Correlation of clinical profile and specific histopathological features of temporal artery biopsies.
This study sought to correlate the clinical features of patients with giant cell arteritis (GCA) who present with ophthalmic symptoms and signs, with 2 specific histopathological findings-the presence of giant cells and arterial wall neoangiogenesis. The goal was to assess if these pathological features might be useful in guiding the approach to patient management. Medical charts were retrospectively reviewed from 58 patients who underwent a temporal artery biopsy at a single institution. Detailed information was collected about the clinical presentation and course, with an emphasis on visual function. Histopathological and immunohistochemical techniques were used to examine temporal artery biopsies for evidence of inflammation. Correlations were made between the clinical data and the presence of giant cells and neoangiogenesis. Twenty-one (34%) biopsies were positive for inflammation consistent with GCA. Although the percentage of positive biopsies with giant cells was high, neither the presence of giant cells nor neoangiogenesis was predictive of a patient's presenting visual symptoms, severity and bilaterality of vision loss, other ophthalmic manifestations of GCA, presence of headache or jaw claudication, or erythrocyte sedimentation rate. Giant cells were more common in patients with recent weight loss. Immunohistochemistry confirmed diagnoses but did not alter the clinical course or treatment plan. There was no correlation between the clinical, specifically visual, features of GCA and the presence or absence of giant cells or neoangiogenesis in temporal artery biopsy specimens. Although the presence of neoangiogenesis may be important in the pathogenesis of GCA, our study showed no correlation between this finding and the clinical course.


Prognostic determinants of infective endocarditis in the 1990s.
The clinical profiles of infective endocarditis (IE) might have changed in recent years, owing to the advent of transesophageal echocardiography, the introduction of new diagnostic criteria, and the increased frequency of intravenous drug abuse. In this retrospective study, we sought to identify factors affecting the in-hospital outcome of IE patients in a single tertiary referral center in the 1990s (1990-1997). Eighty-eight episodes of IE in 80 consecutive patients admitted from January 1990 through June 1997 were evaluated. Clinical variables that were significantly associated with in-hospital mortality in univariate analyses were entered into a multiple logistic regression model. A total of 22 patients (25%) died. Fatal episodes were significantly more likely than non-fatal episodes to involve older patients (> or = 50 years), use of coumadin, short interval between symptom onset and hospitalization (< 15 days), noncardiac shock, and complications of the heart, central nervous system, and kidneys. White blood cell counts and C-reactive protein concentrations were also significantly higher in fatal than in non-fatal episodes of IE. Multivariate analysis showed that in-hospital mortality was associated with noncardiac shock, neurological complications, cardiac complications, and older age (> or = 50 years). Compared with previous reports, our findings suggest that the clinical profiles of IE have undergone some changes in the 1990s. The most important prognostic predictors of in-hospital mortality in patients with IE were noncardiac shock and neurologic complications.


PUB22 and PUB23 U-BOX E3 ligases directly ubiquitinate RPN6, a 26S proteasome lid subunit, for subsequent degradation in Arabidopsis thaliana.
Drought stress strongly affects plant growth and development, directly connected with crop yields, accordingly. However, related to the function of U-BOX E3 ligases, the underlying molecular mechanisms of desiccation stress response in plants are still largely unknown. Here we report that PUB22 and PUB23, two U-box E3 ligase homologs, tether ubiquitins to 19S proteasome regulatory particle (RP) subunit RPN6, leading to its degradation. RPN6 was identified as an interacting substrate of PUB22 by yeast two-hybrid screening, and in vitro pull-down assay confirmed that RPN6 interacts not only with PUB22, but also with PUB23. Both PUB22 and PUB23 were able to conjugate ubiquitins on RPN6 in vitro. Furthermore, RPN6 showed a shorter protein half-life in PUB22 overexpressing plants than in wild-type, besides RPN6 was significantly stabilized in pub22pub23 double knockout plants. Taken together, these results solidify a notion that PUB22 and PUB23 can alter the activity of 26S proteasome in response to drought stress.


[Postradiation pericarditis in lymphogranulomatosis patients].
Postradiation pericarditis was diagnosed in 11 of 52 patients treated for lymphogranulomatosis with radiation applied to enlarged mediastinal lymph nodes. The risk of postradiation pericarditis is greater in cases of high radiation doses (more than 45 Gy) and in patients with postradiation pneumonitis. Postradiation pericarditis can develop both during the exposure and long after radiation therapy; therefore long-term follow-up is required for these patients.


Physical activity and pregnancy: past and present evidence and future recommendations.
In this review, we provide researchers and practitioners with an overview of the physical activity and pregnancy literature to promote prenatal physical activity, improve measurement, further elucidate the role of activity in reducing maternal health complications, and inform future research. We examined past and present physical activity and pregnancy studies and highlight key papers with a focus on maternal health outcomes to best inform physical activity promotion efforts. We discuss: (a) historical overview of prenatal physical activity relative to the physical activity guidelines, how they have changed over time, and how evidence of the effect of prenatal activity on maternal/fetal health outcomes has affected clinical recommendations; (b) existing tools and challenges associated with measuring prenatal physical activity; (c) empirical evidence on multilevel determinants of prenatal activity to guide future intervention work; (d) empirical evidence of prenatal activity on adverse maternal outcomes (gestational diabetes mellitus, preeclampsia, excessive gestational weight gain) from observational and intervention studies; and (e) summary/recommendations for future research and practice. The physical activity and pregnancy literature has evolved over the past 50 years, and there is sufficient empirical evidence to support the promotion of moderate-to-vigorous prenatal physical activity for maternal health benefits. Future studies and interventions should be carefully designed, theoretically driven, and include validated and reliable activity measures. Researchers and practitioners should also consider the multifaceted determinants and outcomes of prenatal physical activity and intervene to promote physical activity before, during, and after pregnancy.


Structured illumination fluorescence microscopy with distorted excitations using a filtered blind-SIM algorithm.
Structured illumination microscopy (SIM) is a powerful technique for obtaining super-resolved fluorescence maps of samples, but it is very sensitive to aberrations or misalignments affecting the excitation patterns. Here, we present a reconstruction algorithm that is able to process SIM data even if the illuminations are strongly distorted. The approach is an extension of the recent blind-SIM technique, which reconstructs simultaneously the sample and the excitation patterns without a priori information on the latter. Our algorithm was checked on synthetic and experimental data using distorted and nondistorted illuminations. The reconstructions were similar to that obtained by up-to-date SIM methods when the illuminations were periodic and remained artifact-free when the illuminations were strongly distorted.


Pathology Associated With an Outbreak of Entamoebiasis in Wild Cane Toads (Rhinella marina) in Tropical Australia.
Infection due to Entamoeba spp. is known to cause serious disease in primates (Entamoeba histolytica) and snakes (Entamoeba invadens), but there are no detailed descriptions of the pathology associated with Entamoeba spp. infection in amphibians. In 2014, an outbreak of entamoebiasis associated with a novel species of Entamoeba induced clinical illness and poor body condition in free-ranging cane toads in Australia's Northern Territory. Here, we describe the gross pathology, histology, and clinical pathology linked to the outbreak. The study compared 25 toads with invasive entamoebiasis, defined as histologically visible amoebas within tissue, and 12 toads without invasive entamoebiasis. Grossly, affected toads had mild to marked congestion of colonic serosal vasculature, with variable thickening of the intestinal wall and serosanguineous to hemorrhagic colonic content. Histologically, invasive entamoebiasis manifested primarily as moderate to severe, variably hyperplastic to ulcerative colitis. The small intestine was affected in 10 of 25 toads, and 5 of 25 toads also had gastric lesions. Amoebas consistent in morphology with Entamoeba sp. were commonly intermingled with mucosal epithelium, frequently along the basement membrane, with deeper invasion into the superficial lamina propria in only 5 toads. Toads with invasive entamoebiasis had neutrophilia, monocytosis, and lymphopenia, and thus elevated neutrophil to lymphocyte ratios, suggestive of an inflammatory and/or stress leukogram.


Intracellular cyclic AMP concentration is decreased in Salmonella typhimurium fur mutants.
It is known that the Fur protein negatively regulates iron-uptake systems in different bacterial species, including Salmonella typhimurium. In this study it has been shown that the intracellular concentration of cyclic AMP (cAMP) is lower in a knockout S. typhimurium fur mutant than in the wild-type strain. According to this, the expression of two cAMP-regulated genes, such as pepE (encoding an alpha-aspartyl dipeptidase) and the Escherichia coli lac operon, is decreased in S. typhimurium fur cells in comparison with wild-type cells. Introduction of an additional mutation in cpdA, encoding a cyclic 3',5'-cAMP phosphodiesterase, recovers wild-type intracellular cAMP concentration in the S. typhimurium fur mutant. Likewise, expression of pepE and the E. coli lac operon was the same in the S. typhimurium fur cpdA double mutant and the wild-type strain. Moreover, these results also demonstrate that the S. typhimurium Fur protein positively regulates the expression of the flhD master operon governing the flagellar regulon. This positive control must be mediated by binding of the S. typhimurium Fur protein to the flhD promoter as indicated by the fact that this promoter tests positive in a Fur titration assay.


Management of anterior segment penetrating injuries with traumatic cataract by Pentagon approach in paediatric age group: constraints and outcome.
To evaluate the efficacy of multiple combined procedure (Pentagon approach) as single-step secondary repair in cases of extensive keratolenticular trauma in paediatric age group. Retrospective evaluation of 18 patients of penetrating injuries with sclerokeratolenticular trauma, who underwent multiple procedure as single-step secondary repair by a single team of two surgeons during a 4 year period. Surgical procedure included reconstruction of anterior segment, synechiolysis, excision of membrane, lensectomy, open sky vitrectomy, PC IOL implantation over frill and penetrating keratoplasty. Meticulous antiamblyopia measures were applied in all cases. Extensive vasoproliferative membrane, complicated cataract and anterior vitreous condensation were significant intra-operative hurdles. Moderate uveitis, secondary glaucoma, persistent epithelial defects were problems noted. Eleven (61.22%) patients attained good visual outcome. Regrafting was required in remaining cases due to delayed graft failure. Despite being a highly complex technique, Pentagon approach provides effective management profile in terms of graft success and functional outcome, especially in keratolenticular trauma, in children.


