[Occupational asthma compensation in the Tunisian Center: cross-sectional study over a period of eight years].
Our study aimed to highlight the epidemiological profile of patients compensated for occupational asthma in the Tunisian Center, to identify their professional characteristics and to determine compensation practices for this occupational disease. We conducted an exhaustive retrospective study over a period of eight years. This case study included workers with occupational asthma diagnosed and compensated in the Tunisian Center by the only two medical commissions empowered to set rates for permanent partial disability caused by either a work-related injury or an occupational diseases in the seven central governorates. A total of 129 workers, with average age of 40.6 ± 7.75 years were compensated for occupational asthma during the study period. Sex ratio was 0.66. The most incriminated etiologic agents were vegetable dust pollution in the textile industry (75.2%), wood dust, flour and isocyanates. Nonspecific bronchial hyperreactivity was found in 38% of cases, a high rate of IgE in 14% of cases and positive skin prick test in 10.9% of cases. The average rate of permanent partial disability was 25.6 ± 14.2%. On the basis of the analytical study, this rate was related to patient's age and to the medical commission which had set this rate. This study of workers compensated for occupational asthma provides relevant data about epidemiological and clinical features of diagnosed patients and committee practices in particular, in term of application of the voluntary indicative scale, but it does not allow an assessment of the prevalence of this pathology which is often underestimated.


The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry.
The chemokine receptor CXCR4 plays critical roles in development, immune function, and human immunodeficiency virus type 1 (HIV-1) entry. Here we demonstrate that, like the CC-chemokine receptors CCR5 and CCR2b, CXCR4 is posttranslationally modified by sulfation of its amino-terminal tyrosines. The sulfate group at tyrosine 21 contributes substantially to the ability of CXCR4 to bind its ligand, stromal derived factor 1 alpha. Tyrosine sulfation plays a less significant role in CXCR4-dependent HIV-1 entry than in CCR5-dependent HIV-1 entry. In some cell lines, CXCR4 is efficiently modified by a chondroitin sulfate chain at serine 18, but neither HIV-1 entry nor stromal derived factor 1 alpha binding was affected by loss of this glycosaminoglycan. These data demonstrate a functional role for tyrosine sulfate in the CXC-chemokine receptor family and underscore a general difference in HIV-1 utilization of CCR5 and CXCR4.


Low-intensity pulsed ultrasound decreases major amputation in patients with critical limb ischemia: 5-year follow-up study.
Various therapeutic strategies for angiogenesis are performed to improve symptoms in patients with critical limb ischemia (CLI). Pre-clinical studies have shown that low-intensity pulsed ultrasound (LIPUS) exposure induces angiogenesis. LIPUS may be a new stratergy for treatment of CLI. The purpose of this pilot trial was to evaluate outcomes in patients with CLI who were treated with LIPUS. Fourteen patients with CLI, who were not candidates for angioplasty or surgical revascularization, were enrolled in this study. Historical control data were obtained from the Hiroshima University PAD database. The primary endpoints were major amputation and death. The outcomes were compared in 16 lower limbs of the 14 patients with CLI who were treated with LIPUS and in 14 lower limbs of 14 patients with CLI as historical controls. All patients were followed for after 5 years after treatment with LIPUS. The mean duration of LIPUS exposure in the LIPUS group was 381± 283 days. During the 5-year follow-up periods, there were 3 major amputations and 7 deaths in the LIPUS group and there were 14 major amputations and 7 deaths in the historical control group. The overall amputation-free survival rate was significantly higher in patients who were treated with LIPUS than in historical controls. There was no significant difference between overall mortality-free survival rates in the LIPUS group and historical control group. LIPUS is a noninvasive option for therapeutic angiogenesis with the potential to reduce the incidence of major amputations in patients with CLI.


A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis.
Diarrhoeal disease is responsible for 8.6% of global child mortality. Recent epidemiological studies found the protozoan parasite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on infants and immunocompromised individuals. There is neither a vaccine nor an effective treatment. Here we establish a drug discovery process built on scalable phenotypic assays and mouse models that take advantage of transgenic parasites. Screening a library of compounds with anti-parasitic activity, we identify pyrazolopyridines as inhibitors of Cryptosporidium parvum and Cryptosporidium hominis. Oral treatment with the pyrazolopyridine KDU731 results in a potent reduction in intestinal infection of immunocompromised mice. Treatment also leads to rapid resolution of diarrhoea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection. Our results suggest that the Cryptosporidium lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) is a target for pyrazolopyridines and that KDU731 warrants further preclinical evaluation as a drug candidate for the treatment of cryptosporidiosis.


Formation of supramolecular assemblies and liquid crystals by purine nucleobases and cyanuric acid in water: implications for the possible origins of RNA.
The free nucleobases and mononucleotides of RNA do not form Watson-Crick base pairs in water, a fact that presents several challenges for the prebiotic synthesis of RNA. 2,6-Diaminopurine and adenosine-5'-monophosphate (AMP) are shown to form supramolecular assemblies with cyanuric acid in water. These assemblies and their propensity to form liquid crystals suggest a possible means by which non-covalent structures might have originally selected the shape of the Watson-Crick base pairs.


Cardiovascular and Autonomic Responses to a Maximal Exercise Test in Elite Youngsters.
To analyze cardiovascular and autonomic responses in elite youngsters, 13 male cyclists (15.43±0.51 years) performed a graded-test until voluntary exhaustion. Oxygen consumption (VO2), blood lactate (BLa), arterial oxygen saturation (SaO2), respiratory exchange ratio (RER) and rating of perceived exertion (RPE) were collected, while heart rate (HR) was registered for heart rate variability (HRV) analyses, looking for linear and nonlinear comparisons. Cyclists reached maximal exertion [RPE: 19.14±0.94; BLa: 8.92±2.51 mmol.L-1; RER: 1.04±0.03; SaO2: 92.43±2.5%] and high-level performance (4.41±0.46 W·Kg-1; 60.77±6.87 ml·Kg·min-1) once over 95% of age-predicted HRmax. VO2 and RPE increased, and RR intervals (RRi) decreased (p<0.005), whereas only the short-term scaling exponent of the Detrended Fluctuation Analysis technique (DFA1) displayed similar adaptive changes regarding intensity (p=0.011). After controlling for W·Kg-1 and RRi, DFA1100% (0.260±0.084) showed large-negative correlations with VO2max (r=-0.83; p<0.05) and RPEmax (r=-0.79; p<0.05), suggesting a strong association between the reduction in self-similar properties of the cardiac signal and the capacity to elicit at maximum in youths. Overall-HRV (lnRMSSD) and short-term variability (lnSD1) did not show any association at maximum, or significant differences regarding intensity. DFA1 might reflect ANS-CNS linkage related to cardiac respiratory controls through exercise, becoming a complementary criterion for VO2max testing in youths.


Cortical Brain-Computer Interface for Closed-Loop Deep Brain Stimulation.
Essential tremor is the most common neurological movement disorder. This progressive disease causes uncontrollable rhythmic motions-most often affecting the patient'sdominant upper extremity-thatoccur during volitional movement and make it difficult for the patient to perform everyday tasks. Medication may also become ineffective as the disorder progresses. For many patients, deep brain stimulation (DBS) of the thalamus is an effective means of treating this condition when medication fails. In current use, however, clinicians set the patient's stimulator to apply stimulation at all times-whether it is needed or not. This practice leads to excess power use, and more rapid depletion of batteries that require surgical replacement. In this paper, for the first time, neural sensing of movement (using chronically implanted cortical electrodes) is used to enable or disable stimulation for tremor. Therapeutic stimulation is delivered onlywhen the patient is actively using their effected limb, thereby reducing the total stimulation applied, and potentially extending the lifetime of surgically implanted batteries. This paper, which involves both implanted and external subsystems, paves the way for fully-implanted closed-loop DBS in the future.


Management and analysis of out-of-hospital health-related responses to simultaneous railway explosions in Madrid, Spain.
On 11 March 2004, 10 simultaneous explosions at four different locations of the rail network in Madrid caused 198 deaths and 2312 persons were injured. The aim of this manuscript is to describe the prehospital health-related activities from the Emergency Medical Service of Madrid and to analyze the responses, the major conclusions, and the lessons learned. Three meetings were held with professionals from the Emergency Medical Service of Madrid who were involved in the catastrophe. Two experts in quality management chaired the meetings. Detailed data were gathered on what occurred at the sites following the explosions. Additional data were gathered from professionals from the Coordination Service of Urgencies and from those who assisted relatives and friends of victims in the days following the bombings. All of the data were collected and were included in the final report. We describe the activities carried out by the Coordination Service of Urgencies at each site immediately after the explosions and during the 11 days following the catastrophe. The successful performances and those that need to be improved at the four sites and elsewhere are detailed. The main reasons for the 'positive responses' are the number of resources that acted, the professional abilities, and the flexibility of the services. The 'areas to be improved' are communications, the establishment of the top of the command at each site, and the organization of supplies for catastrophic assistance. From the analysis, we describe the main lessons learned and we present proposals for improvement, should a future catastrophe occur.


Piezoelectric driving of vibration conveyors: an experimental assessment.
Vibratory feeders or vibratory conveyors have been widely used for the transport and orientation of individual parts and bulk materials in many branches of industrial activity. From the designer's standpoint, the current endeavor is to conceive efficient vibratory feeders, satisfying constraints of power consumption, vibration transmission and noise emission. Moreover, the interest in the reduction of maintenance cost is always present. In this context, this paper investigates experimentally the concept of vibratory conveying based on the use of piezoelectric materials for motion generation. A small-size prototype of a linear conveyor, in which lead-zirconate-titanate (PZT) patches are bonded to the resilient elements, is described. One of the main design goals is that the prototype is intended to be fed directly from the electric network, aiming at avoiding the use of electronic equipment for driving. To comply with this feature and, at the same time, enable to adjust the transport velocity, a mechanical device has been conceived in such a way that the first natural frequency of the conveyor can be changed. It is shown that the transport velocity is determined by the proximity between the excitation frequency and the first natural frequency of the conveyor. The experimental tests performed to characterize the dynamic behavior of the prototype are described and the range of transport velocities is determined.


Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice.
Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO's suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT's endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO's improvement of obesity and glucose homeostasis can be attributed to increased iBAT thermogenic capacity and activation of BAT's endocrine functions.


Knee Extensor Mechanism Complications After Autograft Harvest in ACL Reconstruction: A Systematic Review and Meta-analysis.
Existing systematic reviews have sought to characterize the relative donor-site morbidity of bone-patellar tendon-bone (BTB) and quadriceps tendon (QT) grafts after anterior cruciate ligament reconstruction (ACLR). However, no studies have reported the pooled proportions of patellar fractures and donor tendon ruptures across the body of literature. To estimate the proportion of patellar fractures, patellar tendon ruptures, and QT ruptures associated with BTB or QT autograft harvest during ACLR using published data. Systematic review; Level of evidence, 4. A meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using 3 online databases (PubMed, Scopus, and Web of Science). A total of 800 manuscripts were included in the initial research of peer-reviewed articles in English that reported extensor mechanism complications associated with graft harvest in patients after ACLR. Pooled proportions of patellar fractures, patellar tendon ruptures, and QT ruptures were calculated for each graft type (BTB, QT) using a random-effects model for meta-analysis. A total of 28 studies were analyzed. The pooled proportion of patellar fractures was 0.57% (95% CI, 0.34%-0.91%) for the BTB harvest and 2.03% (95% CI, 0.78%-3.89%) for the QT harvest. The proportion of patellar tendon ruptures was 0.22% (95% CI, 0.14%-0.33%) after the BTB harvest, and the proportion of QT ruptures was 0.52% (95% CI, 0.06%-1.91%) after the QT harvest. The majority of included studies (16/28 [57.1%]) had an evidence level of 4. Based on the current literature, the proportion of extensor mechanism complications after ACLR using either a BTB or a QT autograft is low, indicating that the extensor mechanism harvest remains a safe option. A higher proportion of patellar fractures was noted for QT grafts and a higher proportion of donor tendon ruptures was noted for QT grafts compared with BTB grafts.


Robust spin manipulation in 2D organometallic Kagome lattices: a first-principles study.
The search for 2D ferromagnets with versatile magneto-electronic properties is becoming more active due to their potential applications in spintronic devices. To screen out the optimal compositions, we have explored a series of two-dimensional M3C12X12 (M = 5d transition metals, and X = S, NH, and O) metal-organic frameworks with Kagome lattice patterns through first-principles calculations. By varying the metal center and ligand functional radicals, both the electronic and spin-related properties can be easily tuned to meet the requirements for multifunctional applications in spintronic devices. Among them, Re3C12N12H12 is identified to be a ferromagnetic bipolar magnetic semiconductor with the highest Curie temperature (TC > 330 K). Re3C12O12 is found to be an ideal half-metal with a spin gap of 0.97 eV, which is beneficial for use as a spin-filter. Meanwhile, both Re3C12N12H12 and Re3C12O12 exhibit considerable out-of-plane magnetic anisotropy energies (>26 meV per atom), which benefit the spintronic applications. The theoretical results not only show that the 2D organometallic Kagome lattice is a good platform for designing spintronic materials, but also provides a feasible way to realize robust spin manipulation.


[The criteria and place of limited surgery in treating breast cancer].
The evolution of conceptions regarding the treatment of "operable" mammary cancer has balanced during the past 25 years between amputation of the mamma and non-mutilating treatments. The main achievements concerning the evolution of this site of cancer, as well as the selection criteria for a limited operation, such as they result from the literature and from the studies performed by the authors, are pointed out. These criteria, although numerous, should be very rigorously observed. The cooperation surgeon-radiotherapist-anatomo-pathologist is absolutely compulsory. Authors report 16 cases of women with mammary cancer, in 9 of whom the criteria were carried out. The results obtained are for the time being favourable but as the group is very small, definitive conclusions cannot be drawn.


Using Published Pathway Figures in Enrichment Analysis and Machine Learning.
Pathway Figure OCR (PFOCR) is a novel kind of pathway database approaching the breadth and depth of Gene Ontology while providing rich, mechanistic diagrams and direct literature support. PFOCR content is extracted from published pathway figures currently emerging at a rate of 1000 new pathways each month. Here, we compare the pathway information contained in PFOCR against popular pathway databases with respect to overall and disease-specific coverage. In addition to common pathways analysis use cases, we present two advanced case studies demonstrating unique advantages of PFOCR in terms of cancer subtype and grade prediction analyses.


Application of a fine thread beam to the structure analysis of a hemihedrally twinned crystal of hydroxylamine oxidoreductase.
Accurate diffraction intensity data have been collected from a twinned P6(3) crystal of the 24-haem protein hydroxylamine oxidoreductase, from a nitrifying chemoautotrophic bacterium Nitrosomonas europaea, using synchrotron radiation at station BL6A of the Photon Factory. Estimation of the twinning fraction and deconvoluted intensity data, including native and heavy-atom derivative data, gave an improved Patterson function. Four diffraction data sets were collected from one crystal and an estimation of the twinning fraction to confirm the phenomena was undertaken. The successfully detwinned data sets were utilized in the structure analysis of the present enzyme. The mechanism of twinned-crystal formation is also discussed.


Diversity and abundance of antibiotic resistance genes and their relationship with nutrients and land use of the inflow rivers of Taihu Lake.
Taihu Lake is the third largest freshwater lake in China and an important source for drinking water, flood protection, aquaculture, agriculture, and other activities. This lake is connected to many principal and small rivers with inflow from west and outflow on the eastern side of the lake and these inflow rivers are believed to significantly contribute to the water pollution of the lake. This study was aimed at assessing the diversity and abundance of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), and their relationship with water quality parameters and land use patterns. Water samples were collected from 10 major inflow rivers and the source water protection area of the Taihu Lake in spring and summer 2019. High-throughput profiling was used to detect and quantify 384 ARGs and MGEs and in addition, 11 water quality parameters were analyzed. The results showed that the number of ARGs/MGEs detected in each inflow river ranged from 105 to 185 in spring and 107 to 180 in summer. The aminoglycoside resistance genes were the most dominant types ARGs detected followed by beta-lactam resistance, multidrug resistance, macrolide-lincosamide-streptogramin B (MLSB) resistance genes, which contributed to 65% of the ARGs. The water quality parameters showed significant correlation with absolute abundance of ARGs. Furthermore, significant correlation between ARGs and MGEs were also observed which demonstrates potential gene transfer among organisms through horizontal gene transfer via MGEs. ARGs showed strong positive correlation with cultivated and industrial lands whereas, negative correlation was observed with river, lake, forest, land for green buffer, and land for port and harbor. The overall results indicate that the inflow rivers of Taihu Lake are polluted by various sources including multiple nutrients and high abundance of ARGs, which needs attention for better management of the inflow rivers of this lake.


Unconventional natural gas development and human health: thoughts from the United States.
If unconventional gas development (UGD) continues to expand in Australia, the potential health and environmental impacts should be adequately addressed and preventive public health measures should be implemented. The United States has embraced UGD and has decades of experience that could be beneficial to Australia as stakeholders debate the potential benefits and harms of the technique. Additional research on the health impacts of UGD is necessary. Baseline and trend morbidity and mortality data need to be collected to assess changes in population health over time. To date, few health or epidemiological studies have been conducted, so it remains difficult to assess actual health outcomes. In the absence of scientific consensus, there are two possible risks: failing to develop unconventional natural gas when the harms are manageable; or developing it when the harms are substantial. Many government bodies around the world have chosen to minimise the risk of the latter until the impacts of UGD are better understood. Policies should be informed by empirical evidence based on actual experience rather than assurance of best practices. There is a strong rationale for precautionary measures based on the health and environmental risks identified in the scientific literature.


The effect of psychological intervention on personality change, coping, and psychological distress of Japanese primary breast cancer patients.
The purpose of this study is to estimate the effectiveness of psychological intervention on personality change, enhancing perceived emotional support, and, ultimately, assisting in the adaptive coping and psychological well-being of Japanese primary breast cancer patients. The intervention consists of 3 sessions that include providing medical and psychological information and counseling using the structured association technique. The participants were 28 primary breast cancer patients (14 for the experimental group and 14 for the control group). Participants were assessed at 3 to 4 days after surgery (preintervention) and 3 months (postintervention) and 6 months (follow-up) after discharge using 5 scales: the self-repression scale, the Japanese version of the self-esteem scale, the emotional support scale, the Japanese version of the Mental Adjustment to Cancer Scale, and the Japanese version of the Hospital Anxiety and Depression Scale. The intervention seemed to have enhanced the short-term personality change, adaptive coping, and psychological well-being of primary breast cancer patients. However, further trials will be needed with larger samples to corroborate the findings.


Involvement of the alpha2-adrenergic system in polydipsia in schizophrenic patients: a pilot study.
Animal studies have suggested the involvement of the adrenergic system in drinking behavior. The present study investigated the involvement of the alpha2-adrenergic system in the polydipsia of patients with chronic schizophrenia by use of an alpha2 agonist and an antagonist. Four patients with schizophrenic disorders accompanied by intermittent hyponatremia and polydipsia were the subjects of, and completed, this study. Drinking behavior was assessed by calculating the percent of maximum weight gain [PMWG: (maximum diurnal weight - standard weight) x 100/standard weight]. Standard weight was defined as body weight after 8 h of water restriction. Clonidine (75, 150, and 225 mg/day) increased the PMWG in a dose-dependent manner in the four subjects. In contrast, in three of the subjects, mianserin (30, 60, and 90 mg/day) decreased PMWG, and the severe polydipsia disappeared almost completely. These findings indicate clearly that the alpha2-adrenergic system is involved in the drinking behavior of schizophrenic patients. Mianserin appears to be clinically useful in treating such patients with polydipsia.


