Role of the lncRNA-mRNA network in atherosclerosis using ox-low-density lipoprotein-induced macrophage-derived foam cells.
Atherosclerosis (AS) is the leading cause of coronary heart disease, cerebral infarction, peripheral vascular disease, and other cardiovascular diseases, making it a major risk factor for high morbidity and mortality. Although long non-coding RNAs (lncRNAs) have been reported to play a role in AS, the specific effects of lncRNAs on AS remain largely unknown. Thus the purpose of this study was to explore the roles of mRNAs and lncRNAs in atherosclerosis via an ox-low-density lipoprotein induced macrophage-derived foam cell model. Microarray analysis identified a total of 50 688 mRNAs and 1514 lncRNAs, including 51 lncRNAs and 1730 mRNAs that were significantly dysregulated in the model group (p-adjust < 0.05 and |log 2FC| > 2). The results of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the dysregulated genes were associated with cell proliferation, cell apoptosis, and inflammatory responses. An lncRNA-mRNA co-expression network was created to further analyze the key regulatory genes. The lncRNAs Brip1os, Gm16586, AU020206, 9430034N14Rik, 2510016D11Rik, LNC_000709, Gm15472, Gm20703, and Dubr were identified as potential biomarkers in macrophage-derived foam cells. Based on 9 lncRNAs and 13 mRNAs, key genes influencing the degree of cell proliferation and cell apoptosis and the subsequent development of AS were identified. Q-PCR verified the key dysregulated genes. Thus, our results suggest potential therapeutic targets for AS and provide avenues for further research on AS pathogenesis.


Structural and functional properties of apolipoprotein B in chemically modified low density lipoproteins.
The structural and compositional changes occurring during in vitro chemical modification of apolipoprotein B-100 (apo B), the apolipoprotein component of low density lipoproteins (LDL), were investigated in this study. The functional properties of chemically modified apo B and especially its potential to induce accumulation of cholesterol esters in macrophages were related to the structural changes of apo B. Acetylation, maleylation or malondialdehyde conjugation did not significantly affect the lipid composition of LDL. However, the unsaturated cholesteryl esters content, especially that of cholesteryl arachidonate was significantly decreased through Cu-oxidation. The number of reactive lysine residues in apo B was decreased by Cu-catalyzed LDL oxidation, acetylation, maleylation and by malondialdehyde conjugation. The number of free cysteines decreased from six in native apo B-100 to three in Cu-oxidized LDL. The tryptophan fluorescence intensity decreased most in malondialdehyde-conjugated LDL and in Cu-oxidized LDL, compared with acetylated and maleylated LDL. The secondary structure of native and chemically modified LDL was measured by attenuated total reflection infrared spectroscopy and by circular dichroism. No significant changes were observed in the secondary structure of any of the modified LDL. These data suggest that neither acetylation, malondialdehyde treatment or even Cu-oxidation substantially altered the secondary structure of apo B, in spite of significant modifications in the primary structure. Incubation of chemically modified LDL with J774 macrophages induced an accumulation of cellular cholesteryl esters and foam cell formation. The highest cholesterol accumulation was induced after malondialdehyde treatment of LDL. These data suggest that the cellular uptake and accumulation of modified LDL is not modulated by changes in the apo B structure. Rather it seems dependent upon the net charge of the apo B protein and probably involves the modification of critical lysine residues.


Recidivism in the child protection system: identifying children at greatest risk of reabuse among those remaining in the home.
To identify risk clusters that are associated with higher or lower risk of new abuse reports (rereports) and substantiated rereports (reabuse) in children who remain in the home after an abuse report. A 5-year prospective cohort study. National Survey of Child and Adolescent Well-Being. Children reported to the child protection system for child abuse. Remaining in the home after an abuse report. Incidence of rereports and reabuse. A total of 2578 children remained in the home following an abuse report, and 44% were rereported within the follow-up period. In bivariate analyses, children with behavior problems (49% vs 38%), caregivers with an abuse history (33% vs 16%) or a child welfare history (38% vs 25%), and families with an annual income lower than $20 000 (70% vs 60%) were more likely to be rereported. Forty-five percent of rereports were substantiated reabuse, but 2 risk clusters had a higher incidence: (1) the cluster with a substantiated index report, having a caregiver without parenting class, non-African American race/ethnicity, and caregiver younger than 41.5 years (54%); and (2) the cluster with a substantiated index report, a caregiver with parenting class, and child age younger than 8.5 years (60%). The lowest risk group for reabuse had a substantiated index report, a caregiver without parenting class, non-African American race/ethnicity, and a caregiver 41.5 years or older (26%). Among children remaining in the home following an abuse report, specific risk groups have higher and lower incidence of rereports and reabuse. These risk-group categories may be useful to child protection services and others in identifying at-risk children and making decisions about placement and services.


The Spanish National Network "Grupo Castrillo": 22 Years of Nationwide Neonatal Infection Surveillance.
This study aimed to describe the epidemiology of vertically transmitted sepsis (VS) and nosocomial sepsis (NOS) in very low birth weight (VLBW) neonates (birth weight ≤ 1,500 g) over the past 22 years in Spain. This is a retrospective analysis of prospectively collected VS and NOS in neonates from 1996 to 2018 in the 44 neonatal units integrated in the Spanish Neonatal Network Grupo Castrillo. A total of 2,676 episodes of VS were recorded in 2,196,129 live births (LBs; 1.2/1,000 LBs) over the study period (1996-2018). The incidence declined from 2.4 to 1 to 1.2/1,000 LBs (p < 0.0001). Of the 2,676 episodes, 95.7% were early onset (≤72 hours) and 4.3% cases late onset VS. Group B streptococcus (GBS) (33.1%) and E. coli (29.3%) were the most frequently isolated pathogen. The GBS incidence declined significantly from 1.25 to 0.21/1,000 LBs (p < 0.0001). E. coli incidence showed a significant increase trend in VLBW infants (p < 0.05). The global mortality per 1000 LBs decreased from 0.21 to 0.13/1,000. A total of 7,036 episodes of NOS involving 5,493 VLBW infants were registered over 20,935 neonatal admissions (NAs) in the study period (2006-2018). The incidence was 26.2 per 100 NAs. The median postnatal age at onset was 13 days (interquartile range [IQR]: 9-23 days). Around 80% of cases occurred in infants with a central line in place. Gram positive (GP) bacteria accounted for 66.2% with Staphylococcus epidermidis as the most frequently isolated pathogen, gram negative (GN) bacteria entailed 27.4%, and fungi 6.2%. Klebsiella sp. was the most common GN isolated and Candida albicans the most prevalent fungus. The overall mortality was 8.3%. The causative pathogen of neonatal sepsis may change over time and between countries, therefore a national surveillance network based on a consensus definition could be essential to provide accurate information. · Grupo Castrillo is a Spanish network for neonatal infections surveillance.. · A neonatal sepsis definition based on epidemilogical and not only chronological criteria was established.. · Epidemiology of neonatal sepsis may change over time; therefore, a national surveillance network is essential to provide accurate information..


A study of stress and autonomic nervous function in first year undergraduate medical students.
Psychological stress is a risk factor for hypertension and coronary artery disease. The purpose of this study was to assess the impact of real life stressor, that of stress among first year medical students on cardiac autonomic regulation. Stress levels in 36 non-smoking, healthy first year medical students of either gender were assessed on a self-rating scale. Cardiac autonomic regulation was tested using both conventional tests and spectral analysis of heart rate variability (HRV). Nine subjects who obtained scores on the stress scale in the upper quartile were classified as the "stress" group and the rest constituted the "no stress" group (n = 27). There were no significant differences between the two groups on any of the conventional tests of autonomic nervous activity. The low frequency power in normalized units and low frequency high frequency ratio of heart rate variability in supine posture was significantly higher in the "stress" group compared to the "no stress" group. The low frequency power in normalized units was significantly positively correlated with total stress score. The changes were suggestive of a tilt in the resting cardiac autonomic balance towards increased sympathetic activity.


Multi-luminescent switching of metal-free organic phosphors for luminometric detection of organic solvents.
Metal-free organic phosphors can be an attractive smart optical sensing materials since, in such compounds, intersystem crossing (ISC) and the phosphorescence process are placed in subtle competition with fluorescence, internal conversion (IC), and non-radiative decay pathways. Here, we report a unique environment-dependent multi-luminescence switching behavior of metal-free organic phosphorescent materials. Through combined photophysical measurements and computational electronic structure analysis, we systematically investigated how physicochemical properties of organic solvents affect the photophysical pathways of the metal-free organic phosphors. By rationally adapting the finding into phosphor-doped electrospun polymer fibers, we developed a new luminometric sensory platform and achieved selective detection of eight different common organic solvents. The presented finding provides new possibilities for metal-free organic phosphors to be a novel class of smart optical sensory materials.


Mental health and stress level of Ukrainians seeking psychological help online.
Due to the Russian invasion of Ukraine on February 24th, 2022, more than 8 million Ukrainians have been displaced from their homes. Ukrainians exposed to armed conflict and migration are likely to have low levels of mental health status and seek help. We provide a uniform quantitative assessment of the mental health conditions of Ukrainians seeking help soon after the invasion and resettlement. We screen the mental well-being and psychological distress of 1165 refugees, migrants, internally displaced, and non-displaced individuals from Ukraine who seek psychological help online in Ukraine and across 24 countries of the European Union. We surveyed participants in the study as a part of our online program for adult Ukrainians from June 22nd to July 6th, 2022. We report descriptive results of mental-health status for the aggregate sample and the sub-groups. More than half of the respondents exhibit low levels of mental well-being and high psychological distress, with 81 % being at risk of depression; 57 % having severe psychological distress. Refugees and internally displaced participants show a particularly high risk of depression and severe psychological distress in our sample. Many Ukrainians seeking psychological help work, study, or volunteer, and those who engage in these activities have relatively alleviated mental well-being. Our results indicate a considerable psychological burden on Ukrainians. Although our analysis focuses on Ukrainians seeking help, it shows that the displaced soon after resettlement require particular attention and can be reached in a short time across borders, irrespective of their (officially documented) migration status.


