Modulating Drug Release and Enhancing the Oral Bioavailability of Torcetrapib with Solid Lipid Dispersion Formulations.
The development of drug dispersions using solid lipids is a novel formulation strategy that can help address the challenges of poor drug solubility and systemic exposure after oral administration. The highly lipophilic and poorly water-soluble drug torcetrapib could be effectively formulated into solid lipid microparticles (SLMs) using an anti-solvent precipitation strategy. Acoustic milling was subsequently used to obtain solid lipid nanoparticles (SLNs). Torcetrapib was successfully incorporated into the lipid matrix in an amorphous state. Spherical SLMs with mean particle size of approximately 15-18 μm were produced with high drug encapsulation efficiency (>96%) while SLNs were produced with a mean particle size of 155 nm and excellent colloidal stability. The in vitro drug release and the in vivo absorption of the solid lipid micro- and nanoparticles after oral dosing in rats were evaluated against conventional crystalline drug powders as well as a spray dried amorphous polymer dispersion formulation. Interestingly, the in vitro drug release rate from the lipid particles could be tuned for immediate or extended release by controlling either the particle size or the precipitation temperature used when forming the drug-lipid particles. This change in the rate of drug release was manifested in vivo with changes in Tmax as well. In addition, in vivo pharmacokinetic studies revealed a significant increase (∼6 to 11-fold) in oral bioavailability in rats dosed with the SLMs and SLNs compared to conventional drug powders. Importantly, this formulation approach can be performed rapidly on a small scale, making it ideal as a formulation technology for use early in the drug discovery timeframe.


Antibiotics that specifically block translation in virus-infected cells.
Several antibiotics including anthelmycin, blasticidin S, destomycin A, gougerotin, hygromycin B and edeine complex, known to powerfully block translation in cell-free systems, did neither inhibit protein synthesis in intact mouse L and 3T6 cells, nor in hamster BHK 21 cells, due to failure to cross the cell plasma membrane. However, after viral infection, these antibiotics exhibited a marked blockade of translation, that is related to the permeability changes induced by viral infection. The inhibition of protein synthesis by hygromycin B in virus-infected cells was studied over the time course of infection, both in encephalomyocarditis virus-infected mouse L cells and in Semliki forest virus-infected hamster BHK cells. We have observed that the entry of hygromycin B into virus-infected cells parallels the inhibition of cellular protein synthesis, i.e., the cells became permeable to this antibiotic at the time the shut-off of host translation occurred. A marked inhibition of picornavirus RNA synthesis by hygromycin B was also noticed, likely as a consequence of the inhibition of the viral replicase synthesis. Finally, a reduction in the virus yield by treatment of virus-infected cells with several antibiotics is also described. All these observations are considered in the context of the interference of viral infection with cellular functions and the potential use of inhibitors non-permeable to normal cells as antiviral agents.


Guiding Cardiopulmonary Resuscitation with Focused Echocardiography: A Report of Five Cases.
Background: Focused transthoracic echocardiography has been used to determine etiologies of cardiac arrest and evaluate utility of continuing resuscitation after cardiac arrest. Few guidelines exist advising ultrasound timing within the advanced cardiac life support algorithm. Natural timing of echocardiography occurs during the pulse check, when views are unencumbered by stabilization equipment or vigorous movements. However, recent studies suggest that ultrasound performance during pulse checks prolongs the pause duration of cardiopulmonary resuscitation. Transesophageal echocardiography studies have demonstrated benefits in this regard, but there have been no transthoracic echocardiography studies assessing the physical performance of compressions during cardiopulmonary resuscitation. Objective: The purpose of this study was to describe cases where echocardiography performed at the beginning of the cardiac arrest algorithm offers actionable information to cardiopulmonary resuscitation itself without delaying provision of compressions. Conclusion: Providers using focused echocardiography to evaluate cardiac arrest patients should consider initiating scans at the start of compressions to identify the optimal location for compression delivery and to detect inadequate compressions. Subsequent visualization of full left ventricular compression may be seen after a location change, and combined with end tidal carbon dioxide values, gives indication for improved forward circulatory flow. Although it is not possible in all patients, doing so hastens provision of quality compressions that affect hemodynamic parameters without causing prolongations to the pulse check pause. Further research is needed to determine patient outcomes from both out-of-hospital and in-hospital cardiac arrest when cardiopulmonary resuscitation is visually guided by focused echocardiography.


Engineering DN hydrogels from regenerated silk fibroin and poly(N-vinylcaprolactam).
The development of novel hydrogels that possess adequate elasticity and toughness to withstand mechanically active environments, along with being biocompatible, remains a significant challenge in the design of materials for tissue engineering applications. In this study, a family of regenerated silk fibroin (RSF) based double network (DN) hydrogels were fabricated for the first time using a rapid one-pot method. The DN hydrogels combine the rigid covalently crosslinked RSF with the softer poly(N-vinylcaprolactam) (PVCL) through strong physical interactions. The formation of these DN hydrogels resulted in an improvement of the water uptake capacity, elasticity and toughness compared to the individual RSF hydrogel. The elasticity of the RSF/PVCL DN hydrogels was closer to that of native cartilage, which makes them promising materials for cartilage regeneration applications. An in vitro study on adhesion, proliferation and differentiation of a mouse pre-chondrocyte cell line (ATDC5) conducted using microscopic analysis, a cell proliferation assay and RT-PCR confirmed the cells cultured on the less stiff hydrogels demonstrated the most favourable chondrogenic response. Thus, this study demonstrates the potential of RSF-based hybrid hydrogels for cartilage tissue engineering applications.


Ethics as attention to context: recommendations for the ethics of artificial intelligence.
This article shows that current ethics guidance documents and initiatives for artificial intelligence (AI) tend to be dominated by a principled approach to ethics. Although this brings value to the field, it also entails some risks, especially in relation to the abstraction of this form of ethics that makes it poorly equipped to engage with and address deep socio-political issues and the material impacts of AI. This is particularly problematic considering the risk for AI to further entrench already existing social inequalities and injustices and contribute to environmental damage. To respond to this challenge posed by AI ethics today, this article proposes to complement the existing principled approach with an approach to ethics as attention to context and relations. It does so by drawing from alternative ethical theories to the dominant principled one, especially the ethics of care or other feminist approaches to ethics. Related to this, it encourages the inclusion of social sciences and humanities in the development, deployment and use of AI, as well as in AI ethics discussions and initiatives. This article presents this proposal for an ethics as attention to context and formulates a series of practical recommendations to implement this proposal concretely.


Dentists knowledge of lipid treatment of local anaesthetic systemic toxicity.
: Local anesthetics (LAs) are in widespread use by dental practitioners, and erroneous administration, such as intravenously or exceeding the maximum dose, can cause the life-threatening condition of local anesthetic systemic toxicity (LAST). The objective of the present study was evaluate the ability of dentists to recognize signs of LAST and quantify how often they have used lipids to treat LAST in dentistry patients. The study administered 600 questionnaires that asked about the frequency with which dentists encountered LAST and the symptoms of LAST and its treatment, especially with lipids. The results showed that 520 (86.66%) respondents had never seen LAST, and 404 (67.3%) had no idea about lipid treatment. In addition, 128 (21.3%) had heard about lipid treatment but had inadequate knowledge of it and 59 (9.8%) had read an article about lipid treatment, but only 9 (1.5%) knew how to use lipid treatment. Finally, 80 (13.33%) participants had seen LAST but had used a treatment other than lipids. Dentists and all facilities using LA must be aware of LAST, and knowledge of lipid treatment must be increased by education. Twenty percent lipid solutions must be kept handy in their offices by dentists.


Child- and caregiver-reported problems and concerns in using asthma medications.
The purpose of the study was to (a) describe the types of medication problems/concerns that asthmatic children and their caregivers reported and (b) examine the association between child and caregiver demographic and sociocultural characteristics and reported asthma medication problems/concerns. Children ages 8 through 16 with mild, moderate, or severe persistent asthma and their caregivers were recruited at five pediatric practices in nonurban areas of North Carolina. Children were interviewed and caregivers completed questionnaires after their child's medical visits about reported problems/concerns in using asthma medications. Multivariate logistic regression was used to analyze the data. Three hundred and twenty children were recruited. Eighty-seven percent of the children reported a problem or concern in using their asthma medications. Approximately 40% of children reported side effects and a similar percent stated that it was hard to understand the directions on their medicines; in addition 60% reported that it was hard to remember when to take their medicines. Females and non-White children were significantly more likely to report they were not sure how to use an inhaler than males and White children. Younger and non-White children were significantly more likely to report it was hard to understand the directions on their medicines than older and White children. Caregivers were most likely to report that their children were bothered a little or a lot by side effects (31%) and a similar percent (29%) were not sure their children were using their inhalers properly. Caregivers without Medicaid were significantly more likely to report difficulty paying for the asthma medications. Medication side effects are a significant problem area for both children and their caregivers, and inhaler skill-based training is particularly needed for non-White children. Health care providers should discuss with children and their caregivers the types of problems/concerns that children may have when using their asthma medications.


