Do low-income Cypriots experience food stress? The cost of a healthy food basket relative to guaranteed minimum income in Nicosia, Cyprus.
The aim of the present study was to assess the cost, acceptability and affordability of the healthy food basket (HFB) among low-income families in Cyprus. HFBs were constructed based on the National Guidelines for Nutrition and Exercise for six different types of households. Acceptability was tested through focus groups. Affordability was defined as the cost of the HFB as a percentage of the guaranteed minimum income (GMI). The value of the GMI is set to be equal to €480 for a single individual and increases with the size of the recipient unit in accordance with the Organization for Economic Co-operation and Development equivalence scales. The Ministry of Labour estimates that, on average, nearly 50% of the GMI is required for food. The total monthly budget for HFB is 0.80, 1.11, 1.27, 1.28, 1.44 and 1.48 times higher than the GMI budget for food among different types of households in Cyprus (a single woman, a single man, a couple, a single woman with two children, a single man with two children and a couple with two children, respectively). In particular, a family with two children on GMI would need to spend a large proportion of their income on the HFB (71.68%). The GMI scheme appears not to consider the cost of healthy food, and thus, families on welfare payments in Cyprus are at a high risk of experiencing food stress. Therefore, additional research is required to measure the cost of the six HFBs in various settings.


Anticonvulsant Classes and Possible Mechanism of Actions.
Epilepsy is considered one of the most common neurological disorders worldwide; it needs long-term or life-long treatment. Despite the presence of several novel antiepileptic drugs, approximately 30% patients still suffer from drug-resistant epilepsy. Subsequently, searching for new anticonvulsants with lower toxicity and better efficacy is still in paramount demand. Using target-based studies in the discovery of novel antiepileptics is uncommon owing to the insufficient information on the molecular pathway of epilepsy and complex mode of action for most of known antiepileptic drugs. In this review, we investigated the properties of anticonvulsants, types of epileptic seizures, and mechanism of action for anticonvulsants.


Development of regionalized SPFs for two-lane rural roads in Pennsylvania.
The American Association of State Highway and Transportation Officials' Highway Safety Manual (HSM) contains safety performance functions (SPFs) to predict annual crash frequencies for several roadway types. When applying these SPFs in a jurisdiction whose data were not used to develop the SPF, a calibration factor can be applied to adjust the expected crash frequency estimate to statewide or local conditions. Alternatively, the HSM suggests that transportation agencies may develop their own SPFs in lieu of applying the calibration factor to the HSM SPFs. However, the HSM does not provide guidance on the appropriate level of regionalization that should be adopted for either method, even though safety performance may vary considerably within a state. In light of this, the present study considers the development of local or regionalized SPFs for two-lane rural highways within the Commonwealth of Pennsylvania. Three regionalization levels were considered: statewide, engineering district and individual counties. The expected crash frequency for each level of regionalization was compared to the reported crash frequency over an eight-year analysis period. The results indicate that district-level SPFs with county-level adjustment factors provide better predictive accuracy than the development of a statewide SPF or application of the HSM-calibrated SPF. The findings suggest that there are significant differences in safety performance across engineering districts within Pennsylvania. As such, other state transportation agencies developing SPFs or using calibration factors may also consider how variations across jurisdictions will affect predicted crash frequencies.


Evaluation of a Diabetes Self-Management Program: Claims Analysis on Comorbid Illnesses, Health Care Utilization, and Cost.
An estimated 30.3 million Americans have diabetes mellitus. The US Department of Health and Human Services created national objectives via its Healthy People 2020 initiative to improve the quality of life for people who either have or are at risk for diabetes mellitus, and hence, lower the personal and national economic burden of this debilitating chronic disease. Diabetes self-management education interventions are a primary focus of this initiative. The aim of this study was to evaluate the impact of the Better Choices Better Health Diabetes (BCBH-D) self-management program on comorbid illness related to diabetes mellitus, health care utilization, and cost. A propensity score matched two-group, pre-post design was used for this study. Retrospective administrative medical and pharmacy claims data from the HealthCore Integrated Research Environment were used for outcome variables. The intervention cohort included diabetes mellitus patients who were recruited to a diabetes self-management program. Control cohort subjects were identified from the HealthCore Integrated Research Environment by at least two diabetes-associated claims (International Classification of Diseases-Ninth Revision, ICD-9 250.xx) within 2 years before the program launch date (October 1, 2011-September 30, 2013) but did not participate in BCBH-D. Controls were matched to cases in a 3:1 propensity score match. Outcome measures included pre- and postintervention all-cause and diabetes-related utilization and costs. Cost outcomes are reported as least squares means. Repeated measures analyses (generalized estimating equation approach) were conducted for utilization, comorbid conditions, and costs. The program participants who were identified in HealthCore Integrated Research Environment claims (N=558) were matched to a control cohort of 1669 patients. Following the intervention, the self-management cohort experienced significant reductions for diabetes mellitus-associated comorbid conditions, with the postintervention disease burden being significantly lower (mean 1.6 [SD 1.6]) compared with the control cohort (mean 2.1 [SD 1.7]; P=.001). Postintervention all-cause utilization was decreased in the intervention cohort compared with controls with -40/1000 emergency department visits vs +70/1000; P=.004 and -5780 outpatient visits per 1000 vs -290/1000; P=.001. Unadjusted total all-cause medical cost was decreased by US $2207 in the intervention cohort compared with a US $338 decrease in the controls; P=.001. After adjustment for other variables through structural equation analysis, the direct effect of the BCBH-D was -US $815 (P=.049). Patients in the BCBH-D program experienced reduced all-cause health care utilization and costs. Direct cost savings were US $815. Although encouraging, given the complexity of the patient population, further study is needed to cross-validate the results.


Stable internal reference genes for normalization of real-time RT-PCR in tobacco (Nicotiana tabacum) during development and abiotic stress.
Real-time RT-PCR is a powerful technique for the measurement of gene expression, but its accuracy depends on the stability of the internal reference gene(s) used for data normalization. Tobacco (Nicotiana tabacum) is an important model in studies of plant gene expression, but stable reference genes have not been well-studied in the tobacco system. We address this problem by analysing the expression stability of eight potential tobacco reference genes. Primers targeting each gene (18S rRNA, EF-1alpha, Ntubc2, alpha- and beta-tubulin, PP2A, L25 and actin) were developed and optimized. The expression of each gene was then measured by real-time PCR in a diverse set of 22 tobacco cDNA samples derived from developmentally distinct tissues and from plants exposed to several abiotic stresses. L25 and EF-1alpha demonstrated the highest expression stability, followed by Ntubc2. Measurement of L25 and EF-1alpha was sufficient for accurate normalization in either the developmental or stress-treated samples, but Ntubc2 was also required when considering the entire sample set. Analysis of a tobacco circadian gene (NTCP-23) verified these reference genes in an additional context, and all techniques were optimized to enable a high-throughput approach. These results provide a foundation for the more accurate and widespread use of real-time RT-PCR in tobacco.


Spatial and temporal contrasts in the distribution of crops and pastures across Amazonia: A new agricultural land use data set from census data since 1950.
Amazonia holds the largest continuous area of tropical forests with intense land use change dynamics inducing water, carbon, and energy feedbacks with regional and global impacts. Much of our knowledge of land use change in Amazonia comes from studies of the Brazilian Amazon, which accounts for two thirds of the region. Amazonia outside of Brazil has received less attention because of the difficulty of acquiring consistent data across countries. We present here an agricultural statistics database of the entire Amazonia region, with a harmonized description of crops and pastures in geospatial format, based on administrative boundary data at the municipality level. The spatial coverage includes countries within Amazonia and spans censuses and surveys from 1950 to 2012. Harmonized crop and pasture types are explored by grouping annual and perennial cropping systems, C3 and C4 photosynthetic pathways, planted and natural pastures, and main crops. Our analysis examined the spatial pattern of ratios between classes of the groups and their correlation with the agricultural extent of crops and pastures within administrative units of the Amazon, by country, and census/survey dates. Significant correlations were found between all ratios and the fraction of agricultural lands of each administrative unit, with the exception of planted to natural pastures ratio and pasture lands extent. Brazil and Peru in most cases have significant correlations for all ratios analyzed even for specific census and survey dates. Results suggested improvements, and potential applications of the database for carbon, water, climate, and land use change studies are discussed. The database presented here provides an Amazon-wide improved data set on agricultural dynamics with expanded temporal and spatial coverage. Agricultural census database covers Amazon basin municipalities from 1950 to 2012Harmonized database groups crops and pastures by cropping system, C3/C4, and main cropsWe explored correlations between groups and the extent of agricultural lands.


