homes. Under conditions of modernization the thrifty genotype may be manifesting as high rates of obesity and NIDDM among Polynesians and Micronesians. First, using measurements of adult male weight from 19 Oceanic populations, we demonstrate the extreme nature of their deviation from predicted weight based on Roberts' regression of weight on mean annual temperature. Next, we regress the deviations from predicted weight on NIDDM prevalence for these 19 populations, producing a highly significant regression (R2 = 0.46; P < 0.001), consistent with expectations if the thrifty genotype is responsible for the high weights.


[Cytological characteristics of aspirates from cancer of the prostate].
The results of a macro- and microscopic study of aspirate obtained from prostatic cancer patients in 253 needle biopsies are presented. In well-differentiated cancer, it was abundant, blood-stained, with large layers of the prostatic epithelium and insignificant atypia and polymorphism of tumor cells. Aspirate from moderately-differentiated tumors was scarce, generally blood-free, with small layers of the epithelium and considerable levels of isolated moderately polymorphous cells. In poorly-differentiated tumors, aspirate was also abundant but usually blood-free and contained isolated sharply polymorphous tumor cells.


Inactivation of stressed Escherichia coli O157:H7 cells on the surfaces of rocket salad leaves by chlorine and peroxyacetic acid.
Because Escherichia coli O157:H7 has been frequently associated with many foodborne outbreaks caused by consumption of leafy greens (lettuce, spinach, and celery), this study investigated the ability of deionized water, chlorine, and peroxyacetic acid to detach or inactivate stressed and unstressed cells of E. coli O157:H7 contaminating the surfaces of rocket salad leaves. E. coli O157:H7 cells stressed by acid, cold, starvation, or NaCl exposure, as well as unstressed cells, were inoculated on the surfaces of rocket salad leaves at 4°C. The effectiveness of two sanitizers (200 ppm of chlorine and 80 ppm of peroxyacetic acid) and deionized water for decontaminating the leaves treated with stressed and unstressed E. coli O157:H7 were evaluated during storage at 10 or 25°C for 0.5, 1, 3, and 7 days. It was found that washing with 80 ppm of peroxyacetic acid was more effective and reduced unstressed and stressed cells of E. coli O157:H7 by about 1 log CFU per leaf on the leaves. There was no apparent difference in the ability of stressed and unstressed cells to survive surface disinfection with the tested agents. Treatments to reduce viable E. coli O157:H7 cells on rocket leaves stored at 25°C were more effective than when used on those stored at 10°C. Washing with peroxyacetic acid or chlorine solution did not ensure the safety of rocket leaves, but such treatments could reduce the likelihood of water-mediated transfer of E. coli O157:H7 during washing and subsequent processing.


Methyl 2-Halo-4-Substituted-5-Sulfamoyl-Benzoates as High Affinity and Selective Inhibitors of Carbonic Anhydrase IX.
Among the twelve catalytically active carbonic anhydrase isozymes present in the human body, the CAIX is highly overexpressed in various solid tumors. The enzyme acidifies the tumor microenvironment enabling invasion and metastatic processes. Therefore, many attempts have been made to design chemical compounds that would exhibit high affinity and selective binding to CAIX over the remaining eleven catalytically active CA isozymes to limit undesired side effects. It has been postulated that such drugs may have anticancer properties and could be used in tumor treatment. Here we have designed a series of compounds, methyl 5-sulfamoyl-benzoates, which bear a primary sulfonamide group, a well-known marker of CA inhibitors, and determined their affinities for all twelve CA isozymes. Variations of substituents on the benzenesulfonamide ring led to compound 4b, which exhibited an extremely high observed binding affinity to CAIX; the Kd was 0.12 nM. The intrinsic dissociation constant, where the binding-linked protonation reactions have been subtracted, reached 0.08 pM. The compound also exhibited more than 100-fold selectivity over the remaining CA isozymes. The X-ray crystallographic structure of compound 3b bound to CAIX showed the structural position, while several structures of compounds bound to other CA isozymes showed structural reasons for compound selectivity towards CAIX. Since this series of compounds possess physicochemical properties suitable for drugs, they may be developed for anticancer therapeutic purposes.


Age and drug therapy are key prognostic factors for first clinical fracture in patients with primary osteoporosis.
We evaluated the characteristics of 1,142 women and men who attended Canadian osteoporosis clinics and had T-score < or = -2.0 and no prior fractures to determine the predictors of first clinical fracture. Greater age and failure to start osteoporosis drug treatment increased the risk of first clinical fracture. Although risk factors for osteoporotic fractures are well-known, it is unclear which factors predict poor prognosis in patients with primary osteoporosis. The purpose of this study was to determine prognostic factors for first clinical fracture in patients with T-score < or = -2.0 and no previous clinical fracture. We examined prospectively collected data from 1,142 patients aged 40 and over in the Canadian Database of Osteoporosis and Osteopenia. We used prognosis methodology and performed survival analysis to determine factors that increase the risk of first clinical fracture. Our inception cohort (mean age = 60.6 years, 91% females) had a cumulative fracture incidence of 5.1% (incidence rate: 2.53/100 person-years). Age and osteoporosis drug use predicted incident clinical fractures in multivariable regression analyses. The risk of first fracture increased by 3% per year. Failing to initiate osteoporosis treatment increased fracture risk by 2.4 times. In addition, low physical activity, high body mass index and low T-scores were found to predict fracture risk in certain patient subgroups using tree-structured survival analysis. These findings were robust and did not change with most sensitivity analyses. Age and osteoporosis drug treatment are the main prognostic predictors of first clinical fracture in patients with T-score < or = -2.0.


Exploring Hong Kong nurses' decision-making processes around presenteeism.
Presenteeism among nurses is the common behaviour of being physically present at work when one should not be due to personal health and well-being, a stressful work environment, lack of work-life balance, or a sense of professional identity or obligation. To explore nurses' decision-making process related to presenteeism in a large Hong Kong public hospital. As part of a larger study on nurse presenteeism in Hong Kong, we conducted focus groups with nurses to understand their considerations related to working sick. Eleven major themes emerged from the focus groups, which we grouped into three organizational domains reflecting nurses' decision-making process around presenteeism: consideration for colleagues, organizational factors and professional identity. Presenteeism was a familiar behaviour among Hong Kong nurses in our study. We found both overlap and divergence with prior presenteeism research in the domains and themes identified. Loyalty to colleagues, written and unwritten rules and professional identity as nurses all seemed to encourage presenteeism among Hong Kong nurses. Organizations seeking to discourage presenteeism should evaluate policies such as sick leave certificates, ensure appropriate coverage for all nurse ranks and address subcultural norms encouraging presenteeism.


