Application of the CuSum technique to evaluate changes in recruitment strategies.
While lagging subject enrollment in longitudinal clinical trials is a complex problem, the best recruitment strategy has not been established. Cumulative summation (CuSum) is a statistical process control procedure often applied in quality improvement efforts to detect trend shifts in highly variable serial data. To describe changes in efforts to increase referrals and enrollment in a longitudinal quality-of-life breast cancer study, determine effects of changes in referral strategies on enrollment using a novel application of CuSum, and discuss implications of CuSum as a tool for prospectively managing the subject recruitment process. Ten referrals and eight enrollments per month for a total of 31 months were estimated to meet study subject accrual requirements in the clinical trial. The estimates were used as standards in performing CuSum calculations. CuSum was applied to monthly referral and enrollment data and trend graphs were generated. Alterations in recruitment tactics and strategies were evaluated as to whether changes in trend occasioned such alterations. Unplanned changes in trend were noted. While monthly data were highly variable, an average of 8.42 referrals and 5.92 enrollments were realized during Months 1-12. Based on these figures, projected accrual for 31 months would have enrolled only 184 subjects, 66 subjects short of target. CuSum illustrated this trend. Subsequent shifts in enrollment trends were shown with improvements in referral. Indications for use of CuSum include (a) earlier detection of enrollment trend shifts, and (b) earlier discrimination between effective and ineffective recruitment. Thus, CuSum has implications for both evaluating the effects of planned and unplanned process changes and for managing the recruitment process.


Management of a twin pregnancy in a didelphys uterus: one fetus in each uterine cavity.
We report on a rare case of dicavitary twin pregnancy in a woman with a uterine didelphys. Delivery was performed by elective caesarean section, where live female and male infants were born. Twin pregnancies, in women with uterine anomalies, are high risk and require close surveillance in a specialist centre to monitor for complications such as preterm birth and fetal growth restriction.


Monstrous births and medical networks: debates over forensic evidence, generation theory, and obstetrical authority in France, ca. 1780-1815.
In France between 1780 and 1815, doctors opened a broad correspondence with medical faculties and public officials about foetal anomalies ("monstrosities"). Institutional and legal reforms forced doctors to encounter monstrous births with greater frequency, and they responded by developing new ideas about heredity and embryology to explain malformations to public officials. Though doctors achieved consensus on pathogenesis, they struggled to apply these ideas in forensic cases, especially with doubtful sex. Medical networks simultaneously allowed doctors to explore obstetrical techniques, as licensing regulations forced practitioners into emotional encounters with child anomalies. Doctors thus developed a new ethics for treating monstrosities, viewing them as pathological specimens, forensic objects, and obstetrical tragedies.


Epiphyseal fracture-retrosternal dislocation of the medial end of the clavicle: a case report.
Epiphyseal fracture-retrosternal dislocation of the medeial end of the clavicle is an unusual injury. It may occur as a result of a blow either indirectly on the posterolateral aspect of the shoulder girdle or directly over the sternal end of the clavicle. It is clinically impossible to differentiate from the true posterior dislocation even with the computed tomography, but the treatment for either lesion is the same. Recently we uneventually treated a 15-year-old boy with conservative treatment and got a satisfactory result. The purpose of this paper is to draw the attention of the readers to the rarity and serious nature of such injury and the potential difficulties in establishing diagnosis and achieving reduction.


Space and time-resolved monitoring of phosphorus release from a fertilizer pellet and its mobility in soil using microdialysis and X-ray computed tomography.
Phosphorus is an essential nutrient for crops. Precise spatiotemporal application of P fertilizer can improve plant P acquisition and reduce run-off losses of P. Optimizing application would benefit from understanding the dynamics of P release from a fertilizer pellet into bulk soil, which requires space- and time-resolved measurements of P concentration in soil solutions. In this study, we combined microdialysis and X-ray computed tomography to investigate P transport in soil. Microdialysis probes enabled repeated solute sampling from one location with minimal physical disturbance, and their small dimensions permitted spatially resolved monitoring. We observed a rapid initial release of P from the source, producing high dissolved P concentrations within the first 24 h, followed by a decrease in dissolved P over time compatible with adsorption onto soil particles. Soils with greater bulk density (i.e., reduced soil porosity) impeded the P pulse movement, which resulted in a less homogeneous distribution of total P in the soil column at the end of the experiment. The model fit to the data showed that the observed phenomena can be explained by diffusion and adsorption. The results showed that compared with conventional measurement techniques (e.g., suction cups), microdialysis measurements present a less invasive alternative. The time-resolved measurements ultimately highlighted rapid P dynamics that require more attention for improving P use efficiency.


Invited Commentary: Foreclosures and Health in a Neighborhood Context.
Recent systematic reviews link foreclosure to worse health at both the individual and population levels. In this issue of the Journal, Downing et al. (Am J Epidemiol. 2017;185(6):429-435) add to what is known about foreclosure and health by examining annual measures of glycemic control in relation to local foreclosure activity. They provided evidence that between 2007 and 2010, glycemic control was not associated with rates of completed foreclosure among a continuously insured managed-care population of persons with type 2 diabetes living in 9 California counties. In this commentary, I consider 5 possible interpretations of the null results: 1) foreclosures do not affect health in general, 2) glycated hemoglobin is insensitive to local foreclosure activity, 3) the presence of real estate owned foreclosures (rather than the competed foreclosure rate) affects health, 4) an integrated health-care delivery system buffers patients from the effects of the foreclosure crisis, and 5) community conditions and responses to the foreclosure crisis buffer patients from the effects of the foreclosure crisis. I close by arguing that research on the contextual effects of foreclosure on health should continue despite the ongoing recovery of the housing market.


New drug and biological drug products; evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Final rule.
The Food and Drug Administration (FDA) is amending its new drug and biological product regulations to allow appropriate studies in animals in certain cases to provide substantial evidence of the effectiveness of new drug and biological products used to reduce or prevent the toxicity of chemical, biological, radiological, or nuclear substances. This rule will apply when adequate and well-controlled clinical studies in humans cannot be ethically conducted and field efficacy studies are not feasible. In these situations, certain new drug and biological products that are intended to reduce or prevent serious or life-threatening conditions may be approved for marketing based on evidence of effectiveness derived from appropriate studies in animals and any additional supporting data.


Palliative care--the fourth phase of cancer prevention.
The prevention of suffering represents the fourth phase of a comprehensive cancer control program. The palliative care movement is responsible for the current development of programs which address the suffering of patients with advanced cancer and their families. Palliative care should be integrated with the other elements of cancer controls thus ensuring the continuity of excellent care for patients and strengthening the research and educational base of the palliative care movement.


Anti-inflammatory cytokines: expression and action in the brain.
Transforming growth factor-beta(1) (TGF-beta(1)) and interleukin (IL)-10 gene expression is equivocal in normal brain and upregulated in over a dozen central and peripheral diseases/disorders. The patterns of specific expression of cytokines differ in these diseases. Published data indicate that these cytokines are produced by and act on both neurons and glial cells. Although their actions are commonly viewed as 'anti-inflammatory', they protect neurons and downregulate the responses of glial cells to diseases/disorders in the absence of inflammation. Their actions counterbalance the actions of elevated IL-1 and/or tumor necrosis factor-alpha to maintain homeostasis. Their therapeutic potential will be realized by improving our understanding of their place in neural cytokine networks.


Autoreactive T cells from normal mice recognize mycobacterial 65 kd heat-shock protein from Mycobacterium bovis.
We established a TCR V beta 6+ CD4+ autoreactive T cell line from lymph node cells of unprimed BALB/c mice bred in a specific pathogen-free condition. The T cell line proliferated in the presence of irradiated spleen cells expressing MHC class II I-Ad and/or I-Ed molecules. The proliferative response of the autoreactive T cell line was significantly enhanced in response to 65 kd heat-shock protein (hsp) from Mycobacterium bovis, a member of the hsp60 family, which is highly conserved in both prokaryotes and eukaryotes. Our results suggest that the autoreactive T cells in normal mice may recognize endogenous peptides of self-hsp60 bound to MHC class II gene products and are cross-reactive to mycobacterial 65 kd hsp. The autoreactive hsp-specific T cells may therefore play an important role in the immune surveillance against invasion of various pathogens and tumors by recognizing infected and transformed autologous cells that express high levels of endogenous hsp60.


Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters.
Dexamethasone (Dex), alone or in association with estrogens, is often illegally administered per os at very low dosage as a growth promoter in beef cattle, with effects that are opposite to the muscle wasting and atrophy induced by repeated administration at therapeutic dosages. In vitro and in vivo studies have investigated the catabolic effects of Dex at therapeutic doses on skeletal muscle, demonstrating an increase in the expression of GDF8 (myostatin) gene, a well-known negative regulator of skeletal muscle mass, in a dose-dependent way. This suggested a direct role of myostatin in Dex-induced muscle wasting. In the present study, an oligonucleotide microarray platform was used to compare expression profiles of beef cattle muscle in animals treated with either Dex or Dex plus 17-beta estradiol (Estr) administered at subtherapeutic dosage, against untreated controls. Data analysis demonstrates that the expression profiles were strongly affected by Dex treatment with hundreds of genes upregulated with relevant fold-change, whereas seven genes were downregulated including the myostatin gene. On the contrary, the number of differentially regulated genes was lower in response to the addition of Estr to the Dex treatment. Differentially regulated genes were analyzed to describe the effects of these treatments on muscle physiology, highlighting the importance of specific pathways (e.g., Wnt or cytokine signaling) and cellular processes (e.g., cell shape and motility). Finally, the observed differences in the expression profile will allow the development of indirect bio-markers to detect illegal Dex treatments in beef cattle using quantitative RT-PCR.