Quantifying pattern recognition-based myoelectric control of multifunctional transradial prostheses.
We evaluated real-time myoelectric pattern recognition control of a virtual arm by transradial amputees. Five unilateral patients performed 10 wrist and hand movements using their amputated and intact arms. In order to demonstrate the value of information from intrinsic hand muscles, this data was included in EMG recordings from the intact arm. With both arms, motions were selected in approximately 0.2 s on average, and completed in less than 1.25 s. Approximately 99% of wrist movements were completed using either arm; however, the completion rate of hand movements was significantly lower for the amputated arm (53.9% +/- 14.2%) than for the intact arm ( 69.4% +/- 13.1%). For the amputated arm, average classification accuracy for only 6 movements-including a single hand grasp-was 93.1% +/- 4.1%, compared to 84.4% +/- 7.2% for all 10 movements. Use of 6 optimally-placed electrodes only reduced this accuracy to 91.5% +/- 4.9%. These results suggest that muscles in the residual forearm produce sufficient myoelectric information for real-time wrist control, but not for performing multiple hand grasps. The outcomes of this study could aid the development of a practical multifunctional myoelectric prosthesis for transradial amputees, and suggest that increased EMG information-such as made available through targeted muscle reinnervation-could improve control of these prostheses.


Nordic welfare states-still standing or changed by the COVID-19 crisis?
Nordic welfare states are known for their universalistic and all-encompassing approach to welfare and having a long tradition for active labour market policy as tool in economic crises with adverse impact on employment. They have had a long tradition for strong egalitarian approaches and their residents are consistently among the happiest in the world. A key issue is whether a crisis like the COVID-19 outbreak is changing the Nordic welfare states. This article focuses on providing a description of what instruments the Nordic countries have taken or expect to use as part of dealing with the welfare challenges resulting from rising unemployment and greater social and economic insecurity in the wake of the crisis. The tentative conclusion is that the crisis so far has strengthened key characteristics of the Nordic welfare states by the state taking on a strong central role not only for the functioning of the market but also continued in a path-dependent way with universal and relatively generous benefits such as for those who become unemployed or have reduced income because of the crisis.


Evening primrose oil in patients with rheumatoid arthritis and side-effects of non-steroidal anti-inflammatory drugs.
Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospective 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day. Nineteen patients received active therapy (as evening primrose oil 6 g/day) and 21 received placebo (olive oil 6 g/day). No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose. Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil. Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis, olive oil may itself have hitherto unrecognized benefits.


Neurocognitive predictors of posttraumatic stress disorder symptoms in children 6 months after traumatic brain injury: A prospective study.
Various neurocognitive mechanisms have been proposed to explain the development of Posttraumatic Stress Disorder (PTSD) symptoms. However, the neurocognitive mechanisms underlying comorbid PTSD following Traumatic Brain Injury (TBI) have not been fully investigated, especially among children. This study prospectively examined the influence of theorized neurocognitive deficits at 3 months post pediatric TBI on the development of PTSD symptoms 6 months postinjury. One hundred sixty-six children aged between 6 and 14 years were recruited after sustaining a TBI. Their demographic information and injury severity were assessed at 2 months postinjury, their neurocognitive outcomes in selective attention, sustained attention, verbal learning, working memory, and processing speed were assessed at 3 months postinjury, and PTSD symptoms were measured at 6 months postinjury. Consistent with the Neurobiological Theory of PTSD, sustained attention deficits 3 months postinjury emerged as the key predictor for greater future PTSD severity at 6 months, especially following a mild TBI. However, contrary to the expectations of the Emotional Processing Theory and Dual Representation Theory, verbal learning and working memory deficits at 3 months postinjury protected children from the development of PTSD symptoms 6 months postinjury. PTSD involves a complex interplay between attention and memory functions post pediatric TBI. When trauma memory is relatively intact, difficulties disengaging from distractors contribute to the development of PTSD symptoms. (PsycINFO Database Record


[Intracerebral neurosurgery in the treatment of chronic pain].
Brain surgery is generally considered a treatment of last resort for chronic pain resistant to all other therapeutic measures. The neurosurgical treatment of pain may be either destructive (e.g., thalamotomy) or augmentative (e.g., electrical stimulation through an electrode connected to an implanted neurologic pacemaker). For pain of the neurogenic type (neuropathic or deafferentation pain), the preferred target is either the sensory nucleus of the thalamus, at a site corresponding somatotopically to the location of the pain, or the precentral cortex. For somatic (nociceptive) pain, stimulation of the periventricular or periaqueductal gray matter, or intraventricular infusion of morphine, may be useful. These operations are now indicated only in exceptional cases, as will be explained with reference to the author's long experience.


Spontaneous mutations in the ammonium transport gene AMT4 of Chlamydomonas reinhardtii.
Evidence in several microorganisms indicates that Amt proteins are gas channels for NH(3) and CH(3)NH(2), and this has been confirmed structurally. Chlamydomonas reinhardtii has at least four AMT genes, the most reported for a microorganism. Under nitrogen-limiting conditions all AMT genes are transcribed and Chlamydomonas is sensitive to methylammonium toxicity. All 16 spontaneous methylammonium-resistant mutants that we analyzed had defects in accumulation of [(14)C]methylammonium. Genetic crosses indicated that 12 had lesions in a single locus, whereas two each had lesions in other loci. Lesions in different loci were correlated with different degrees of defect in [(14)C]methylammonium uptake. One mutant in the largest class had an insert in the AMT4 gene, and the insert cosegregated with methylammonium resistance in genetic crosses. The other 11 strains in this class also had amt4 lesions, which we characterized at the molecular level. Properties of the amt4 mutants were clearly different from those of rh1 RNAi lines. They indicated that the physiological substrates for Amt and Rh proteins, the only two members of their protein superfamily, are NH(3) and CO(2), respectively.


Toxicological responses of red-backed salamanders (Plethodon cinereus) to subchronic soil exposures of 2,4,6-trinitrotoluene.
Since World War I, trinitrotoluene (TNT) has been the most commonly used explosive. Environmental contamination associated with synthesis, manufacture of weapons, and use during training exercises has been extensive, with soil concentrations reaching 145,000 mg/kg. Some of these areas include habitats for amphibian species. Earlier studies have shown that salamanders dermally absorb TNT from soil. To ascertain what soil concentrations of TNT are toxic to amphibians, red-backed salamanders (Plethodon cinereus) were exposed to one of five concentrations of TNT in soil for 28 d and evaluated for indicators of toxicity. A total of 100 salamanders were randomly sorted by weight and assigned to target TNT concentrations in soil of either 3,000, 1,500, 750, 325, or 0 mg/kg dry weight. Food consisted of uncontaminated flightless Drosophila melanogaster. Survival was reduced in salamanders exposed to 1,500 and 3,000 mg/kg by 10 and 55%, respectively. Most mortality/morbidity occurred within the first week of exposure. Salamanders had a reduction in hemoglobin at 750 mg/kg or greater and a reduction in red blood cell concentration at 1,500 mg/kg or greater. Food consumption was affected in salamanders at 750 mg/kg or greater; a reduction in body mass and liver glycogen content also occurred at and above this concentration. Splenic congestion also was observed in salamanders from these groups. These data suggest that soil TNT concentrations of 373 +/- 41.0 mg/kg or greater result in reduced body mass, reduced feed intake, and hematological effects.


Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding.
Von Willebrand factor (VWF) is a large, multimeric plasma glycoprotein that critically mediates hemostasis at sites of vascular injury. Very large VWF multimers have the greatest thrombogenic activity, which is attenuated by cleavage in the A2 domain by the metalloproteinase ADAMTS13. ADAMTS13 proteolysis requires mechanical force to expose the scissile bond and is regulated by a calcium-binding site within A2. In this study, we characterized the interaction between VWF A2 and calcium by examining the effect of calcium on VWF A2 stability and mechanical unfolding and refolding. Isothermal calorimetry yielded a calcium binding K(d) = 3.8 ± 1.0 μM and reversible thermal denaturation showed that 5 mM calcium stabilized the unfolding transition from 56.7 ± 0.1 to 69.1 ± 0.1 °C. Using optical tweezers to apply tensile force to single domains, we found that calcium did not affect VWF A2 unfolding, but rather enhanced refolding kinetics fivefold, resulting in a 0.9 kcal/mol stabilization in the folding activation energy in the presence of calcium. Taken together, our data demonstrate that VWF binds calcium at physiologic calcium concentrations and that calcium stabilizes VWF A2 by accelerating refolding.


Myoclonus induced by the use of gabapentin.
Myoclonus is a rare side effect of gabapentin (GBP) and has been reported in patients with preexisting myoclonus, mental retardation, chronic static encephalopathy, diffuse brain damage, impaired renal function, or end stage renal disease. We report a case of myoclonus in a patient with normal renal function and no previous disorders. A 69-year-old female underwent diskectomy and foraminotomy at the left L4-L5 level. Postoperatively, she complained of paresthesia in her left leg, which was thought to be due to root manipulation during surgery. To relieve the paresthesia, she was given tramadol, an oral opioid agonist, and GBP. One week after GBP was increased to 900 mg per day, myoclonus developed, which severely impaired her normal activity. Her symptoms resolved 2 days after discontinuation of GBP. The coadministration of tramadol and GBP may mutually enhance the myoclonic potential of each drug. The causal relationship between GBP and myoclonus was suggested by cessation of myoclonus after GBP discontinuation despite continued therapy with tramadol.