Geminin has dimerization, Cdt1-binding, and destruction domains that are required for biological activity.
Geminin is an unstable regulatory protein that affects both cell division and cell differentiation. Geminin inhibits a second round of DNA synthesis during S and G(2) phase by binding the essential replication protein Cdt1. Geminin is also required for entry into mitosis, either by preventing replication abnormalities or by down-regulating the checkpoint kinase Chk1. Geminin overexpression during embryonic development induces ectopic neural tissue, inhibits eye formation, and perturbs the segmental patterning of the embryo. In order to define the structural and functional domains of the geminin protein, we generated over 40 missense and deletion mutations and tested their phenotypes in biological and biochemical assays. We find that geminin self-associates through the coiled-coil domain to form dimers and that dimerization is required for activity. Geminin contains a typical bipartite nuclear localization signal that is also required for its destruction during mitosis. Nondegradable mutants of geminin interfere with DNA replication in succeeding cell cycles. Geminin's Cdt1-binding domain lies immediately adjacent to the dimerization domain and overlaps it. We constructed two nonbinding mutants in this domain and found that they neither inhibited replication nor permitted entry into mitosis, indicating that this domain is necessary for both activities. We identified several missense mutations in geminin's Cdt1 binding domain that were deficient in their ability to inhibit replication yet were still able to allow mitotic entry, suggesting that these are separate functions of geminin.


Costs and cost-effectiveness of a telemedicine intensive care unit program in 6 intensive care units in a large health care system.
The purpose of this study is to estimate the costs and cost-effectiveness of a telemedicine intensive care unit (ICU) (tele-ICU) program. We used an observational study with ICU patients cared for during the pre-tele-ICU period and ICU patients cared for during the post-tele-ICU period in 6 ICUs at 5 hospitals that are part of a large nonprofit health care system in the Gulf Coast region. We obtained data on a sample of 4142 ICU patients: 2034 in the pre-tele-ICU period and 2108 in the post-tele-ICU period. Economic outcomes were hospital costs, ICU costs and floor costs, measured for average daily costs, costs per case, and costs per patient. After the implementation of the tele-ICU, the hospital daily cost increased from $4302 to $5340 (24%); the hospital cost per case, from $21,967 to $31,318 (43%); and the cost per patient, from $20,231 to $25,846 (28%). Although the tele-ICU intervention was not cost-effective in patients with Simplified Acute Physiology Score II 50 or less, it was cost-effective in the sickest patients with Simplified Acute Physiology Score II more than 50 (17% of patients) because it decreased hospital mortality without increasing costs significantly. Hospital administrators may conclude that a tele-ICU program aimed at the sickest patients is cost-effective.


Trans fatty acid analyses in samples of marine origin: the risk of false positives.
At conditions commonly applied for trans fatty analyses by gas chromatography, fatty acids naturally occurring in marine lipids may overlap chromatographically with C16 and C18 trans fatty acids and lead to false positives. Elution patterns were studied by tracking retention indices at shifting temperature conditions on two cyanopropyl-coated capillary columns. Most overlaps can be avoided by selecting the right chromatographic conditions, but it was not possible to find a single condition that eliminates the risk of overlap between trans fatty acids and interferents. In total, 17 compounds were identified as potential interferents, and the amounts of these compounds were quantified in various samples of marine origin. The interferents that will most likely contribute to incorrect assessments of trans fatty acids in marine lipids are probably 18:3 n-4 and 18:1 n-11.


Active transport into the human erythrocyte; evidence from comparative kinetics and competition among monosaccharides.
1. Applicability of the previously postulated active transport system for conveying glucose into the human red cell was tested in connection with a number of related substances, comprising 6-carbon aldoses and ketoses, 5-carbon aldoses, and 5- or 6-carbon polyhydric alcohols. 2. The alcohols did not perceptibly penetrate the cells; all the sugars penetrated, the rates differing, but all of the same order of magnitude. 3. All the aldoses penetrated according to the pattern previously reported for glucose, in that the rate of penetration was not directly related to the gradient, but subject to some limiting factor. 4. The ketoses penetrated approximately according to the pattern of passive diffusion. 5. When present in equal concentrations, any aldose prevented or greatly delayed the entrance of a ketose, while the ketose did not perceptibly alter the rate of aldose uptake. Within each class, similar inhibitory relations were observed. 6. Penetration of all the sugars showed a high temperature coefficient and was inhibited by the mercuric ion or p-chloromercuribenzoate; certain of the sugars showed a residual degree of penetration not thus inhibitable. 7. Penetration of the ketoses was selectively inhibited by barbital. 8. These observations are interpreted in terms of simple equilibria between the various sugars and a hypothetical carrier molecule in the membrane, with which the sugars form a complex during their passage through the membrane. Comparisons between the sugars in relation to their reactions with the carrier system are indicated.


Clinical Use of Continuous Glucose Monitoring in Adults with Type 2 Diabetes.
Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management.


Immunohistochemical evidence for the NO cGMP signaling pathway in respiratory ciliated epithelia of rat.
Airway epithelia play a crucial role in protecting the lung from the external environment. Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms to defend against respiratory tract infection. Both of these activities are regulated by nitric oxide (NO)-dependent mechanisms. To better understand the role of the NO-cGMP signal transduction cascade in these responses, we investigated the localization of endothelial nitric oxide synthase (eNOS), soluble guanylyl cyclase (sGC), cGMP-dependent protein kinase (PKG) I-alpha, and PKG I-beta in the tracheas and lungs of normal rats by immunohistochemistry. Mouse anti-eNOS, rabbit anti-sGC, PKG I-alpha, and PKG I-beta antibodies were used. Strong immunostaining for eNOS was detected in ciliated tracheal, bronchial, and bronchiolar epithelia, in Clara cells, and in Type II alveolar cells. The pattern of sGC and PKG I-beta immunostaining showed striking parallels with that of eNOS staining. No staining was detectable in ciliated epithelium with the anti-PKG I-alpha antibody. Taken together, these observations suggest that PKG I-beta might transduce NO-sGC signaling into biological responses in ciliated respiratory epithelia.(J Histochem Cytochem 47:1369-1374, 1999)