Denoising array-based comparative genomic hybridization data using wavelets.
Array-based comparative genomic hybridization (array-CGH) provides a high-throughput, high-resolution method to measure relative changes in DNA copy number simultaneously at thousands of genomic loci. Typically, these measurements are reported and displayed linearly on chromosome maps, and gains and losses are detected as deviations from normal diploid cells. We propose that one may consider denoising the data to uncover the true copy number changes before drawing inferences on the patterns of aberrations in the samples. Nonparametric techniques are particularly suitable for data denoising as they do not impose a parametric model in finding structures in the data. In this paper, we employ wavelets to denoise the data as wavelets have sound theoretical properties and a fast computational algorithm, and are particularly well suited for handling the abrupt changes seen in array-CGH data. A simulation study shows that denoising data prior to testing can achieve greater power in detecting the aberrant spot than using the raw data without denoising. Finally, we illustrate the method on two array-CGH data sets.


The Impact of Workers' Compensation on Patient-Reported Outcomes Measurement Information System Upper Extremity and Legacy Outcome Measures in Patients Undergoing Arthroscopic Rotator Cuff Repair.
To examine the preoperative performance of the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE) Computer Adaptive Test (CAT) with respect to legacy scores in patients receiving rotator cuff repair (RCR). In addition, to define the impact of Workers' Compensation (WC) status on both performance and floor and ceiling effects. The PROMIS UE CAT was administered preoperatively alongside legacy patient-reported outcome measures (PROMs) to patients undergoing isolated arthroscopic RCR from November 2017 to September 2018. Performance was assessed using Spearman correlation coefficients, and floor and ceiling effects were examined. One hundred twenty-two patients (WC, n = 32; non-WC, n = 90; 62.3% male, 53.6 ± 11.5 years) were included. PROMs assessing physical function (r = 0.41-0.77) correlated more strongly to the PROMIS UE CAT than did multidomain or mental health PROMs (r = 0.25-0.61). In WC patients, the PROMIS UE CAT demonstrated diminished correlative strength relative to shoulder function PROMs. WC patients also demonstrated relative floor effects for Single Assessment Numerical Evaluation (SANE; 18.8%) and Constant-Murley (15.6%) and relative ceiling effects for the Brief Resilience Scale (53.1%), Short Form 12 Mental Component Score (50%), and Veterans Rand 12 Mental Component Score (53.1%) and were more likely to report the minimum SANE score (P < .01) and the maximum Brief Resilience Scale score (P < .01). No absolute or relative floor/ceiling effects for the PROMIS UE CAT were found. Compared with a non-WC cohort, WC patients have significantly lower preoperative PROMIS UE CAT scores, are more likely to report the absolute minimum and maximum scores for various PROMs, and demonstrated relative floor and ceiling effects for PROMs assessing mental health. The absence of significant floor/ceiling effects for the PROMIS UE CAT may suggest improved outcome discrimination and may support the adoption of PROMIS UE for the assessment of functional status in WC patients with rotator cuff pathology. Level III, retrospective comparative trial.


Twenty Important Research Questions in Microbial Exposure and Social Equity.
Social and political policy, human activities, and environmental change affect the ways in which microbial communities assemble and interact with people. These factors determine how different social groups are exposed to beneficial and/or harmful microorganisms, meaning microbial exposure has an important socioecological justice context. Therefore, greater consideration of microbial exposure and social equity in research, planning, and policy is imperative. Here, we identify 20 research questions considered fundamentally important to promoting equitable exposure to beneficial microorganisms, along with safeguarding resilient societies and ecosystems. The 20 research questions we identified span seven broad themes, including the following: (i) sociocultural interactions; (ii) Indigenous community health and well-being; (iii) humans, urban ecosystems, and environmental processes; (iv) human psychology and mental health; (v) microbiomes and infectious diseases; (vi) human health and food security; and (vii) microbiome-related planning, policy, and outreach. Our goal was to summarize this growing field and to stimulate impactful research avenues while providing focus for funders and policymakers.


The nature of mind wandering during reading varies with the cognitive control demands of the reading strategy.
Prior studies of mind wandering find the default network active during mind wandering, but these studies have yielded mixed results concerning the role of cognitive control brain regions during mind wandering. Mind wandering often interferes with reading comprehension, and prior neuroimaging studies of discourse comprehension and strategic reading comprehension have shown that there are at least two networks of brain regions that support strategic discourse comprehension: a domain-general control network and a network of regions supporting coherence-building comprehension processes. The present study was designed to further examine the neural correlates of mind wandering by examining mind wandering during strategic reading comprehension. Participants provided ratings of mind wandering frequency that were used to investigate interactions between the strategy being performed and brain regions whose activation was modulated by wind wandering. The results support prior findings showing that cognitive control regions are at times more active during mind wandering than during a task with low control demands, such as rereading. This result provides an initial examination of the neural correlates of mind wandering during discourse comprehension and shows that the processes being engaged by the primary task need to be considered when studying mind wandering. The results also replicate, in a different learning domain, prior findings of key brain areas associated with different reading strategies.


Papillary endothelial hyperplasia in association with vascular malformation of the hand.
Vascular malformations are uncommonly encountered in the hand. This case report involves the unique case of a rapidly enlarging mass associated with a known vascular malformation. Final pathology revealed dense reactive fibrous tissue, with prominent blood vessels, consistent with a venous malformation and associated papillary endothelial hyperplasia. The intraoperative finding of two separately identifiable masses, one fibrotic and one vascular, has not previously been reported.


Tuning Rashba-Dresselhaus effect with ferroelectric polarization at asymmetric heterostructural interface.
The spin-orbit interaction (SOI) plays an essential role in materials properties, and controlling its intensity has great potential in the design of materials. In this work, asymmetric [(La0.7Sr0.3MnO3)8/(BaTiO3)t/(SrTiO3)2]8 superlattices were fabricated on (001) SrTiO3 substrate with SrO or TiO2 termination, labelled as SrO-SL and TiO2-SL, respectively. The in-plane angular magnetoresistance of the superlattices shows a combination of two- and four-fold symmetry components. The coefficient of two-fold symmetry component has opposite sign with current I along [100] and [110] directions for TiO2-SL, while it has the same sign for SrO-SL. Detailed study shows that the asymmetric cation inter-mixing and ferroelectricity-modulated electronic charge transfer induce asymmetric electronic potential for SrO-SL with dominating Rashba SOI, and symmetric electronic potential for TiO2-SL with dominating Dresselhaus SOI induced by BaTiO3. This work shows that the Rashba and Dresselhaus SOIs are sensitive to the ferroelectric polarization in the asymmetric structure.


The office laboratory director's guide.
More than 90% of primary care physicians have access to an office laboratory. These physicians serve as the director of their laboratory services and are legally responsible for test results. This responsibility has become a greater challenge as more sophisticated laboratory testing is available for office use. Yet clinicians find few reliable sources to help them face these changes. This article is intended to serve as a guide for the clinician facing the new responsibilities as laboratory director.


New onset epilepsy following unintentional durotomy in a patient on anti-psychiatric medication.
We would like to present a rare case report describing a case in which new-onset tonic-clonic seizures occurred following an unintentional durotomy during lumbar discectomy and decompression. Unintentional durotomy is a frequent complication of spinal surgical procedures, with a rate as high as 17%. To our knowledge a case of new onset epilepsy has never been reported in the literature. Although dural tears during surgery and CSF hypovolaemia are thought to be the main contributing factors, one postulates on the effects of anti-psychiatric medication with epileptogenic properties. Amisulpride and Olanzapine can lower seizure threshold and should be used with caution in patients previously diagnosed with epilepsy. However manufacturers do not state that in cases where the seizure threshold is already lowered by CSF hypotension, new onset epilepsy might be commoner. Finally, strong caution and aggressive post-operative monitoring is advised for patients with CSF hypotension in combination with possible epileptogenic medication.


Temperature changes in the pulp chamber and bleaching gel during tooth bleaching assisted by diode laser (445 nm) using different power settings.
The aim of this in vitro study was to investigate the safety of using blue diode laser (445 nm) for tooth bleaching with regard to intrapulpal temperature increase operating at different average power and time settings. Fifty human mandibular incisors (n = 10) were used for evaluating temperature rise inside the pulp chamber and in the bleaching gel during laser-assisted tooth bleaching. The change in temperature was recorded using K thermocouples for the five experimental groups (without laser, 0.5, 1, 1.5 and 2 W) at each point of time (0, 10, 20, 30, 40, 50 and 60 s). As the average power of the diode laser increases, the temperature inside the pulp chamber also increases and that of the bleaching gel was significantly higher in all the experimental groups (p < 0.05). However, the intrapulpal temperature rise was below the threshold for irreversible thermal damage of the pulp (5.6 °C). Average power of a diode laser (445 nm) ranging between 0.5-2 W and irradiation time between 10-60 s should be considered safe regarding the pulp health when a red-colored bleaching gel is used. Clinical studies should confirm the safety and effectiveness of such tooth bleaching treatments. The outcomes of the present study could be a useful guide for dental clinicians, who utilize diode lasers (445 nm) for in-office tooth bleaching treatments in order to select appropriate power parameters and duration of laser irradiation without jeopardizing the safety of the pulp.