An ethical appraisal of the choice of vaccines against Poliomyelitis.
Medical ethics is invoked for immunisation of children as it involves an interaction between a healthcare professional and the child. Immunisation under the national immunisation programme is a public health intervention and the common belief is that ethics is not relevant. Two vaccines with contrasting safety and efficacy profiles were available against polio before the national immunisation programme was launched: the inactivated poliovirus vaccine (IPV) and the live attenuated oral poliovirus vaccine (OPV). India chose OPV and excluded IPV. We carried out an ethical appraisal of that choice. Principles of medical ethics comprising four elements-non-maleficence, beneficence, autonomy and justice-was already in vogue at the time. Applying each of them, a head-to-head comparison between IPV and OPV is made. The results clearly show that the choice of vaccine was made without using ethical principles, resulting in serious adverse effects in hundreds of thousands of children. We recommend that medical ethics must be applied to all choices of public health interventions.


Bronchopulmonary dysplasia and inflammatory biomarkers in the premature neonate.
Bronchopulmonary dysplasia (BPD) is the most common, serious sequela of premature birth. Inflammation is a major contributor to the pathogenesis of BPD. Often initiated by a pulmonary fetal inflammatory response, lung inflammation is exacerbated by mechanical ventilation and exposure to supplemental oxygen. In response to these initiators of injury, a complex interaction occurs between proteins that attract inflammatory cells (ie, chemokines), proteins that facilitate the transendothelial migration of inflammatory cells from blood vessels (ie, adhesion molecules), proteins that promote tissue damage (ie, pro-inflammatory cytokines and proteases), and proteins that modulate the process (eg, anti-inflammatory cytokines, binding proteins and receptor antagonists). In addition, during recovery from inflammatory injury, growth factors and other substances that control normal lung growth and mediate repair influence subsequent lung structure. In this review, we discuss the role of each aspect of the inflammatory process in the development of BPD. This discussion will include data from measurements of biomarkers in samples of fluid aspirated from the airways of human infants relevant to each phase of inflammation. Despite their limitations, these measurements provide some insight into the role of inflammation in the development of BPD and may be useful in identifying infants at risk for the disease.


The conjugated oligoelectrolyte DSSN+ enables exceptional coulombic efficiency via direct electron transfer for anode-respiring Shewanella oneidensis MR-1-a mechanistic study.
Shewanella oneidensis MR-1 was cultivated on lactate with poised graphite electrode acceptors (E = +0.2 V vs. Ag/AgCl) in order to explore the basis for sustained increases in anodic current output following the addition of the lipid-intercalating conjugated oligoelectrolyte (COE), 4,4'-bis(4'-(N,N-bis(6''-(N,N,N-trimethylammonium)hexyl)amino)-styryl)stilbene tetraiodide (DSSN+). Microbial cultures, which were spiked with DSSN+, exhibit a ∼2.2-fold increase in charge collected, a ∼3.1-fold increase in electrode colonization by S. oneidensis, and a ∼1.7-fold increase in coulombic efficiency from 51 ± 10% to an exceptional 84 ± 7% without obvious toxicity effects. Direct microbial biofilm voltammetry reveals that DSSN+ rapidly and sustainably increases cytochrome-based direct electron transfer and subsequently increases flavin-based mediated electron transfer. Control experiments indicate that DSSN+ does not contribute to the current in the absence of bacteria.


Musculoskeletal model-guided, customizable selection of shoulder and elbow muscles for a C5 SCI neuroprosthesis.
Individuals with C5/C6 spinal cord injury (SCI) have a number of paralyzed muscles in their upper extremities that can be electrically activated in a coordinated manner to restore function. The selection of a practical subset of paralyzed muscles for stimulation depends on the specific condition of the individual, the functions targeted for restoration, and surgical considerations. This paper presents a musculoskeletal model-based approach for optimizing the muscle set used for functional electrical stimulation (FES) of the shoulder and elbow in this population. Experimentally recorded kinematics from able-bodied subjects served as inputs to a musculoskeletal model of the shoulder and elbow, which was modified to reflect the reduced muscle force capacities of an individual with C5 SCI but also the potential of using FES to activate paralyzed muscles. A large number of inverse dynamic simulations mimicking typical activities of daily living were performed that included 1) muscles with retained voluntary control and 2) many different combinations of stimulated paralyzed muscles. These results indicate that a muscle set consisting of the serratus anterior, infraspinatus and triceps would enable the greatest range of relevant movements. This set will become the initial target in a C5SCI neuroprosthesis to restore shoulder and elbow function.


Effects of Aqua Aerobic Therapy Exercise for Older Adults on Muscular Strength, Agility and Balance to Prevent Falling during Gait.
[Purpose] The purpose of the present study was to examine the effects of an aqua aerobic therapy exercise for older adults on biomechanical and physiological factors affecting gait. [Subjects] A total of 15 subjects participated in this study and they were randomly divided into the experimental and the control group. [Methods] Physiological variables, leg strength, power and flexibility, and biomechanical variables, both kinematic and kinetic, were measured before and after the aqua aerobic therapy exercise. Each subject was instructed to walk along an elevated walkway and during the trials a trapdoor opened at random to create a 10 cm falling perturbation. Full body motion and kinetics was gathered during the gait. [Results] There were significant reductions in body weight, and body fat mass, and stride time after the perturbation. Significant increases in leg strength corresponded to the maximum joint moment of the landing leg showing that the subjects' ability for recovery of balance after the perturbation improved. [Conclusion] As the results showed significant improvements in gait pattern and recovery time after perturbed gait, we conclude that aqua aerobic therapy is an effective exercise method for training older adults to reduce their risk of falling.


Diurnal proteome profile of the mouse cerebral cortex: Conditional deletion of the Bmal1 circadian clock gene elevates astrocyte protein levels and cell abundance in the neocortex and hippocampus.
Circadian oscillators, defined by cellular 24 h clock gene rhythms, are found throughout the brain. Cerebral cortex-specific conditional knockout of the clock gene Bmal1 (Bmal1 CKO) leads to depressive-like behavior, but the molecular link from clock gene to altered behavior is unknown. Further, diurnal proteomic data on the cerebral cortex are currently unavailable. With the aim of determining the diurnal proteome profile and downstream targets of the cortical circadian clock, we here performed a proteomic analysis of the mouse cerebral cortex. Proteomics identified approximately 2700 proteins in both the neocortex and the hippocampus. In the neocortex, 15 proteins were differentially expressed (>2-fold) between day and night, mainly mitochondrial and neuronal plasticity proteins. Only three hippocampal proteins were differentially expressed, suggesting that daily protein oscillations are more prominent in the neocortex. The number of differentially expressed proteins was reduced in the Bmal1 CKO, suggesting that daily rhythms in the cerebral cortex are primarily driven by local clocks. The proteome of the Bmal1 CKO cerebral cortex was dominated by upregulated proteins expressed in astrocytes, including GFAP (4-fold) and FABP7 (>20-fold), in both the neocortex and hippocampus. These findings were confirmed at the transcript level. Cellular analyses of astrocyte components revealed an increased number of GFAP-positive cells in the Bmal1 CKO cerebral cortex. Further, BMAL1 was found to be expressed in both GFAP- and FABP7-positive astrocytes of control animals. Our data show that Bmal1 is required for proper cellular composition of the cerebral cortex, suggesting that increased cortical astrocyte activity may induce behavioral changes.


[The early history of child and adolescent psychiatry. A review of research on historical aspects of the concepts of child psychiatric thought and processes].
This sociohistorical essay attempts to trace back to the enlightenment the roots of contemporary child psychiatry. Five examples are used for illustrative purposes: the emergence of the concepts of human development, classification, compensation for deficits and psychohygiene (now mental hygiene), and the problems arising from the differentiation of schooling. Historical considerations provide numerous reasons for regarding child psychiatry as a medical specialty. These arguments would seem to outweight any need, deriving from economic pressure, to defend this field as an entity separate from its "parent disciplines" (pediatrics, psychiatry and psychosomatic medicine).


Plasmid-Based Lassa Virus Reverse Genetics.
Several mammarenaviruses cause hemorrhagic fever (HF) disease in humans and pose a significant public health problem in their endemic regions. The Old World (OW) mammarenavirus Lassa virus (LASV) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF) cases, a disease associated with high morbidity and mortality. No licensed vaccines are available to combat LASV infection, and anti-LASV drug therapy is limited to the off-label use of ribavirin whose efficacy remains controversial. The development of reverse genetics approaches has provided investigators with a powerful approach for the investigation of the molecular, cell biology and pathogenesis of mammarenaviruses. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in viral genome replication and gene transcription, assembly, and budding, which has facilitated the identification of several anti-mammarenavirus candidate drugs. Likewise, it is possible now to rescue infectious recombinant mammarenaviruses from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of viral pathogenesis. Reverse genetics have also allowed the generation of mammarenaviruses expressing foreign genes to facilitate virus detection, to identify antiviral drugs, and to generate live-attenuated vaccine (LAV) candidates. Likewise, reverse genetics techniques have allowed the generation of single-cycle infectious, reporter-expressing mammarenaviruses to study some aspects of the biology of HF-causing human mammarenavirus without the need of high security biocontainment laboratories. In this chapter, we describe the experimental procedures to generate recombinant (r)LASV using state-of-the-art plasmid-based reverse genetics.