A Bundle of Services Increased Ascertainment of Tuberculosis among HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa.
To report on trends of tuberculosis ascertainment among HIV patients in a rural HIV cohort in Tanzania, and assessing the impact of a bundle of services implemented in December 2012, consisting of three components: (i) integration of HIV and tuberculosis services; (ii) GeneXpert for tuberculosis diagnosis; and (iii) electronic data collection. Retrospective cohort study of patients enrolled in the Kilombero Ulanga Antiretroviral Cohort (KIULARCO), Tanzania.). HIV patients without prior history of tuberculosis enrolled in the KIULARCO cohort between 2005 and 2013 were included.Cox proportional hazard models were used to estimate rates and predictors of tuberculosis ascertainment. Of 7114 HIV positive patients enrolled, 5123 (72%) had no history of tuberculosis. Of these, 66% were female, median age was 38 years, median baseline CD4+ cell count was 243 cells/µl, and 43% had WHO clinical stage 3 or 4. During follow-up, 421 incident tuberculosis cases were notified with an estimated incidence of 3.6 per 100 person-years (p-y) [95% confidence interval (CI) 3.26-3.97]. The incidence rate varied over time and increased significantly from 2.96 to 43.98 cases per 100 p-y after the introduction of the bundle of services in December 2012. Four independent predictors of tuberculosis ascertainment were identified:poor clinical condition at baseline (Hazard Ratio (HR) 3.89, 95% CI 2.87-5.28), WHO clinical stage 3 or 4 (HR 2.48, 95% CI 1.88-3.26), being antiretroviralnaïve (HR 2.97, 95% CI 2.25-3.94), and registration in 2013 (HR 6.07, 95% CI 4.39-8.38). The integration of tuberculosis and HIV services together with comprehensive electronic data collection and use of GeneXpert increased dramatically the ascertainment of tuberculosis in this rural African HIV cohort.


Minority Stress and Mental Health of Gay Men in Turkey: The Mediator Roles of Shame and Forgiveness of Self.
Proximal minority stressors (i.e., internalized homonegativity, anticipation of rejection, and concealment of sexual identity) lead to depression and anxiety. General psychological factors mediate the association of proximal stressors with depression and anxiety. Based on this, the present study aimed to investigate the sequential mediating roles of shame and forgiveness of self on the relations of proximal stressors with depression and anxiety in a sample of self-identified gay men in Turkey (N = 200). The findings revealed that proximal stressors significantly predicted depression and anxiety indirectly through shame and self-forgiveness. Thus, the link between minority stress and shame should be considered in clinical practice, and self-forgiveness should be integrated into intervention programs to eliminate the negative impacts of shame on depression and anxiety among this population. Limitations and directions for future studies are presented.


Structured viscoelastic substrates as linear foundations.
The linear (Winkler) foundation is a simple model widely used for decades to account for the surface response of elastic bodies. It models the response as purely local, linear, and perpendicular to the surface. We extend this model to the case in which the foundation is made of a structured material such as a polymer network, which has characteristic scales of length and time. We use the two-fluid model of viscoelastic structured materials to treat a film of finite thickness, supported on a rigid solid and subjected to a concentrated normal force at its free surface. We obtain the foundation modulus (Winkler constant) as a function of the film's thickness, intrinsic correlation length, and viscoelastic moduli, for three choices of boundary conditions. The results can be used to readily extend earlier applications of the Winkler model to more complex, microstructured substrates. They also provide a way to extract the intrinsic properties of such complex materials from mechanical surface measurements.


Meaning of sustainability of innovations in healthcare organizations: A systematic review.
There is pressure on healthcare organizations to provide high-quality care to all patients while innovating the way care is delivered. As they take on the challenge of delivering high-quality, innovative services, any gains made tend to stall before a radical change impacts key outcomes given the difficulty in sustaining innovations over time. A systematic search was performed in 5 electronic databases using the PRISMA structure that resulted in 1313 articles, of which 260 were duplicated, leaving 1053 articles. After reading their abstracts, 877 had an inadequate scope for analysis because they did not deal with research on the sustainability of innovations. After a full assessment of the remaining 176 articles, only 10 studies met the inclusion criteria with the snowball strategy generating one additional paper, leading to 11 empirical studies. A theoretical discussion and the proposition of a framework were used to analyze the data. Studies in university hospitals shed light on determining sustainability factors of innovations not yet fully explored such as the meaning given by individuals to innovation, culture, partnerships, and multidisciplinary collaboration, which complement the literature. This research sought to contribute to the dialogue between management theory and practice in studies on the sustainability of health innovations based on experiences observed in university hospitals. Health managers can verify how sustainability relates to the challenges presented and identify a path that helps them overcome the limitations imposed on the process. The literature shows that the understanding of sustainability as a mediating dimension can collaborate in sustained innovations in order to allow managers to identify actions related to the individual-organization dimension that may be compromising the process and thus act in a more efficient, assertive way in determining the factors that sustain ongoing innovations. A relevant point is that innovation sustainability needs to be an objective to be achieved where managers/individuals must incorporate this perspective of innovation continuity since the beginning of the process, otherwise this may represent a greater propensity for discontinuity. This analysis can potentially be applied in university hospitals, but it can also be applicable to other types of hospitals and public or private institutions as long as it is an organization that adopts, implements, and seeks to sustain innovations in service delivery.


ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology.
Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.


Base excision repair in nucleosomes lacking histone tails.
Recently, we developed an in vitro system using human uracil DNA glycosylase (UDG), AP endonuclease (APE), DNA polymerase beta (pol beta) and rotationally positioned DNA containing a single uracil associated with a 'designed' nucleosome, to test short-patch base excision repair (BER) in chromatin. We found that UDG and APE carry out their catalytic activities with reduced efficiency on nucleosome substrates, showing a distinction between uracil facing 'out' or 'in' from the histone surface, while DNA polymerase beta (pol beta) is completely inhibited by nucleosome formation. In this report, we tested the inhibition of BER enzymes by the N-terminal 'tails' of core histones that take part in both inter- and intra-nucleosome interactions, and contain sites of post-translational modifications. Histone tails were removed by limited trypsin digestion of 'donor' nucleosome core particles and histone octamers were exchanged onto a nucleosome-positioning DNA sequence containing a single G:U mismatch. The data indicate that UDG and APE activities are not significantly enhanced with tailless nucleosomes, and the distinction between rotational settings of uracil on the histone surface is unaffected. More importantly, the inhibition of pol beta activity is not relieved by removal of the histone tails, even though these tails interact with DNA in the G:U mismatch region. Finally, inclusion of X-ray cross complement group protein 1 (XRCC1) or Werner syndrome protein (WRN) had no effect on the BER reactions. Thus, additional activities may be required in cells for efficient BER of at least some structural domains in chromatin.


An interpretable machine learning model based on a quick pre-screening system enables accurate deterioration risk prediction for COVID-19.
A high-performing interpretable model is proposed to predict the risk of deterioration in coronavirus disease 2019 (COVID-19) patients. The model was developed using a cohort of 3028 patients diagnosed with COVID-19 and exhibiting common clinical symptoms that were internally verified (AUC 0.8517, 95% CI 0.8433, 0.8601). A total of 15 high risk factors for deterioration and their approximate warning ranges were identified. This included prothrombin time (PT), prothrombin activity, lactate dehydrogenase, international normalized ratio, heart rate, body-mass index (BMI), D-dimer, creatine kinase, hematocrit, urine specific gravity, magnesium, globulin, activated partial thromboplastin time, lymphocyte count (L%), and platelet count. Four of these indicators (PT, heart rate, BMI, HCT) and comorbidities were selected for a streamlined combination of indicators to produce faster results. The resulting model showed good predictive performance (AUC 0.7941 95% CI 0.7926, 0.8151). A website for quick pre-screening online was also developed as part of the study.


Bimetallic Hollow Nanostructures for Colorimetric Detection of Picomolar Level of Mercury.
In this paper, we report the use of bimetallic hollow nanostructures (BHNS), consisting of gold and silver metals, for colorimetric detection of mercury. The sodium dodecyl sulphate (SDS)-capped BHNS were prepared by galvanic etching of silver nanoparticles (AgNPs) using gold chloride resulting in a partially hollow AgNPs with the gold layer at its surface. These BHNS were interacted with an aqueous solution of mercury ions (Hg2+) in the concentration range of 10 pM-10 mM. Interestingly, at higher concentration range (10 μM-10 mM), a noticeable change in the solution color was observed with a prominent decrease in the absorption intensity and blue-shift in the peak plasmonic wavelength. This could be attributed to (i) complexation reaction between the anionic BHNS (due to the negatively charged SDS capping) and cationic Hg2+ and (ii) oxidative etching of silver from BHNS causing its depletion and resulting into Ag-Hg amalgam and/or aggregation of the nanostructures. In contrast, at lower concentration range (i.e., 10 pM-10 nM), an increase in the absorption intensity was observed, which was possibly due to the oxidative etching of silver from BHNS without aggregation of the nanostructures. The low amount of Hg2+ was not sufficient enough to interact with SDS capping layer present on the BHNS surface, unlike the higher concentrations of mercury and therefore, did not cause any aggregation. The developed colorimetric sensor showed high sensitivity and selectivity towards Hg2+ detection with a limit of detection of 10 pM and good linearity (R² = 0.97) in the concentration range of 10 pM-10 nM.


