Planning to Learn: A Novel Algorithm for Active Learning during Model-Based Planning.
Active Inference is a recently developed framework for modeling decision processes under uncertainty. Over the last several years, empirical and theoretical work has begun to evaluate the strengths and weaknesses of this approach and how it might be extended and improved. One recent extension is the "sophisticated inference" (SI) algorithm, which improves performance on multi-step planning problems through a recursive decision tree search. However, little work to date has been done to compare SI to other established planning algorithms in reinforcement learning (RL). In addition, SI was developed with a focus on inference as opposed to learning. The present paper therefore has two aims. First, we compare performance of SI to Bayesian RL schemes designed to solve similar problems. Second, we present and compare an extension of SI - sophisticated learning (SL) - that more fully incorporates active learning during planning. SL maintains beliefs about how model parameters would change under the future observations expected under each policy. This allows a form of counterfactual retrospective inference in which the agent considers what could be learned from current or past observations given different future observations. To accomplish these aims, we make use of a novel, biologically inspired environment that requires an optimal balance between goal-seeking and active learning, and which was designed to highlight the problem structure for which SL offers a unique solution. This setup requires an agent to continually search an open environment for available (but changing) resources in the presence of competing affordances for information gain. Our simulations demonstrate that SL outperforms all other algorithms in this context - most notably, Bayes-adaptive RL and upper confidence bound (UCB) algorithms, which aim to solve multi-step planning problems using similar principles (i.e., directed exploration and counterfactual reasoning about belief updates given different possible actions/observations). These results provide added support for the utility of Active Inference in solving this class of biologically-relevant problems and offer added tools for testing hypotheses about human cognition.


Mobile Media Promotes Orientation of 2D/3D Hybrid Lead Halide Perovskite for Efficient Solar Cells.
2D/3D hybrid perovskites have shown great environmental stability for use as solar cells. Yet insulating organic cation spacers affect the formation of vertically oriented crystalline grains to hamper carrier transport. To date, the selection of cation spacers is limited because crystal growth kinetics should be strictly obeyed. Here, we adopted a mobile-media-assisted method to fabricate highly oriented 2D/3D hybrid perovskite films, wherein bulky molecules of (C(CH3)3NH3, TBA) are used as cation spacers. We found the compositional volatile salt promote the orientation of perovskite polycrystalline films with various compositions universally. And we obtained efficient solar cells with a photoelectric conversion efficiency (PCE) of 17.38% and a certified PCE of 19.30% based on 2D/3D hybrid perovskites an overall stoichiometry matching n = 10 and 20, respectively, which are one of the highest efficiencies among all 2D/3D hybrid perovskite based solar cells so far. These findings largely broaden the selection category of bulky cations and promote further exploration of more functional organic cations.


Functional state of the epidermal growth factor-receptor complexes during their internalization in A-431 cells.
Functional state of internalized epidermal growth factor (EGF) receptor in A-431 cells has been studied. The use of photoaffinity [125I]EGF derivative allowed us to establish that inside the cell the EGF retains its connection with the receptor. With the help of polyclonal antibodies to phosphotyrosine, it has been shown that EGF-receptor complexes maintain their phosphorylated state during internalization. The internalized EGF receptor kinase as well as that localized in the plasma membrane appeared to be able to phosphorylate synthetic peptide substrate introduced into the cell.


Association Between Facial Rejuvenation and Observer Ratings of Youth, Attractiveness, Success, and Health.
Surgical procedures for the aging face-including face-lift, blepharoplasty, and brow-lift-consistently rank among the most popular cosmetic services sought by patients. Although these surgical procedures are broadly classified as procedures that restore a youthful appearance, they may improve societal perceptions of attractiveness, success, and health, conferring an even larger social benefit than just restoring a youthful appearance to the face. To determine if face-lift and upper facial rejuvenation surgery improve observer ratings of age, attractiveness, success, and health and to quantify the effect of facial rejuvenation surgery on each individual domain. A randomized clinical experiment was performed from August 30 to September 18, 2016, using web-based surveys featuring photographs of patients before and after facial rejuvenation surgery. Observers were randomly shown independent images of the 12 patients; within a given survey, observers saw either the preoperative or postoperative photograph of each patient to reduce the possibility of priming. Observers evaluated patient age using a slider bar ranging from 30 to 80 years that could be moved up or down in 1-year increments, and they ranked perceived attractiveness, success, and health using a 100-point visual analog scale. The bar on the 100-point scale began at 50; moving the bar to the right corresponded to a more positive rating in these measures and moving the bar to the left, a more negative rating. A multivariate mixed-effects regression model was used to understand the effect of face-lift and upper facial rejuvenation surgery on observer perceptions while accounting for individual biases of the participants. Ordinal rank change was calculated to understand the clinical effect size of changes across the various domains after surgery. A total of 504 participants (333 women, 165 men, and 6 unspecified; mean age, 29 [range, 18-70] years) successfully completed the survey. A multivariate mixed-effects regression model revealed a statistically significant change in age (-4.61 years; 95% CI, -4.97 to -4.25) and attractiveness (6.72; 95% CI, 5.96-7.47) following facial rejuvenation surgery. Observer-perceived success (3.85; 95% CI, 3.12-4.57) and health (7.65; 95% CI; 6.87-8.42) also increased significantly as a result of facial rejuvenation surgery. The data presented in this study demonstrate that patients are perceived as younger and more attractive by the casual observer after undergoing face-lift and upper facial rejuvenation surgery. These procedures also improved ratings of perceived success and health in our patient population. These findings suggest that facial rejuvenation surgery conveys an even larger societal benefit than merely restoring a youthful appearance to the face. NA.


Role of Glutathionylation in Infection and Inflammation.
Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.


Noncontingent reinforcement competes with response performance.
Noncontingent reinforcement is a commonly used procedure to decrease levels of problem behavior. Goals of this intervention are to decrease motivation, responding, and the functional relation between behavior and consequences, but it could also possibly compete with performance of alternative desirable responses. In the current study, we assessed the effects of noncontingent reinforcement arranged from 0% to 100% of sessions on performance of alternative responding across two experiments. Experiment 1 assessed manding (i.e., requests) maintained by attention and tangibles with a child with developmental disabilities and Experiment 2 assessed keypecking maintained by food with six pigeons. We extended previous research by (a) showing that noncontingent reinforcement competes with both the acquisition and maintenance (performance) of an alternative response, (b) extending the generality of the findings across nonhuman and human participants, and (c) eliminating influence of sequence effects through random manipulations of noncontingent value in pigeons. Overall, greater amounts of noncontingent reinforcement competed with both acquisition and maintenance of alternative responding.


Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant.
Fecal microbiota transplantation (FMT) is an emerging therapy for recurrent or refractory Clostridioides difficile infection and is being actively investigated for other conditions. We describe two patients in whom extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteremia occurred after they had undergone FMT in two independent clinical trials; both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died. Enhanced donor screening to limit the transmission of microorganisms that could lead to adverse infectious events and continued vigilance to define the benefits and risks of FMT across different patient populations are warranted.


Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications.
Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts.


NLRP3 inflammasome is essential for the development of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is now recognized as an inflammatory disease and the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome was speculated to participate into its pathophysiological process, however, a direct role of NLRP3 has yet to be clearly shown. COPD model was established by tobacco inhalation, COPD modeling and NLRP3 knockout mice were treated with similar dose and duration of tobacco inhalation for 12 months, the lung function, lung damage and immune responses were evaluated between control, wild type COPD and NLRP3 knock out C57B1/6 mice. 10 months after tobacco inhalation, the respiratory system resistance indexes of COPD mice was significantly higher than that of control and NLRP3 knockout mice (2.8 ± 0.5 vs. 1.2 ± 0.3 and 1.3 ± 0.1 cm H2O ml(-1) s(-1), P < 0.05); the respiratory system compliance indexes of COPD was significantly lower than that of control and NLRP3 knockout mice (0.31 ± 0.02 vs. 0.43 ± 0.04, and 0.39 ± 0.01 ml/cm H2O); the NLRP3 knockout mice displayed no distinguishable pathological damage in the lung. Of the broncho-alveolar lavage fluid (BALF), the concentration of IL-1 and IL-18 of the COPD were significantly higher than that of control and NLRP3 knockout mice (IL-1: 286.8 ± 1.7 vs. 23.8 ± 2.1 and 24.2 ± 1.3 pg/mL, P < 0.05; IL-18: 104.5 ± 4.2 vs. 12.6 ± 2.1 and 15.7 ± 2.8 pg/mL, P < 0.05); the total numbers of macrophages, eosinophils, lymphocyte and neutrophil of control, COPD and NLRP3 knockout mice were 2.3 ± 0.4, 0.5 ± 0.2, 10.3 ± 3.4 and 2.8 ± 2.7; 8.7 ± 1.1, 12.5 ± 1.1, 45.3 ± 3.3 and 29.2 ± 4.2; and 3.2 ± 0.7, 1.8 ± 0.4, 18.1 ± 1.1 and 12.8 ± 3.4 × 10(4) mL, respectively; the rates of NLRP3 positive macrophages in the BALF of control, COPD and NLRP3 knockout mice were 5.0 ± 1.0%, 78.1 ± 9.2% and 2.0 ± 0.9%, respectively. NLRP3 inflammasome is essential for the development of COPD and blockade of NLRP3 might be a possible therapeutic strategy for COPD.


Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer.
Polyphenolic compounds, widely present in fruits, vegetables, and cereals, have potential benefits for human health and are protective agents against the development of chronic/degenerative diseases including cancer. More recently these bioactive molecules have been gaining great interest as anti-inflammatory and immunomodulatory agents, mainly in neoplasia where the pro-inflammatory context might promote carcinogenesis. Colorectal cancer (CRC) is considered a major public healthy issue, a leading cause of cancer mortality and morbidity worldwide. Epidemiological, pre-clinical and clinical investigations have consistently highlighted important relationships between large bowel inflammation, gut microbiota (GM), and colon carcinogenesis. Many experimental studies and clinical evidence suggest that polyphenols have a relevant role in CRC chemoprevention, exhibit cytotoxic capability vs. CRC cells and induce increased sensitization to chemo/radiotherapies. These effects are most likely related to the immunomodulatory properties of polyphenols able to modulate cytokine and chemokine production and activation of immune cells. In this review we summarize recent advancements on immunomodulatory activities of polyphenols and their ability to counteract the inflammatory tumor microenvironment. We focus on potential role of natural polyphenols in increasing the cell sensitivity to colon cancer therapies, highlighting the polyphenol-based combined treatments as innovative immunomodulatory strategies to inhibit the growth of CRC.


Exogenous stress hormones alter energetic and nutrient costs of development and metamorphosis.
Variation in environmental conditions during larval life stages can shape development during critical windows and have lasting effects on the adult organism. Changes in larval developmental rates in response to environmental conditions, for example, can trade off with growth to determine body size and condition at metamorphosis, which can affect adult survival and fecundity. However, it is unclear how use of energy and nutrients shape trade-offs across life-stage transitions because no studies have quantified these costs of larval development and metamorphosis. We used an experimental approach to manipulate physiological stress in larval amphibians, along with respirometry and 13C-breath testing to quantify the energetic and nutritional costs of development and metamorphosis. Central to larval developmental responses to environmental conditions is the hypothalamic-pituitary-adrenal/interrenal (HPA/I) axis, which regulates development, as well as energy homeostasis and stress responses across many taxa. Given these pleiotropic effects of HPA/I activity, manipulation of the HPA/I axis may provide insight into costs of metamorphosis. We measured the energetic and nutritional costs across the entire larval period and metamorphosis in a larval amphibian exposed to exogenous glucocorticoid (GC) hormones - the primary hormone secreted by the HPA/I axis. We measured metabolic rates and dry mass across larval ontogeny, and quantified lipid stores and nutrient oxidation via 13C-breath testing during metamorphosis, under control and GC-exposed conditions. Changes in dry mass match metamorphic states previously reported in the literature, but dynamics of metabolism were influenced by the transition from aquatic to terrestrial respiration. GC-treated larvae had lower dry mass, decreased fat stores and higher oxygen consumption during stages where controls were conserving energy. GC-treated larvae also oxidized greater amounts of 13C-labelled protein stores. These results provide evidence for a proximate cause of the physiological trade-off between larval growth and development, and provide insight into the energetic and nutrient costs that shape fitness trade-offs across life stages.


Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms.
Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein and daidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal stem cells (BMSCs). Herein, the effects of daidzein analogs on the osteogenic differentiation efficiency of human BMSC and adipose-derived stromal/stem cells (ASC) were explored. BMSCs and ASCs underwent osteogenic differentiation in the presence of vehicle, 17β-estradiol (E2), phytoestrogens, or daidzein analogs. Cells were stained for alkaline phosphatase (ALP) enzymatic activity, calcium deposition by alizarin red s, and phosphate mineralization by silver nitrate. Gene expression analysis was conducted on cells treated with daidzein analogs. Cells treated with E2, daidzein, or genistein increased calcium deposition by 1.6-, 1.5-, and 1.4-fold, respectively, relative to vehicle-treated BMSCs and 1.6-, 1.7-, and 1.4-fold relative to vehicle-treated ASCs, respectively. BMSCs treated with daidzein analog 2c, 2g, and 2l demonstrated a 1.6-, 1.6-, and 1.9-fold increase in calcium deposition relative to vehicle-treated BMSCs, respectively, while ASCs treated with daidzein analog 2c, 2g, or 2l demonstrated a 1.7-, 2.0-, and 2.2-fold increase in calcium deposition relative to vehicle-treated ASCs, respectively. Additional analysis with BMSCs and ASCs was conducted in the more efficient compounds: 2g and 2l. ALP activity and phosphate mineralization was increased in 2g- and 2l-treated cells. The analysis of lineage specific gene expression demonstrated increased expression of key osteogenic genes (RUNX2, c-FOS, SPARC, DLX5, SPP1, COL1A1, IGF1, SOST, and DMP1) and earlier induction of these lineage specific genes, following treatment with 2g or 2l, relative to vehicle-treated cells. Estrogen receptor (ER) inhibitor studies demonstrated that ER antagonist fulvestrant inhibited the osteogenic differentiation of 2g in BMSCs and ASCs, while fulvestrant only attenuated the effects of 2l, suggesting that 2l acts by both ER dependent and independent pathways. These studies provide support for exploring the therapeutic efficacy of daidzein derivatives for the treatment of osteoporosis. Furthermore, the patterns of gene induction differed following treatment with each daidzein analog, suggesting that these daidzein analogs activate distinct ER and non-ER pathways to induce differentiation in BMSCs and ASCs.


Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.
Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.


The effects of prenatal alcohol on the central nervous system.
Prenatal alcohol exposure has a profound effect on the developing brain. In fetal alcohol syndrome (FAS), mental retardation and microcephaly are commonly observed. A partial syndrome, fetal alcohol effects (FAE) can result in neurobehavioral sequelae, which may present at birth or appear later in development. This chapter discusses the clinical evidence supporting the concept of FAE, the range of cognitive disturbances seen in FAS and FAE children, and studies on long-term outcome. We review studies that suggest that even in the absence of the stigmata of FAS, neonatal signs of central nervous system dysfunction may predict later developmental deviation. However, the clinical research on the cognitive and behavioral disorders in the FAE population is limited. Examination of electroencephalograms, evoked potentials, and sleep pattern provide additional evidence that the functional integrity of the brain has been altered. An abbreviated review of behavioral animal studies provides additional support for the clinical investigations presented.


Avascular necrosis of the spine in solid posterior fusion segments.
Case report. We present a rare case of avascular necrosis of a vertebral body in solid posterior fusion segments without trauma and its possible mechanism. The reported case is that of a 56-year old woman with posterior spinal fusion (T10-L2) for a fracture of T12 presenting with progressive kyphosis, back pain and neurologic deficits developing with no history of trauma. Serial radiographs, computed tomography, and magnetic resonance imaging scans confirmed avascular necrosis of the 11th thoracic vertebral body. This is a retrospective review of a case seen at our hospital. The symptoms were successfully treated by resection of the necrotic vertebral body and correction of the deformity. Despite solid posterior fusion segments, avascular necrosis of a vertebral body developed without trauma. This may be attributed to a wedged vertebra that causes repeated microtrauma and resulting avascular necrosis on the adjacent vertebra. Surgical treatment is required in avascular necrosis of a vertebral body with progressive collapse and neurologic compromise secondary to osteoporotic fracture adjacent to a wedge-shaped vertebra at the thoracolumbar junction.


Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: a meta-analysis.
To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography (ERCP). PubMed, Embase, Science Citation Index, and Cochrane Controlled Trials Register were searched to identify relevant trials published in English. Inclusion and exclusion criteria were used to screen for suitable studies. Two reviewers independently judged the study eligibility while screening the citations. The methodological quality of the included trials was assessed using the Jadad scoring system. All results were expressed as OR and 95%CI. Data were analyzed using Stata12.0 software. Ten eligible randomized controlled trials were selected, including 1176 patients. A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of post-ERCP pancreatitis (PEP) in high-risk patients (OR = 0.25; 95%CI: 0.17-0.38; P < 0.001). Pancreatic stents also alleviated the severity of PEP (mild pancreatitis after ERCP: OR = 0.33; 95%CI: 0.21-0.54; P < 0.001; moderate pancreatitis after ERCP: OR = 0.30; 95%CI: 0.13-0.67; P = 0.004). The result of severe pancreatitis after ERCP was handled more rigorously (OR = 0.24; 95%CI: 0.05-1.16; P = 0.077). Serum amylase levels were not different between patients with pancreatic stents and control patients (OR = 1.08; 95%CI: 0.82-1.41; P = 0.586). Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.