Agonist-specific behaviour of the intracellular Ca2+ response in rat hepatocytes.
A variety of agonists stimulate in hepatocytes a response that takes the shape of repetitive cytosolic free Ca2+ transients called Ca2+ oscillations. The shape of spikes and the pattern of oscillations in a given cell differ depending on the agonist of the phosphoinositide pathway that is applied. In this study, the response of individual rat hepatocytes to maximal stimulation by arginine vasopressin (AVP), phenylephrine and ADP was investigated by fluorescence microscopy and flash photolysis. Hepatocytes loaded with Ca2+-sensitive probes were stimulated with a first agonist to evoke a maximal response, and then a second agonist was added. When phenylephrine or ADP was used as the first agonist, AVP applied subsequently could elicit an additional response, which did not happen when AVP was first applied and phenylephrine or ADP was applied later. Cells microinjected with caged myo-inositol 1,4,5-trisphosphate (IP3) were challenged with the different agonists and, when a maximal response was obtained, photorelease of IP3 was triggered. Cells maximally stimulated with AVP did not respond to IP3 photorelease, whereas those stimulated with phenylephrine or ADP responded with a fast Ca2+ spike above the elevated steady-state level, which was followed by an undershoot. In contrast, with all three agonists, IP3 photorelease triggered at the top of an oscillatory Ca2+ transient was able to mobilize additional Ca2+. These experiments indicate that the differential response of cells to agonists is found not only during Ca2+ oscillations but also during maximal agonist stimulation and that potency and efficacy differences exist among agonists.


Fast and reliable estimation of multiple parametric images using an integrated method for dynamic SPECT.
Dynamic single photon emission computed tomography (SPECT) has demonstrated the potential to quantitatively estimate physiological parameters in the brain and the heart. The generalized linear least square (GLLS) method is a well-established method for solving linear compartment models with fast computational speed. However, the high level of noise intrinsic in the SPECT data leads to reliability and instability problems of GLLS for generating parametric images. An integrated method is proposed to restrict the noise in both the temporal and spatial domains to estimate multiple parametric images for dynamic SPECT. This method comprises three steps which are optimum image sampling schedule in the projection space, cluster analysis applied postreconstruction and parametric image generation with GLLS. The simulation and experimental studies for the neuronal nicotine acetylcholine receptor tracer of 5-[123I]-iodo-A-85380 were employed to evaluate the performance of the proposed method. The results of influx rate of K1 and volume of distribution of Vd demonstrated that the integrated method was successful in generating low noise parametric images for high noise SPECT data without enhancing the partial volume effect. Furthermore, the integrated method is computationally efficient for potential clinical applications.


Quantum chemistry of the oxygen evolution reaction on cobalt(ii,iii) oxide - implications for designing the optimal catalyst.
Density functional theory is used to examine the changes in electronic structure that occur during the oxygen evolution reaction (OER) catalyzed by active sites on three different surface terminations of Co3O4. These three active sites have reactive oxo species with differing degrees of coordination by Co cations - a μ(3)-oxo on the (311) surface, a μ(2)-oxo on the (110)-A surface, and an η-oxo on the (110)-B surface. The kinetically relevant step on all surfaces over a wide range of applied potentials is the nucleophilic addition of water to the oxo, which is responsible for formation of the O-O bond. The intrinsic reactivity of a site for this step is found to increase as the coordination of the oxo decreases with the μ(3)-oxo on the (311) surface being the least reactive and the η-oxo on the (110)-B surface being the most reactive. A detailed analysis of the electronic changes occurring during water addition on the three sites reveals that this trend is due to both a decrease in the attractive local Madelung potential on the oxo and a decrease in electron withdrawal from the oxo by Co neighbors. Applying a similar electronic structure analysis to the oxidation steps preceding water addition in the catalytic cycle shows that analogous electronic changes occur during this process, explaining a correlation observed between the oxidation potential of a site and its intrinsic reactivity for water addition. This concept is then used to specify criteria for the design of an optimal OER catalyst at a given applied potential.


[The use of permanent magnets in the orthodontic clinic].
The author reviews published literature on the use of permanent magnets as an alternative to traditional methods of instrumental treatment in orthodontics. Use of magnetic technology in orthodontics should be further researched and improved.


A novel method for the evaluation of powered toothbrush oscillation characteristics.
To assess the vibration characteristics of oscillating objects with the scanning laser vibrometer (SLV). A laser is scanned over the surface of a vibrating target and the reflected, Doppler frequency shifted beam is used to determine the displacement amplitude and frequency of the vibration. This communication reports on a preliminary investigation to assess unloaded powered toothbrush oscillations, using Scanning Laser Vibrometry. Four powered toothbrushes were selected for this study including the Sonicare, Philips/Jordan Sensiflex HX2520, Braun 3D and Braun D8. Each toothbrush was clamped in position and 10 area scans of their heads were taken from the side orientation to determine the displacement amplitude and frequency of oscillation. The fundamental frequency of oscillation of each brush was determined: Sonicare: 262.5Hz; Philips: 62.5Hz; 3D: 75Hz and D8: 62.5Hz. The maximum displacement amplitude (half the peak-to-peak excursion) for each brush (at the tips of the longest bristles) was Sonicare; 2.51 +/- 0.32mm, Philips; 2.60 +/- 0.15mm, Braun 3D; 2.14 +/- 0.18mm and Braun D8; 2.14 +/- 0.21.


New developments in gastric bypass procedures and physiological mechanisms.
Since the gastric bypass was first described for weight-reduction surgery almost 50 years ago, a number of remarkable contributions have been made to the field. These advances have led to significant modifications of the technique, evolution of laparoscopic bariatric surgery equipment, and improvement of long-term results. Despite the currently wide-spread practice of laparoscopic bariatric surgery, the precise technique for laparoscopic gastric bypass still varies from institution to institution, and the surgery continues to carry a morbidity rate. Advances in laparoscopic equipment, technology, and our understanding of the pathophysiology behind weight loss, have allowed surgeons to modify the procedure described originally to minimize the morbidity and maximize long-term weight loss. This chapter describes the technique of laparoscopic gastric bypass used at a major academic center that performs over 1000 bariatric procedures each year. In addition, the many recent advances in methodology and pathophysiology are described in detail.


Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma.
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC). It has been shown that miR-375 inhibits P-gp expression via inhibition of astrocyte elevated gene-1 (AEG-1) expression in HCC, and induces apoptosis in HCC cells by targeting AEG-1 and YAP1. In this study, we prepared lipid-coated hollow mesoporous silica nanoparticles (LH) containing doxorubicin hydrochloride (DOX) and miR-375 (LHD/miR-375) to deliver the two agents into MDR HCC cells in vitro and in vivo. We found that LHD/miR-375 overcame drug efflux and delivered miR-375 and DOX into MDR HepG2/ADR cells or HCC tissues. MiR-375 delivered by LHD/miR-375 was taken up through phagocytosis and clathrin- and caveolae-mediated endocytosis. Following release from late endosomes, it repressed the expression of P-gp in HepG2/ADR cells. The synergistic effects of miR-375 and hollow mesoporous silica nanoparticles (HMSN) resulted in a profound increase in the uptake of DOX by the HCC cells and prevented HCC cell growth. Enhanced antitumor effects of LHD/miR-375 were also validated in HCC xenografts and primary tumors; however, no significant toxicity was observed. Mechanistic studies also revealed that miR-375 and DOX exerted a synergistic antitumor effect by promoting apoptosis. Our study illustrates that delivery of miR-375 using HMSN is a feasible approach to circumvent MDR in the management of HCC. It, therefore, merits further development for potential clinical application.


Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.
Dominant mutations of ATP1A3, a neuronal Na,K-ATPase α subunit isoform, cause neurological disorders with an exceptionally wide range of severity. Several new mutations and their phenotypes are reported here (p.Asp366His, p.Asp742Tyr, p.Asp743His, p.Leu924Pro, and a VUS, p.Arg463Cys). Mutations associated with mild or severe phenotypes [rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), or early infantile epileptic encephalopathy (EIEE)] were expressed in HEK-293 cells. Paradoxically, the severity of human symptoms did not correlate with whether there was enough residual activity to support cell survival. We hypothesized that distinct cellular consequences may result not only from pump inactivation but also from protein misfolding. Biosynthesis was investigated in four tetracycline-inducible isogenic cell lines representing different human phenotypes. Two cell biological complications were found. First, there was impaired trafficking of αβ complex to Golgi apparatus and plasma membrane, as well as changes in cell morphology, for two mutations that produced microcephaly or regions of brain atrophy in patients. Second, there was competition between exogenous mutant ATP1A3 (α3) and endogenous ATP1A1 (α1) so that their sum was constant. This predicts that in patients, the ratio of normal to mutant ATP1A3 proteins will vary when misfolding occurs. At the two extremes, the results suggest that a heterozygous mutation that only impairs Na,K-ATPase activity will produce relatively mild disease, while one that activates the unfolded protein response could produce severe disease and may result in death of neurons independently of ion pump inactivation.


Thermal decomposition pathways of hydroxylamine: theoretical investigation on the initial steps.
Hydroxylamine (NH(2)OH) is an unstable compound at room temperature, and it has been involved in two tragic industrial incidents. Although experimental studies have been carried out to study the thermal stability of hydroxylamine, the detailed decomposition mechanism is still in debate. In this work, several density functional and ab initio methods were used in conjunction with several basis sets to investigate the initial thermal decomposition steps of hydroxylamine, including both unimolecular and bimolecular reaction pathways. The theoretical investigation shows that simple bond dissociations and unimolecular reactions are unlikely to occur. The energetically favorable initial step of decomposition pathways was determined as a bimolecular isomerization of hydroxylamine into ammonia oxide with an activation barrier of approximately 25 kcal/mol at the MPW1K level of theory. Because hydroxylamine is available only in aqueous solutions, solvent effects on the initial decomposition pathways were also studied using water cluster methods and the polarizable continuum model (PCM). In water, the activation barrier of the bimolecular isomerization reaction decreases to approximately 16 kcal/mol. The results indicate that the bimolecular isomerization pathway of hydroxylamine is more favorable in aqueous solutions. However, the bimolecular nature of this reaction means that more dilute aqueous solution will be more stable.


