Genetic Diversity, Distribution, and Genomic Characterization of Antibiotic Resistance and Virulence of Clinical Pseudomonas aeruginosa Strains in Kenya.
Pseudomonas aeruginosa is a leading cause of nosocomial infections worldwide. It can produce a range of debilitating infections, have a propensity for developing antimicrobial resistance, and present with a variety of potent virulence factors. This study investigated the sequence types (ST), phenotypic antimicrobial susceptibility profiles, and resistance and virulence genes among clinical isolates from urinary tract and skin and soft tissue infections. Fifty-six P. aeruginosa clinical isolates were obtained from six medical centers across five counties in Kenya between 2015 and 2020. Whole-genome sequencing (WGS) was performed to conduct genomic characterization, sequence typing, and phylogenetic analysis of the isolates. Results showed the presence of globally distributed high-risk clones (ST244 and ST357), local high-risk clones (ST2025, ST455, and ST233), and a novel multidrug-resistant (MDR) clone carrying virulence genes (ST3674). Furthermore, 31% of the study isolates were found to be MDR with phenotypic resistance to a variety of antibiotics, including piperacillin (79%), ticarcillin-clavulanic acid (57%), meropenem (34%), levofloxacin (70%), and cefepime (32%). Several resistance genes were identified, including carbapenemases VIM-6 (ST1203) and NDM-1 (ST357), fluoroquinolone genes, crpP, and qnrVCi, while 14 and 22 different chromosomal mutations were detected in the gyrA and parC genes, respectively. All isolates contained at least three virulence genes. Among the virulence genes identified, phzB1 was the most abundant (50/56, 89%). About 21% (12/56) of the isolates had the exoU+/exoS- genotype, while 73% (41/56) of the isolates had the exoS+/exoU- genotype. This study also discovered 12 novel lineages of P. aeruginosa, of which one (ST3674) demonstrated both extensive antimicrobial resistance and the highest number of virulence genes (236/242, 98%). Although most high-risk clones were detected in Nairobi County, high-risk and clones of interest were found throughout the country, indicating the local spread of global epidemic clones and the emergence of new strains. Thus, this study illustrates the urgent need for coordinated local, regional, and international antimicrobial resistance surveillance efforts.


[Towards cultivation of the abilities of young uro-andrological surgeons in clinical practice and research in the big data era].
With the rise of individualized medicine, precision medicine and translational medicine in the big data era, the application of Internet big data in the medical field is becoming an irresistible trend. Confronted with this new trend, it is urgent to improve the abilities of young uro-andrological surgeons in clinical practice and research exploration with the help of big data. This paper explored the methods of cultivating the abilities of young uro-andrological surgeons in clinical practice and research using big data bases.


Non-Coding RNAs as Predictive Biomarkers to Current Treatment in Metastatic Colorectal Cancer.
The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could lead to an improvement in the success rate of the proposed therapies. Although the process of biomarker selection and validation could be a long one, requiring solid statistics, large cohorts and multicentric validations, non-coding RNAs (ncRNAs) and in particular microRNAs, proved to be extremely promising in this field. Here we summarize some of the main studies correlating specific ncRNAs with sensitivity/resistance to chemotherapy, anti-VEGF therapy, anti-EGFR therapy and immunotherapy in colorectal cancer (CRC).


Cellular memory in spinal nociceptive circuitry.
Besides transmitting and processing, neurons may also store information for prolonged periods of time (e.g. by use-dependent change in synaptic strength). In 1966 long-term potentiation (LTP) of synaptic transmission was discovered in the hippocampus, an area implicated in learning and memory. Recent studies show that similar mechanisms apply to pain pathways, at least in the spinal cord, and may account for some forms of clinical problems like hyperalgesia, allodynia, and deafferentation pain states, such as phantom pain. In this review, we briefly summarize key aspects of synaptic plasticity known from the brain and in the spinal cord. Then we describe and discuss related changes in spinal nociceptive neurons based on results from our own laboratory.