Engineered thermostable fungal cellulases exhibit efficient synergistic cellulose hydrolysis at elevated temperatures.
A major obstacle to using widely available and low-cost lignocellulosic feedstocks to produce renewable fuels and chemicals is the high cost and low efficiency of the enzyme mixtures used to hydrolyze cellulose to fermentable sugars. One possible solution entails engineering current cellulases to function efficiently at elevated temperatures in order to boost reaction rates and exploit several other advantages of a higher temperature process. Here, we describe the creation of the most stable reported fungal endoglucanase, a derivative of Hypocrea jecorina (anamorph Trichoderma reesei) Cel5A, by combining stabilizing mutations identified using consensus design, chimera studies, and structure-based computational methods. The engineered endoglucanase has an optimal temperature that is 17°C higher than wild type H. jecorina Cel5A, and hydrolyzes 1.5 times as much cellulose over 60 h at its optimum temperature compared to the wild type enzyme at its optimal temperature. This enzyme complements previously engineered highly active, thermostable variants of the fungal cellobiohydrolases Cel6A and Cel7A in a thermostable cellulase mixture that hydrolyzes cellulose synergistically at an optimum temperature of 70°C over 60 h.The thermostable mixture produces three times as much total sugar as the best mixture of the wild type enzymes operating at its optimum temperature of 60°C, clearly demonstrating the advantage of higher temperature cellulose hydrolysis.


Photodynamic therapy in endodontics: a literature review.
Recently, several in vitro and in vivo studies demonstrated promising results about the use of photodynamic therapy during root canal system disinfection. However, there is no consensus on a standard protocol for its incorporation during root canal treatment. The purpose of this study was to summarize the results of research on photodynamic therapy in endodontics published in peer-reviewed journals. A review of pertinent literature was conducted using the PubMed database, and data obtained were categorized into sections in terms of relevant topics. Studies conducted in recent years highlighted the antimicrobial potential of photodynamic therapy in endodontics. However, most of these studies were not able to confirm a significant improvement in root canal disinfection for photodynamic therapy as a substitute for current disinfection methods. Its indication as an excellent adjunct to conventional endodontic therapy is well documented, however. Data suggest the need for protocol adjustments or new photosensitizer formulations to enhance photodynamic therapy predictability in endodontics.


Adenosine A(2A) receptors mediate coronary microvascular dilation to adenosine: role of nitric oxide and ATP-sensitive potassium channels.
Adenosine is a potent vasodilator that plays an important role in the regulation of coronary microvascular diameter. Although multiple adenosine receptor subtypes have been recently cloned, the specific adenosine receptor subtypes and the underlying mechanisms responsible for the vasodilation to adenosine in the coronary microcirculation remain unknown. Therefore, in the present study we determined the receptor subtypes for coronary arteriolar dilation to adenosine and investigated the role of nitric oxide (NO) and ATP-sensitive potassium (K(ATP)) channels in this vasodilatory response. Pig coronary arterioles (50-100 microm in situ) were isolated, cannulated, and pressurized without flow for in vitro study. Arterioles developed basal tone and dilated in a concentration-dependent manner to adenosine and to adenosine receptor agonists (2S)-N(6)-[2-endo-norbornyl]adenosine (A(1)), 2-[p-(2-carboxyethyl)]phenylethyl-amino-5'-N-ethylcarboxamidoadenosin e (CGS21680; A(2A)), N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (A(3)), and N-ethylcarboxamidoadenosine (nonselective adenosine receptor activation). The selective A(2A) receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-y l amino]ethyl)phenol attenuated vasodilation to adenosine and to all adenosine receptor agonists tested, suggesting that the vasodilatory responses were primarily mediated by A(2A) receptors. Adenosine- and CGS21680-induced dilations were attenuated in a similar manner by endothelial removal and by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. In denuded vessels, both adenosine- and CGS21680-induced dilations were nearly abolished by the K(ATP) channel inhibitor glibenclamide. The selective A(2A) agonist CGS21680 mechanistically mimics the vasodilation in response to adenosine. Collectively, our results suggest that the dilation of coronary arterioles to adenosine is mediated predominantly by A(2A) receptors. Activation of this receptor subtype elicits vasodilation by endothelial release of NO and by the smooth muscle opening of K(ATP) channels.


Predictors of Mortality in Patients with COVID-19 Infection-associated Acute Kidney Injury.
To determine clinical characteristics, renal replacement therapy (RRT) requirements, and predictors of mortality in critically ill patients with COVID-19 associated AKI. Descriptive study. Sakarya University Education and Training Hospital, Sakarya, Turkey, between April 1 and 30, 2020. The study included 55 patients who were admitted with diagnosis of COVID-19, and whose illnesses showed a critical course that leads to AKI. The variables were studied as per objective. During the follow-up, 43 out of 55 patients (78.2%) died and 12 (21.8%) were discharged with recovery. The mortality was higher in patients at stage 3 (88.9% mortality) compared to stage 2 (53.8% mortality) (p=0.014). In the nonsurvivor group, RDW (red cell distribution width) and albumin levels were lower at admission; whereas, the LDH levels and CRP/albumin ratios were higher. On regression analysis, low albumin level (OR: 12.793, p = 0.010), high LDH level (OR: 8.454, p = 0.026), and presence of stage 3 AKI (OR: 10.268, p = 0.020) were found as independent risk factors for mortality in COVID-19 patients, who developed AKI. In critically ill patients with COVID-19 pneumonia, who developed AKI, it was seen that the presence of low albumin, high LDH, and stage 3 AKI at the time of admission could be used as predictors of mortality. Moreover,, it was shown for the first time that in these patients, the high CRP/albumin ratio and low RDW could be associated with mortality. Key Words: Acute kidney injury, Mortality, COVID-19.


The DNA damage repair protein Ku70 interacts with FOXO4 to coordinate a conserved cellular stress response.
In this study, we searched for proteins regulating the tumor suppressor and life-span regulator FOXO4. Through an unbiased tandem-affinity purification strategy combined with mass spectrometry, we identified the heterodimer Ku70/Ku80 (Ku), a DNA double-strand break repair component. Using biochemical interaction studies, we found Ku70 to be necessary and sufficient for the interaction. FOXO4 mediates its tumor-suppressive function in part through transcriptional regulation of the cell cycle arrest p27(kip1) gene. Immunoblotting, luciferase reporter assays, and flow cytometry showed that Ku70 inhibited FOXO4-mediated p27(kip1) transcription and cell cycle arrest induction by >40%. In contrast, Ku70 RNAi but not control RNAi significantly increased p27(kip1) transcription. In addition, in contrast to wild-type mouse embryonic stem (ES) cells, Ku70(-/-) ES cells showed significantly increased FOXO activity, which was rescued by Ku70 reexpression. Immunofluorescence studies demonstrated that Ku70 sequestered FOXO4 in the nucleus. Interestingly, the Ku70-FOXO4 interaction stoichiometry followed a nonlinear dose-response curve by hydrogen peroxide-generated oxidative stress. Low levels of oxidative stress increased interaction stoichiometry up to 75%, peaking at 50 μM, after which dissociation occurred. Because the Ku70 ortholog in the roundworm Caenorhabditis elegans was shown to regulate life span involving C. elegans FOXO, our findings suggest a conserved critical Ku70 role for FOXO function toward coordination of a survival program, regulated by the magnitude of oxidative damage.


Medical status and complications in relation to periodontal disease experience in insulin-dependent diabetics.
The aim of this study was to define a population of diabetics exhibiting an increased risk of developing severe periodontitis by comparing the medical status of 2 groups of diabetics, 1 with no/minor periodontal disease and 1 with severe periodontal disease. The case-control study consisted of 2 parts, a baseline study and a follow-up study. 39 case-control pairs were selected. They were adult, long-duration, insulin-dependent diabetics matched according to sex, age and diabetes duration. One individual in each pair (the CASE) exhibited severe periodontal disease while the other (the CONTROL) exhibited gingivitis or only minor alveolar bone loss. The median age of the cases was 58 years (range 36 to 70 years) and of the controls 59 years (range 37 to 69 years). The median disease duration in cases and controls was 24 years and 25 years, respectively. The median follow-up time was 6 years. The medical variables analysed were weight, insulin dose, systolic and diastolic blood pressure, vibratory threshold, triglycerides, total-cholesterol, HDL-cholesterol, creatinine, HbA1, proteinuria, ECG, retinopathy, stroke, transient ischemic attacks (TIA), angina, myocardial infarct, heart failure, hypertension, intermittent claudication, foot ulcer, death, cause of death, and smoking habit. Biochemical analyses and clinical variables used as a routine in the monitoring of diabetics failed to differentiate between diabetics with severe and minor periodontal disease. In the follow-up study, significantly higher prevalences of proteinuria and cardiovascular complications such as stroke, TIA, angina, myocardial infarct and intermittent claudication were found in the case group. An association between renal disease, cardiovascular complications and severe periodontitis seems to exist. This indicates that a closer cooperation between the diabetologist and the dentist is necessary in monitoring the diabetic patient.


Risk-benefit assessment of ivabradine in the treatment of chronic heart failure.
Heart rate is not only a major risk marker in heart failure but also a general risk marker. Within the last few years, it has been demonstrated that reduction of resting heart rate to <70 bpm is of significant benefit for patients with heart failure, especially those with impaired left ventricular systolic function. Ivabradine is the first innovative drug synthesized to reduce heart rate. It selectively and specifically inhibits the pacemaker I f ionic current, which reduces cardiac pacemaker activity. Therefore, the main effect of ivabradine therapy is a substantial lowering of heart rate. Ivabradine does not influence intracardiac conduction, contractility, or ventricular repolarization. According to the European Society of Cardiology guidelines, ivabradine should be considered in symptomatic patients (New York Heart Association functional class II-IV) with sinus rhythm, left ventricular ejection fraction ≤35%, and heart rate ≥70 bpm despite optimal treatment with a beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and a mineralocorticoid receptor antagonist. As shown in numerous clinical studies, ivabradine improves clinical outcomes and quality of life and reduces the risk of death from heart failure or cardiovascular causes. Treatment with ivabradine is very well tolerated and safe, even at maximal recommended doses.