Down-regulation of protease-activated receptor-1 is regulated by sorting nexin 1.
Degradation or "down-regulation" of protease-activated receptor-1 (PAR1), a G protein-coupled receptor for thrombin, is critical for termination of receptor signaling. Toward understanding the molecular mechanisms by which activated PAR1 is internalized, sorted to lysosomes, and degraded, we investigated whether PAR1 interacted with sorting nexin 1 (SNX1). SNX1 is a membrane-associated protein that functions in lysosomal sorting of the epidermal growth factor receptor. In vitro biochemical binding assays revealed a specific interaction between a glutathione S-transferase fusion of SNX1 and PAR1. In HeLa cells, activated PAR1 colocalized with endogenous SNX1 and coimmunoprecipitated SNX1. SNX1 contains a phox homology domain predicted to bind phosphatidylinositol-3-phosphate and a C-terminal coiled-coil region. To assess SNX1 function, we examined the effects of SNX1 deletion mutants on PAR1 trafficking. Neither the N terminus nor phox homology domain of SNX1 affected PAR1 trafficking. By contrast, overexpression of SNX1 C-terminal domain markedly inhibited agonist-induced degradation of PAR1, whereas internalization remained virtually intact. Immunofluorescence microscopy studies revealed substantial PAR1 accumulation in an early endosome antigen-1-positive compartment in agonist-treated cells expressing SNX1 C terminus. By contrast, lysosome-associated membrane protein-1 distribution was unperturbed. Together, these findings strongly suggest a role for SNX1 in sorting of PAR1 from early endosomes to lysosomes. Moreover, this study provides the first example of a protein involved in lysosomal sorting of a G protein-coupled receptor in mammalian cells.


Identification of the BCL2/adenovirus E1B-19K protein-interacting protein 2 (BNIP-2) as a granzyme B target during human natural killer cell-mediated killing.
Cytotoxic lymphocytes eliminate infected cells and tumours via the perforin-mediated delivery of pro-apoptotic serine proteases known as granzymes. Granzyme B triggers apoptosis via the cleavage of a repertoire of cellular proteins, leading to caspase activation and mitochondrial depolarization. A simple bioinformatics strategy identified a candidate granzyme B cleavage site in the widely expressed BNIP-2 (BCL2/adenovirus E1B-19K protein-interacting protein 2). Granzyme B cleaved recombinant BNIP-2 in vitro and endogenous BNIP-2 was cleaved during the NK (natural killer) cell-mediated killing of tumour cells. Cleavage required the site identified in the bioinformatics screen and was caspase-independent. Expression of either full-length BNIP-2 or a truncated molecule mimicking the granzyme B cleaved form was pro-apoptotic and led to the caspase-dependent cleavage of BNIP-2 at a site distinct from granzyme B cleavage. Inhibition of BNIP-2 expression did not affect the susceptibility to NK cell-mediated killing. Furthermore, target cells in which BID (BH3-interacting domain death agonist) expression was inhibited also remained highly susceptible to NK cell-mediated killing, revealing redundancy in the pro-apoptotic response to human cytotoxic lymphocytes. Such redundancy reduces the opportunity for escape from apoptosis induction and maximizes the chances of immune-mediated clearance of infected cells or tumour cells.


Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application.
One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Contrast-agent-induced nephropathic changes are more closely related to the magnitude of lipid peroxidation than protein oxidation.


Expression of Hoxb-1 during gastrulation and segmentation stages of carp (Cyprinus carpio).
This report describes the cDNA sequence and embryonic RNA expression pattern of carp Hoxb-1. Carp Hoxb-1 is a labial-like, homeobox-containing gene of the 3' end of the Hox gene cluster. The expression pattern in carp is compared to that of homologs in other vertebrates. As holds for other Hox genes, carp Hoxb-1 is expressed with highest intensity at a sharp anterior boundary, and expression fades out towards posterior. At later stages, gaps were found in the domain. The gene is expressed from late gastrulation onwards, first mainly in the hypoblast but later in all germ layers. Its most prominent expression area is rhombomere 4 (r4) of the hindbrain. Transcripts were also found in the neural tube, mesoderm (lateral, head and presomite), epidermis and neural crest. At 30 hours post fertilization, Hoxb-1 was still expressed in r4, in the anterior trunk neural tube and in the branchial arches posterior to r4. Hox genes are thought to be involved in the specification of positional values along the embryonic anterior-posterior axis, and Hoxb-1 expression in r4 is supposed to be important for specifying the unique identity of this hindbrain segment. The conserved expression in r4 suggests that this is also true for carp Hoxb-1.


Efficacy of metformin for prevention of weight gain in psychiatric populations: a review.
There is uncertainty with regard to the appropriate use of metformin for the prevention and management of second-generation antipsychotic-induced weight gain and metabolic abnormalities. We aim to systematically review the primary literature and to provide recommendations with regard to the use of metformin in psychiatric populations prescribed second-generation antipsychotics. The authors undertook a literature search of Medline, EMBASE, and PsycINFO using the search terms; antipsychotic OR atypical antipsychotic AND weight AND metformin. Narrative review was undertaken without additional statistical analysis. The search provided 198 results from which 10 original research papers were identified: six randomized controlled trials and one open-label study for adults and two randomized controlled trials and one open-label study for children and adolescents. Four meta-analyses were also identified. We concluded that if weight gain occurs after second-generation antipsychotic initiation, despite lifestyle intervention, metformin should be considered. Further studies with adequate statistical power are required to determine the efficacy of metformin in those with chronic psychotic illness.


Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/β-Catenin Pathway in Autistic Mice.
Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway. On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.


Low molecular weight serine proteinase inhibitors of the human intervertebral disc.
Human lumbar disc tissue when extracted with 4M GuHCl and subjected to dissociative CsCl density gradient ultracentrifugation yielded trypsin inhibitor activity in the low bouyant density fractions (rho less than or equal to 1.38 g/ml). Disc proteoglycans sedimented in the high bouyant density fractions (rho greater than or equal to 1.5 g/ml). Sephadex G75F gel filtration of the low bouyant density protein fractions afforded a major low molecular weight (Kav = 0.5) trypsin inhibitor pool which was further purified by trypsin affinity chromatography. This latter step facilitated separation of the trypsin inhibitors from neutral proteinase activity also present. The trypsin inhibitor fraction so isolated was shown to possess potent inhibitory activity against a range of human serine proteinases including leukocyte elastase and cathepsin G, urokinase, kallikrein, plasmin and thrombin. Significantly this serine proteinase inhibitor preparation effectively prevented degradation of proteoglycans by a neutral proteinase also isolated from the human intervertebral disc.


Thoracic endovascular aortic repair for aortic complications after esophagectomy for cancer: report of three cases.
Aortic complications after esophageal cancer surgery are rare and usually fatal. Here, we report three patients who underwent thoracic endovascular aortic repair (TEVAR) for aortic complications after esophagectomy for cancer. In the first case, aortic rupture was caused by pyothorax due to residual tumor after esophagectomy. In the second case, aortic rupture was caused by pyothorax due to anastomotic leakage. In the third case, a pseudoaneurysm was caused by surgical injury during esophagectomy. TEVAR was safe and effective for severe aortic complications when graft infection was avoided. The first case died of sepsis on the 84th postoperative day, and the other two cases have survived 4 years and 2 years to date.


Extracellular Vesicles Arising from Apoptotic Cells in Tumors: Roles in Cancer Pathogenesis and Potential Clinical Applications.
It is known that apoptotic cells can have diverse effects on the tumor microenvironment. Emerging evidence indicates that, despite its renowned role in tumor suppression, apoptosis may also promote oncogenic evolution or posttherapeutic relapse through multiple mechanisms. These include immunomodulatory, anti-inflammatory, and trophic environmental responses to apoptosis, which drive tumor progression. Our group has introduced the term "onco-regenerative niche (ORN)" to describe a conceptual network of conserved cell death-driven tissue repair and regeneration mechanisms that are hijacked in cancer. We propose that, among the key elements of the ORN are extracellular vesicles (EVs), notably those derived from apoptotic tumor cells. EVs are membrane-delimited subcellular particles, which contain multiple classes of bioactive molecules including markers of the cell from which they are derived. EVs are implicated in an increasing number of physiological and pathological contexts as mediators of local and systemic intercellular communication and detection of specific EVs may be useful in monitoring disease progression. Here, we discuss the mechanisms by which EVs produced by apoptotic tumor cells-both constitutively and as a consequence of therapy-may mediate host responsiveness to cell death in cancer. We also consider how the monitoring of such EVs and their cargoes may in the future help to improve cancer diagnosis, staging, and therapeutic efficacy.


[Assessment of reversibility in airway obstruction].
In the medical literature there have been described some methods to determine bronchodilator response. They are different because of the required percentage increase in FEV1 and /or FVC and the way of expressing results -as the percent of predicted or initial value. This study on 38 subjects evaluated that there is better bronchodilator responses when the results are presented as the percentage of the initial value compared with the predicted value. The intensity of improvement in FEV1 depends on the baseline airway obstruction. There are more meaningful responses in subjects with 'poor' initial value when using the criteria of change in FEV1 as a percentage of initial value. About 10% of positive responses are misunderstood as 'poor' when it was considered improvement only in FEV1 (they are positive with reference only to FVC).