alpha-Hydroxytamoxifen, a metabolite of tamoxifen with exceptionally high DNA-binding activity in rat hepatocytes.
It has been proposed that the antiestrogen tamoxifen induces liver tumors in rats and genotoxic effects in vitro through metabolic activation involving, initially, alpha-hydroxylation of the ethyl group. To test this hypothesis, the extent of DNA adduct formation in primary rat hepatocytes treated with tamoxifen and alpha-hydroxytamoxifen was investigated. Hepatocytes from female Fischer F-344 rats were treated with 1 or 10 microM concentrations of either alpha-hydroxytamoxifen or tamoxifen. DNA was isolated and analyzed for the presence of DNA adducts by 32P postlabeling. Chromatography on polyethyleneimine cellulose thin layer chromatography and reverse-phase high performance liquid chromatography revealed that the same pattern of adducts was formed by both compounds. However, the level of adduct formation was 25 and 49 times greater with alpha-hydroxytamoxifen than with tamoxifen at 1 and 10 microM, respectively. The formation of alpha-hydroxytamoxifen as a metabolite of tamoxifen was demonstrated by mass spectrometric analysis of the extracted culture medium. alpha-Hydroxytamoxifen was found to react with DNA in the absence of metabolizing enzymes. These results demonstrate the involvement of alpha-hydroxylation in the metabolic activation of tamoxifen.


Delayed recurrent thromboembolism of the allograft kidney.
Renal artery thromboembolism is a rare event in native kidneys and has never been reported to occur in allograft kidney. We report a case of allograft kidney infarction secondary to embolisation from thrombus in the hypogastric artery supplying the allograft on two separate occasions 1 and 2 years after transplant. Anticoagulation therapy alone was given and the patient responded well with partial recovery of renal function.


Is the world finally waking up to HIV/AIDS in prisons? A report from the XV International AIDS Conference.
Issues related to HIV/AIDS in prisons have traditionally received little attention at the International AIDS Conference, despite the fact that levels of HIV prevalence within prison populations tend to be much higher than in the general population. However, the conference in Bangkok may represent a turning point. This article highlights some of the relevant findings presented at the conference. A longer version of this article, including background information about HIV/AIDS in prisons worldwide, has been published in the September 2004 issue of Infectious Diseases in Corrections Report.


[Study on propagation form of nerve impulse waves].
Hodgkin-Huxley model is the indispensable mathematics basis for the study of neuro-electro-physiology. But so far, there is few analytic study about H-H neuron model. In this paper, the features of the classical H-H model are analyzed, and then a simplified H-H model and Nagumo equation are proposed, and their solitary wave solutions are first obtained with the homogeneous balance method. The study shows that nerve impulse may propagate with the mode of solitary wave.


Perinatal results following the prenatal ultrasound diagnosis of single umbilical artery.
To study the perinatal results in our population, following the prenatal ultrasound diagnosis of a single umbilical artery (SUA), as this alteration is associated with fetal malformations, chromosomal abnormality, and poor perinatal results. A retrospective review of all obstetric ultrasounds carried out between October 2000 and December 2003 in our service, obtaining the postnatal results of the fetuses diagnosed with an SUA. From a total of 5,987 pregnant patients examined by ultrasound scan at 20th week, an SUA was found in 40 cases, representing an incidence of 0.7%. Of these, 84.6% were normal pregnancies at birth and 15.4% presented other malformations and/or chromosomal abnormalities. No aneuploidy was found in pregnancies where there were no other associated findings in the ultrasound scan at 20 weeks. All cases with serious congenital malformations accompanying the SUA were diagnosed prenatally. There was a 5% of perinatal mortality rate among our fetuses with SUA, which represents a mortality rate 10 times greater than the overall rate among our patients. The ultrasound discovery of an SUA implies the meticulous search for other associated malformations, and in the absence of these, the risk of a chromosomal abnormality is very low, unless it is a high-risk patient. However, the growth and wellbeing of the fetus must be carefully monitored in the last 3 months, although the ultrasound scan does not show any other associated alterations.


Different effects of sevoflurane, desflurane, and isoflurane on early and late left ventricular diastolic function in young healthy adults.
Knowledge on the effects of volatile anaesthetics on left ventricular (LV) diastolic function in humans in vivo is limited. We tested the hypothesis that sevoflurane, desflurane, and isoflurane do not impair LV diastolic function in young healthy humans. Sixty otherwise healthy subjects (aged 18-48 yr) undergoing minor procedures under general anaesthesia were studied. After randomization for the anaesthetic, transthoracic echocardiographic examinations were performed at baseline and under anaesthesia with 1 minimum alveolar concentration (MAC) of the volatile anaesthetics during spontaneous breathing and intermittent positive pressure ventilation (IPPV). Peak early (E') and late (A') diastolic velocities of the mitral annulus were studied as the main echocardiographic indicators of diastolic function. During anaesthesia with 1 MAC under spontaneous breathing, E' increased with desflurane (P<0.001), was not significantly different with isoflurane (P=0.030), and decreased with sevoflurane (P=0.006). During IPPV, E' was similar to baseline with desflurane (P=0.550), insignificantly decreased with isoflurane (P=0.029), and decreased with the sevoflurane group (P<0.001). In contrast, A' was similarly reduced in all groups during spontaneous breathing without further changes during IPPV. Haemodynamic changes were comparable in all study groups. The findings of this in vivo study indicate that desflurane and isoflurane, and most likely sevoflurane, have no relevant direct negative effect on early diastolic relaxation in young healthy humans. In contrast, all three volatile anaesthetics appear to impair late diastolic LV filling during atrial contraction.