The career plans of Irish interns: results of a national survey.
In anticipation of major changes in medical manpower in Ireland, we surveyed all interns about their career plans. Three hundred (65% of those surveyed) responded. There were clear gender differences in career plans and overall, only 15% planned a career in general practice. There was a negative perception about the quality of postgraduate training in Ireland and 93% planned to go overseas for training. These findings need to influence the debate on medical manpower and postgraduate training.


Chronic degeneration of dorsal raphe serotonergic neurons modulates cortical spreading depression: a possible pathophysiology of migraine.
The vascular serotonergic system in the brain has been implicated in the pathophysiology of migraine, however, involvement of the serotonergic nervous system of the brain parenchyma in the pathophysiology remains unclear. To investigate whether the brain parenchymal serotonergic nervous system is involved in the etiology of migraine, we prepared an experimental model of migraine by generation of cortical spreading depression (SD), characterized by spreading of neuronal/glial membrane depolarization accompanied by temporal elevation of the cerebral blood flow (CBF) throughout the cerebral cortical hemisphere in rats, which underwent pharmacological treatment for degeneration of serotonergic neurons in the dorsal raphe nucleus. We show here that (1) significant degeneration of serotonergic neurons in the dorsal raphe nucleus and serotonergic fibers in the cerebral cortex was observed in treated rats, (2) spreading velocity of the CBF changes was significantly increased in these rats, and (3) calculated width of the depolarization wave was significantly extended in these rats. These results indicate that the dorsal raphe serotonergic neurons modulate cortical spreading depression and might be involved in migraine pathology via a similar mechanism.


Tuberculosis incidence in foreign-born people residing in European countries in 2020.
BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.


Opioid Prescription Trends in a US Dental School Clinic, 2014-2018: A Retrospective Study Using Electronic Health Record Data.
Opioid misuse and abuse continues to be a grave public health concern in the United States. The aim of this study was to use electronic health records (EHRs) from a US dental school clinic to retrospectively analyze trends in opioid prescription frequencies. A database review was conducted using EHR data from 20 patient care clinics in a dental school over a 5-year period during which local, state, and national policies and guidelines to mitigate harm from opioid misuse were introduced. University of Michigan School of Dentistry, state of Michigan. Descriptive statistics using measures of frequency and distribution of opioid prescriptions written were compared over a 5-year period by dental school clinic specialty, CDT (Code on Dental Procedures and Nomenclature) procedure, drug type, and patient age/gender. From 2014 to 2018, a total of 12 401 opioid-based prescriptions were written by dental providers in the school's patient care clinics. An ARIMA (autoregressive integrated moving average) model time trend analysis demonstrated a significant decrease in the number of prescribed opioids after 2016. While causal relationships cannot be drawn between drug abuse and prescription trends alone, this exploratory study provided a better understanding of prescription frequency patterns that can help monitor distribution of opioids and identify areas where future public health interventions may be needed. Dental education institutions have an obligation to ensure a competent health care workforce as well as unique opportunities to support regional and national public health strategies aimed at reducing misuse of opioids.


Rapidly increasing macroalgal cover not related to herbivorous fishes on Mesoamerican reefs.
Long-term phase shifts from coral to macroalgal dominated reef systems are well documented in the Caribbean. Although the impact of coral diseases, climate change and other factors is acknowledged, major herbivore loss through disease and overfishing is often assigned a primary role. However, direct evidence for the link between herbivore abundance, macroalgal and coral cover is sparse, particularly over broad spatial scales. In this study we use a database of coral reef surveys performed at 85 sites along the Mesoamerican Reef of Mexico, Belize, Guatemala and Honduras, to examine potential ecological links by tracking site trajectories over the period 2005-2014. Despite the long-term reduction of herbivory capacity reported across the Caribbean, the Mesoamerican Reef region displayed relatively low macroalgal cover at the onset of the study. Subsequently, increasing fleshy macroalgal cover was pervasive. Herbivorous fish populations were not responsible for this trend as fleshy macroalgal cover change was not correlated with initial herbivorous fish biomass or change, and the majority of sites experienced increases in macroalgae browser biomass. This contrasts the coral reef top-down herbivore control paradigm and suggests the role of external factors in making environmental conditions more favourable for algae. Increasing macroalgal cover typically suppresses ecosystem services and leads to degraded reef systems. Consequently, policy makers and local coral reef managers should reassess the focus on herbivorous fish protection and consider complementary measures such as watershed management in order to arrest this trend.


Semi-Supervised Sparse Representation Based Classification for Face Recognition With Insufficient Labeled Samples.
This paper addresses the problem of face recognition when there is only few, or even only a single, labeled examples of the face that we wish to recognize. Moreover, these examples are typically corrupted by nuisance variables, both linear (i.e., additive nuisance variables, such as bad lighting and wearing of glasses) and non-linear (i.e., non-additive pixel-wise nuisance variables, such as expression changes). The small number of labeled examples means that it is hard to remove these nuisance variables between the training and testing faces to obtain good recognition performance. To address the problem, we propose a method called semi-supervised sparse representation-based classification. This is based on recent work on sparsity, where faces are represented in terms of two dictionaries: a gallery dictionary consisting of one or more examples of each person, and a variation dictionary representing linear nuisance variables (e.g., different lighting conditions and different glasses). The main idea is that: 1) we use the variation dictionary to characterize the linear nuisance variables via the sparsity framework and 2) prototype face images are estimated as a gallery dictionary via a Gaussian mixture model, with mixed labeled and unlabeled samples in a semi-supervised manner, to deal with the non-linear nuisance variations between labeled and unlabeled samples. We have done experiments with insufficient labeled samples, even when there is only a single labeled sample per person. Our results on the AR, Multi-PIE, CAS-PEAL, and LFW databases demonstrate that the proposed method is able to deliver significantly improved performance over existing methods.


Cyclic ADP-Carbocyclic-Ribose and -4-Thioribose, as Stable Mimics of Cyclic ADP-Ribose, a Ca2+-Mobilizing Second Messenger.
Cyclic ADP-ribose (cADPR), a general mediator involved in Ca2+ signaling, has the characteristic 18-membered ring consisting of an adenine, two riboses and a pyrophosphate, in which the two primary hydroxy groups of the riboses are linked by a pyrophosphate unit. This review focuses on chemical synthetic studies of cADPR analogues of biological importance. Although cADPR analogues can be synthesized by enzymatic and chemo-enzymatic methods using ADP-ribosyl cyclase, the analogues obtained by these methods are limited due to the substrate-specificity of the enzymes. Consequently, chemical synthetic methods providing a greater variety of cADPR analogues are required. Although early chemical synthetic studies demonstrated that construction of the large 18-membered ring structure is difficult, the construction was achieved using the phenylthiophosphate-type substrates by treating with AgNO3 or I2. This is now a general method for synthesizing these types of biologically important cyclic nucleotides. Using this method as the key step, the chemically and biologically stable cADPR mimic, cADP-carbocyclic-ribose (cADPcR) and -4-thioribose (cADPtR), were synthesized.


Time sequence diffeomorphic metric mapping and parallel transport track time-dependent shape changes.
Serial MRI human brain scans have facilitated the detection of brain development and of the earliest signs of neuropsychiatric and neurodegenerative diseases, monitoring disease progression, and resolving drug effects in clinical trials for preventing or slowing the rate of brain degeneration. To track anatomical shape changes in serial images, we introduce new point-based time sequence large deformation diffeomorphic metric mapping (TS-LDDMM) to infer the time flow of within-subject geometric shape changes that carry known observations through a period. Its Euler-Lagrange equation is generalized for anatomies whose shapes are characterized by point sets, such as landmarks, curves, and surfaces. The time-dependent momentum obtained from the TS-LDDMM encodes within-subject shape changes. For the purpose of across-subject shape comparison, we then propose a diffeomorphic analysis framework to translate within-subject deformation in a global template without incorporating across-subject anatomical variations via parallel transport technique. The analysis involves the retraction of the within-subject time-dependent momentum along the TS-LDDMM trajectory from each time to the baseline, the translation of the momentum in a global template, and the reconstruction of the TS-LDDMM trajectory starting from the global template.


ACTH-secreting medullary thyroid cancer: a case series.
Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour that originates from the parafollicular cells of the thyroid gland. The most common presentation of MTC is with a single nodule; however, by the time of diagnosis, most have spread to the surrounding cervical lymph nodes. Cushing's syndrome is a rare complication of MTC and is due to ectopic adrenocorticotrophic hormone (ACTH) secretion by tumour cells. Cushing's syndrome presents a challenging diagnostic and management issue in patients with MTC. Tyrosine kinase inhibitors (TKI) previously used for the management of metastatic MTC have become an important therapeutic option for the management of ectopic ACTH in metastatic MTC. The article describes three cases of ectopic ACTH secretion in MTC and addresses the significant diagnostic and management challenges related to Cushing's syndrome in metastatic MTC. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour.Cushing's syndrome is a rare complication of MTC that has a significant impact on patients' morbidity and mortality.Tyrosine kinase inhibitors (TKI) provide an important therapeutic option for the management of ectopic ACTH in metastatic MTC.