Analysis of nonmotile mutants of the dimorphic bacterium Caulobacter crescentus.
A total of 69 spontaneous nonmotile mutants were isolated from the dimorphic bacterium Caulobacter crescentus. The majority of the mutants were unable to assemble a flagellar filament (Fla-), although eight were able to synthesize a short stub of a flagellum. A third mutant class assembled flagella of normal morphology but were nonmotile (Mot-). Genetic analysis by phiCr30-mediated transduction revealed 27 linkage groups for the fla and stub-forming mutations, and three linkage groups for the mot mutations. Intracellular flagellin detected by immunodiffusion was at the limit of detectability in most of the Fla- and stub-forming mutants but normal in the Mot- mutants. The Fla- and stub-forming mutants also showed decreased sensitivity to the swarmer-specific phages phiCbK and phiCb5 and phiCr40. One additional strain was totally resistant to phiCbK, and the mutation in this strain has been designated pleA. Each of the mutants containing mot mutations showed wild-type sensitivity to all of the phages tested.


MPG protection against radiation sickness and weight loss and its correlation with mortality of mice after whole-body gamma-irradiation.
The radiation-induced mortality together with the loss of body-weight and development of radiation sickness was studied in young adult Swiss albino mice after exposure to 1500 R of 60Co gamma-radiation in the presence and absence of 2-mercaptopropionyl-glycine (MGP), and results from both the groups were compared. It was found that the time of onset of radiation sickness was delayed in the drug-treated group, the mean survival time was also increased to 6 days as compared to 4.5 days in the untreated control group. These changes showed a direct correlation with the body-weight changes as the loss of weight in the drug-treated group was less marked and more gradual than in the untreated controls.


Co-assessment of OCT-A and choroidal vascularity index data in multiple sclerosis patients.
To evaluate optical coherence tomography-angiography (OCT-A) findings and choroidal vascular index (CVI) in patients with multiple sclerosis (MS). 113 patients, including multiple sclerosis patients with optic neuritis attack (MSON+) and no optic neuritis attack (MSON-) and healthy control group (HCG), participated in this cross-sectional study. OCT-A images of all patients were taken and CVI was calculated. Superior flow (SF), deep flow (DF), foveal, and parafoveal superior vascular density (sVD) were decreased in the MSON+ group compared to HCG (p < 0.05). Optic disk flow (ODF) and optic disk head density (ONHD) values decreased in the MS group (p < 0.05). CVI was decreased in the MSON+ group compared to HCG (p < 0.05). There is a correlation between CVI and foveal and parafoveal sVD. Non-invasive diagnostic tools such as OCT-A and CVI can be used for early diagnosis and follow-up of microvascular pathologies in inflammatory diseases such as MS.


New insight into the causal relationship between Graves' disease liability and drug eruption: a Mendelian randomization study.
Graves' disease (GD) and drug eruption are closely associated and frequently observed in the clinical setting. However, it remains unclear whether a causal relationship exists between these two conditions. The aim of the study is to investigate whether GD is causal to drug eruptions using two-sample Mendelian randomization. We launched a two-sample MR to investigate whether GD is causal to drug eruption using Genome-wide association study (GWAS) summary data from Biobank Japan and FinnGen. Genetic variants were used as instrumental variables to avoid confounding bias. Statistical methods including inverse variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO were conducted to identify the robustness of the causal effect. Genetically predicted GD may increase the risk of drug eruption by 30.3% (OR=1.303, 95% CI 1.119-1.516, p<0.001) in the Asian population. In European populations, GD may increase the generalized drug eruption by 15.9% (OR=1.159, 95%CI 0.982-1.367, p=0.080). We found GD is potentially causal to drug eruption. This finding expanded the view of the frequently observed co-existence of GD and adverse drug reactions involving the skin. The mechanism remains for further investigation.


Effect of optical absorbance on the Raman spectra of Ce(0.9)Tb(0.1)O(2-delta) solid solution.
Concentration of oxygen vacancies, optical absorption and microstructure of Ce(0.9)Tb(0.1)O(2-) (delta) material under different atmospheres (O(2), He and H(2)) and temperatures are characterized by in situ X-ray diffraction, in situ Raman spectroscopy and confocal microscopy. In this paper, we focus on how the change in optical absorption of the sample significantly affects the observed Raman information (peak intensity and the variation rule of oxygen vacancy concentration) under in situ conditions. With increasing temperature, the optical absorption of the sample decreases because of the release of oxygen and consequent changes of the microstructure. The decline in the optical absorption enables the Raman laser to increase its sampling depth, therefore, the deeper layer phonons in the structure are also sampled and contribute to the Raman scattering when the same excitation laser line is used. A more pronounced effect is observed when 514 nm laser line is used rather than 785 nm excitation, because both Tb and oxygen vacancies are enriched on the surface of the material and the 514 nm light provides surface information, while 785 nm light provides almost complete information on the sample.


[Lipid peroxidation at early stages of loach development].
The activity of the nonenzymatic lipid peroxidation system in the lipids of eggs and embryos of Misgurnus fossilis during the first 6 hours of development is low, on the average, still being somewhat changed. Based on the thermochemoluminescent data, one may assume that the low activity of this system results from the presence of lipophilic antioxidants. Maximum induction periods of thermochemoluminescence have been found for mitochondrial fraction lipid, the minimum one--for microsomal lipid fraction. During 6 hours of the development the induction periods of thermochemoiuminescence of mitochondrial, lysosomal and of microsomal lipid fractions undergo some changes. During the development changes in the effective activation energy of peroxidation of embryo yolk and blastoderm lipids are observed as well.


Discrimination between primary and secondary dengue virus infection by an immunoglobulin G avidity test using a single acute-phase serum sample.
For clinical and epidemiological purposes, it is necessary to be able to classify serological responses during dengue virus infection. Thus, it is important to develop a test that can distinguish between primary and secondary serological responses. The hemagglutination inhibition (HI) test, which is currently recommended by the World Health Organization, is complicated to perform. We developed an enzyme-linked immunosorbent assay based on changes in the avidity of immunoglobulin G during the infectious episode. This test can discriminate between primary and secondary infections by using a single serum sample collected during the acute phase of infection. We took 1,140 avidity measurements with 118 pairs of serum samples or sequential samples taken from patients classified as having primary or secondary infection according to World Health Organization laboratory criteria. The mean percent avidity was significantly lower during primary infection (25.9%) than during secondary infection (66.3%) (Student t test, P < 0.001). The test had a sensitivity of 82.7% (95% confidence interval [CI] = 79.0 to 86.6) and a specificity of 77.5% (95% CI = 73.3 to 81.7). Based on analysis of only blood samples collected between the third and seventh days of the illness, during which most clinical complications occur, the sensitivity and specificity of the test were 95.1% (95% CI = 92.6 to 97.7) and 80.0% (95% CI = 75.3 to 84.7), respectively. This rapid and simple test appears to be an excellent alternative to the HI test for discriminating between primary and secondary dengue virus infections during the acute phase of dengue.


Relationship between pedestrian headform tests and injury and fatality rates in vehicle-to-pedestrian crashes in the United States.
Pedestrian protection evaluations have been developed to encourage vehicle front-end designs that mitigate the consequences of vehicle-to-pedestrian crashes. The European New Car Assessment Program (Euro NCAP) evaluates pedestrian head protection with impacts against vehicle hood, windshield, and A-pillars. The Global Technical Regulation No. 9 (GTR 9), being evaluated for U.S. regulation, limits head protection evaluations to impacts against vehicle hoods. The objective of this study was to compare results from pedestrian head impact testing to the real-world rates of fatal and incapacitating injuries in U.S. pedestrian crashes. Data from police reported pedestrian crashes in 14 states were used to calculate real-world fatal and in- capacitating injury rates for seven 2002-07 small cars. Rates were 2.17-4.04 per 100 pedestrians struck for fatal injuries and 10.45-15.35 for incapacitating injuries. Euro NCAP style pedestrian headform tests were conducted against windshield, A-pillar, and hoods of the study vehicles. When compared with pedestrian injury rates, the vehicles' Euro NCAP scores, ranging 5-10 points, showed strong negative correlations (-0.6) to injury rates, though none were statistically significant. Data from the headform impacts for each of the study vehicles were used to calculate that vehicle's predicted serious injury risk. The predicted risks from both the Euro NCAP and GTR 9 test zones showed high positive correlations with the pedestrian fatal and incapacitating injury rates, though few were statistically significant. Whether vehicle stiffness is evaluated on all components of vehicle front ends (Euro NCAP) or is limited to hoods (GTR 9), softer vehicle components correspond to a lower risk of fatality.


Assay of HBV DNA in the plasma of HBV-carrier chimpanzees superinfected with non-A, non-B hepatitis.
A dot hybridisation technique was used to monitor the levels of hepatitis B virus (HBV) DNA in the plasma of two HBV-carrier chimpanzees which had been inocula ed with documented infectious non-A, non-B hepatitis agents. A marked decrease in the quantity of HBV DNA in the plasma during the acute phase of the non-A, non-B hepatitis was observed in both carriers. The possible role of interferon or a similar antiviral agent in modulation of the HBV-carrier state is discussed. Hybridisation may become, in due course, the method of choice for examining blood samples for infectious hepatitis B virus.


[Legal aspects of the Code of Deontology for nursing personnel].
The author compares the rules contained in the Code of Deontology, of the Nursing Federal Council, and in the Code of Ethics, of the Brazilian Nurses' Association, with the equivalent precepts of the Civil Code and Penal Code of Brazil.