ABP1 and ROP6 GTPase signaling regulate clathrin-mediated endocytosis in Arabidopsis roots.
The dynamic spatial and temporal distribution of the crucial plant signaling molecule auxin is achieved by feedback coordination of auxin signaling and intercellular auxin transport pathways. Developmental roles of auxin have been attributed predominantly to its effect on transcription; however, an alternative pathway involving AUXIN BINDING PROTEIN1 (ABP1) has been proposed to regulate clathrin-mediated endocytosis in roots and Rho-like GTPase (ROP)-dependent pavement cell interdigitation in leaves. In this study, we show that ROP6 and its downstream effector RIC1 regulate clathrin association with the plasma membrane for clathrin-mediated endocytosis, as well as for its feedback regulation by auxin. Genetic analysis revealed that ROP6/RIC1 acts downstream of ABP1 to regulate endocytosis. This signaling circuit is also involved in the feedback regulation of PIN-FORMED 1 (PIN1) and PIN2 auxin transporters activity (via its constitutive endocytosis) and corresponding auxin transport-mediated processes, including root gravitropism and leave vascular tissue patterning. Our findings suggest that the signaling module auxin-ABP1-ROP6/RIC1-clathrin-PIN1/PIN2 is a shared component of the feedback regulation of auxin transport during both root and aerial development.


Cryptosporidium and Giardia Infections in Children: A Review.
Diarrheal disease remains the second leading cause of mortality in children in developing countries. Cryptosporidium is a leading cause and its importance stands to increase as rotavirus vaccine becomes used around the world. Cryptosporidium is particularly problematic in children younger than 2 years old and in the immunocompromised. Giardia lamblia is a common intestinal protozoan that is associated with diarrhea and, perhaps, growth faltering in impoverished settings. This review establishes the current prevalence of these infections in global settings and reviews current diagnosis and management approaches.


Eccentric Exercise to Enhance Neuromuscular Control.
Neuromuscular alterations are a major causal factor of primary and secondary injuries. Though injury prevention programs have experienced some success, rates of injuries have not declined, and after injury, individuals often return to activity with functionality below clinical recommendations. Considering alternative therapies to the conventional concentric exercise approach, such as one that can target neuromuscular injury risk and postinjury alterations, may provide for more effective injury prevention and rehabilitation protocols. Peer-reviewed sources available on the Web of Science and MEDLINE databases from 2000 through 2016 were gathered using searches associated with the keywords eccentric exercise, injury prevention, and neuromuscular control. Eccentric exercise will reduce injury risk by targeting specific neural and morphologic alterations that precipitate neuromuscular dysfunction. Clinical review. Level 4. Neuromuscular control is influenced by alterations in muscle morphology and neural activity. Eccentric exercise beneficially modifies several underlying factors of muscle morphology (fiber typing, cross-sectional area, working range, and pennation angle), and emerging evidence indicates that eccentric exercise is also beneficial to peripheral and central neural activity (alpha motorneuron recruitment/firing, sarcolemma activity, corticospinal excitability, and brain activation). There is mounting evidence that eccentric exercise is not only a therapeutic intervention influencing muscle morphology but also targets unique alterations in neuromuscular control, influencing injury risk.