Effects of toxic levels of lead on gene regulation in the male axis: increase in messenger ribonucleic acids and intracellular stores of gonadotrophs within the central nervous system.
Lead is a male reproductive toxicant. Lead exposure results in a general suppression of the hypothalamic-pituitary-testicular (HPT) axis in male rats. The mechanism(s) for this disruption by lead is unknown. Toxic lead levels seem to disrupt central nervous system (CNS) control of the HPT system, resulting in a decrease in serum testosterone levels and sperm concentrations. A study designed to elucidate the mechanisms accounting for the disruption of the normal function of the male axis by toxic lead levels at the molecular level demonstrated a 2-3-fold enhancement of mRNA levels of GnRH and the tropic hormone LH. A 3-fold increase of intracellular stores of LH was also found. Because mRNA levels of LH and GnRH and pituitary levels of stored LH are proportional to blood levels of lead, we hypothesize that lead interferes with the normal release of tropic hormones and disrupts hormonal feedback mechanisms. The observed pleiotropic effects of lead upon the male axis and other systems may be explained by simple and unique competition by lead with normal metal ion binding sites that govern genetic control of specific genes.


Reactive cysteine in the active-site motif of Bacteroides thetaiotaomicron dipeptidyl peptidase III is a regulatory residue for enzyme activity.
Dipeptidyl peptidase III (DPP III), a member of the metallopeptidase family M49, was considered as an exclusively eukaryotic enzyme involved in intracellular peptide catabolism and pain modulation. In 2003, new data on genome sequences revealed the first prokaryotic orthologs, which showed low sequence similarity to eukaryotic ones and a cysteine (Cys) residue in the zinc-binding motif HEXXGH. Here we report the cloning and heterologous expression of DPP III from the human gut symbiont Bacteroides thetaiotaomicron. The catalytic efficiency of bacterial DPP III for preferred synthetic substrate hydrolysis was very similar to that of the human host enzyme. Substitution of Cys450 from the active-site motif by serine did not substantially change the enzymatic activity. However, this residue was wholly responsible for the inactivation effect of sulfhydryl reagents. Molecular modeling indicated seven basic amino acid residues in the local environment of Cys450 as a possible cause for its high reactivity. Sequence analysis of 81 bacterial M49 peptidases showed conservation of the HECLGH motif in 68 primary structures with the majority of proteins lacking an active-site Cys originated from aerobic bacteria. Data obtained suggest that Cys450 of B. thetaiotaomicron DPP III is a regulatory residue for the enzyme activity.


Is Work Group Social Capital Associated With Sickness Absence? A Study of Workplace Registered Sickness Absence at the Work Group Level.
The concept of social capital has its focus on cooperative relations in the workplace. This study investigates the association between social capital and sickness absence among workers in 41 work groups in the Danish dairy industry and examines the possible effects of an intervention on social capital in the workplace on sickness absence. A sample of 791 dairy workers working in 41 work groups that participated in an intervention study on social capital filled in a questionnaire on four subtypes of social capital, and social capital scores from individual participants were aggregated to the level of work groups. Sickness absence was measured at the level of work groups in company registers as the two-year average percentage of working time lost to sickness absence. Group-level associations between social capital and sickness absence were analyzed using multilevel linear regression analysis. Analyses were adjusted for age, gender, group size, and random effects at the workplace level. We found statistically significant associations between social capital within work groups, social capital in relation to the immediate manager, and social capital toward the workplace as a whole on the one side and sickness absence on the other side. We found no support for any effects of the intervention on sickness absence. The work group level of social capital is associated with the work group level of sickness absence. However, the intervention to enhance group-level social capital had no effect on reducing sickness absence in the intervention group.


Therapeutic Alliance as Active Inference: The Role of Therapeutic Touch and Synchrony.
Recognizing and aligning individuals' unique adaptive beliefs or "priors" through cooperative communication is critical to establishing a therapeutic relationship and alliance. Using active inference, we present an empirical integrative account of the biobehavioral mechanisms that underwrite therapeutic relationships. A significant mode of establishing cooperative alliances-and potential synchrony relationships-is through ostensive cues generated by repetitive coupling during dynamic touch. Established models speak to the unique role of affectionate touch in developing communication, interpersonal interactions, and a wide variety of therapeutic benefits for patients of all ages; both neurophysiologically and behaviorally. The purpose of this article is to argue for the importance of therapeutic touch in establishing a therapeutic alliance and, ultimately, synchrony between practitioner and patient. We briefly overview the importance and role of therapeutic alliance in prosocial and clinical interactions. We then discuss how cooperative communication and mental state alignment-in intentional communication-are accomplished using active inference. We argue that alignment through active inference facilitates synchrony and communication. The ensuing account is extended to include the role of (C-) tactile afferents in realizing the beneficial effect of therapeutic synchrony. We conclude by proposing a method for synchronizing the effects of touch using the concept of active inference.


Goniotomy and congenital glaucoma.
A survey is presented of the operative results obtained in 45 eyes suffering from congenital glaucoma, primarily operated on using micro-surgical techniques, either goniotomy as described by Worst, or trabeculotomy. Thirty-eight of the 45 eyes have, during an observation period of 1-10 years, average 5.5 years, a normal pressure of less than or equal to 18 mmHg measured using Draeger's technique. A relatively high frequency of recurrence has been found following an average observation period of 3.5 years in patients who were primarily normalized by Worst's goniotomy.


[Hereditary colon cancer in Lynch syndrome/HNPCC syndrome in Germany].
Hereditary nonpolyposis colorectal cancer (Lynch/HNPCC syndrome) is based on a germline mutation inducing increased occurrence of colorectal cancer and extracolonic carcinomas in young age. The German HNPCC consortium aims to increase awareness for detection of hereditary colon cancer among patients and physicians. Reliable detection of HNPCC patients is based on a thorough documentation of patients' medical history and on further diagnostics delivered by human genetics and surgical pathology. This manuscript presents a standardized diagnostic concept. Relevant literature is reviewed and discussed and diagnostic parameters are outlined. In addition, operating figures of the German HNPCC consortium are presented. The German HNPCC consortium is based on an efficient cooperation between clinical physicians, human geneticists, and surgical pathologists. After a funding period from the Deutsche Krebshilfe, HNPCC diagnostics and preventive medical examinations were transferred into standard care in Germany. In total, 5770 families (8873 patients) were included in HNPCC diagnostics. To date, in 1296 families, mutations of the MLH1-, MSH2-, MSH6-, PMS2-, or EPCAM-gene have been detected. Furthermore, 612 pathogenic variants and 325 variants of unknown significance were found. Reliable detection of HNPCC patients is based on a standardized diagnostic concept, which has been established within the German HNPCC consortium.


Reduced activity of hypothalamic corticotropin-releasing hormone neurons in transgenic mice with impaired glucocorticoid receptor function.
Loss of central glucocorticoid receptor (GR) function is thought to be involved in the development of neuroendocrine and psychiatric disorders associated with corticotropin-releasing hormone (CRH) hyperactivity. The possible causal relationship between defective GR function and altered activity of CRH neurons was studied in transgenic mice (TG) expressing antisense RNA against GR. Immunocytochemical studies showed significant reductions in CRH immunoreactive neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP) stores in the external zone of the median eminence. Concomitantly, stimulus-evoked CRH secretion from mediobasal hypothalami of TG mice in vitro was reduced significantly. However, CRH mRNA levels in the PVN of TG mice were marginally lower than those in wild-type (WT) mice. 125I-CRH binding autoradiography revealed no differences between WT and TG animals in any of the brain regions that were studied. Basal plasma corticosterone (cort) levels and 125I-CRH binding, CRH-R1 mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary gland were similar in WT and TG mice. Intraperitoneal injection of interleukin-1beta (IL-1beta) increased plasma cort levels, CRH mRNA in the PVN, and anterior pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline significantly reduced anterior pituitary CRH-R1 mRNA levels in WT mice, but not in TG mice, whereas IL-1beta produced a decrease in these mRNA levels in both strains. The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R1 mRNA to stimulus-induced downregulation. Moreover, the hypothalamic changes observed in this model suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.


Recurrent cough in childhood and its relation to asthma.
Risk factors for recurrent cough (RC) in childhood, and its relation to asthma were investigated as part of the prospective, longitudinal Tucson Children's Respiratory Study. RC, defined as > or = 2 episodes of cough without a cold in the past year, was assessed by questionnaire in 987 children at age 6. Children having RC without wheeze (n = 154) did not differ from children with neither symptom (n = 610) in serum IgE levels, skin test response, size-corrected forced expiratory flow, or percentage of decline following cold air challenge. In contrast, children with both RC and wheeze (n = 116) had significantly more respiratory illness, more atopy, lower flow at end-tidal expiration (V'maxFRC), and greater declines in lung function following cold air challenge than children with neither symptom. Current parental smoking was a risk for RC without wheeze, whereas male gender, maternal allergy, wheezing lower respiratory tract illness (LRI) in early life, and high IgE were significant risks for RC with wheeze, compared with children having neither symptom. RC early in life resolved in the majority of children, between ages 2-3 yr and age 6, and between age 6 and age 11. High IgE and positive skin prick test were associated with persistence of RC to age 6 among children who wheezed, and markers of allergy were associated with persistence of RC between 6 and 11 yr. These findings suggest that recurrent cough in the absence of wheeze differs in important respects from classic asthma, and using the same label to refer to these distinct syndromes may obscure their diverse pathophysiologies.


The macroecology of sustainability.
The discipline of sustainability science has emerged in response to concerns of natural and social scientists, policymakers, and lay people about whether the Earth can continue to support human population growth and economic prosperity. Yet, sustainability science has developed largely independently from and with little reference to key ecological principles that govern life on Earth. A macroecological perspective highlights three principles that should be integral to sustainability science: 1) physical conservation laws govern the flows of energy and materials between human systems and the environment, 2) smaller systems are connected by these flows to larger systems in which they are embedded, and 3) global constraints ultimately limit flows at smaller scales. Over the past few decades, decreasing per capita rates of consumption of petroleum, phosphate, agricultural land, fresh water, fish, and wood indicate that the growing human population has surpassed the capacity of the Earth to supply enough of these essential resources to sustain even the current population and level of socioeconomic development.