N-terminal acetylation of cellular proteins creates specific degradation signals.
The retained N-terminal methionine (Met) residue of a nascent protein is often N-terminally acetylated (Nt-acetylated). Removal of N-terminal Met by Met-aminopeptidases frequently leads to Nt-acetylation of the resulting N-terminal alanine (Ala), valine (Val), serine (Ser), threonine (Thr), and cysteine (Cys) residues. Although a majority of eukaryotic proteins (for example, more than 80% of human proteins) are cotranslationally Nt-acetylated, the function of this extensively studied modification is largely unknown. Using the yeast Saccharomyces cerevisiae, we found that the Nt-acetylated Met residue could act as a degradation signal (degron), targeted by the Doa10 ubiquitin ligase. Moreover, Doa10 also recognized the Nt-acetylated Ala, Val, Ser, Thr, and Cys residues. Several examined proteins of diverse functions contained these N-terminal degrons, termed AcN-degrons, which are a prevalent class of degradation signals in cellular proteins.


Normal organ weights, serum chemistry, hematology, and cecal and nasopharyngeal bacterial cultures in the gray short-tailed opossum (Monodelphis domestica).
Gray short-tailed opossums (Monodelphis domestica) currently are used in genetic, developmental, oncology, and neurologic research. Little is known about their natural flora or potential for pathogenic infectious disease. The present study aims to improve existing comparative normal blood and organ weight values available to researchers and to describe flora of clinically normal M. domestica to obtain an understanding of potential pathogenic flora in clinically abnormal animals. For evaluation of serum hematology and serum chemistry, clinically normal animals were assigned to 1 of 6 groups stratified by age (younger than 1 y, 1 to 2 y, and 2 to 3 y) and sex. Hemoglobin and phosphorus levels were higher in male than female opossums, whereas monocyte and eosinophil counts were greater in females than males. Hemoglobin concentration decreased with increasing age. The youngest group had significantly higher levels of serum alkaline phosphatase and lower serum protein levels compared with older age groups. Liver and kidney weights of adult animals (1 to 3 y) were greater in female than male opossums. The predominant nasopharyngeal flora in 20 clinically normal animals from the 2- to 3-y-old group were Streptococcus viridans, Escherichia coli, and coagulase-negative Staphylococcus spp.; predominant cecal organisms were Escherichia coli and Citrobacter spp. The availability of reference hematologic values and flora for Monodelphis domestica will aid researchers in comparisons and analysis of experimental data and in diagnosis and evaluation of potential pathogens in clinically ill animals.


Screen Media Exposure and Obesity in Children and Adolescents.
Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children's preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context.


Spacing-adjustable multi-wavelength source from a stimulated Brillouin scattering assisted erbium-doped fiber laser.
We demonstrate room-temperature operation of a spacing-adjustable multi-wavelength erbium-doped fiber laser using stimulated Brillouin scattering. With the use of an intra-cavity birefringent loop mirror filter, the laser output wavelengths can be well defined without applying an external Brillouin pump. By adjusting the comb spacing of the filter, a wide range of mode spacings can be obtained to support the oscillations of up to 49 output wavelengths.


Indications and patterns of use of benzodiazepines and opioids in severe interstitial lung disease: a population-based longitudinal study.
Despite evidence that opioids might relieve chronic breathlessness, physicians may still be reluctant to prescribe them due to safety concerns. By contrast, benzodiazepine (BDZ) prescribing often seeks to reduce chronic breathlessness despite no evidence of net benefit. Prescribing patterns and indications for these medications in severe interstitial lung disease (ILD) are unknown. Here, our objective was to evaluate the indications, medications and temporal patterns of BDZ and opioid prescriptions in people with oxygen-dependent ILD. This was an observational, population-based, longitudinal study of adults starting long-term oxygen therapy (LTOT) for ILD between 2005 and 2014 in the Swedish National Registry for Respiratory Failure (Swedevox). People dispensed BDZs (n=2000) and opioids (n=2000) from 6 months before start of LTOT throughout follow-up (first of death or study end) were analysed. Of 1635 included patients, 651 (39.8%) received BDZs and 710 (43.4%) received opioids during the study period; 373 (22.8%) patients received both. The most frequently prescribed BDZs and opioids were oxazepam (85.6%) and oxycodone (28.7%), respectively. Indications for breathlessness were uncommon for BDZs (1.4%) and opioids (6.4%). During the last year of life, opioid indications for breathlessness increased from 2.5% (12-10 months before death) to 10.2% in the last 3 months of life (p=0.048). In oxygen-dependent ILD, opioids are rarely prescribed for breathlessness even in the last months of life, when chronic breathlessness often increases in prevalence and intensity.


Effect of Behavioral Therapy With In-Clinic or Telephone Group Visits vs In-Clinic Individual Visits on Weight Loss Among Patients With Obesity in Rural Clinical Practice: A Randomized Clinical Trial.
Rural populations have a higher prevalence of obesity and poor access to weight loss programs. Effective models for treating obesity in rural clinical practice are needed. To compare the Medicare Intensive Behavioral Therapy for Obesity fee-for-service model with 2 alternatives: in-clinic group visits based on a patient-centered medical home model and telephone-based group visits based on a disease management model. Cluster randomized trial conducted in 36 primary care practices in the rural Midwestern US. Inclusion criteria included age 20 to 75 years and body mass index of 30 to 45. Participants were enrolled from February 2016 to October 2017. Final follow-up occurred in December 2019. All participants received a lifestyle intervention focused on diet, physical activity, and behavior change strategies. In the fee-for-service intervention (n = 473), practice-employed clinicians provided 15-minute in-clinic individual visits at a frequency similar to that reimbursed by Medicare (weekly for 1 month, biweekly for 5 months, and monthly thereafter). In the in-clinic group intervention (n = 468), practice-employed clinicians delivered group visits that were weekly for 3 months, biweekly for 3 months, and monthly thereafter. In the telephone group intervention (n = 466), patients received the same intervention as the in-clinic group intervention, but sessions were delivered remotely via conference calls by centralized staff. The primary outcome was weight change at 24 months. A minimum clinically important difference was defined as 2.75 kg. Among 1407 participants (mean age, 54.7 [SD, 11.8] years; baseline body mass index, 36.7 [SD, 4.0]; 1081 [77%] women), 1220 (87%) completed the trial. Mean weight loss at 24 months was -4.4 kg (95% CI, -5.5 to -3.4 kg) in the in-clinic group intervention, -3.9 kg (95% CI, -5.0 to -2.9 kg) in the telephone group intervention, and -2.6 kg (95% CI, -3.6 to -1.5 kg) in the in-clinic individual intervention. Compared with the in-clinic individual intervention, the mean difference in weight change was -1.9 kg (97.5% CI, -3.5 to -0.2 kg; P = .01) for the in-clinic group intervention and -1.4 kg (97.5% CI, -3.0 to 0.3 kg; P = .06) for the telephone group intervention. Among patients with obesity in rural primary care clinics, in-clinic group visits but not telephone-based group visits, compared with in-clinic individual visits, resulted in statistically significantly greater weight loss at 24 months. However, the differences were small in magnitude and of uncertain clinical importance. ClinicalTrials.gov Identifier: NCT02456636.


Kirschner wire reconstruction of medial and lateral column periosteal hinge in the treatment of multidirectionally unstable supracondylar fracture of the humerus in children.
To compare the clinical effect of reconstruction of internal and lateral column periosteal hinge-assisted treatment with Kirschner wire and internal fixation with Kirschner wire in the treatment of multidirectional unstable supracondylar fractures of humerus in children. A retrospective cohort study was conducted to analyze the clinical data of 48 patients (31 male, 17 female; mean age: 6.7 ± 2.4 years old) with multidirectionally unstable supracondylar fractures of the humerus treated in our Hospital from August 2020 to August 2022. Twenty-five cases were treated with Kirschner wire reconstruction of the internal and lateral column periosteal hinge assisted by closed reduction and Kirschner wire internal fixation (study group). Twenty-three cases were treated with closed reduction and Kirschner wire internal fixation (control group). The operation time, intraoperative fluoroscopy times, percentage of patients who underwent open reduction after failure of closed reduction, fracture healing time, Baumann angle (BA), shaft-condylar angle (SCA), range of motion (ROM), and Flynn score of elbow at the last follow-up were compared between two groups. Complications such as infection and irritation of Kirschner wire tail were observed in two groups 2 months after the operation. All patients were followed up for 10-22 months ([13.85 ± 2.89] months). The average operation time of the control group was 82.1 min, which was significantly longer than that of the study group 32.3 min (P < 0.05). The number of intraoperative fluoroscopy (29.4 ± 9.2) in the control group was significantly higher than that in the study group (15.2 ± 6.3) (P < 0.05). The incision rate of the control group was 17% while that of the study group was 0 (P < 0.05). According to Flynn score, the excellent and good rate of the elbow joint in the control group was 86.9% (20/23). The excellent and good rate of the elbow joint in the study group was 92.0% (23/25) (P > 0.05). There was no significant difference in fracture healing time, BA, SCA, and ROM between the two groups (P > 0.05). No infection or Kirschner wire tail irritation occurred in the two groups during the 2-month follow-up. Reconstruction of internal and lateral periosteal hinges with Kirscher wire has similar effects to closed reduction and Kirschner wire fixation in the treatment of multidirectionally unstable supracondylar fractures of the humerus in children, but it can shorten the operation time and reduce intraoperative fluoroscopy times and incision rate.