Evolution of hemodynamic forces in the pulmonary tree with progressively worsening pulmonary arterial hypertension in pediatric patients.
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling resulting in right ventricular (RV) dysfunction and ultimately RV failure. Mechanical stimuli acting on the vessel walls of the full pulmonary tree have not previously been comprehensively characterized. The goal of this study is to characterize wall shear stress (WSS) and strain in pediatric PAH patients at different stages of disease severity using computational patient-specific modeling. Computed tomography, magnetic resonance imaging and right heart catheterization data were collected and assimilated into pulmonary artery (PA) models for patients with and without PAH. Patients were grouped in three disease severity groups (control, moderate and severe) based on clinical evaluations. A finite element solver was employed to quantify hemodynamics and wall strains. To estimate WSS in the distal small PAs with diameters ranging from 50 to 500 [Formula: see text], a morphometric tree model was created, with inputs coming from outlets of the 3D model. WSS in the proximal PAs decreased with disease severity (control 20.5 vs. moderate 15.8 vs. severe 6.3 [Formula: see text], [Formula: see text]). Oscillatory shear index increased in the main pulmonary artery (MPA) with disease severity (0.13 vs. 0.13 vs. 0.2, [Formula: see text]). Wall strains measured by the first invariant of Green strain tensor decreased with disease severity (0.16 vs. 0.12 vs. 0.11, [Formula: see text]). Mean WSS for the distal PAs between 100 and 500 [Formula: see text] significantly increased with disease severity (20 vs. 52 vs. 116 [Formula: see text], [Formula: see text]). In conclusion, 3D flow simulations showed that WSS is significantly decreased in the MPA with disease while the mathematical morphometric model suggested increased WSS in the distal small vessels. Computational models can reveal mechanical stimuli acting on vessel walls that may inform patient risk stratification and flow shear experiments.


New perspectives on multilocus ancestry informativeness.
We present an axiomatic approach for multilocus informativeness measures for determining the amount of information that a set of polymorphic genetic markers provides about individual ancestry. We then reveal several surprising properties of a decision-theoretic based measure that is consistent with the set of proposed criteria for multilocus informativeness. In particular, these properties highlight the interplay between information originating from population priors and the information extractable from the population genetic variants. This analysis then reveals a certain deficiency of mutual information based multilocus informativeness measures when such population priors are incorporated. Finally, we analyse and quantify the inevitable inherent decrease in informativeness due to learning from finite population samples.


1,5-diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets.
A number of organic molecules which contain the 1,5-diaryl-3-oxo-1,4-pentadienyl group, referred to hereafter as the dienone moiety, have antineoplastic properties. Emphasis is made on the attachment of this structural moiety to several molecular scaffolds, namely piperidines, N-acylpiperidines, cycloalkanes and 3,4-dihydro-1H-napthalenes. Many of these compounds are potent cytotoxins having micromolar and nanomolar IC(50) values towards a wide range of neoplastic and transformed cells. On occasions, greater toxicity towards neoplasms than normal cells has been demonstrated. A number of these compounds have in vivo anticancer properties and in general excellent tolerability in rodents is demonstrated. The way in which a number of physicochemical properties such as redox potentials, torsion angles, atomic charges and logP values govern cytotoxic potencies are presented. The importance of the shapes of different compounds as determined by molecular modeling in contributing to antineoplastic properties is outlined. Arguments are presented in favour of designing antineoplastics which have multiple sites of action in contrast to those bioactive molecules which have only one molecular target. A number of compounds which possess the dienone group have different modes of action some of which are chronicled in this review, such as inducing apoptosis, affecting respiration in mitochondria, inhibiting macromolecular biosynthesis and both inhibiting and stimulating certain enzymes. Other important properties of these compounds are discussed including their anti-angiogenic, MDR-revertant and antioxidant properties. It is hoped that this eulogy of the importance of the dienone group will encourage researchers to consider incorporating this structural unit into candidate cytotoxins in the future.


Real-Time Multi-Modal Estimation of Dynamically Evoked Emotions Using EEG, Heart Rate and Galvanic Skin Response.
Emotion estimation systems based on brain and physiological signals such as electro encephalography (EEG), blood-volume pressure (BVP), and galvanic skin response (GSR) are gaining special attention in recent years due to the possibilities they offer. The field of human-robot interactions (HRIs) could benefit from a broadened understanding of the brain and physiological emotion encoding, together with the use of lightweight software and cheap wearable devices, and thus improve the capabilities of robots to fully engage with the users emotional reactions. In this paper, a previously developed methodology for real-time emotion estimation aimed for its use in the field of HRI is tested under realistic circumstances using a self-generated database created using dynamically evoked emotions. Other state-of-the-art, real-time approaches address emotion estimation using constant stimuli to facilitate the analysis of the evoked responses, remaining far from real scenarios since emotions are dynamically evoked. The proposed approach studies the feasibility of the emotion estimation methodology previously developed, under an experimentation paradigm that imitates a more realistic scenario involving dynamically evoked emotions by using a dramatic film as the experimental paradigm. The emotion estimation methodology has proved to perform on real-time constraints while maintaining high accuracy on emotion estimation when using the self-produced dynamically evoked emotions multi-signal database.


Biotransformation of Cyclodextrine-Complexed Semisynthetic Betulin Derivatives by Plant Cells.
In this study, three semisynthetic betulonic acid-based compounds, 20(29)-dihydrolup-2-en[2,3-d]isoxazol-28-oic acid, 1-betulonoylpyrrolidine, and lupa-2,20(29)-dieno[2,3-b]pyrazin-28-oic acid, were studied in biotransformation experiments using Nicotiana tabacum and Catharanthus roseus cell suspension cultures. Biotransformation was performed using cyclodextrin to aid dissolving poorly water-soluble substrates. Several new derivatives were found, consisting of oxidized and glycosylated (pentose- and hexose-conjugated) products.


DNA phylogeny, morphology and pathogenicity of Botryosphaeria species on grapevines.
Several species of Botr yosphaeria are known to occur on grapevines, causing a wide range of disorders including bud mortality, dieback, brown wood streaking and bunch rot. In this study the 11 Botryosphaeria spp. associated with grapevines growing in various parts of the world, but primarily in South Africa, are distinguished based on morphology, DNA sequences (ITS-1, 5.8S, ITS-2 and EF1-α) and pathological data. Botryosphaeria australis, B. lutea, B. obtusa, B. parva, B. rhodina and a Diplodia sp. are confirmed from grapevines in South Africa, while Diplodia porosum, Fusicoccum viticlavatum and F. vitifusiforme are described as new. Although isolates of B. dothidea and B. stevensii are confirmed from grapevines in Portugal, neither of these species occurred in South Africa, nor were any isolates of B. ribis confirmed from grapevines. All grapevine isolates from Portugal, formerly presumed to be B. ribis, are identified as B. parva based on their EF1-α equence data. From artificial inoculations on grapevine shoots, we conclude that B. australis, B. parva, B. ribis and B. stevensii are more virulent than the other species studied. The Diplodia sp. collected from grapevine canes is morphologically similar but phylogenetically distinct from D. sarmentorum. Diplodia sarmentorum is confirmed as anamorph of Otthia spiraeae, the type species of the genus Otthia (Botryosphaeriaceae). A culture identified as O. spiraeae clustered within Botryosphaeria and thus is regarded as probable synonym. These findings confirm earlier suggestions that the generic concept of Botryosphaeria should be expanded to include genera with septate ascospores and Diplodia anamorphs.


Application of "the Sequential Organ Failure Assessment (SOFA) score" in predicting outcome in ICU patients with SIRS.
Various scoring systems have been developed to prioritize patient admission and management in ICU. The objective of this prospective, observational cohort study was to evaluate application of one such system, the Sequential Organ Failure Assessment (SOFA) Score in predicting outcome in ICU patients with SIRS. Fifty patients admitted to a six bed multidisciplinary ICU with SIRS were consecutively enrolled in the study and SOFA scores were calculated at zero hour, after 48 hrs, and after 96 hrs and patients followed till discharge from hospital. When compared to outcome, the non survivors had high initial, mean and highest SOFA scores as compared to survivors. (p value = 0.002, <0.001, <0.001 respectively). Delta SOFA was not significantly associated with outcome. (p value= 0.117). The initial SOFA score > 11 predicted a mortality of 90%. (OR 23.72, 95%CI2.68-209.78, p=0.004). Similarly, mean SOFA score of > 7 predicted a mortality of 73.9% (OR 22.7, 95%CI 5.0 - 103.5, p<0.001) and high SOFA score > 11 predicted a mortality of 87.5% (OR 32.66, 95%CI 5.82-183.179, p< 0.001). Area under receiver operating characteristic (ROC) curve for mean SOFA was 0.825, for high SOFA was 0.817 and for initial SOFA was 0.708. Thus mean, high and initial SOFA scores were helpful in predicting between the survivors and the non survivors. The SOFA scoring system is useful in predicting outcomes in ICU and thus help in proper utilization of ICU resources.


Leapfrog dynamics in phage-bacteria coevolution revealed by joint analysis of cross-infection phenotypes and whole genome sequencing.
Viruses and their hosts can undergo coevolutionary arms races where hosts evolve increased resistance and viruses evolve counter-resistance. Given these arms race dynamics (ARD), both players are predicted to evolve along a single trajectory as more recently evolved genotypes replace their predecessors. By coupling phenotypic and genomic analyses of coevolving populations of bacteriophage λ and Escherichia coli, we find conflicting evidence for ARD. Virus-host infection phenotypes fit the ARD model, yet genomic analyses revealed fluctuating selection dynamics. Rather than coevolution unfolding along a single trajectory, cryptic genetic variation emerges and is maintained at low frequency for generations until it eventually supplants dominant lineages. These observations suggest a hybrid 'leapfrog' dynamic, revealing weaknesses in the predictive power of standard coevolutionary models. The findings shed light on the mechanisms that structure coevolving ecological networks and reveal the limits of using phenotypic or genomic data alone to differentiate coevolutionary dynamics.


[Condyloms, dysplasia and carcinomas of cervix: a twenty years experience (1980 - 1999)].
After twenty years of semi-regular detection(1980-1990) concerning 100,358 cervical smears carried out in the Cytology Laboratory in the CHU of Dakar, we have determined the types of cervical lesions in our study. We've found 21.03% of precancerous and cancerous lesions with 17.56% of CIN1, 2.49% of CIN2 and 0.49% of CIN3 and carcinomas. We've observed 9.07% of normal smears, 69.89% of benign cellular modifications, 17.56% of low grade lesions of Bethesda and 3.47% of high grade lesions of Bethesda. These very high figures show that on the one hand precancerous cervical lesions represent a serious public health concern in Senegal, on the other hand regular detection has become an urgent need in Dakar and in the other regions of Senegal where it's not carried out at all at the present time.


Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.
Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.


The use of the 5-year-olds' index: comparison between study models and intraoral photographs.
To determine if photographs may be used instead of dental study models to assess the outcome of primary surgery in 5- to 6-year-olds who were born with complete unilateral cleft lip and palate. Retrospective method comparison study. Five U.K. cleft units. Records of 96 children born with complete unilateral cleft lip and palate. Dental study models and photographs including an overjet measurement taken from both the most prominent and retrusive tooth in each case were scored using the 5-year-olds' index. There was moderate to very good agreement between the methods of using study models or photographs. Intraexaminer agreement was moderate to very good for study models. For the photographs it was good to very good. Overall interexaminer agreement was moderate for both study models and photographs. When impressions are difficult to obtain, intraoral photographs with clinically recorded overjet measurements may be used for the 5-year-olds' index.


Molecular characterization of multidrug-resistant avian pathogenic Escherichia coli isolated from septicemic broilers.
Avian pathogenic Escherichia coli (APEC) causes extensive mortality in poultry flocks, leading to extensive economic losses. To date, little information has been available on the molecular basis of antimicrobial resistance in APEC in Hebei, China. Therefore, the objective of this study was to characterize the virulence and antimicrobial resistance of multidrug-resistant APEC isolated from septicemic broilers at the molecular level. Among 87 nonrepetitive E. coli isolates, 41 (47.1%) carried 3 or more of the APEC virulence genes iroN, ompT, iss, iutA, and hlyF. All 87 APEC isolates showed multidrug-resistant phenotypes, particularly against ampicillin, kanamycin, ciprofloxacin, levofloxacin, streptomycin, gentamycin, ofloxacin, norfloxacin, and ceftriaxone. The β-lactamase-encoding genes blaTEM, blaCMY-2, blaOXA-30, blaCTX-M-15, and blaSHV-2; the aminoglycoside-modifying enzymes (AME) strA, strB, aph(3')-IIa, aac(3)-IIa, aac(6')-Ib, and ant(3″)-Ia; and the plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, and qnrS, were also identified in 66 (75.9%), 65 (74.7%), and 6 (6.9%) isolates, respectively. All isolates were evaluated in terms of replicon type. The plasmid replicons were identified in 63 (72.4%) isolates, and the FIB, B/O, and K replicons were the most present. To the best of our knowledge, this is the first report of molecular characterization of antimicrobial resistance in APEC strains from China.


[Treatment of anterior megalophthalmos cataract with reverse optic capture intraocular lens implantation: a case report].
A 56-year-old male patient sought medical attention due to a gradual decline in bilateral visual acuity, which had been ongoing for a year and had rapidly worsened over the past three months. He received an initial diagnosis of bilateral concurrent cataracts and bilateral anterior megalophthalmos. Subsequently, cataract removal surgery was performed. During the surgery, it was observed that the patient had lax and fragile zonules of the crystalline lens. To address this issue, the surgical team employed reverse optic capture technique for the implantation of a three-piece intraocular lens. Following the surgery, the patient experienced a substantial improvement in uncorrected visual acuity. Remarkably, the patient remained free from adverse reactions, such as elevated intraocular pressure, during a follow-up period extending to 11 years.


Promoting a Healthy Diet in Young Adults: The Role of Nutrition Labelling.
The use of the nutrition facts label has been associated with healthy eating behaviors for adults. However, the relationship between nutrition facts label use and overall diet quality is not well known in young adults, a vulnerable group that acquire lifelong eating behaviors during this period of life. This study aimed to assess if the use of information on the nutrition facts label is associated with a higher diet quality in young adults. In this cross-sectional study, 958 university students aged 18⁻34 years were recruited. Nutrition facts label use was recorded. Dietary intake was assessed using 24-h dietary recall. Healthy Eating Index-2005 (HEI-2005) scores were calculated. HEI-2005 score was significantly associated with using nutrition facts label (p < 0.001). The mean total HEI-2005 score was 60.7 ± 10.11, 62.4 ± 11.43 and 67.1 ± 12.23 respectively for never, sometimes and everytime users of nutrition facts label (p < 0.001). Sub-group scores of HEI-2005 for total fruits, whole fruits, total vegetables, whole grains, milk, oils, saturated fat, and calories from solid fat, alcohol and added sugar (SoFAAS) were significantly higher in regular nutrition facts label users (p < 0.05, for each). This study showed that young adults who regularly use the nutrition facts label have a higher diet quality.


Human thyroid autoantigens and proteins of Yersinia and Borrelia share amino acid sequence homology that includes binding motifs to HLA-DR molecules and T-cell receptor.
We previously reported that the spirochete Borrelia burgdorferi could trigger autoimmune thyroid diseases (AITD). Subsequently, we showed local amino acid sequence homology between all human thyroid autoantigens (human thyrotropin receptor [hTSH-R], human thyroglobulin [hTg], human thyroperoxidase [hTPO], human sodium iodide symporter [hNIS]) and Borrelia proteins (n = 6,606), and between hTSH-R and Yersinia enterocolitica (n = 1,153). We have now updated our search of homology with Borrelia (n = 11,198 proteins) and extended our search on Yersinia to the entire species (n = 40,964 proteins). We also searched the homologous human and microbial sequences for peptide-binding motifs of HLA-DR molecules, because a number of these class II major histocompatibility complex (MHC) molecules (DR3, DR4, DR5, DR8, and DR9) are associated with AITD. Significant homologies were found for only 16 Borrelia proteins (5 with hTSH-R, 2 with hTg, 3 with hTPO, and 6 with hNIS) and only 19 Yersinia proteins (4 with hTSH-R, 2 with hTg, 2 with hTPO, and 11 with hNIS). Noteworthy, segments of thyroid autoantigens homologous to these microbial proteins are known to be autoantigenic. Also, the hTSH-R homologous region of one Borrelia protein (OspA) contains an immunodominant epitope that others have found to be homologous to hLFA-1. This is of interest, as the hLFA-1/ICAM-1 ligand/receptor pair is aberrantly expressed in the follicular cells of thyroids affected by Hashimoto's thyroiditis. A computer-assisted search detected antigenic peptide binding motifs to the DR molecules implicated in AITD. In conclusion, our in silico data do not directly demonstrate that Borrelia and Yersinia proteins trigger AITD but suggest that a restricted number of them might have the potential to, at least in persons with certain HLA-DR alleles.


Attenuation of phytochrome A and B signaling pathways by the Arabidopsis circadian clock.
In higher plants, environmental cues such as light signals are integrated with circadian clock signals to control precisely the daily rhythms observed for many biological functions. We have used a fusion of the promoter of a chlorophyll a/b binding protein gene, CAB2, with firefly luciferase (cab2::luc) to monitor the detailed kinetics of transcription in response to photoreceptor activation in Arabidopsis. Using this marker in phototransduction and circadian-dysfunctional mutants, we studied how signals from phytochrome and the circadian clock are integrated for the regulation of CAB2 transcription. Results from these mutant studies demonstrate that similar expression features, namely, the acute and circadian responses, are present in both etiolated and green seedlings and that the acute and circadian responses are genetically separable. We also demonstrate that persistent Pfr signaling occurs in red light-pulsed etiolated seedlings, which suggests that the circadian clock antagonizes Pfr-mediated signal transduction. Based on these genetic studies, we propose a model for the regulation of CAB2 transcription in which individual photoreceptors and phototransduction components have been assigned to specific pathways for the regulation of discrete kinetic components of the CAB2 expression pattern.


Membrane platform protein PulF of the Klebsiella type II secretion system forms a trimeric ion channel essential for endopilus assembly and protein secretion.
Type IV pili and type II secretion systems are members of the widespread type IV filament (T4F) superfamily of nanomachines that assemble dynamic and versatile surface fibers in archaea and bacteria. The assembly and retraction of T4 filaments with diverse surface properties and functions require the plasma membrane platform proteins of the GspF/PilC superfamily. Generally considered dimeric, platform proteins are thought to function as passive transmitters of the mechanical energy generated by the ATPase motor, to somehow promote insertion of pilin subunits into the nascent pilus fibers. Here, we generate and experimentally validate structural predictions that support the trimeric state of a platform protein PulF from a type II secretion system. The PulF trimers form selective proton or sodium channels which might energize pilus assembly using the membrane potential. The conservation of the channel sequence and structural features implies a common mechanism for all T4F assembly systems. We propose a model of the oligomeric PulF-PulE ATPase complex that provides an essential framework to investigate and understand the pilus assembly mechanism.


Bruxism physiology and pathology: an overview for clinicians.
Awake bruxism is defined as the awareness of jaw clenching. Its prevalence is reported to be 20% among the adult population. Awake bruxism is mainly associated with nervous tic and reactions to stress. The physiology and pathology of awake bruxism is unknown, although stress and anxiety are considered to be risk factors. During sleep, awareness of tooth grinding (as noted by sleep partner or family members) is reported by 8% of the population. Sleep bruxism is a behaviour that was recently classified as a 'sleep-related movement disorder'. There is limited evidence to support the role of occlusal factors in the aetiology of sleep bruxism. Recent publications suggest that sleep bruxism is secondary to sleep-related micro-arousals (defined by a rise in autonomic cardiac and respiratory activity that tends to be repeated 8-14 times per hour of sleep). The putative roles of hereditary (genetic) factors and of upper airway resistance in the genesis of rhythmic masticatory muscle activity and of sleep bruxism are under investigation. Moreover, rhythmic masticatory muscle activity in sleep bruxism peaks in the minutes before rapid eye movement sleep, which suggests that some mechanism related to sleep stage transitions exerts an influence on the motor neurons that facilitate the onset of sleep bruxism. Finally, it remains to be clarified when bruxism, as a behaviour found in an otherwise healthy population, becomes a disorder, i.e. associated with consequences (e.g. tooth damage, pain and social/marital conflict) requires intervention by a clinician.