Main Pathogens Causing Infections And Antibiotic Resistance Profile In Major Burns In Brazil Comparing Two Periods: 2015/2016 And 2019/2020.
Sepsis is the main cause of death in major burns. In this retrospective study conducted in a reference hospital in Brazil, the main agents causing infection and the resistance profile to antibiotics were identified. Additionally, the epidemiological profile, length of hospital stay, type of burn and total body surface area (TBSA) in major burns were collected from medical records, comparing the years 2015/2016 and 2019/2020. In both time periods, there was a predominance of males with a mean age of 43 years. Burns with less than 30% of TBSA predominated. There was a significant increase in positive cultures (p=0.00026), from 58.7% to 80%, and an increase in skin punch culture collection from 25.6% to 43.9% in the years 2019/2020. The predominant etiological agent was Pseudomonas aeruginosa, followed by Acinetobacter baumannii resistant to carbapenems, and Staphylococcus aureus in both evaluated periods. The percentage of deaths was higher in 2019/2020 (26.2% vs 14.6%; p=0.026). The length of hospital stay was shorter in the latter period (p=0.0081). Sepsis was the cause of death in 81.2% of cases in 2015/2020 and 78.3% in 2019/2020. Among the deaths, Pseudomonas aeruginosa was the main agent identified. There was no change in the main pathogens and bacterial antibiotic resistance between the two time periods.


Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry.
Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.


Investigating the correlation between DNA methylation and immune‑associated genes of lung adenocarcinoma based on a competing endogenous RNA network.
In recent years, there have been major breakthroughs in immunotherapies for the treatment of cancer. However, different patients have different responses to immunotherapy. Numerous studies have shown that the accumulation of epigenetic abnormalities, such as DNA methylation, serve an important role in the immune response of lung adenocarcinoma (LUAD). To investigate the effects of DNA methylation on tumor immunity with survival and prognosis, relevant studies can be performed based on the regulatory mechanisms of RNA molecules. For example, long non‑coding RNAs (lncRNAs), which regulate gene expression through epigenetic levels. By constructing an immune-associated competitive endogenous RNA (ceRNA) network, the present study identified the regulatory associations among 3 key immune‑associations mRNAs, 2 microRNAs (miRs) and 29 lncRNAs that were closely associated with the prognosis of patients with LUAD. The molecular biology analysis indicated that hypomethylation of the 1101320‑1104290 regions of chromosome 1 resulted in the low expression levels of LINC00337 and that LINC00337 may affect the expression levels of CHEK1 by competitively binding with human (has)‑miR‑373 and hsa‑miR‑195. Therefore, abnormal DNA methylation in lncRNA‑associated regions caused their abnormal expression levels, which further affected the interactions between RNA molecules. The interactions between these RNA molecules may have regulatory effects on tumor immunity and the prognosis of patients with LUAD.


Beta-receptor properties in soleus muscles from spontaneously hypertensive rats.
We have compared the properties of beta-adrenergic receptors in slow-twitch, oxidative skeletal muscles (soleus) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at three different ages. The investigation was based on the hypothesis that the increase in Na+ content and decrease in fatigue resistance observed previously in the soleus of SHR might be the result of a down regulation of muscle beta-receptors. Activation of beta-adrenergic receptors in skeletal muscle stimulates sarcolemmal sodium-potassium adenosine triphosphatase, which produces an efflux of Na+ and an influx of K+. Receptor down-regulation would be expected to reduce hormonal stimulation of Na+ pump activity, particularly during exercise. The results of receptor binding studies, however, and an investigation of cyclic adenosine monophosphate (cAMP) production in response to applied epinephrine indicated that there were no significant differences in receptor properties in the soleus muscles of SHR and WKY rats. Receptor number and affinity were the same in the two strains, and the rate, magnitude, and duration of the increase in cAMP in response to 10(-6) M epinephrine were also similar. beta-Adrenergic receptor down-regulation does not appear to be a generalized phenomenon in tissues of SHR, despite the appearance of other physiological changes in the tissue.


Anti-cancer effectiveness of a novel ceramide analog on chemo-sensitive and chemo-resistant breast cancers.
Ceramides are known to show anti-cancer activity. A novel ceramide analog, (S,E)-3-hydroxy-2-(2-hydroxybenzylidene)amino-N-tetradecylpropanamide (analog 315) was developed as part of a larger study focused on finding more effective breast cancer treatments. To assess whether analog 315 shows any or a combination of the following effects in breast cancer cells in vitro: inhibiting proliferation, inducing apoptosis, and altering protein expression. Also, to determine whether it inhibits chemo-resistant breast cancer tumor growth in vivo mouse model. In vitro cell proliferation and apoptosis after treatment with analog 315 were assessed in three breast cancer cell lines (MCF-7, MCF-7TN-R, and MDA-MB-231) and reported. Protein expression was assessed by microarray assay. For the in vivo studies, chemo-resistant breast cancer cells were used for tumor development in two groups of mice (treated and control). Analog 315 (25 mg/kg/day) or control (dimethyl sulfoxide) was administered intraperitoneally for 7 days. Effects of analog 315 on inhibiting the growth of chemo-resistant breast cancer tumors after treatment are reported. Analog 315 reduced MCF-7TN-R chemo-resistant tumor burden (volume and weight) in mice. Liver metastasis was observed in control mice, but not in the treated animals. Ki-67, a proliferation marker for breast cancer cells, increased significantly (P < 0.05) in control tumor tissue. In vitro studies showed that analog 315 inhibited cell proliferation, altered protein expression and induced apoptosis in all three breast cancer cell lines studied, of which the effects on MCF-7TN-R cells were the most significant. Analog 315 reduced tumor growth in chemo-resistant breast cancer, inhibited cell proliferation, altered protein expression, and induced apoptosis in all three cell lines studied.


Influencia de los hábitos y los conocimientos sobre alimentación en la sobrecarga ponderal según el ámbito de residencia: estudio transversal.
comprobar la influencia de los conocimientos y los hábitos alimenticios en la sobrecarga ponderal según el ámbito de residencia (urbano o rural). se administró un cuestionario a 451 personas, residentes en la zona básica de salud de Villaviciosa (Asturias, España), entre 35 y 65 años, distribuidas en zona rural y urbana, formulario compuesto por preguntas sobre datos sociodemográficos, hábitos y conocimientos nutricionales. Se calcularon frecuencias relativas (%) para las variables cualitativas, y medias aritméticas (desviaciones estándar) para las cuantitativas. Se empleó la correlación de Pearson para comprobar o descartar la relación entre la puntuación en el cuestionario de conocimientos sobre nutrición y el índice de masa corporal (IMC). Para estudiar la relación entre cada pregunta del cuestionario de hábitos y el ámbito de residencia se empleó la prueba chi-cuadrado. Para comparar las medias del IMC por ámbito se aplicó la prueba t para muestras independientes. Se realizaron regresiones logísticas para calcular las odds ratio (OR) entre la variable dependiente (sobrecarga ponderal) y las variables sociodemográficas. la edad media de los encuestados fue de 49.96 años y el IMC promedio de 26.87 kg/m2, presentando sobrecarga ponderal el 57.6 % total. No leer las etiquetas nutricionales aumenta el riesgo de tener sobrecarga ponderal (OR = 2.2; p = 0.001); quienes consideran que comen en exceso muchas veces presentan mayor probabilidad de sobrecarga ponderal (OR = 8.6; p < 0.001); comer fuera de casa varias veces por semana (OR = 11.6; p = 0.019), así como el consumo de refrescos o zumos procesados (OR = 3.3; p = 0.013) y alcohol de baja graduación (OR = 2.8; p = 0.003) durante las comidas aumentan la probabilidad de sobrecarga ponderal. los hábitos alimenticios y los patrones de actividad física son los principales responsables de sobrecarga ponderal. El adecuado conocimiento en la población puede ayudar a la elaboración de un plan preventivo que permita frenar el crecimiento del sobrepeso y la obesidad.


Transdermal buprenorphine for in-hospital transition from full agonist opioids to sublingual buprenorphine: a retrospective observational cohort study.
Patients with opioid use disorder may have difficulty transitioning from full-agonist opioids to sublingual buprenorphine due to the risk of precipitated opioid withdrawal. Novel strategies have been developed to facilitate this transition, including the use of micro-dosing with transdermal buprenorphine. We began using a transdermal buprenorphine transition strategy at our hospital in 2019. We performed a retrospective observational cohort study of patients treated with transdermal buprenorphine to facilitate transition from full-agonist opioids (prescribed or recreational) while hospitalized between January 2019 and December 2020. Patients were excluded if transdermal buprenorphine was given for pain, if they did not receive at least one dose of sublingual buprenorphine while hospitalized, or if their clinical course precluded analysis of their tolerance of the transition protocol. Data on the doses and timing of medications, symptoms during transition, and hospital outcomes were abstracted from the electronic medical record. We identified 41 cases that satisfied inclusion and exclusion criteria. Thirty-five cases involved a transition from medically indicated opioids; of these, 8 cases involved a transition from methadone. Six cases involved a transition from illicit opioids used prior to hospital presentation. For patient transitioning from medically indicated opioids, the median milligram morphine equivalent (MME) on the day prior to transdermal buprenorphine application was 63.8 (range 0-900, IQR 153.8) and the median MME on the day of transdermal buprenorphine application was 34.5 (range 0-600, IQR 65.3). The median initial dose of sublingual buprenorphine administered was 8 mg (range 2-8mg, IQR 6mg), the median total first-day dose was 16mg (range 2-24mg, IQR 16mg), and the median total daily dose on the last day of follow-up was 16mg (range 2-24mg, IQR 16mg). In 38 cases, patients completed the transition to sublingual buprenorphine and were still taking buprenorphine at the time they left the hospital. The transition protocol was fairly well-tolerated, with 59% of cases tolerating it well and 32% tolerating it fairly. Our findings suggest that the use of transdermal buprenorphine to facilitate transition to sublingual buprenorphine is generally well-tolerated, and may be helpful in hospitalized patients. We identified several areas for improvement in future practice by reviewing the clinical courses of patients who tolerated transition poorly. Limitations of the study include its retrospective chart review design, the lack of a standardized transition protocol during the study period, and the lack of standardized data in the medical record regarding patients' tolerance of the transition protocol. Future research should include prospective studies using a standardized protocol and structured, pre-planned assessments of opioid withdrawal during the transition period. The use of transdermal buprenorphine to facilitate induction of sublingual buprenorphine therapy in hospitalized patients with OUD was generally well-tolerated in this single-center retrospective observational study. Further prospective research is needed to demonstrate efficacy and optimize treatment protocols.


