Exploring the speech and language of individuals with non-syndromic submucous cleft palate: a preliminary report.
Submucous cleft palate (SMCP) has a heterogeneous presentation and is often identified late or misdiagnosed. Diagnosis is prompted by speech, resonance or feeding symptoms associated with velopharyngeal insufficiency. However, the broader impacts of SMCP on communication have rarely been examined and therefore are poorly understood. To describe the communicative profile of individuals with non-syndromic SMCP by examining speech, language and pragmatics (social language). Fifteen participants with SMCP aged 5;1-12;8, without a genetic diagnosis, participated in the study. Participants completed standardized assessments examining language, resonance, speech and non-verbal intellect. Parents also completed the Children's Communication Checklist (CCC-2), which provided a measure of overall communicative ability, including pragmatic skills. Formal language outcomes were compared with two cohorts: 36 individuals with overt non-syndromic clefts and 129 individuals with no history of clefting. Speech intelligibility was reduced secondary to hypernasality, disordered articulation and/or impaired phonology (n = 7) in children with SMCP. Poorer overall language outcomes were observed for children with SMCP compared with both those with overt clefts and no history of clefting (p < 0.001). Language scores for children with SMCP ranged from impaired (n = 6) to above the standardized mean (n = 4). Receptive and expressive language performance were independently correlated with non-verbal IQ (p < 0.01). Those with severe language impairment (n = 4) also had borderline or impaired non-verbal IQ. Parents reported that speech and semantics were the most affected sub-domains of communication, while scores were the highest for the initiation domain. Speech and language skills were correlated strongly with pragmatics (r = 0.877, p < 0.01). Overall, performance was variable within the SMCP group across speech, language and pragmatic assessments. In addition to well-documented speech difficulties, children with SMCP may have language or pragmatic impairments, suggesting that further neurodevelopmental influences may be at play. As such, for individuals with SMCP, additional clinical screening of language and pragmatic abilities may be required to ensure accurate diagnosis and guide both cleft and non-cleft related therapy programmes.


Nicotinamide adenine dinucleotide-dependent and nicotinamide adenine dinucleotide-independent lactate dehydrogenases in homofermentative and heterofermentative lactic acid bacteria.
Three homofermentative (Lactobacillus plantarum B38, L. plantarum B33, Pediococcus pentosaceus B30) and three heterofermentative (Leuconostoc mesenteroides 39, L. oenos B70, Lactobacillus brevis) lactic acid bacteria were examined for the presence or absence of nicotinamide adenine dinucleotide (NAD)-dependent and NAD-independent d- and l-lactate dehydrogenases. Two of the six strains investigated, P. pentosaceus and L. oenos, did not exhibit an NAD-independent enzyme activity capable of reducing dichlorophenol indophenol. The pH optima of the lactic dehydrogenases were determined. The NAD-dependent enzymes from homofermentative strains exhibited optima at pH 7.8 to 8.8, whereas values from 9.0 to 10.0 were noted for these enzymes from heterofermentative organisms. The optima for the NAD-independent enzymes were between 5.8 and 6.6. The apparent Michaelis-Menten constants determined for both NAD and the substrates demonstrated the existence of a greater affinity for d- than l-lactic acid. A comparison of the specific NAD-dependent and NAD-independent lactate dehydrogenase activities revealed a direct correlation of the d/l ratios of these activities with the type of lactic acid produced during the growth of the organism.


The relationship between physical fitness attributes and sports injury in female, team ball sport players: a systematic review.
Understanding the relationships between physical fitness characteristics and sports injury may assist with the development of injury minimisation programs. The purpose of this systematic review was to investigate the association between physical fitness attributes and sports injury in female, team ball sport players. Four scientific databases (MEDLINE, EMBASE, SPORTDiscus, Scopus) and reference lists of relevant research were searched for eligible studies up to September 2, 2019. Full-text articles examining the relationship between physical fitness and sports injury in female, team ball sport players were included. A modified Downs and Black checklist was used to assess methodological quality. Data synthesis determined summary conclusions based on the number of significant relationships divided by the total relationships investigated and reported as a percentage. Level of certainty was identified for summary conclusions based on level of evidence. Sub-analyses regarding competition level, age, and single injury types were also conducted. A total of 44 studies were included. Data synthesis revealed no associations (low to moderate certainty) between body composition (1/9; 11%), flexibility (18-20%), and balance (2/8; 25%) and 'any injury' classification. No associations (mostly of moderate certainty) were found between flexibility (0-27%), muscular strength (0-27%), and body composition (14-33%) and various body region injury classifications, whereas mixed summary conclusions were shown for balance (0-48%). Many associations between physical fitness and sports injury were deemed 'unknown' or with an insufficient level of certainty. Sub-analyses revealed no association between strength and noncontact ACL injuries (0/5; 0%) or ankle sprains (0/12; 0%), and between flexibility and ankle sprains (1/5; 20%); however, insufficient certainty of these results exists. Clear associations were concluded between balance and lower body injuries in female, non-elite (10/16; 63%) and junior (9/12; 75%) team ball sport players, with moderate and insufficient certainty of these results, respectively. Limited evidence is available to demonstrate relationships between physical fitness and sports injury in female, team ball sport players. High-quality evidence investigating the multifactorial nature of sports injury, including the interactions physical fitness qualities have with other injury determinants, is needed to better understand the role of physical fitness in minimising sports injuries in female, team ball sport players. CRD42017077374 (PROSPERO on September 14, 2017).


Tau immunization: a cautionary tale?
The amyloid β (Aβ)-protein and microtubule-associated protein, tau, are the major components of the amyloid plaques and neurofibrillary tangles that typify Alzheimer's disease (AD) pathology. As such both Aβ and tau have long been proposed as therapeutic targets. Immunotherapy, particularly targeting Aβ, is currently the most advanced clinical strategy for treating AD. However, several Aβ-directed clinical trials have failed, and there is concern that targeting this protein may not be useful. In contrast, there is a growing optimism that tau immunotherapy may prove more efficacious. Here, for the first time, we studied the effects of chronic administration of an anti-tau monoclonal antibody (5E2) in amyloid precursor protein transgenic mice. For our animal model, we chose the J20 mouse line because prior studies had shown that the cognitive deficits in these mice require expression of tau. Despite the fact that 5E2 was present and active in the brains of immunized mice and that this antibody appeared to engage with extracellular tau, 5E2-treatment did not recover age-dependent spatial reference memory deficits. These results indicate that the memory impairment evident in J20 mice is unlikely to be mediated by a form of extracellular tau recognized by 5E2. In addition to the lack of positive effect of anti-tau immunotherapy, we also documented a significant increase in mortality among J20 mice that received 5E2. Because both the J20 mice used here and tau transgenic mice used in prior tau immunotherapy trials are imperfect models of AD our results recommend extensive preclinical testing of anti-tau antibody-based therapies using multiple mouse models and a variety of different anti-tau antibodies.


Interaction of internal Na+ and external K+ with the erythrocyte Na+, K+ cotransport system in essential hypertension.
External K+ inhibits the maximal rate of outward Na+, K+ cotransport in human red cells with no effect on the apparent affinity for internal Na+. The K+ concentration giving half-maximal inhibition (KIK) varied from 16 to 30 mM in 24 normotensive control subjects. Six of the 38 hypertensive patients showed a KIK above the upper limit of this normal range. Only three hypertensive patients showed a KIK below normal range. The internal Na+ content giving half-maximal stimulation of outward Na+, K+ cotransport (KSNa) was measured in the hypertensive patients (a normal range of KSNa = 9 to 16 mmol/liter cells was previously established in 50 normotensive control subjects). Eighteen hypertensive patients showed an abnormally high KSNa, as previously described in hypertensive patients whose Na+, K+ cotransport system had a low affinity for internal Na+ (Co -). Comparison of KSNa with KIK showed that all six hypertensive patients with high KIK and all three hypertensive patients with low KIK were Co - hypertensive.


Cooperation and antagonism in information exchange in a growth scenario with two species.
We consider a simple information-theoretic model of communication, in which two species of bacteria have the option of exchanging information about their environment, thereby improving their chances of survival. For this purpose, we model a system consisting of two species whose dynamics in the world are modelled by a bet-hedging strategy. It is well known that such models lend themselves to elegant information-theoretical interpretations by relating their respective long-term growth rate to the information the individual species has about its environment. We are specifically interested in modelling how this dynamics are affected when the species interact cooperatively or in an antagonistic way in a scenario with limited resources. For this purpose, we consider the exchange of environmental information between the two species in the framework of a game. Our results show that a transition from a cooperative to an antagonistic behaviour in a species results as a response to a change in the availability of resources. Species cooperate in abundance of resources, while they behave antagonistically in scarcity.


Oral ibuprofen and diclofenac in post-operative pain: a quantitative systematic review.
Surveys show consistently that pain is not treated well. Improvement depends on knowing which treatments are the most effective. We used systematic review to compare the relative efficacy of two common analgesics, ibuprofen and diclofenac, in post-operative pain. Studies were identified by searching MEDLINE (1966 to Dec 1996), EMBASE (1980 to Jan 1997), the Cochrane Library (Aug 1996), Biological Abstracts (Jan 1985 to Dec 1996) and the Oxford Pain Relief Database (1950 to 1994). We sought randomised, controlled, single-dose comparisons of oral ibuprofen or diclofenac against placebo. Summed pain relief or pain intensity difference over 4-6 h was extracted and converted into dichotomous information yielding the number of patients with at least 50% pain relief. This was then used to calculate the relative benefit and the number-needed-to-treat for one patient to achieve at least 50% pain relief. Thirty-four reports compared ibuprofen and placebo (3591 patients), six compared diclofenac with placebo (840 patients), and there were two direct comparisons of diclofenac 50 mg and ibuprofen 400 mg (130 patients). In post-operative pain, the numbers-needed-to-treat for ibuprofen 200 mg were 3.3 (95% confidence interval 2.8-4.0) compared with placebo, for ibuprofen 400 mg 2.7 (2.5-3.0), for ibuprofen 600 mg 2.4 (1.9-3.3), for diclofenac 50 mg 2.3 (2.0-2.7) and for diclofenac 100 mg 1.8 (1.5-2.1). Direct comparisons of diclofenac 50 mg with ibuprofen 400 mg showed no significant difference between the two. Both drugs worked well. Choosing between them is an issue of dose, safety and cost. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.