Analysis of a Putative Late Domain Using an Ebola Virus Transcription and Replication-Competent Virus-Like Particle System.
The Ebola virus (EBOV) matrix protein VP40 drives budding of virions and encodes 2 overlapping late domain motifs at amino acid positions 7-13 (PTAPPEY). However, these motifs are not absolutely essential for replication in cell culture, and recently a potential third late domain motif (YPx(6)I) was proposed at amino acid positions 18-26 of VP40. To analyze the importance of this motif in viral budding, we used a transcription and replication-competent virus-like particle system. Using this system, we show that this motif does not contribute to EBOV budding or particle propagation.


Anti-colon cancer activity of Bifidobacterium metabolites on colon cancer cell line SW742.
Bacteria species, which are used as probiotics, are lactic acid bacteria. The majority of them are under the genera Bifidobacterium and Lactobacillus. The aim of the present study was to isolate and identify Bifidobacterium and to evaluate the effects of their 24 h and 120 h cell-free supernatants (CFS) from both cultures on colon cancer cell line. In the present study, 84 samples of dairy products, infant feces, and probiotic capsule were collected, and Bifidobacterium was isolated. Gram stain, biochemical tests, and molecular identification were done for the isolation and identification of Bifidobacterium. Cytotoxicity effects of CFS derived from both cultures of isolated Bifidobacterium were assessed on colon cancer cell lines. In the present study, 17 isolates of Bifidobacterium were identified. The results show that Bifidobacterium was most frequently associated with infant feces and dairy products, whereas the lowest rate was associated with local milk. After the effects of CFS on colon cancer cell line, two isolates were identified from infant feces and probiotic capsule; they had the highest ability in inhibiting the growth of cancer cells. Bifidobacterium bifidum was effective in combating cancer cells and was associated with a substantial improvement in gastrointestinal cancer. The study has shown that the regular ingested probiotics could prevent the development of colorectal cancer. During the present study, the produced CFS could inhibit the growth of colon cancer cells. In conclusion, probiotics have good potential to be introduced as a new approach to colon cancer treatment.


Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort.
Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown. To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon. In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound. Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison). Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.


Impacts of Operational Failures on Primary Care Physicians' Work: A Critical Interpretive Synthesis of the Literature.
Operational failures are system-level errors in the supply of information, equipment, and materials to health care personnel. We aimed to review and synthesize the research literature to determine how operational failures in primary care affect the work of primary care physicians. We conducted a critical interpretive synthesis. We searched 7 databases for papers published in English from database inception until October 2017 for primary research of any design that addressed problems interfering with primary care physicians' work. All potentially eligible titles/abstracts were screened by 1 reviewer; 30% were subject to second screening. We conducted an iterative critique, analysis, and synthesis of included studies. Our search retrieved 8,544 unique citations. Though no paper explicitly referred to "operational failures," we identified 95 papers that conformed to our general definition. The included studies show a gap between what physicians perceived they should be doing and what they were doing, which was strongly linked to operational failures-including those relating to technology, information, and coordination-over which physicians often had limited control. Operational failures actively configured physicians' work by requiring significant compensatory labor to deliver the goals of care. This labor was typically unaccounted for in scheduling or reward systems and had adverse consequences for physician and patient experience. Primary care physicians' efforts to compensate for suboptimal work systems are often concealed, risking an incomplete picture of the work they do and problems they routinely face. Future research must identify which operational failures are highest impact and tractable to improvement.


Non-invasive anaesthetic methods for dermatological laser procedures: a systematic review.
Pain is a common side-effect of dermatological laser procedures. Non-invasive anaesthetic drugs and anaesthetic procedures can be used to provide pain relief and increase patient satisfaction and treatment efficacy. However, it remains unclear which method provides the best pain relief. The objective of this systematic review was therefore to assess the efficacy and safety of non-invasive anaesthetic methods during dermatological laser procedures. A systematic literature search was conducted. Randomized and non-randomized controlled clinical trials (RCTs and CCTs) were included. Two authors independently assessed study eligibility, extracted data and assessed the risk of bias. The quality of evidence was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Twenty RCTs and 12 CCTs were included, involving nine different laser indications: hair removal (n = 9), resurfacing/rejuvenation (n = 5), port wine stains (n = 8), leg telangiectasia (n = 3), facial telangiectasia (n = 2), tattoo removal (n = 2), naevus of Ota (n = 1), solar lentigines (n = 1) and HPV lesions (n = 1). The non-invasive anaesthetic methods (i.e. topical anaesthetic drugs, skin cooling, and pneumatic skin flattening [PSF]), types of lasers, laser settings, application time, and types of pain scales varied widely among the included studies. All of the studies had an unclear or high risk of bias, and the overall quality of evidence was rated as low. In general, active non-invasive anaesthetic methods seemed to provide favourable results compared to placebo or no anaesthesia, and topical anaesthetic drugs and PSF seemed to result in a better pain reduction than skin cooling. However, the current evidence is insufficient to provide recommendations for daily clinical practice. There is a need for more high-quality (head-to-head) RCTs. Future studies should also evaluate sex differences in pain perception, have uniformity with regard to validated pain measurement scales and address clinically significant differences in pain reduction besides statistically significant differences.


Symposium on surgical manpower in the smaller community. Is there a future for the community general surgeon?
The author attempts to assess the factors affecting the future of surgery in Canadian communities with a population of 10 000 to 30 000. Five problems are identified: (a) unrealistic patient expectations, (b) government cutbacks causing reduced equipment budgets, (c) difficulty in getting competent, modern anesthesia from well-trained general practitioners, (d) undergraduate and postgraduate training focus and (e) political enlargement of medical schools and reduced funding for health care. The proposed solutions are as follows: realistic patient expectations should be possible through authoritarian advertising compaigns; residency training should be keyed to community surgery; community health care standards can be promoted and maintained by creating a link between the community surgeon (specialist) and the tertiary hospital of his choice. This can be accomplished by creating a new class of staff appointment in the tertiary hospital, the "referring consultant" (i.e., the community surgeon).


Electromagnetic stimulation and inhibition of nerve conduction in frog isolated sciatic nerve-gastrocnemius muscle preparation.
The effect of electromagnetic stimulation on nerve conduction and on muscle contraction was studied in isolated frog sciatic nerve-gastrocnemius muscle preparation. The nerve trunk was passed through an induction copper coil and current was induced from a d.c. source 1.5-4 V at a frequency of 100 min-1, for 20-120 s duration, via an operating switch. Normal indirectly-elicited twitch (0.5 Hz with 0.6 V, supramaximal, and 1 ms pulse duration) tension was elicited, repetitively, and this was interrupted by magnetic induction. Inhibition of the twitch tension was taken as a measure of conduction block. The results showed that magnetic stimulation inhibited or blocked the twitch contractions (control 3.2 +/- 0.1 g, tension, mean +/- s.e., n = 8), in 4-5 min, and hence it blocked nerve conduction in this preparation. Recovery was achieved within 4-5 min, after washing out the preparation in Ringer solution. The mechanism of inhibition was interpreted in terms of an interference with ionic fluxes across the cell membrane. A comparison of electrical and magnetic stimulation was made and this was related to their clinical and experimental implications.


Influence of patient age on capsular contracture after aesthetic breast augmentation.
The influence of age on capsular contracture rates remains unclear. Most studies have only investigated early capsule development and not whether a link between age at primary surgery and the later development of capsular fibrosis exists. To clarify whether patient age impacts the development of late capsular fibrosis, the authors conducted a retrospective case study involving 43 patients who presented for surgical revision of capsular contracture (Baker grade ≥III) between four and 40 years after primary breast augmentation. Possible correlations between age and implant placement were analyzed. Late presentation of capsular fibrosis occurred a mean of 15.6 years after primary augmentation, with a slightly negative, but not significant, correlation between age at primary operation and duration of implant placement. Patients <40 years of age underwent an operative revision after a mean of 18.9 years, while patients ≥40 years of age needed an operative revision a mean of 11.9 years after primary breast augmentation (P=0.0368). The results suggest that with advancing age, the average time to develop capsular fibrosis is significantly shorter in individuals who develop capsular contracture. As more data are collected, appropriate advice can be provided to patients regarding factors that influence the long-term outcomes of breast augmentation.