Protoveratrines A and B increase sleep apnea index in Sprague-Dawley rats.
The action of protovertarines A and B, which stimulate carotid sinus baroreceptors and vagal sensory endings in the heart as well as pulmonary bed, were assessed on spontaneous and postsigh central sleep apneas in freely moving Sprague-Dawley rats. During the 6-h recording period, animals were simultaneously monitored for sleep by using electroencephalogram and electromyogram recordings, for respiration by single-chamber plethysmography, and for blood pressure and heart period by using radiotelemetry. After administration of 0.2, 0.5, or 1 mg/kg sc of protoveratrines, cardiopulmonary changes lasting at least 6 h were observed in all three behavioral states [heart period increased up to 23% in wakefulness, 21% in non-rapid-eye-movement (non-REM) sleep, and 20% in REM sleep; P < 0.005 for each]. At the same time, there was a substantial increase in the number of spontaneous (375% increase; P = 0.04) and postsigh (268% increase, P = 0.0002) apneas. Minute ventilation decreased by up to 24% in wakefulness, 25% in non-REM, and 35% in REM sleep (P < 0.05 for each). We conclude that pharmacological stimulation of baroreflexes promotes apnea expression in the sleeping rat.


Molecular dynamics and entropy effects in hydrogen-bonded supramolecular polymer N,N'-di(2-methyl-2-pentylheptyl)urea dissolved in nonpolar medium.
On the basis of the static dielectric permittivity temperature behavior of the supramolecular polymer formed by N,N'-di(2-methyl-2-pentylheptyl)urea (MPHU) in carbon tetrachloride diluted solution (10% in mole fraction) and that of neat acetonitrile, it was found that two liquids of the same macroscopic polarity (expressed by the same value of the dielectric permittivity approximately 35) exhibit an essential difference in the field-induced orientational entropy change. A much higher entropy effect is observed for the liquid composed of not too numerous but highly polar molecular entities (MPHU + CCl(4)) than for the liquid composed of numerous but less polar entities (neat acetonitrile). The analysis of the dielectric relaxation spectra of MPHU + CCl(4) solutions was performed with the Davidson-Cole (DC) model. It was found that the DC exponent beta changes its value in a quite important range of 0.4-0.8, depending on MPHU concentration and temperature. This reflects an important deviation of the relaxation mechanism occurring in the supramolecular system investigated from that corresponding to the normal Brownian rotational diffusion (beta = 1).


Desquamative interstitial pneumonia as the initial manifestation of systemic sclerosis.
Interstitial lung disease (ILD) is a frequent pulmonary complication of systemic sclerosis (SSc), and nonspecific interstitial pneumonia is the most commonly recognized pattern of lung injury in these patients. In this report, we describe a never-smoker female presenting with Raynaud phenomenon and ILD that demonstrated desquamative interstitial pneumonia (DIP) on surgical lung biopsy. After 8 months, she was diagnosed with pulmonary hypertension at which time clinical examinations and serologic findings established the diagnosis of SSc. This case report expands the spectrum of patterns of ILD seen in association with SSc to include DIP.


Does Voice Therapy Improve Vocal Outcomes in Vocal Fold Atrophy?
Vocal fold atrophy is increasingly identified in the geriatric population. Current literature shows varying outcomes with voice therapy. Our goal was to analyze multidimensional vocal outcomes of these patients who underwent voice therapy. Secondary aims included determining compliance and analyzing differences in patients who undergo surgery. 197 patients with vocal fold atrophy were included and reviewed. Patients were categorized by treatment received. Patient-reported, perceptual, aerodynamic, and acoustic voice outcomes were analyzed before and after therapeutic intervention. Changes were calculated and significance determined using Wilcoxon signed-rank and rank-sum tests. 89(45%) received no therapy, 43(22%) incomplete therapy, 51(26%) complete therapy, 8(4%) surgery only, and 6(3%) therapy followed by surgery. Those who completed voice therapy showed significant improvement in voice related quality of life (VRQOL) (P = .0225), glottal function index (GFI) (P < .001), grade, roughness, breathiness, asthenia, strain (GRBAS) (P < .001), maximum phonation time (MPT) (P = .0081), and fundamental frequency in women (P = .0024). No significant changes were found in mean airflow. When comparing patients who underwent surgery versus voice therapy, statistically significant differences were present between pre-treatment VRQOL (P = .0269) and GFI (P = .0166). Only 29% of patients with vocal atrophy completed voice therapy when recommended. Within this patient cohort, voice therapy results in significant improvement in multidimensional voice outcomes. Patients with vocal atrophy that undergo surgical treatment differ from those treated with voice therapy alone in their pre-treatment patient-reported measures.


Overview of common practices in calf raising facilities.
In this literature review, we overview some of the common management practices associated with calf rearing in specialized operations of the United States. Given the growing importance of dairy-beef calves entering the beef production of the United States, we overview aspects related to housing, nutrition, and health events during the pre- and post-weaning period. Based on data on dairy animals, we hypothesize how early life experiences could impact the feedlot performances of dairy-beef animals. Most of the large calf raising operations, where the majority of dairy-beef animals are raised, are located in the Central Great Plains and West regions of the United States. Approximately 80% of calves are individually housed, but the type of housing (e.g., outside hutch, inside a barn) varies based on location of calf-raising facilities. Milk-replacer is fed in more than 80% of operations, while milk (saleable or nonsaleable) is fed in approximately 30% of calf raising facilities (some operations fed more than one type of liquid diet). In addition to liquid feed, water and calf starter are offered ad libitum to calves. Adequate starter intake at weaning is crucial for feed transition from pre- to post-weaning period, which occurs at approximately 2 months of age. Then, calves are mainly housed in group pens and transition from calf-starter to total mixed ration (TMR). Health challenges such as scours and bovine respiratory disease (BRD) can hinder the performance of calves and are major causes of morbidity and mortality in calf ranches. Transportation at a very young age and comingling with animals from other dairies can increase the risk of diseases. Current research efforts are focusing on determining individual factors such as body weight (BW) at arrival or biomarkers of inflammation and stress that can be predictive of disease morbidity, mortality, and performance of calves. Future research should focus on how to utilize this information to optimize management and to develop targeted preventative strategies to reduce incidence of diseases and mortality and improve performance during the pre-weaned period. Also, more research is needed to understand how colostrum management, housing, and nutrition can impact the adult performance of dairy-beef animals.


Indication of myomectomy during pregnancy from Doppler ultrasonography.
Myomas during pregnancy must be evaluated carefully, especially in relation to possible premature delivery or spontaneous miscarriage. We wanted to find out whether the addition of Doppler assessment could help in the management of these cases. We found that from all cases of myomas during pregnancy, the most common association with impairment of the fetoplacental unit flow was found in the cases with submucous myomas and the subgroup of those with intramural myomes which show etc. growth during pregnancy. However myomectomy is generally not considered to be indicated to prevent pregnancy complications except for women with a history of myoma-related complications. In pregnancies with myomas, preserving the pregnancy is one goal but different risk factors have to be taken into account at the same time.


An animal model of corpus callosum impingement as seen in patients with normal pressure hydrocephalus.
Callosal impingement has been postulated to cause the symptoms associated with normal pressure hydrocephalus. The authors developed an animal model for the investigation of corpus callosum impingement by the falx cerebri. The corpus callosum was compressed from above by a plastic blade and surgically placed in the interhemispheric fissure in adult Sprague-Dawley rats. Magnetic resonance imaging (MRI) was performed both preoperatively and postoperatively. The brains of the rats also were examined grossly at the time of autopsy. All rats survived the surgical procedure. MRI proved to be a suitable method to image the corpus callosum, to confirm the location of the blade, and to demonstrate the corpus callosum impingement. MRI correlated well with necroscopy sections. It was possible to surgically produce callosal impingement in rats, and this impingement could be confirmed by MRI. In the future, this rat model of callosal impingement will be used to search for evidence of changes in metabolism, neuroelectrical activity, behavior, and neuronal anatomy which are known or are thought to be associated with hydrocephalus.


Trends in Stroke Presentations before and during the COVID-19 Pandemic: A Meta-Analysis.
There are reports of decline in the rates of acute emergency presentations during coronavirus disease 2019 (COVID-19) pandemic including stroke. We performed a meta-analysis of the impact of COVID-19 pandemic on rates of stroke presentations and on rates of reperfusion therapy. Following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines, we systematically searched the literature for studies reporting changes in stroke presentations and treatment rates before and during the COVID-19 pandemic. Aggregated data were pooled using meta-analysis with random-effect models. We identified 37 observational studies (n=375,657). Pooled analysis showed decline in rates of all strokes (26.0%; 95% confidence interval [CI], 22.4 to 29.7) and its subtypes; ischemic (25.3%; 95% CI, 21.0 to 30.0), hemorrhagic (27.6%; 95% CI, 20.4 to 35.5), transient ischemic attacks (41.9%; 95% CI, 34.8 to 49.3), and stroke mimics (45.6%; 95% CI, 33.5 to 58.0) during months of pandemic compared with the pre-pandemic period. The decline was most evident for mild symptoms (40% mild vs. 25%-29% moderate/severe). Although rates of intravenous thrombolytic (IVT) and endovascular thrombectomy (EVT) decreased during pandemic, the likelihood of being treated with IVT and EVT did not differ between the two periods, both in primary and in comprehensive stroke centers (odds ratio [OR], 1.08; 95% CI, 0.94 to 1.24 and OR, 0.95; 95% CI, 0.83 to 1.09, respectively). Rates of all strokes types decreased significantly during pandemic. It is of paramount importance that general population should be educated to seek medical care immediately for stroke-like symptoms during COVID-19 pandemic. Whether delay in initiation of secondary prevention would affect eventual stroke outcomes in the long run needs further study.