Production of consistent pain by intermittent infusion of sterile 5% hypertonic saline, followed by decrease of pain with cryotherapy.
It is suggested that postinjury pain is difficult to examine; thus, investigators have developed experimental pain models. To minimize pain, cryotherapy (cryo) is applied, but reports on its effectiveness are limited. To investigate a pain model for the anterior knee and examine cryo in reducing the pain. Controlled laboratory study. Therapeutic modality laboratory. 30 physically active healthy male subjects who were free from any lower extremity orthopedic, neurological, cardiovascular, or endocrine pathologies. Perceived pain was measured every minute. Surface temperature was also assessed in the center of the patella and the popliteal fossa. There was a significant interaction between group and time (F68,864 = 3.0, P = .0001). At the first minute, there was no difference in pain between the 3 groups (saline/cryo = 4.80 ± 4.87 mm, saline/sham = 2.80 ± 3.55 mm, no saline/cryo = 4.00 ± 3.33 mm). During the first 5 min, pain increased from 4.80 ± 4.87 to 45.90 ± 21.17 mm in the saline/cryo group and from 2.80 ± 3.55 to 31.10 ± 20.25 mm in the saline/sham group. Pain did not change within the no-saline/cryo group, 4.00 ± 3.33 to 1.70 ± 1.70 mm. Pain for the saline/sham group remained constant for 17 min. Cryo decreased pain for 16 min in the saline/cryo group. There was no difference in preapplication surface temperature between or within each group. No change in temperature occurred within the saline/sham. Cooling and rewarming were similar in both cryo groups. Ambient temperature fluctuated less than 1°C during data collection. Intermittent infusion of sterile 5% hypertonic saline may be a useful experimental pain model in establishing a constant level of pain in a controlled laboratory setting. Cryotherapy decreased the induced anterior knee pain for 16 min.


Cadmium toxicity induced contrasting patterns of concentrations of free sarcosine, specific amino acids and selected microelements in two Noccaea species.
Cadmium (Cd) toxicity affects numerous metabolic processes in plants. In the presence of Cd, plants accumulate specific amino acids which may be beneficial to developing Cd tolerance. Our study aimed to characterize the changes in the metabolism of selected free amino acids that are associated with Cd tolerance, and investigate the levels of selected microelements in order to relate these changes to the adaptation strategies of two metallophytes-Noccaea caerulescens (Redlschlag, Austria) and Noccaea praecox (Mežica, Slovenia). The plants were exposed to Cd contamination (90 mg Cd/kg soil) for 120 days in a pot experiment. Our results showed higher Cd accumulation in N. praecox compared to N. caerulescens. Cadmium contamination reduced the zinc and nickel levels in both species and a mixed effect was determined for copper and manganese content. Differences in free amino acid metabolism were observed between the two metallophytes growing under Cd-free and Cd-loaded conditions. Under Cd-free conditions, aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) were accumulated more in the leaves of N. praecox than in N. caerulescens. Cd stress increased the content of these amino acids in both species but this increase was significant only in N. caerulescens leaves. Marked differences in the responses of the two species to Cd stress were shown for alanine, phenylalanine, threonine and sarcosine. Cadmium contamination also induced an increase of threonine as alanine and sarcosine decrease, which was larger in N. caerulescens than in N. praecox. All these factors contribute to the higher adaptation of N. praecox to Cd stress.


Male-specific cuticular compounds of the six Drosophila paulistorum semispecies: structural identification and mating effect.
We have identified cuticular pheromones that sustain the integrity of the six Drosophila paulistorum semispecies. Hexane extracts of male and female cuticles were separated on a silica gel column and analyzed using gas chromatography/mass spectrometry. Both sexes of each of the six semispecies have the same fifteen major cuticular components, all hydrocarbons ranging from C31 to C37. However, all males have four additional ester compounds. Bioassay observations showed that this four-component ester complex imparts a strong anti-aphrodisiac effect on intra-semispecific mating behavior, thus confirming its pheromonal role. The three major ester components are methyl (Z)-9-tetradecenoate (C(15)H(28)O(2)), 11-docosenyl acetate (C(24)H(46)O(2)), and 19-triacontenyl acetate (C(32)H(62)O(2)). The fourth ester is a di-unsaturated acetate with molecular formula C(32)H(60)O(2), but the positions of unsaturation have not been determined. Bioassays indicate that the male-specific complex of the transitional semispecies, the relict ancestor, imparts anti-aphrodisiac effects on the other semispecies as well, but effectiveness decreases with phylogenetic distances. Across the six semispecies, the male-specific compounds are the same, but vary quantitatively. Apparently, the quantitative differences among these incipient species act efficiently to preclude hybridization in nature. Because Drosophila paulistorum is a cluster of incipient species, this opportunity to observe pheromonal influences on speciation is unique.


Diet quality over time is associated with better development in rural Nepali children.
Developmental delays affect between 150 and 200 million children <5 years of age worldwide. Outside of diet supplement studies, relatively little is known about the relationships between diet quality and developmental status in resource-poor settings. We examined associations between different aspects of dietary quality (dietary diversity score [DDS] and animal-source food [ASF] consumption) and child development (assessed using the Ages and Stages Questionnaire-3 [ASQ-3]) among children whose families were enrolled in a community development intervention trial (implemented by Heifer Nepal) in western Nepal. Two sets of analyses were performed: (a) cross-sectional Sample (N = 629) seen at the endline survey and (b) longitudinal sample (N = 269) with complete dietary records (six surveys over 48 months). In both samples, child development was significantly related to household wealth, maternal education, and especially home environmental quality. In the cross-sectional sample, greater consumption of eggs (adjusted odds ratio [aOR] 0.80, p = .04) or dairy products (aOR 0.95, p = .05) over the previous 7 days significantly reduced odds of low total ASQ score, by logistic regression analysis. In the longitudinal sample, only egg consumption and cumulative DDS and ASF scores were associated with significantly reduced odds of low total ASQ score (aORs 0.59-0.89). In adjusted linear regression analysis, both cumulative DDS (β [CI]: 1.92 [0.4, 3.5]) and ASF scores (2.46 [0.3, 4.7]) were significantly associated with greater continuous total child development. Programmes targeting child development must address home environmental quality as well as long-term diet quality.


Study of business ethics in occupational medicine.
To investigate the views of specialists in occupational medicine about business ethics in occupational medicine. A qualitative study with face to face focus groups and successive reviews of the draft consensus was undertaken of all accredited specialists in occupational medicine who were members of the south Wales and west of England group of the Society of Occupational Medicine, and of all regional specialty advisers and deputies from the Faculty of Occupational Medicine. There was widespread agreement for the need of a code of business ethics. In all, during the four draft stages of preparing a consensus, 72% (28/39) of members of the south Wales and west of England group of the Society of Occupational Medicine, and 31% (20/64) of regional specialty advisers and deputies provided detailed comment for inclusion in it. Consensus of their views was reached among study participants for issues of business ethics involving advertising, competence, qualifications, fees, commitment, changes in provider contracts, regulation, and supervision of trainees. It provides a basis for further debate.


Chronic nicotine toxicity is prevented by aqueous garlic extract.
Based on the potent antioxidant effects of garlic, we investigated the putative protective role of aqueous garlic extract (AGE) against nicotine-induced oxidative organ damage. Male Wistar albino rats (200-250 g) were injected with nicotine hydrogen bitartrate (0.6 mg/kg; i.p.) alone or with aqueous garlic extract (125 mg/kg; i.p.) for 21 days. At the end of the experimental period (22nd day) rats were killed by decapitation. The aorta, heart, kidney and urinary bladder tissues were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Blood urea nitrogen (BUN) and creatinine concentrations and lactate dehydrogenase (LDH) levels in blood were measured for the evaluation of renal functions and tissue damage, respectively. Tissues were also examined microscopically. The decrease in GSH levels and increases in MDA level, MPO activity and collagen contents induced by chronic nicotine administration indicated that tissue injury involves free radical formation. Treatment of rats with AGE restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the tissues by chronic nicotine were reversed back to the control levels with AGE. Since AGE administration reversed these oxidant responses, improved renal function and histological damage, it seems likely that AGE protects the tissues against nicotine-induced oxidative damage.


Effect of halo-vest components on stabilizing the injured cervical spine.
An in vitro biomechanical study. The objectives were to develop a new biofidelic skull-neck-thorax model capable of quantifying motion patterns of the cervical spine in the presence of a halo-vest; to investigate the effects of vest loosening, superstructure loosening, and removal of the posterior uprights; and to evaluate the ability of the halo-vest to stabilize the neck within physiological motion limits. Previous clinical and biomechanical studies have investigated neck motion with the halo-vest only in the sagittal plane or only at the injured spinal level. No previous studies have quantified three-dimensional intervertebral motion patterns throughout the injured cervical spine stabilized with the halo-vest or studied the effect of halo-vest components on these motions. The halo-vest was applied to the skull-neck-thorax model. Six osteoligamentous whole cervical spine specimens (occiput through T1 vertebra) were used that had sustained multiplanar ligamentous injuries at C3/4 through C7-T1 during a previous protocol. Flexibility tests were performed with normal halo-vest application, loose vest, loose superstructure, and following removal of the posterior uprights. Average total range of motion for each experimental condition was statistically compared (P < 0.05) with the physiologic rotation limit for each spinal level. Cervical spine snaking was observed in both the sagittal and frontal planes. The halo-vest, applied normally, generally limited average spinal motions to within average physiological limits. No significant increases in average spinal motions above physiologic were observed due to loose vest, loose superstructure, or removal of the posterior uprights. However, a trend toward increased motion at C6/7 in lateral bending was observed due to loose superstructure. The halo-vest, applied normally, effectively immobilized the cervical spine. Sagittal or frontal plane snaking of the cervical spine due to the halo-vest may reduce its immobilization capability at the upper cervical spine and cervicothoracic junction.