Failure of adjuvant heparin to reduce myocardial ischemia in the early treatment of patients with unstable angina.
Although the efficacy of long-term administration of antithrombotic agents in unstable angina has been established, short-term effects on myocardial ischemia are unknown. A retrospective analysis was performed in 47 patients undergoing three-channel continuous ST segment monitoring as part of a multicenter trial using esmolol in unstable angina, in which 20 patients received a continuous heparin infusion during the initial assessment of chest pain. Concomitant medications included calcium channel blockers, beta-adrenergic blockers, nitrates, and aspirin in the majority of patients. Clinical variables between the heparin and no heparin groups were similar, except for fewer males and fewer total artery occlusions in the heparin group. No significant differences in the incidence or duration of ischemia were found in a 36 +/- 16 hour monitoring period. Forty percent of the heparin group had 35 episodes of ischemia with a mean of 11 +/- 10 minutes per episode and a total ischemic time of 48 +/- 39 minutes per patient with ischemia. Forty-four percent of the no heparin group had 47 episodes of ischemia with a mean of 13 +/- 13 minutes per episode and a total ischemic time of 58 +/- 47 minutes per patient with ischemia. Multiple linear regression analysis to adjust for intergroup differences did not alter the results. Eighty-five percent of all episodes were asymptomatic. Clinical events, such as episodes of chest pain, emergency coronary arteriography, or coronary revascularization, were also similar between groups. Thus the short-term administration of heparin did not alter the incidence or duration of ischemia in patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)


[Conformational states of pancreatic lipase].
Spin-label method was applied to the studies of conformation properties of pancreatic lipase. Spin-labelled derivatives of the enzyme in SH- and NH2-groups were obtained. ESR-spectra of both samples belong to the immobilized type, in the first case the ESR-spectrum corresponding to strong immobilization of the spin-label, and in the second--to the average one. In both cases the rotation correlation time of the enzyme molecule was measured. The time proved the same independent of the site of the label attachment; it corresponded to the rotation of macromolecule with molecular weight 50000. This fact points to the absence of both intramolecular flexibility of the enzyme molecule and of the association of lipase molecules in solution. It has been shown that introduction of substrates and inhibitors of the enzyme and the interface as well, induces no changes in the ESR spectra, which points to the absence of local conformation changes of protein near the spin-labels introduced.


[Evaluation of the nutritional state in patients with congenital cardiopathy].
Several anthropometrical, immunological and biochemical parameters have been utilized for the detection of chronic undernourishment and inflammation. The present work proposes a comparative study between a control group and other of 24 cardiac patients, with the intention of valuating their nutritional and inflammatory state. We have used the index proposed by Ingenbleek (PINI = prognostic inflammatory and nutritional index) in which nutritional scoreboards and biochemical inflammatories correlate. We find some statistically significant differences between cases and controls, both with regard to the value of the PINI, and with regard to each of this variables. In the same way, we do not find any important correlations within each group among the nutritional biochemical, inflammatory and anthropometrical parameters. The clinical impression shows that the classification by groups of risk obtained according to the value of the PINI is very near to reality. We consider that the PINI index is useful as a predictive and evolutive parameter, and it can be used in children with a chronic illness.


Variation in the ontogenetic allometry of horn length in bovids along a body mass continuum.
Allometric relationships describe the proportional covariation between morphological, physiological, or life-history traits and the size of the organisms. Evolutionary allometries estimated among species are expected to result from species differences in ontogenetic allometry, but it remains uncertain whether ontogenetic allometric parameters and particularly the ontogenetic slope can evolve. In bovids, the nonlinear evolutionary allometry between horn length and body mass in males suggests systematic changes in ontogenetic allometry with increasing species body mass. To test this hypothesis, we estimated ontogenetic allometry between horn length and body mass in males and females of 19 bovid species ranging from ca. 5 to 700 kg. Ontogenetic allometry changed systematically with species body mass from steep ontogenetic allometries over a short period of horn growth in small species to shallow allometry with the growth period of horns matching the period of body mass increase in the largest species. Intermediate species displayed steep allometry over long period of horn growth. Females tended to display shallower ontogenetic allometry with longer horn growth compared to males, but these differences were weak and highly variable. These findings show that ontogenetic allometric slope evolved across species possibly as a response to size-related changes in the selection pressures acting on horn length and body mass.


Intein-based Design Expands Diversity of Selenocysteine Reporters.
The presence of selenocysteine in a protein confers many unique properties that make the production of recombinant selenoproteins desirable. Targeted incorporation of Sec into a protein of choice is possible by exploiting elongation factor Tu-dependent reassignment of UAG codons, a strategy that has been continuously improved by a variety of means. Improving selenoprotein yield by directed evolution requires selection and screening markers that are titratable, have a high dynamic range, enable high-throughput screening, and can discriminate against nonspecific UAG decoding. Current screening techniques are limited to a handful of reporters where a cysteine (Cys) or Sec residue normally affords activity. Unfortunately, these existing Cys/Sec-dependent reporters lack the dynamic range of more ubiquitous reporters or suffer from other limitations. Here we present a versatile strategy to adapt established reporters for specific Sec incorporation. Inteins are intervening polypeptides that splice themselves from the precursor protein in an autocatalytic splicing reaction. Using an intein that relies exclusively on Sec for splicing, we show that this intein cassette can be placed in-frame within selection and screening markers, affording reporter activity only upon successful intein splicing. Furthermore, because functional splicing can only occur when a catalytic Sec is present, the amount of synthesized reporter directly measures UAG-directed Sec incorporation. Importantly, we show that results obtained with intein-containing reporters are comparable to the Sec incorporation levels determined by mass spectrometry of isolated recombinant selenoproteins. This result validates the use of these intein-containing reporters to screen for evolved components of a translation system yielding increased selenoprotein amounts.


Anomalous renal artery is potential cause of resistant hypertension in a 53 year old patient: case report.
Drug-resistant hypertension can be attributable to secondary hypertension and other causes. Anomalous renal artery is uncommon but can be a potential cause of resistant hypertension. We highlight the challenges in management of resistant hypertension and describe its unusual association with renal artery anomaly in 53 years old man who was referred to our nephrology clinic from a peripheral general hospital on account of poorly controlled hypertension. At presentation, BP was severely elevated at 208/100mmHg but no remarkable findings in the rest of the examination. Several investigations done including abdominal ultrasound scan and Computerised Tomography (CT) Renal angiogram revealed a Left anomalous renal artery. Patient declined all suggested urologic interventions and he was then managed conservatively. We found that anomalous renal arteries can be a potential cause of resistant hypertension. We therefore recommend ultrasound scan of the abdomen as a screening modality due to its being non-invasive.


Goodpasture antigen-binding protein is a soluble exportable protein that interacts with type IV collagen. Identification of novel membrane-bound isoforms.
Goodpasture-antigen binding protein (GPBP) is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Various studies have questioned these findings and proposed that GPBP serves as transporter of ceramide between the endoplasmic reticulum and the Golgi apparatus. Here we show that cells expressed at least two GPBP isoforms resulting from canonical (77-kDa) and noncanonical (91-kDa) mRNA translation initiation. The 77-kDa polypeptide interacted with type IV collagen and localized as a soluble form in the extracellular compartment. The 91-kDa polypeptide and its derived 120-kDa polypeptide associated with cellular membranes and regulated the extracellular levels of the 77-kDa polypeptide. A short motif containing two phenylalanines in an acidic tract and the 26-residue Ser-rich region were required for efficient 77-kDa polypeptide secretion. Removal of the 26-residue Ser-rich region by alternative exon splicing rendered the protein cytosolic and sensitive to the reduction of sphingomyelin cellular levels. These and previous data implicate GPBPs in a multicompartmental program for protein secretion (i.e. type IV collagen) that includes: 1) phosphorylation and regulation of protein molecular/supramolecular organization and 2) interorganelle ceramide trafficking and regulation of protein cargo transport to the plasma membrane.


Biomechanical properties of the superior sagittal sinus-bridging vein complex.
Finite element models (FEM) of the head are frequently used to simulate traumatic brain injury, leading to a better understanding of brain injury tolerance. The strength of a FEM of the head is dependent on the use of correct material characteristics, experimentally derived for each intracranial tissue, including parasagittal bridging veins (BV). These veins are prone to rupture in their subdural portion upon head impact, giving rise to an acute subdural hematoma (ASDH). The junction of these veins to the superior sagittal sinus (SSS) has been described as an area with distinct vein wall architecture. To understand the biomechanical characteristics of acute subdural hematoma, we studied the SSS-BV complex by loading it to failure in a tensile test. 37 BVs from 9 fresh cadavers were dissected, leaving small strips of SSS attached to the veins. The units were clamped on the SSS and the cortical end of the BV. Strain rates ranged from 0.1-3.8 s(-1). From force-time and strain-time histories, we calculated ultimate strain (epsilon(U)), ultimate stress (sigma(U)), yield strain (epsilon(Y)), yield stress(sigma(Y)) and Young's modulus (E). A mixed-model multivariate analysis of variance (MANOVA) was used to study correlations and strain rate sensitivity of these parameters. We found no strain rate sensitivity. The biomechanical response of the SSS-BV unit in this study was found to be stiffer than reported biomechanical behavior of bridging veins. We conclude that the SSS-BV junction plays an important role in bridging vein rupture, and warrants further investigation to provide FEM with correct material properties for bridging veins.