Maternal Chronic Hypertension Elevates the Risk for Long-Term Selected Endocrine and Metabolic Morbidity in the Offspring, Particularly Childhood Obesity.
Background: Maternal hypertensive disorders during pregnancy are known to be associated with high rates of perinatal complications for both mother and child. We aimed at determining whether maternal chronic hypertension impacts long-term pediatric endocrine and metabolic morbidity. Methods: A population-based, retrospective cohort study was performed. Exposure was defined as the presence of maternal chronic hypertension. Hospitalizations of the offspring up to the age of 18 years involving endocrine and metabolic morbidity were evaluated. A Kaplan-Meier survival curve was employed to compare the cumulative morbidity incidence between both groups (exposed and unexposed offspring). Cox proportional hazards models were used to control for confounders. Results: During the study period, 232,841 singleton deliveries met the inclusion criteria. Of them, 1.1% (n = 2655) were exposed to maternal chronic hypertension during pregnancy. Total hospitalization rate involving endocrine-metabolic morbidities was doubled in the hypertensive group (1% vs. 0.5% in the normotensive group, p < 0.001). Specifically, childhood obesity was significantly more common in offspring of mothers with chronic hypertension (0.7% vs. 0.2%, respectively, p < 0.001). The survival curve demonstrated significantly higher cumulative incidence of total endocrine and metabolic morbidity in the exposed group (log rank p = 0.002). In a Cox regression model, maternal chronic hypertension exhibited an independent association with long-term childhood endocrine or metabolic morbidity (adjusted hazard ratio = 1.5, 95% confidence interval 1.01-2.2, p = 0.045). Conclusions: Maternal chronic hypertension appears to be an independent and a significant risk factor for long-term pediatric endocrine and metabolic morbidity, and specifically for childhood obesity, in the offspring.


[Meckel's diverticulum detected by virtual enteroscopy in a patient with nonsteroidal anti-inflammatory drug-induced enteropathy].
A 68-year-old female presented to our hospital with abdominal discomfort and obscure gastrointestinal bleeding. She had been prescribed aspirin for retinal venous occlusion. Video capsule endoscopy (VCE) revealed multiple erosions, annular ulcers, and bleeding, confirming a diagnosis of nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Virtual enteroscopy (VE) was performed to evaluate stenosis of the small intestine, during which a 5-cm long diverticulum was incidentally detected at a site 99cm from the ileocecal valve. On the basis of the location, size, and shape, a diagnosis of Meckel's diverticulum was made. Second look of the VCE images could not detect the Meckel's diverticulum. After the cessation of taking aspirin, the patient had no more abdominal symptoms, and we concluded NSAID-induced enteropathy was the cause of the symptoms. Meckel's diverticula are sometimes difficult to diagnose, but VE was able to depict the lesion clearly. Meckel's diverticulum is one of the best indications for VE.


[Biochemical basis of tolerance to osmotic stress in phytopathogenic fungus: The case of Macrophomina phaseolina (Tassi) Goid.]
Fungus Macrophomina phaseolina (Tassi) Goid. is the causative agent of charcoal rot disease which causes significant yield losses in major crops such as maize, sorghum, soybean and common beans in Mexico. This fungus is a facultative parasite which shows broad ability to adapt itself to stressed environments where water deficits and/or high temperature stresses commonly occur. These environmental conditions are common for most cultivable lands throughout Mexico. Here we describe some basic facts related to the etiology and epidemiology of the fungus as well as to the importance of responses to stressed environments, particularly to water deficits, based on morphology and growth traits, as well as on physiology, biochemistry and pathogenicity of fungus M. phaseolina. To conclude, we show some perspectives related to future research into the genus, which emphasize the increasing need to improve the knowledge based on the application of both traditional and biotechnological tools in order to elucidate the mechanisms of resistance to environmental stress which can be extrapolated to other useful organisms to man.


Single-cell RNA sequencing uncovers the individual alteration of intestinal mucosal immunocytes in Dusp6 knockout mice.
Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase six knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotation based on ImmGen database. Composition assessments found that D6KO-derived intestinal leukocytes tend to stay inactivate or immature status. The enrichment analysis showed that D6KO-derived intestinal leukocytes are less sensitive to microbes. The mod PhEA phenotypic analysis showed that the D6KO leukocytes may link to not only immune-associated but also diverse previously non-immune-related diseases. Integrating our dataset with the published dataset GSE124880 generated a comprehensive dataset for exploring intestinal immunity. Down-regulation of Ccl17 gene was found in the D6KO-derived dendritic cells. Our results demonstrated the advantage of applying scRNA-seq for dissecting the individual alteration of intestinal leukocytes, particularly in the D6KO mice at a naive state.


Daphnetin inhibits inflammation in the NZB/W F1 systemic lupus erythematosus murine model via inhibition of NF-κB activity.
Daphnetin is a compound extracted from Chinese medicinal herbs, which exerts analgesic and anti-inflammatory effects. The present study aimed to investigate the potential therapeutic effect of daphnetin on inflammation in the NZB/W F1 systemic lupus erythematosus (SLE) murine model. Female NZB/WF1 mice (age, 16-18 weeks) were intraperitoneally injected with daphnetin once a day for 12 weeks. It was revealed that daphnetin treatment significantly increased animal survival rates, reduced renal damage and blood urea nitrogen levels, and suppressed serum autoantibody production in the SLE-prone NZB/W F1 mice. In addition, daphnetin treatment significantly decreased the serum levels of tumor necrosis factor-α and interleukin-6, inhibited nuclear factor (NF)-κB activity, suppressed the protein expression of nuclear factor of activated T-cells and promoted A20 protein expression in SLE-prone NZB/W F1 mice. In conclusion, daphnetin inhibited inflammation in the NZB/W F1 murine SLE model via inhibition of NF-κB mediated by upregulation of A20.


Loxapine versus olanzapine in the treatment of delirium following traumatic brain injury.
The use of typical neuroleptics has always been the mainstay of treatment for delirium following traumatic brain injury (TBI). Given the recent application of atypical neuroleptics to various psychiatric conditions formerly treated with typical neuroleptics, one questions whether this new class of drugs is superior to its predecessor in treating delirium post-TBI. We present a case of one patient with TBI-induced delirium where in fact the use of the typical mid-potency neuroleptic, loxapine, appeared to have a better clinical effect over the atypical neuroleptic, olanzapine.


Purification and properties of selenoprotein W from rat muscle.
Following injection with [75Se]selenite, a low molecular weight 75Se-selenocysteine containing protein was purified from rat muscle. The purification procedure involved ammonium sulfate fractionation, Sephadex G-50 gel filtration, cation exchange chromatography on CM-Sephadex, and reverse phase high pressure liquid chromatography using a C-18 Vydac column. Four forms of the protein were separated by the cation exchange and reverse phase chromatography steps. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of the four proteins revealed masses of 9550 +/- 1, 9596 +/- 1.2, 9858 +/- 1.3, and 9898 +/- 1.1 daltons. Glutamate, glycine, lysine, leucine, and valine are the major amino acids in this protein. About 0.92 g atoms of selenium was found per g mol of protein, and this selenium was present as selenocysteine. Thus, this appears to be a new selenoprotein, and we have named it selenoprotein W.


NMR imaging of the diffusion of water at 310 K into semi-IPNs of PEM and poly(HEMA-co-THFMA) with and without chlorhexidine diacetate.
Magnetic resonance imaging has been used to monitor the diffusion of water at 310 K into a series of semi-IPNs of poly(ethyl methacrylate), PEM, and copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA. The diffusion was found to be well described by a Fickian kinetic model in the early stages of the water sorption process, and the diffusion coefficients were found to be slightly smaller than those for the copolymers of HEMA and THFMA, P(HEMA-co-THFMA), containing the same mole fraction of HEMA in the matrix. A second stage sorption process was identified in the later stage of water sorption by the PEM/PTHFMA semi-IPN and for the systems containing a P(HEMA-co-THFMA) component with a mole fraction HEMA of 0.6 or less. This was characterized by the presence of water near the surface of the cylinders with a longer NMR T(2) relaxation time, which would be characteristic of mobile water, such as water present in large pores or surface fissures. The presence of the drug chlorhexidine in the polymer matrixes at a concentration of 5.625 wt % was found not to modify the properties significantly, but the diffusion coefficients for the water sorption were systematically smaller when the drug was present.


Heroin mismatch in the Motor City: addiction, segregation, and the geography of opportunity.
In this article, the authors used data from economic and ethnographic interviews with heroin users from Detroit, Michigan, as well as other sources, to illustrate the relationship between heroin users' mobility patterns and urban and suburban environments, especially in terms of drug acquisition and the geography of opportunity. The authors found that although geographic location and social networks associated with segregation provided central city residents and African Americans with a strategic advantage over White suburbanites in locating and purchasing heroin easily and efficiently, this same segregation effectively focuses the negative externalities of heroin markets in central city neighborhoods. Finally, the authors consider how the heroin trade reflects and reproduces the segregated post-industrial landscape and discuss directions for future research about the relationship between ethnic and economic ghettos and regional drug markets.


A microsystem integrating photodegradable hydrogel microstructures and reconfigurable microfluidics for single-cell analysis and retrieval.
We developed a micropatterned photodegradable hydrogel array integrated with reconfigurable microfluidics to enable cell secretion analysis and cell retrieval at the single-cell level. The activity of protease molecules secreted from single cells was monitored using FRET peptides entrapped inside microfabricated compartments. Antibody-modified gel islands tethering cells to the surface could be degraded by UV exposure to release specific single cells of interest.