Resource implications of adopting a restrictive neonatal blood transfusion policy.
Blood transfusions (BTFs) are not without risk and pose a significant financial burden on resource-limited services. In line with current international evidence, the nursery at Groote Schuur Hospital (GSH), Cape Town, South Africa, introduced a restrictive BTF protocol to minimise transfusions and manage costs. To determine whether adopting a restrictive BTF policy results in fewer transfusions. Data were retrospectively collected on all infants who received BTFs in the GSH nursery over a 6-month period following adoption of a restrictive BTF policy in 2010. BTF figures for a similar time period before the restrictive policy, during 2008, were obtained for comparison. After introduction of the restrictive BTF policy, 42 of 1 097 infants admitted (3.8%) received a total of 64 BTFs. In comparison, 102 of a total of 940 infants (10.9%) admitted during a period of the same length before introduction of the restrictive BTF policy received a total of 121 transfusions. Comparison between the number of BTFs administered before and after the restrictive policy showed a highly statistically significant difference (p<0.001). The total cost of the blood products used in the two 6-month periods was R91 870 v. R48 640, based on current prices. By adopting a restrictive policy, we were able to halve the number of BTFs, reduce risks associated with transfusions, and achieve significant cost benefits. Following evidence-based guidelines results in high standards of care, while also making the most effective use of resources.


Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory.
Clinical laboratories are increasingly receiving requests to perform nucleic acid amplification tests for the detection of a wide variety of infectious agents. In this paper, the efficiency of nucleic acid amplification techniques for the diagnosis of respiratory tract infections is reviewed. In general, these techniques should be applied only for the detection of microorganisms for which available diagnostic techniques are markedly insensitive or nonexistent or when turnaround times for existing tests (e.g., viral culture) are much longer than those expected with amplification. This is the case for rhinoviruses, coronaviruses, and hantaviruses causing a pulmonary syndrome, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Coxiella burnetii. For Legionella spp. and fungi, contamination originating from the environment is a limiting factor in interpretation of results, as is the difficulty in differentiating colonization and infection. Detection of these agents in urine or blood by amplification techniques remains to be evaluated. In the clinical setting, there is no need for molecular diagnostic tests for the diagnosis of Pneumocystis carinii. At present, amplification methods for Mycobacterium tuberculosis cannot replace the classical diagnostic techniques, due to their lack of sensitivity and the absence of specific internal controls for the detection of inhibitors of the reaction. Also, the results of interlaboratory comparisons are unsatisfactory. Furthermore, isolates are needed for susceptibility studies. Additional work remains to be done on sample preparation methods, comparison between different amplification methods, and analysis of results. The techniques can be useful for the rapid identification of M. tuberculosis in particular circumstances, as well as the rapid detection of most rifampin-resistant isolates. The introduction of diagnostic amplification techniques into a clinical laboratory implies a level of proficiency for excluding false-positive and false-negative results.


Molecular effects of homocysteine on cbEGF domain structure: insights into the pathogenesis of homocystinuria.
Homocystinuria is an inborn error of methionine metabolism that results in raised serum levels of the highly reactive thiol-containing amino acid homocysteine. Homocystinurics often exhibit phenotypic abnormalities that are similar to those found in Marfan syndrome (MFS), a heritable connective tissue disorder that is caused by reduced levels of, or defects in, the cysteine-rich extracellular matrix (ECM) protein fibrillin-1. The phenotypic similarities between homocystinuria and MFS suggest that elevated homocysteine levels may result in an altered function of fibrillin-1. We have used recombinant calcium binding epidermal growth factor-like (cbEGF) domain fragments from fibrillin-1, and an unrelated protein Notch1, to analyse the effects of homocysteine on the native disulphide (cystine) bonds of these domains. We show using analytical reverse phase, high performance liquid chromatography (HPLC), electrospray ionisation mass spectrometry (ESI-MS) and limited proteolysis that homocysteine attacks intramolecular disulphide bonds causing reduction of cystine and domain misfolding, and that the effects of homocysteine are dependent on its concentration. We also identify the importance of calcium binding to cbEGF domains for their stabilisation and protection against homocysteine attack. Collectively, these data suggest that reduction of intramolecular cbEGF domain disulphide bonds by homocysteine and the resulting disruption of this domain fold may contribute to the change in connective tissue function seen in homocystinuria. Furthermore, since we show that the effects of homocysteine are not unique to fibrillin-1, other cbEGF-containing proteins may be implicated in the pathogenic mechanisms underlying homocystinuria.


Different aberrations raise contrast thresholds for single-letter identification in line with their effect on cross-correlation-based confusability.
We previously showed that different types of aberration defocus, coma, and secondary astigmatism affect reading performance via different mechanisms. In this paper, we show the contrary result that, for identification of isolated letters, the effects of rendering different types of aberration can be described by a single cross-correlation-based metric. Aberrations reduce the effective resolution of an optical system, quantified by the high-frequency fall-off of the modulation transfer function. They additionally cause spatial-frequency-dependent phase and contrast changes, which have a size-dependent effect on letter forms. We used contrast threshold as our performance measure, instead of distance acuity, to separate the effects of form alterations from those of resolution limits. This measure is additionally appropriate in comparing single-letter-based performance to reading at a fixed distance. The relationship between a cross-correlation-based measure of letter confusability and performance was the same for all three types of aberration. For reading, we had found a different relationship for coma than for defocus and secondary astigmatism. We conclude that even when two tasks--letter identification and reading--use the same component stimulus set, the combination of multiple letters in a reading task produces functional differences between the effects of these aberrations that are not present for isolated letters.


High-capacity thermo-responsive magnetic molecularly imprinted polymers for selective extraction of curcuminoids.
Thermo-responsive magnetic molecularly imprinted polymers (TMMIPs) for selective recognition of curcuminoids with high capacity and selectivity have firstly been developed. The resulting TMMIPs were characterized by TEM, FT-IR, TGA, VSM and UV, which indicated that TMMIPs showed thermo-responsiveness [lower critical solution temperature (LCST) at 33.71°C] and rapid magnetic separation (5s). The polymerization, adsorption and release conditions were optimized in detail to obtain the highest binding capacity, selectivity and release ratio. We found that the adopted thermo-responsive monomer [N-isopropylacrylamide (NIPAm)] could be considered not only as inert polymer backbone for thermo-responsiveness but also as functional co-monomers combination with basic monomer (4-VP) for more specific binding sites when ethanol was added in binding solution. The maximum adsorption capacity with highest selectivity of curcumin was 440.3μg/g (1.93 times that on MMIPs with no thermosensitivity) at 45°C (above LCST) in 20% (v/v) ethanol solution on shrunk TMMIPs, and the maximum release proportion was about 98% at 20°C (below LCST) in methanol-acetic acid (9/1, v/v) solution on swelled TMMIPs. The adsorption process between curcumin and TMMIPs followed Langumuir adsorption isotherm and pseudo-first-order reaction kinetics. The prepared TMMIPs also showed high reproducibility (RSD<6% for batch-to-batch evaluation) and stability (only 7% decrease after five cycles). Subsequently, the TMMIPs were successfully applied for selective extraction of curcuminoids from complex natural product, Curcuma longa.


Public hospital management in times of crisis: lessons learned from Cienfuegos, Cuba (1996-2008).
Cuba's public health system is well known for its integrated first line services based on family medicine. Less publicized is the country's experience in public hospital management. After a harsh economic crisis in the first half of the 1990s had brought the Cienfuegos hospital near to collapse, from 1996 onwards the hospital management team took advantage of the incipient economic recovery to launch an ambitious recovery process. This article reconstructs this endeavor, based on annual hospital reports, scientific publications by the hospital staff, and interviews with key decision-makers. First the endless waiting list for elective surgery was tackled through a more efficient use of the surgery department, and an increase of ambulatory surgery. Next, overall hospital efficiency was improved in the aim to drastically reduce the average length of stay, reaching a decrease from an average stay of 12 days to a little more than 6 days in 1999. Also the emergency department was reorganized, setting up a triage system based on a color code, linked to specific emergency protocols. Attention for improving the clinical efficiency for AMI and stroke coincided with a drop in their intrahospital lethality. Clinical guidelines for the most important diagnoses were collectively developed, adapting international evidence to the local setting. An individual and collective performance evaluation system was elaborated in a participatory way, and further evolved into a 'total quality management' process. This experience of Cienfuegos hospital provides an interesting example on how a public hospital--embedded in a well developed national public health system--can be effective and efficient, even in circumstances of limited resources.


Metagenome plasticity of the bovine abomasal microbiota in immune animals in response to Ostertagia ostertagi infection.
Infections in cattle by the abomasal nematode Ostertagia ostertagi result in impaired gastrointestinal function. Six partially immune animals were developed using multiple drug-attenuated infections, and these animals displayed reduced worm burdens and a slightly elevated abomasal pH upon reinfection. In this study, we characterized the abomasal microbiota in response to reinfection using metagenomic tools. Compared to uninfected controls, infection did not induce a significant change in the microbial community composition in immune animals. 16S rRNA gene-based phylogenetic analysis identified 15 phyla in the bovine abomasal microbiota with Bacteroidetes (60.5%), Firmicutes (27.1%), Proteobacteria (7.2%), Spirochates (2.9%), and Fibrobacteres (1.5%) being the most predominant. The number of prokaryotic genera and operational taxonomic units (OTU) identified in the abomasal microbial community was 70.8±19.8 (mean ± SD) and 90.3±2.9, respectively. However, the core microbiome comprised of 32 genera and 72 OTU. Infection seemingly had a minimal impact on the abomasal microbial diversity at a genus level in immune animals. Proteins predicted from whole genome shotgun (WGS) DNA sequences were assigned to 5,408 Pfam and 3,381 COG families, demonstrating dazzling arrays of functional diversity in bovine abomasal microbial communities. However, none of COG functional classes were significantly impacted by infection. Our results demonstrate that immune animals may develop abilities to maintain proper stability of their abomasal microbial ecosystem. A minimal disruption in the bovine abomasal microbiota by reinfection may contribute equally to the restoration of gastric function in immune animals.