A High-throughput HPLC-MS/MS Assay for the Detection, Quantification and Simultaneous Structural Confirmation of 136 Drugs and Metabolites in Human Urine.
Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays on various mass spectrometry platforms have been described in the literature, most methods either analyze only a limited number of compounds and/or require tedious and time-consuming sample preparation. A major challenge in urine toxicology screening is the minimization of false-negative and false-positive results. This was addressed by screening for a comprehensive panel of 136 compounds of importance for pain and drug addiction clinics, using high-end, high-sensitivity, fast-scanning mass spectrometry in combination with simultaneous structural confirmation based on ion ratios. The assay was validated and successfully participated in proficiency challenges. The assay met all predefined acceptance criteria. The lower limit of quantifications ranged from 10 to 100 ng/mL. Interday trueness and imprecisions ranged from 73.8% to 116.2% and 2.4%-20.0%, respectively. The total assay run time was 10 minutes. We developed and successfully validated a robust, sensitive, and specific liquid chromatography coupled with tandem mass spectrometry-based urine toxicology screening platform that allows for the addition of drugs to quickly adjust to new clinical needs. To date, more than 3000 clinical samples have successfully been analyzed. Our results also indicated that such a quantitative multianalyte assay is pushing against the limits of current fast-scanning MS/MS instrumentation and that the number of analytes and their internal standards must be balanced with acceptable sensitivity, reproducibility, structural confirmation, and the ability to reliably quantify, all of which was achieved.


[Research on the effect of shen xian sheng mai ye on experimental sick sinus syndrome].
The effects of shen xian sheng mai ye (SXSMY) on experimental sick sinus syndrome (SSS) were observed. By applying 20% formaldehyde to the rabbits' sino-atrial node area, we got the acute animal model of SSS. By observing the rabbits' heart rate (HR), arrhythmia and cardioelectric physiologic index in different periods, the results were as follows: (1) Increasing heart rate: SXSMY could increase rabbits' HR 10-30 times per minute by observing electrocardiogram within 2 hours (P less than 0.05-0.001). (2) Correcting arrhythmia: SXSMY could reduce arrhythmia of sinus nodal arrest and nodal rhythm remarkably. (3) Improving sinus atrial node function: SXSMY could improve sinus node recovery time (SNRT) and sinus atrial conducting time (SACT) with the method of atrial pacing (AP) (P less than 0.01-0.001). But the above results did not appear in atropine and glucose groups.


Neuroprotection in vascular dementia.
Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD), and one of the major causes of mental and physical disability in developed countries. As such, the identification and implementation of strategies which prevent the development of the condition or enable improvements in patients with VaD are healthcare objectives of the first order. VaD is now regarded as a combined group of clinical-pathological entities rather than one disease, that is, multiple pathogenic mechanisms and lesion types underlie a cognitive impairment of vascular origin. The clinical diagnosis of VaD is complex and difficult because of the heterogeneous nature of its clinical presentation and progression and the low sensitivity of existing clinical criteria. Moreover, there is growing evidence of the epidemiological significance of mixed forms of dementia, and that ischemic processes may precipitate and exacerbate cognitive impairment in AD. Numerous compounds have been proposed as potentially useful in the treatment of patients with VaD, comprising vasodilatative, antithrombotic, hemorrheological, nootropic, antiserotoninergic and, most recently, antiglutamatergic and cholinergic approaches. In spite of some initially favorable reports based on the use of memantine, donepezil and galantamine, there is as yet no conclusive evidence of a definitive treatment for VaD. Unsatisfactory results from VaD drug trials may be attributed in part to the diversity of the patients included (underlying pathogenic mechanisms, number, type, and location of vascular lesions), and to methodological limitations in the design of the trials (outcome measures, end-points, size, follow-up period). The treatment of modifiable vascular risk factors - hypertension, diabetes mellitus, hypercholesterolemia and heart disease - is an important strategy for the reduction of the risk of dementia, and is likely to slow the progress of cognitive decline.


Studies, with a luminogenic peptide substrate, on blood coagulation factor X/Xa produced by mouse peritoneal macrophages.
The formation and secretion of coagulation Factor X/Xa by mouse peritoneal macrophages was studied with a luminogenic peptide substrate (S-2613; t-butyloxycarbonylisoleucylglutamyl-gamma-piperidylglycylarginylisoluminol). Amidolysis was quantified by measuring the light emitted during oxidation of isoluminol, released by Factor Xa. A lower detection limit of about 0.5ng of Factor Xa was established; the assay was linear with enzyme concentration up to at least 100ng/ml. Factor X was determined after treatment with the Factor X-activating component of Russell's-viper (Vipera russelli) venom. Macrophages, cultured in the absence of serum, released Factor X/Xa into the culture medium. The concentration of coagulation enzyme in the medium increased in an essentially linear fashion over a period of at least 3 days, at a rate corresponding to 6-8ng produced/24h per 10(6) cells. The ratio of Factor Xa/X+Xa varied from about 60 to 100%, showing that activation of Factor X to Xa is not prerequisite to release of the enzyme from the cells. Factor Xa activity was suppressed in the presence of warfarin [3-(alpha-acetonylbenzyl)-4-hydroxycoumarin; 12.5mug/ml of medium], but could be restored by adding vitamin K (0.1mug/ml) along with the warfarin. Cultures to which Sepharose beads containing covalently bound anti-(Factor X) antibodies had been added showed decreased amounts of free Factor X/Xa in the culture medium. The missing activity could be demonstrated by incubating the recovered conjugate with the substrate peptide S-2613. Factor Xa produced by the macrophages was efficiently inactivated by heparin in the presence of antithrombin, heparin with high affinity for antithrombin being more effective than the corresponding low-affinity species.


A case of diffuse nodular lymphoid hyperplasia.
Diffuse nodular lymphoid hyperplasia represents a rare disease that is grossly characterized by the presence of numerous visible mucosal nodules measuring up to, and rarely exceeding, 0.5 cm in diameter. These may involve the entire small intestine, the large intestine, or both. The etiology is unknown. When diffuse nodular lymphoid hyperplasia is found predominantly in the colon, it can mimic a variety of polyposis syndromes and this may cause difficulties in diagnosis. The disease may be associated with other pathologies, especially gastrointestinal malignancies. This causes controversy when deciding the treatment options. Following patients without any treatment may lead to malignant progression, while surgical treatment may result in unnecessary radical resections because of obscurity in the diagnosis. We report here a diffuse nodular lymphoid hyperplasia case who underwent a radical resection because of obscurity in the diagnosis.


A low-frequency wave motion mechanism enables efficient energy transport in carbon nanotubes at high heat fluxes.
The great majority of investigations of thermal transport in carbon nanotubes (CNTs) in the open literature focus on low heat fluxes, that is, in the regime of validity of the Fourier heat conduction law. In this paper, by performing nonequilibrium molecular dynamics simulations we investigated thermal transport in a single-walled CNT bridging two Si slabs under constant high heat flux. An anomalous wave-like kinetic energy profile was observed, and a previously unexplored, wave-dominated energy transport mechanism is identified for high heat fluxes in CNTs, originated from excited low frequency transverse acoustic waves. The transported energy, in terms of a one-dimensional low frequency mechanical wave, is quantified as a function of the total heat flux applied and is compared to the energy transported by traditional Fourier heat conduction. The results show that the low frequency wave actually overtakes traditional Fourier heat conduction and efficiently transports the energy at high heat flux. Our findings reveal an important new mechanism for high heat flux energy transport in low-dimensional nanostructures, such as one-dimensional (1-D) nanotubes and nanowires, which could be very relevant to high heat flux dissipation such as in micro/nanoelectronics applications.


Prophylaxis and treatment of infection of the immunocompromised host by granulocyte transfusions.
Granulocyte transfusions are expensive and involve healthy donors in a procedure which is time-consuming, uncomfortable and not without risk. It is therefore important to consider carefully the circumstances which justify their use. The indiscriminate transfusion of inadequate quantities of granulocytes from random donors into sensitized recipients should be discouraged. Severely neutropenic patients with bacterial infection persisting in the face of maximum antibiotic therapy are clearly appropriate recipients of granulocyte transfusion therapy. Well-designed programmes of prophylactic granulocyte transfusion can reduce the acquisition of bacterial infection in granulocytopenic patients. However, there are very few clinical situations in which their use is justified. A wider use of granulocytes must await better techniques of granulocyte procurement and donor selection.


Bipolar affective puerperal psychosis associated with consanguinity.
Most clinical and genetic evidence suggests that puerperal psychosis is closely related to bipolar affective disorder. During a linkage study of bipolar disorder we ascertained a British family in which puerperal psychosis was associated with consanguinity in three sisters. All three subjects had lifetime RDC diagnoses of bipolar I or manic disorder. An inbred brother also had bipolar I disorder. The only female member of the sibship to escape puerperal psychosis was outbred. These findings are consistent with several genetic models for bipolar disorder in this family. The most interesting possibility is a single major susceptibility locus of recessive effect. Under this assumption, the family could be used for homozygosity mapping to help localise the putative recessive locus. If other inbred families can be found in which the same putative recessive locus is operating, the power to localise the gene by homozygosity mapping would be greatly increased.