The feasibility and acceptability of assessing inhibitory control and working memory among adolescents via an ecological momentary assessment approach.
Early adolescence is a critical period for the development of executive function (EF). EF deficits are associated with increased engagement in multiple health risk behaviors and may be influenced by momentary factors, such as state mindfulness and physical activity. Ecological momentary assessment (EMA) leverages the increasing ubiquity of smart-phones to assess moment-to-moment changes in neurocognition and behavior with minimal recall bias and high ecological validity. As such, EMA is a promising method for delivering performance-based EF tasks and assessing the degree to which EF is influenced by momentary variation in its putative antecedents (e.g. state mindfulness and PA). This study adapts the (1) State Mindfulness Attention Awareness Scale, (2) physical activity/sedentary behavior recall items, (3) complex symmetry span working memory task, and (4) the child flanker inhibitory control task into an EMA tool delivered via iPhone using Inquisit Web. This tool was piloted with a sample of 32 seventh graders over a 72 h period. Participants' posttest survey responses indicated that they found these study activities to be enjoyable, non-burdensome, not overly difficult, and preferable to pencil-and-paper instruments. Baseline correlations between flanker task performance and both BRIEF inhibitory control (σ = .23) and working memory subscales (σ = .34) were moderate. Correlations between symmetry span working memory task performance and BRIEF inhibitory control (σabsolute = .28; σpartial = .16) and working memory subscales (σabsolute = .19; σpartial = .15) were slightly lower, demonstrating associations consistent with previous studies. This study supports the feasibility and acceptability of administering two common performance-based EF tasks to adolescents via an EMA approach.


High frequency of splenic anti-class I cytotoxic T lymphocyte precursors correlates with in vivo rejection of K/D region disparate thyroid and islet grafts in mice.
The relationship between the ability of different recombinant mouse strains to reject thyroid and pancreatic islet grafts that differ in class I antigens and the frequencies of the recipients' cytolytic T lymphocyte precursors (CTL-P) directed against donor antigens was examined. We analyzed three different pairs of D region histoincompatible recombinant mouse strains in which unidirectional thyroid graft rejection occurred. Frequency analysis of their splenic CTL-P demonstrated that the mouse strains that rejected the grafts exhibit a relatively high CTL-P frequency against the donor D region-encoded alloantigens at a magnitude similar to that directed against a third party, which differ in the entire H-2 complex. Mouse strains that did not reject thyroid grafts exhibited a relatively low CTL-P frequency against the donor alloantigens, but a normal high frequency against alloantigens encoded by the entire H-2 complex of a third party strain. The effect of different routes of immunization on the two parameters was tested in B10.S(7R) mice, which accept B10.S thyroid grafts permanently. Immunization of B10.S(7R) mice by injection of 50 X 10(6) B10.S spleen cells i.p. did not confer the ability to reject B10.S thyroid grafts and did not affect the low splenic anti-B10.S CTL-P frequency. By contrast, B10.S(7R) mice that were immunized by transplantation of B10.S skin rejected a subsequent B10.S thyroid graft and at the same time demonstrated a fourfold increase in the specific CTL-P frequency. We found that the ability to reject thyroid and pancreatic islet grafts always correlated with high CTL-P frequency against the donor alloantigens; however, acceptance of allografts was not always correlated with low CTL-P frequency. We assume, therefore, that the high frequency of CTL-P against donor alloantigens may be a prerequisite (but is not always sufficient) for rejection of K/D region disparate thyroid and pancreatic islet grafts.


Chemical Constituents and Antimicrobial Activity of Indian Green Leafy Vegetable Cardiospermum halicacabum.
The present study was carried out to analyze chemical constituents and antibacterial activity of ethanolic leaf extract of Cardiospermum halicacabum (ECH). The FT-IR spectrum confirmed the presence of alcohols, phenols, alkanes, alkynes, aliphatic ester and flavonoids in ECH. The GC-MS analysis revealed that ECH contained about twenty four compounds. The major chemical compounds identified were cyclohexane-1, 4, 5-triol-3-one-1-carboxylic acid, benzene acetic acid, caryophyllene, phytol and neophytadiene. The ECH was screened for its antibacterial activity against different bacterial strains and anti fungal activity against Candida albicans by agar well diffusion and minimum inhibitory concentration (MIC) assay. ECH exhibited antibacterial and antifungal activity. All the tested bacterial strains showed MIC values ranging from 80 to 125 μg of extract/ml and C. albicans showed 190 μg of extract/ml as a MIC. The maximum activity ECH was observed against human pathogen Staphylococcus aureus followed by Escherichia coli and the fish pathogen Aeromonas hydrophila. ECH exhibited moderate activity against some of the tested multidrug resistant strains.


Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM.
Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 ≤ 1.45 and > 1.45 were examined using multistate Markov models. Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range = 8-18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95-1.05] before AHCVI, 1.31 (95% CI = 1.25-1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4 cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and ≥ 3.25, respectively. Older age, lower CD4 cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 ≤ 1.45. In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 ≥ 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression.


Moving theranostics trom bench to bedside in an interdisciplinary research team.
The Laboratory of Molecular Imaging and Nanomedicine of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health has been led by Xiaoyuan Chen since 2009. The Laboratory of Molecular Imaging and Nanomedicine contains three interdisciplinary, versatile groups: the Theranostic Nanomedicine; PET/Optical Imaging Probe; and Biological Molecular Imaging Sections, consisting of chemists, engineers, biologists and clinicians working together to transfer biomedical technology from bench to bedside. To find out more about our laboratory and meet our group, please visit us at www.nibib.nih.gov/Research/Intramural/xchen.


Risk factors for failure of endoscopic third ventriculostomy for obstructive hydrocephalus.
This is a retrospective study to identify risk factors for failure in the treatment of obstructive hydrocephalus with endoscopic third ventriculostomy (ETV). The records for 89 patients, including 32 with ventriculoperitoneal or ventriculoatrial shunt malfunctions or infections, who underwent ETVs between 1993 and 1998, at our institution, were examined. Multiple variables possibly related to failure were considered. These included age, sex, cause of hydrocephalus, presence and function of ventriculoperitoneal/ventriculoatrial shunts, history of shunt revisions or infections, symptoms, preoperative imaging results, presence of retained shunt catheters, postoperative meningitis, and postoperative ventricular size. Twenty-nine patients (32.6%) required subsequent shunt replacement and/or ETV revision. Of these 29 reoperations, 12 procedures (41.4%) were performed within 2 weeks and only 3 were performed more than 10 months after the initial ETV procedure. The ventricular size remained unchanged in 75% of the cases on the day after ETV, in 57.4% at 3 months, in 48.2% at 6 months, and in 41.8% at 1 year. Cine phase-contrast magnetic resonance imaging findings were consistent with postoperative symptomatic resolution in 96.3% of the cases. Seven patients (7.9%) experienced complications related to ETV, all of which were transient. Significant risk factors in univariate analyses were as follows: presence of Chiari Type I malformation (P = 0.003), shunt infection at presentation (P = 0.014), history of shunt infections (P = 0.0004), three or more previous shunt revisions (P = 0.0018), and postoperative meningitis (P = 0.0001). Late-onset idiopathic aqueductal stenosis was a significant predictor of good outcomes (P = 0.044). These factors were reanalyzed in a multivariate analysis, which confirmed a history of shunt infections and postoperative meningitis as independent risk factors. The risk of failure increases with intracerebral infection, likely because of obliteration of cerebrospinal fluid pathways.


Characteristics of metals used in implants.
The performance of any material in the human body is controlled by two sets of characteristics: biofunctionality and biocompatibility. With the wide range of materials available in the mid-1990s, it is relatively easy to satisfy the requirements for mechanical and physical functionality of implantable devices. Therefore, the selection of materials for medical applications is usually based on considerations of biocompatibility. When metals and alloys are considered, the susceptibility of the material to corrosion and the effect the corrosion has on the tissue are the central aspects of biocompatibility. Corrosion resistance of the currently used 316L stainless steel, cobalt-chromium, and titanium-based implant alloys relies on their passivation by a thin surface layer of oxide. Stainless steel is the least corrosion resistant, and it is used for temporary implants only. The titanium and Co-Cr alloys do not corrode in the body; however, metal ions slowly diffuse through the oxide layer and accumulate in the tissue. When a metal implant is placed in the human body, it becomes surrounded by a layer of fibrous tissue of a thickness that is proportional to the amount and toxicity of the dissolution products and to the amount of motion between the implant and the adjacent tissues. Pure titanium may elicit a minimal fibrous encapsulation under some conditions, whereas the proliferation of a fibrous layer as much as 2 mm thick is encountered with the use of stainless steel implants. Superior fracture and fatigue resistance have made metals the materials of choice for traditional load-bearing applications. In this review, the functionality of currently used metals and alloys is discussed with respect to stenting applications. In addition, the "shape memory" and "pseudo-elasticity" properties of Nitinol-an alloy that is being considered for the manufacturing of urologic stents-are described.