[The range of congenital malformations associated with cleft lip and palate].
The congenital malformations associated to cleft lip and cleft palate cover a wide range of pathologies with incidence and acuteness that vary according to the authors. In the 284 patients followed and/or referred to the Cleft Consultation of Dona Estefânia Hospital, 78 had associated malformations (27.5%). In three cases there was consanguinity in parents. A familial incidence of cleft and/or other congenital malformations was found in 13 and 10 patients respectively. Thirty patients had malformative syndromes. In the remaining 48, 127 associated congenital malformations (M.C.A.) were identified, in accordance with the Smith criteria, 81 major and 46 minor. The most frequent associated malformations are those of the face (25.9%) and of the cardiovascular system (16.5%). The multiple anomalies (of various systems) are the most frequent (47.9%), followed by the isolated anomaly (29.1%) and the multiple of one system (22.9%). In what concerns the association of syndromes with the type of cleft, primary, secondary or total palate, those of the secondary were the most frequent, particularly that of the Pierre Robin sequence (S.P.R.)--19 in 36 secondary cleft palate.


Colonic delivery of compression coated nisin tablets using pectin/HPMC polymer mixture.
Nisin containing pectin/HPMC compression coated tablets were prepared and their in vitro behavior tested for colonic delivery. Nisin is a 34-amino-acid residue long, heat stable peptide belonging to the group A lantibiotics with wide antimicrobial activity against Gram-positive bacteria. The invention can be useful for treating colonic infectious diseases such as by Clostridium difficile, and also by colonization of vancomycin-resistant enterococci. In this study, each 100mg core tablet of nisin was compression coated with 100% pectin, 90% pectin-10% HPMC, 85% pectin-15% HPMC, 80% pectin-20% HPMC, 75% pectin-25% HPMC, 100% HPMC at a coat weight of 400mg. The concentration and the activity of nisin were quantified using Well Diffusion Agar Assay. Drug release studies were carried out in pH 3.3 buffer solution. System degradation/erosion experiments were carried out in pH 1.2, 3.3, and 6.8 buffers using a pectinolytic enzyme. The biological activity and NMR studies were performed to assess the stability of nisin during the processing and after the in vitro tests. It was found that pectin alone was not sufficient to protect the nisin containing core tablets. At the end of the 6h 40% degradation was observed for 100% pectin tablets. HPMC addition required to control the solubility of pectin, a 5% increase in HPMC ratio in pectin/HPMC mixture provided a 2-h lag time for nisin release. Eighty percent pectin-20% HPMC appeared to be an optimum combination for further evaluation. Tablets maintained their integrity during the 6-h dissolution test, approximating the colon arrival times. Nisin was found to be active/stable during processing and after in vitro tests. Effect of polymer hydration on pectin degradation was found to be crucial for the enzyme activity. Sufficiently hydrated pectin degraded faster. The pectin/HPMC envelope was found to be a good delivery system for nisin to be delivered to the colon.


Cross-national comparison of the link between socioeconomic status and emotional and behavioral problems in youths.
In previous longitudinal studies in the US, lower socioeconomic status (SES) was associated with more emotional and behavioral problems. It remains unclear whether these findings can be generalized outside the US, as different countries vary in their health care systems and prevention of psychopathology in youth. Therefore, we studied the same associations in a comparable sample in The Netherlands and directly tested for differences between the US and The Netherlands. The US (N=833) and Dutch (N=708) population samples were followed-up for 9 years. Age at baseline ranged from 8 to 16 years. Parents filled out behavior checklists. Analyses revealed very few differences between the two countries. In both countries, SES predicted syndrome scores and cumulative prevalence rates for internalizing and externalizing problems (withdrawn and aggressive behavior) and for thought and attention Problems. The SES gradient in syndrome scores was stable over time. Only for withdrawn behavior, the gradient was larger in young adulthood. Although the health care systems differ between the US and The Netherlands, the socioeconomic disparities in emotional and behavioral problems were similar.


No ordinary mainstream illness: how HIV doctors perceive the virus.
Research has shown that social representations of HIV can constitute barriers to health workers' willingness to provide HIV care. Considering a growing shortage in the HIV primary workforce in Western countries, we examine how HIV is perceived today by doctors involved in its care. In 1989 Sontag predicted that once the virus became better understood and treatable, the dehumanizing meanings that defined the early epidemic would vanish and HIV would turn into an ordinary illness. However, research shows that HIV still carries stigma, including in the health care sector. Drawing on qualitative interviews, we found that HIV doctors in Australia perceived HIV as a far-from-ordinary chronic illness because of its extraordinary history and its capacity to extend in multiple clinical and social directions. These rarely explored perspectives can contribute to the social reframing of HIV and to strategies to build a dedicated HIV workforce in Australia and elsewhere.


[In vivo experimental modelling of the infectious process caused by stable L forms of the causative agent of typhoid].
To simulate the infectious process and to study the persistence of L-forms, rabbits and guinea pigs were infected with S. typhi stable L-forms. The materials presented in this work indicate that both subconjunctival and intraperitoneal infection led to the development of the clinically indistinct, but morphologically pronounced pathological process with characteristic localization and typical changes in the gastrointestinal tract. The typical features of the process were the generalized immunomorphological reaction of the lymphoid apparatus with the appearance of light-colored reticulomacrophagal elements, the signs of the activation of humoral and cell-mediated immunity and the formation of small epitheloidocellular granulomas. The results of the investigation indicate that the stable cultures of S. typhi L-forms are highly pathogenic and capable of inducing the infectious process in experimental animals.


Role of gallbladder mucin in pathophysiology of gallstones.
A critical step in the formation of cholesterol gallstones in nucleation (i.e., the formation of cholesterol monohydrate crystals from supersaturated bile). The rate of nucleation of cholesterol depends upon a critical balance between pronucleating and antinucleating factors in bile. Mucin, a high molecular weight glycoprotein secreted by the gallbladder and biliary duct epithelium, is a pronucleating agent in experimental and human gallstone disease. Gallbladder mucin shares with other epithelial mucins the ability to bind lipids and bile pigment. The hydrophobic binding sites in the polypeptide core of mucin may provide a favorable environment for nucleation of cholesterol monohydrate from supersaturated bile. In nearly all animal models of cholelithiasis, mucin hypersecretion is prominent. The stimulus for gallbladder mucin hypersecretion appears to be a component of lithogenic bile. Prostaglandins regulate mucin release in gallbladder epithelium in vitro and probably in vivo. In the cholesterol-fed prairie dog, blockage of mucin release with aspirin inhibits gallstone formation. These findings suggest that inhibition of mucin release may prevent cholesterol stone formation during high-risk periods or after dissolution therapy with bile salts.


Risk of post-thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study.
Risk factors for post-thrombotic syndrome (PTS) remain poorly understood. In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with the development of PTS. Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5-7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation. Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for ≤ 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval [CI] 1.10-2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13-3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14-3.00) [crude] and 1.88 (95% CI 1.15-3.07) [adjusted]. Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.


Phenotypes of gene disruptants in relation to a putative mitochondrial malate-citrate shuttle protein in citric acid-producing Aspergillus niger.
The mitochondrial citrate transport protein (CTP) functions as a malate-citrate shuttle catalyzing the exchange of citrate plus a proton for malate between mitochondria and cytosol across the inner mitochondrial membrane in higher eukaryotic organisms. In this study, for functional analysis, we cloned the gene encoding putative CTP (ctpA) of citric acid-producing Aspergillus niger WU-2223L. The gene ctpA encodes a polypeptide consisting 296 amino acids conserved active residues required for citrate transport function. Only in early-log phase, the ctpA disruptant DCTPA-1 showed growth delay, and the amount of citric acid produced by strain DCTPA-1 was smaller than that by parental strain WU-2223L. These results indicate that the CTPA affects growth and thereby citric acid metabolism of A. niger changes, especially in early-log phase, but not citric acid-producing period. This is the first report showing that disruption of ctpA causes changes of phenotypes in relation to citric acid production in A. niger.


Dreams that lie in tatters: the changing fortunes of nurses who left the British NHS to own and run residential homes for elderly people.
During the 1980s many nurses left the British National Health Service to own and run private residential care homes for elderly people. At the time, a public policy of guaranteed financial support for residents underpinned the rapid expansion in the sector and residential homes were considered as profitable low-risk business ventures. However, since the introduction of the 1990 National Health Service and Care in the Community Act, this automatic funding has been withdrawn and residential homes have had to compete amongst each other for a finite number of clients funded by limited local budgets. The withdrawal of guaranteed state support and the introduction of social care markets have had negative impacts on many residential home businesses. Indeed, many homes are facing financial difficulties. This paper considers the actions and attitudes of former nurse proprietors under the new conditions based on a three-stage survey in Devon, England. Proprietors are experiencing increased levels of stress and many are unhappy with their current work experiences. The paper concludes that although the small business private sector may seem attractive to nurses, any move into private sector ownership has an associated risk. Social policy conditions may change with concurrent consequences for businesses and business owners.


Nitrogen-use efficiency in maize (Zea mays L.): from 'omics' studies to metabolic modelling.
In this review, we will present the latest developments in systems biology with particular emphasis on improving nitrogen-use efficiency (NUE) in crops such as maize and demonstrating the application of metabolic models. The review highlights the importance of improving NUE in crops and provides an overview of the transcriptome, proteome, and metabolome datasets available, focusing on a comprehensive understanding of nitrogen regulation. 'Omics' data are hard to interpret in the absence of metabolic flux information within genome-scale models. These models, when integrated with 'omics' data, can serve as a basis for generating predictions that focus and guide further experimental studies. By simulating different nitrogen (N) conditions at a pseudo-steady state, the reactions affecting NUE and additional gene regulations can be determined. Such models thus provide a framework for improving our understanding of the metabolic processes underlying the more efficient use of N-based fertilizers.