Selectivity of Explosives Analysis with Ambient Ionization Single Quadrupole Mass Spectrometry: Implications for Trace Detection.
Ambient ionization (AI) is a rapidly growing field in mass spectrometry (MS). It allows for the direct analysis of samples without any sample preparation, making it a promising technique for the detection of explosives. Previous studies have shown that AI can be used to detect a variety of explosives, but the exact gas-phase reactions that occur during ionization are not fully understood. This is further complicated by differences in mass spectrometers and individual experimental set ups between researchers. This study investigated the gas-phase ion reactions of five different explosives using a variety of AI techniques coupled to a Waters QDa mass spectrometer to identify selective ions for explosive detection and identification based on the applied ambient ionization technique. The results showed that the choice of the ion source can have a significant impact on the number of ions observed. This can affect the sensitivity and selectivity of the data produced. The findings of this study provide new insights into the gas-phase ion reactions of explosives and could lead to the development of more sensitive and selective AI-based methods for their detection.


Shared genetic influences among childhood shyness, social competences, and cortical responses to emotions.
Visual event-related potentials (ERPs) evoked by facial expressions are useful to map socioemotional responses among shy children and to predict transition into social phobia. We investigated the sources of covariation among childhood shyness, social competences, and ERPs to other children's happy, neutral, and angry expressions. Electrophysiological and twin analyses examined the phenotypic and etiological association among an index of childhood shyness, an index of social competences, and ERP responses to facial expressions in 200 twins (mean age=9.23years). Multivariate twin analyses showed that the covariation among shyness, social competences, and a composite of a frontal late negative component occurring around 200-400ms in response to happy, neutral, and angry expressions could be entirely explained by shared genetic factors. A coherent causal structure links childhood shyness, social competences, and the cortical responses to facial emotions. A common genetic substrate can explain the interrelatedness of individual differences for childhood shyness, social competences, and some associated electrophysiological responses to socioemotional signals.


The role of blue copper proteins in the oxidation of methylamine by an obligate methylotroph.
Organism 4025, an obligate methylotroph, when grown on methylamine in the presence of a high concentration of copper, contained high concentrations of methylamine dehydrogenase and two blue copper proteins, amicyanin and an azurin-type protein; these were purified to homogeneity and characterized. The methylamine dehydrogenase is a basic protein (pI 8.8) and consists of light and heavy subunits (Mr 14100 and 43000; total Mr 112000). This dehydrogenase differed slightly from other methylamine dehydrogenases in its absorption spectrum and in its lack of thermal stability. Amicyanin, the more abundant blue copper protein, had an Mr of 11500, a midpoint redox potential of 294mV at pH 7.0, and a much lower isoelectric point (pI5.3) than other amicyanins. Its absorption maximum was 620 nm (7-24 nm higher than those of other amicyanins); its absorption coefficient (at 620 nm) was 3.8 mM-1 X cm-1. The 'azurin' (6% of the blue copper protein) had an Mr of 12500, a midpoint redox potential of 323 mV and a high isoelectric point (pI 9.4). Its absorption maximum was 620 nm, the absorption coefficient (16 mM-1 X cm-1) at this wavelength being considerably greater than that of any blue copper protein described previously. The partially-purified soluble cytochromes cH and cL were similar to those of other methylotrophs. The interactions of the purified redox proteins were investigated in order to elucidate their role in methylamine oxidation. Methylamine dehydrogenase was able to donate electrons only to amicyanin, the rate of reaction being 2.04 mmol/min per mumol of methylamine dehydrogenase; this is sufficient to account for the rate of respiration in whole bacteria. The blue copper proteins were able to react rapidly with each other and with both the soluble cytochromes c.


Class 1 and class 2 integrons in poultry carcasses from broiler house and poultry processing environments.
Integrons have been identified as major genetic contributors to the dissemination of antimicrobial resistance in bacteria. The objective of this study was to examine the prevalence of integrons in poultry processing at the broiler house and in processing plants. Class 1 and class 2 integrons were found throughout the processing environment. Of the two classes of integrons, class 1 was the most prevalent in all processing areas. The levels of both classes of integrons decreased from the farm to the processing plant. Within the chiller tank in the processing plant, the persistence of these sequences appears to be related to the free chlorine concentration of the chiller tank water. The variable regions of the amplified integrons showed size diversity (from 680 to 2,000 bp), suggesting diversity in types of antibiotic-resistance-coding gene cassettes. The presence of the class 1 and class 2 integrons in the chlorinated chiller tank suggests that these sequences are capable of withstanding this critical step in the reduction of microbial loads on poultry carcasses. The persistence of the integron gene sequences on the farm and throughout processing highlights the stability of these transmissible antibiotic-resistance-coding nucleotide sequences and their potential role as reservoirs of antibiotic-resistance-coding genetic elements within the poultry rearing and processing environments.


Low tidal volume ventilation is associated with mortality in COVID-19 patients-Insights from the PRoVENT-COVID study.
Low tidal volume ventilation (LTVV) is associated with mortality in patients with acute respiratory distress syndrome. We investigated the association of LTVV with mortality in COVID-19 patients. Secondary analysis of a national observational study in COVID-19 patients in the first wave of the pandemic. We compared COVID-19 patients that received LTVV, defined as controlled ventilation with a median tidal volume ≤ 6 mL/kg predicted body weight over the first 4 calendar days of ventilation, with patients that did not receive LTVV. The primary endpoint was 28-day mortality. In addition, we identified factors associated with use of LTVV. Of 903 patients, 294 (32.5%) received LTVV. Disease severity scores and ARDS classification was not different between the two patient groups. The primary endpoint, 28-day mortality, was met in 68 out of 294 patients (23.1%) that received LTVV versus in 193 out of 609 patients (31.7%) that did not receive LTVV (P < 0.001). LTVV was independently associated with 28-day mortality (HR, 0.68 (0.45 to 0.95); P = 0.025). Age, height, the initial tidal volume and continuous muscle paralysis was independently associated with use of LTVV. In this cohort of invasively ventilated COVID-19 patients, approximately a third of patients received LTVV. Use of LTVV was independently associated with reduced 28-day mortality. The initial tidal volume and continuous muscle paralysis were potentially modifiable factors associated with use of LTVV. These findings are important as they could help clinicians to recognize patients who are at risk of not receiving LTVV.


Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.
A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.


Supplementary grandchild care, social integration, and depressive symptoms: longitudinal findings from Korea.
Despite growing concerns about the heavy reliance on supplementary grandchild care in Korea, understanding of its longitudinal effects on the grandparents' mental health has been limited. This study examined whether transition patterns of grandchild care among Korean grandparents were associated with changes in the grandparents' depressive symptoms, directly or indirectly, through changes in two domains of social integration (intergenerational contact and social activities) after controlling for socioeconomic characteristics and baseline levels of depressive symptoms and social integration. Using the Korean Longitudinal Study of Aging (N = 4,362), a nationally representative multiwave survey, we examined four possible statuses of grandchild care over a three-year period: started (n = 64), continuous (n = 73), and discontinued (n = 103) caregiving, and non-caregiving (n = 4,121). The proposed mediation model was analyzed using structural equation modeling with non-caregivers as a reference group, and Wald tests were conducted to further examine differences in the effects across the three caregiving groups. The direct effects of grandchild care on depressive symptoms in Korean grandparents were not significant. Rather, those who started or continuously provided caregiving had significantly reduced depressive symptoms via increased intergenerational contact compared to the non-caregiving group. These findings indicated beneficial effects of grandchild care on depressive symptoms in Korean grandparents through increased social integration within the family. Implications of the study findings were discussed.


Hydrolytic reactions of thymidine 5'-o-phenyl-N-alkylphosphoramidates, models of nucleoside 5'-monophosphate prodrugs.
To obtain detailed data on the kinetics of hydrolytic reactions of triester-like nucleoside 5'-O-aryl-N-alkylphosphoramidates, potential prodrugs of antiviral nucleoside monophosphates, the hydrolysis of diastereomeric (Rp/Sp) thymidine 5'-{O-phenyl-N-[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (3), a phosphoramidate derived from the methyl ester of L-alanine, has been followed by reversed-phase HPLC over the range from Ho=0 to pH 8 at 90 degrees C. According to the time-dependent product distributions, the hydrolysis of 3 proceeds at pH<4 by two parallel routes, namely by nucleophilic displacement of the alaninyl ester moiety by a water molecule and by hydrolysis of the carboxylic ester linkage that allows intramolecular attack of the carboxy group on the phosphorus atom, thereby resulting in the departure of either thymidine or phenol without marked accumulation of any intermediates. Both routes represent about half of the overall disappearance of 3. The departure of phenol eventually leads to the formation of thymidine 5'-phosphate. At pH>5, the predominant reaction is hydrolysis of the carboxylic ester linkage followed by intramolecular displacement of a phenoxide ion by the carboxylate ion and hydrolysis of the resulting cyclic mixed anhydride into an acyclic diester-like thymidine 5'-phosphoramidate. The latter product accumulated quantitatively without any indication of further decomposition. Hydroxide-ion-catalyzed P--OPh bond cleavage of the starting material 3 occurred as a side reaction. Comparative measurements with thymidine 5'-{N-[(1S)-2-oxo-2-methoxy-1-methylethyl]phosphoramidate} (4) revealed that, under acidic conditions, this diester-like compound is hydrolyzed by P--N bond cleavage three orders of magnitude more rapidly than the triester-like 3. At pH>5, the stability order is reversed, with 3 being hydrolyzed six times as rapidly as 4. Mechanisms of the partial reactions are discussed.