Oral administration of Lactobacillus fermentum CRL1446 improves biomarkers of metabolic syndrome in mice fed a high-fat diet supplemented with wheat bran.
This work aimed to evaluate the effect of oral administration of probiotic Lactobacillus (L.) fermentum CRL1446, with feruloyl esterase (FE) activity, on metabolic biomarkers and intestinal microbiota of mice with high fat diet-induced Metabolic Syndrome (MS) and supplemented with wheat bran as a source of esterified ferulic acid. Six-week-old male Swiss albino mice developed the components of MS when fed with high fat diet supplemented with wheat bran (HFD + WB) for 14 weeks. Positive impact of L. fermentum CRL1446 administration on these animals was reflected in a decrease in body weight gain and adiposity index compared to the animals that did not receive the probiotic strain. In addition, a decrease in plasma leptin levels, improvement of inflammatory profile, reduction of fatty infiltration in hepatocytes and modification of lipid profile (increased HDL-cholesterol and decreased LDL-cholesterol and triglyceride levels) were observed. On the other hand, L. fermentum CRL1446 reduced fasting glucose and insulin levels, improving the HOMA index in mice with MS. Postprandial glucose levels were also reduced in the oral glucose tolerance test. Consumption of L. fermentum CRL1446 with HFD + WB (HFD + WB-Lf mice group) had a great impact on host metabolism, modulating intestinal microbiota, with an increase in Bacteroidetes and a decrease in Firmicutes abundance being observed. Increased intestinal FE activity, improved oxidative status and increased abundance of 3-hydroxyphenylpropionic acid and butyric acid concentration in colonic content, were also demonstrated in HFD + WB-Lf mice. Results obtained suggest that supplementation with L. fermentum CRL1446 enhances beneficial effects of a bran diet, attenuating the risk factors associated with MS.


Shielding assessment of a mobile electron accelerator for intra-operative radiotherapy.
The purpose of this investigation is to measure, characterize and report stray photon leakage and scatter radiation measurements from the Mobetron, an intraoperative electron linear accelerator designed for use in an operating room environment. The study is needed due to recent changes to the shielding design of the Mobetron, and also to provide specific information that may be required by regulation in various jurisdictions. An analysis is performed on a number of manufactured units to deter-mine an average 3D stray photon radiation map. This information provides a basis for determining patient-based load restrictions and/or additional shielding for the operating room. The data presented evaluates the number of procedures for which the Mobetron may be safely operated in a typical unshielded operating room.


Anti-N-methyl-aspartate receptor encephalitis in identical twin sisters: role for oophorectomy.
Anti-N-methyl-aspartate receptor encephalitis is a potentially fatal form of encephalitis and frequently associated with ovarian teratomas. Surgical removal of ovarian teratomas improves clinical outcome, but it is unclear whether bilateral salpingo-oophorectomy for normal-appearing ovaries is of clinical benefit. Our report describes a unique clinical scenario of identical twin sisters with anti-N-methyl-aspartate receptor encephalitis. Neither patient responded to immunosuppressive therapy. Imaging studies showed normal-appearing ovaries. The first twin continued on medical therapy only and died of the disease. The second twin underwent a bilateral salpingo-oophorectomy followed by gradual recovery. Based on our experience in two genetically identical individuals, we suggest considering the removal of normal-appearing ovaries in patients with anti-N-methyl-aspartate receptor encephalitis who fail to respond to medical treatment.


Symptomatology and health care utilization of women primary care patients who experienced childhood sexual abuse.
The purpose of this study was to (1) determine the symptomatology of women primary care patients who experienced childhood sexual abuse (CSA), using both a self-report survey and a chart review, and (2) determine their health care utilization patterns, using chart and information system reviews. An ex post facto research design was used. Women primary care patients who experienced CSA were compared with those who reported no CSA. Participants were recruited from a random sample of women patients from a large primary care clinic. They were mailed the survey; chart and information system reviews were conducted on those who returned surveys. Of the 395 participants, 23% reported past CSA on the survey. Women who experienced CSA reported 44 out of 51 physical and psychosocial symptoms more frequently than their counterparts who reported no past CSA. Further, they experienced these symptoms more intensely and in greater number. In their charts, however, far fewer differences in symptoms between groups were found. Nonetheless, women who experienced CSA visited the primary care clinic an average of 1.33 more times than women with no CSA, and they incurred an average of $150 more in primary care charges over a 2-year period. The findings indicate that many women primary care patients who experienced CSA suffer multiple symptoms that are not reflected in their charts. In addition, the findings demonstrate that not only is CSA associated with increased primary care visits, but also increased primary care costs, as measured by charges.


Lack of weight recording in patients being administered narrow therapeutic index antibiotics: a prospective cross-sectional study.
Patient weight is a key measure for safe medication management and monitoring of patients. Here we report the recording of patient's body weight on admission in three hospitals in West London and its relationship with the prescription of antibiotic drugs where it is essential to have the body weight of the patient. A prospective cross-sectional study was conducted in three teaching hospitals in West London. Data were collected during March 2011-September 2011 and July 2012-August 2012, from adult admissions units, medical and surgical wards. Data from each ward were collected on a single day to provide a point prevalence data on weight recording. Patient medication charts, nursing and medical notes were reviewed for evidence of weight and height recording together with all the medication prescribed for the patients. An observational study collecting data on the weight recording process was conducted on two randomly selected wards to add context to the data. Data were collected on 1012 patients. Weight was not recorded for 46% (474) of patients. Eighty-nine patients were prescribed a narrow therapeutic antibiotic, in 39% (35/89) of these weight was not recorded for the patient. Intravenous vancomycin was the most commonly prescribed antibiotic requiring therapeutic monitoring. In total 61 patients were receiving intravenous vancomycin and of these 44% (27/61) did not have their weight recorded. In the observational study, the most frequently identified barrier to weight not being recorded was interruptions to the admission process. Despite the clinical importance of body weight measurement it is poorly recorded in hospitalised patients, due to interruptions to the workflow and heavy staff workloads. In antibiotics a correct, recent patient weight is required for accurate dosing and to keep drugs within the narrow therapeutic index, to ensure efficacy of prescribing and reduce toxicity.


Active engineering of four-wave mixing spectral correlations in multiband hollow-core fibers.
We demonstrate theoretically and experimentally a high level of control of the four-wave mixing process in an inert gas-filled inhibited-coupling guiding hollow-core photonic crystal fiber. The specific multiple-branch dispersion profile in such fibers allows both correlated and separable bi-photon states to be produced. By controlling the choice of gas and its pressure and the fiber length, we experimentally generate various joint spectral intensity profiles in a stimulated regime that is transferable to the spontaneous regime. The generated profiles may cover both spectrally separable and correlated bi-photon states and feature frequency tuning over tens of THz, demonstrating a large dynamic control that will be very useful when implemented in the spontaneous regime as a photon pair source.


Degradation rates of acetylcholine receptors can be modified in the postjunctional plasma membrane of the vertebrate neuromuscular junction.
Denervation of vertebrate muscle causes an acceleration of acetylcholine receptor turnover at the neuromuscular junction. This acceleration reflects the composite behavior of two populations of receptors: "original receptors" present at the junction at the time of denervation, and "new receptors" inserted into the denervated junction to replace the original receptors as they are degraded (Levitt, T. A., and M. M. Salpeter, 1981, Nature (Lond.), 291:239-241). The present study examined the degradation rate of original receptors to determine whether reinnervation could reverse the effect of denervation. Sternomastoid muscles in adult mice were denervated by either cutting or crushing the nerve, and the nerves either allowed to regenerate or ligated to prevent regeneration. The original receptors were labeled with 125I-alpha-bungarotoxin at the time of denervation, and their degradation rate followed by gamma counting. We found that when the nerve was not allowed to regenerate, the degradation decreased from a t1/2 of approximately 8-10 d to one of approximately 3 d (as reported earlier for denervated original receptors) and remained at that half-life throughout the experiment (approximately 36 d). If the axons were allowed to regenerate (which occurred asynchronously between day 14 and day 30 after nerve cut and between day 7 and 13 after nerve crush), the accelerated degradation rate of the original receptors reverted to a t1/2 of approximately 8 d. Our data lead us to conclude that the effect of denervation on the degradation rate of original receptors can be reversed by reinnervating. The nerve can thus slow the degradation rate of receptors previously inserted into the postsynaptic membrane.


Use of epidermal growth factor receptor mutation analysis in patients with advanced non-small-cell lung cancer to determine erlotinib use as first-line therapy.
Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in the United States. Moreover, advanced non-small-cell lung cancer (NSCLC) is considered an incurable disease and current treatment approaches provide marginal improvement in overall survival at the expense of substantial morbidity and mortality, highlighting the need for new, less toxic treatment approaches. Tyrosine kinase inhibitors, such as erlotinib (Tarceva®), have been developed and approved as maintenance, second- and third-line treatment options in unselected advanced NSCLC patients (2, 15). However, subgroup analyses from the initial clinical trials consistently showed that patients with epidermal growth factor receptor (EGFR) mutations who received erlotinib had higher rates of response and better progression-free and overall survival, leading to clinical trials specifically focused on the use of tyrosine kinase inhibitors as first-line therapy in these patients. We examined the published literature on the analytic validity, clinical validity, and clinical utility of EGFR mutational testing in guiding first-line therapy use of erlotinib to treat advanced NSCLC and we briefly summarized the current lung cancer screening guidelines. The primary goal was to provide a basic overview of EGFR mutational testing and use of erlotinib as first-line therapy and identify gaps in knowledge and evidence that affect the recommendation and adoption of the test in advanced NSCLC treatment management strategies.