Frequency of Hepatitis C in hospitalized patients with chronic kidney disease.
Hepatitis C and chronic kidney disease (CKD) are major global health problems and are highly prevalent in Pakistan. There is limited information on prevalence of hepatitis C in patients with CKD not yet on dialysis. The objective of this study was to determine the frequency of hepatitis C in hospitalized chronic kidney disease patients at a tertiary care center in Pakistan. The study design was cross-sectional in nature. Patients between ages of 20-80 years with CKD not previously on renal replacement therapy and who were admitted to nephrology ward at a tertiary care facility were included. Hepatitis C was tested using 3rd generation enzyme linked immunosorbent assay (ELISA). Hepatitis C RNA was tested by polymerase chain reaction (PCR) in patients with positive ELISA. A total of 180 patients were included in the study. Mean age of patients was 48.7±14.9 years. Of all patients, 105 (58.3%) were males and 75 (41.7%) were females, 152 (84.4%) had hypertension, 113 (62.8%) had diabetes mellitus and 26 (14.9%) had known cardiovascular disease. Mean eGFR of patients was 11.4±9.4 ml/min/1.73 m2. Of all patients with CKD, 49 (27.2%) had hepatitis C test positive by ELISA. Hepatitis C PCR testing was done in 39 patients with hepatitis C ELISA positive status and 29 (74.4%) tested positive. Risk factors and clinical characteristics of patients with and without positive hepatitis C antibody by ELISA were similar. A significant proportion of hospitalized CKD patients have hepatitis C. Strict universal infection control measures should be implemented in nephrology wards to prevent transmission of hepatitis C infection.


Regulation of lipid synthesis genes and milk fat production in human mammary epithelial cells during secretory activation.
Expression of genes for lipid biosynthetic enzymes during initiation of lactation in humans is unknown. Our goal was to study mRNA expression of lipid metabolic enzymes in human mammary epithelial cell (MEC) in conjunction with the measurement of milk fatty acid (FA) composition during secretory activation. Gene expression from mRNA isolated from milk fat globule (MFG) and milk FA composition were measured from 6 h to 42 days postpartum in seven normal women. Over the first 96 h postpartum, daily milk fat output increased severalfold and mirrored expression of genes for all aspects of lipid metabolism and milk FA production, including lipolysis at the MEC membrane, FA uptake from blood, intracellular FA transport, de novo FA synthesis, FA and glycerol activation, FA elongation, FA desaturation, triglyceride synthesis, cholesterol synthesis, and lipid droplet formation. Expression of the gene for a key lipid synthesis regulator, sterol regulatory element-binding transcription factor 1 (SREBF1), increased 2.0-fold by 36 h and remained elevated over the study duration. Expression of genes for estrogen receptor 1, thyroid hormone-responsive protein, and insulin-induced 2 increased progressively to plateau by 96 h. In contrast, mRNA of peroxisome proliferator-activated receptor-γ decreased severalfold. With onset of lactation, increased de novo synthesis of FA was the most prominent change in milk FA composition and mirrored the expression of FA synthesis genes. In conclusion, milk lipid synthesis and secretion in humans is a complex process requiring the orchestration of a wide variety of pathways of which SREBF1 may play a primary role.


Nuclear resonant scattering measurements on (57)Fe by multichannel scaling with a 64-pixel silicon avalanche photodiode linear-array detector.
We developed a silicon avalanche photodiode (Si-APD) linear-array detector for use in nuclear resonant scattering experiments using synchrotron X-rays. The Si-APD linear array consists of 64 pixels (pixel size: 100 × 200 μm(2)) with a pixel pitch of 150 μm and depletion depth of 10 μm. An ultrafast frontend circuit allows the X-ray detector to obtain a high output rate of >10(7) cps per pixel. High-performance integrated circuits achieve multichannel scaling over 1024 continuous time bins with a 1 ns resolution for each pixel without dead time. The multichannel scaling method enabled us to record a time spectrum of the 14.4 keV nuclear radiation at each pixel with a time resolution of 1.4 ns (FWHM). This method was successfully applied to nuclear forward scattering and nuclear small-angle scattering on (57)Fe.


Does Pacifier Use in Infancy Decrease the Risk of Obesity?
Nonnutritive sucking using a finger or pacifier is a natural reflex for infants. We hypothesized that infants may overfeed if the bottle or breast is constantly offered. Our goal was to determine whether pacifier use in early infancy is associated with lower incidence of obesity at later age. Parents of 399 infants, 9 to 15 months old, were interviewed and asked whether a pacifier was used consistently for ≥9 months. Body mass indexes at birth, 6 months, and on the day of interview were calculated. In all, 204 (51%) infants used a pacifier, and 195 (49%) were nonusers. More infants in the nonuser group were either overweight-40 (21%)-or obese-32 (16%)-than in the user group-22 (11%) and 22 (11%), respectively ( P = .003). Pacifier use in infancy was associated with lower incidence of obesity at 9 to 15 months of age. Offering a pacifier can be protective against infantile obesity.