Effects of microplastic particles and leaching additive on the life history and morphology of Daphnia magna.
Plastic waste is continuously introduced not only into marine, but also freshwater environments, where it fragments into microplastics. Organisms may be affected by the particles themselves due to ingestion and indirectly via incorporated additives such as plasticizers, since these substances have the ability to leach out of the polymer matrix. Although it has been indicated that the likelihood of additives leaching out into the gut lumen of organisms exposed to microplastics is low, studies distinguishing between the effects of the synthetic polymer itself and incorporated additives of the same polymer are scarce. Since this is obligatory for risk assessment, we analyzed the chronic effects of flexible polyvinylchloride (PVC), a widely used polymer, containing the plasticizer diisononylphthalate (DiNP) on morphology and life history of the freshwater crustacean Daphnia magna and compared these effects with the effects of rigid PVC, lacking DiNP, as well as a glass bead control. After up to 31 days of exposure, rigid PVC and glass beads did not affect body length and relative tail spine length of D. magna, whereas flexible PVC led to an increased body length and a reduced number of offspring. None of the treatments increased the mortality significantly. We were able to show that 2.67μg/L DiNP leached out of the flexible PVC into the surrounding medium using GC-MS. Yet, we were not able to measure leachate inside the gut lumen of D. magna. The effects emerged towards the end of the experiment, due to the time dependent process of leaching. Therefore, the results highlight the relevance of long-term chronic exposure experiments, especially as leaching of additives takes time. Further, our study shows the importance to distinguish between microplastics containing leachable additives and the raw polymer in ecotoxicological testing.


The effect of Plantago major supplementation on leptin and VEGF-A serum levels, endothelial dysfunction and angiogenesis in obese women - a randomised trial.
Obesity is associated with increased serum leptin level, endothelial dysfunction and angiogenesis. In vitro studies have shown that vascular endothelial growth factor (VEGF) synthesis is increased by leptin. Animal studies revealed the effectiveness of Plantago supplementation treatment of obesity. The study aim was to evaluate the effect of Plantago major supplementation on serum leptin and VEGF blood concentration, endothelial dysfunction and angiogenesis in obese women. Seventy-two obese women received oral Plantago major supplement (Plantago group, n = 35) or placebo (placebo group, n = 37) for 12 weeks. At baseline and after completion, anthropometric and body composition measurements were performed, and blood samples were collected. Serum concentrations of leptin, VEGF-A, adiponectin, tumour necrosis factor α and soluble intercellular adhesion molecule have been determined. At completion, the leptin level was higher in the Plantago group (39 781.55 ± 20 360.73 pg ml-1) compared to both the baseline (36 138.71 ± 25 401.51 pg ml-1) and placebo group (30 502.81 ± 19 003.18 pg ml-1). Also, leptin concentration in the Plantago group at completion correlated positively with an increase in VEGF-A level (R = 0.45), and baseline VEGF-A level correlated negatively with the increase in leptin concentration (R = -0.47). Plantago major supplementation increases leptin serum level, enhances leptin influence on VEGF-A serum level increase and by this mechanism may intensify endothelial dysfunction and angiogenesis in obese women.


Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis.
Little is known about plasma drug concentrations relative to quantitative susceptibility in patients with multidrug-resistant tuberculosis (MDR-TB). We previously described a TB drug activity (TDA) assay that determines the ratio of the time to detection of plasma-cocultured Mycobacterium tuberculosis versus control growth in a Bactec MGIT system. Here, we assess the activity of individual drugs in a typical MDR-TB regimen using the TDA assay. We also examined the relationship of the TDA to the drug concentration at 2 h (C2) and the MICs among adults on a MDR-TB regimen in Tanzania. These parameters were also compared to the treatment outcome of sputum culture conversion. Individually, moxifloxacin yielded superior TDA results versus ofloxacin, and only moxifloxacin and amikacin yielded TDAs equivalent to a -2-log killing. In the 25 patients enrolled on a regimen of kanamycin, levofloxacin, ethionamide, pyrazinamide, and cycloserine, the C2 values were found to be below the expected range for levofloxacin in 13 (52%) and kanamycin in 10 (40%). Three subjects with the lowest TDA result (<1.5, a finding indicative of poor killing) had significantly lower kanamycin C2/MIC ratios than subjects with a TDA of ≥1.5 (9.8 ± 8.7 versus 27.0 ± 19.1; P = 0.04). The mean TDAs were 2.52 ± 0.76 in subjects converting to negative in ≤2 months and 1.88 ± 0.57 in subjects converting to negative in >2 months (P = 0.08). In Tanzania, MDR-TB drug concentrations were frequently low, and a wide concentration/MIC range was observed that affected plasma drug activity ex vivo. An opportunity exists for pharmacokinetic optimization in current MDR-TB regimens, which may improve treatment response.


Acute Gastric Volvulus Successfully Treated by Endoscopic Reduction in a 6-Year-Old Girl and a Review of the Japanese Literature.
A previously healthy 6-year-old girl suddenly developed severe abdominal pain and nausea. She was diagnosed with acute gastric volvulus, and a nasogastric tube was inserted to decompress the stomach. The volvulus did not reduce spontaneously; therefore, we performed endoscopic reduction on day 3 and were able to treat her successfully. We reviewed the Japanese literature on endoscopic reduction for gastric volvulus in children. Fifteen cases have been reported since 1994. There are no reports of perforation during the procedure. Patients whose general condition is stable and who have no severe anatomic anomalies are good candidates for endoscopic reduction.


Mucin-like glycoprotein secreted by cultured hamster tracheal epithelial cells. Biochemical and immunological characterization.
We isolated mucin-like glycoproteins from the conditioned medium of primary hamster tracheal epithelial (HTE) cell culture and characterized them biochemically and immunologically. These glycoproteins were purified on Sepharose CL-4B after Streptomyces hyaluronidase treatment and then by CsCl-density-gradient centrifugation in the presence of 4 M-guanidinium chloride. The purified glycoproteins were resistant to digestion by chondroitin AC lyase, heparinase, heparitinase and endo-N-acetylglucosaminidases A, D and H, but susceptible to endo-beta-galactosidase and keratanase. SDS/PAGE demonstrated no contamination by low-molecular-mass proteins. The purified glycoproteins showed a peak buoyant density of 1.56 g/ml in CsCl-density-gradient centrifugation, and contained 10% peptide and 90% carbohydrate by weight. Carbohydrates in these glycoproteins contained N-acetylglucosamine, N-acetylgalactosamine, galactose, fucose, sialic acid and a trace amount of mannose, but no uronic acid. Serine and threonine together accounted for 27% of the total amino acid residues. In addition, the mucin-like glycoproteins exhibited blood-group A and B activities, and very strong inhibitory activity for influenza A virus haemagglutination. With the use of the purified glycoprotein as an antigen, six monoclonal antibodies that stained mucus granules in hamster tracheal epithelium were obtained. We characterized the antibody produced by one of the clones, HM D46. We conclude that HTE cells cultured in the serum-free medium secrete a glycoprotein with physicochemical properties similar to those known in various airways mucins.


Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons.
α-Synuclein becomes misfolded and aggregated upon damage by various factors, for example, by reactive oxygen species. These aggregated forms have been proposed to have differential toxicities and their interaction with mitochondria may cause dysfunction within this organelle that contributes to the pathogenesis of Parkinson's disease (PD). In particular, the association of α-synuclein with mitochondria occurs through interaction with mitochondrial complex I and importantly defects of this protein have been linked to the pathogenesis of PD. Therefore, we investigated the relationship between aggregated α-synuclein and mitochondrial dysfunction, and the consequences of this interaction on cell survival. To do this, we studied the effects of α-synuclein on cybrid cell lines harbouring mutations in either mitochondrial complex I or IV. We found that aggregated α-synuclein inhibited mitochondrial complex I in control and complex IV-deficient cells. However, when aggregated α-synuclein was applied to complex I-deficient cells, there was no additional inhibition of mitochondrial function or increase in cell death. This would suggest that as complex I-deficient cells have already adapted to their mitochondrial defect, the subsequent toxic effects of α-synuclein are reduced.


Breaking through Multiple Myeloma: A Paradigm for a Comprehensive Tumor Ecosystem Targeting.
Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.


Fall Risk Classification in Community-Dwelling Older Adults Using a Smart Wrist-Worn Device and the Resident Assessment Instrument-Home Care: Prospective Observational Study.
Little is known about whether off-the-shelf wearable sensor data can contribute to fall risk classification or complement clinical assessment tools such as the Resident Assessment Instrument-Home Care (RAI-HC). This study aimed to (1) investigate the similarities and differences in physical activity (PA), heart rate, and night sleep in a sample of community-dwelling older adults with varying fall histories using a smart wrist-worn device and (2) create and evaluate fall risk classification models based on (i) wearable data, (ii) the RAI-HC, and (iii) the combination of wearable and RAI-HC data. A prospective, observational study was conducted among 3 faller groups (G0, G1, G2+) based on the number of previous falls (0, 1, ≥2 falls) in a sample of older community-dwelling adults. Each participant was requested to wear a smart wristband for 7 consecutive days while carrying out day-to-day activities in their normal lives. The wearable and RAI-HC assessment data were analyzed and utilized to create fall risk classification models, with 3 supervised machine learning algorithms: logistic regression, decision tree, and random forest (RF). Of 40 participants aged 65 to 93 years, 16 (40%) had no previous falls, whereas 8 (20%) and 16 (40%) had experienced 1 and multiple (≥2) falls, respectively. Level of PA as measured by average daily steps was significantly different between groups (P=.04). In the 3 faller group classification, RF achieved the best accuracy of 83.8% using both wearable and RAI-HC data, which is 13.5% higher than that of using the RAI-HC data only and 18.9% higher than that of using wearable data exclusively. In discriminating between {G0+G1} and G2+, RF achieved the best area under the receiver operating characteristic curve of 0.894 (overall accuracy of 89.2%) based on wearable and RAI-HC data. Discrimination between G0 and {G1+G2+} did not result in better classification performance than that between {G0+G1} and G2+. Both wearable data and the RAI-HC assessment can contribute to fall risk classification. All the classification models revealed that RAI-HC outperforms wearable data, and the best performance was achieved with the combination of 2 datasets. Future studies in fall risk assessment should consider using wearable technologies to supplement resident assessment instruments.