[A quantitative study on DNA content of salivary gland carcinomas by image analysis technique].
DNA content was quantitatively determined in 30 cases of salivary gland carcinoma (SGC) by image analysis technique using paraffin-embedded sections stained with Feulgen method. The results showed that the nuclear DNA content was related to the malignancy of SGC, based on the clinical and morphological criteria such as tumor size, mobility, property of growth, mitotic rate, degree of differentiation and the histological type of the tumor. The number of nuclei above 5 C DNA, expressing aneuploidy, seems to be of more prognostic significance. Aneuploidy greater than 10% may be indicative of a poor prognosis for SGC. Thus, it is suggested that the quantitative analysis of DNA content may be able to provide an objective and quantitative reference for evaluating the prognosis of SGC.


Clinical and genotypic characteristics of extensively drug-resistant and multidrug-resistant tuberculosis.
The aims of this study were to compare the clinical features of patients with extensively drug-resistant tuberculosis (XDRTB) and multidrug-resistant tuberculosis (MDRTB) and the genotypic characteristics of these Mycobacterium tuberculosis isolates. A total of 90 non-HIV-infected patients having MDRTB (n = 80, not including XDRTB, 88.9%) and XDRTB (n = 10, 11.1%) were identified from 2000 to 2007. Genotypes of the 39 available isolates were evaluated by spoligotyping and the 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) scheme. Patients with XDRTB were more likely to have previous history of TB and cavitary lung lesions than patients with MDRTB (P < 0.05). Among the 39 isolates for spoligotyping analysis, the Beijing genotype was the most common (n = 21, 53.8%). Four (44.4%) isolates of XDRTB and 17 (56.7%) isolates of MDRTB belonged to Beijing family genotypes. There was no significant difference in the anti-tuberculosis drug resistance rates between Beijing and non-Beijing genotype isolates or in the clinical features of infected patients. In conclusion, significant differences in clinical manifestations existed among patients with XDRTB and MDRTB. The clinical features of patients infected with the Beijing genotype and the drug resistance profile of the Beijing genotype isolates were similar to those for the non-Beijing family genotype.


Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells.
Vascular endothelial growth factor (VEGF) and basic (b) fibroblast growth factor (FGF-2/bFGF) are involved in vascular development and angiogenesis. Pulmonary artery smooth muscle cells express VEGF and FGF-2 and are subjected to mechanical forces during pulsatile blood flow. The effect of stretch on growth factor expression in these cells is not well characterized. We investigated the effect of cyclic stretch on the expression of VEGF and FGF-2 in ovine pulmonary artery smooth muscle cells. Primary confluent cells from 6-wk-old lambs were cultured on flexible silicon membranes and subjected to cyclic biaxial stretch (1 Hz; 5-25% stretch; 4-48 h). Nonstretched cells served as controls. Expression of VEGF and FGF-2 was determined by Northern blot analysis. Cyclic stretch induced expression of both VEGF and FGF-2 mRNA in a time- and amplitude-dependent manner. Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold). These results demonstrate that mechanical stretch regulates VEGF and FGF-2 gene expression, which could play a role in pulmonary vascular development or in postnatal pulmonary artery function or disease.


The complex clinical and genetic classification of inherited ataxias. I. Dominant ataxias.
The clinical classification of autosomal dominant cerebellar ataxias (ADCAs) is intricate due to the variable and unpredictable association of signs and symptoms of central nervous system (CNS) and peripheral nervous system (PNS) deterioration during the life of a patient. However, for many purposes, particularly patient management, clinical systematics is the most useful method for labelling patients; in some instances there is no basis for any more fundamental classification of phenotypes. On the other hand, recent molecular-genetic approaches to dominant ataxias have had a profound impact in nosology, diagnostic procedures and the management of patients, since they are based on the fact that all mendelian neurological diseases can be precisely classified according to the locus involved as well as the particular mutant allele at that locus. Therefore, a clinical and genetic classification of dominant ataxias is herewith proposed as the best nosographical choice. Clinical, neuropathological, genetic, and pathogenetic aspects of ADCAs are reviewed and discussed to help the clinical neurologist guide diagnostic procedures and manage ataxic patients.


Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10-year forecasting model.
To predict the future health and economic burden of cardiovascular disease (CVD) in type 2 diabetes (T2D) in Qatar. A dynamic multistate model was designed to simulate the progression of fatal and non-fatal CVD events among people with T2D in Qatar aged 40-79 years. First CVD events [i.e. myocardial infarction (MI) and stroke] were calculated via the 2013 Pooled Cohort Equation, while recurrent CVD events were sourced from the REACH registry. Key model outcomes were fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years, total direct medical costs and total productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective. Sensitivity analyses were performed to test the robustness of estimates. Over 10 years among people with T2D, model estimates 108 195 [95% uncertainty interval (UI) 104 249-112 172] non-fatal MIs, 62 366 (95% UI 60 283-65 520) non-fatal strokes and 14 612 (95% UI 14 472-14 744) CVD deaths. The T2D population accrued 4 786 605 (95% UI 4 743 454, 4 858 705) total years of life lived and 3 781 833 (95% UI 3 724 718-3 830 669) total quality-adjusted life years. Direct costs accounted for 57.85% of the total costs, with a projection of QAR41.60 billion (US$11.40 billion) [95% UI 7.53-147.40 billion (US$2.06-40.38 billion)], while the total indirect costs were expected to exceed QAR30.31 billion (US$8.30 billion) [95% UI 1.07-162.60 billion (US$292.05 million-44.55 billion)]. The findings suggest a significant economic and health burden of CVD among people with T2D in Qatar and highlight the need for more enhanced preventive strategies targeting this population group.


Theory development and application in medical education.
The role and status of theory is by no means a new topic in medical education. Yet summarizing where we have been and where we are going with respect to theory development and application is difficult because our community has not yet fully elucidated what constitutes medical education theory. In this article, we explore the idea of conceptualizing theory as an effect on scholarly dialogue among medical educators. We describe theory-enabled conversation as argumentation, which frames inquiry, permits the evaluation of evidence, and enables the acquisition of community understanding that has utility beyond investigators' local circumstances. We present ideas for assessing argumentation quality and suggest approaches to increasing the frequency and quality of argumentation in the exchange among diverse medical education scholars.


Systolic blood pressure on admission predicts in-hospital mortality among patients presenting with acute coronary syndromes: the Greek study of acute coronary syndromes.
The authors sought to evaluate whether the level of systolic blood pressure (SBP) on hospital admission is an independent prognostic factor for in-hospital mortality of patients hospitalized with acute coronary syndrome (ACS). From October 2003 to September 2004, 2172 consecutive patients with ACS were included in the study (76% men). The in-hospital mortality rate was 3.2% in male and 5.7% in female patients (overall, 82 deaths; P=.009). An inverse association was observed between in-hospital mortality rate and levels of SBP (<100 mm Hg, death rate 17.8%; 100-120 mm Hg, 3.7%; 120-140 mm Hg, 2.9%; >140 mm Hg, 2.6%; P<.001). Women, hypertensives, diabetics, dyslipidemics, and older patients had higher levels of SBP compared with other groups. The SBP of patients who received thrombolytic agents was lower than that of those who did not receive this therapy. Multi-adjusted analysis revealed that a 10-mm Hg increment in SBP was associated with a 27% lower likelihood of death during hospitalization (odds ratio, 0.73; 95% confidence interval, 0.66-0.90).


Single-atom catalysts supported on a hybrid structure of boron nitride/graphene for efficient nitrogen fixation via synergistic interfacial interactions.
Hexagonal boron nitride (BN) shows significant chemical stability and promising thermal nitrogen reduction reaction (NRR) activity but suffers from low conductivity in electrolysis with a wide band gap. To overcome this problem, two-dimensional (2D) BN and graphene (G) are designed as a heterostructure, namely BN/G. According to density functional theory (DFT), the higher conductivity of G narrows the band gap of BN by inducing some electronic states near the Fermi energy level (Ef). Once transition metals (TMs) are anchored in the BN/G structure as single atom catalysts (SACs), the NRR activity improves as the inert BN basal layer activates with moderate *NH2 binding energy and further the band gap is reduced to zero. V (vanadium) and W (tungsten) SACs exhibit the best performance with limiting potentials of -0.22 and -0.41 V, respectively. This study helps in understanding the improvement of the NRR activity of BN, providing physical insights into the adsorbate-TM interaction.