[Clinical and neurologic characteristic and principles of therapy of late-onset Myasthenia gravis].
In the present work the results of the clinic-epidemiological analysis of 223 patients with the onset of the myasthenia at 60 y. o. and later, admitted and treated in the clinic of neurology for the passed 25years are represented. A dynamic growth of incidence of the late-onset myasthenia through the passed 10 years was administered. We administered a prevalence of the generalized form of the myasthenia gravis (61,5 %). The whole clinical table of the myasthenia was developed during an year in 76,7 % of the cases. A wide range of the concomitant somatic pathology in this group of the patients (especially, with a cardio-vascular pathology - 93,3 %) was found to worsen the course of the myasthenia itself. We found that the set of the therapeutic measures in myasthenia in the elderly is determined by the course of the myasthenia and the multiple organ failure due to the concomitant diseases. The scheme of complex corrective therapy of myasthenia gravis in elderly was developed.


Acoustic information masking effects of natural sounds on traffic noise based on psychological health in open urban spaces.
The use of existing resources, such as natural sounds, to promote the mental health of citizens is an area of research that is receiving increasing attention. This research contributes to existing knowledge by combining a field psychological walk method and an experimental acoustic control method to compare the acoustic information masking effects of water and birdsong sounds on traffic noise based on the psychological health responses of 30 participants to such effects. The influence of traffic noise and contextual sounds on the psychological health of participants identified the potential of natural sounds in the acoustic information masking of traffic noise. Furthermore, it was found that 65.0 dBA water sounds did not mask 60.0 dBA traffic noises. However, 45.0 dBA birdsong sounds did mask it, but this effect was not significant. Additionally, contextual factors with and without crowd activity sounds were not significant in influencing psychological health through birdsong. This study contributes to public health cost savings. It may also guide the development of new ideas and methods for configuring open urban spaces according to public health needs.


Some histological and histochemical studies of the pancreas of the Brasilian sloth, Bradypus tridactylus.
The histological and histochemical study of the pancreas of the three-toed sloth, Bradypus tridactylus, demonstrated that with the methods employed the pancreatic islets are apparently formed by A cells exclusively. Two different types of argyrophilic cells were noticed in the exocrine secretory units when Grimelius' method was used. The methods for the demonstration of D cells showed negative results. Aldehyde fuchsin-positive granules were only noticed at the apex of the exocrine pancreatic cells. These results are discussed in relation to current hypotheses concerning the evolution of insulin secretion mechanisms.


Kin recognition: evidence that humans can perceive both positive and negative relatedness.
The evolution of spite entails actors imposing costs on 'negative' relatives: those who are less likely than chance to share the actor's alleles and therefore more likely to bear rival alleles. Yet, despite a considerable body of research confirming that organisms can recognize positive relatives, little research has shown that organisms can recognize negative relatives. Here, we extend previous work on human phenotype matching by introducing a cue to negative relatedness: negative self-resembling faces, which differ from an average face in the opposite direction to the way an individual's own face differs from the average. Participants made trustworthiness and attractiveness judgements of pairs of opposite-sex positive and negative self-resembling faces. Analyses revealed opposing effects of positive and negative self-resembling faces on trustworthiness and attractiveness judgements. This is the first clear evidence that humans are sensitive to negative relatedness cues, and suggests the potential for the adaptive allocation of spiteful behaviour.


Morphology of an Early Oligocene beaver Propalaeocastor irtyshensis and the status of the genus Propalaeocastor.
The Early to Late Oligocene Propalaeocastor is the earliest known beaver genus from Eurasia. Although many species of this genus have been described, these species are defined based on very fragmentary specimens. Propalaeocastor irtyshensis from the Early Oligocene Irtysh River Formation in northwestern Xinjiang, China is one of the earliest-known members of Propalaeocastor. This species is defined on a single maxillary fragment. We revise the diagnosis of P. irtyshensis and the genus Propalaeocastor, based on newly discovered specimens from the Irtysh River Formation. The dental morphology of P. irtyshensis is very similar to other early castorids. The caudal palatine foramen of P. irtyshensis is situated in the maxillary-palatine suture. This is a feature generally accept as diagnostic character for the castorids. On the other hand, P. irtyshensis has two upper premolars, a rudimentarily developed sciuromorph-like zygomatic plate, and a relatively large protrogomorph-like infraorbital foramen. Some previous researchers suggested that Propalaeocastor is a junior synonym of Steneofiber, while other took it as a valid genus. Our morphological comparison and phylogenetic analysis suggest that Propalaeocastor differs from Steneofiber and is a valid genus. We also suggest that Agnotocastor aubekerovi, A. coloradensis, A. galushai, A. readingi, Oligotheriomys primus, and "Steneofiber aff. dehmi" should be referred to Propalaeocastor. Propalaeocastor is the earliest and most basal beaver. The origin place of Propalaeocastor and castorids is uncertain. The Early Oligocene radiation of castorids probably is propelled by the global climate change during the Eocene-Oligocene transition.