Up-to-date role of the dehydrated human amnion/chorion membrane (AMNIOFIX) for wound healing.
Chronic wounds pose a significant burden on patients, society, and the health-care setup. Higher costs, protracted clinical course, and increased risk of complications necessitate identifying novel treatment modalities that hasten healing and wound closure. This article covers newer available treatment modalities for chronic wounds, namely the dehydrated amniotic membrane products, biological skin substitutes, and similar therapies aimed at the healing of chronic non-healing wounds. It presents product description for Amniofix (dehydrated human amniotic/chorionic membrane) and its efficacy, compared to other similar products. In our experience and review of available literature, we expect Amniofix to offer wound care specialists with a more effective, easy-to-use, and convenient treatment modality for chronic wounds. Amniofix and other dHACM (dehydrated human amniotic/chorionic membrane) therapies reported faster and complete healing with lower complication rates, when compared to other similar products. These features encourage the use of Amniofix in Diabetic foot ulcers and Venous Leg Ulcers, besides other conditions such as plantar fasciitis.


On the Front Lines: The Impact of Managerialism on the New York City Addiction Treatment Workforce.
Since the mid-1970s, neoliberal policies have relied on privatization and other tactics to down-size the state, transforming human service organizations in the process. The impact of this approach, also known as managerialism, has not been examined in addiction treatment, where the opioid epidemic has intensified the need for services. Using qualitative semi-structured interviews, we explore how managerialism has affected the workforce, service delivery, and the quality of care in New York City addiction treatment programs. Front-line and managerial staff identified threats to working conditions, including high caseloads and productivity demands; threats to service quality including standardization of practice, loss of professional discretion and serving only those most likely to succeed; and threats to worker well-being marked by stress, burn-out, and low morale. The contradictions between the goals of managerialism and addiction treatment threaten the ability to meet the needs of people struggling with addiction.


Risk factors for urinary infection after retrograde upper urinary lithotripsy: Implication for nursing.
There are needs to evaluate the risk factors for urinary infection after retrograde upper urinary lithotripsy, to provide insights into the management and nursing care of patients with retrograde upper urinary lithotripsy.Patients who received retrograde upper urinary lithotripsy with a Foley 20 urinary tube insertion from June 1, 2019 to December 31, 2020 in our hospital were selected. Patients were grouped urinary infection and no infection group according to the culture results of urine, and the clinical data of the 2 groups of patients were collected and compared. Single factor and logistic regression analysis were used to analyze the risk factors of urinary tract infection after retrograde upper urinary lithotripsy.Four hundred ten patients with retrograde upper urinary lithotripsy were included, of whom 62 patients had the urinary tract infection, the incidence of urinary tract infection was 15.12%. There were significant differences in the gender, age, diabetes, stone diameter, duration of urinary tube insertion and duration of surgery between infection and no-infection group (all P < .05). The Escherichia coli (62.90%) was the most commonly seen bacterial in patients with urinary tract infection. Female (odds ratio [OR]: 1.602, 95% confidence interval 95% [CI]: 1.132∼2.472), age >50 years (OR: 2.247, 95% CI: 1.346∼3.244), diabetes (OR: 2.228, 95% CI: 1.033∼3.451), stone diameter ≥2 cm (OR: 2.152, 95% CI: 1.395∼3.099), duration of urinary tube insertion ≥3 days (OR: 1.942, 95% CI:1.158∼2.632), duration of surgery ≥90 minutes (OR: 2.128, 95% CI: 1.104∼3.846) were the independent risk factors for the postoperative urinary tract infection in patients with retrograde upper urinary lithotripsy (all P < .05).The incidence of urinary tract infection in patients undergoing retrograde upper urinary lithotripsy was high, counteractive measures targeted on those risk factors are needed to prevent and reduce the postoperative urinary infection in clinical settings.


Radiofrequency pulse design for the selective excitation of dissolved 129Xe.
To optimize radiofrequency (RF) pulses for the selective excitation of dissolved phase (129)Xe that take into account the very short T2*, while simultaneously, minimally exciting the much larger gas signal. Numerical simulations of Shinnar le-Roux pulses and binomial coefficient composite-element pulses were performed and experimentally implemented on a 1.5 Tesla (T) clinical scanner. These were compared with pulses commonly used for short T2* imaging from the literature. The pulses were then experimentally tested in vivo with healthy volunteers inhaling hyperpolarized (129)Xe using nuclear MR spectroscopy on a 1.5T clinical scanner. Standard RF excitation pulses inadvertently excite the gas compartment, or are long enough that the T2* of the dissolved compartment deteriorates the received signal. Amplitude modulated binomial composite pulses perform well being short and having high selectivity, however, deteriorate at high amplifier gain setting. Composite pulses using pulse width modulation provide the desired frequency response even in these nonlinear, high gain regimes. Composite pulses provide a means of very narrow band frequency selectivity in a short duration pulse that is well suited to dissolved (129)Xe imaging. Pulse width modulation maintains the desired frequency response even in the presence of amplitude distortion.


Comparative Analysis of Chloroplast Genome Structure and Phylogenetic Relationships Among Six Taxa Within the Genus Catalpa (Bignoniaceae).
Species within the Genus Catalpa are mostly semievergreen or deciduous trees with opposite or whorled leaves. C. bungei, C. fargesii f. duclouxii and C. fargesii are sources of traditional precious wood in China, known as the "kings of wood". Due to a lack of phenotypic and molecular studies and insufficient sequence information, intraspecific morphological differences, common DNA barcodes and partial sequence fragments cannot clearly reveal the phylogenetic or intraspecific relationships within Catalpa. Therefore, we sequenced the complete chloroplast genomes of six taxa of the genus Catalpa and analyzed their basic structure and evolutionary relationships. The chloroplast genome of Catalpa shows a typical tetrad structure with a total length ranging from 157,765 bp (C. fargesii) to 158,355 bp (C. ovata). The length of the large single-copy (LSC) region ranges from 84,599 bp (C. fargesii) to 85,004 bp (C. ovata), that of the small single-copy (SSC) region ranges from 12,662 bp (C. fargesii) to 12,675 bp (C. ovata), and that of the inverted repeat (IR) regions ranges from 30,252 bp (C. fargesii) to 30,338 bp (C. ovata). The GC content of the six chloroplast genomes were 38.1%. In total, 113 unique genes were detected, and there were 19 genes in IR regions. The 113 genes included 79 protein-coding genes, 30 tRNA genes and four rRNA genes. Five hypervariable regions (trnH-psbA, rps2-rpoC2, rpl22, ycf15-trnl-CAA and rps15) were identified by analyzing chloroplast nucleotide polymorphisms, which might be serve as potential DNA barcodes for the species. Comparative analysis showed that single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) were highly diverse in the six species. Codon usage patterns were highly similar among the taxa included in the present study. In addition to the stop codons, all codons showed a preference for ending in A or T. Phylogenetic analysis of the entire chloroplast genome showed that all taxa within the genus Catalpa formed a monophyletic group, clearly reflecting the relationships within the genus. This study provides information on the chloroplast genome sequence, structural variation, codon bias and phylogeny of Catalpa, which will facilitate future research efforts.


Natural History of Untreated HBeAg-Positive Chronic HBV Infection With Persistently Elevated HBV DNA but Normal Alanine Aminotransferase.
Nucleos(t)ide analogues (NUCs) are not routinely recommended for patients with hepatitis B e antigen-positive chronic hepatitis B virus (HBV) infection who have persistently elevated serum HBV DNA level (>20,000 IU/mL) but normal alanine aminotransferase (<40 IU/L) level. Here, we evaluated the cumulative risks of hepatocellular carcinoma (HCC) in such patients (the untreated persistently elevated serum HBV DNA [pEDNA] group) compared with inactive carriers (the IC group). Patients with untreated pEDNA (n = 126) and IC (n = 621) were enrolled between 2006 and 2012. Patients with cirrhosis or HCC at enrollment or a history of NUC treatment were excluded. The cumulative HCC risks at 5 and 9 years in the untreated pEDNA group were 1.1% and 1.9%, which were comparable with those of the IC group (P = 0.549). Inverse probability of treatment weighting and propensity score matching also showed similar HCC risks. In the untreated pEDNA group, there were no cases of HCC in the subgroup with serum HBV DNA level >1,000,000 IU/mL (immune-tolerant phase), which was significantly (P = 0.002) different compared with those with an intermediate serum HBV DNA level (20,000-1,000,000 IU/mL). The cumulative HCC risk in the untreated pEDNA group was minimal and comparable with that of the IC group. Further studies are required to determine whether early NUC treatment, indeed, reduces the HCC risk in patients with an intermediate serum HBV DNA level.


Global economic costs of alien birds.
The adverse impacts of alien birds are widespread and diverse, and associated with costs due to the damage caused and actions required to manage them. We synthesised global cost data to identify variation across regions, types of impact, and alien bird species. Costs amount to US$3.6 billion, but this is likely a vast underestimate. Costs are low compared to other taxonomic groups assessed using the same methods; despite underreporting, alien birds are likely to be less damaging and easier to manage than many other alien taxa. Research to understand why this is the case could inform measures to reduce costs associated with biological invasions. Costs are biassed towards high-income regions and damaging environmental impacts, particularly on islands. Most costs on islands result from actions to protect biodiversity and tend to be low and one-off (temporary). Most costs at mainland locations result from damage by a few, widespread species. Some of these costs are high and ongoing (permanent). Actions to restrict alien bird invasions at mainland locations might prevent high, ongoing costs. Reports increased sharply after 2010, but many are for local actions to manage expanding alien bird populations. However, the successful eradication of these increasingly widespread species will require a coordinated, international response.


Assessment of Facial Injury by "Slock" in Incarcerated Patients.
A "slock" is a padlock in a sock used as a weapon in correctional facilities to induce trauma. This assessment examined the prevalence, pattern, and degree of slock- and padlock-induced facial fractures. This quality assessment initiative was performed through retrospective analysis of 435 incarcerated patients treated surgically for facial fractures at an academic medical center from 2011 to 2019. Fifty-seven patients (16%) described injury from a padlock, of whom 23 (6%) specified a slock. The prevalence of padlock-induced facial fractures doubled from 2012 to 2017. Padlock-induced facial fractures were determined to be more complex than those by a fist (p < .001). These findings support reducing the facial trauma in Louisiana correctional facilities by removing access to padlocks.