[Three-dimensional model of the fibrin(ogen) molecule and fibrin fibril].
The paper deals with the three-dimensional model of fibrin(ogen) molecule and fibrin fibril, based on the electron microscopy data on fibrin(ogen) molecule and on fibrin fibril structure, data on symmetry of fibrinogen primary structure, on domain structure of molecule, on location of sites of polymerization and on the data on polymerization mechanism of fibrin.


Same-sex relationships in Yorùbá culture and orature.
It is widely believed that lesbianism and homosexuality are foreign concepts and colonial imports to Sub-Saharan Africa. This popular view is not unconnected with hegemonic heterosexual orientation of the society. The pitfall of heterosexual orientation, which hinges on politics of sexual representation, is worth an academic investigation. Therefore, this study seeks to close the analytical gap by examining Yorùbá oral literature, which is regarded as the repertoire of their traditional and cultural beliefs and nuances, to unravel the subject of lesbianism and homosexuality from a sociological approach. Drawing on interviews and oral literature, this article examines the vital ideas of lesbianism and gay culture among the Yorùbá people of southwestern Nigeria. This article argues that the preconceived obscenity of lesbianism and homosexuality among the Yorùbá hinges on the culture of silence within the cultural milieu of the people. The study concludes that the representation of lesbianism and gay in diverse oral literature, as the repertoire of people's experiences and worldview, rubberstamped its presence and practices in the Yorùbá society.


Silastic implant for reconstruction of pectus excavatum: an update.
Twenty-seven patients were operated on for pectus excavatum between 1985 and 1996 and had a custom-made subcutaneous Silastic implant inserted. We have reviewed their medical records to evaluate the clinical course, and used a questionnaire to assess the subjective outcome. There were no major surgical complications. Sixteen of the 27 patients reported improved appearance, and 11 would definitely recommend the operation to other patients under similar circumstances. Increased familiarity with the technique has led to implants with better size and shape, shorter hospital stay, and also to patients being more confident with the outcome. Augmentation with a custom-made Silastic implant is still a simple and straightforward way of concealing the deformity and alleviating the subjective discomfort in patients with pectus excavatum, whose cardiopulmonary function is within the normal range.


[Guidelines for periodontal diagnosis in Belgium].
Proper examination of patients is essential in assessing treatment needs. This includes at least a thorough anamnesis and clinical examination. As periodontal diseases are highly-prevalent in Belgium, every patient should be examined as such on a routine basis in general practice. After all, early detection of pathology avoids extensive periodontal therapy and favours tooth retention in the end, which is the ultimate goal. This manuscript offers the clinician, in particular the general practitioner, a number of guidelines in reference to periodontal diagnosis.


Cutaneous burn caused by radiofrequency ablation probe during shoulder arthroscopy.
It is common in shoulder surgery to perform an arthroscopic acromioplasty for patients with varying degrees of rotator cuff disease. One method for helping the surgeon stay oriented to the location of the arthroscopic instruments during this procedure is to place spinal needles into the subacromial space to demarcate bony landmarks. It is also common during arthroscopic partial acromioplasty to use an electrocautery device for hemostasis and tissue ablation. Although many complications of using an electrothermal device have been described, this is the first published report of a skin burn from direct contact of the device with the spinal needle used for demarcation during acromioplasty. We report this case to highlight the need to take precautions to prevent the metal needles used in arthroscopic surgery from overheating by contact with an ablation device.


Reactive arthritis or chronic infectious arthritis?
Microbes reach the synovial cavity either directly during bacteraemia or by transport within lymphoid cells or monocytes. This may stimulate the immune system excessively, triggering arthritis. Some forms of ReA correspond to slow infectious arthritis due to the persistence of microbes and some to an infection triggered arthritis linked to an extra-articular site of infection.


Displacement of cortisol from human heart by acute administration of a mineralocorticoid receptor antagonist.
Mineralocorticoid receptor (MR) antagonists have beneficial effects in patients with heart failure and myocardial infarction, often attributed to blocking aldosterone action in the myocardium. However, binding of aldosterone to MR requires local activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates cortisol to cortisone and thereby prevents receptor occupancy by cortisol. In vivo activity of 11β-HSD2 and potential occupancy of MR by cortisol in human heart have not been quantified. This study aimed to measure in vivo activity of 11β-HSD2 and to establish whether cortisol binds MR in human heart. Nine patients without heart failure undergoing diagnostic coronary angiography were infused to steady state with the stable isotope tracers 9,11,12,12-[(2)H]4-cortisol and 1,2-[(2)H]2-cortisone to quantify cortisol and cortisone production. Samples were obtained from the femoral artery and coronary sinus before and for 40 minutes after bolus iv administration of an MR antagonist, potassium canrenoate. Coronary sinus blood flow was measured by venography and Doppler flow wire. There was no detectable production of cortisol or cortisone across the myocardium. After potassium canrenoate administration, plasma aldosterone concentrations increased substantially but aldosterone was not detectably released from the myocardium. In contrast, plasma cortisol concentrations did not change in the systemic circulation but tissue-bound cortisol was released transiently from the myocardium after potassium canrenoate administration. Human cardiac 11β-HSD2 activity appears too low to inactivate cortisol to cortisone. Cortisol is displaced acutely from the myocardium by MR antagonists and may contribute to adverse MR activation in human heart.


Coexistence of three specialist aphids on common milkweed, Asclepias syriaca.
Coexistence of host-specific herbivores on plants is believed to be governed by interspecific interactions, but few empirical studies have systematically unraveled these dynamics. We investigated the role of several factors in promoting coexistence among the aphids Aphis nerii, Aphis asclepiadis, and Myzocallis asclepiadis that all specialize on common milkweed (Asclepias syriaca). Competitive exclusion is thought to occur when interspecific competition is stronger than intraspecific competition. Consequently, we investigated whether predators, mutualists, or resource quality affected the strength of intra- vs. interspecific competition among aphids in factorial manipulations of competition with exposure to predation, ants, and variable plant genotypes in three separate experiments. In the predation x competition experiment, predators reduced aphid per capita growth by 66%, but the strength of intra- and interspecific competition did not depend on predators. In the ants x competition experiment, ants reduced per capita growth of A. nerii and M. asclepiadis (neither of which were mutualists with ants) by approximately one-half. In so doing, ants ameliorated the negative effects of these competitors on ant-tended A. asclepiadis by two-thirds, representing a novel benefit of ant-aphid mutualism. Nevertheless, ants alone did not explain the persistence of competitively inferior A. asclepiadis as, even in the presence of ants, interspecific competition remained stronger than intraspecific competition. In the plant genotype x competition experiment, both A. asclepiadis and M. asclepiadis were competitively inferior to A. nerii, with the strength of interspecific competition exceeding that of intraspecific competition by 83% and 23%, respectively. Yet these effects differed among milkweed genotypes, and there were one or more plant genotypes for each aphid species where coexistence was predicted. A synthesis of our results shows that predators play little or no role in preferentially suppressing competitively dominant A. nerii. Nonetheless, A. asclepiadis benefits from ants, and A. asclepiadis and M. asclepiadis may escape competitive exclusion by A. nerii on select milkweed genotypes. Taken as a whole, the coexistence of three host-specific aphid species sharing the same resource was promoted by the dual action of ants as antagonists and mutualists and by genetic diversity in the plant population itself.


Glucocorticoids-All-Rounders Tackling the Versatile Players of the Immune System.
Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia.


A design study for an accelerator-based epithermal neutron beam for BNCT.
An achievable design concept for a boron neutron capture therapy (BNCT) facility, based on a high-current, low-energy proton accelerator, is described. Neutrons are produced within a thick natural lithium target, under bombardment from protons with an initial energy between 2.5 and 3.0 MeV. The proton current will be up to 10 mA. After gamma-ray filtering, the neutrons are partially moderated to epithermal energies within a heavy-water moderator, poisoned with 6Li to remove thermal neutrons. Monte Carlo modelling has been used to predict system performance in terms of neutron fluence rate and neutron and gamma-ray dose at the patient position. The relationship between the system performance and key parameters, such as proton energy, moderator depth and 6Li concentration, has been investigated. With a proton current of 10 mA, the facility is capable of providing a therapy beam with a useful neutron fluence rate of 10(9) cm-2 s-1 and a neutron dose per unit fluence of less than 6 x 10(-13) Gy cm2, with a gamma-ray contamination of the therapy beam of about 10(-13) Gy cm2.


Difference in the response of two hybrid stocks of mice to X-ray induction of chromosome aberrations in spermatogonial stem cells.
Ionizing radiation induces balanced reciprocal translocations in spermatogonial stem cells of mice. From cells carrying these rearrangements, which can be scored cytologically in the diakinesis-metaphase I stage, balanced normal, balanced translocated and unbalanced (duplication/deficiency) sperm can be produced. The relationship between expected (calculated from cytological data) and observed frequencies of embryonic lethality (presumably as a result of unbalanced sperm fertilizing the egg) following exposure of spermatogonial stem cells to X-rays was studied in two hybrid stocks. A marked difference in the incidence of induced embryonic lethality was found between the two stocks. Similarly, a difference in the cytological frequencies of translocations was also found, although smaller than that observed for embryonic lethality. Thus, it appears that the difference between the two stocks in the frequencies of embryonic lethality may be attributable both to processes occurring prior to metaphase I and to a difference in the rate of transmission of unbalanced chromosome constitutions.