Assessing the Impact of COVID-19 on IBD Outcomes Among Vulnerable Patient Populations in a Large Metropolitan Center.
With the onset of COVID-19, there were rapid changes in healthcare delivery as remote access became the norm. The aim of this study was to determine the impact of changes in healthcare delivery during the COVID-19 pandemic on patients with inflammatory bowel disease (IBD), in both well-resourced and vulnerable populations. Using a mixed methods, observational study design, patients receiving IBD care at a university or a safety-net hospital were identified by the electronic health record. Patient demographics, IBD history, and disease activity were acquired from the electronic health record. IBD-related outcomes were compared from the onset of the pandemic in the United States until December 2020 (COVID-19 pandemic year 1) and compared with outcomes in the previous year. A subset of participants provided their perspective on how changes in healthcare delivery and financial stability impacted their IBD through a standardized questionnaire and semi-structured interview. Data from a total of 1449 participants were captured, 1324 at the tertiary care university hospital and 125 at the safety-net hospital. During COVID-19, there was a decrease in healthcare utilization at both sites. Race/ethnicity and primary language were not associated with IBD-related hospitalizations or admissions. Patients that were employed and those with insurance had a higher number of IBD-related emergency department visits at both the university and safety-net hospitals (P = .03 and P = .01, respectively). Patients who did not speak English were more likely to report challenges using technology with telehealth and difficulty contacting IBD providers. For IBD populations, during COVID-19, in both hospital settings, emergency department visits, hospitalizations, outpatient surgery, and clinic visits were reduced compared with the year prior. Patients with lower socioeconomic status and limited English proficiency reported facing more challenges with changes to healthcare delivery, healthcare access, and conveying changes in IBD activity. These results highlight the need for payors and providers to specifically attend to those populations most susceptible to these systemic and lasting changes in care delivery and promote greater equity in healthcare.


Acetylcholine receptor antibody positivity rate in ocular myasthenia gravis: a matter of age?
Anti-acetylcholine receptor antibodies (AChR Abs) are detected in 85% of myasthenia gravis (MG) patients, at higher rates in patients with late-onset disease. AChR Ab frequency is generally thought to be much lower in ocular MG (OMG), although recent studies reported positivity rates higher than 70%. We hypothesized that the improved AChR Ab diagnostic yield in OMG could be related to an increased frequency of late-onset disease, as observed in generalized MG. We compared OMG patients, with disease onset before or after 1998, for the age of onset, sex, presence of thymoma, immunosuppressive therapy rate, AChR Ab positivity, and follow-up duration. All patients had a follow-up ≥ 2 years. AChR Abs were tested by radioimmunoassay. The study included 133 patients. Disease onset occurred before 1998 in 54/133 cases (41%). Age of onset, the proportion of late-onset patients, and AChR Ab positivity rate were significantly increased in the more recent population. Thymoma frequency was similar in the two series. On multivariate analysis, the only variable predicting AChR Ab positivity was the age at onset ≥ 50 years (OR = 6.50, 95% CI = 2.70-15.63, p < 0.0001). Our results confirm that current AChR Ab positivity in OMG may be higher than generally thought. In our population, this finding was associated with an increased frequency of late-onset cases.


The myth of genetic enhancement.
The ongoing revolution in molecular genetics has led many to speculate that one day we will be able to change the expression or phenotype of numerous complex traits to improve ourselves in many different ways. The prospect of genetic enhancements has generated heated controversy, with proponents advocating research and implementation, with caution advised for concerns about justice, and critics tending to see the prospect of genetic enhancements as an assault on human freedom and human nature. Both camps base their arguments on the unquestioned assumption that the science will realize either their dreams or nightmares. In this paper, I show that their beliefs are based upon two fundamental mistakes. First, they are based upon an unwarranted reliance in a genetic determinism that takes for granted that the traits that we might most want to enhance, like intelligence, aggression, shyness, and even athletic ability, can be causally directed by specific genes. In so doing, character descriptions are reified to be concrete and discrete entities, in this case, genes. Second, they have accepted on faith that there is, or will be, a science to translate their hopes or worries into reality when, in fact, that is unlikely to occur because of the irreducible complexity of phenotypic expression.


Bipolaron in different configuration of quantum confinement.
The authors used Landau-Pekar variational method to investigate a strong-coupling singlet optical bipolaron in different configuration of quantum confinement. Numerical and analytical results showed that when configuration changes from quantum dot and wire to well, confinement shows different effect on the formation of a bipolaron. In contrast to a bipolaron in a quantum dot or wire, the binding energy of a bipolaron in a quantum well increases with increasing confinement, indicating that confinement favors bipolaron formation in a quantum well.


[Apnea as a presenting symptom in human metapneumovirus infection].
Human metapneumovirus (hMPV), a recently described pathogen of lower respiratory tract infections (LRTI), has been detected in 5,4% of Chilean infants hospitalized for LRTI whom are negative for adenovirus, respiratory syncytial virus, influenza and parainfluenza viruses. hMPV may cause bronchiolitis or pneumonia in hospitalized patients, and ocassionally require admission to intensive care units and mechanical ventilation. The infection has been associated with apnea, especially in preterm infants. Nosocomial dissemination has also been described. We present the case of a one-month-of age premature infant with apnea, and infection caused by hMPV of probable nosocomial aquisition. Clinical features of hMPV infection are reviewed and its association with apnea and nosocomial transmission is discussed. hMPV should be included in the routine diagnosis of respiratory viruses in infants with apnea and should be considered among the respiratory pathogens associated with nosocomial transmission.


A New, Carbon-Negative Precipitated Calcium Carbonate Admixture (PCC-A) for Low Carbon Portland Cements.
The production of Portland cement accounts for approximately 7% of global anthropogenic CO₂ emissions. Carbon CAPture and CONversion (CAPCON) technology under development by the authors allows for new methods to be developed to offset these emissions. Carbon-negative Precipitated Calcium Carbonate (PCC), produced from CO₂ emissions, can be used as a means of offsetting the carbon footprint of cement production while potentially providing benefits to cement hydration, workability, durability and strength. In this paper, we present preliminary test results obtained for the mechanical and chemical properties of a new class of PCC blended Portland cements. These initial findings have shown that these cements behave differently from commonly used Portland cement and Portland limestone cement, which have been well documented to improve workability and the rate of hydration. The strength of blended Portland cements incorporating carbon-negative PCC Admixture (PCC-A) has been found to exceed that of the reference baseline-Ordinary Portland Cement (OPC). The reduction of the cement clinker factor, when using carbon-negative PCC-A, and the observed increase in compressive strength and the associated reduction in member size can reduce the carbon footprint of blended Portland cements by more than 25%.


Placental transfer of the hypolipidemic drug, clofibrate, induces CYP4A expression in 18.5-day fetal rats.
Rats at day 15.5 of gestation were dosed intraperitoneally with 300 mg.kg-1 of clofibrate for three consecutive days at 24-hr intervals and were culled 24 hr after the final injection. This regime produced maximal induction of the cytochrome P4504A (CYP4A) mRNAs in the maternal liver and kidney and in 18.5-day fetal tissues. The maternal hepatic and renal CYP4A mRNA levels had risen 12- and 2-fold, respectively, above the constitutive levels seen in untreated pregnant rats at an equivalent stage of gestation. Clofibrate was capable of traversing the placenta and modulating the fetal CYP4A mRNA expression as demonstrated by a 3-fold elevation in the mRNA levels in those fetuses explanted from drug-induced mothers, compared with those fetuses removed from untreated mothers. The CYP4A mRNAs were demonstrated in the fetal liver via dot-blot and Northern blot analyses. In addition, low levels of CYP4A mRNA expression were detected in the induced placenta via Northern blot analysis. Western blot analysis revealed that the CYP4A protein levels increased in the maternal liver and in the kidney and fetal livers after exposure to clofibrate. Peroxisome proliferation, a phenomenon associated with induction of CYP4A1 expression in rodents, was demonstrated in both maternal and fetal livers, with the use of light and electron microscopy.


Structural basis of functions of the mitochondrial cytochrome bc1 complex.
The crystal structure of the cytochrome bc1 complex (ubiquinol-cytochrome c reductase) from bovine heart submitochondria was determined at 2.9 A resolution. The bc1 complex in crystal exists as a closely interacting dimer, suggesting that the dimer is a functional unit. Over half of the mass of the complex, including subunits core 1 and core 2, are on the matrix side of the membrane, while most of the cytochrome b subunit is located within the membrane. There are 13 transmembrane helices in each monomer, eight of them belonging to cytochrome b. Two large cavities are made of the transmembrane helices D, C, F and H in one monomer and helices D' and E' from the other monomer of cytochrome b, and the transmembrane helices of c1, iron-sulfur protein (ISP), and subunits 10 and 11. These cavities provide entrances for ubiquinone or inhibitor and connect the Qi pocket of one monomer and the Qo pocket of the other monomer. Ubiquinol made at the Qi site of one monomer can proceed to the nearby Qo site of the other monomer without having to leave the bc1 complex. The soluble parts of cytochrome c1 and ISP, including their redox prosthetic groups, are located on the cytoplasmic side of the membrane. The distances between the four redox centers in the complex have been determined, and the binding sites for several electron transfer inhibitors have been located. Structural analysis of the protein/inhibitor complexes revealed that the extramembrane domain of the Rieske iron-sulfur protein may undergo substantial movement during the catalytic cycle of the complex. The Rieske protein movement and the larger than expected distance between FeS and cytochrome c1 heme suggest that electron transfer reaction between FeS and cytochrome c1 may involve movements or conformational changes in the soluble domain of iron-sulfur protein. The inhibitory function of E-beta-methoxyacrylate-stilbene and myxothiazol may result from the increase of mobility in ISP, whereas the function of stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole may result from the immobilization of ISP.