Soluble proteins of chemical communication in the social wasp Polistes dominulus.
Members of the odorant-binding protein (OBP) and chemosensory protein (CSP) families were identified and characterised in the sensory tissues of the social wasp Polistes dominulus (Hymenoptera: Vespidae). Unlike most insects so far investigated, OBPs were detected in antennae, legs and wings, while CSPs appeared to be preferentially expressed in the antennae. The OBP is very different from the homologous proteins of other Hymenopteran species, with around 20% of identical residues, while the CSP appears to be much better conserved. Both OBP and CSP, not showing other post-translational modifications apart from disulphide bridges, were expressed with high yields in a bacterial system. Cysteine pairing in the recombinant and native proteins follows the classical arrangements described for other members of these classes of proteins. OBPs isolated from the wings were found to be associated with a number of long-chain aliphatic amides and other small organic molecules. Binding of these ligands and other related compounds was measured for both recombinant OBP and CSP.


Registration bone scan in the evaluation of wrist pain.
We assessed the value of bone scintigraphy combined with X-ray registration for the diagnosis and management of wrist pain in 65 patients. Studies were reported independently by two observers before and after registration. Registration improved localization of scan abnormalities in 53% (observer 1) and 61% (observer 2). In these patients, the bone scan contributed to the diagnosis independently of the X-ray in 37% and the management was altered in 31%. The value of the bone scan in the early diagnosis and management of wrist pain is increased when it is registered with X-rays.


Inflammasomes in Inflammation-Induced Cancer.
The inflammasome is an important multiprotein complex that functions during inflammatory immune responses. The activation of inflammasome will lead to the autoactivation of caspase-1 and subsequent cleavage of proIL-1β and proIL-18, which are key sources of inflammatory manifestations. Recently, the roles of inflammasomes in cancers have been extensively explored, especially in inflammation-induced cancers. In different and specific contexts, inflammasomes exhibit distinct and even contrasting effects in cancer development. In some cases, inflammasomes initiate carcinogenesis through the extrinsic pathway and maintain the malignant cancer microenvironment through the intrinsic pathway. On the contrary, inflammasomes also exert anticancer effects by specialized programmed cell death called pyroptosis and immune regulatory functions. The phases and compartments in which inflammasomes are activated strongly influence the final immune effects. We systemically summarize the functions of inflammasomes in inflammation-induced cancers, especially in gastrointestinal and skin cancers. Besides, information about the current therapeutic use of inflammasome-related products and potential future developing directions are also introduced.


The action of certain polyvalent cations on the voltage-clamped lobster axon.
Calcium appears to be an essential participant in axon excitation processes. Many other polyvalent metal ions have calcium-like actions on axons. We have used the voltage-clamped lobster giant axon to test the effect of several of these cations on the position of the peak initial (sodium) and steady-state (potassium) conductance vs. voltage curves on the voltage axis as well as on the rate parameters for excitation processes. Among the alkaline earth metals, Mg(+2) is a very poor substitute for Ca(+2), while Ba(+2) behaves like "high calcium" when substituted for Ca(+2) on a mole-for-mole basis. The transition metal ions, Ni(+2), Co(+2), and Cd(+2) also act like high calcium when substituted mole-for-mole. Among the trivalent ions, La(+3) is a very effective Ca(+2) replacement. Al(+3) and Fe(+3) are extremely active and seem to have some similar effects. Al(+3) is effective at concentrations as low as 10(-5)M. The data suggest that many of these ions may interact with the same cation-binding sites on the axon membrane, and that the relative effects on the membrane conductance and rate parameters depend on the relative binding constants of the ions. The total amount of Na(+) transferred during a large depolarizing transient is nearly independent of the kind or amount of polyvalent ion applied.


Serotype-specific restriction of wild-type adenoviruses by the cellular Mre11-Rad50-Nbs1 complex.
During viral replication in the nucleus, the DNA genomes of adenoviruses are accessible to cellular DNA-binding proteins. Human adenovirus type 5 (Ad5) targets the cellular Mre11-Rad50-Nbs1 complex (MRN) to evade detection by the DNA damage response (DDR). Ad5 mutants that cannot target MRN have reduced viral propagation. Previous studies showed that diverse adenovirus serotypes interact differently with MRN. While these studies revealed diverse MRN interactions among serotypes, it remains unclear how these differences influence viral replication. Here, we examined effects of the DDR on several adenovirus serotypes. We demonstrate that wild-type Ad9 and Ad12 do not overcome MRN impairment. We also examined viral proteins involved in targeting MRN and found that unlike Ad5-E4orf3, expression of Ad9-E4orf3 is not sufficient for MRN mislocalization observed during infection. We conclude that adenovirus serotypes target MRN in distinct ways, and the MRN complex can impair DNA replication of wild-type viruses across the adenovirus family.


Simple and Fast Sample Preparation Followed by Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS) for the Analysis of 2- and 4-Methylimidazole in Cola and Dark Beer.
We have developed a simple and fast sample preparation technique in combination with a gas chromatography-tandem mass spectrometry (GC-MS/MS) for the quantification of 2-methylimidazole (2-MeI) and 4-methylimidazole (4-MeI) in colas and dark beers. Conventional sample preparation technique for GC-MS requires laborious and time-consuming steps consisting of sample concentration, pH adjustment, ion pair extraction, centrifugation, back-extraction, centrifugation, derivatization, and extraction. Our sample preparation technique consists of only 2 steps (in situ derivation and extraction) which requires less than 3 min. This method provided high linearity, low limit of detection and limit of quantification, high recovery, and high intra- and interday repeatability. It was found that internal standard method with diluted stable isotope (4-MeI-d6 ) and 2-ethylimidazole (2-EI) could not correctly compensate the matrix effects. Thus, standard addition technique was used for the quantification of 2- and 4-MeI. The established method was successfully applied to colas and dark beers for the determination of 2-MeI and 4-MeI. The 4-MeI contents in colas and dark beers ranged from 8 to 319 μg/L and from trace to 417 μg/L, respectively. Small quantity (0 to 8 μg/L) of 2-MeI was found only in dark beers. The contents of 4-MeI (22 μg/L) in colas obtained from fast food restaurants were significantly lower than those (177 μg/L) in canned or bottled colas.


The Polarization-Index: A Simple Calculation to Distinguish Polarized From Non-polarized Training Intensity Distributions.
The training intensity distribution (TID) of endurance athletes has retrieved substantial scientific interest since it reflects a vital component of training prescription: (i) the intensity of exercise and its distribution over time are essential components for adaptation to endurance training and (ii) the training volume (at least for most endurance disciplines) is already near or at maximum, so optimization of training procedures including TID have become paramount for success. This paper aims to elaborate the polarization-index (PI) which is calculated as log10(Zone 1/Zone 2∗Zone 3∗100), where Zones 1-3 refer to aggregated volume (time or distance) spent with low, mid, or high intensity training. PI allows to distinguish between non-polarized and polarized TID using a cut-off > 2.00 a.U. and to quantify the level of a polarized TID. Within this hypothesis paper, examples from the literature illustrating the usefulness of PI-calculation are discussed as well as its limitations. Further it is elucidated how the PI may contribute to a more precise definition of TID descriptors.


Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.
Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.


Physicochemical evaluation of the hot-injection method, a synthesis route for monodisperse nanocrystals.
The quintessence of the hot-injection method, a synthesis route for monodisperse, highly luminescent semiconductor nanocrystals, is reviewed. The separate stages of nucleation and growth of the nanocrystals are discussed in the framework of classical nucleation theory and an equilibrium model proposed by Debye. We also review the numerous adaptations of the original synthesis that currently provide colloidal nanocrystals with well-defined, size-dependent optical, electrical, and magnetic properties. The availability of these remarkable materials is one of the most promising developments in nanoscience and nanotechnology.


A nationwide study on parathyroid carcinoma.
Parathyroid carcinoma (PC) is rare and diagnostically challenging. Reported outcomes are rather poor and the incidence might be increasing. We performed a nationwide study on all cases (n= 32) diagnosed in 2000-2011 in Finland, and compared clinical and histopathological characteristics and outcome to atypical parathyroid (APA; n= 28) and parathyroid adenomas (PA; n= 72). The incidence in years 1955-1999 was compared to that in 2000-2013. Preoperatively, calcium and parathyroid hormone concentrations were higher in PC compared to APA and PA (1.76, 1.56 and 1.44 mmol/l, p < .001; and 989, 355 and 160 μmol/l, p < .001, respectively). Calcium was ≤1.77 mmol/l for all PAs. Hospitalization (44% vs. 22% and 3%, respectively, p = .01), renal (50% vs. 48% vs. 22%, respectively, p = .01) and bone (47% vs. 15% vs. 38%, respectively p = .002) manifestations were more common. PC and APA tumors were larger than PA (p < .001). Histopathological characteristics of PC compared to PA are increased mitotic activity (p= .001), chief cells (p = .003), diffuse growth pattern (p < .001), higher Ki67 (p< .001) and negative parafibromin (p < .001). One PC (1/18) and one APA (1/16) patient had a CDC73 mutation. After 6.7 (2-13.9) years of follow-up, 9.4% of PC had residual, 21% recurrent disease and 12.5% died of disease. Overall mortality did not differ between subgroups (p = .094). Recurrent PC was characterized by vascular invasion, lymph node metastases, high mitotic activity, necrosis and negative parafibromin. Incidence increased from 1.42 (range 0.52-2.14) to 7.14 (range 3.42-10.38)/10.000.000/years; (p < .001). PC associates with severe primary hyperparathyroidism and must be suspected if calcium ≥1.77 mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.