Older and (emotionally) smarter? Emotional intelligence as a mediator in the relationship between age and emotional labor strategies in service employees.
BACKGROUND/STUDY CONTEXT: The purpose of the current study was to investigate whether age was related to emotional labor strategies (surface and deep acting), and whether emotional intelligence partially explained this relationship. Additionally, employee well-being was examined as an outcome in this model. A total of 519 participants (age 18-68), working in a variety of service occupations, participated in a cross-sectional survey study. Validated measures for emotional intelligence, emotional labor strategies, positive affectivity, and employee well-being were administered. A structural equation model supported the hypothesis that age was related positively to deep acting and negatively to surface acting, relationships partially mediated by emotional intelligence. Emotional labor strategy, in turn, affected well-being. Implications were discussed in employee selection and employee well-being, particularly in the customer service context. It is recommended that future research investigates how aging is related to emotional labor strategies in other occupations that have different emotional requirements (e.g., negative display rules).


Triethanolamine zinc phosphite, (C6H13NO3)Zn2(HPO3): a templated network or a network of clusters?
(C6H13NO3)Zn2(HPO3) (I) displays an extended hybrid organic/inorganic structure in which the triethanolamine organic species acts as an anionic tetradentate ligand, rather than a typical protonated cationic template. Crystal data for I: Mr = 357.89, monoclinic, P2(1)/c (no. 14), a = 8.4216(4) angstroms, b = 9.9262(5) angstroms, c = 12.8494(6) angstroms, beta = 91.824(1) degrees, V = 1073.6(1) angstroms3, Z = 4.


The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells.
gamma-Glutamyl hydrolase has been partially purified and characterized from conditioned culture medium of H35 hepatoma cells. Evidence for heterogeneity of the enzyme is derived from its elution as three distinct peaks of enzymatic activity when the enzyme is purified by TSK-butyl-Sepharose column chromatography. These three enzyme fractions appear to have identical catalytic properties but, as yet, the basis for their resolution is not understood. A rapid, sensitive and simple assay based on reverse-phase HPLC fluorescent detection with pre-column derivatization using o-phthalaldehyde (OPA) was developed to separate OPA-derivatives of poly-gamma-glutamates and glutamic acid. Using this assay and the standard HPLC assay for pteroylpolyglutamates, the enzyme appears to be an endopeptidase with respect to pteroylpenta-gamma-glutamate (PteGlu5), methotrexate penta-gamma-glutamate (4-NH2-10-CH3PteGlu5) and p-aminobenzoyl-penta-gamma-glutamate (pABAGlu5). The initial products are PteGlu1 (or 4-NH2-10-CH3PteGlu1 or pABAGlu1) and intact tetra-gamma-glutamate, which is subsequently degraded to glutamic acid. When penta-gamma-glutamate is the substrate, the cleavage of the gamma-bonds by the enzyme is less ordered, with the early appearance of mono-, di-, tri- and tetraglutamate. Poly-alpha-glutamate is not a substrate nor are pABA-gamma-Glu5 or penta-gamma-glutamate covalently linked to albumin. 4-NH2-10-CH3PteGlu2 or Glu5 bound to dihydrofolate reductase is not a substrate for the enzyme, offering further evidence that protein-associated poly-gamma-glutamates are poor substrates for gamma-glutamyl hydrolase from H35 hepatoma cells.


Developmental dysplasia of the hip and clubfoot treated by Pavlik and Ponseti methods.
Children having both typical developmental dysplasia of the hip (DDH) and clubfoot are rare, and early treatments of both conditions are recommended. The aim of this study was to evaluate the effects of the Ponseti method of clubfoot treatment on hips with DDH. After institutional review board approval, we identified children treated by the Ponseti and Pavlik methods between 2003 and 2016. During the Ponseti method treatment, the duration of manipulations, number of casts, tenotomies performed, and days in clubfoot orthosis were recorded. During DDH treatment, we registered duration for Pavlik and hip brace usage. Hips had dynamic sonography and radiographic evaluations. The cases were grouped according to the combination of DDH and clubfoot treatments: (a) concurrent, (b) sequential, and (c) hip observation. Seven cases of DDH and clubfoot were identified. The average number of Ponseti casts was 5.8 (range: 4-8 casts). The average number of days following the post-Achilles-tenotomy casting to the end of clubfoot bracing was 870 days (range: 90-1605 days). Eleven (four bilateral cases and three unilateral) clubfeet were corrected initially by the Ponseti method. The average number of days for Pavlik harness treatment was 74 (range: 10-126 days). Additionally, a hip orthosis was utilized in three children for an average of 131 days. At follow-up, all children had a high femoral neck-shaft angle averaging 152° (range: 144°-164°). One child (case 5) developed avascular necrosis of the femoral head, Kalamchi type I. Children with typical and nonsyndromic DDH and clubfoot treated by Pavlik harness and Ponseti methods are associated with abnormal hip development (coxa valga).