Transcriptomic responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in liver: comparison of rat and mouse.
Mouse and rat models are mainstays in pharmacology, toxicology and drug development -- but differences between strains and between species complicate data interpretation and application to human health. Dioxin-like polyhalogenated aromatic hydrocarbons represent a major class of environmentally and economically relevant toxicants. In mammals dioxin exposure leads to a broad spectrum of adverse affects, including hepatotoxicity of varying severity. Several studies have shown that dioxins extensively alter hepatic mRNA levels. Surprisingly, though, analysis of a limited portion of the transcriptome revealed that rat and mouse responses diverge greatly (Boverhof et al. Toxicol Sci 94:398-416, 2006). We employed oligonucleotide arrays to compare the response of 8,125 rat and mouse orthologs. We confirmed that there is limited inter-species overlap in dioxin-responsive genes. Rat-specific and mouse-specific genes are enriched for specific functional groups which differ between species, conceivably accounting for species-specificities in liver histopathology. While no evidence for the involvement of copy-number variation was found, extensive inter-species variation in the transcriptional-regulatory network was identified; Nr2f1 and Fos emerged as candidates to explain species-specific and species-independent responses, respectively. Our results suggest that a small core of genes is responsible for mediating the similar features of dioxin hepatotoxicity in rats and mice but non-overlapping pathways are simultaneously at play to result in distinctive histopathological outcomes. The extreme divergence between mouse and rat transcriptomic responses appears to reflect divergent transcriptional-regulatory networks. Taken together, these data suggest that both rat and mouse models should be used to screen the acute hepatotoxic effects of drugs and toxic compounds.


Rare variants in neuronal excitability genes influence risk for bipolar disorder.
We sequenced the genomes of 200 individuals from 41 families multiply affected with bipolar disorder (BD) to identify contributions of rare variants to genetic risk. We initially focused on 3,087 candidate genes with known synaptic functions or prior evidence from genome-wide association studies. BD pedigrees had an increased burden of rare variants in genes encoding neuronal ion channels, including subunits of GABAA receptors and voltage-gated calcium channels. Four uncommon coding and regulatory variants also showed significant association, including a missense variant in GABRA6. Targeted sequencing of 26 of these candidate genes in an additional 3,014 cases and 1,717 controls confirmed rare variant associations in ANK3, CACNA1B, CACNA1C, CACNA1D, CACNG2, CAMK2A, and NGF. Variants in promoters and 5' and 3' UTRs contributed more strongly than coding variants to risk for BD, both in pedigrees and in the case-control cohort. The genes and pathways identified in this study regulate diverse aspects of neuronal excitability. We conclude that rare variants in neuronal excitability genes contribute to risk for BD.


Masses and malformations of the third ventricle: normal anatomic relationships and differential diagnoses.
The third ventricle lies in the center of the brain. It is surrounded by critical nuclear structures (the hypothalamus and thalami) and important glandular structures (the pituitary and pineal glands). Although a wide array of pathologic processes may involve the third ventricle, most are extrinsic masses. By understanding the anatomic boundaries of the third ventricle and its relationship to adjacent structures, it is possible to create short lists of differential diagnoses. Third ventricle masses can be classified as arising in or immediately adjacent to one of five locations: anterior, posterior, inferior, foramen of Monro, and intraventricular. Anterior masses involve the optic and infundibular recesses, posterior masses affect or arise in the posterior commissure and pineal gland, and inferior masses involve or affect the ventricle floor. Masses may also arise at or adjacent to the foramen of Monro or entirely within the third ventricle. Of the intraventricular masses, chordoid glioma-a rare low-grade primary neoplasm-is unique to the third ventricle. Congenital malformations of the third ventricle are uncommon and are most often noted during childhood. Most commonly, these anomalies represent malformations of the neurohypophysis, which may manifest as hormonal abnormalities, or stenosis of the aqueduct of Sylvius, which manifests as dilatation of the third and lateral ventricles (hydrocephalus).


Schistosoma japonicum risk in Jiangsu province, People's Republic of China: identification of a spatio-temporal risk pattern along the Yangtze River.
The risk for Schistosoma japonicum infection in Jiangsu province, People's Republic of China, was investigated by a mouse bioassay. Various investigations were conducted in the period 2009-2011 with the presentation here representing the summary of the results from 45-50 sites in the marshlands along the Yangtze River's course through the province. Indices representing three aspects of the infection were collected to assess risk: (i) the proportion of sentinel points where at least one mouse infection was recorded; (ii) the proportion of infected mice at each of these sites; and (iii) the average worm burdens. Directional distribution analysis and scan statistics were used to explore the spatio-temporal risk pattern. The spatial distribution was oriented along the Yangtze River and the directional distributions for the proportion of infected mice and mean worm burdens were similar for the positive sentinel sites. Four statistically significant clusters were detected in 2009, but only one in 2010 and 2011, respectively. Temporal windows for infection risk were seen in June and September. The study illustrates the utility of spatio-temporal analysis in assessing the risk for schistosomiasis. This approach should be useful with respect to surveillance and response that can be expected to be increasingly applied when moving from morbidity control to transmission control.


Listeria monocytogenes responds to cell density as it transitions to the long-term-survival phase.
Listeria monocytogenes was recently found to enter a long-term-survival (LTS) phase, which may help explain its persistence in natural environments and within food processing plants. The purpose of this study was to investigate the effects of initial cell density, initial pH and type of broth (fresh vs. spent) on the transition of L. monocytogenes to the LTS phase and model the change in viable population density with time. Initial cell density (~10(6)-~10(10)CFU/ml) and initial pH (5.36-6.85) both significantly affected the transition of L. monocytogenes to the LTS phase (P<0.001) with initial cell density being the main determining factor. In contrast, type of broth did not significantly affect cell density change during the transition of stationary-phase cells at high initial density to the LTS phase (P>0.05). After 30-d incubation no significant differences in cell densities were observed between either type of broth or between any of the initial cell density/pH treatment combinations (P>0.05), where the mean viable cell density was 4.3±1.1×10(8)CFU/ml. L. monocytogenes responded to viable cell density in accordance with the logistic equation during transition to the LTS phase. The Agr quorum-sensing system does not appear to play a role in the transition to the LTS phase. Further research is needed to better understand the control mechanisms utilized by L. monocytogenes as it transitions to a coccoid, resistant and stable density state in the LTS phase.