GW100: A Slater-Type Orbital Perspective.
We calculate complete basis set (CBS) limit-extrapolated ionization potentials (IPs) and electron affinities (EA) with Slater-type basis sets for the molecules in the GW100 database. To this end, we present two new Slater-type orbital (STO) basis sets of triple-(TZ) and quadruple-ζ (QZ) quality, whose polarization is adequate for correlated-electron methods and which contain extra diffuse functions to be able to correctly calculate EAs of molecules with a positive lowest unoccupied molecular orbital (LUMO). We demonstrate that going from TZ to QZ quality consistently reduces the basis set error of our computed IPs and EAs, and we conclude that a good estimate of these quantities at the CBS limit can be obtained by extrapolation. With mean absolute deviations (MAD) from 70 to 85 meV, our CBS limit-extrapolated IP are in good agreement with results from FHI-AIMS, TURBOMOLE, VASP, and WEST, while they differ by more than 130 meV on average from nanoGW. With a MAD of 160 meV, our EA are also in good agreement with the WEST code. Especially for systems with positive LUMOs, the agreement is excellent. With respect to other codes, the STO-type basis sets generally underestimate EAs of small molecules with strongly bound LUMOs. With 62 meV for IPs and 93 meV for EAs, we find much better agreement with CBS limit-extrapolated results from FHI-AIMS for a set of 250 medium to large organic molecules.


27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular damage in MC3T3-E1 osteoblastic cells.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that exerts its toxicity through a variety of signaling mechanisms. The present study evaluated the effects of 27-deoxyactein, one of the major constituents isolated from Cimicifuga racemosa, on TCDD-induced toxicity in osteoblastic MC3T3-E1 cells. TCDD reduced cell survival, markedly increased apoptosis, and enhanced autophagy activity. However, pre-treatment with 27-deoxyactein attenuated all TCDD-induced effects and significantly decreased intracellular calcium (Ca2+) concentrations, the collapse of the mitochondrial membrane potential (MMP), the level of reactive oxygen species (ROS), and cardiolipin peroxidation compared to the TCDD-treated controls. Additionally, TCDD-induced increases in the levels of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), and extracellular signal-regulated kinase (ERK) were significantly inhibited by 27-deoxyactein. The mRNA levels of superoxide dismutase (SOD), ERK1, and nuclear factor kappa B (NF-κB) were also effectively restored by pre-treatment with 27-deoxyactein. Furthermore, 27-deoxyactein significantly increased the expressions of genes associated with osteoblast differentiation, including alkaline phosphatase (ALP), osteocalcin, bone sialoprotein (BSP), and osterix. Taken together, the present findings demonstrate the preventive effects of 27-deoxyactein on TCDD-induced damage in osteoblasts.


A new species of Goniothalamus (Annonaceae) from Palawan, and a new nomenclatural combination in the genus from Fiji.
A new species, Goniothalamus palawanensis C.C.Tang & R.M.K.Saunders, sp. nov. (Annonaceae), is described from Palawan, Philippines. Goniothalamus palawanensis is most closely related to Goniothalamus amuyon (Blanco) Merr., but differs in its shorter inner petals, hairy ovaries, and funnel-shaped stigmas. A new nomenclatural combination, Goniothalamus angustifolius (A.C.Sm.) B.Xue & R.M.K.Saunders, comb. nov., is furthermore validated to reflect the phylogenetic affinities of a Fijian species previously assigned to Polyalthia.


Ultrasonographic study of ovarian follicular dynamics in ewes during the oestrous cycle.
Transrectal ovarian ultrasonography was performed daily in eight ewes during one interovulatory interval, using a 7.5 MHz, rigid, human prostate transducer, and a realtime B-mode scanner to record the numbers, diameters and position of all follicles > or = 2 mm in diameter and the corpora lutea in both ovaries. Blood samples were taken once a day and were analysed for concentrations of FSH, progesterone and oestradiol. During the interovulatory interval of 17.2 +/- 0.4 days, antral follicles (follicles > 2 mm in diameter) emerged on all days except for days 1, 5, 15, 16 and 17. A significant increase in the numbers of follicles emerging was seen on days 2 and 11. The ovulatory follicle (6.9 +/- 0.1 mm diameter) was retrospectively traced to emergence on day 11.1 +/- 0.3 and grew over a period of 4.1 +/- 0.1 days at a growth rate of 1.2 +/- 0.04 mm day-1. The largest nonovulatory follicles of the same period grew at the same rate as ovulatory follicles and regressed over a period of 2.6 +/- 0.2 days at a rate of 1.2 +/- 0.07 mm day-1. The mean diameter of the largest follicles seen on each day of the oestrous cycle was lowest on the day of ovulation (2.9 +/- 0.2 mm), increased from day 3 to day 5 (4.1 +/- 0.4 mm) and again from day 11 to the day before ovulation (6.9 +/- 0.1 mm; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Key issues to address with bottle-feeding.
Proper feeding during a baby's first year of life is crucial for a sound nutritional foundation. Because of this, there are several issues that must be addressed to ensure the child is fed properly. First, bottle-feeding moms should not be made to feel guilty about their feeding decision. It is also important to review feeding practices to avoid overfeeding and encourage positive nurturing techniques. Mothers should learn the key signals to watch for from their baby, such as sleep patterns and bowel movements. Also, it is crucial to teach parents the essential issues related to preparing bottles, such as cleaning the bottles and nipples and properly mixing the formula.


Assessing functions of stimuli associated with rich-to-lean transitions using a choice procedure.
Under fixed-ratio schedules, transitions from more to less favorable conditions of reinforcement (rich-to-lean transitions) usually generate extended pausing. One possible explanation for this effect is that stimuli associated with rich-to-lean transitions are aversive and, thus, extended pausing functions as escape. The purpose of this study was to characterize further the aversive function of different transitions, and the stimuli associated with them, by allowing pigeons to choose to complete select ratios in the presence of either a mixed-schedule stimulus or a transition-specific multiple-schedule stimulus. The mixed schedule was preferred during transitions that signaled an upcoming lean reinforcer (rich-to-lean and lean-to-lean), whereas the multiple schedule was preferred during transitions that signaled an upcoming rich reinforcer (lean-to-rich and rich-to-rich). These findings support the notion that stimuli associated with rich-to-lean (and to some extent lean-to-lean) transitions can function aversively; whereas stimuli associated with other transitions (e.g., lean-to-rich and rich-to-rich) can function as conditioned reinforcers. When the opportunity to choose between schedule-correlated stimuli was available, however, choice latency was controlled exclusively by the multiple-schedule stimulus. That is, the opportunity to select the mixed schedule did not attenuate rich-to-lean pauses, suggesting that extended pausing may be more than simply escape.


Bilateral Ovarian Torsion during Follow-up for Antenatally Detected Ovarian Cysts.
Ovarian torsion is a surgical emergency demanding timely diagnosis and treatment to prevent loss of the ovaries which if happens may result in functional and emotional consequences. Simple (less than 5cm in size) ovarian cysts require follow-up for potential self-resolution. We describe a case of antenatally detected bilateral ovarian cysts that developed bilateral ovarian torsions on follow-up, postnatally.


[Tuberculosis of the pancreas: an unsuspected cause of abdominal pain and fever].
Tuberculosis is frequently the form of presentation of human immunodeficiency virus (HIV) infection even in patients who have not developed acquired immune deficiency syndrome (AIDS). Nevertheless, pancreatic affection is uncommon. Tuberculosis of the pancreas (TBP) is a clinical rarity and mimics pancreatic carcinoma both clinically and radiologically. We present the case of a 42-year-old man with a 5-day evolution of moderate abdominal pain in the right lower quadrant and fever and vomiting without diarrhea. The patient had no history of abdominal surgery. CT scan revealed a heterogeneously enhancing, multicystic structure in the pancreatic head. Due to suspicion of malignancy, a pancreatoduodenectomy was performed with pathological result of pancreatic tuberculosis. The patient was discharged on the 10th postoperative day without surgical complications. He died 10 months later of Pneumocystis jirovecii pneumonia. By that time he had a positive serum HIV antibodies test. TBP diagnosis can be missed or significantly delayed because it is often not suspected prior to laparotomy unless there is evidence of pulmonary tuberculosis. TBP should be considered in the differential diagnosis of a mass in the head of the pancreas. The response to early antituberculosis treatment is very effective.


[Modern management of otologic consequences of Wegener's granulomatosis - a case report and review of the literature].
Wegener's granulomatosis - or, in other words, granulomatosis with polyangiitis - is an anti-neutrophil cytoplasmic antibody associated granuloma forming vasculitis, mainly affecting the respiratory tract and the renal system. Otologic manifestations of Wegener's disease can be otitis media with effusion or chronic silent mastoiditis with conductive hearing loss, but sensorineural hearing loss can also evolve. The diagnosis is based on the clinical appearance as well as the immunoserological and histopathological results. It is of paramount importance to begin a combined immunosuppressive treatment immediately, besides eradicating the otologic manifestations. The intractable cases of chronic otitis media due to Wegener's granulomatosis are challenging any ear surgeons. Subtotal petrosectomy has proved to be an effective solution in such cases to create a dry ear and to provide a safe surgical field for hearing restoration. The authors reviewed the literature and report a case history to present the modern management of Wegener's granulomatosis with otologic manifestation. Orv Hetil. 2019; 160(4): 151-157.