[Hepatitis C: natural history, biology, treatment monitoring].
This article presents the laboratory tests used to diagnose hepatitis C, to evaluate the severity of the chronic fibrosing disease, and to monitor the efficacy of treatment. Histological examination of liver biopsies is of the utmost importance for evaluating the development of fibrosis. Factors that precipitate fibrosis are reviewed. The annual rate of fibrosis progression can be assessed based on the estimated duration of hepatitis C virus contamination and on the fibrosis score established using the METAVIR classification. This allows to distinguish slow, fast, and intermediate fibrosis and to estimate the mean time to cirrhosis development. Combined use of interferon alpha (3 million units three times a week) and of Ribavirine (1000-1200 mg per day orally according to body weight) for 6 to 12 months is currently the standard treatment for hepatitis C. Treatment efficacy varies with a number of virus-related factors (genotype, viral burden) and patient-related factor (hepatic fibrosis, age, sex). In nonresponders, the value of treatment should not be assessed in terms of efficacy but in terms of slowing of fibrosis progression.


Pulmonary embolism in chronic hypoxemic patients with and without secondary polycythemia--analysis of risk factors in prospective clinical study.
Prospectively evaluate the incidence of pulmonary embolism and risk factors for this life-threatening disease on chronic hypoxemic patients treated in intensive respiratory care unit. The study enrolled 842 consecutive patients with severe exacerbation of chronic obstructive pulmonary disease or respiratory failure. The initial assessment included clinical history collection, physical examination, hematological and biochemical analysis, gas analysis, chest X ray, 12 lead electrocardiography and determination of value of D-dimer. Of all enrolled patients, 211 met the exclusion criteria. Of 631 included patients, 269 (42.6%) had normal D-dimer. D-dimer level ≥ 500 μg/L was found in 362 (57.5%) patients who were referred to Doppler echocardiography, lower limb color Doppler ultrasonography and thoracic multidetector helical computed tomography. According the value of hematocrit, all patients were divided in two groups: group I (100 patients) with polycythema and group II (262 patients) without polycythemia. The first outcome of the study was the significantly higher incidence of pulmonary embolism in group I of patients than in group II, 39 (39%) and 29 (11.06%), respectively. Patients in group I had significantly worse disturbance of pulmonary function and higher degree of pulmonary hypertension (58.4 ± 3.66 vs. 30.3 ± 9.41). Apart from polycythemia in group I, the most common risk factors were arrhythmia, absolute and varicose veins. Polycythemia is a single most significant risk factor for pulmonary embolism in chronic hypoxemic patients. Value of D-dimer ≥ 500 μg /L, as well as presence of comorbidity, particularly vein varicose, in these patients should raise clinical suspicion of PE. Key words: chronic obstructive pulmonary disease, multidetector computed tomography, arrhythmia, varicose veins, pulmonary hypertension.


Liddle's syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel gamma subunit.
To characterize novel type of mutations of the epithelial sodium channel (ENaC) or subunits in patients with Liddle's syndrome, an autosomal dominant form of hypertension. DNA samples from two probands with early-onset, treatment-resistant hypertension and suppressed plasma renin activity were initially screened for mutations in the C-terminal exons of the ENaC or subunit genes, using amplification by polymerase chain reaction and direct DNA sequencing. Two novel mutations causing Liddle's syndrome were identified. One mutation due to a single nucleotide insertion in the exon 13 of ENaC results in a frameshift at codon 601 and abrogates the PY motif similar to all the previously described ENaC mutations causing Liddle's syndrome. The other mutation, substituting serine for asparagine at codon 530 (Asn530Ser) of the extracellular loop of ENaC subunit, was found in a 25-year-old man with hypertension, hypokalemia, low plasma renin activity and low serum aldosterone levels. Hypertension and hypokalemia favorably responded to amiloride or triamterene administration both in the proband and his affected mother. Expression of the mutant Asn530Ser ENaC subunit in oocytes demonstrated a two-fold increase in ENaC activity, compared with the wild-type, without a significant change in cell surface expression of ENaC. This suggests that the gammaENaC Asn530Ser mutation increases the channel open probability, and is consistent with an abnormally high sodium reabsorption in the distal nephron. This study describes the first mutation located in the extracellular domain of an ENaC subunit associated with an increased ENaC activity and Liddle's syndrome.


Dose volume uniformity index: a simple tool for treatment plan evaluation in brachytherapy.
In radiotherapy treatment planning, dose homogeneity inside the target volume plays a significant role in the final treatment outcome. Especially in brachytherapy where there is a steep dose gradient in the dose distribution inside the target volume, comparing the plans based on the dose homogeneity helps in assessing the high dose volume inside the final treatment plan. In brachytherapy, the dose inhomogeneity inside the target volume depends on many factors such as the type of sources, placement of these radioactive sources, distance between the applicators/implant tubes, dwell time of the source, etc. In this study, a simple index, the dose volume uniformity index (DVUI), has been proposed to study the dose homogeneity inside the target volume. This index gives the total dose volume inhomogeneity inside a given prescription isoline. To demonstrate the proposed DVUI in this study, a single plane implant (breast: 6 catheters), a double plane implant (breast: 9 catheters) and a tongue implant (5 catheters) were selected. The catheters were reconstructed from the CT image datasets in the Plato treatment planning system. The doses for the single, double and tongue implants were prescribed to the reference dose rate as per the Paris technique. DVUI was computed from the cumulative dose volume histogram. For a volume receiving a uniform dose inside the prescription isoline, the DVUI is 1. Any value of DVUI > 1 shows the presence of a relatively high dose volume inside the prescription isoline. In addition to the concept of DVUI, a simple conformality index, the dose volume conformality index (DVCI), has also been proposed in this study based on the DVUI. The DVUI and the proposed DVCI in this study provide an easy way of comparing the rival plans in brachytherapy.


Paraoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in R-allele-carrier but not in QQ homozygous elderly subjects on a tomato-rich diet.
The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Paraoxonase (PON1) protects LDL from oxidation and may therefore retard the development of atherosclerosis. The PON1-192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects. To investigate the effect of tomato juice consumption on PON1 activity and other parameters related to oxidative stress in healthy elderly subjects. Furthermore, the PON1-192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1-192 polymorphism. Fifty elderly subjects were randomly assigned to control (mineral water) or intervention group (tomato juice). Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks. Antioxidant status was measured as LDL oxidation, plasma malondialdehyde, ferric reducing ability of plasma (FRAP) and PON1 activity. The PON1-192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Plasma carotenoids were analyzed by HPLC. Tomato juice consumption reduced LDL-oxidation and improved antioxidant status in R-allele carriers, but not in the QQ genotype group. PON1 activity increased irrespective of the genotype in both, control and intervention group. The changes in antioxidant status after tomato juice consumption seem to depend on the PON1-192 genotype. Healthy elderly, carrying the R-allele, could specifically reduce their higher cardiovascular risk by changing dietary habits.


Immunoregulatory T cell function in multiple myeloma.
Multiple myeloma is a malignancy characterized by uncontrolled monoclonal B cell differentiation and immunoglobulin production. In most instances, there is concomitant reduction in polyclonal differentiation and immunoglobulin synthesis both in vivo and in vitro. In in vitro pokeweed mitogen-induced B cell differentiation assays, proliferation and polyclonal immunoglobulin secretion optimally requires T cell help and can be inhibited both by monocytes and suppressor T cells. Helper function and monocyte-mediated suppression are relatively radio-resistant whereas T suppressor function is sensitive to 2,000 rad x-irradiation. We have examined myeloma T cell subset function in this assay using recombinations of isolated patient and normal B cells, T cells, and T cell subsets. Monocytes were removed by a carbonyl iron ingestion technique, normal and myeloma T cells were fractionated on the basis of Fc receptors for immunoglobulin (Ig) G (Tgamma) or IgM (Tmu or T non-gamma), and proliferation and IgG secretion after co-culture determined by [(3)H]thymidine incorporation and radio-immunoassay, respectively. Myeloma B cells demonstrate quantitatively and qualitatively normal blastogenic responses and are appropriately regulated by either autologous or allogeneic T helper and suppressor subsets. Despite normal proliferation, however, myeloma B cells remain deficient in subsequent differentiation and immunoglobulin secretion even when co-cultured in the absence of monocytes or suppressor T cells and the presence of normal helper cells. Myeloma T cell populations, in contrast, are entirely normal in helper capacity over a range of T:B ratios but are markedly deficient in radiosensitive and concanavalin A-induced suppressor activity. T suppressor cell dysfunction in multiple myeloma is apparently due to a deficit in the T non-gamma suppressor subset, whereas Tgamma cells, although proportionately reduced, are functionally normal. This unique T suppressor deficit reflects the heterogeneity of suppressor mechanisms in this disease and may represent a compensatory response to the monoclonal proliferation or the involvement of regulatory T cells in the pathogenesis of the malignancy.


Pervasive misannotation of microexons that are evolutionarily conserved and crucial for gene function in plants.
It is challenging to identify the smallest microexons (≤15-nt) due to their small size. Consequently, these microexons are often misannotated or missed entirely during genome annotation. Here, we develop a pipeline to accurately identify 2,398 small microexons in 10 diverse plant species using 990 RNA-seq datasets, and most of them have not been annotated in the reference genomes. Analysis reveals that microexons tend to have increased detained flanking introns that require post-transcriptional splicing after polyadenylation. Examination of 45 conserved microexon clusters demonstrates that microexons and associated gene structures can be traced back to the origin of land plants. Based on these clusters, we develop an algorithm to genome-wide model coding microexons in 132 plants and find that microexons provide a strong phylogenetic signal for plant organismal relationships. Microexon modeling reveals diverse evolutionary trajectories, involving microexon gain and loss and alternative splicing. Our work provides a comprehensive view of microexons in plants.