[50-year-old man with fatigue and monoclonal gammopaty].
This article presents an extremely rare case of monoclonal gammopathy of undetermined importance (MGUS) (known for 16 years) that progressed to multiple myeloma during cytotoxic treatment of malignant lymphoma. Morphological and immunochemical studies were used to characterize the two blood diseases. Identification of type 2 (malignant lymphoma) and type 1(multiple myeloma) disease indicate that the condition was biclonal. The malignant lymphoma responded completely to treatment with chlorambucil and the multiple myeloma responded partially to treatment with melphalan and prednisolone some months later. Diagnosis and follow up of MGUS is commented on.


[Immunoenzyme analysis of the antigenic orientation of "anti-brain" autoantibodies in the serum of epileptics].
With the help of a solid-phase ELISA and the test system of rat brain antigens (protein fractions divided by isoelectrofocusing into zones differing in pI values) the authors discovered autoantibodies to species-nonspecific protein antigens of the brain in the blood sera of epileptic patients and obtained data on the spectra of the antigenic orientation of these autoantibodies. It has been noted that the epileptics' blood sera are characterized by high titres of autoantibodies to glial brain-specific proteins of the group S-100, as well as by undifferentiated proteins, with pI values 3-3.5 and 5-5.5. There were no significant differences in the spectra of the antigenic orientation of autoantibodies in patients with different frequencies of seizures and the localization of the epileptic focus. Considerable differences in the orientation of cerebral autoantibodies in patients with different disease standing were discovered.


Decreased oxidative phosphorylation and PGAM deficiency in horses suffering from atypical myopathy associated with acquired MADD.
Earlier research on ten horses suffering from the frequently fatal disorder atypical myopathy showed that MADD (multiple acyl-CoA dehydrogenase deficiency) is the biochemical derangement behind atypical myopathy. From five horses that died as a result of this disease and seven healthy control horses, urine and plasma were collected ante mortem and muscle biopsies were obtained immediately post-mortem (2 patients and 7 control horses), to analyse creatine, purine and carbohydrate metabolism as well as oxidative phosphorylation. In patients, the mean creatine concentration in urine was increased 17-fold and the concentration of uric acid approximately 4-fold, compared to controls. The highest degree of depletion of glycogen was observed in the patient with the most severe myopathy clinically. In this patient, glycolysis was more active than in the other patients and controls, which may explain this depletion. One patient demonstrated very low phosphoglycerate mutase (PGAM) activity, less than 10% of reference values. Most respiratory chain complex activity in patients was 20-30% lower than in control horses, complex II activity was 42% lower than normal, and one patient had severely decrease ATP-synthase activity, more than 60% lower than in control horses. General markers for myopathic damage are creatine kinase (CK) and lactic acid in plasma, and creatine and uric acid in urine. To obtain more information about the cause of the myopathy analysis of carbohydrate, lipid and protein metabolism as well as oxidative phosphorylation is advised. This study expands the diagnostic possibilities of equine myopathies.


Four mechanisms in the reactions of 3-aminopyrrole with 1,3,5-triazines: inverse electron demand Diels-Alder cycloadditions vs S(N)Ar reactions via uncatalyzed and acid-catalyzed pathways.
Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. S(N)Ar was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used--1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial S(N)Ar product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S(N)Ar reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.


Roxatidine- and cimetidine-induced angiogenesis inhibition suppresses growth of colon cancer implants in syngeneic mice.
Cimetidine is known to suppress the growth of several tumors, including gastrointestinal cancer, in humans and animals. Nonetheless, whether other histamine H(2)-receptor antagonists exert such tumor suppressive effects remains unclear. The effect of roxatidine acetate hydrochloride (roxatidine), an H(2)-receptor antagonist, on the growth of colon cancer implanted in mice was examined and compared with that of cimetidine. Drugs were orally delivered for 26 - 29 days beginning before or after implantation of syngeneic colon cancer (Colon 38) in C57BL/6 mice. Tumor volume was determined throughout and histochemical analysis was also performed. Tumor tissue and serum vascular endothelial growth factor (VEGF) levels were measured. In vitro cell growth was assessed by the MTT assay. Both roxatidine and cimetidine significantly suppressed the growth of Colon 38 tumor implants. Histologic analysis revealed that such antagonists markedly increased necrotic areas and decreased the density of microvessels in tumor tissue. Both H(2)-receptor antagonists suppressed VEGF levels in tumor tissue and significantly decreased serum VEGF levels in Colon 38-bearing mice. Such drugs, however, failed to suppress in vitro growth of the cell line. In conclusion, both roxatidine and cimetidine were found to exert suppressive effects on the growth of colon cancer implants in mice by inhibiting angiogenesis via reducing VEGF expression.


A Novel Interaction Between RAD23A/B and Y-family DNA Polymerases.
The Y-family DNA polymerases - Pol ι, Pol η, Pol κ and Rev1 - are most well-known for their roles in the DNA damage tolerance pathway of translesion synthesis (TLS). They function to overcome replication barriers by bypassing DNA damage lesions that cannot be normally replicated, allowing replication forks to continue without stalling. In this work, we demonstrate a novel interaction between each Y-family polymerase and the nucleotide excision repair (NER) proteins, RAD23A and RAD23B. We initially focus on the interaction between RAD23A and Pol ι, and through a series of biochemical, cell-based, and structural assays, find that the RAD23A ubiquitin-binding domains (UBA1 and UBA2) interact with separate sites within the Pol ι catalytic domain. While this interaction involves the ubiquitin-binding cleft of UBA2, Pol ι interacts with a distinct surface on UBA1. We further find that mutating or deleting either UBA domain disrupts the RAD23A-Pol ι interaction, demonstrating that both interactions are necessary for stable binding. We also provide evidence that both RAD23 proteins interact with Pol ι in a similar manner, as well as with each of the Y-family polymerases. These results shed light on the interplay between the different functions of the RAD23 proteins and reveal novel binding partners for the Y-family TLS polymerases.


Major League Baseball Pitching Performance After Tommy John Surgery and the Effect of Tear Characteristics, Technique, and Graft Type.
Return to play and player satisfaction have been quite high after ulnar collateral ligament reconstruction (UCLR); however, there has been little reported on how outcomes are affected by surgical technique, graft type, and tear characteristics. To evaluate surgical techniques, graft type, and tear characteristics on Major League Baseball (MLB) performance after UCLR. Cohort study; Level of evidence, 2. MLB pitchers who underwent primary UCLR at a single institution were included. Tear characteristics included tear location, tear grade, and acuity. Surgical technique and graft type were also collected. Pitching performance statistics, including earned run average (ERA), walks and hits per innings pitched (WHIP), innings pitched, and fastball velocity were evaluated 3 years before and after UCLR. Forty-six MLB pitchers were identified as having primary UCLR. Return to play was 96%, with 82% returning to MLB play. Technique performed showed no difference in performance. As compared with pitchers with gracilis grafts, pitchers with palmaris grafts were younger ( P = .043), played longer after surgery ( P = .012), and returned to play at 100% (35 of 35) versus 82% (9 of 11, P = .010). When compared with pitchers with proximal tears, pitchers with distal tears pitched at higher velocity (93.0 vs 90.6 mph, P = .023) and had better performance before surgery (ERA, P = .003; WHIP, P = .021); however, those with proximal tears improved to match this performance and velocity after reconstruction. As compared with those having partial tears, pitchers with complete tears played longer after surgery (5.9 vs 4.0 years, P = .033), had a better ERA before injury ( P = .041), and had better WHIP ( P = .037) and strikeouts per 9 innings ( P = .025) after reconstruction. Pitchers with chronic tears had a significant improvement in postoperative ERA, from 4.49 to 3.80 ( P = .040). Technique performed and graft type used did not affect performance; however, pitchers with palmaris grafts returned at a higher rate than those with gracilis grafts. Distal tears occurred in pitchers with greater velocity and better performance before injury, yet pitchers with proximal tears matched this performance after reconstruction. Pitchers with complete tears played longer after reconstruction. Pitchers who had partial tears had worse performance before injury and after reconstruction, and those with chronic tears saw a significant improvement in ERA with reconstruction.


Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.Significance: Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg Cancer Res; 78(20); 5980-91. ©2018 AACR.


Rational Design and Synthesis of Methyl-β-d-galactomalonyl Phenyl Esters as Potent Galectin-8N Antagonists.
Galectin-8 is a β-galactoside-recognizing protein having an important role in the regulation of bone remodeling and cancer progression and metastasis. Methyl β-d-galactopyranoside malonyl aromatic esters have been designed to target and engage with particular amino acid residues of the galectin-8N extended carbohydrate-binding site. The chemically synthesized compounds had in vitro binding affinity toward galectin-8N in the range of 5-33 μM, as evaluated by isothermal titration calorimetry. This affinity directly correlated with the compounds' ability to inhibit galectin-8-induced expression of chemokines and proinflammatory cytokines in the SUM159 breast cancer cell line. X-ray crystallographic structure determination revealed that these monosaccharide-based compounds bind galectin-8N by engaging its unique arginine (Arg59) and simultaneously cross-linking to another arginine (Arg45) located across the carbohydrate-binding site. This structure-based drug design approach has led to the discovery of novel monosaccharide galactose-based antagonists, with the strongest-binding compound (Kd 5.72 μM) holding 7-fold tighter than the disaccharide lactose.