Nonoccupational physical activity by degree of urbanization and U.S. geographic region.
To estimate levels of nonoccupational leisure-time physical activity (LTPA) by degree of urbanization and geographic region of the United States. Participants were respondents to the Behavioral Risk Factor Surveillance System (BRFSS) in 2001 (N = 137,359). Moderate- and vigorous-intensity LTPA was categorized as meeting recommended levels, insufficient, or inactive. The U.S. Department of Agriculture rural-urban continuum codes were used to describe degrees of urbanization (metro, large urban, small urban, and rural). Geographic regions were defined by the U.S. Bureau of the Census (Northeast, Midwest, South, and West). Prevalence estimates were calculated using sample weights to account for the design of the BRFSS. Multivariate logistic regression analyses examined regional differences in the odds of physical inactivity (physically inactive vs insufficient or meets) by degree of urbanization after adjustment for sex, age, race, BMI, education, and occupational physical activity. Large urban areas (49.0%) and the western United States (49.0%) had the highest prevalence of recommended levels of LTPA. Rural areas (24.1%) and the southern United States (17.4%) had the highest prevalence of inactivity. Adults living in the four urbanization categories of the midwestern (metro (OR = 1.47, 95% CI = 1.31, 1.65), large urban (OR = 1.83, 95% CI = 1.51, 2.23), small urban (OR = 1.99, 95% CI = 1.65, 2.40), and rural (OR = 2.59, 95% CI = 1.35, 4.97)); and southern (metro (OR = 1.70, 95% CI = 1.53, 1.88), large urban (OR = 2.04, 95% CI = 1.72, 2.41), small urban (OR = 2.32, 95% CI = 2.02, 2.67), and rural (OR = 5.49, 95% CI = 2.82, 10.68)) U.S. regions were more likely to be inactive than adults living in similar areas of the western United States. Adults in northeast metro and large urban areas (OR = 1.62, 95% CI = 1.45, 1.81; and OR = 1.37, 95% CI = 1.08, 1.74, respectively) were more likely to be inactive than those residing in western metro and large urban areas. The prevalence of physical inactivity varies by degree of urbanization and geographic region of the United States.


Adapting mHealth to Workflow - A Case Study in South Africa.
Community Health Workers (CHW) perform important healthcare and health promotion in many low and middle income countries. They are increasingly supported in their work by the use of mHealth. This study aims to explore how mHealth services can support the everyday work for CHWs when delivering home care in rural areas in South Africa. A single case study was performed, mapping CHWs workflow and investigating where and when CHW can be supported by mHealth services. Despite the very positive feedback from the CHWs and the fact that the studied mHealth solutions appears to support the majority of the important activities in the CHWs work process, the application is no longer in use. Financial and strategic decisions are behind the discontinuation of the project, further stressing the importance of taking all socio-technical dimensions into account when evaluating success or failure of implementation projects.


On the convergence of multi-scale free energy simulations.
In this work we employ simple model systems to evaluate the relative performance of two of the most important free energy methods: The Zwanzig equation (also known as "Free energy perturbation") and Bennett's acceptance ratio method (BAR). Although our examples should be transferable to other kinds of free energy simulations, we focus on applications of multi-scale free energy simulations. Such calculations are especially complex, since they connect two different levels of theory with very different requirements in terms of speed, accuracy, sampling and parallelizability. We try to reconcile all those different factors by developing some simple criteria to guide the early stages of the development of a free energy protocol. This is accomplished by quantifying how many λ intermediate steps and how many potential energy evaluations are necessary in order to reach a certain level of convergence.


MR imaging of the aging brain: patchy white-matter lesions and dementia.
Magnetic resonance (MR) imaging studies of the brain in five elderly patients with non-Alzheimer dementia were compared with those in two groups of nondemented control subjects. Group 1 included five subjects aged 59-66; group 2 included nine subjects aged 74-81. In all of the demented patients and in three of the subjects in the older control group, MR showed diffuse, patchy white-matter lesions. A rating scale was used to grade the severity of the changes. The results suggest a higher incidence of white-matter lesions in elderly patients with non-Alzheimer dementia and in cognitively normal elderly with advancing age.


Well-being of Canadian Armed Forces Veterans and Spouses of Veterans During the COVID-19 Pandemic: Protocol for a Prospective Longitudinal Survey.
The COVID-19 pandemic has resulted in significant changes to everyday life, including social distancing mandates, changes to health care, and a heightened risk of infection. Previous research has shown that Canadian Armed Forces (CAF) veterans are at higher risk of developing mental and physical health conditions. Veterans and their families may face unique social challenges that can compound with pandemic-related disruptions to negatively impact well-being. This study aims to longitudinally characterize the mental health of CAF veterans and spouses of CAF veterans throughout the pandemic and to understand the dynamic influences of pandemic-related stressors on psychological health over time. We employed a prospective longitudinal panel design using an online data collection platform. Study participation was open to all CAF veterans and spouses of CAF veterans residing in Canada. Participants were asked to complete a comprehensive battery of assessments representing psychological well-being, chronic pain, health care access patterns, physical environment, employment, social integration, and adjustment to pandemic-related lifestyle changes. Follow-up assessments were conducted every 3 months over an 18-month period. This study was approved by the Western University Health Sciences and Lawson Health Research Institute Research Ethics Boards. Baseline data were collected between July 2020 and February 2021. There were 3 population segments that participated in the study: 1047 veterans, 366 spouses of veterans, and 125 veterans who are also spouses of veterans completed baseline data collection. As of November 2021, data collection is ongoing, with participants completing the 9- or 12-month follow-up surveys depending on their date of self-enrollment. Data collection across all time points will be complete in September 2022. This longitudinal survey is unique in its comprehensive assessment of domains relevant to veterans and spouses of veterans during the COVID-19 pandemic, ranging from occupational, demographic, social, mental, and physical domains, to perceptions and experiences with health care treatments and access. The results of this study will be used to inform policy for veteran and veteran family support, and to best prepare for similar emergencies should they occur in the future. DERR1-10.2196/34984.