Associations of physical frailty with incidence and mortality of overall and site-specific cancers: A prospective cohort study from UK biobank.
Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking.


Development and evaluation of antimicrobial herbal formulations containing the methanolic extract of Samadera indica for skin diseases.
Samadera indica Gaetrn (Simaroubaceae) is claimed to possess various pharmacological activities like antioxidant, antifungal, antitumor, antiviral, and so on, but its taste is bitter. The aim of the present study is to investigate the toxicity of the methanolic extract and to develop suitable herbal formulations of the methanolic extract of Samadera indica, having efficient antimicrobial activity. The methanolic extract prepared from the dried leaves of Samadera indica by continuous hot percolation, were used to examine the toxicity, according to the OECD 423 guidelines, in Swiss Albino mice. Topical formulations were prepared by incorporating Samadera indica (5% w / w) in an emulsifying ointment and a carbopol gel base and evaluated for physical parameters and in-vitro antimicrobial activity (S. aureus, P. aeruginosa and C. albicans). The study reveals that no animals under the study showed any clinical signs of toxicity or mortality when administered a dose of 5 - 2000 mg / kg body weight. Therefore, the maximum tolerated dose of the methanolic extract of Samadera indica was above 2000 mg / kg body weight. The formulated ointment and gel had acceptable physical parameters that showed that they were compatible with the skin, and in addition to this, these formulations passed the short-term stability studies. The in-vitro antimicrobial activity studies showed that the formulated ointment showed significantly strong (p < 0.05) activity against S. aureus, P. aeruginosa and C. albicans than the formulated gel. Thus, the present study concludes that the formulated ointment and gel are safe and efficient antimicrobial formulations for the topical delivery of the methanolic extract of Samadera indica.


[A new approach to the prophylaxis and therapy of puerperal mastitis (author's transl)].
The prolactin-inhibitor Bromocriptin was examined in an open study in comparison with Hexoestrol, a synthetic estrogen compound, in 31 patients with severe postpartal breast engorgement and in 38 patients with acute puerperal mastitis. In both indications a significantly faster clinical improvement was achieved with Bromocriptin. Also the incision-rate in cases of breast abscess was significantly lower in the Bromocriptin group. The inhibition of prolactin is considered the method of choice, as well in the prophylaxis as in the treatment of puerperal mastitis.


Successful sofosbuvir-based therapy in HIV/hepatitis C virus coinfected liver transplant recipients with recurrent hepatitis C virus infection.
Recurrent hepatitis C virus (HCV) infection contributes to unfavourable outcomes in HIV/HCV coinfected liver transplant recipients. Direct-acting antiviral (DAA) therapies for HCV offer an opportunity to improve patient and allograft survival in this patient population. We evaluated treatment outcomes with sofosbuvir (SOF)-based DAA therapy among HIV/HCV coinfected liver transplant recipients. Single centre prospective cohort study. We identified eight HIV/HCV coinfected liver transplant recipients who were prospectively followed in the Northwestern University Viral Hepatitis Registry and who received SOF-based DAA therapy. We evaluated responses to therapy, including sustained HCV viral response 12 weeks after therapy completion (SVR12) and adverse effects. Seven recipients (87.5%) completed 12 weeks of SOF-based therapy: SOF/simeprevir for genotype 1 (n = 6), SOF/ribavirin for genotype 2 (n = 1). Of persons who completed therapy, all achieved SVR12. Strategies for the management of expected and observed drug interactions consequent to the addition of simeprevir to preexisting complex medication regimens included modifications of HIV antiretroviral regimens (n = 4) and tacrolimus dosing (n = 4) and frequent monitoring of tacrolimus trough levels. Minor adverse effects were observed after DAA initiation. One episode of allograft rejection and one death occurred that were deemed unlikely related to HCV therapy. High rates of HCV treatment success and no treatment-limiting adverse effects were observed in this HIV/HCV liver transplant cohort. Complex drug interactions were successfully managed in the context of multidisciplinary specialty care. Further studies are needed to assess the long-term effects of DAA therapy on patient and allograft survival among HIV/HCV coinfected liver transplant recipients.


Training the trainees in radiation oncology with telemedicine as a tool in a developing country: a two-year audit.
Purpose. The estimated new cancer patient load in the Indian state of Uttar Pradesh is 0.1-0.12 million per year. Approximately two thirds of these require treatment by a radiation oncologist. Radiation oncologists: cancer patient ratio in this state is 1 : 2000 as compared to the recommended 1 : 250. This problem is compounded by the poor infrastructure of radiation oncology departments in the state which is suboptimal for teaching, training of resident doctors, and treatment in most barring a few departments. To bridge some gap in the sociodemographics stated above and enhancement of training of residents, we submitted a project for establishment of a telemedicine facility in our department to the Department of Science and Technology, Government of India. We present the design, implementation, and a two-year audit of our tele-education activities. Materials and Methods. After the sanction of the project, we established telemedicine linkage with another medical institute in the city located 25 kms away in 2007. After implementation of the project, academic sessions designed for trainee residents in our department were shared with the remote end. A record of these activities and a feedback of the activities were audited at the end of 2 years of implementation of this project. Results. Regular videoconferencing sessions comprising of lectures on clinical oncology, medical physics, and radiobiology were held. Feedback from the users revealed satisfaction with the content of the academic sessions for the purpose of MD training. Conclusions. Distance education in radiation oncology is an important tool for training of the trainee residents.


New colistin population pharmacokinetic data in critically ill patients suggesting an alternative loading dose rationale.
Colistin is an old antibiotic that has recently gained a considerable renewal of interest as the last-line defense therapy against multidrug-resistant Gram-negative bacteria. It is administered as colistin methanesulfonate (CMS), an inactive prodrug, and it was shown that due to slow CMS conversion, colistin plasma concentrations increase very slowly after treatment initiation, which constitutes the rationale for a loading dose in critically ill patients. However, faster CMS conversion was observed in healthy volunteers but using a different CMS brand, which may also have a major impact on colistin pharmacokinetics. Seventy-three critically ill patients not undergoing dialysis received multiple doses of CMS. The CMS concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and a pharmacokinetic analysis was conducted using a population approach. We confirmed that CMS renal clearance and colistin concentrations at steady state are mostly governed by creatinine clearance, but we predict a typical maximum concentration of drug in serum (Cmax) of colistin close to 2 mg/liter, occurring 3 h after an initial dose of 2 million international units (MIU) of CMS. Accordingly, the estimated colistin half-life (t1/2) was relatively short (3.1 h), with rapid attainment of steady state. Our results are only partially consistent with other recently published results. We confirm that the CMS maintenance dose should be adjusted according to renal function in critically ill patients. However, much higher than expected colistin concentrations were observed after the initial CMS dose, with rapid steady-state achievement. These discrepancies challenge the pharmacokinetic rationale for a loading dose, which may still be appropriate for rapid bacterial eradication and an improved clinical cure rate.


Exploration of the functional consequences of fixational eye movements in the absence of a fovea.
A recent theory posits that ocular drifts of fixational eye movements serve to reformat the visual input of natural images, so that the power of the input image is equalized across a range of spatial frequencies. This "spectral whitening" effect is postulated to improve the processing of high-spatial-frequency information and requires normal fixational eye movements. Given that people with macular disease exhibit abnormal fixational eye movements, do they also exhibit spectral whitening? To answer this question, we computed the power spectral density of movies of natural images translated in space and time according to the fixational eye movements (thus simulating the retinal input) of a group of observers with long-standing bilateral macular disease. Just as for people with normal vision, the power of the retinal input at low spatial frequencies was lower than that based on the 1/f2 relationship, demonstrating spectral whitening. However, the amount of whitening was much less for observers with macular disease when compared with age-matched controls with normal vision. A mediation analysis showed that the eccentricity of the preferred retinal locus adopted by these observers and the characteristics of ocular drifts are important factors limiting the amount of whitening. Finally, we did not find a normal aging effect on spectral whitening. Although these findings alone cannot form a causal link between macular disease and spectral properties of eye movements, they suggest novel potential means of modifying the characteristics of fixational eye movements, which may in turn improve functional vision for people with macular disease.