Plant-derived drugs acting on cellular Ca2+ mobilization in vascular smooth muscle: tetramethylpyrazine and tetrandrine.
The pharmacological profiles of the active ingredients extracted and purified from two well-known Chinese traditional medicinal plants were reviewed. These herbal drugs include tetramethylpyrazine (TMP) and tetrandrine (TET); both have been clinically used in China for the treatment of cardiovascular diseases due to their vasodilatory actions. Studies from this laboratory have confirmed previously reported characteristics of TMP as a Ca2+ antagonist in vascular tissues. However, it also elicited inhibitory effects in response to a wide variety of receptor stimulations as indicated by functional studies and radioligand binding studies using isolated subcellular membranes. TET also inhibited the vascular contraction in response to depolarization by KCl and phenylephrine. It has been found to interact directly with the L-type Ca2+ channel and alpha-adrenoceptor subtypes. Recently, its action on T-type Ca2+ channels has also been demonstrated. These findings collectively suggest that studies of the vasodilatory and antihypertensive effects of these plant-derived drugs on the regulation of cytosolic Ca2+ in vascular smooth muscle are consistent with the current hypothesis of Ca2+ dysfunction as an important etiological factor for the pathogenesis of hypertension.


Specific features of suicidal behavior in patients with narcissistic personality disorder.
Suicidal behavior is a clinically significant but underestimated cause of mortality in narcissistic personality disorder. Currently, there are no reliable estimates of suicidal behavior for this population. The main objective of this study was to test whether or not suicide attempters diagnosed with narcissistic personality disorder are different in terms of impulsivity and expected lethality from suicide attempters with other cluster B personality disorders. In a sample of 446 suicide attempters, patients with cluster B personality disorder diagnoses (n = 254) as assessed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), version of the International Personality Disorder Examination-Screening Questionnaire (IPDE-SQ) were compared in terms of expected lethality and impulsivity (measured by the Beck Suicidal Intent Scale and the Barratt Impulsiveness Scale, respectively). The subjects were admitted to the emergency departments of the Ramón y Cajal Hospital and the Fundación Jiménez Diaz University Hospital in Madrid, Spain, between January 1999 and January 2003. Suicide attempts of subjects diagnosed with narcissistic personality disorder had higher expected lethality than those of subjects without narcissistic personality disorder (t = -4.24, df = 439, P < .001). There were no differences in expected lethality of the attempts when comparing subjects with and without histrionic personality disorder (t = 0.28, df = 439, P = .795), antisocial personality disorder (t = 0.66, df = 439, P = .504), and borderline personality disorder (t = 1.13, df = 439, P = .256), respectively. Suicide attempters diagnosed with narcissistic personality disorder did not significantly differ from suicide attempters without narcissistic personality disorder in terms of impulsivity measures (t = -0.33, df = 442, P = .738), while suicide attempters diagnosed with antisocial personality disorder, histrionic personality disorder, and borderline personality disorder were significantly more impulsive than suicide attempters without these diagnoses (t = -3.96, df = 442, P < .001; t = -3.88, df = 442, P < .001; and t = -7.44, df = 442, P < .001, respectively). Narcissistic personality disorder seems to be a distinct group among cluster B personality disorders with regard to suicidal behavior. In contrast to suicide attempters with other cluster B personality disorders, suicide attempters diagnosed with narcissistic personality disorder are less impulsive and have suicide attempts characterized by higher lethality. These distinctions may offer a basis for targeted therapies aimed at decreasing suicidal risk in patients with narcissistic personality disorder.


Speciation-by-depth on coral reefs: Sympatric divergence with gene flow or cryptic transient isolation?
The distributions of many sister species in the sea overlap geographically but are partitioned along depth gradients. The genetic changes leading to depth segregation may evolve in geographic isolation as a prerequisite to coexistence or may emerge during primary divergence leading to new species. These alternatives can now be distinguished via the power endowed by the thousands of scorable loci provided by second-generation sequence data. Here, we revisit the case of two depth-segregated, genetically isolated ecotypes of the nominal Caribbean candelabrum coral Eunicea flexuosa. Previous analyses based on a handful of markers could not distinguish between models of genetic exchange after a period of isolation (consistent with secondary contact) and divergence with gene flow (consistent with primary divergence). Analyses of the history of isolation, genetic exchange and population size based on 15,640 new SNP markers derived from RNAseq data best support models where divergence began 800K BP and include epochs of divergence with gene flow, but with an intermediate period of transient isolation. Results also supported the previous conclusion that recent exchange between the ecotypes occurs asymmetrically from the Shallow lineage to the Deep. Parallel analyses of data from two other corals with depth-segregated populations (Agaricia fragilis and Pocillopora damicornis) suggest divergence leading to depth-segregated populations may begin with a period of symmetric exchange, but that an epoch of population isolation precedes more complete isolation marked by asymmetric introgression. Thus, while divergence-with-gene flow may account for much of the differentiation that separates closely related, depth-segregated species, it remains to be seen whether any critical steps in the speciation process only occur when populations are isolated.


ACR Appropriateness Criteria® clinically suspected adnexal mass.
Adnexal masses are a common problem clinically and imaging-wise, and transvaginal US (TVUS) is the first-line imaging modality for assessing them in the vast majority of patients. The findings of US, however, should be correlated with the history and laboratory tests, as well as any patient symptoms. Simple cysts are uniformly benign, and most warrant no further interrogation or treatment. Complex cysts carry more significant implications, and usually engender serial ultrasound(s), with a minority of cases warranting a pelvic MRI.Morphological analysis of adnexal masses with gray-scale US can help narrow the differential diagnosis. Spectral Doppler analysis has not proven useful in most well-performed studies. However, the use of color Doppler sonography adds significant contributions to differentiating between benign and malignant masses and is recommended in all cases of complex masses. Malignant masses generally demonstrate neovascularity, with abnormal branching vessel morphology. Optimal sonographic evaluation is achieved by using a combination of gray-scale morphologic assessment and color or power Doppler imaging to detect flow within any solid areas.The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


Classification of older adults who have diabetes by comorbid conditions, United States, 2005-2006.
Older adults who have diabetes vary widely in terms of comorbid conditions; these conditions help determine the risks and benefits of intensive glycemic control. Not all people benefit from intensive glycemic control. The objective of this study was to classify by comorbid conditions older American adults who have diabetes to identify those who are less likely to benefit from intensive glycemic control. We used latent class analysis to identify subgroups of a nationally representative sample of community-dwelling older adults (aged 57-85 y) who have diabetes (n = 750). The subgroups were classified according to 14 comorbid conditions prevalent in the older population. Using the Akaike Information Criterion, the Bayesian Information Criterion (BIC), the sample-size adjusted BIC, and the χ(2) goodness-of-fit statistic, we assessed model fit. We found 3 distinct subgroups. Class 1 (63% of the sample) had the lowest probabilities for most conditions. Class 2 (29% of the sample) had the highest probabilities of cancer, incontinence, and kidney disease. Class 3 (9% of the sample) had the highest probabilities (>90%) of congestive heart failure and myocardial infarction. Class 1 had only 0, 1, or 2 comorbid conditions, and both class 2 and class 3 had 6 or more comorbid conditions. The 5-year death rates for class 2 (17%) and class 3 (33%) were higher than the rate for class 1 (9%). Older adults who have diabetes, cardiovascular disease, and 6 or more comorbid conditions may represent a subgroup of older adults who are less likely to benefit from intensive glycemic control.


Translesion synthesis by yeast DNA polymerase zeta from templates containing lesions of ultraviolet radiation and acetylaminofluorene.
In the yeast Saccharomyces cerevisiae, DNA polymerase zeta (Polzeta) is required in a major lesion bypass pathway. To help understand the role of Polzeta in lesion bypass, we have performed in vitro biochemical analyses of this polymerase in response to several DNA lesions. Purified yeast Polzeta performed limited translesion synthesis opposite a template TT (6-4) photoproduct, incorporating A or T with similar efficiencies (and less frequently G) opposite the 3' T, and predominantly A opposite the 5' T. Purified yeast Polzeta predominantly incorporated a G opposite an acetylaminofluorene (AAF)-adducted guanine. The lesion, however, significantly inhibited subsequent extension. Furthermore, yeast Polzeta catalyzed extension DNA synthesis from primers annealed opposite the AAF-guanine and the 3' T of the TT (6-4) photoproduct with varying efficiencies. Extension synthesis was more efficient when A or C was opposite the AAF-guanine, and when G was opposite the 3' T of the TT (6-4) photoproduct. In contrast, the 3' T of a cis-syn TT dimer completely blocked purified yeast Polzeta, whereas the 5' T was readily bypassed. These results support the following dual-function model of Polzeta. First, Polzeta catalyzes nucleotide incorporation opposite AAF-guanine and TT (6-4) photoproduct with a limited efficiency. Secondly, more efficient bypass of these lesions may require nucleotide incorporation by other DNA polymerases followed by extension DNA synthesis by Polzeta.


Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels.
Orai1 and TRPC1 have been proposed as core components of store-operated calcium release-activated calcium (CRAC) and store-operated calcium (SOC) channels, respectively. STIM1, a Ca(2+) sensor protein in the endoplasmic reticulum, interacts with and mediates store-dependent regulation of both channels. We have previously reported that dynamic association of Orai1, TRPC1, and STIM1 is involved in activation of store-operated Ca(2+) entry (SOCE) in salivary gland cells. In this study, we have assessed the molecular basis of TRPC1-SOC channels in HEK293 cells. We report that TRPC1+STIM1-dependent SOCE requires functional Orai1. Thapsigargin stimulation of cells expressing Orai1+STIM1 increased Ca(2+) entry and activated typical I(CRAC) current. STIM1 alone did not affect SOCE, whereas expression of Orai1 induced a decrease. Expression of TRPC1 induced a small increase in SOCE, which was greatly enhanced by co-expression of STIM1. Thapsigargin stimulation of cells expressing TRPC1+STIM1 activated a non-selective cation current, I(SOC), that was blocked by 1 microm Gd(3+) and 2-APB. Knockdown of Orai1 decreased endogenous SOCE as well as SOCE with TRPC1 alone. siOrai1 also significantly reduced SOCE and I(SOC) in cells expressing TRPC1+STIM1. Expression of R91WOrai1 or E106QOrai1 induced similar attenuation of TRPC1+STIM1-dependent SOCE and I(SOC), whereas expression of Orai1 with TRPC1+STIM1 resulted in SOCE that was larger than that with Orai1+STIM1 or TRPC1+STIM1 but not additive. Additionally, Orai1, E106QOrai1, and R91WOrai1 co-immunoprecipitated with similar levels of TRPC1 and STIM1 from HEK293 cells, and endogenous TRPC1, STIM1, and Orai1 were co-immunoprecipitated from salivary glands. Together, these data demonstrate a functional requirement for Orai1 in TRPC1+STIM1-dependent SOCE.


Fatal bilateral chylothorax in mice lacking the integrin alpha9beta1.
Members of the integrin family of adhesion receptors mediate both cell-cell and cell-matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha9beta1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha9beta1, we have generated mice lacking expression of the alpha9 subunit. Mice homozygous for a null mutation in the alpha9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha9(-/-) mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha9 deficiency could be one cause of congenital chylothorax.


Architectural proteins CTCF and cohesin have distinct roles in modulating the higher order structure and expression of the CFTR locus.
Higher order chromatin structures across the genome are maintained in part by the architectural proteins CCCTC binding factor (CTCF) and the cohesin complex, which co-localize at many sites across the genome. Here, we examine the role of these proteins in mediating chromatin structure at the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR encompasses nearly 200 kb flanked by CTCF-binding enhancer-blocking insulator elements and is regulated by cell-type-specific intronic enhancers, which loop to the promoter in the active locus. SiRNA-mediated depletion of CTCF or the cohesin component, RAD21, showed that these two factors have distinct roles in regulating the higher order organization of CFTR. CTCF mediates the interactions between CTCF/cohesin binding sites, some of which have enhancer-blocking insulator activity. Cohesin shares this tethering role, but in addition stabilizes interactions between the promoter and cis-acting intronic elements including enhancers, which are also dependent on the forkhead box A1/A2 (FOXA1/A2) transcription factors (TFs). Disruption of the three-dimensional structure of the CFTR gene by depletion of CTCF or RAD21 increases gene expression, which is accompanied by alterations in histone modifications and TF occupancy across the locus, and causes internalization of the gene from the nuclear periphery.


Seeking order amidst chaos: a systematic review of classification systems for causes of stillbirth and neonatal death, 2009-2014.
Each year, about 5.3 million babies die in the perinatal period. Understanding of causes of death is critical for prevention, yet there is no globally acceptable classification system. Instead, many disparate systems have been developed and used. We aimed to identify all systems used or created between 2009 and 2014, with their key features, including extent of alignment with the International Classification of Diseases (ICD) and variation in features by region, to inform the World Health Organization's development of a new global approach to classifying perinatal deaths. A systematic literature review (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and unpublished studies and national reports describing new classification systems or modifications of existing systems for causes of perinatal death, or that used or tested such systems, between 2009 and 2014. Studies reporting ICD use only were excluded. Data were independently double-extracted (except from non-English publications). Subgroup analyses explored variation by extent and region. Eighty-one systems were identified as new, modifications of existing systems, or having been used between 2009 and 2014, with an average of ten systems created/modified each year. Systems had widely varying characteristics: (i) comprehensiveness (40 systems classified both stillbirths and neonatal deaths); (ii) extent of use (systems were created in 28 countries and used in 40; 17 were created for national use; 27 were widely used); (iii) accessibility (three systems available in e-format); (iv) underlying cause of death (64 systems required a single cause of death); (v) reliability (10 systems tested for reliability, with overall Kappa scores ranging from .35-.93); and (vi) ICD alignment (17 systems used ICD codes). Regional databases were not searched, so system numbers may be underestimated. Some non-differential misclassification of systems was possible. The plethora of systems in use, and continuing system development, hamper international efforts to improve understanding of causes of death. Recognition of the features of currently used systems, combined with a better understanding of the drivers of continued system creation, may help the development of a truly effective global system.


COP1 mediates the coordination of root and shoot growth by light through modulation of PIN1- and PIN2-dependent auxin transport in Arabidopsis.
When a plant germinates in the soil, elongation of stem-like organs is enhanced whereas leaf and root growth is inhibited. How these differential growth responses are orchestrated by light and integrated at the organismal level to shape the plant remains to be elucidated. Here, we show that light signals through the master photomorphogenesis repressor COP1 to coordinate root and shoot growth in Arabidopsis. In the shoot, COP1 regulates shoot-to-root auxin transport by controlling the transcription of the auxin efflux carrier gene PIN-FORMED1 (PIN1), thus appropriately tuning shoot-derived auxin levels in the root. This in turn directly influences root elongation and adapts auxin transport and cell proliferation in the root apical meristem by modulating PIN1 and PIN2 intracellular distribution in the root in a COP1-dependent fashion, thus permitting a rapid and precise tuning of root growth to the light environment. Our data identify auxin as a long-distance signal in developmental adaptation to light and illustrate how spatially separated control mechanisms can converge on the same signaling system to coordinate development at the whole plant level.


Depression and Abuse During Medical Internships in Peruvian Hospitals.
To estimate the prevalence of depression and abuse and identify the associated factors in medical interns in Peruvian hospitals. We conducted a multicentre, cross-sectional and analytical study during the months of March to May 2016. We included medical interns from 18 Peruvian hospitals, in Lima and provinces. We used a survey that included sociodemographic data and a scale to measure the perception of abuse (psychological, physical and sexual). In addition, we used the Spanish version of the PHQ-9 to evaluate depression. We used Poisson regression with robust variances to calculate prevalence ratios (PRs). A total of 402 medical interns participated in the study, the median age was 25 [IQR: 21-33], and 52.7% were male. Moreover, 25.4% of them suffered from depression. In the adjusted model, the variables associated with depression were age (PRa=1.15), the number of hours they sleep per day (PRa=1.23), being a woman (PRa=3.33), performing the internship in a province (PRa=0.25), studying at a public university (PRa=0.64), living with parents (PRa=0.65) or alone (PRa=0.33), and having perceived some type of abuse (PRa=1.07). A quarter of surveyed medical interns had depression. Early screening is necessary to identify perceived abuse and other triggering depression factors that may adversely affect work performance and overall mental health during medical internships.


Laparoscopic sentinel node navigation surgery for early gastric cancer.
Currently, the most accurate method for identifying lymph node metastasis is intraoperative diagnosis by sentinel node (SN) biopsy. Based on the SNNS study-a recent large-scale, nationwide, multicenter prospective study-the SN concept seems to be scientifically valid in patients with early gastric cancer. SN biopsy is a multistep technique consisted of six essential elements: indication, the selection of a tracer, a proper tracer injection method, the objective detection of SNs, a reliable biopsy technique, and the precise detection of nodal metastasis. For SN biopsy of gastric cancer, these elements have been validated as follows: the indication should be limited to clinical T1 less than 4 cm in diameter; combination mapping with radioactive colloid and blue dye is used as the standard; and endoscopic submucosal injection is the standard tracer injection. Detection of SNs and a reliable biopsy technique are enabled by adaptation of lymphatic basin dissection, a proper biopsy technique for gastric cancer. Lymphatic basin dissection is a selective lymphadenectomy procedure for dissecting basins en bloc, collecting lymph nodes and lymphatic vessels stained with dye. Lymphatic basin dissection is superior to the ordinary pick-up method, not only for minimizing the rate of missed SNs, but also in terms of oncological safety as it complements an intraoperative frozen section diagnosis by serving as a backup dissection. Moreover, indocyanine green (ICG) fluorescence mapping has been developed in recent years. ICG fluorescence mapping is superior because of its high sensitivity and signal stability. Moreover, it is feasible for both open and laparoscopic gastrectomy in treating early gastric cancer. SN biopsy has brought dramatic changes to laparoscopic surgery for early gastric cancer. With laparoscopic SN biopsy using ICG fluorescence navigation, laparoscopic surgery for early gastric cancer has changed from the uniform standard gastrectomy with D1+ into a tailor-made function-preserving surgical procedure, such as local resection with lymphatic basin dissection.


Three-Dimensional Branched TiO2 Architectures in Controllable Bloom for Advanced Lithium-Ion Batteries.
Three-dimensional branched TiO2 architectures (3D BTA) with controllable morphologies were synthesized via a facile template-free one-pot solvothermal route. The volume ratio of deionized water (DI water) and diethylene glycol in solvothermal process is key to the formation of 3D BTA assembled by nanowire-coated TiO2 dendrites, which combines the advantages of 3D hierarchical structure and 1D nanoscale building blocks. Benefiting from such unique structural features, the BTA in full bloom achieved significantly increased specific surface areas and shortened Li(+) ion/electrons diffusion pathway. The lithium-ion batteries based on BTA in full bloom exhibited remarkably enhanced reversible specific capacity and rate performance, attributing to the high contact area with the electrolyte and the short solid state diffusion pathway for Li(+) ion/electrons promoting lithium insertion and extraction.


The development of an ergonomics training program to identify, evaluate, and control musculoskeletal disorders among nursing assistants at a state-run veterans' home.
Nursing assistants (NAs) who work in nursing and personal care facilities are twice and five times more likely, respectively, to suffer a musculoskeletal disorder compared to service industries and other health care facilities, respectively. The purpose of this study was to develop an ergonomics training program for selected NAs at a state-run veterans' home to decrease musculoskeletal disorders by 1) developing questionnaires to assess musculoskeletal stress, 2) evaluating the work environment, 3) developing and using a training package, and 4) determining the application of the information from the training package by NAs on the floor. Results show two new risk factors not previously identified for nursing personnel in the peer-reviewed literature. Quizzes given to the nursing personnel before and after training indicated a significant improvement in understanding the principles of ergonomics and patient-handling techniques. Statistical analysis comparing the pre-training and post-training questionnaires indicated no significant decrease in musculoskeletal risk factors and no significant reduction in pain or discomfort or overall mental or physical health.


Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability.
Cyclodextrin complex of nintedanib was prepared aiming for increased bio-activity and improved transport across intestinal membrane with reduced p-glycoprotein (p-gp) efflux. Based on preliminary phase solubility studies and molecular modeling, sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD, Captisol®) was selected to prepare inclusion complex. Complexation was confirmed using FTIR, 1H NMR, DSC, and XRD. Bioactivity of the formed complex was tested using lung fibroblast cells, WI-38 for anti-proliferative activity and effect on collagen deposition and cells migration. In-vitro permeability studies were performed using epiIntestinal tissue model to assess the effect of complexation on transport and p-gp efflux. Results of the study demonstrated that cyclodextrin complexation increased stability of nintedanib in PBS (pH 7.4) and simulated intestinal fluid (SIF). Further, bioactivity of nintedanib also improved. Interestingly, complexation has increased transport of nintedanib across intestinal membrane and reduced efflux ratio, suggesting the role of cyclodextrin complexation in modulating p-gp efflux.


Open source software for quantification of cell migration, protrusions, and fluorescence intensities.
Cell migration is frequently accompanied by changes in cell morphology (morphodynamics) on a range of spatial and temporal scales. Despite recent advances in imaging techniques, the application of unbiased computational image analysis methods for morphodynamic quantification is rare. For example, manual analysis using kymographs is still commonplace, often caused by lack of access to user-friendly, automated tools. We now describe software designed for the automated quantification of cell migration and morphodynamics. Implemented as a plug-in for the open-source platform, ImageJ, ADAPT is capable of rapid, automated analysis of migration and membrane protrusions, together with associated fluorescently labeled proteins, across multiple cells. We demonstrate the ability of the software by quantifying variations in cell population migration rates on different extracellular matrices. We also show that ADAPT can detect and morphologically profile filopodia. Finally, we have used ADAPT to compile an unbiased description of a "typical" bleb formed at the plasma membrane and quantify the effect of Arp2/3 complex inhibition on bleb retraction.


Analysis of a unique Clostridium botulinum strain from the Southern hemisphere producing a novel type E botulinum neurotoxin subtype.
Clostridium botulinum strains that produce botulinum neurotoxin type E (BoNT/E) are most commonly isolated from botulism cases, marine environments, and animals in regions of high latitude in the Northern hemisphere. A strain of C. botulinum type E (CDC66177) was isolated from soil in Chubut, Argentina. Previous studies showed that the amino acid sequences of BoNT/E produced by various strains differ by < 6% and that the type E neurotoxin gene cluster inserts into the rarA operon. Genetic and mass spectral analysis demonstrated that the BoNT/E produced by CDC66177 is a novel toxin subtype (E9). Toxin gene sequencing indicated that BoNT/E9 differed by nearly 11% at the amino acid level compared to BoNT/E1. Mass spectrometric analysis of BoNT/E9 revealed that its endopeptidase substrate cleavage site was identical to other BoNT/E subtypes. Further analysis of this strain demonstrated that its 16S rRNA sequence clustered with other Group II C. botulinum (producing BoNT types B, E, and F) strains. Genomic DNA isolated from strain CDC66177 hybridized with fewer probes using a Group II C. botulinum subtyping microarray compared to other type E strains examined. Whole genome shotgun sequencing of strain CDC66177 revealed that while the toxin gene cluster inserted into the rarA operon similar to other type E strains, its overall genome content shared greater similarity with a Group II C. botulinum type B strain (17B). These results expand our understanding of the global distribution of C. botulinum type E strains and suggest that the type E toxin gene cluster may be able to insert into C. botulinum strains with a more diverse genetic background than previously recognized.


Patterns of tobacco use in the United Arab Emirates Healthy Future (UAEHFS) pilot study.
Self-reported tobacco use in the United Arab Emirates is among the highest in the region. Use of tobacco products other than cigarettes is widespread, but little is known about specific behavior use patterns. There have been no studies that have biochemically verified smoking status. The UAE Healthy Future Study (UAEHFS) seeks to understand the causes of non-communicable diseases through a 20,000-person cohort study. During the study pilot, 517 Emirati nationals were recruited to complete a questionnaire, provide clinical measurements and biological samples. Complete smoking data were available for 428 participants. Validation of smoking status via cotinine testing was conducted based on complete questionnaire data and matching urine samples for 399 participants, using a cut-off of 200ng/ml to indicate active smoking status. Self-reported tobacco use was 36% among men and 3% among women in the sample. However, biochemical verification of smoking status revealed that 42% men and 9% of women were positive for cotinine indicating possible recent tobacco use. Dual and poly-use of tobacco products was fairly common with 32% and 6% of the sample reporting respectively. This is the first study in the region to biochemically verify tobacco use self-report data. Tobacco use in this study population was found to be higher than previously thought, especially among women. Misclassification of smoking status was more common than expected. Poly-tobacco use was also very common. Additional studies are needed to understand tobacco use behaviors and the extent to which people may be exposed to passive tobacco smoke. This study is the first in the region to biochemically verify self-reported smoking status.


Fertilization and ooplasmic movements in the ascidian egg.
Using light microscopy techniques, we have studied the movements that follow fertilization in the denuded egg of the ascidian Phallusia mammillata. In particular, our observations show that, as a result of a series of movements described below, the mitochondria-rich subcortical myoplasm is split in two parts during the second phase of ooplasmic segregation. This offers a potential explanation for the origin of larval muscle cells from both posterior and anterior blastomeres. The first visible event at fertilization is a bulging at the animal pole of the egg, which is immediately followed by a wave of contraction, travelling towards the vegetal pole with a surface velocity of 1.4 microns s-1. This wave accompanies the first phase of ooplasmic segregation of the mitochondria-rich subcortical myoplasm. After this contraction wave has reached the vegetal pole after about 2 min, a transient cytoplasmic lobe remains there until 6 min after fertilization. Several new features of the morphogenetic movements were then observed: between the extrusion of the first and second polar body (at 5 and 24-29 min, respectively), a series of transient animal protrusions form at regular intervals. Each animal protrusion involves a flow of the centrally located cytoplasm in the animal direction. Shortly before the second polar body is extruded, a second transient vegetal lobe ('the vegetal button') forms, which, like the first, resembles a protostome polar lobe. Immediately after the second polar body is extruded, three events occur almost simultaneously: first, the sperm aster moves from the vegetal hemisphere to the equator. Second, the bulk of the vegetally located myoplasm moves with the sperm aster towards the future posterior pole, but interestingly about 20% remains behind at the anterior side of the embryo. This second phase of myoplasmic movement shows two distinct subphases: a first, oscillatory subphase with an average velocity of about 6 microns min-1, and a second steady subphase with a velocity of about 26 microns min-1. The myoplasm reaches its final position as the male pronucleus with its surrounding aster moves towards the centre of the egg. Third, the female pronucleus moves towards the centre of the egg to meet with the male pronucleus. Like the myoplasm, the migrations of both the sperm aster and the female pronucleus shows two subphases with distinctly different velocities. Finally, the pronuclear membranes dissolve, a small mitotic spindle is formed with very large asters, and at about 60-65 min after fertilization, the egg cleaves.


In vitro study and biocompatibility of calcined mesoporous silica microparticles in mouse lung.
We report on the pneumatocyte structure and function of mouse lung specimens exposed in vitro to two calcined mesoporous silica particles, MCM41-cal (spheres, ∼300 to 1000 nm in diameter) and SBA15-cal (irregular rods averaging ∼500 nm in diameter and ∼1000 nm in length). These mesoporous silica particles are in consideration for potential medical application as delivery vehicles for genes, drugs, and bio-imagers. In the study, lung specimens (about 10 mg each) were excised from male Balb/c mice, immediately immersed in Krebs-Henseleit buffer, ice-cold, and continuously gassed with O(2):CO(2) (95:5). The samples were incubated at 37°C in the same buffer with and without 200 μg/mL MCM41-cal or SBA15-cal for 5-14 h. The tissues were then rinsed thoroughly and processed for light and electron microscopy. Normal alveolar morphology was evident in all the studied specimens. There was no significant difference in the number of apoptotic cells between the treated and untreated samples. Despite their relatively large sizes, the particles were abundantly present in pneumocytes, macrophages, endothelial cells, fibroblasts, and interstitium. They were seen in different areas of the cytoplasm, suggesting intracellular movements. Their presence did not appear to disturb cellular configuration or micro-organelles. Due to their rigidity and surface charges, some were firmly attached to (indenting) the nuclear membrane. The rate of respiration (cellular mitochondrial O(2) consumption, in μM O(2)/min/mg) in specimens exposed to 200 μg/mL particles for up to 12 h was the same as untreated specimens. These findings confirm "reasonable" bioavailability and biocompatibility of calcined mesoporous silicas with mouse lung within at least 5-14 h of exposure time.