Haboob Dust Storms and Motor Vehicle Collision-related Trauma in Phoenix, Arizona.
The Sonoran Desert region, encompassing most of southern Arizona, has an extreme climate that is famous for dust storms known as haboobs. These storms lead to decreased visibility and potentially hazardous driving conditions. In this study we evaluate the relationship between haboob events and emergency department (ED) visits due to motor vehicle collisions (MVCs) in Phoenix, Arizona. This study is a retrospective analysis of MVC-related trauma presentations to Phoenix, AZ, hospitals before and following haboob dust storms. These events were identified from 2009-2017 primarily using Phoenix International Airport weather data. De-identified trauma data were obtained from the Arizona Department of Health Services (ADHS) Arizona State Trauma Registry (ASTR) from seven trauma centers within a 10-mile radius of the airport. We compared MVC-related trauma using six- and 24-hour windows before and following the onset of haboob events. There were 31,133 MVC-related trauma encounters included from 2009-2017 and 111 haboob events meeting meteorological criteria during that period. There was a 17% decrease in MVC-related ED encounters in the six hours following haboob onset compared to before onset (235 vs 283, P = 0.04), with proportionally more injuries among males (P < 0.001) and higher mortality (P = 0.02). There was no difference in frequency of presentations (P = 0.82), demographics, or outcomes among the 24-hour pre-and post-haboob groups. Haboob dust storms in Phoenix, Arizona, are associated with a decrease in MVC-related injuries during the six-hour period following storm onset, likely indicating the success of public safety messaging efforts. Males made up a higher proportion of those injured during the storms, suggesting a target for future interventions. Future public-targeted weather-safety initiatives should be accompanied more closely by monitoring and evaluation efforts to assess for effectiveness.


PAHs underfoot: contaminated dust from coal-tar sealcoated pavement is widespread in the United States.
We reported in 2005 that runoff from parking lots treated with coal-tar-based sealcoat was a major source of polycyclic aromatic hydrocarbons (PAHs) to streams in Austin, Texas. Here we present new data from nine U.S. cities that show nationwide patterns in concentrations of PAHs associated with sealcoat. Dust was swept from parking lots in six cities in the central and eastern U.S., where coal-tar-based sealcoat dominates use, and three cities in the western U.S., where asphalt-based sealcoat dominates use. For six central and eastern cities, median SigmaPAH concentrations in dust from sealcoated and unsealcoated pavement are 2200 and 27 mg/kg, respectively. For three western cities, median SigmaPAH concentrations in dust from sealcoated and unsealcoated pavement are similar and very low (2.1 and 0.8 mg/kg, respectively). Lakes in the central and eastern cities where pavement was sampled have bottom sediments with higher PAH concentrations than do those in the western cities relative to degree of urbanization. Bottom-sediment PAH assemblages are similar to those of sealcoated pavement dust regionally, implicating coal-tar-based sealcoat as a PAH source to the central and eastern lakes. Concentrations of benzo[a]pyrene in dustfrom coal-tarsealcoated pavement and adjacent soils greatly exceed generic soil screening levels, suggesting that research on human-health risk is warranted.


Effect of two defined formula diets on jejunal and colonic uptake of hexoses in control and ileal resected rabbits.
An in vitro technique was used to measure the jejunal and colonic uptake of glucose and galactose in sham-operated control (CONT) rabbits and in animals with a surgical resection of the distal half of the small intestine (RES) performed six weeks previously. CONT and RES were fed ad libitum or pair-fed amounts of standard Purina chow, or ad libitum amounts of Ensure or Flexical HN for two weeks. Flexical NH differs from Ensure in its higher content of carbohydrate, essential fatty acids and polyunsaturated fatty acids but lower total dietary content of fat. The ad libitum chow-fed animals gained weight whereas the animals fed the defined formula diets lost weight. Weight gain was greater in RES than CONT fed chow, and weight loss was greater in RES than CONT fed Ensure or Flexical HN. Despite these differences in body weight, the dry and wet weights of the jejunum, and the adherent mucosal fluid volumes remained unchanged in CONT and RES fed the different diets. The intestinal morphology was unaffected by feeding Ensure or Flexical HN to control animals, whereas the villus cell size, villus and mucosal surface areas were lower in resected rabbits fed these diets than in resected animals fed chow. Glucose uptake was greatest in CONT and RES fed Flexical HN. Glucose uptake was higher in RES than CONT fed chow or Ensure but was lower in RES than CONT fed Flexical HN. In CONT fed Flexical HN, there was a lower value of the apparent Michaelis constant, Km*, and a higher value of the apparent passive permeability coefficient (Pd*) than in animals fed chow or Ensure. In RES there was lower Pd* in Ensure and Flexical HN-fed rabbits than in those fed chow, but the Km* was lower and the maximal transport rate, Jdm, was higher in animals given Flexical HN. The colonic uptake of glucose and the jejunal uptake of galactose was also influenced by feeding Ensure and Flexical HN. These differences in uptake in animals fed Ensure or Flexical-HN could not be explained by differences in body weight gain, since a different pattern of changes in glucose and galactose uptake was observed in CONT or RES rabbits exposed to restricted chow intake.(ABSTRACT TRUNCATED AT 400 WORDS)


AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.
AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties.


Fundus Tessellated Density of Pathologic Myopia.
The study aimed to quantitatively evaluate the fundus tessellated density (FTD) in different categories of pathologic myopia (PM) using fundus photographs with the application of artificial intelligence. A retrospective review of 407 PM (META-PM, Category 2-Category 4) eyes was conducted, employing a biomimetic mechanism of human vision and integrated image processing technologies for FTD extraction and calculation. Different regions of interest were analyzed, including circle O4.5 (optic disc centered, diameter of 4.5 mm) and circle M1.0, M3.0, M6.0 (macular centered, diameter of 1.0, 3.0, and 6.0 mm), using 2 partitioning methods ("X" and "+"). The density of patchy (Category 3) or macular atrophy (Category 4) areas was quantified. Univariate and multivariate linear regression analyses were performed to assess the association with FTD. The mean FTD of total PM eyes was 0.283, ranging from 0.002 to 0.500, and demonstrating a negative correlation with the PM category. In multivariate analysis, age was found to be significantly associated with FTD (P<0.05), while axial length did not show a significant association. Fundus tessellation of circle O4.5 and circle M6.0 displayed associations with the FTD across different PM categories. The "X" partitioning method better fit the circle M6.0 region, while both methods were suitable for the circle O4.5 region. After excluding the patchy and macular atrophic areas, the mean FTD values were 0.346 in Category 2, 0.261 in Category 3, and 0.186 in Category 4. The study revealed a decreasing trend in FTD values across different categories of PM, regardless of the presence or absence of patchy or macular atrophic areas. Quantifying FTD in PM could be a valuable tool for improving the existing PM classification system and gaining insights into the origin of posterior staphyloma and visual field defects in high myopia.


[Multiple bacterial resistance in daily practice].
Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians. Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription. The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests. Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected. When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens. Therapies should be shorter and questionable antibioprophylaxis should also be avoided. A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription.


An unusual cause of spontaneous hemothorax: cardiac angiosarcoma.
Angiosarcoma, the most common primary malignant neoplasm of the heart in adults, usually presents as pericardial effusion or right-sided heart failure. Rupture of an angiosarcoma-infiltrated cardiac chamber as a cause of hemothorax is very rare in the literature. In this report, we describe a 34-year-old male patient, who presented to emergency service with sudden chest pain and dyspnea. The diagnostic work-up revealed spontaneous right-sided hemothorax and a large right atrial (RA) mass with suspicious atrial perforation. An urgent surgery showed a vascularized irregular RA mass invading the parietal pericardium and pleura and a perforation of the RA free wall. Histopathologic examination confirmed the diagnosis of angiosarcoma, and the patient was subsequently referred for radiotherapy and chemotherapy.


Weilby-Burton arthroplasty of the trapeziometacarpal joint of the thumb.
Twenty-three patients (25 thumbs) were treated by tendon interposition arthroplasty for trapeziometacarpal arthrosis as described by Weilby and modified slightly as described by Burton and Pellegrini. There was good (4/25, 16%) or complete (19/25, 76%) pain relief in 23 (92%) of the cases. Activities of daily living were generally easier. Mobility and strength of the thumb were satisfactory. One patient had signs of instability during a stress test. We conclude that our technique produces a stable and pain-free thumb joint. However, careful selection of the patients for this procedure is essential, and the patient must be given comprehensive information about all stages.


Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy.
Decreased p27(Kip1) levels are a poor prognostic factor in many malignancies, and can occur through up-regulation of SCF(Skp2) E3 ligase function, resulting in enhanced p27 ubiquitination and proteasome-mediated degradation. While proteasome inhibitors stabilize p27(Kip1), agents inhibiting SCF(Skp2) may represent more directly targeted drugs with the promise of enhanced efficacy and reduced toxicity. Using high-throughput screening, we identified Compound A (CpdA), which interfered with SCF(Skp2) ligase function in vitro, and induced specific accumulation of p21 and other SCF(Skp2) substrates in cells without activating a heat-shock protein response. CpdA prevented incorporation of Skp2 into the SCF(Skp2) ligase, and induced G(1)/S cell-cycle arrest as well as SCF(Skp2)- and p27-dependent cell killing. This programmed cell death was caspase-independent, and instead occurred through activation of autophagy. In models of multiple myeloma, CpdA overcame resistance to dexamethasone, doxorubicin, and melphalan, as well as to bortezomib, and also acted synergistically with this proteasome inhibitor. Importantly, CpdA was active against patient-derived plasma cells and both myeloid and lymphoblastoid leukemia blasts, and showed preferential activity against neoplastic cells while relatively sparing other marrow components. These findings provide a rational framework for further development of SCF(Skp2) inhibitors as a novel class of antitumor agents.


Improving precision and power in randomized trials for COVID-19 treatments using covariate adjustment, for binary, ordinal, and time-to-event outcomes.
Time is of the essence in evaluating potential drugs and biologics for the treatment and prevention of COVID-19. There are currently 876 randomized clinical trials (phase 2 and 3) of treatments for COVID-19 registered on clinicaltrials.gov. Covariate adjustment is a statistical analysis method with potential to improve precision and reduce the required sample size for a substantial number of these trials. Though covariate adjustment is recommended by the U.S. Food and Drug Administration and the European Medicines Agency, it is underutilized, especially for the types of outcomes (binary, ordinal, and time-to-event) that are common in COVID-19 trials. To demonstrate the potential value added by covariate adjustment in this context, we simulated two-arm, randomized trials comparing a hypothetical COVID-19 treatment versus standard of care, where the primary outcome is binary, ordinal, or time-to-event. Our simulated distributions are derived from two sources: longitudinal data on over 500 patients hospitalized at Weill Cornell Medicine New York Presbyterian Hospital and a Centers for Disease Control and Prevention preliminary description of 2449 cases. In simulated trials with sample sizes ranging from 100 to 1000 participants, we found substantial precision gains from using covariate adjustment-equivalent to 4-18% reductions in the required sample size to achieve a desired power. This was the case for a variety of estimands (targets of inference). From these simulations, we conclude that covariate adjustment is a low-risk, high-reward approach to streamlining COVID-19 treatment trials. We provide an R package and practical recommendations for implementation.


Long-term test-retest reliability of event-related potential (ERP) recordings during treadmill walking using the mobile brain/body imaging (MoBI) approach.
Advancements in acquisition technology and signal-processing techniques have spurred numerous recent investigations on the electro-cortical signals generated during whole-body motion. This approach, termed Mobile Brain/Body Imaging (MoBI), has the potential to elucidate the neural correlates of perceptual and cognitive processes during real-life activities, such as locomotion. However, as of yet, no one has assessed the long-term stability of event-related potentials (ERPs) recorded under these conditions. Therefore, the objective of the current study was to evaluate the test-retest reliability of cognitive ERPs recorded while walking. High-density EEG was acquired from 12 young adults on two occasions, separated by an average of 2.3years, as they performed a Go/No-Go response inhibition paradigm. During each testing session, participants performed the task while walking on a treadmill and seated. Using the intraclass correlation coefficient (ICC) as a measure of agreement, we focused on two well-established neurophysiological correlates of cognitive control, the N2 and P3 ERPs. Following ICA-based artifact rejection, the earlier N2 yielded good to excellent levels of reliability for both amplitude and latency, while measurements for the later P3 component were generally less robust but still indicative of adequate to good levels of stability. Interestingly, the N2 was more consistent between walking sessions, compared to sitting, for both hits and correct rejection trials. In contrast, the P3 waveform tended to have a higher degree of consistency during sitting conditions. Overall, these results suggest that the electro-cortical signals obtained during active walking are representative of stable indices of neurophysiological function.


Association of Neighborhood Disadvantage in Childhood With DNA Methylation in Young Adulthood.
DNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health. To ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years. This longitudinal cohort study analyzed data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of children born between 1994 and 1995 in England and Wales and followed up from age 5 to 18 years. Data analysis was performed from March 15, 2019, to June 30, 2019. High-resolution neighborhood data (indexing deprivation, dilapidation, disconnection, and dangerousness) collected across childhood. DNA methylation in whole blood was drawn at age 18 years. Associations between neighborhood socioeconomic disadvantage and methylation were tested using 3 prespecified approaches: (1) testing probes annotated to candidate genes involved in biological responses to growing up in socioeconomically disadvantaged neighborhoods and investigated in previous epigenetic research (stress reactivity-related and inflammation-related genes), (2) polyepigenetic scores indexing differential methylation in phenotypes associated with growing up in disadvantaged neighborhoods (obesity, inflammation, and smoking), and (3) a theory-free epigenome-wide association study. A total of 1619 participants (806 female individuals [50%]) had complete neighborhood and DNA methylation data. Children raised in socioeconomically disadvantaged neighborhoods exhibited differential DNA methylation in genes involved in inflammation (β = 0.12; 95% CI, 0.06-0.19; P < .001) and smoking (β = 0.18; 95% CI, 0.11-0.25; P < .001) but not obesity (β = 0.05; 95% CI, -0.01 to 0.11; P = .12). An epigenome-wide association study identified multiple CpG sites at an arraywide significance level of P < 1.16 × 10-7 in genes involved in the metabolism of hydrocarbons. Associations between neighborhood disadvantage and methylation were small but robust to family-level socioeconomic factors and to individual-level tobacco smoking. Children raised in more socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their less disadvantaged peers. This finding suggests that epigenetic regulation may be a mechanism by which the childhood neighborhood environment alters adult health.


[Cardiological pathology in geological professionals].
The staff of the Medical Center "MEDGEO" have surveyed the working conditions and everyday life determined by the specific features of their watch-and-expeditionary work for their impact on the health status of geological workers. Since 1975, more than 13,000 specialists of the industry and members of their families have been examined in different climatic and geographical regions of the country, including 5,689 persons directly in their working places. More than 3,000 specialists have been studied in the clinical setting by using comprehensive diagnostic techniques. The authors' findings indicate that in the study cohort, there is a paradoxical epidemiological situation with a high risk of death due to arterial hypertension whereas the prevalence of this disease in the watch-and-expeditionary workers do not differ from that in the country's population. According to the authors' data, the reasons for the poor situation associated with circulatory diseases are associated with both the high spread of total risk factors for cardiovascular diseases and the adverse impact of some occupational conditions. The situation is also aggravated by inadequate medical control and by the psychological peculiarities of specialists working in the watch-and-expeditionary manner.


Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study.
The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.


Minimization of sludge production and stable operational condition of a submerged membrane activated sludge process.
Modification of conventional activated sludge process by adding microfiltration type hollow fiber membrane module offers various advantages. The membrane module is immersed directly in the bioreactor to separate the treated water from the sludge and the modified process is called submerged membrane activated sludge process (SMASP). Bench scale SMASP units were operated at constant flux to study the possibility of minimizing the excess sludge production and stable operation at different SRT and BOD loading. The long SRT developed high stabilized MLSS concentration in the bioreactor and decreased the sludge loading rate [kg-BOD/kg-MLSS-d]. In SMASP, very low sludge yield coefficients (0.04-0.09 kg-MLSS/kg-BOD) were obtained at long SRT (500 d) and small BOD loading (< or =0.5 kg/(m3 x d)) as compared to conventional activated sludge process and these coefficients showed considerable minimization in excess activated sludge production. At the same operation conditions, suction pressure was also maintained low (<25 kPa), and then SMASP was operated stably for long time (approximately 200 d).


The ribosomes of Drosophila. III. RNA and protein homology between D. melanogaster and D. virilis.
The extent of interspecific homology between D. melanogaster and D. virilis for ribosomal RNA and ribosomal protein was examined using the techniques of two-dimensional gel electrophoresis, and RNA-DNA filter hybridization. Only 2 of the 71 ribosomal proteins resolved were found to be species specific, while comparisons of soluble larval hemolymph protein patterns showed little similarity. Depending on the technique employed, the sequence homology for 18S + 28S ribosomal RNA was found to be between 83-94%, and sequence homology for 5S rRNA was judged to be complete.