Long Non-Coding RNA Taurine Upregulated Gene 1 Targets miR-185 to Regulate Cell Proliferation and Glycolysis in Acute Myeloid Leukemia Cells in vitro.
Acute myeloid leukemia (AML) is a group of malignant hematopoietic system diseases. Taurine-upregulated gene 1 (TUG1) is a long non-coding RNA that has been associated with human cancers, including AML. However, the role and molecular mechanisms of TUG1 in AML remains to be defined. Expression of TUG1 and miR-185 was detected using RT-qPCR. Cell viability and apoptotic rate were measured by MTT assay and flow cytometry, respectively. Glycolysis was determined by commercial glucose and lactate assay kits and Western blot. The target binding between TUG1 and miR-185 was predicted on Starbase online database and confirmed by luciferase reporter assay and RNA immunoprecipitation. TUG1 was upregulated and miR-185 was downregulated in the peripheral blood mononuclear cells of AML specimens and cells (HL-60, KG-1, MOLM-14, and MOLM-13). Both TUG1 knockdown and miR-185 overexpression via transfection could suppress cell viability, glucose consumption, lactate production, and hexokinase 2 expression, but promote apoptotic rate in HL-60 and KG-1 cells. Notably, TUG1 functioned as a sponge of miR-185 by target binding. Moreover, downregulation of miR-185 could partially overturn the effect of TUG1 knockdown on cell proliferation and glycolysis in HL-60 and KG-1 cells. Expression of TUG1 was upregulated in AML patients and cells, and its knockdown repressed cell proliferation and glycolysis in AML cells in vitro by targeting miR-185.


Characterising biomolecular interactions and dynamics with mass photometry.
We review recent advances in our ability to characterise biomolecular structure, interactions and associated dynamics by mass photometry (MP), the label-free detection and mass measurement of individual biomolecules in solution. Molecular counting and identification provides direct access to relative abundance, and thereby affinities, while associated dynamics yield on- and off-rates. The molecular resolution afforded by MP enables these measurements as a function of stoichiometry and assembly at equilibrium, as opposed to the majority of existing solution-based methods. Together with future improvements in terms of assays and technological performance, MP is likely to provide mechanistic details of complex biomolecular processes.


Interferon regulatory factors 4 and 8 induce the expression of Ikaros and Aiolos to down-regulate pre-B-cell receptor and promote cell-cycle withdrawal in pre-B-cell development.
Pre-B lymphocytes consist of 2 distinct cell populations: large pre-B and small pre-B. The large pre-B cells are newly generated pre-B cells that express pre-B-cell receptor (pre-BCR) on the surface and are highly proliferative; small pre-B cells are derived from large pre-B cells that have down-regulated pre-BCR and withdrawn from cell cycle. The molecular events that mediate the transition from cycling pre-B to small, resting pre-B have not been fully elucidated. Here, we show that interferon regulatory factors 4 and 8 (IRF4,8) suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells. Our studies further reveal that IRF4,8 induce the expression of Ikaros and Aiolos in pre-B cells, and reconstitution of expression of either one is sufficient to suppress surrogate light chain expression and down-regulate pre-BCR in pre-B cells lacking IRF4,8. Interestingly, our results also indicate that pre-B cells undergo growth inhibition and cell-cycle arrest in the presence of IRF4,8. Moreover, we provide evidence that Ikaros and Aiolos are indispensable for the down-regulation of pre-BCR and the cell-cycle withdrawal mediated by IRF4,8. Thus, IRF4,8 orchestrate the transition from large pre-B to small pre-B cells by inducing the expression of Ikaros and Aiolos.


Little evidence for sympatric speciation in island birds.
It has been suggested that the presence of sister species in small circumscribed areas, such as isolated lakes or islands, might imply that these species originated sympatrically. To investigate this possibility in birds, we searched for endemic, congeneric species on isolated islands in the ocean. Among 46 islands and small archipelagos chosen because they contain at least one species of endemic land bird, we identified seven pairs of endemic congeners (excluding flightless rails). Of these seven, only four pairs are potentially sister species and thus possible candidates for sympatric speciation. However, three of these four pairs have always been considered the results of double invasion from a mainland source (in two of these cases, molecular-phylogenetic work has either confirmed a double invasion or is ambiguous). The one remaining pair may have speciated allopatrically on a small archipelago. Additional phylogenetic studies are required to understand these cases, and our results should also be considered in light of the large number of island-bird extinctions in historic time. We conclude that, at present, there is little evidence for sympatric speciation in island birds.


Pustulotic arthro-osteitis (Sonozaki Syndrome): A rare case report.
Pustulotic arthro-osteitis is a rare disease involving the skin and musculoskeletal system that was first described by Sonozaki. Onset is frequently seen at age 30-40. The prevalences between the sexes are similar. Palmoplantar pustulosis and sternoclavicular joint involvement are the most typical findings. It may be difficult to distinguish seronegative spondyloarthropathies and SAPHO syndrome due to sacroiliac joint, vertebral column and peripheral joint involvement. Arthritis being non-erosive and short-lived in character and the absence of deformity or contracture in the joints are significant clinical characteristics. Anti-inflammatory and immunesuppressive drugs are used in the treatment of the disease, the course of which involves remission and flare-ups. We describe the case of a 43-year-old male patient diagnosed with pustulotic arthro-osteitis.


Kinetic studies with the use of proton-magnetic-resonance spectroscopy of the specific alpha-deuteration of amino acids by Escherichia coli aspartate aminotransferase.
Escherichia coli aspartate aminotransferase was exposed to aspartate or phenylalanine without oxo acid in buffered 2H2O. The alpha-hydrogen of the amino acids underwent first-order exchange with respect to both substrate and enzyme. P.m.r. spectroscopy gave consistent reaction-rate constants. The deuterium-exchange rate was only moderately increased by addition of oxo acids and was of the same order as the transamination rate. No beta-deuteration was observed. The C(alpha)-H-bond-breaking step is discussed as a part of the entire transamination mechanism.


Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials.
To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus (T2DM). PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception up to July 2020, to identify randomised controlled trials (RCTs) that enrolled patients with T2DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs alone. The primary outcomes were haemoglobin A1c (HbA1c) and fasting blood glucose (FBG). The secondary outcomes included 2-h blood glucose (2hBG), fasting insulin (FINS), homeostatic model assessment for insulin resistance (HOMA-IR), and acupuncture-related adverse events. Mean difference (MD) and 95% confidence interval (CI) were used as the effect measure in the meta-analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Twenty-one RCTs (n=1,188) were included. The meta-analytic results showed that the acupuncture group had greater reductions in FBG (MD -6.46 mg/dL, 95% CI -11.95 to -0.98; moderate-quality evidence) and HOMA-IR (MD -1.23, 95% CI -2.16 to -0.31; low-quality evidence), but comparable changes in HbA1c (MD -0.39%, 95% CI -0.84 to 1.61; very-low-quality evidence), 2hBG (MD -4.99 mg/dL, 95% CI -20.74 to 10.76; low-quality evidence), and FINS (MD -1.32 µIU/mL, 95% CI -3.76 to 1.12; low-quality evidence). No data on the incidence of diabetic complications were found. All acupuncture-related adverse events reported were mild. The current evidence suggests that acupuncture, as a complementary therapy to antidiabetic drugs, has a small but statistically significant effect on decreasing FBG and improving insulin resistance. The effects of acupuncture on HbA1c, 2hBG, and FINS remain uncertain. Acupuncture is generally safe in patients with mild diabetes. More evidence for the long-term effects of acupuncture on T2DM is needed. (Trial registration No. CRD42018115639).