Polycomb Repressive Complex 2 in Eukaryotes-An Evolutionary Perspective.
Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals and plants. The composition, biochemistry, and developmental function of PRC2 in animal and flowering plant model species are relatively well described. Recent evidence demonstrates the presence of PRC2 complexes in various eukaryotic supergroups, suggesting conservation of the complex and its function. Here, we provide an overview of the current understanding of PRC2-mediated repression in different representatives of eukaryotic supergroups with a focus on the green lineage. By comparison of PRC2 in different eukaryotes, we highlight the possible common and diverged features suggesting evolutionary implications and outline emerging questions and directions for future research of polycomb repression and its evolution.


[How to develop an anti-arrhythmia agent in 1990. The cardiologist's viewpoint].
The development of an antiarrhythmic drug in 1990 follows well established pathways. The first step is animal experimentation to establish the antiarrhythmic effect and to estimate the risk of toxicity, but clinical trial is the fundamental stage which confers on a product the title of antiarrhythmic. Several models may be used, one of which is ventricular extrasystoles. However, the data so obtained must not be extrapolated to a wider context. All methods for evaluating an antitachycardia effect have imperfections. Obviously, arrhythmias treated in hospital are privileged although they may only represent a special subgroup of more severe arrhythmias. Potential antiarrhythmics are more often assessed by their effects on tachycardias reproduced by programmed pacing, leaving other arrhythmias, including atrial fibrillation, to one side. In addition, long-term efficacy is more often suspected than demonstrated. The action on malignant ventricular tachyarrhythmias escapes all valid assessment mainly because of the difficulty of using a control group of patients with life-threatening arrhythmias. The use of automatic defibrillator devices could, in the near future, bring a more rigorous approach to this problem. One of the most important objectives of antiarrhythmic drugs is the prevention of sudden death. Results have been relatively disappointing until now. This may be due to deleterious, above all proarrhythmic, side-effects counterbalancing the benefits of the drug. The unwanted side-effects must be evaluated systematically in the future. The methodology needed is not yet established and requires further research.


[Effect of oral propafenon on accessory pathways of atrioventricular conduction].
Fifteen consecutive patients with accessory AV pathways comprising 12 cases of the Wolff-Parkinson-White syndrome and 3 cases with exclusively retrograde conduction diagnosed by endocavitary electrophysiological investigation were studied. 5 patients had paroxysmal atrial fibrillation and the other 10 had reciprocating orthodromic tachycardia. 12 patients underwent electrophysiological investigation to measure the refractory periods and anterograde and retrograde conduction times in sinus rhythm and induced reciprocating tachycardia treatment with oral propafenone at a dose of 900 mg/day for 3 to 6 days. The refractory periods of anterograde conduction and the conduction times were then measured using an endocavitary atrial recording electrode left in position after the initial investigation. The anterograde Wenckebach point decreased from 259 +/- 35/min to 158 +/- 13/min (p less than 0.001). The refractory periods were increased from 270 +/- 45 ms to 371 +/- 100 ms (p less than 0.05). Atrial fibrillation could only be initiated in 2 cases with a mean rate which had decreased from 258 to 130/min. Reciprocating tachycardia could only be initiated in 5 cases and then with a slower rate (average cycle length increasing from 352 +/- 52 ms to 430 +/- 41 ms). Eight of these patients continued the treatment for over one year without recurrence of their arrhythmias, confirming the long-term efficacy of propafenone in the prevention of arrhythmias complicating accessory AV conduction pathways.


Cumulative parenthood rates in 1735 couples: impact of male factor infertility.
Most studies assessing the outcome of assisted reproductive technologies (ARTs) have reported live birth rates in couples by taking mainly the female factor into account. However, infertility is a couple's concern, and the majority of publications do not take into consideration the true impact of male infertility on having the desired number of children. We carried out a follow-up study to evaluate the probability of having a child during treatments at the Toulouse Male Sterility Centre and after discontinuation from 2000 through 2008. Couples were followed for at least 4 years until discontinuation of treatment or delivery of a live infant. We were able to contact 65% of the 1735 male partners by telephone. Of the 1131 respondents, 56% had become parents (60% if adoption is included), 28% after ART, 16% by natural pregnancy, 8% after non-ART treatment and 4% after ART in another centre. The cumulative rates of success reached 64% [95% confidence interval (CI), 60-67] for men ≤35 years and women ≤35 years after 9 years, and 31% (95% CI, 24-39) in older patients. With optimistic analysis, which assumes that patients for whom no information was available have the same chance of success in having a child as those whose reproductive outcome was known, the cumulative rate of success was 48% (95% CI, 45-50) in the 1735 couples. More than half of couples consulting for male infertility succeeded in having a child. Male age over 35 years old appears as a key risk factor as well as the woman's age, and these findings should encourage couples to attempt parenthood earlier.


A novel TRIM22 gene polymorphism promotes the response to PegIFNα therapy through cytokine-cytokine receptor interaction signaling pathway in chronic hepatitis B.
Pegylated interferon alfa (PegIFNα) has limited efficacy in the treatment of chronic hepatitis B (CHB). Although many biomarkers related to hepatitis B virus (HBV) have been proposed to stratify patients, the response rate to PegIFNα is still unsatisfactory. Herein, our data suggest that the single-nucleotide polymorphism (SNP) rs10838543 in TRIM22 potentiates a positive clinical response to PegIFNα treatment in patients with hepatitis B e antigen-positive CHB by increasing the levels of IFNL1, CCL3, and CCL5. These observations can help guide treatment decisions for patients with CHB to improve the response rate to PegIFNα.


A double standard when group members behave badly: transgression credit to ingroup leaders.
This research tested the hypothesis that people forgive serious transgressions by ingroup leaders but not by other group members or outgroup leaders. They apply a double standard in judgments of ingroup leaders. A series of studies (N = 623), using an array of different ingroups and outgroups, tested how group members judged ingroup or outgroup leaders and nonleaders who unexpectedly transgressed or did not transgress in important intergroup scenarios. Experiments 1, 2, and 4 focused on captains and players in either soccer or netball sports competitions. Across studies, transgressive captains of ingroup teams were evaluated more favorably than captains from outgroup teams and (Experiments 1, 2, and 4) more favorably than transgressive ingroup players. Experiment 3 demonstrated the double standard in a minimal group paradigm. Experiment 5 showed that the double standard is only applied if the leader is perceived as serving the group's interest. Across studies, the double standard is evident in evaluations toward, inclusion and punishment of, and rewards to the transgressive targets. Implications for sport, politics, and business and intergroup conflict are discussed.


Rheumatoid Arthritis: Defining Clinical and Ultrasound Deep Remission.
The prognosis of patients with rheumatoid arthritis (RA) has improved substantially in the last two decades due to the appearance of biological therapies, but above all, due to the improvement in the strategy and management of the disease. Our goal in RA should be to achieve remission, or in its absence, the lowest inflammatory activity. Achieving remission will prevent from structural and functional damage highly associated with RA itself. Clinical remission is defined as the absence of significant signs and symptoms of inflammatory disease activity, as well as the abrogation of any signs of systemic inflammation. Currently, there are some controversies about remission. Which is the real remission? Which remission criteria should be used and when? Does clinical remission mean ultrasound remission? In the present review, we try to answer and put some light into it, focusing on clinical and ultrasound deep remission.


Elementary constraints on autocorrelation function scalings.
Elementary algebraic constraints on the form of an autocorrelation function C(t(w)+tau,t(w)) rule out some two-time scalings found in the literature as possible long-time asymptotic forms. The same argument leads to the realization that two usual definitions of many-time scale relaxation for aging systems are not equivalent.


[Morphological observation of amifostine's protective effect on radiation induced early middle ear injury].
To assess the radio-protective effect of amifostine on the middle ear in animal models by observing the morphological changes of middle ear mucosa. Adult guinea pigs (n=38) were divided into the radiation group, the radiation-amifostine group and the control group. The first two groups were exposed to total 45 Gy of Gamma radiation which was administered to the right ear of each guinea pig with 3.0 Gy/fraction, 5 times per week, using a cobalt-60 machine. And the radiation+amifostine group was pretreated with the radio protector amifostine 100 mg/kg intra-peritoneally 30 min before each fraction of radiation. Sterile saline was administered intra-peritoneally in radiation group before ear irradiation. Two normal guinea pigs given no treatment were chosen as the control. The tympanic bullas were removed and the mucosae was processed for light microscope and scanning electron microscope examination on the 2nd and 30th days post irradiation to observe mucosa thickness, leukocyte and cilia. Light microscope and scanning transmission electron microscope examination showed in radiation groups that the middle ear effusion occurred; the cilia and micro cilia fell off, fused or collapsed; their directions changed; the mucosa became thicker; and leukocytes were also found infiltrating into the mucosa. On the 30th day,the damage was more serious. As comparison, there was no manifest damage of the middle ear mucosa in radiation+amifostine group. The mucosa thickness and the leukocyte quantity of radiation group were obviously higher than that of radiation+amifostine group (P < 0.01). The middle ear mucosa was found to change over time after irradiation. Amifostine has a protective effect on radiation induced early middle ear injury.