Mpox and Chicken Pox Coinfection Complicated by Acute Urinary Retention: A Case Report.
Mpox and Chicken pox have similar presentations, sometimes causing a diagnostic dilemma. Reports have emerged of coinfections, mostly in the central African region. Index patient is a 23-year-old female who presented with a 2-week history of exanthematous vesiculopustular rashes which started from her genital and groin area with accompanying vulvar swelling. It was then followed by other similar rashes involving mainly her face and limbs with some on her trunk. There was also an associated high grade continuous fever. Rashes were painful and itchy with associated cervical and axillary lymphadenopathy. Following admission, patient had increasing dysuria with accompanying acute urinary retention due to the discomfort accompanying micturition which was relieved by urethral catheterization and resolved with intravenous infusion and parenteral empirical antibiotics for superimposed bacterial infection. Polymerase chain reaction from her skin lesion sample was positive for both monkey pox and chicken pox. She was also given a course of acyclovir and made an uneventful recovery after 12 days of admission and was discharged. We report a rare manifestation of acute urinary retention in a HIV-negative female patient with Mpox and chicken pox co-infection.


Genomic organization and expression profile of the human and mouse WAVE gene family.
The WAVE gene family, which contains three members, has been shown to play a major role in the actin polymerization and cytoskeleton organization processes. We have identified the WAVE3 gene from Chromosome (Chr) 13q12, as being involved in one of the breakpoints of a t(1:13)(q21:q12) reciprocal translocation, in a patient with ganglioneuroblastoma (Sossey-Alaoui et al. 2002; Oncogene 21: 5967-5974). We have also reported the cloning of the mouse Wave3. During our analysis of the human gene map, we also noted that WAVE2 maps to Chr region lp35-36, which frequently undergoes loss of heterozygosity and deletion in advanced stage neuroblastoma. These data clearly indicate a possible involvement of the WAVE genes in the pathogenesis of neuroblastoma. In this study, we report the complete genomic organization and expression profile of the three human WAVE genes and their mouse orthologs. We show that the WAVE genes have distinctive expression patterns in both adult and fetal human and mouse tissues. We also show a high level of conservation between these genes, in both the nucleotide and protein sequences. We finally show that the genomic structure is highly conserved among these genes and that the mouse Wave genes map to chromosome regions that have synteny in the human genome. The gene content in these syntenic regions is also conserved, suggesting that the WAVE genes are derived from a common ancient ancestor by genome duplication. The genomic characterization and expression analysis of the WAVE genes provide the basis towards understanding the function of these genes. It also provides the first steps towards the development of mouse models for the role of the WAVE genes in actin and cytoskeleton organization in general, and in the development of neuroblastoma in particular.


Secular trends of salted fish consumption and nasopharyngeal carcinoma: a multi-jurisdiction ecological study in 8 regions from 3 continents.
Despite salted fish being a classical risk factor of Nasopharyngeal Carcinoma (NPC), whether secular trends in salted fish consumption worldwide accounted for changes in NPC rates were unknown. The relationship between vegetable and cigarette consumption to NPC risk worldwide were also largely uncertain. We investigated the longitudinal trends in standardised NPC incidence/mortality rates across 8 regions and their associations with secular trends in salted fish, vegetable and tobacco consumptions. Age standardised mortality rate (ASMR) and age standardised incidence rate (ASIR) of NPC were obtained from the WHO cancer mortality database and Hong Kong Cancer Registry. Per capita consumption of salted fish, tobacco and vegetables in Hong Kong and 7 countries (China, Finland, Japan, Portugal, Singapore, United Kingdom and United States) were obtained from the Food and Agriculture Organization of the United Nation (FAO) and Hong Kong Trade and Census Statistics. Pearson correlation and multivariate analysis were performed to examine both crude and adjusted associations. There were markedly decreasing trends of NPC ASIR and ASMR in Hong Kong over the past three decades, which were correlated with corresponding secular changes in salted fish consumption per capita (Pearson r for 10 cumulative years : ASIR = 0.729 (male), 0.674 (female); ASMR = 0.943 (male), 0.622 (female), all p < 0.05 except for female ASMR). However such associations no longer correlated with adjustments for decreasing tobacco and increasing vegetable consumption per capita (Pearson r for 10 cumulative years: ASIR = 2.007 (male), 0.339 (female), ASMR = 0.289 (male), 1.992 (female), all p > 0.05). However, there were no clear or consistent patterns in relations between NPC ASIR and ASMR with salted fish consumption across 7 regions in 3 continents. Our results do not support the notion that changes in salted fish consumption had played an important role in explaining secular trends of NPC rates in Hong Kong and worldwide. Further studies should explore other lifestyle and genetic factors. However, our findings do support the potentially protective effects of vegetable consumption against NPC.


Early-stage COVID-19 pandemic observations on pulmonary embolism using nationwide multi-institutional data harvesting.
We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10-4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.


Evidence for the progression through S-phase in the ectopic cell cycle re-entry of neurons in Alzheimer disease.
Aberrant neuronal re-entry into the cell cycle is emerging as a potential pathological mechanism in Alzheimer disease (AD). However, while cyclins, cyclin dependent kinases (CDKs), and other mitotic factors are ectopically expressed in neurons, many of these proteins are also involved in other pathological and physiological processes, generating continued debate on whether such markers are truly indicative of a bona fide cell cycle process. To address this issue, here we analyzed one of the minichromosome maintenance (Mcm) proteins that plays a role in DNA replication and becomes phosphorylated by the S-phase promoting CDKs and Cdc7 during DNA synthesis. We found phosphorylated Mcm2 (pMcm2) markedly associated with neurofibrillary tangles, neuropil threads, and dystrophic neurites in AD but not in aged-matched controls. These data not only provide further evidence for cell cycle aberrations in AD, but the cytoplasmic, rather than nuclear, localization of pMcm2 suggests an abnormal cellular distribution of this important replication factor in AD that may explain resultant cell cycle stasis and consequent neuronal degeneration.


The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer's Disease-related Pathogenesis.
Several studies have revealed that the transcription factor nuclear receptor related 1 (Nurr1) plays several roles not only in the regulation of gene expression related to dopamine synthesis, but also in alternative splicing, and miRNA targeting. Moreover, it regulates cognitive functions and protects against inflammation-induced neuronal death. In particular, the role of Nurr1 in the pathogenesis of Parkinson's disease (PD) has been well investigated; for example, it has been shown that it restores behavioral and histological impairments in PD models. Although many studies have evaluated the connection between Nurr1 and PD pathogenesis, the role of Nurr1 in Alzheimer's disease (AD) remain to be studied. There have been several studies describing Nurr1 protein expression in the AD brain. However, only a few studies have examined the role of Nurr1 in the context of AD. Therefore, in this review, we highlight the overall effects of Nurr1 under the neuropathologic conditions related to AD. Furthermore, we suggest the possibility of using Nurr1 as a therapeutic target for AD or other neurodegenerative disorders.


Outcomes of chronic total occlusion percutaneous coronary intervention from the RAIAN (RAjaie - Iran) registry.
While most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program. This is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year. A global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients' health status improved significantly only in successful group. No significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.


[Survival of single surface ART-restorations in Zimbabwe after 3 years].
A 3 year longitudinal study to assess the survival of single-surface ART restorations, was carried out among first year secondary school students in and around Harare, Zimbabwe, during the period 1993-1996 and 1994-1997. The treatments were provided by dentists and dental therapists. The evaluation was carried out by independent evaluators, one of which was an expert from the USA. Actuarial life-table analysis was applied for survival estimations. The survival of ART restorations after 3 years was 85.3% in 1993-1996 and 88.3% in 1994-1997. The 3-years survival percentage per operator ranged from 96.1% (1993-1996) and 94.3% (1994-1997) for one of the dentists to 69.3% (1993-1996) and 65.4% (1994-1997) for one of the junior dental therapists. In 1994-1997, reasons for failure were predominantly operator and material related. Secondary caries was observed in 0.5% of the ART restorations evaluated. The 3-years survival outcomes of single-surface ART restorations are promising. The study has demonstrated that ART with glass-ionomer restorative material provided quality restorative dental care to these student populations. ART has become one of the treatment modalities available to oral health workers in managing dental caries. There is a need for further research into the efficacy of the ART approach and into its application in various types of communities.