Dairy products and total calcium intake at 13 years of age and its association with obesity at 21 years of age.
Dairy products and specifically calcium have been suggested to play a role in obesity development but more longitudinal evidence is still needed. The objective of this study was to assess the association between dairy products and total calcium intake at age 13 and body mass index at age 21. This longitudinal study included 2159 individuals from the Epidemiological Health Investigation of Teenagers cohort (EPITeen), Porto, Portugal, evaluated at ages 13 and 21. Assessment consisted of anthropometrics measurements and structured questionnaires namely a semi-quantitative food frequency questionnaire to appraise food consumption in the past 12 months. Linear regression models were run in 941 individuals with complete information of confounders: gender, follow-up period, parents' education, physical activity, energy, and total calcium intake. Negative association was found on total calcium intake at age 13 with BMI at age 21 (model 0: β = -0.059 (95% CI: -0.113, -0.004) and model 1: -0.057 (95% CI: -0.113, -0.002)), however, no statistically significant association was found when adjusting for energy intake (model 2: β = -0.031 (95% CI: -0.110, 0.047). There were no associations between milk, yogurt, and cheese consumption at age 13 and BMI at age 21 when adjusting for confounders. This study did not support an independent effect of dairy products or total calcium intake in adolescence on later early adulthood adiposity.


The inactivation of rfaP, rarA or sspA gene improves the viability of the Escherichia coli DNA polymerase III holD mutant.
The Escherichia coli holD mutant is poorly viable because the stability of holoenzyme polymerase III (Pol III HE) on DNA is compromised. Consequently, the SOS response is induced and the SOS polymerases DinB and Pol II further hinder replication. Mutations that restore the holD mutant viability belong to two classes, those that stabilize Pol III on DNA and those that prevent the deleterious effects of DinB over-production. We identified a dnaX mutation and the inactivation of rfaP and sspA genes as belonging to the first class of holD mutant suppressors. dnaX encodes a Pol III clamp loader subunit that interacts with HolD. rfaP encodes a lipopolysaccharide kinase that acts in outer membrane biogenesis. Its inactivation improves the holD mutant growth in part by affecting potassium import, previously proposed to stabilize Pol III HE on DNA by increasing electrostatic interactions. sspA encodes a global transcriptional regulator and growth of the holD mutant in its absence suggests that SspA controls genes that affect protein-DNA interactions. The inactivation of rarA belongs to the second class of suppressor mutations. rarA inactivation has a weak effect but is additive with other suppressor mutations. Our results suggest that RarA facilitates DinB binding to abandoned forks.


Brain neurons and glial cells express Neu differentiation factor/heregulin: a survival factor for astrocytes.
Neu differentiation factor (NDF, also called heregulin) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins. Earlier in situ hybridization analysis showed that NDF was transcribed predominantly in the central nervous system during embryonic development. To gain insights into the role of NDF in brain we analyzed its distribution by immunohistochemistry and in situ hybridization. Late-gestation (day 17) rat embryos displayed high NDF immunoreactivity in both motor (e.g., putamen) and limbic (e.g., septum) regions. Lower levels of the factor were exhibited by adult brain, except for the cerebellum, where NDF expression was increased postnatally. Both neurons and glial cells were identified by immunohistochemistry as NDF-producing cells (e.g., pyramidal neurons in the cerebral cortex and glial cells in the corpus callosum). By establishment of primary cultures of rat brain cells we confirmed that NDF was expressed in neurons as well as in astrocytes. In addition, by using such primary cultures we observed that NDF treatment exerted only a limited mitogenic effect, which was accompanied by significant acceleration of astrocyte maturation. Furthermore, long-term incubation with the factor specifically protected astrocytes from apoptosis, implying that NDF functions in brain as a survival and maturation factor for astrocytes.


The PPAR pan-agonist bezafibrate ameliorates cardiomyopathy in a mouse model of Barth syndrome.
The PGC-1α/PPAR axis has been proposed as a potential therapeutic target for several metabolic disorders. The aim was to evaluate the efficacy of the pan-PPAR agonist, bezafibrate, in tafazzin knockdown mice (TazKD), a mouse model of Barth syndrome that exhibits age-dependent dilated cardiomyopathy with left ventricular (LV) dysfunction. The effect of bezafibrate on cardiac function was evaluated by echocardiography in TazKD mice with or without beta-adrenergic stress. Adrenergic stress by chronic isoproterenol infusion exacerbates the cardiac phenotype in TazKD mice, significantly depressing LV systolic function by 4.5 months of age. Bezafibrate intake over 2 months substantially ameliorates the development of LV systolic dysfunction in isoproterenol-stressed TazKD mice. Without beta-adrenergic stress, TazKD mice develop dilated cardiomyopathy by 7 months of age. Prolonged treatment with suprapharmacological dose of bezafibrate (0.5% in rodent diet) over a 4-month period effectively prevented LV dilation in mice isoproterenol treatment. Bezafibrate increased mitochondrial biogenesis, however also promoted oxidative stress in cardiomyocytes. Surprisingly, improvement of systolic function in bezafibrate-treated mice was accompanied with simultaneous reduction of cardiolipin content and increase of monolysocardiolipin levels in cardiac muscle. Thus, we demonstrate that bezafibrate has a potent therapeutic effect on preventing cardiac dysfunction in a mouse model of Barth syndrome with obvious implications for treating the human disease. Additional studies are needed to assess the potential benefits of PPAR agonists in humans with Barth syndrome.


Hybridisation has shaped a recent radiation of grass-feeding aphids.
Aphids are common crop pests. These insects reproduce by facultative parthenogenesis involving several rounds of clonal reproduction interspersed with an occasional sexual cycle. Furthermore, clonal aphids give birth to live young that are already pregnant. These qualities enable rapid population growth and have facilitated the colonisation of crops globally. In several cases, so-called "super clones" have come to dominate agricultural systems. However, the extent to which the sexual stage of the aphid life cycle has shaped global pest populations has remained unclear, as have the origins of successful lineages. Here, we used chromosome-scale genome assemblies to disentangle the evolution of two global pests of cereals-the English (Sitobion avenae) and Indian (Sitobion miscanthi) grain aphids. Genome-wide divergence between S. avenae and S. miscanthi is low. Moreover, comparison of haplotype-resolved assemblies revealed that the S. miscanthi isolate used for genome sequencing is likely a hybrid, with one of its diploid genome copies closely related to S. avenae (~ 0.5% divergence) and the other substantially more divergent (> 1%). Population genomics analyses of UK and China grain aphids showed that S. avenae and S. miscanthi are part of a cryptic species complex with many highly differentiated lineages that predate the origins of agriculture. The complex consists of hybrid lineages that display a tangled history of hybridisation and genetic introgression. Our analyses reveal that hybridisation has substantially contributed to grain aphid diversity, and hence, to the evolutionary potential of this important pest species. Furthermore, we propose that aphids are particularly well placed to exploit hybridisation events via the rapid propagation of live-born "frozen hybrids" via asexual reproduction, increasing the likelihood of hybrid lineage formation.


Solitary hepatic lymphangioma: a one-case report.
Hepatic lymphangiomas, malformations of the liver lymphatic system, are extremely rare conditions in adults. A 41-year-old man presented with right upper abdominal pain for 6 months was introduced in this report. Ultrasound (US) and computed tomography (CT) scan demonstrated a giant cystictumor with a pedunculatedextrahepatic growth pattern. Due to diagnostic uncertainty, a partial hepatectomy was performed and pathological results confirmed the diagnosis of solitary hepatic lymphangioma. In this article, we reviewed the clinical and pathology features, preoperative diagnostic challenges, and treatments of hepaticlymphangiomas.


An intersectional framework for counterfactual fairness in risk prediction.
Along with the increasing availability of health data has come the rise of data-driven models to inform decision making and policy. These models have the potential to benefit both patients and health care providers but can also exacerbate health inequities. Existing "algorithmic fairness" methods for measuring and correcting model bias fall short of what is needed for health policy in two key ways. First, methods typically focus on a single grouping along which discrimination may occur rather than considering multiple, intersecting groups. Second, in clinical applications, risk prediction is typically used to guide treatment, creating distinct statistical issues that invalidate most existing techniques. We present novel unfairness metrics that address both challenges. We also develop a complete framework of estimation and inference tools for our metrics, including the unfairness value ("u-value"), used to determine the relative extremity of unfairness, and standard errors and confidence intervals employing an alternative to the standard bootstrap. We demonstrate application of our framework to a COVID-19 risk prediction model deployed in a major Midwestern health system.


Cooking and disgust sensitivity influence preference for attending insect-based food events.
Insects are energy-efficient and sustainable sources of animal protein in a world with insufficient food resources to feed an ever-increasing population. However, much of the western world refuses to eat insects because they perceive them as disgusting. This research finds that both animal reminder disgust and core disgust reduced people's willingness to attend a program called "Bug Appétit" in which insects were served as food. Additionally, people who were low in sensitivity to animal reminder disgust were more willing to attend this program after having been primed to think about cooking. Cooking is a process by which raw ingredients are transformed into finished products, reducing the "animalness" of meat products that renders them disgusting. Sensitivity to core disgust did not interact with cooking to influence willingness to attend the program. While prior research has emphasized that direct education campaigns about the benefits of entomophagy (the consumption of insects) can increase willingness to attend events at which insect-based food is served, this is the first demonstration that indirect priming can have a similar effect among a subset of the population.


Effectiveness, side effects and long-term status of nightguard vital bleaching.
In this clinical trial of nightguard vital bleaching for six weeks, 92 percent of the patients experienced some lightening of treated teeth. About 97 percent of patients with teeth stained through aging, inherent discoloration, brown fluorosis or trauma experienced lightening, as did 75 percent with tetracycline-stained teeth. Sixty-six percent experienced side effects, which resolved in 24 to 48 hours. Earliest re-treatment was done after one year in less time. Minimal color change occurred for 74 percent after 1 1/2 years and 62 percent after three years.