Quantitative metaproteomics reveals composition and metabolism characteristics of microbial communities in Chinese liquor fermentation starters.
Daqu, the Chinese liquor fermentation starter, contains complex microbial communities that are important for the yield, quality, and unique flavor of produced liquor. However, the composition and metabolism of microbial communities in the different types of high-temperature Daqu (i.e., white, yellow, and black Daqu) have not been well understood. Herein, we used quantitative metaproteomics based on data-independent acquisition (DIA) mass spectrometry to analyze a total of 90 samples of white, yellow, and black Daqu collected in spring, summer, and autumn, revealing the taxonomic and metabolic profiles of different types of Daqu across seasons. Taxonomic composition differences were explored across types of Daqu and seasons, where the under-fermented white Daqu showed the higher microbial diversity and seasonal stability. It was demonstrated that yellow Daqu had higher abundance of saccharifying enzymes for raw material degradation. In addition, considerable seasonal variation of microbial protein abundance was discovered in the over-fermented black Daqu, suggesting elevated carbohydrate and amino acid metabolism in autumn black Daqu. We expect that this study will facilitate the understanding of the key microbes and their metabolism in the traditional fermentation process of Chinese liquor production.


Perinatal social work with childbearing adolescents.
Issues relating to adolescent childbearing have rapidly moved to the forefront of this nation's agenda. The implications of an adolescent's decision to have a baby have health, social and economic consequences for the adolescent, her offspring, partner and family and for all of society. This article will discuss the health, social and developmental consequences of adolescent childbearing and provide an overview of social work practice with childbearing adolescents.


Wear estimation of trapezoidal and circular shaped hip implants along with varying taper trunnion radiuses using finite element method.
The hip joint is the vital joint that is responsible for the bodyweight transfer from the upper body to the lower body. Due to age these joints are worn out and need to be replaced by artificial hip implants. Wear is the predominant factor that is responsible for the loosening of hip implants. The wear occurs between the joints due to various reasons. The wear estimation at the design stage gives a clear idea about the life of the implants and also minor changes in the design may also significantly increase the life expectancy of the implant which can further reduce the rate of revision surgery. The linear wear rate is estimated in the taper trunnion surface. In this study, the circular and trapezoidal-shaped stem implant is designed, and wear studies are performed at the trunnion junction. The femoral head of size 28 mm, acetabular cup thickness of 4 mm, and a backing cup of thickness 2 mm are considered for the study. The neck taper radiuses at the top surface are altered. Ansys is used to perform the simulations. At the time of assembly of the femoral head into the stem, the stresses were found to be increasing with an increase in the top surface radius of the neck taper junctions. However, when the walking conditions are considered for wear estimation of implants the circular implants with the 12/14 mm taper exhibited the lesser linear wear rate of 0.003 mm/year. The trapezoidal implants with the 10/14 mm taper exhibited a lesser linear wear rate of 0.032 mm/year. Wear is an important parameter that leads to the revision of implants due to loosening. It is found that with the decrease in the taper radius at the top surface against the standard 12/14 mm taper there is no significant decrease in the wear rate at the taper junction. Overall the circular implants exhibited less wear rate results over the trapezoidal-shaped stem implants. Due to the less linear wear rate, the circular implant has a higher life over the trapezoidal-shaped implant. Further, these implants can be manufactured to test using a hip simulator with the same conditions to validate the obtained results.


A simple technique for controlled subretinal injections.
Recently developed vitrectomy techniques for management of choroidal neovascular membranes and subretinal hemorrhages often involve the subretinal injection of fluid materials. A simple, inexpensive infusion system that allows for the controlled injection of fluid, allowing use of a minimal amount of fluid and maximizing surgeon control, is described.


[Specific antibody deficiency: cases serie].
Specific antibody deficiency is a common antibody immunodeficiency defined as a poor antibody response to pneumococcal polysaccharides antigens present in the 23-valent pneumococcal vaccine, with normal immunoglobulins and normal response to protein antigens. Clinical manifestations include recurrent sinopulmonary infections, severe infections and asthma. The aim of this presentation is to describe clinical manifestations and evolution of a cohort of children with specific antibody deficiency diagnosed and followed in our center between 1998 and 2012.


Dual-Function Conductive Copper Hollow Fibers for Microfiltration and Anti-biofouling in Electrochemical Membrane Bioreactors.
Membrane bioreactors (MBRs) with polymeric/ceramic microfiltration (MF) membranes have been commonly used for wastewater treatment today. However, membrane biofouling often results in a dramatically-reduced service life of MF membranes, which limits the application of this technology. In this study, Cu hollow fiber membranes (Cu-HFMs) with low resistivity (104.8-309.8 nΩ·m) and anti-biofouling properties were successfully synthesized. Further analysis demonstrated that Cu-HFMs reduced at 625°C achieved the bimodal pore size distribution of ~1 μm and a porosity of 46%, which enable high N2 permeance (1.56 × 10-5 mol/m2 s pa) and pure water flux (5812 LMH/bar). The Cu-HFMs were further applied as the conductive cathodes, as well as MF membranes, in the electrochemical membrane bioreactor (EMBR) system that was enriched with domestic wastewater at an applied voltage of 0.9 V. Excellent permeate quality (Total suspended solids (TSS) = 11 mg/L) was achieved at a flux of 9.47 LMH after Cu-HFM filtration, with relatively stable transmembrane pressure (TMP) and low Cu2+ dissolvability (<25 μg/L). The anti-biofouling over time was demonstrated by SEM characterization of the rare biofilm formation on the Cu-HFM cathode surface. By using Cu-HFMs in EMBR systems, an effective strategy to control the membrane biofouling is developed in this study.


PML Body Component Sp100A Restricts Wild-Type Herpes Simplex Virus 1 Infection.
Sp100 (speckled protein 100 kDa) is a constituent component of nuclear structure PML (promyelocytic leukemia) bodies, playing important roles in mediating intrinsic and innate immunity. The Sp100 gene encodes four isoforms with distinct roles in the transcriptional regulation of both cellular and viral genes. Since Sp100 is a primary intranuclear target of infected-cell protein 0 (ICP0), an immediate early E3 ligase encoded by herpes simplex virus 1 (HSV-1), previous investigations attempting to analyze the functions of individual Sp100 variants during HSV-1 infection mostly avoided using a wild-type virus. Therefore, the role of Sp100 under natural infection by HSV-1 remains to be clarified. Here, we reappraised the antiviral capacity of four Sp100 isoforms during infection by a nonmutated HSV-1, examined the molecular behavior of the Sp100 protein in detail, and revealed the following intriguing observations. First, Sp100 isoform A (Sp100A) inhibited wild-type HSV-1 propagation in HEp-2, Sp100-/-, and PML-/- cells. Second, endogenous Sp100 is located in both the nucleus and the cytoplasm. During HSV-1 infection, the nuclear Sp100 level decreased drastically upon the detection of ICP0 in the same subcellular compartment, but cytosolic Sp100 remained stable. Third, transfected Sp100A showed subcellular localizations similar to those of endogenous Sp100 and matched the protein size of endogenous cytosolic Sp100. Fourth, HSV-1 infection induced increased secretion of endogenous Sp100 and ectopically expressed Sp100A, which copurified with extracellular vesicles (EVs) but not infectious virions. Fifth, the Sp100A level in secreting cells positively correlated with its level in EVs, and EV-associated Sp100A restricted HSV-1 in recipient cells. IMPORTANCE Previous studies show that the PML body component Sp100 protein is immediately targeted by ICP0 of HSV-1 in the nucleus during productive infection. Therefore, extensive studies investigating the interplay of Sp100 isoforms with HSV-1 were conducted using a mutant virus lacking ICP0 or in the absence of infection. The role of Sp100 variants during natural HSV-1 infection remains blurry. Here, we report that Sp100A potently and independently inhibited wild-type HSV-1 and that during HSV-1 infection, cytosolic Sp100 remained stable and was increasingly secreted into the extracellular space, in association with EVs. Furthermore, the Sp100A level in secreting cells positively correlated with its level in EVs and the anti-HSV-1 potency of these EVs in recipient cells. In summary, this study implies an active antiviral role of Sp100A during wild-type HSV-1 infection and reveals a novel mechanism of Sp100A to restrict HSV-1 through extracellular communications.


Mining in Papua New Guinea: A complex story of trends, impacts and governance.
Mining is often portrayed as a contributor to sustainable development, especially so in developing countries such as Papua New Guinea (PNG). Since 1970, several large mines have been developed in PNG (e.g. Panguna, Ok Tedi, Porgera, Lihir, Ramu) but always with controversial environmental standards and social impacts often overlooked or ignored. In PNG, mine wastes are approved to be discharged to rivers or oceans on a very large scale, leading to widespread environmental and social impacts - to the point of civil war in the case of Panguna. The intimate links between indigenous communities and their environment have invariably been under-estimated or ignored, leading many to question mining's role in PNG's development. Here, we review the geology of PNG, its mineral resources, mining history, key trends for grades and resources, environmental metrics (water, energy, carbon), mine waste management, and regulatory and governance issues. The study provides a unique and comprehensive insight into the sustainable development contribution of the mining industry in PNG - especially the controversial practices of riverine and marine mine waste disposal. The history of mining is a complex story of the links between the anthroposphere, biosphere, hydrosphere and geosphere. Ultimately, this study demonstrates that the scale of environmental and social impacts and risks are clearly related to the vast scale of mine wastes - a fact which remains been poorly recognised. For PNG, the promise of mining-led development remains elusive to many communities and they are invariably left with significant social and environmental legacies which will last for decades to centuries (e.g. mine waste impacts on water resources). Most recently, the PNG government has moved to ban riverine tailings disposal for future projects and encourage greater transparency and accountability by the mining sector, including its interactions with communities. There remains hope for better outcomes in the future.