Simultaneous confirmatory factor analysis of the wechsler memory scale - revised for two standardization samples: a comparison of groups from Japan and the United States.
We employed a simultaneous confirmatory factor analysis to assess the hypothesized three-factor structure of the Wechsler Memory Scale - Revised (i.e., Attention/Concentration, Immediate Memory, Delayed Recall factors) in samples from Japan and the United States. The aim of the study was to provide a rigorous test of the hypothesis that the factor structure of the Wechsler Memory Scale - Revised is invariant across languages. We found configural invariance in two groups, that is, the same number of factors was found and the factor patterns were similar across the two samples. Our results tended to support the potential utility of the Wechsler Memory Scale - Revised in the analysis of the Japanese population, and the present findings appeared to be consistent with the contention that the Wechsler Memory Scale - Revised represents universal dimensions of memory. However, the factor patterns were slightly different between the two groups in the visual recall tests. The slight difference of the factor patterns may be caused with linguistic differences and/or difference among neural substrates in the brain associated with each group.


Characterization of an internal ribosomal entry segment in the 5' leader of murine leukemia virus env RNA.
The 5' untranslated region, also called the leader, of oncoretroviruses and lentiviruses is long and is formed of several structured domains critically important in virus replication. The 5' leader of murine leukemia virus (MLV) RNA contains an internal ribosomal entry segment (IRES) which promotes synthesis of Gag and glyco-Gag polyprotein precursors. In the present study we investigated the translational features of the 5' leader of MLV subgenomic RNA (env RNA) encoding the Env polyprotein precursor. When the env leader was inserted between two genes, such as lacZ and the neomycin resistance cassette, in a dicistronic vector, it allowed IRES-dependent translation of the 3' cistron in the rabbit reticulocyte lysate system and in murine cells. The drug rapamycin and the foot-and-mouth disease virus L protease, known to inhibit cap-dependent translation, caused an enhancement of the translation driven by the env leader sequence, consistent with an IRES activity promoting Env expression. Analysis of several deletion mutants led us to localize the minimal env IRES between the splice junction and the env AUG start codon.


Preparation of a Major Metabolite of Iguratimod and Simultaneous Assay of Iguratimod and Its Metabolite by HPLC in Rat Plasma.
Iguratimod is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis. A new method using recombinant human CYP450s yeast cells containing c-DNA expressed P450s was applied to identify the metabolic pathways of iguratimod and to prepare its metabolite. The metabolite was isolated, and its structure was identified by quadrupole time-of-flight-mass spectrometry and nuclear magnetic resonance. Furthermore, a selective and sensitive high performance liquid chromatography (HPLC) method was developed for the simultaneous quantification of iguratimod and its major metabolite in rat plasma for the first time. The results indicated that iguratimod was mainly metabolized to a metabolite by CYP2C9 and CYP2C19 in in-vitro study. The structure of the metabolite was identified as M2 (N-[3-(acetamido)-4-oxo-6-phenoxy-4H-chromen-7-yl]methanesulfonamide). HPLC assay was achieved on a C18 column using methanol-water containing 0.1% trifluoroacetic acid (55:45 v/v) at a flow rate of 1 mL/min with UV detection at 257 nm. Standard calibration curves were obtained in the concentration range of 0.5-20 µg/mL for iguratimod and its metabolite M2. The lower limits of detection of iguratimod and M2 in rat plasma were 0.1 and 0.25 µg/mL, respectively. The intra- and inter-day precision (RSD%) were within 5% for the two analytes. The average recoveries of the analytes were greater than 90%. In conclusion, recombinant human CYP450s whole-yeast transformation system could be successfully used to identify and prepare the major metabolite of iguratimod. The HPLC method we developed could be successfully applied to evaluate pharmacokinetics of iguratimod and its metabolite M2 in rats.


[The AIRE Study: data analysis of 753 European children with asthma].
To analyse the paediatric data from the AIRE study (Asthma insights and reality in Europe) describing the standard of asthma control in Europe. Among the 73,880 households contacted by telephone in 7 countries 753 children under the age of 16 were identified. An interview was conducted with a close relative to determine the frequency and severity of symptoms during the recent month, visits to casualty and hospital admissions during the past year, the medications used, the effects on the lives of the children, the opinions of the parents on the level of control of asthma and the monitoring methods used. 38.2% of children reported diurnal symptoms and 28% disturbance of sleep at least once a week. The consequences were important: limitation of sporting activities (29.5%) and absence from school (42.7% in the past year). Treatment was inadequate: 26% of children used inhaled steroids yet 45.9% had persistent asthma. The level of control was overestimated: 61% of parents of children with severe persistent asthma considered the asthma to be well controlled. European asthmatic children are poorly controlled, under-treated and rarely followed up. The consequences, particularly absence from school, should stimulate an improvement in their therapeutic and educational management.


Assessment of Change in Palatal Sensation in Obstructive Sleep Apnea Patients by Using Two-Point Palatal Discrimination.
Patients with obstructive sleep apnea syndrome (OSAS) have impaired responses to inspiratory resistive loading during sleep. This may be due, in part, to a change in the upper airway sensation. Therefore, we hypothesized that patients with OSAS have diminished upper airway sensation due to snoring. A total of 53 participants were selected based on clinical evaluation and polysomnography. Two-point discrimination was measured with modified calipers in the tongue and soft palate. A total of 10 participants were included in the control group, 12 participants in the simple snoring group, and 27 participants in the OSAS group. There were 12 patients in the impaired sensation group of the OSAS group. On comparing polysomnography, patients with impairment of their palatal sensory input in two-point discrimination (TPD) had a more protracted duration of the longest snoring episode than those with simple snoring and normal sensation. Patients with decreased sensory input in TPD had longer average duration of snoring episodes and relative snoring time than those with simple snoring and normal sensory input in cold uvular TPD. Comparison of the cold uvular TPD for normal sensation and impaired sensation in patients with OSAS after treatment showed a different trend. Impaired sensation of the soft palate was correlated with the longest snoring episode duration, average snoring episode duration, and relative snoring time. It is helpful in detecting the early stage of neural degradation in OSAS patients by assessing snoring components of polysomnography and TPD in the soft palate.


Towards 2011 output geographies: exploring the need for, and challenges involved in, maintenance of the 2001 output geographies.
This article describes and presents early results from the ESRC-funded Census 2011Geog project, which aims to develop and evaluate automated procedures to maintain (split, merge or re-design) the 2001 Census output geographies in order to create the 2011 output geographies for England and Wales. The article explores population change at the small area level between 2001 and 2005-06, and considers the extent to which the 2001 Census output geographies are likely to be appropriate for the release of 2011 Census data. It concludes that the vast majority of output geography areas are unlikely to have breached population thresholds by 2011, but that a small proportion of areas will require maintenance. The article finishes with a discussion of the key decisions that need to be made before the automated procedures can be implemented operationally.


The Cosmos Collaborative: A Vendor-Facilitated Electronic Health Record Data Aggregation Platform.
Learning healthcare systems use routinely collected data to generate new evidence that informs future practice. While implementing an electronic health record (EHR) system can facilitate this goal for individual institutions, meaningfully aggregating data from multiple institutions can be more empowering. Cosmos is a cross-institution, single EHR vendor-facilitated data aggregation tool. This work aims to describe the initiative and illustrate its potential utility through several use cases. Cosmos is designed to scale rapidly by leveraging preexisting agreements, clinical health information exchange networks, and data standards. Data are stored centrally as a limited dataset, but the customer facing query tool limits results to prevent patient reidentification. In 2 years, Cosmos grew to contain EHR data of more than 60 million patients. We present practical examples illustrating how Cosmos could further efforts in chronic disease surveillance (asthma and obesity), syndromic surveillance (seasonal influenza and the 2019 novel coronavirus), immunization adherence and adverse event reporting (human papilloma virus and measles, mumps, rubella, and varicella vaccination), and health services research (antibiotic usage for upper respiratory infection). A low barrier of entry for Cosmos allows for the rapid accumulation of multi-institutional and mostly de-duplicated EHR data to power research and quality improvement queries characteristic of learning healthcare systems. Limitations are being vendor-specific, an "all or none" contribution model, and the lack of control over queries run on an institution's healthcare data. Cosmos provides a model for within-vendor data standardization and aggregation and a steppingstone for broader intervendor interoperability.


Dietary niches of creodonts and carnivorans of the late Eocene Cypress Hills Formation.
Modern North American carnivorous mammal assemblages consist of species from a single clade: the Carnivora. Carnivorans once coexisted with members of other meat-eating clades, including the creodonts (Hyaenodontida and Oxyaenida). Creodonts, however, went extinct in North America during the late Eocene and early Oligocene, potentially due to niche overlap and resource competition with contemporary carnivorans. In this study, we employ a community ecology approach to understand whether the dietary niches of coexisting creodonts and carnivorans overlapped during the late Eocene (Chadronian North American Land Mammal Age), a time when creodonts were dwindling and carnivorans were diversifying. We quantify niche overlap based on inferences of diet from carnassial tooth shape estimated using Orientation Patch Count, Dirichlet's Normal Surface Energy, and linear dental measurements as well as from body mass for all species in the Calf Creek Local Fauna of Cypress Hills, Saskatchewan (Treaty 4 land). Although creodonts and carnivorans shared characteristics of their carnassial tooth shape, suggesting similar chewing mechanics and feeding habits, we find that marked differences in body size likely facilitated niche partitioning, at least between the largest creodonts and carnivorans. Calculations of prey focus masses and prey mass spectra indicate that only the smallest creodont may have experienced significant competition for prey with the coeval carnivorans. We suggest that the ultimate extinction of creodonts from North America during the late Eocene and Oligocene was unlikely to have been driven by factors related to niche overlap with carnivorans.