[Temporal layers of the clone. Remarks on a conceptual history].
This paper aims at a history of the clone concept in 20th-century life science and culture. The first part of the paper is concerned with conceptual history approaches. Here, the idea of 'Zeitschichten' by Reinhart Koselleck is discussed and its implications for the history of science are explored. In the following parts of the paper, I trace the historical dynamics of the clone concept in various fields of 20th-century life sciences. I argue that the clone concept, which originated in plant breeding around 1900, soon developed into a technical tool in a variety of research areas. With this, specific meanings became attached: the idea of standardization, genetic identity, and mass reproduction. A further connotation of the clone was the idea of stagnancy with respect to processes in time: The clone was seen as something that was exempt from evolutionary changes. In the last section of the paper, I trace the shifting meanings of the clone concept in the 1960s and 1970s, when the clone became a widespread metaphor that pointed to future biotechnologically driven possibilities to reshape the nature of human beings. In this regard, the debates of the 1970s are analyzed as a turning point: Whereas utopian and eugenic visions predominated the debates in the 1960s (when the human clone was seen as something which will occur in a distant future), the 1970s discussion focused on the advent of a biotechnological era and the human clone had became a reality.


Disseminated intravascular coagulation in infectious disease.
Severe infection and inflammation almost invariably lead to hemostatic abnormalities, ranging from insignificant laboratory changes to severe disseminated intravascular coagulation. Systemic inflammation as a result of severe infection leads to activation of coagulation, due to tissue factor-mediated thrombin generation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Proinflammatory cytokines play a central role in the differential effects on the coagulation and fibrinolysis pathways. Vice versa, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The relevance of the cross-talk between inflammation and coagulation is underlined by the results of the treatment of severe systemic infection with modulators of coagulation and inflammation.


A review of factors that moderate autobiographical memory performance in patients with major depressive disorder.
Studies of autobiographical recall in patients with major depressive disorder (MDD) reveal overgeneralization, where autobiographical memory (AM) comprises primarily factual or repeated information as opposed to details specific in time and in place and definitive of episodic re-experiencing. In addition to reviewing AM impairment in MDD, we explore the contribution of key method, demographic, and clinical variables to this dysfunction. Several candidate variables emerge, including testing method, emotion, mood state, illness burden, medication status, electroconvulsive therapy (ECT), comorbidity, trauma, age, ruminative state, and executive and memory function. These variables appear to interact in a complex manner to influence AM performance in MDD.


Risk and resilience in autism spectrum disorder: a missed translational opportunity?
The objective of this review is to provide a narrative summary of risk and resiliency in autism spectrum disorder (ASD) over the lifespan. In recent years, much has been learned about risk factors for ASD which include both genetic and environmental mechanisms. Resiliency in ASD is much less studied but examples can be gleaned by exploring studies that allow for heterogeneity in causation and outcome. Possible examples come from the literature on sex difference, infant siblings, and natural history. Exciting translational opportunities can be achieved through a greater focus on understanding protective factors and resiliency in ASD than the field's almost exclusive focus on risk factors and the ability to predict poor outcomes. Although the exact nature of processes that protect in ASD are not yet known, putting a resiliency lens on research and clinical practice may prove illuminating. Resiliency in autism spectrum disorder is a function of the vast variation seen in etiology and outcome. A focus on strengthening protective factors may improve long-term outcome.


Spatio-Temporal Distribution of Acinetobacter baumannii in Germany-A Comprehensive Systematic Review of Studies on Resistance Development in Humans (2000-2018).
Acinetobacter (A.) baumannii has gained global notoriety as a significant nosocomial pathogen because it is frequently associated with multi-drug resistance and hospital-based outbreaks. There is a substantial difference in the incidence of A. baumannii infections between different countries and within Germany. However, its continuous spread within Germany is a matter of concern. A systematic literature search and analysis of the literature published between 2000 and 2018 on A. baumannii in humans was performed. Forty-four studies out of 216 articles met the criteria for inclusion, and were selected and reviewed. The number of published articles is increasing over time gradually. Case reports and outbreak investigations are representing the main body of publications. North Rhine-Westphalia, Hesse and Baden-Wuerttemberg were states with frequent reports. Hospitals in Cologne and Frankfurt were often mentioned as specialized institutions. Multiresistant strains carrying diverse resistance genes were isolated in 13 of the 16 German states. The oxacillinase blaOXA-23-like, intrinsic blaOXA-51-like, blaOXA-58 variant, blaNDM-1, blaGES-11, blaCTX-M and blaTEM are the most predominant resistance traits found in German A. baumannii isolates. Five clonal lineages IC-2, IC-7, IC-1, IC-4 and IC-6 and six sequence types ST22, ST53, ST195, ST218, ST944/ST78 and ST348/ST2 have been reported. Due to multidrug resistance, colistin, tigecycline, aminoglycosides, fosfomycin, ceftazidime/avibactam and ceftolozan/tazobactam were often reported to be the only effective antibiotics left to treat quadruple multi-resistant Gram-negative (4MRGN) A. baumannii. Dissemination and infection rates of A. baumannii are on the rise nationwide. Hence, several aspects of resistance development and pathogenesis are not fully understood yet. Increased awareness, extensive study of mechanisms of resistance and development of alternative strategies for treatment are required. One-Health genomic surveillance is needed to understand the dynamics of spread, to identify the main reservoirs and routes of transmission and to develop targeted intervention strategies.


Glutamine synthetase in cerebrospinal fluid, serum, and brain: a diagnostic marker for Alzheimer disease?
To determine whether the glutamine synthetase (GS) level in cerebrospinal fluid (CSF) is a useful biochemical marker in the diagnosis of Alzheimer disease (AD), and to assess the source of GS (brain vs. blood derived) in CSF. Sandwich enzyme immunoassay and immunoblotting were applied to detect GS in CSF and in serum from neurologically healthy control subjects and patients with neurodegenerative diseases, including AD. The origin of GS was estimated by the concentration gradients of CSF to serum and ventricular to lumbar CSF. In addition, postmortem brain tissue from controls and patients with AD was analyzed using immunohistochemistry for expression of GS. Levels of GS were significantly increased in lumbar CSF from patients with AD (20+/-12 pg/mL; P = .01) and to a lesser extent in patients with vascular dementia and amyotrophic lateral sclerosis. In CSF of controls, GS levels were 4+/-3 pg/mL. The GS concentration gradients were less than 1:10 for CSF to serum and 2:1 for ventricular to lumbar CSF. Immunoreactivity of GS was most prominent in astrocytes from temporal neocortex of patients with AD, suggesting a relationship between astrocyte reactions and increased GS levels in CSF. Level of GS in lumbar CSF of patients with AD is increased significantly but nonspecifically, probably related to the strong astrogliosis in brain. Glutamine synthetase in lumbar CSF is mainly brain derived.


Genomic and phenotypic analyses of Pseudomonas psychrotolerans PRS08-11306 reveal a turnerbactin biosynthesis gene cluster that contributes to nitrogen fixation.
Plant-microbe interactions can provide agronomic benefits, such as enhancing nutrient uptake and providing fixed nitrogen. The Pseudomonas psychrotolerans strain PRS08-11306 was isolated from rice seeds and can enhance plant growth. Here, we analyzed the P. psychrotolerans genome, which is ∼5Mb, with 4389 coding sequences, 77 tRNAs, and 7 rRNAs. Genome analysis identified a cluster of turnerbactin biosynthetic genes, which are responsible for the production of a catecholate siderophore and contribute to nitrogen fixation for the host. Analysis of the transcription factor mutant ΔrpoS, which does not express this gene cluster, confirmed the relationship between the gene cluster and siderophore production. The nitrogen fixation characteristics of the cluster were confirmed in a plant growth-promoting experiment. The annotated full genome sequence of this strain sheds light on the role of P. psychrotolerans PRS08-11306 as a plant beneficial bacterium.


A case-control study of bladder cancer in the United States rubber and tyre industry.
A case-control study of bladder cancer was conducted in five United States rubber and tyre companies to determine if there were high-risk jobs and work areas within the industry. The study included 220 male cases of bladder cancer, of whom 107 were identified from hospital record reviews and 113 from death certificates. Each case was matched individually with two industry controls by sex, race, year of birth, and company. One control was matched additionally by year of hire and duration of employment. Comparisons of cases and controls not matched by year of hire and age of hire showed no differences for those variables, which suggests that age and calendar period of first exposure to the industry were not risk determinants. When the work histories of both cases and controls were contrasted it was found that cases were more likely than controls to have worked in milling (odds ratio (OR) = 1.91) and calender operation (OR = 2.21) jobs. The relative risk estimates for milling and calender operation both exhibited linear trends of increase with duration of exposure. Milling and calender operation jobs entail potential exposures to volatilised reaction products from heated rubber stock. A better understanding of aetiological associations with job type will require more detailed characterisation of the work environment with regard to the sources and levels of aromatic amines and other suspected bladder carcinogens.


Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma, and serum.
We describe a direct radioimmunoassay for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. We raised antisera in rabbits against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a 200-microL sample. Within-day precision (CV) is 4.3%, between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n = 21) or low-pressure hydrocephalus (n = 10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.


Real-time in vivo mitochondrial redox assessment confirms enhanced mitochondrial reactive oxygen species in diabetic nephropathy.
While increased mitochondrial reactive oxygen species have been commonly implicated in a variety of disease states, their in vivo role in the pathogenesis of diabetic nephropathy remains controversial. Using a two-photon imaging approach with a genetically encoded redox biosensor, we monitored mitochondrial redox state in the kidneys of experimental models of diabetes in real-time in vivo. Diabetic (db/db) mice that express a redox-sensitive Green Fluorescent Protein biosensor (roGFP) specifically in the mitochondrial matrix (db/dbmt-roGFP) were generated, allowing dynamic monitoring of redox changes in the kidneys. These db/dbmt-roGFP mice exhibited a marked increase in mitochondrial reactive oxygen species in the kidneys. Yeast NADH-dehydrogenase, a mammalian Complex I homolog, was ectopically expressed in cultured podocytes, and this forced expression in roGFP-expressing podocytes prevented high glucose-induced increases in mitochondrial reactive oxygen species. Thus, in vivo monitoring of mitochondrial roGFP in diabetic mice confirms increased production of mitochondrial reactive oxygen species in the kidneys.