Return to play after anterior cruciate ligament reconstruction in National Football League athletes.
Rupture of the anterior cruciate ligament (ACL) is a common and potentially career-threatening injury in the National Football League (NFL). The return to play (RTP) percentage and the factors affecting RTP after ACL reconstruction in NFL players are not well defined. To determine the actual rate of return to professional football play in the NFL after ACL reconstruction surgery and to determine what factors can predict ability to RTP. We hypothesize that the RTP percentage in this unique patient population will differ from previously reported populations. Case series; Level of evidence, 4. Forty-nine NFL athletes who had undergone primary ACL reconstruction at our institution were followed to determine their RTP percentages and factors predicting RTP. Sixty-three percent (31 of 49) of NFL athletes returned to NFL game play at an average of 10.8 months after surgery. Age at time of surgery, position, and the type and number of procedures were not significantly different between those who did and did not return to play. The average number of games before surgery was 51 for those who did return to play and 28 for those who did not (P = .039). The odds ratio favoring RTP was 5.5 (P = .016) for those players who had more than 4 years of NFL experience before surgery. The average NFL draft round was 3.4 for the group who returned to play and 6.4 for those who did not (P < .001). The odds ratio favoring RTP was 12.2 (P < .001) for those players drafted in the first 4 rounds of the NFL draft compared with those drafted after the fourth round. The RTP rates after ACL reconstruction in NFL football players are lower than previously perceived. More experienced and established athletes are more likely to return to competition at the same level after this procedure than those with less professional experience. Being selected in the first 4 rounds of the NFL draft was highly predictive of RTP.


Plant height affects Fusarium crown rot severity in wheat.
Effects of plant height on Fusarium crown rot (FCR) disease severity were investigated using 12 pairs of near-isogenic lines (NILs) for six different reduced height (Rht) genes in wheat. The dwarf isolines all gave better FCR resistance when compared with their respective tall counterparts, although the Rht genes involved in these NILs are located on several different chromosomes. Treating plants with exogenous gibberellin increased FCR severity as well as seedling lengths in all of the isolines tested. Analysis of the expression of several defense genes with known correlation with resistance to FCR pathogens between the Rht isolines following FCR inoculation indicated that the better resistance of the dwarf isolines was not due to enhanced defense gene induction. These results suggested that the difference in FCR severity between the tall and dwarf isolines is likely due to their height difference per se or to some physiological and structural consequences of reduced height. Thus, caution should be taken when considering to exploit any FCR locus located near a height gene.


Anti-ENA profiles related with anti-SS-A/Ro. The detection of Ro52 and Ro60 according to the presence of SS-B/La, and ANA pattern and titer.
Anti-Ro52 (Ro52) and anti-Ro60 (Ro60) antibodies are associated with different clinical entities. We investigated their relationship with the presence of anti-SS-B/La (SSB) antibody, the pattern and titer of antinuclear antibody (ANA), and the variations in antibody profiles related with anti-SS-A/Ro (SSA) positivity. Our aim was to develop a strategy to increase the efficiency of anti-extractable nuclear antigen (ENA) determinations. Statistical analyses were based on the Chi-squared test for categorical variables, the Mann-Whitney U test to compare profiles, and the odds ratio (OR) and 95% confidence interval (95% CI) to estimate the risk of variability. We analyzed 800 SSA-positive samples with Ro52 or Ro60 reactivity. The most frequent profiles were Ro52+Ro60+SSB (n=349, 43.6%); Ro52+Ro60 (n=126, 15.8%); Ro52 (n=121, 15.1%) and Ro60 (n=71, 8.9%). In samples positive only for SSA and an ANA titer ≤1:640, the most likely profile was positivity for either Ro52 or Ro60, whereas when the ANA titer was >1:640, positivity for both Ro52 and Ro60 simultaneously was more likely (p<0.001). In samples positive for both SSA and SSB, the most likely profile was Ro52+Ro60+SSB regardless of the ANA titer (p=0.001). When only SSA was positive and the ANA staining pattern was nucleolar, centromeric or cytoplasmic, Ro52 positivity was most likely (p<0.001). When both SSA and SSB were positive, both Ro52 and Ro60 were likely to be positive regardless of the ANA staining pattern. In 28.7% of the patients the profile was variable. Variability was significantly greater in those with the SSA profile (23/67) than with the SSA+SSB profile (15/105; OR=1.9, 95% CI=1.1-3.3; p=0.025), and the difference in variability was greatest between the Ro52+Ro60 profile (8/23) and the Ro52+Ro60+SSB profile (8/68; OR=4.2, 95% CI=1.9-9.5; p<0.001). We conclude that to increase efficiency in the immunology laboratory, positivity for Ro52 and Ro60 individually or simultaneously can be deduced from SSB status and the ANA pattern and titer. In general, for the most frequent anti-ENA findings, priority should be given to retesting autoantibodies not detected in the initial analysis.


Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects.
KRN568 is a calcimimetic compound which acts on the calcium sensing receptors (CaR) on the parathyroid gland to suppress secretion of PTH. A recent report has demonstrated that CaRs are expressed on cultured human antral gastrin cells and that gastrin secretion is stimulated by an increase in extracellular calcium level. However, the effect of KRN568 on serum gastrin levels has yet to be clinically assessed. We therefore studied the effect of this calcimimetic on gastrin secretion in healthy subjects enrolled in the phase 1 study for KRN568 currently carried out in Japan. Single doses of KRN568, ranging from 25 mg to 400 mg, were orally administered to 6 healthy male volunteers at fasting and after meal. One subject proved to be a poor metabolizer (PM) for this compound and showed more than 10-fold high concentrations of plasma KRN568 (fasting Cmax 90.8 and non-fasting 83.8 ng/ml) compared to the other 5 individuals (Cmax 6.5 +/- 2.2 and 7.4+/- 1.6 ng/ml, respectively). Plasma gastrin levels showed mild but apparent increase (from 30 to 125 pg/ml) in this particular subject, while there were no significant increases in the other five people (from 34 +/- 6 to 63 +/- 3 pg/ml) after oral administration of 400 mg KRN568 at fasting. In the PM, administration of KRN568 resulted in extraordinarily high serum drug levels associated with transient increase of gastrin levels. This observation suggested that calcium-induced stimulation of gastrin secretion in human was mediated by a mechanism involving CaR. Potential side effects related to the increased gastrin secretion may be warranted in the practical use of this compound.