Umbilical cord blood gases.
The intrapartum acid-base status of the fetus is an important component in establishing the link between intrapartum events and neonatal condition. The analysis of cord blood gases from the umbilical artery is believed to be the best representation of the fetal acid-base status immediately before birth. Blood gas analysis is able to objectively confirm or exclude the presence of damaging acidemia. Although measurements may be affected by several factors related to the method of sampling, storage, and assessment, a wide margin of accuracy exists when prompt assessment is unavailable. Because a substantial deviation from the standard procedure is required before a sample is alleged to be imprecise, it is unlikely that standard sampling methods would be ineligible in litigation.


In vitro growth and shoot multiplication in Terminalia bellerica roxB. under controlled carbon dioxide environment.
The shoot cultures of Terminalia bellerica Roxb. were grown on Murashige and Skoog's medium containing 1.5 mg 1(-1) BAP (6- benzyl aminopurine), and supplemented with or without sucrose (3%). A range of CO2 concentrations (0.0, 0.6, 10, 40 g(-3)) was provided in small acrylic chambers by using different concentrations and combinations of NaHCO3 (sodium bicarbonate), Na2CO3 (sodium carbonate), KHCO3 (potassium bicarbonate) and K2CO3 (potassium carbonate). To obtain a CO2-free environment, a saturated solution of 10% of KOH (potassium hydroxide) was kept in the chamber. Complete absence of carbon source caused death of shoots within 20 days. Under controlled and enriched CO2, the shoots grew fully photoautotropically on sucrose-free medium. The growth of cultures was better with carbon dioxide (40 g(-3)) than sucrose (3%) in the medium. Maximum number of shoots, number of leaves per cluster, fresh and dry weight and chlorophyll contents were recorded when both sucrose and CO2 (40 g(-3)) were provided to the culture.


Radiological characterization of gilthead seabream (Sparus aurata) by X-ray computed tomography.
In recent years, the increasing use of fish as new animal models in scientific research and the growth of fish farming (mainly for human consumption) have highlighted the need for advanced technology to deepen our knowledge of fish biology. Hence, the present study was carried out to radiologically analyse the whole body of gilthead seabream (Sparus aurata) specimens using X-ray computed tomography (CT). Images were acquired in an Albira SPECT/PET/CT tri-modal preclinical-scanner. Segmentation, measurements and three-dimensional reconstruction were made using the Carestream Molecular imaging Albira CT system in conjunction with Pmod, AMIDE and Amira software packages. The results showed that the density values of gilthead seabream are in the range -700 to +2500 HU for the whole body. We also determined the density ranges that topographically coincide with the swim bladder, soft tissues, fat, skin and skeleton. This work describes, validates and demonstrates the application of a fully automated image analysis technique to study and quantify fish body composition, whether segmented or as a whole. In addition, the basis for applying this image technique in other in vivo studies is established.


US policy support for telehealth: organizational response to a new policy environment.
A sample of 40 from 176 public policy organizations in Washington, DC, was studied. The organizations were those whose leadership was deemed necessary to develop a new strategic vision of electronic technologies to support public health. The results showed that large, secure and well positioned organizations became active only to the extent of their mandates, while smaller and less influential groups, which were freer to think and act innovatively, had an incentive to work with other organizations to gain effective support for their policy positions. The conclusion is that the constituencies of leading policy organizations will have to ensure that well connected leaders and environmental scanning structures guide their organizations and that they have the institutional capacity to develop unconventional strategies to meet health challenges.


Fluorescent probes for the analysis of DNA strand scission in base excision repair.
We have developed fluorescent probes for the detection of strand scission in the excision repair of oxidatively damaged bases. They were hairpin-shaped oligonucleotides, each containing an isomer of thymine glycol or 5,6-dihydrothymine as a damaged base in the center, with a fluorophore and a quencher at the 5'- and 3'-ends, respectively. Fluorescence was detected when the phosphodiester linkage at the damage site was cleaved by the enzyme, because the short fragment bearing the fluorophore could not remain in a duplex form hybridized to the rest of the molecule at the incubation temperature. The substrate specificities of Escherichia coli endonuclease III and its human homolog, NTH1, determined by using these probes agreed with those determined previously by gel electrophoresis using (32)P-labeled substrates. Kinetic parameters have also been determined by this method. Since different fluorophores were attached to the oligonucleotides containing each lesion, reactions with two types of substrates were analyzed separately in a single tube, by changing the excitation and detection wavelengths. These probes were degraded during an incubation with a cell extract. Therefore, phosphorothioate linkages were incorporated to protect the probes from nonspecific nucleases, and the base excision repair activity was successfully detected in HeLa cells.


Broadband tunable InAs/InP quantum dot external-cavity laser emitting around 1.55 μm.
We report a broadband tunable external-cavity laser based on InAs/InP quantum dots (QDs) grown by metal-organic vapor phase epitaxy. It is found that high AsH₃ flow during the interruption after QD deposition greatly promotes QD ripening, which improves the optical gain of QD active medium in lower energy states. Combined with anti-reflection/high-reflection facet coatings, a broadly tunable InAs/InP QD external-cavity laser was realized with a tuning range of 140.4 nm across wavelengths from 1436.6 nm to 1577 nm at a maximum output power of 6 mW.


Development and Validation of a Competitive ELISA Based on Bovine Monoclonal Antibodies for the Detection of Neutralizing Antibodies against Foot-and-Mouth Disease Virus Serotype A.
The level of neutralizing antibodies in vaccinated animals is directly related to their level of protection against a virus challenge. The virus neutralization test (VNT) is a "gold standard" method for detecting neutralizing antibodies against foot-and-mouth disease virus (FMDV). However, VNT requires high-containment facilities that can handle live viruses and is not suitable for large-scale serological surveillance. In this study, a bovine broadly neutralizing monoclonal antibody (W145) against FMDV serotype A was successfully produced using fluorescence-based single-B-cell antibody technology. Using biotinylated W145 as a detector antibody and another bovine cross-reactive monoclonal antibody, E32, which was produced previously as a capture antibody, a competitive enzyme-linked immunosorbent assay for the detection of neutralizing antibodies (NAC-ELISA) against FMDV serotype A was developed. The specificity and sensitivity of the assay were evaluated to be 99.04% and 100%, respectively. A statistically significant correlation (r = 0.9334, P < 0.0001) was observed between the NAC-ELISA titers and the VNT titers, suggesting that the NAC-ELISA could detect neutralizing antibodies against FMDV serotype A and could be used to evaluate protective immunity.


Near infrared hyperspectral imaging in quality and safety evaluation of cereals.
The requirements of cereal research, as well as grading and evaluation of food products, have encouraged the development of nondestructive, rapid, and accurate analytical techniques to evaluate grain quality and safety. NIR hyperspectral imaging integrates spectroscopy and imaging techniques in one analytical system, allowing direct identification of chemical components and their distribution within the sample. It is a promising technique that may be implemented on-line, enabling the cereal industry to move away from subjective, manual classification and measuring methods. NIR hyperspectral imaging has gained popularity for rapidly acquiring information to enable the quantification, identification or differentiation of a variety of cereal properties. The technique can potentially replace multiple conventional chemical, microbial or physical tests with a single, automated image acquisition. Individual kernels can be analyzed nondestructively, enabling one to follow changes in the same kernel over time (e.g. fungal development). Although NIR hyperspectral imaging has not been extensively implemented in industry, it shows great potential for the development of an evaluation system to assess cereal grains, especially regarding variety discrimination and grading/classification properties. This review outlines the theory and principles of NIR hyperspectral imaging, and focuses specifically on its application in cereal science research and industry.


Effect of copper on growth, yield and concentration of Fe, Mn, Zn and Cu in wheat plants (Triticum aestivum L.).
A pot experiment was conducted at six graded levels of copper (Cu) viz., 0, 0.5, 1.0, 1.5, 2.0 and 2.5 mg kg(-1) to test the response of wheat plants grown in a copper-responsive alluvial soil (entisol) under glass house conditions. The growth attributes like plant height, fresh and dry matter yield, percent dry matter enhanced with increasing Cu levels and was maximum at 1.5 mg kg(-1) Cu while the number of tillers was minimum at this level. The grain yield at 1.5 mg kg(-1) Cu was enhanced by 62.9% from the control. The increase in weight of 1000 grains ranged from 33.93 to 41.35 g in comparison to control (32.58 g). Harvest index (%) also increased and ranged from 39.42 to 47.73 in different treatments in comparison to control (35.92). Both 1000 grain weight and harvest index were maximum in the plants at 1.5 mg kg(-1) copper. Cu concentrations in leaves, grain and straw enhanced with increasing levels of Cu application. The Fe concentration in leaves was significantly reduced by Cu application and the reduction was 10.3% at 2.5 mg kg(-1) Cu and was not influenced in by Cu application in grain and straw. The Mn concentration was not affected by Cu application in any of the plant part studied. However, Zn concentration decreased significantly at higher levels of Cu (2.0 and 2.5 mg kg(-1)) in leaves and remained unaffected in the grain and straw.


Responses to deceleration during car following: roles of optic flow, warnings, expectations, and interruptions.
More than 25% of accidents are rear-end collisions. It is essential to identify the factors that contribute to such collisions. One such factor is a driver's ability to respond to the deceleration of the car ahead. In Experiment 1, we measured effects of optic flow information and discrete visual and auditory warnings (brake lights, tones) on responses to deceleration during car following. With computer simulations of car-following scenes, university students pressed a button when the lead car decelerated. Both classes of information affected responses. Observers relied on discrete warnings when optic flow information was relatively less effective as determined by the lead car's headway and deceleration rate. This is consistent with DeLucia's (2008) conceptual framework of space perception that emphasized the importance of viewing distance and motion (and task). In Experiment 2, we measured responses to deceleration after a visual interruption. Scenes were designed to tease apart the role of expectations and optic flow. Responses mostly were consistent with optic flow information presented after the interruption rather than with putative mental expectations that were set up by the lead car's motion prior to the interruption. The theoretical implication of the present results is that responses to deceleration are based on multiple sources of information, including optical size, optical expansion rate and tau, and discrete warnings that are independent of optic flow. The practical implication is that in-vehicle collision-avoidance warning systems may be more useful when optic flow is less effective (e.g., slow deceleration rates), implicating a role for adaptive collision-warning systems.