Third-generation percutaneous vertebral augmentation systems.
Currently, there is no general consensus about the management of osteoporotic vertebral fractures (OVF). In the past, conservative treatment for at least one month was deemed appropriate for the majority of vertebral fractures. When pain persisted after conservative treatment, it was necessary to consider surgical interventions including: vertebroplasty for vertebral fractures with less than 30% loss of height of the affected vertebral body and kyphoplasty for vertebral fractures with greater than 30% loss of height. Currently, this type of treatment is not feasible. Herein we review the characteristics and methods of operation of three of the most common percutaneous vertebral augmentation systems (PVAS) for the treatment of OVF: Vertebral Body Stenting(®) (VBS), OsseoFix(®) and Spine Jack(®). VBS is a titanium device accompanied by a hydraulic (as opposed to mechanical) working system which allows a partial and not immediate possibility to control the opening of the device. On the other hand, OsseoFix(®) and Spine Jack(®) are accompanied by a mechanical working system which allows a progressive and controlled reduction of the vertebral fracture. Another important aspect to consider is the vertebral body height recovery. OsseoFix(®) has an indirect mechanism of action: the compaction of the trabecular bone causes an increase in the vertebral body height. Unlike the Vertebral Body Stenting(®) and Spine Jack(®), the OsseoFix(®) has no direct lift mechanism. Therefore, for these characteristics and for the force that this device is able to provide. In our opinion, Spine Jack(®) is the only device also suitable for the treatment OVF, traumatic fracture (recent, old or inveterate) and primary or secondary bone tumors.


Sexual orientation-related oral health disparities in the United States.
Recent reports have documented health disparities according to sexual orientation and used the minority stress model as a framework for understanding their origins. To date, however, sexual orientation-related disparities in the oral health domain have not been evaluated. Accordingly, this study sought to investigate potential health disparities in objectively-assessed and subjective reports of oral heath among lesbian, gay, and bisexual adults relative to the heterosexual community-dwelling US population. We used three consecutive cycles (2009-2014) of National Health and Nutrition Examination Survey (NHANES) data for men and women aged 18-59 years. We examined clinical measures of dental caries, tooth loss, chronic periodontitis, and oral human papillomavirus (HPV) as well as subjective reports of oral health status and use of dental services. Clinical measures of oral disease did not differ according to sexual orientation; however, bisexual adults were more likely to rate their oral health unfavorably (41%) than heterosexual adults (27%). Gay men reported "bone loss around teeth" more frequently (35%) than heterosexual (11%) and bisexual (10%) men. Bisexual individuals were more likely to confront barriers to accessing dental care (30%) versus heterosexual adults (19%). While clinical measures of oral health did not substantially differ between sexual orientation strata, subjective measures of oral health were worse among gay, lesbian, and bisexual adults versus heterosexual adults. Further study of the psychosocial construction of oral health among sexual minorities is warranted.


Clique-Based Neural Associative Memories with Local Coding and Precoding.
Techniques from coding theory are able to improve the efficiency of neuroinspired and neural associative memories by forcing some construction and constraints on the network. In this letter, the approach is to embed coding techniques into neural associative memory in order to increase their performance in the presence of partial erasures. The motivation comes from recent work by Gripon, Berrou, and coauthors, which revisited Willshaw networks and presented a neural network with interacting neurons that partitioned into clusters. The model introduced stores patterns as small-size cliques that can be retrieved in spite of partial error. We focus on improving the success of retrieval by applying two techniques: doing a local coding in each cluster and then applying a precoding step. We use a slightly different decoding scheme, which is appropriate for partial erasures and converges faster. Although the ideas of local coding and precoding are not new, the way we apply them is different. Simulations show an increase in the pattern retrieval capacity for both techniques. Moreover, we use self-dual additive codes over field [Formula: see text], which have very interesting properties and a simple-graph representation.


Approximate confidence and prediction intervals for least squares support vector regression.
Bias-corrected approximate 100(1-α)% pointwise and simultaneous confidence and prediction intervals for least squares support vector machines are proposed. A simple way of determining the bias without estimating higher order derivatives is formulated. A variance estimator is developed that works well in the homoscedastic and heteroscedastic case. In order to produce simultaneous confidence intervals, a simple Šidák correction and a more involved correction (based on upcrossing theory) are used. The obtained confidence intervals are compared to a state-of-the-art bootstrap-based method. Simulations show that the proposed method obtains similar intervals compared to the bootstrap at a lower computational cost.


Automatized, Standardized, and Patient-Tailored Progressive Walking-Adaptability Training: A Proof-of-Concept Study.
Treadmill training augmented with visual images projected on the belt's surface can help improve walking adaptability. Moreover, patient-tailored automatization and standardization can increase the feasibility of walking-adaptability therapy. We developed C-Gait, a treadmill protocol consisting of a baseline walking-adaptability assessment involving 7 putatively distinct walking-adaptability tasks and a decision algorithm, to automatically update training content and execution parameters to a patients' performance and perceived challenge. The main objective was to examine the feasibility, acceptability, and clinical potential of C-Gait training. The secondary objective was to evaluate the validity of the baseline assessment. This was a longitudinal proof-of-concept study with pretraining, posttraining, and retention tests encompassing baseline assessment and walking-related clinical measures. Twenty-four healthy adults, 12 healthy older persons, and 28 patients with gait and/or balance deficits performed the baseline assessment; the gait deficit group received 10 C-Gait training sessions over a 5-week period. Baseline assessment scores and walking-related clinical measures served as outcome measures. C-Gait training exhibited significant progression in training content and execution, with considerable between-patient variation and minimal overruling by therapists. C-Gait training was well accepted and led to improvements in walking adaptability and general walking ability, which persisted after training cessation. Baseline assessment scores differed over groups and difficulty levels, had no-to-moderate correlations with walking-related clinical measures, and had limited correlations among walking-adaptability tasks. C-Gait was evaluated in a small yet diverse cohort. More encompassing studies are required to further establish its apparent merits. The validity of treadmill-based walking-adaptability assessment against an overground standard remains to be established. C-Gait offers automatized, standardized, and patient-tailored walking-adaptability training that is feasible and well accepted, with good potential for improving task-specific and generic measures of walking.


Mesenchymal cell transfer for articular cartilage repair.
Mature articular cartilage has a poor reparative response to injury and its irreparable breakdown is the common feature of degenerative joint diseases. If articular cartilage lesions become symptomatic, the orthopaedic surgeon must decide on a treatment option. The treatment options include conversion of chondral lesions to osteochondral lesions, which facilitates migration of cells from the marrow space to effect repair. In recent years, a greater emphasis has been placed on tissue engineering strategies and thus several new treatment options have been introduced, including the use of cell transplantation. Several tissue sources and cell types can potentially be used for this type of therapy. These include autologous or allograft chondrocytes and mesenchymal progenitor cells from various tissues. These cells may be delivered to articular cartilage lesions by a variety of methods including direct cell injection to the lesion or seeding in a biodegradable scaffold prior to implantation. In this review, the potential of cell transplantation for articular cartilage repair and regeneration will be discussed. The authors will focus on the available technologies and the present limitations of cell-based therapies.


Can support from the father of the baby buffer the adverse effects of depressive symptoms on risk of preterm birth in Black families?
While maternal depressive symptoms during pregnancy have been linked to preterm birth (PTB; birth before 37 completed weeks of gestation), little has been reported on potential buffering factors, particularly specific to Black women who are at much higher risk. We examined the association between depressive symptoms and PTB in pregnant Black women, with father of the baby (FOB) support as a potential buffering factor. Data were obtained from the life-course influences on fetal environments study (2009-2011), a cohort of 1,410 Black women in metropolitan Detroit, Michigan (71% response rate) using maternal interviews and medical record abstraction collected during the postpartum hospitalization. The 20-item Center for Epidemiologic Studies Depression (CES-D) scale was used to measure depressive symptoms. The 14-item social networks in adult relations questionnaire was used to assess the mother's relationship with the FOB. Logistic regression was used to explore the interaction between CES-D and FOB support with regard to PTB risk. We adjusted for maternal advanced age, income, education level, smoking status, hypertension, prenatal care and BMI. The PTB rate in this cohort was 17.7%. Among women with FOB scale < 60 (less support), the odd ratio (OR) of PTB for women with CES-D scores ≥ 23 (severe depressive symptoms) as compared to CES-D scores < 23 (no severe depressive symptoms) was 2.57 [95% confidence interval (CI): 1.68, 3.94; p < 0.001]. Among women with FOB scores ≥ 60 (more support), the odds of PTB in women with CES-D scores ≥ 23 did not significantly differ from the odds of PTB in women with CES-D scores < 23 (OR = 1.34; 95% CI: 0.74, 2.44; p = 0.3). After adjustment for covariates, among women with FOB scores < 60, the OR of PTB for women with CES-D scores ≥ 23 compared to < 23 was 2.79 (95% CI: 1.75, 4.45; p < 0.001). Among women with FOB scores ≥ 60, the odds of PTB in women with CES-D scores ≥ 23 was not statistically significantly different compared to the odds of PTB in women with CES-D scores < 23 (OR = 1.21; 95% CI: 0.62, 2.35; p = 0.6). The interaction term was statistically significant (p = 0.04). The adverse effect of depressive symptoms on risk of PTB may be buffered by factors such as a supportive relationship with the FOB.


Separation of adenosine triphosphatase of HK and LK sheep red cell membranes by density gradient centrifugation.
Membrane fragments from high potassium (HK) and low potassium (LK) sheep red cells were separated by density gradient centrifugation. Three preparations were studied: (1) HK membranes sonicated for 20 minutes, (2) HK membranes sonicated for 3 minutes, and (3) LK membranes sonicated for 3 minutes. The adenosine triphosphatase (ATPase) activity in the maximally disrupted preparation (1) was not sensitive to Na + K and was recovered in relatively small but heavy (specific gravity 1.19) fragments which made up no more than 8 per cent of the total membrane. Both Na + K-sensitive (S) and Na + K-insensitive (I) ATPase activity were found in the more gently broken up preparations (2) and (3) but the ratio of S- to I-ATPase was much greater in HK than in LK membrane fragments. S-ATPase activity in preparation (2) was about 50 per cent that observed in HK membranes prior to sonication. S-ATPase activity was recovered from the density gradient in relatively large but light (specific gravity 1.10) fragments. As was the case with the maximally disrupted preparation (1), I-ATPase activity in both preparations (2) and (3) was recovered in small but heavy (specific gravity > 1.20) fragments. The possibility that sensitivity of sheep red cell membrane ATPase to Na + K depends on the association between units containing the enzyme(s) and large, light, phospholipid-containing components is discussed.