Interactive Effects of Rising Temperature and Nutrient Enrichment on Aquatic Plant Growth, Stoichiometry, and Palatability.
The abundance and stoichiometry of aquatic plants are crucial for nutrient cycling and energy transfer in aquatic ecosystems. However, the interactive effects of multiple global environmental changes, including temperature rise and eutrophication, on aquatic plant stoichiometry and palatability remain largely unknown. Here, we hypothesized that (1) plant growth rates increase faster with rising temperature in nutrient-rich than nutrient-poor sediments; (2) plant carbon (C): nutrient ratios [nitrogen (N) and phosphorus (P)] respond differently to rising temperatures at contrasting nutrient conditions of the sediment; (3) external nutrient loading to the water column limits the growth of plants and decreases plant C:nutrient ratios; and that (4) changes in plant stoichiometry affect plant palatability. We used the common rooted submerged plant Vallisneria spiralis as a model species to test the effects of temperature and nutrient availability in both the sediment and the water column on plant growth and stoichiometry in a full-factorial experiment. The results confirmed that plants grew faster in nutrient-rich than nutrient-poor sediments with rising temperature, whereas external nutrient loading decreased the growth of plants due to competition by algae. The plant C: N and C: P ratios responded differently at different nutrient conditions to rising temperature. Rising temperature increased the metabolic rates of organisms, increased the nutrient availability in the sediment and enhanced plant growth. Plant growth was limited by a shortage of N in the nutrient-poor sediment and in the treatment with external nutrient loading to the water column, as a consequence, the limited plant growth caused an accumulation of P in the plants. Therefore, the effects of temperature on aquatic plant C:nutrient ratios did not only depend on the availability of the specific nutrients in the environment, but also on plant growth, which could result in either increased, unaltered or decreased plant C:nutrient ratios in response to temperature rise. Plant feeding trial assays with the generalist consumer Lymnaea stagnalis (Gastropoda) did not show effects of temperature or nutrient treatments on plant consumption rates. Overall, our results implicate that warming and eutrophication might interactively affect plant abundance and plant stoichiometry, and therefore influence nutrient cycling in aquatic ecosystems.


[Anti-chromatin antibodies in juvenile rheumatoid arthritis].
to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs) in juvenile rheumatoid arthritis (JRA). IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA), in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset). As control group, 33 age- and-sex-matched healthy children (HC) were also examined. Abs to chromatin were detected in 24/94 (25.5%) of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4%) and polyarticular (23.7%) onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003). Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21.7%). Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNF-alpha therapy (p< 0.0001). our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present history of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies.


Prediction of RECRUITment In randomized clinical Trials (RECRUIT-IT)-rationale and design for an international collaborative study.
Poor recruitment of patients is the predominant reason for early termination of randomized clinical trials (RCTs). Systematic empirical investigations and validation studies of existing recruitment models, however, are lacking. We aim to provide evidence-based guidance on how to predict and monitor recruitment of patients into RCTs. Our specific objectives are the following: (1) to establish a large sample of RCTs (target n = 300) with individual patient recruitment data from a large variety of RCTs, (2) to investigate participant recruitment patterns and study site recruitment patterns and their association with the overall recruitment process, (3) to investigate the validity of a freely available recruitment model, and (4) to develop a user-friendly tool to assist trial investigators in the planning and monitoring of the recruitment process. Eligible RCTs need to have completed the recruitment process, used a parallel group design, and investigated any healthcare intervention where participants had the free choice to participate. To establish the planned sample of RCTs, we will use our contacts to national and international RCT networks, clinical trial units, and individual trial investigators. From included RCTs, we will collect patient-level information (date of randomization), site-level information (date of trial site activation), and trial-level information (target sample size). We will examine recruitment patterns using recruitment trajectories and stratifications by RCT characteristics. We will investigate associations of early recruitment patterns with overall recruitment by correlation and multivariable regression. To examine the validity of a freely available Bayesian prediction model, we will compare model predictions to collected empirical data of included RCTs. Finally, we will user-test any promising tool using qualitative methods for further tool improvement. This research will contribute to a better understanding of participant recruitment to RCTs, which could enhance efficiency and reduce the waste of resources in clinical research with a comprehensive, concerted, international effort.


An intelligent digital microfluidic system with fuzzy-enhanced feedback for multi-droplet manipulation.
The complexity of droplet hydrodynamics on a digital microfluidic (DMF) system eventually weakens its potential for application in large-scale chemical/biological micro-reactors. We describe here an intelligent DMF technology to address that intricacy. A wide variety of control-engaged droplet manageability is proposed and demonstrated through the operation of our modular DMF prototype, which comprises: (i) rigid profiling ability of different droplet's hydrodynamics under a real-time trajectory track of droplet-derived capacitance, permitting accurate and autonomous multi-droplet positioning without visual setup and heavy image signal processing; (ii) fuzzy-enhanced controllability saving up to 21% charging time when compared with the classical approach, enhancing the throughput, fidelity and lifetime of the DMF chip, while identifying and renouncing those weakened electrodes deteriorated over time, and (iii) expert manipulability of multi-droplet routings under countermeasure decisions in real time, preventing droplet-to-droplet or task-to-task interference. Altogether, this work exhibits the first modular DMF system with built-in electronic-control software-defined intelligence to enhance the fidelity and reliability of each droplet operation, allowing future manufacturability of a wide range of life science analyses and combinatorial chemical screening applications.


Impairments in glycaemic control do not increase linearly with repeated nights of sleep restriction in healthy adults: a randomised controlled trial.
Evidence suggests reduced glycaemic control following sleep restriction in healthy individuals. However, it remains unknown if impairments in glycaemic control increase with each additional night of sleep restriction in a linear manner. This randomised crossover study aimed to determine if the impairment in glycaemic control increases with each additional night of sleep restriction. Ten healthy individuals underwent 4 nights of control sleep (8 hours in bed) and 4 nights of sleep restriction (4 hours in bed) in a sleep laboratory. An oral glucose tolerance test was conducted each morning. Serum glucose and insulin were measured. Glucose and insulin area under the curve were higher overall in the sleep restriction trial compared with control (p < 0.001 and p = 0.033); however, no effect of day (p = 0.620 and p = 0.863) or interaction effect (p = 0.152 and p = 0.285) were observed. This supports previous literature showing a detrimental impact of sleep restriction on glucose regulation. The present findings, however, suggest the impairment in glycaemic control does not increase in a linear manner with an increasing number of nights of sleep restriction. This may have implications for the design of future studies examining sleep restriction and glycaemic control. Novelty: Four nights of sleep restriction impaired glycaemic control in healthy individuals, but did not do so in a linear manner. No effect of number of nights of restriction was found for glucose or insulin, which may have implications for future studies.


Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene.
Donor T cells play a pivotal role in facilitating alloengraftment but also cause graft-versus-host disease (GVHD). Ex vivo T-cell depletion (TCD) of donor marrow is the most effective strategy for reducing GVHD but can compromise engraftment. This study examined an approach whereby donor T cells are selectively eliminated in vivo after transplantation using transgenic mice in which a thymidine kinase (TK) suicide gene is targeted to the T cell using a CD3 promoter/enhancer construct. Lethally irradiated B10.BR mice transplanted with major histocompatibility complex (MHC)-incompatible TCD C57BL/6 (B6) bone marrow (BM) plus TK(+) T cells were protected from GVHD after treatment with ganciclovir (GCV) in a schedule-dependent fashion. To examine the effect of GCV treatment on alloengraftment, sublethally irradiated AKR mice underwent transplantation with TCD B6 BM plus limiting numbers (5 x 10(5)) of B6 TK(+) T cells. Animals treated with GCV had comparable donor engraftment but significantly reduced GVHD when compared with untreated mice. These mice also had a significantly increased number of donor splenic T cells when assessed 4 weeks after bone marrow transplantation. Thus, the administration of GCV did not render recipients T-cell deficient, but rather enhanced lymphocyte recovery. Adoptive transfer of spleen cells from GCV-treated chimeric mice into secondary AKR recipients failed to cause GVHD indicating that donor T cells were tolerant of recipient alloantigens. These studies demonstrate that administration of TK gene-modified donor T cells can be used as an approach to mitigate GVHD without compromising alloengraftment.


[Prevention of papillomavirus-associated cancer].
In March 2007, the Directing Board of Italian Agency for Drugs Administration (AIFA) established commercialization and reimbursement rules for the first anti-Human Papillomavirus (HPV) Vaccine. HPV free vaccination campaign for a strictly defined age-cohort (12 year old) will start in 2008. HPV-Vaccine will be proposed to approximately 280,000 subjects with an annual charge, for Italian NHS, estimated in 75 millions Euro. For subjects between 13 and 26 years, not included in the designed cohorts, vaccination is available in pharmacies under prescription but at a very high cost (Euro 188 each dose, Euro 564 for the three doses). At the end of 2007 a second HPV vaccine will become available.


Lysine metabolism in mammals.
The enzymes involved in the initial degradative steps of lysine metabolism, lysine-2-oxoglutarate reductase and saccharopine dehydrogenase, were studied and their activities in different mammals compared. Values obtained in human, rat, pig, dog, cat, ox and sheep liver indicated that in vitro, appreciable degradation of lysine to saccharopine (4-6nmol/min per mg of protein) occurred. The specific activity of saccharopine dehydrogenase in most species studied was higher than that of lysine-oxoglutarate reductase. The rate of production of glutamate from saccharopine in each animal species was investigated and related to the rate of production of alpha-aminoadipate. The rate of formation of lysine from saccharopine, catalysed by saccharopine oxidoreductase, was examined and correlated with the dietary intake of lysine in each species studied.