[The advance in researches for biomedical intelligent polymer materials].
The properties of biomedical intelligent polymer materials can be changed obviously when there is a little physical or chemical change in external condition. They are in the forms of solids, solutions and polymers on the surface of carrier, including aqueous solution of hydrophilic polymers, cross-linking hydrophilic polymers (i.e. hydrogels) and the polymers on the surface of carrier. In this paper are reviewed the progress in researches and the application of biomedical intelligent polymer materials.


Favorable internal hernia rate achieved using retrocolic, retrogastric alimentary limb in laparoscopic Roux-en-Y gastric bypass.
The present study was performed at a tertiary care university hospital. The present study examined the incidence of internal hernia (IH) in our series of laparoscopic Roux-en-Y gastric bypass (LRYGB) with retrocolic, retrogastric routing of the alimentary limb accompanied by routine secure closure of all mesenteric defects. During a 4-year period, 847 patients underwent LRYGB. Our operative technique included retrocolic, retrogastric placement of the alimentary limb. The enteroenterostomy mesenteric defect, mesocolic defect, and Petersen defect were routinely closed in running fashion with nonabsorbable suture. The study population had a mean age of 42.4 +/- 9.3 years and a mean preoperative body mass index of 45.3 +/- 5.6 kg/m(2). The mean operative time was 154 +/- 25 minutes. The mean excess body weight loss at 1 year was 70%. The incidence of IH among this large study population was 0%. A total of 11 patients (1.3%) presented with symptoms concerning for IH, most commonly nausea, vomiting, and crampy abdominal pain, from 1 month to 6 years after the initial surgery. On re-exploration, 4 patients had adhesive small bowel obstruction, 4 had adhesions without obstruction, 1 had small bowel intussusception, and 2 patients had negative findings. IH is a serious complication of LRYGB that can lead to catastrophic morbidity and mortality. We advocate vigilant screening for this complication and laparoscopic exploration for patients with worrisome symptoms. Our data have indicated that a routine and consistent technique to securely close the mesenteric defects can significantly reduce the risk of IH associated with retrocolic, retrogastric placement of the alimentary limb during LRYGB.


Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ.
Endothelin receptor A (ETAR) promotes tumorigenesis by stimulating cell proliferation, migration, and survival. However, the mechanism of ETAR in promoting tumor growth is largely unknown. In this study, we demonstrate that ETAR stimulates colon cell proliferation, migration, and tumorigenesis through the activation of YAP/TAZ, two transcription coactivators of the Hippo tumor suppressor pathway. Endothelin-1 treatment induced YAP/TAZ dephosphorylation, nuclear accumulation, and transcriptional activation in multiple colon cancer cells. ETAR stimulation acted via downstream G-protein Gαq/11 and Rho GTPase to suppress the Hippo pathway, thus leading to YAP/TAZ activation, which was required for ETAR-induced tumorigenesis. Overall, these results indicate a critical role of the YAP/TAZ axis in ETAR signaling. Cancer Res; 77(9); 2413-23. ©2017 AACR.


Importance of early electrocardiographic recognition and timely management of hyperkalemia in geriatric patients.
Hyperkalemia is a potentially life-threatening electrolyte imbalance that can be difficult to diagnose due to the paucity of specific signs and symptoms. Because hyperkalemia can lead to sudden death from cardiac arrhythmias and asystole, any patient whose history, physical examination or laboratory studies raise clinical suspicion of hyperkalemia requires an immediate 12-lead electrocardiogram to ascertain whether electrocardiographic manifestations of electrolyte imbalance are present. The current report describes a case involving an elderly man who developed hyperkalemia secondary to acute-on-chronic kidney injury. Factors affecting the vulnerability of geriatric patients to hyperkalemia, the electrocardiographic manifestations of elevated serum potassium levels, and the importance of timely recognition and management are discussed. Understanding the factors that contribute to hyperkalemia, timely recognition of electrocardiogram changes and timely initiation of appropriate therapy are all critical in the approach to hyperkalemia in the geriatric patient.