Trends in Patient Care for Traumatic Spinal Injuries in the United States: A National Inpatient Sample Study of the Correlations With Patient Outcomes From 2001 to 2012.
A retrospective database review. The aim of this study was to examine whether patient characteristics, distribution of care, and patient outcomes for spinal cord injury (SCI) in the United States have changed between 2001 and 2012. Although patient outcomes after cranial injury are better at high-volume centers with specialized, multidisciplinary teams, similar assessments have not been done for spinal injuries. We retrospectively reviewed the National and Nationwide Inpatient Samples for the years 2001, 2002, 2011, and 2012 to identify patients with spinal fracture with or without SCI. The demographic characteristics of the patient cohort, clinical course, hospital characteristics, interhospital transfer, and disposition were statistically analyzed relative to patient mortality, total hospital costs, and length of stay. How these data changed over this 11-year period was also evaluated. A total of 159,875 cases were identified, with 141,737 fractures without SCI and 18,138 SCIs with or without fracture. There was a statistically significant decrease in the percentage of patients transferred with spine injury from 4.2% to 3.4% (P < 0.001) from the early years to the later years and in patient transfers for SCIs (8.1% vs. 6.5%, P < 0.001). Interestingly, the overall mortality rate (3.5% vs. 3.6%) remained unchanged (P = 0.679), but mortality from SCI increased (6.6-7.4%, P = 0.021). From 2002 to 2012, the rate of interhospital transfer of spinal injury patients declined, while the mortality rate for patients with SCI increased. Interestingly, there was an increase in transfers after spinal surgery at the index hospital. The decentralization of spine care may be responsible for the increase in mortality. 4.


Harmonizing recreational fisheries and conservation objectives for aquatic biodiversity in inland waters.
The importance of recreational fisheries to local and national economies, and as a generator of immense social welfare throughout the developed world, is well established. Development in the sector and its interaction with non-fishery-related nature conservation objectives for aquatic biodiversity, however, have the potential to generate conflict. This article reviews the intersection between recreational fisheries and nature conservation goals for aquatic biodiversity with specific reference to inland waters in industrialized countries, and the principal management activities and constraints that can lead to conflicts. A SWOT (strengths, weaknesses, opportunities and threats) analysis was used to review the issues facing sectoral development and identify options for future advancement of recreational fisheries to ameliorate potential conflicts with nature conservation goals. It is concluded that reconciliation of recreational fisheries and modern conservation perspectives is both possible and desirable, because many conservation problems also benefit fisheries quality. Angler buy-in to conservation is probable if (1) management scales are small, (2) threats to conservation originate from outside the fisheries sectors and (3) ecological awareness for the conservation problem is high. If these aspects are not present, reconciliation of recreational fisheries and nature conservation goals is less likely, risking both the aquatic biodiversity and the future of angling. To address these issues, enforcement of legislation and continued communication with angler communities is necessary, as well as development of integrated management policies that build on the instrumental values of aquatic biodiversity for recreational fisheries, while curtailing the more insidious threats to such biodiversity that originate directly from the recreational fisheries sector.


Clinical and angiographic outcome of directional atherectomy followed by stent implantation in de novo lesions located at the ostium of the left anterior descending coronary artery.
Lesions located at the ostium of the left anterior descending coronary artery (LAD) are considered an ideal target for directional atherectomy (DCA), but few data are available about the value of using this strategy before stenting in comparison with stenting alone. To investigate the immediate and mid term clinical and angiographic results of DCA followed by stent implantation for ostial LAD lesions. Retrospective comparison of the immediate and mid term angiographic and clinical results of a series of 117 consecutive patients with de novo lesions located at the ostium of the LAD. Of these, 46 underwent DCA before stenting and 71 were treated with stenting alone. Technical success in the two groups was similar at around 98%. DCA plus stenting provided a larger minimum lumen diameter at the end of the procedure than stenting alone (3.57 (0.59) mm v 3.33 (0.49) mm, p = 0.022). There were no differences for in-hospital major adverse events (MACE) (7.5% for atherectomy plus stenting, and 5.3% for stenting alone; p = 0.41). All patients had clinical follow up at a mean of 7.9 (2.7) months. Angiographic follow up was done in 89 patients (76%) at a mean of 5.9 (2.2) months. The atherectomy plus stenting group had a larger minimum lumen diameter than the stenting group (2.79 (0.64) mm v 2.26 (0.85) mm, p = 0.004) and a lower binary restenosis rate (13.8% v 33.3%, p = 0.031). Six month MACE were reduced in the atherectomy plus stenting group (8.7% v 23.9%, p = 0.048). Debulking before stenting in de novo lesions located at the ostium of the LAD is safe and is associated with a high rate of technical success. Follow up data show that DCA plus stenting results in a significantly larger minimum lumen diameter and a lower incidence of restenosis than stenting alone.


Pacifier-sucking and breast-feeding: a comparison between the 1960 s and the 1990 s.
Pacifiers and their forerunners have been condemned in past centuries, probably beginning in the 17(th) and 18(th) centuries when alcohol and opiates were incorporated as fillings in sucking rags in Great Britain. Nowadays, the modern pacifier is criticized for reducing breast-feeding time and encouraging weaning. The purpose of this study was to analyze if pacifier-sucking has been detrimental to breast-feeding in the past few decades. In the present study, 2 groups of young children born 30 years apart (1967 and 1995 to 1997) in the same geographic area were analyzed in the first 6 months of age regarding their sucking and feeding habits, including initial and prolonged pacifier-sucking and breast-feeding. Findings do not support the commonly held opinion that pacifier-sucking reduces breast-feeding time. In the 30 years that separate the 2 groups, the pacifier-sucking habit increased by 32% and prolonged use of a pacifier increased. At the same time, breast-feeding at 6 months old has increased 20-fold in the contemporary group (born between 1995 and 1997) as compared with the 1967 group. The results suggest that mothers might be unable to satisfy their child's sucking urge through breast-feeding alone, and that they use the pacifier as a supplement. Pacifier use does not negatively affect the prevalence of breast-feeding.