Embryonic Fundulus heteroclitus responses to sediment extracts from differentially contaminated sites in the Elizabeth River, VA.
Sites along the Elizabeth River are contaminated with polycyclic aromatic hydrocarbons (PAHs) from historical creosote production and other industrial processes. Previous studies have demonstrated that Atlantic killifish collected from sites throughout the Elizabeth River display resistance to the teratogenic effects of PAH-exposure in a manner commensurate with sediment PAH concentrations. The current study characterized various chemical pollutants in sediment and investigated the effects of aqueous sediment extracts from sites along the Elizabeth River to the cardiac development of Atlantic killifish embryos from fish collected from an uncontaminated reference site. Embryonic cardiac deformities were more prevalent after exposure to extracts from sites with high PAH loads. However, activation of cytochrome P4501A, a gene up-regulated by PAH-induction of the aryl hydrocarbon receptor and measured using an in ovo EROD assay, did not consistently increase with PAH concentrations. This work further characterizes sediments in the Elizabeth River, as well as provides insight into the evolutionary pressures at each ER site.


Topical tacrolimus solution in autoimmune polyglandular syndrome-1-associated keratitis.
To evaluate the efficacy of topical tacrloimus eye drops in the treatment of keratitis associated with autoimmune polyglandular syndrome (APS)-1. This is a retrospective review of 10 patients with APS-1. The patients were treated with topical tacrolimus 0.01% solution at The Eye Center, between 1 March 2012 and 30 April 2016. The outcome measures included improvement in visual acuity, photophobia and keratitis following treatment. Clinical assessment was carried out before, during and on the last visit following initiation of therapy. A total of 10 patients were included. There were five male and five female patients. The mean age was 11 years with age range of 3-42 years. The mean duration of treatment with topical tacrolimus was 26 months (range 8-46 months). There was improvement of photophobia in 7 out of 10 patients following therapy with topical tacrolimus. In three patients, the photophobia was persistent. There was no clinically detectable improvement in the severity of keratitis in all patients. The mean best corrected visual acuity was 0.1 before and following therapy. Topical tacrolimus is effective in reducing the photophobia in patients with APS-1-associated keratitis, but showed no effects on the severity of keratitis.


Migration and investments in the health of children left behind: the role of remittances in children's healthcare utilization in Cambodia.
Remittances, financial support from family members who have migrated for work, are an increasingly important source of income for households left behind in many lower- and middle-income countries. While remittances have been shown to affect the health status of children left behind, evidence is very limited as to whether and how they affect children's healthcare utilization. Yet, this is an important consideration for policymakers seeking to improve equitable access to quality care in settings where migration is common. I examine whether children under age five whose household receives remittances are more likely to utilize higher quality healthcare providers than those without remittances in Cambodia, a country with high rates of migration and a pluralistic health system. The analysis includes 2230 children reporting recent illness in three waves of the Cambodia Socio-Economic Survey with data on migration, remittances and children's health expenditures. I use mixed-effects and fixed-effects regression analysis to estimate the effect of remittances on children's likelihood of entering care with a formally trained provider, and among those attending a formally trained provider, likelihood of using a public-sector facility. Treatment expenditures are lower among households with remittances, while transportation expenditures do not vary significantly by remittance status. In mixed-effects and fixed-effect regression models, children who receive remittances have a lower likelihood of utilizing qualified providers (adjusted OR = 0.66, 95% confidence interval 0.44-0.98), though this effect is attenuated in fixed-effects models, and there is no association between remittances and attending a public-sector facility. These findings underscore that remittances alone are not sufficient to increase children's utilization of qualified providers in migrant-sending areas, and suggest that policymakers should to address barriers to care beyond cost to promote utilization and equity of access to higher quality care where remittances are a common source of income.


Infant mortality in Sudan: Health equity, territorial disparity and social determinants of health.
Recognition of, and acting on, Social Determinants of Health is crucial for reducing health inequalities and territorial disparities and hence improving health of the whole population. Although Sudan was among the first countries which adopted a roadmap for Health in All Policies, health inequity remains an important challenge for health makers in this country. This paper illustrates the urgent need to reduce health inequalities in Sudan by acting on Social Determinants of Health. Descriptive statistics and Principal Components Analysis were used to get summarized multidimensional data information. Statistical significance of differences was tested by Pearson's chi-squared. A large territorial disparity was found between the 18 states. Infant mortality rate is more than three times higher in East Darfur (88.5) than in River Nile (28.1). Ratios of 1.9 and 1.6 were indicated for income and mother education respectively. A lower gap was seen for milieu (1.2) and gender (1.34). The difference was statistically significant for states (p-value <0.0001), income (p-value <0.001) and education (p-value <0.005). Urgent strategies are needed by acting sufficiently on social determinants of health like milieu, gender, education, income and territoriality in order to reduce avoidable heath inequalities and unacceptable territorial disparities in Sudan.


Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2.
Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.


Are drought-resistance promoting bacteria cross-compatible with different plant models?
The association between plant and plant growth promoting bacteria (PGPB) contributes to the successful thriving of plants in extreme environments featured by water shortage. We have recently shown that, with respect to the non-cultivated desert soil, the rhizosphere of pepper plants cultivated under desert farming hosts PGPB communities that are endowed with a large portfolio of PGP traits. Pepper plants exposed to bacterial isolates from plants cultivated under desert farming exhibited a higher tolerance to water shortage, compared with untreated control. This promotion was mediated by a larger root system (up to 40%), stimulated by the bacteria, that enhanced plant ability to uptake water from dry soil. We provide initial evidence that the nature of the interaction can have a limited level of specificity and that PGPB isolates may determine resistance to water stress in plants others than the one of the original isolation. It is apparent that, in relation to plant resistance to water stress, a feature of primary evolutionary importance for all plants, a cross-compatibility between PGPB and different plant models exists at least on a short-term.


Prediction and control of operant behavior: What you see is not all there is.
Prediction and control of operant behavior are major goals of behavior analysis. We suggest that achieving these goals can benefit from doing more than identifying the three-term contingency between the behavior, its setting stimulus, and its consequences. Basic research now underscores the idea that prediction and control require consideration of the behavior's history. As one example, if an operant is a goal-directed action, it is controlled by the current value of the reinforcer, as illustrated by the so-called reinforcer devaluation effect. In contrast, if the behavior is a habit, it occurs automatically, without regard to the reinforcer's value, as illustrated by its insensitivity to the reinforcer devaluation effect. History variables that distinguish actions and habits include the extent of their prior practice and their schedule of reinforcement. Other operants can appear to have very low or zero strength. However, if the behavior has reached that level through extinction or punishment, it may precipitously increase in strength by changing the context, allowing time to pass, presenting the reinforcer contingently or noncontingently, or extinguishing an alternative behavior. Behaviors that are not suppressed by extinction or punishment are not affected the same way. When predicting the strength of an operant behavior, what you see is not all there is. The behavior's history counts.


Association of body composition with disability in rheumatoid arthritis: impact of appendicular fat and lean tissue mass.
To explore the association of measures of body composition with disability in patients with rheumatoid arthritis (RA). Patients with RA underwent total body dual-energy x-ray absorptiometry for measurement of total and regional body fat and lean mass. The associations of measures of fat and lean mass with disability, measured with the Health Assessment Questionnaire (HAQ), were explored for the total cohort and by sex, controlling for pertinent demographic, lifestyle, and RA disease and treatment covariates. We studied 197 subjects (118 women, 79 men). Median (interquartile range) HAQ score was 0.625 (0.125-1.25) and was significantly higher, indicating worse physical function, in women than in men. HAQ score was strongly correlated with depression, pain, RA duration, duration of morning stiffness, Disease Activity Score in 28 joints, radiographic damage scores, levels of physical and sedentary activities, and body composition, with increasing fat and decreasing lean mass associated with higher HAQ scores. Appendicular fat and lean mass demonstrated the strongest association per kilogram with HAQ. Mean HAQ score was 0.52 units higher for subjects in the highest versus the lowest quartile of appendicular fat mass (P<0.001), and 0.81 units higher for subjects in the lowest versus the highest quartile of appendicular lean mass (P<0.001). Adjusting for demographic and RA characteristics partially attenuated these associations. The joint associations of appendicular fat and lean mass on HAQ were additive without significant interaction. Body composition, particularly the amount of fat and lean mass located in the arms and legs, is strongly associated with disability in RA patients.


JCPP--The Journal of Child Psychology and Psychiatry: a history from the inside.
As the JCPP marks its 50th year of publication, this paper revisits the founding philosophy and traces the journey from the first issue through to the present. The history of the JCPP reflects the many changes that have come about in the fields of developmental psychology and child and adolescent psychiatry and the changes introduced both to meet the needs and shape the practices of clinicians and researchers. It documents the achievements of the Journal and the contributions made by many in enabling its success. As the JCPP moves forward it will enjoy the benefits of the major technological and other advances being made in research, in the evolving and expanding knowledge base, and in the modes of publication, as well as needing to manage the associated challenges that will inevitably impact on its future.