Surgical Management of Thoracolumbar Kyphosis in Patients With Mucopolysaccharidosis: A Systematic Review.
Systematic review. To determine the indications and outcomes for surgical treatment of thoracolumbar kyphosis in patients with mucopolysaccharidoses (MPS) to define future studies. Improvements in the medical treatment of MPS have increased lifespan and improved quality of life for many patients, but with no effect on thoracolumbar kyphosis. A greater number of these challenging patients may now be considered spinal surgical candidates. In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a PubMed database search was conducted using relevant keywords to identify articles describing MPS patients with thoracolumbar kyphosis treated surgically. Information was collected regarding demographics, indications for surgery, surgical details and outcomes. Sixteen articles describing 58 patients were included for review. The median age at surgery was 7 years (range 2.4-65 years) and median follow up was 3.7 years (range 7 weeks-10.3 years). The most commonly reported surgical indication was progression of deformity in 39/58 patients (67%). Preoperative neurological compromise was reported in 7/58 (12%) patients and resolved completely postoperatively in all pediatric patients. Three pediatric patients had died before final follow up. Postoperative paraplegia was reported in 2/51 patients who were neurologically intact preoperatively. Additional significant perioperative medical complications were reported in nine patients. Thoracolumbar spinal surgery is most commonly performed in MPS I. Preoperative neurological compromise associated with thoracolumbar kyphosis was reported only in MPS IV and VI, where it was associated with factors other than the degree of kyphosis. Perioperative complications are common, may be catastrophic and relate to the complexity of the MPS condition. The indications for thoracolumbar kyphosis surgery in other conditions of short stature cannot be extrapolated to MPS patients. 4.


Sex differences in the effects of physical training on sweat gland responses during a graded exercise.
We assessed sex differences in the sweat gland response to changes in exercise intensity with respect to subjects' physical training status. In total, 37 subjects participated (10 trained and 10 untrained females, and 8 trained and 9 untrained males). Each subject cycled continuously at 35, 50 and 65% of their maximal O(2) uptake (V(O2max)) for 60 min at an ambient temperature of 30°C and a relative humidity of 45%. The mean local sweating rate (SR) on the forehead, chest, back, forearm and thigh was significantly greater in the trained subjects than in the untrained subjects of both sexes. The degree of the increase in SR with physical training was greater in males than in females at higher levels of exercise intensity. This increase in SR depended primarily on an increase in the sweat output per gland (SGO) in both sexes. However, control of the SR increase with increasing exercise intensity was altered by training in females, i.e. the increase in SR from exercise at 50 to 65% V(O2max) depended only on an increase in SGO in trained females and males and untrained males, but it depended on increases in activated sweat glands and the SGO in untrained females. It was concluded that training improved the sweating response, and a sex difference was observed in the degree of improvement in the sweating response due to physical training. This sex difference became more pronounced with increasing exercise intensity. A sex difference was observed in the control of sweating rate to an increase in exercise intensity, i.e. the maximal activated sweat gland responses of untrained females required a higher body temperature or work intensity than the other groups.


Event segmentation improves event memory up to one month later.
When people observe everyday activity, they spontaneously parse it into discrete meaningful events. Individuals who segment activity in a more normative fashion show better subsequent memory for the events. If segmenting events effectively leads to better memory, does asking people to attend to segmentation improve subsequent memory? To answer this question, participants viewed movies of naturalistic activity with instructions to remember the activity for a later test, and in some conditions additionally pressed a button to segment the movies into meaningful events or performed a control condition that required button-pressing but not attending to segmentation. In 5 experiments, memory for the movies was assessed at intervals ranging from immediately following viewing to 1 month later. Performing the event segmentation task led to superior memory at delays ranging from 10 min to 1 month. Further, individual differences in segmentation ability predicted individual differences in memory performance for up to a month following encoding. This study provides the first evidence that manipulating event segmentation affects memory over long delays and that individual differences in event segmentation are related to differences in memory over long delays. These effects suggest that attending to how an activity breaks down into meaningful events contributes to memory formation. Instructing people to more effectively segment events may serve as a potential intervention to alleviate everyday memory complaints in aging and clinical populations. (PsycINFO Database Record


[Non-strain methods of hernioplasty in the treatment of postoperative ventral hernias].
In the last 2 years we performed 26 nonstrain hernioplasties for postoperative ventral hernias (16 laparoscopic and 10 open operations). Indications for laparoscopic operation were hernias after "primary" laparotomy, multiple aponeurosis defects, and also demand of simultaneous operations. We preferred open plastics in recurrent hernias, repeated abdominal operations, laparoscopic hernioplasty impossibility revealed during the operation. Fast rehabilitation and their early return to work are advantages of nonstrain hernioplasty. Mean hospital stay was 7.5 days with a general disability of 22.3 days. We believe that open hernioplasty is most simple and reliable. As to laparoscopic hernioplasty, we think it less reliable.


Modification of hemopoietic stem cells of BALB/c mice by Rauscher leukemia virus.
Bone marrow and spleen from Rauscher leukemia virus (RLV) infected BALB/c mice were tested for proliferative activity at various time intervals after infection using the spleen colony assay. Both bone marrow and spleen derived colonies showed a modified maturation behavior. The erythroid colonies were classified into three consecutive stages of maturation according to morphologic criteria. Both bone marrow and spleen derived erythroid colonies exhibited a retardation of maturation upon RLV infection of the donor mice; the spleen derived erythroid colonies showed the most severe changes. RLV itself could not mimic this phenomenon; moreover it was shown by immunofluorescence that only low amounts of RLV were present in the spleen colonies. It is therefore suggested that RLV modifies part of the stem cell compartment leading to a prolonged cycle time of proerythroblasts and hence to a retardation of colony growth.


[Warning signs of eating, depressive, learning disorders and violent behavior among teenagers in Cantabria, Spain].
Teenagers relatively frequently suffer from eating, depressive learning and violent behavior disorders which are often detected late. This study was aimed at investigating the presence of warning signs among teenagers in view of these disorders and to relate them to the social and family environment and living habits. A descriptive, cross-sectional study by means of a survey of 2,178 teenagers in the 12-16 age range, representative of the teenagers of Cantabria. The warning signs were defined based on the American Medical Association and American Psychiatric Association criteria. Warning signs of learning disorders related to the male gender, attending public schools and repeating a year were found among 4.2% of the teenagers. Warning signs of eating disorders and depressive disorders, both related to the female gender, were found respectively among 4.3% and 10.2% of the teenagers. A total of 8.4% showed warning signs of violent behavior, more often among males. The signs investigated are spread homogeneously, increasing with age, and are significantly related to a higher degree of smoking, drinking and illegal drugs, episodes of drunkenness and a certain use of free time on the part of the teenagers, with a higher degree of consumption of addictive substances among friends and family members. The routine assessment during the teen years of warning signs of having the disorders studied would make their early detection possible.


John Charnley Award: Randomized Clinical Trial of Direct Anterior and Miniposterior Approach THA: Which Provides Better Functional Recovery?
The choice of surgical approach for THA remains controversial. Some studies suggest that the direct anterior approach (DAA) leads to less muscle damage than the miniposterior approach (MPA), but there is little high-quality evidence indicating whether this accelerates recovery, or whether this approach-which may be technically more demanding-is associated with component malposition or more complications. (1) Does the DAA result in faster return to activities of daily living than the MPA? (2) Does the DAA have superior patient-reported outcome measures than the MPA? (3) Does the DAA result in improved radiographic outcomes than the MPA? (4) Does the DAA have a higher risk of complications than the MPA? Between March 1, 2013, and May 31, 2016, 116 patients undergoing primary unilateral THA were randomized to either the DAA or MPA; 15 patients withdrew after randomization, and one died 6 months after surgery from a stroke unrelated to the procedure. Recruitment stopped when 52 patients had been randomized into the DAA group and 49 in the MPA group (n = 101). After patient randomization, one high-volume surgeon performed all of the DAAs and three high-volume surgeons performed the MPA THAs. The groups did not differ in age (65 years; SD 11; range, 38-86 years), sex (52% women), or body mass index (mean 29 kg/m; SD 6 kg/m; range, 21-40 kg/m; all p > 0.40). Functional results included time to discontinue gait aids, discontinue all narcotics, and independence with various activities of daily living; accelerometer data evaluated activity level. Clinical and radiographic outcomes, Hip disability and Osteoarthritis Outcome Score, SF-12, and Harris hip scores to 1 year were also tabulated. The minimum followup was 365 days (mean ± SD, 627 ± 369 days). There were slight differences in early functional recovery that favored the DAA versus the MPA: time to discontinue walker use (10 versus 15 days, p = 0.01) and time to discontinue all gait aids (17 versus 24 days, p = 0.04). There were no other differences in early functional milestones, although at 2 weeks after surgery, mean steps per day were 3897 (SD 2258; range, 737-11,010) for the DAA versus 2235 for the MPA (SD 1688; range, 27-7450; p < 0.01). There was no difference in activity monitoring at 1 year. There were no differences in patient-reported outcome scores between the groups. There was no difference in the radiographic parameters measured in the two groups, including leg length discrepancy, component position, or offset, and there was no subsidence observed in any hip. There was no difference in complications between the DAA and the MPA groups (8% [four of 52] versus 10% [five of 49]; p = 0.33). Both the DAA and MPA approaches provided excellent early recovery with a low risk of complications. Patients undergoing the DAA had a slightly faster recovery, as measured by milestones of function and quantified by activity monitor data, but no substantive differences were evident at 2 months. Because the DAA is the less studied approach, longer term (> 1 year) complications may yet accrue, will be important to quantify, and may offset early benefits. Level I, therapeutic study.