Clinical preventability of 30-day readmission after percutaneous coronary intervention.
Early readmission after PCI is an important contributor to healthcare expenditures and a target for performance measurement. The extent to which 30-day readmissions after PCI are preventable is unknown yet essential to minimizing their occurrence. PCI patients readmitted to hospital at which PCI was performed within 30 days of discharge at the Massachusetts General Hospital and Brigham and Women's Hospital were identified, and their medical records were independently reviewed by 2 physicians. Each reviewer used an ordinal scale (0, not; 1, possibly; 2, probably; and 3, definitely preventable) to rate clinical preventability, and a total sum score ≥2 was considered preventable. Characteristics of preventable and unpreventable readmissions were compared, and predictors of clinical preventability were assessed by using multivariate logistic regression. Of 9288 PCIs performed, 9081 (97.8%) patients survived to initial hospital discharge and 1007 (11.1%) were readmitted to the index hospital within 30 days. After excluding repeat readmissions, 893 readmissions were reviewed. Fair agreement between physician reviewers was observed (weighted κ statistic 0.44 [95% CI 0.39 to 0.49]). After aggregation of scores, 380 (42.6%) readmissions were deemed preventable and 513 (57.4%) were deemed not preventable. Common causes of preventable readmissions included staged PCI without new symptoms (14.7%), vascular/bleeding complications of PCI (10.0%), and congestive heart failure (9.7%). Nearly half of 30-day readmissions after PCI may have been prevented by changes in clinical decision-making. Focusing on these readmissions may reduce readmission rates.


Absence of interstitial lung disease at initial visit may predict a favorable outcome for Japanese patients with systemic sclerosis with anti-topoisomerase I antibody.
Interstitial lung disease (ILD) is recognized a prognostic factor and leading cause of death in patients with systemic sclerosis (SSc). The aim of the present study is to clarify factors at an initial visit that are associated with the deterioration of ILD in SSc patients with anti-topoisomerase I (anti-topo I) antibodies. This was a single-center, retrospective, observational study. Fifty-three consecutive SSc patients with anti-topo I antibodies were included in this study. Of the 53 patients, 43 had ILD at their initial visit, whereas 10 did not. We examined the clinical and immunological factors at an initial visit that were associated with the deterioration of ILD. The deterioration of ILD was defined as the administration of intravenous cyclophosphamide (IVCY) therapy. In this cohort, 45 (85%) patients had ILD at the time of the final observation, and only two who did not have ILD at their initial visit developed ILD during the follow-up period. Until the final observation, 26 (49%) patients received IVCY therapy for the progression of ILD. The age at onset, disease duration, SSc subtype, and skin score were similar between patients with and those without IVCY therapy. Approximately 60% (26 of 43) of patients with ILD at their initial visit received IVCY therapy. On the other hand, none of the 10 patients without ILD at their initial visit received IVCY therapy. Our multivariate analyses using Cox proportional hazards regression model revealed that the presence of ILD at an initial visit was an independent factor associated with the introduction of IVCY therapy (odds ratio, 2.8e+7 [95% confidence interval, 1.8e+17-uncalculated], p = 0.0048). Although anti-topo I antibodies are strongly associated with ILD, it was unlikely for SSc patients with anti-topo I antibodies to receive IVCY therapy when they did not have ILD at an initial visit.


A mouse model of pulmonary Mycobacteroides abscessus infection.
There is no preclinical mouse model to investigate pulmonary Mycobacteroides abscessus (formerly Mycobacterium abscessus) infection in an immunocompetent mouse strain, especially in the context of antibiotic testing and regimen development. We developed a mouse model of pulmonary M. abscessus infection using the aerosolized route of infection that leads to an increase in bacterial burden post- implantation and develops pathology as a result. In this mouse model, treatment with corticosteroid allows for initial proliferation and sustained M. abscessus pulmonary infection and permits evaluation of efficacies of antibiotics. Administration of corticosteroids that permitted higher levels of bacterial burden in the lungs were more likely to have pathology. Treatment of mice with antibiotics administered intranasally or subcutaneously significantly reduced lung M. abscessus burden. In addition to the reference strain, independent clinical isolates of M. abscessus also readily establish infection and proliferate in the lungs of mice in this model.


Study of electromagnetic radiation pollution in an Indian city.
Electromagnetic radiation emitted by cell phone towers is a form of environmental pollution and is a new health hazard, especially to children and patients. The present studies were taken to estimate the microwave/RF pollution by measuring radiation power densities near schools and hospitals of Chandigarh city in India. The cell phone radiations were measured using a handheld portable power density meter TES 593 and specific absorption rates were estimated from the measured values. These values of electromagnetic radiation in the environment were compared with the levels at which biological system of humans and animals starts getting affected. The values were also compared with the international exposure limits set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The highest measured power density was 11.48 mW/m(2) which is 1,148% of the biological limit. The results indicated that the exposure levels in the city were below the ICNIRP limit, but much above the biological limit.


An overview of female voiding dysfunction.
Female voiding dysfunction is a complex condition and has a number of possible causes. It lacks definition and is poorly understood. This article outlines what is considered normal voiding function and the factors that have been identified to cause voiding dysfunction in females. Assessment through careful questioning, use of an assessment tool and examination are essential to help form a diagnosis. Investigations may be simple and non-invasive or complex depending on the outcome of the assessment. Management options are dependent on the factor causing the problem; it is important to remember that lower urinary tract function can affect renal function and this must be preserved when considering management or treatment options.


A Secure Vitals Monitoring Point-of-Care Device.
Point-of-care (POC) devices continuously monitor vital signs and provide health suggestions to users. However, the devices are not affordable to everyone due to their cost. Here, we design a POC device that can continuously estimate vital signs using fewer sensors and lower costs. We do so by measuring photoplethysmogram signals and temperature and then estimating the heart rate, blood oxygen saturation, respiration rate, and blood pressure. For keeping the vital data secure, an auto-encoder and a convolutional neural network were also used for encryption and abnormality detection, respectively. Tests on the hardware showed the design accurately obtained users' vitals. The proposed design is expected to be generalized to obtain other vitals and fabricated at a low cost, making it affordable to all people.