Serum estradiols versus pelvic sonography in monitoring HMG therapy.
Therapy with human menopausal gonadotropin (HMG) conventionally has been monitored by estrogen measurements. Pelvic sonography may offer a more accurate method of monitoring HMG therapy. In this study 67 anovulatory patients were treated with HMG until at least one follicle had a diameter of 17 mm. The serum estradiol level was noted at the time a mature follicle was achieved. There was a correlation between the ultrasound data and the serum estradiol range in 57% of the cases. However, in 24% it was necessary to push the estradiol level above the allowable maximum of 2000 pg/mL. Twenty percent of the patients attained a 17-mm follicle before reaching the minimum required estradiol level of 500 pg/mL. Sonographic monitoring should improve the efficacy of HMG therapy.


A role for proapoptotic Bax and Bak in T-cell differentiation and transformation.
Proapoptotic Bax and Bak are the key B-cell lymphoma-2 family members mediating apoptosis through the intrinsic pathway. Cells doubly deficient for Bax and Bak are profoundly resistant to apoptotic stimuli originating from multiple stimuli. Here we describe mice in which Bax and Bak have been deleted specifically in T-cells using Lck-Cre. In these T cell-specific BaxBak-deficient mice, early T-cell progenitors accumulate in the thymus, with relative depletion of more mature T cells. In addition, bone marrow progenitor cells fail to progress to the double positive stage when cultured on OP9 stromal cells expressing the Notch ligand Delta-like 1, consistent with a critical role for Bax and Bak in early T-cell development. Over time, T cell-specific BaxBak-deficient mice progress to an aggressive T-cell lymphoblastic leukemia/lymphoma. Interestingly, quantitative real-time polymerase chain reaction analysis of BaxBak-deficient T-cell lymphomas does not display amplification of the Notch signal transduction pathway, commonly activated in T-cell leukemia in both mouse and man. Bax and Bak, key regulators of the intrinsic pathway of apoptosis, are thus required to prevent T-cell malignancy, and for normal T-cell differentiation, regulating early T-cell development at the stage of early T-lineage progenitor cells.


[fs-Lentotomy: presbyopia reversal by generating gliding planes inside the crystalline lens].
Based on the Helmholtz theory for accommodation, increasing sclerosis of the lens nucleus and cortex is the main cause for the development of presbyopia. Existing therapies, however, do not reverse the stiffness of the crystalline lens and thus do not regain real accommodation ability. A new approach to restore the flexibility of the lens has been realised by utilising the non-linear interaction of ultrafast laser pulses with transparent tissue, the so-called photodisruption. This process has been used to create micro-incisions which act as gliding planes inside the crystalline lens without opening the eye globe. This treatment method, known as fs-lentotomy, enables regeneration of real dynamic accommodation. For the first time, 3D structures for gliding planes were successfully generated in experiments with human donor lenses of different ages. An average increase in anterior-posterior lens thickness of 100 mum accompanied by a decrease of equatorial lens diameter was observed as a direct consequence of fs-lentotomy. This is attributed to the increased flexibility, as the force of the capsule bag moulds the lens tissue more spherically. Moreover, in vivo experiments on rabbit eye lenses did not induce an increasing opacification (cataract) over a six-month follow-up period. However, the incisions were still detectable using Scheimpflug imaging and histopathological techniques, although the visibility of the incisions was declining. Furthermore, no side effects were observed during the wound healing process and during a six-months follow-up period. Based on these findings fs-lentotomy might have the potential to become a procedure for the reversal of presbyopia.


A narrative review of the safety concerns of deprescribing in older adults and strategies to mitigate potential harms.
As with prescribing or continuing medications, deprescribing brings with it the potential for harm as well as benefit. Uncertainty and avoidance of harm has been reported as a barrier to deprescribing in practice and may contribute to continuation of inappropriate medications. This narrative review covers four main safety concerns/potential harms of deprescribing in older adults: adverse drug withdrawal events, return of medical condition(s), reversal of drug-drug interactions and damage to the doctor-patient relationship. These are discussed in relation to medications in general, with some examples of medication classes used to illustrate the potential safety concerns. The majority of these harms can be minimized or even prevented by using a patient-centered, structured deprescribing process with planning, tapering and close monitoring during, and after medication withdrawal. More research is needed into the safety concerns of deprescribing, however, avenues exist during drug development and post-marketing surveillance to gain knowledge on this topic. Questions remain about when it is suitable to discontinue certain medications/medication classes and there is uncertainty about the harms and benefits of both medication continuation and discontinuation in complex older adults.


A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study.
As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8-19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30-40) at baseline to 12.5 (5-30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0-1880.0) μg/g at baseline to 592.0 (140.7-1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.


The Impacts on Greenhouse Gases Emission during the COVID-19 lockdown in the US: An Economic Input-Output Life Cycle Assessment.
The SARS-CoV-2 virus pandemic (COVID-19) is causing disruptions to energy, finance, tourism, and trade industries all around the world. These disruptions are the result of quarantining and lockdowns that cause reductions in production and consumptions. This change in production and consumption rates has environmental consequences. This study investigates the environmental effects of COVID-19 lockdown in the United States by Input-Output Life Cycle Assessment (IO-LCA) approach. The analysis is based on extraction of economic data in the US. The simulated results are based on different durations and strategies of lockdown measures. Among all industrial categories, utilities, which include power generation and supply, water supply, and natural gas supply sectors, saw the most significant reductions by approximately 110 kt CO2-eq in the first quarter and 265 kt CO2-eq in the second quarter of 2020. The assessed reductions were the results of both direct emission reductions caused by the shutdown of certain industries and also indirect emission reductions from upstream industries. The proposed methodology provides an effective guideline to predict the greenhouse gases emissions, which can be used as a prediction method for different regions in the world.


Milk yield and composition during abomasal infusion of conjugated linoleic acids in dairy cows.
Conjugated linoleic acids refer to a mixture of positional and geometric isomers of linoleic acid with conjugated double bounds. Three supplements of conjugated linoleic acids which differed in isomer enrichment were infused into the abomasum of lactating dairy cows to determine postruminal effect on milk yield and composition. Four Holstein cows were used in a 4 x 4 Latin square design. Treatments were 3-d abomasal infusion of 1) control, 5 kg of skim milk (carrier for conjugated linoleic acid supplements), 2) conjugated linoleic acid supplement 1 (28.8 g/d; 6.9 g of cis/trans 9,11; 6.4 g of cis/trans 8,10), 3) conjugated linoleic acid supplement 2 (48.5 g/d; 7.1 g of cis/trans 9,11; 4.1 g of cis/trans 8,10; 8.3 g of cis/trans 10,12; 5.5 g of cis/trans 11,13), and 4) conjugated linoleic acid supplement 3 (16.3 g/d; 7.1 g of cis/trans 9,11; 7.2 g of cis/trans 10,12). Infusions increased the conjugated linoleic acids content of milk fat from 0.43 g/100 g of fat for the control treatment to 1.02, 1.52, and 0.95 g/100 g of fat for conjugated linoleic acid supplements 1, 2, and 3, respectively. Apparent efficiency of transfer in milk fat was 25.2, 33.5, 21.0, and 28.4% for cis/trans 8,10, cis/trans 9,11, cis/trans 10,12, and cis/trans 11,13, respectively. Infusion of conjugated linoleic acids had no effect on dry matter intake, milk yield, and milk protein content. However, conjugated linoleic acid supplements reduced the content and yield of milk fat by 28 and 25%, respectively. The similarity of response for the different conjugated linoleic acid supplements did not allow us to identify the specific role of different isomers, but the changes in milk fatty acid composition indicated that effects were primarily on de novo fatty acid synthesis and the desaturation process.


Transconjunctival approach to the zygomatico-frontal limb of orbitozygomatic complex fractures.
Fractures of the orbitozygomatic complex represent one of the most common injuries of the facial skeleton. Repair of the fractures often requires multiple surgical access points and the necessity for skin incisions. As surgeons attuned to aesthetics, we strive to minimize the signs of injury and treatment. We propose an approach designed to treat orbitozygomatic fractures without the use of skin incisions. The objective of this article is to outline the surgical technique designed by the senior author (PRL) to address the zygomatico-frontal fracture component of orbitozygomatic complex fractures through an upper lid lateral transconjunctival approach. Relevant anatomy and technique is described. The combination of previously described lower lid transconjunctival and gingivobuccal sulcus incisions with this new upper lid lateral transconjunctival approach provides adequate access for rigid fixation of all major components of orbitozygomatic fractures without skin incisions.


An analysis of thirty years of contributions to the British anaesthetic literature (1953-1982).
A thirty-year review of the two major British anaesthetic journals, Anaesthesia and the British Journal of Anaesthesia, was undertaken. Overseas contributors accounted for 30% of the total articles published, with North America providing the greatest proportion. The remainder of the contributions came from the United Kingdom. The British contributions were analysed for content and origin. The North West Thames Region with 9%, contributed the single largest percentage of the British articles. There was a marked difference in the Regional contributions, not invariably linked to the size of the Authority or the number of University Departments. Over the thirty-year period there was a progressive increase in the number of published articles and an increase in the proportion of overseas contributors.