Ultrasound-guided ophthalmic regional anesthesia.
Needle-based and cannula-based eye blocks are 'blind' techniques prone to rare but serious complications. Ultrasound, an established adjunct for peripheral nerve block, may be beneficial for ophthalmic anesthesia application. The present review details the evolution of ultrasound-guided eye blocks, outlines safety issues, and reviews recent studies and editorial opinions. Ultrasound-assisted ophthalmic regional anesthesia allows imaging of key structures such as the globe, orbit, and optic nerve. Recent findings reveal that needle path is not reliably predictable by clinical evaluation. Needle tips are frequently found to be intraconal, extraconal, or transfixed in the muscle cone independent of the intended type of block. In addition, contemporary human and animal studies confirm that real-time observation of local anesthetic spread inside of the muscle cone correlates directly with block success. Ultrasound-guided ophthalmic regional anesthesia is evolving beyond simple visualization of the anatomy. Recent research emphasizes the imprecision of needle tip location without ultrasound and the key role of imaging local anesthetic dispersion. There is ongoing debate in the literature regarding the utility of routine ultrasound for eye blocks.


The transcription factor Spalt and human homologue SALL4 induce cell invasion via the dMyc-JNK pathway in Drosophila.
Cancer cell metastasis is a leading cause of mortality in cancer patients. Therefore, revealing the molecular mechanism of cancer cell invasion is of great significance for the treatment of cancer. In human patients, the hyperactivity of transcription factor Spalt-like 4 (SALL4) is sufficient to induce malignant tumorigenesis and metastasis. Here, we found that when ectopically expressing the Drosophila homologue spalt (sal) or human SALL4 in Drosophila, epithelial cells delaminated basally with penetration of the basal lamina and degradation of the extracellular matrix, which are essential properties of cell invasion. Further assay found that sal/SALL4 promoted cell invasion via dMyc-JNK signaling. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway through suppressing matrix metalloprotease 1, or basket can achieve suppression of cell invasion. Moreover, expression of dMyc, a suppressor of JNK signaling, dramatically blocked cell invasion induced by sal/SALL4 in the wing disc. These findings reveal a conserved role of sal/SALL4 in invasive cell movement and link the crucial mediator of tumor invasion, the JNK pathway, to SALL4-mediated cancer progression.This article has an associated First Person interview with the first author of the paper.


Role of S100A8/A9 for Cytokine Secretion, Revealed in Neutrophils Derived from ER-Hoxb8 Progenitors.
S100A9, a Ca2+-binding protein, is tightly associated to neutrophil pro-inflammatory functions when forming a heterodimer with its S100A8 partner. Upon secretion into the extracellular environment, these proteins behave like damage-associated molecular pattern molecules, which actively participate in the amplification of the inflammation process by recruitment and activation of pro-inflammatory cells. Intracellular functions have also been attributed to the S100A8/A9 complex, notably its ability to regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. However, the complete functional spectrum of S100A8/A9 at the intracellular level is far from being understood. In this context, we here investigated the possibility that the absence of intracellular S100A8/A9 is involved in cytokine secretion. To overcome the difficulty of genetically modifying neutrophils, we used murine neutrophils derived from wild-type and S100A9-/- Hoxb8 immortalized myeloid progenitors. After confirming that differentiated Hoxb8 neutrophil-like cells are a suitable model to study neutrophil functions, our data show that absence of S100A8/A9 led to a dysregulation of cytokine secretion after lipopolysaccharide (LPS) stimulation. Furthermore, we demonstrate that S100A8/A9-induced cytokine secretion was regulated by the nuclear factor kappa B (NF-κB) pathway. These results were confirmed in human differentiated HL-60 cells, in which S100A9 was inhibited by shRNAs. Finally, our results indicate that the degranulation process could be involved in the regulation of cytokine secretion by S100A8/A9.


Behavioral Counseling Interventions to Prevent Sexually Transmitted Infections: US Preventive Services Task Force Recommendation Statement.
Approximately 20 million new cases of bacterial or viral sexually transmitted infections (STIs) occur each year in the US, and about one-half of these cases occur in persons aged 15 to 24 years. Rates of chlamydial, gonococcal, and syphilis infection continue to increase in all regions. Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others. Serious consequences of STIs include pelvic inflammatory disease, infertility, cancer, and AIDS. To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions for preventing STI acquisition. This recommendation statement applies to all sexually active adolescents and to adults at increased risk for STIs. The USPSTF concludes with moderate certainty that behavioral counseling interventions reduce the likelihood of acquiring STIs in sexually active adolescents and in adults at increased risk, including for example, those who have a current STI, do not use condoms, or have multiple partners, resulting in a moderate net benefit. The USPSTF recommends behavioral counseling for all sexually active adolescents and for adults at increased risk for STIs. (B recommendation).


Piecewise Mapping in HEVC Lossless Intra-Prediction Coding.
The lossless intra-prediction coding modality of the High Efficiency Video Coding standard provides high coding performance while allowing frame-by-frame basis access to the coded data. This is of interest in many professional applications, such as medical imaging, automotive vision, and digital preservation in libraries and archives. Various improvements to lossless intra-prediction coding have been proposed recently, most of them based on sample-wise prediction using differential pulse code modulation (DPCM). Other recent proposals aim at further reducing the energy of intra-predicted residual blocks. However, the energy reduction achieved is frequently minimal due to the difficulty of correctly predicting the sign and magnitude of residual values. In this paper, we pursue a novel approach to this energy-reduction problem using piecewise mapping (pwm) functions. In particular, we analyze the range of values in residual blocks and apply accordingly a pwm function to map specific residual values to unique lower values. We encode the appropriate parameters associated with the pwm functions at the encoder, so that the corresponding inverse pwm functions at the decoder can map values back to the same residual values. These residual values are then used to reconstruct the original signal. This mapping is, therefore, reversible and introduces no losses. We evaluate the pwm functions on 4 × 4 residual blocks computed after DPCM-based prediction for lossless coding of a variety of camera-captured and screen content sequences. Evaluation results show that the pwm functions can attain the maximum bitrate reductions of 5.54% and 28.33% for screen content material compared with DPCM-based and block-wise intra-prediction, respectively. Compared with intra-block copy, piecewise mapping can attain the maximum bit-rate reductions of 11.48% for a camera-captured material.


Air leak syndrome after endoscopic retrograde cholangiopancreatography: a rare and fatal complication.
Endoscopic retrograde cholangiopancreatography (ERCP) is a state of the art diagnostic and therapeutic procedure for various pancreatic and biliary problems. In spite of the well-established safety of the procedure, there is still a risk of complications such as pancreatitis, cholangitis, bleeding and perforation. Air leak syndrome has rarely been reported in association with ERCP and the optimal management of this serious condition can be difficult to establish. Our group successfully managed a case of air leak syndrome following ERCP which was caused by a 3cm Stapfer type I perforation in the posterolateral aspect of the second part of the duodenum and was repaired surgically. Hereby, we describe the presentation and subsequent therapeutic approach.


Reel Syndrome--the Ratchet mechanism.
Twiddler's Syndrome and Reel Syndrome are potentially harmful lead-related complications in patients with implantable defibrillators and pacemakers. Twiddler's Syndrome is caused by device rotations around the devices long axis. A ratchet mechanism, possibly involving lead fixation sleeves and not device rotations around the transverse axis is suggested to be responsible for the Reel Syndrome. No detailed information about the underlying mechanisms of the Reel Syndrome is available. A case of a patient with a CRT-D and Reel Syndrome is reported; the mechanisms making the Reel Syndrome possible are illustrated and discussed.


A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women.
Untested alternative weight loss diets, such as very low carbohydrate diets, have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors. Therefore, we designed a randomized, controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors. Subjects were randomized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30% of the calories as fat. Anthropometric and metabolic measures were assessed at baseline, 3 months, and 6 months. Fifty-three healthy, obese female volunteers (mean body mass index, 33.6 +/- 0.3 kg/m(2)) were randomized; 42 (79%) completed the trial. Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months. The very low carbohydrate diet group lost more weight (8.5 +/- 1.0 vs. 3.9 +/- 1.0 kg; P < 0.001) and more body fat (4.8 +/- 0.67 vs. 2.0 +/- 0.75 kg; P < 0.01) than the low fat diet group. Mean levels of blood pressure, lipids, fasting glucose, and insulin were within normal ranges in both groups at baseline. Although all of these parameters improved over the course of the study, there were no differences observed between the two diet groups at 3 or 6 months. beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months (P = 0.001). Based on these data, a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and, over 6 months, is not associated with deleterious effects on important cardiovascular risk factors in healthy women.


Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice.
The newly generated single-positive (SP) thymocytes undergo further maturation in the thymic medulla before their emigration to the periphery. The present study was undertaken to validate a developmental program we proposed for CD4SP medullary thymocytes and to explore the mechanisms regulating this process. During mouse ontogeny, the emergence of different subsets of CD4SP thymocytes followed a strict temporal order from SP1 to SP4. Parallel to the transition in surface phenotype, a steady increase in function was observed. As further evidence, purified SP1 cells were able to sequentially give rise to SP2, SP3, and SP4 cells in intrathymic adoptive transfer and in culture. Notably, the development of CD4SP cells in the medulla seemed to be critically dependent on a functionally intact medullary epithelial cell compartment because Relb and Aire deficiency were found to cause severe blockage at the transition from SP3 to SP4. Taken together, this work establishes an ontogenetically and functionally relevant maturation program for CD4SP thymocytes. Precise dissection of this program should facilitate further inquiry into the molecular mechanisms governing normal thymocyte development and its disturbance in pathological conditions.


Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers.
The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2+/-23.7 and 41.9+/-17.9 microg/cm2 per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.


Aortic valve-sparing procedure in the pediatric population.
Aortic valve-sparing procedures have been established as a mainstream treatment option for adult patients with aortic root aneurysms. However, data regarding their use in the pediatric population is limited. This study reports on our experience with aortic valve-sparing procedures in children. A retrospective review was conducted of all patients who underwent an aortic valve-sparing procedure at the Royal Children's Hospital, Melbourne, Australia between April 2006 and April 2016. Clinical and echocardiographic data were analyzed. The study included 17 patients, with a median age of 15.7 years and a majority of patients being male (82.4%). The most common diagnosis was transposition of great arteries after arterial switch operation, followed by Loeys-Dietz syndrome and Marfan syndrome. Preoperative echocardiography showed more than moderate aortic regurgitation in 94.1% of the patients. The David procedure was performed in all 17 patients, with no mortality during follow-up. Reoperation was required in 29.4% of patients, and 23.5% required aortic valve replacement. Freedom from reoperation for aortic valve replacement at 1, 5, and 10 years was 93.8%, 93.8% and 68.2% respectively. Aortic valve-sparing surgery can be successfully performed in the pediatric population. However, it requires a highly skilled surgeon due to the often dysplastic or distorted nature of these valves and the need for additional procedures on the aortic valve leaflets.


Arrestin-3 binds the MAP kinase JNK3α2 via multiple sites on both domains.
Although arrestins bind dozens of non-receptor partners, the interaction sites for most signaling proteins remain unknown. Here we report the identification of arrestin-3 elements involved in binding MAP kinase JNK3α2. Using purified JNK3α2 and MBP fusions containing separated arrestin-3 domains and peptides exposed on the non-receptor-binding surface of arrestin-3 we showed that both domains bind JNK3α2 and identified one element on the N-domain and two on the C-domain that directly interact with JNK3α2. Using in vitro competition we confirmed that JNK3α2 engages identified N-domain element and one of the C-domain peptides in the full-length arrestin-3. The 25-amino acid N-domain element has the highest affinity for JNK3α2, suggesting that it is the key site for JNK3α2 docking. The identification of elements involved in protein-protein interactions paves the way to targeted redesign of signaling proteins to modulate cell signaling in desired ways. The tools and methods developed here to elucidate the molecular mechanism of arrestin-3 interactions with JNK3α2 are suitable for mapping of arrestin-3 sites involved in interactions with other partners.


Factorial invariance in preventive intervention: modeling the development of intelligence in low birth weight, preterm infants.
The paper addresses the issue of measurement invariance in the analysis of preventive intervention data. Procedures for testing the invariance of covariance matrices, measurement models, and structural growth models are illustrated using data from an early intervention program for low birth weight, preterm infants. Intelligence Quotient (IQ) measured at 5 time points was modeled using piecewise growth curve analysis. Change over time in children's cognitive development was modeled separately for the pre- and postintervention periods. The first period was during the intervention, which lasted from birth through age 3 years. The second was during the postintervention period, which included follow-up assessments at ages 5 and 8 years. The analytical approach is illustrated with findings indicating that the development of IQ was different for higher low birth weight (HLBW: 2001-2500 g) and lower low birth weight (LLBW: <2001 g) infants. Examination of the effects of covariates on the IQ trajectories associated with the two birth weight groups indicated differential effects on IQ depending on the period of development and birth weight. Neonatal health and maternal age were predictors of IQ change in the LLBW group whereas maternal education was related to change in the HLBW group. During the posttreatment period, only Hispanic ethnicity and treatment group status were related to change. Hispanic participants exhibited an accelerated trajectory between program end and age 8 years. Intervention recipients exhibited a flatter trajectory during the same time period whereas participants in the control group exhibited an accelerated development, essentially catching up with their counterparts in the treatment group. Results clearly illustrate the utility of invariance testing in modeling developmental trajectories in response to preventive intervention.


[Effect of previous culture conditions and the presence of the rpoS gene on the survival of Salmonella typhimurium in sea water exposed to sunlight].
The effect of sunlight exposure on Salmonella typhimurium isogenic strains harboring an rpoS gene functional (rpoS+) or not functional (rpoS-) was investigated in microcosms of sterile sea water at 20 degrees C. The two strains rapidly lost their ability to produce colonies on solid culture media. The detrimental action of sunlight was more important when the salinity of sea water increased. The survival of stationary phase cells was influenced by RpoS. Bacteria grown in media with high salinity or osmolarity and transferred to sea water in stationary phase were more resistant to irradiation than those grown in media with low salinity. Prior growth under oxidative (0.2 mmol/L of H2O2) or amino acid starved (minimal medium) conditions did not modify the survival of either strain when they were exposed to sunlight. Bacteria were more resistant when cells were incubated in sea water in the dark prior to being exposed to sunlight. The resistance to sunlight irradiation was also greater in clones of both strains isolated from microcosms exposed to sunlight for 90 min, then further inoculated into sea water and reexposed to sunlight.


Analgesic and anti-inflammatory activities of bupropion in animal models.
Antidepressants are widely used for the treatment of various neuropathic pain conditions in humans. Recent studies have demonstrated that bupropion is effective for the treatment of neuropathic pain. Also antidepressants like bupropion showed anti-inflammatory properties. So in the present study, the analgesic and anti-inflammatory effects of bupropion in mice and rat were investigated. The acetic acid, formalin and hot plate tests were used in male mice to assess analgesic activity. For evaluation of anti-inflammatory effect, carrageenan-induced rat paw edema and croton oil-induced ear edema were used. Bupropion was administered at the doses of 10, 20 and 40 mg/kg (i.p.). Bupropion at a dose of 40 mg/kg significantly reduced acetic acid-induced abdominal writhes and also was effective in suppression of formalin-induced behavior and showed significant analgesia in hot plate test. While 40 mg/kg bupropion showed considerable anti-inflammatory response in carrageenan test, but no effect was observed in croton oil-induced ear edema. The results showed that bupropion has analgesic and anti-inflammatory effects in animal models and further studies are needed to find out its mechanism of action.


MicroRNA-152 and -181a participate in human dermal fibroblasts senescence acting on cell adhesion and remodeling of the extra-cellular matrix.
Ageing of human skin is associated with phenotypic changes in the cutaneous cells; the major functional markers of ageing occur as consequences of dermal and epidermal cell senescence and of structural and compositional remodeling of normally long-lived dermal extracellular matrix proteins. Understanding the contribution of the dermal cells in skin ageing is a key question, since this tissue is particularly important for skin integrity and its properties can affect the epidermis. Several microRNAs have been shown to be involved in the regulation of pathways involved in cellular senescence and exerted important effects on tissues ageing. In this study, we demonstrate that the expression of miR-152 and miR-181a increased during the human dermal fibroblasts senescence and that their overexpression, is sufficient to induce cellular senescence in early-passage cells. The increase of these miRNAs during cells senescence was accompanied by a decrease in integrin α5 and collagen XVI expression at mRNA and/or protein levels resulting in reduced cellular adhesion and suggesting extracellular matrix remodeling. These findings indicate that changes in miRNAs expression, by modulating the levels of adhesion proteins and extra-cellular matrix components, such as integrin α5 and collagen XVI, could contribute to the compositional remodelling of the dermis and epidermis occurring during skin aging.


First paleoparasitological results from late Holocene in Patagonian coprolites.
These are the first paleoparasitological results from the Late Holocene in Patagonian coprolites. Coprolites collected from layers dated at 3,480 and 2,740 yr before present (B.P.), from the archaeological site Cerro Casa de Piedra, were examined. The site is a hill located in a forest steppe ecotone in Perito Moreno National Park. The coprolites could belong to humans or to other carnivores such as canids. After rehydration and spontaneous sedimentation of the samples, the parasite contents were examined. Results obtained showed the common presence of eggs of a Calodium sp., eggs of other capillariids and trichostrongylids, oocysts of Eimeria macusaniensis (Apicomplexa), and eggs of taeniids (Cestoda). Although the generic identification of some parasites could not be provided, the presence of tapeworm eggs represents the first record for the Late Holocene in Patagonia and shows that parasitism by cestodes existed in the region in pre-Columbian times. Results indicate that in the Late Patagonic Holocene, zoonotic helminths may have been commonly present in the inhabitants of Patagonia. The parasites found in the coprolites allow us to deduce what these people were eating and, thus, indicate what other pathogens, such as viruses, bacteria, and parasitic protozoans, may have infected them via the same sources.