Hydrogen and Oxygen Isotope Fractionation Effects in Different Organ Tissues of Grapes under Drought Conditions.
A study of different grapevine tissues and organs (root, stem, leaf, fruit) water isotope fractionation models from high-quality wine grapes produced in the Helan Mountains, a key wine-producing area in northwestern China, was undertaken. Results showed that δ2H values of local groundwater sources were more negative than rivers and precipitation. Soil water δ2H and δ18O values were significantly higher than those of other environmental water sources. Water from the soil surface layer (0-30 cm, δ2H and δ18O values) was more positive than the deeper layer (30-60 cm), indicating that soil water has undergone a positive fractionation effect. δ2H and δ18O values of tissues and organs from different grape varieties followed a similar pattern but were more negative than the local atmospheric precipitation line (slope between 4.1 to 5.2). The 2H and 18O fractionation relationship in grapevine organs was similar, and 18O has a higher fractionation effect than 2H. δ2H and δ18O values showed a strong fractionation effect during the transportation of water to different grape organs (trend of stem > fruit > leaf). This study showed that 18/16O fractionation in grapes is more likely to occur under drought conditions and provides a theoretical basis to improve traceability accuracy and origin protection of wine production areas.


Antioxidant activity in mung bean sprouts and safety of extracts for cosmetic use.
The antioxidant activity of mung bean sprouts was studied in this research. Active ingredients in different lengths of mung bean sprouts were extracted with water. Concentrations of the main proteins and polyphenols were determined. Antioxidizing capacities of the extracts were measured in vitro using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test, ferric reducing antioxidant power method, and chelation abilities of ferrous ion. The safety of the extracts was determined using the red blood cell (RBC) test, chick chorioallantoic membrane (CAM) assay, and human skin patch test. Results show that DPPH radical scavenging rates at different shoot lengths were all greater than 85%, while the total antioxidant capacity of the extracts reached more than 4.0 and the chelation abilities of first-day sprout extract is nearly 80%, indicating that mung bean sprouts have excellent anti-oxygenic property. Results of RBC (hemolysis ratio), CAM (vascular morphological), and human skin patch tests (changed subjects) illustrated extracts of mung bean sprouts are safe and can be used as additives in antiaging cosmetic products.


Design and qualification of a bench-scale model for municipal waste-to-energy combustion.
This paper reports the design and qualification of the first purpose-built, bench-scale reactor system to model the municipal waste-to-energy combustion of fluorinated polymers. Using the principle of similarity, the gas-phase combustion zone of a typical municipal waste-to-energy plant has been scaled down to the bench with a focus on chemical similarity. Chemical similarity is achieved in large part through the use of methanol as a surrogate for municipal solid waste (MSW). Review of prior research shows that methanol is one of the major volatile products expected during MSW thermal conversion in the fuel bed of waste-to-energy plants. Like full-scale waste-energy plants, the design of the bench-scale model includes a flame zone and a post-flame zone. Maintaining steady methanol vapor flow premixed with air to the model reactor system ensures stable combustion resulting in bench-scale CO emission levels comparable to those of full-scale waste-to-energy plants. Since investigation of fluorinated polymer combustion includes trace analysis of exhaust gas for perfluorooctanoic acid (PFOA), qualification testing focused on PFOA collection efficiency. High PFOA collection efficiency (>90%) demonstrated the capability of the reactor system in transporting and absorbing PFOA that may be generated during high-temperature combustion testing of fluorinated polymers. Overall, the bench-scale system is qualified for its intended use to investigate potential generation of PFOA from combustion of fluorinated polymers under conditions representative of waste-to-energy combustion.Implications: Decision-makers depend on environmental researchers to provide reliable predictions of pollutant emissions from waste combustion of polymers at end of product life. Reliable predictions are especially important with regard to questions about potential PFOA emissions from municipal waste combustion of fluorinated polymers. Results from qualification testing confirm that the novel bench-scale model reactor system is capable of representing gas-phase municipal waste combustion behavior upstream of air pollution control and generating representative exhaust gas samples for off-line trace-level analysis of PFOA.


SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis.
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. One hundred and six MB samples were examined. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA, FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and α-synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA revealed the ability of this gene to inhibit tumor invasion and induce apoptosis. Methylation-specific PCR and pyrosequencing analysis showed that epigenetic mechanisms, rather than DNA hypermethylation, might play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.


[Adenomatoid tumor of the uterus--2 case reports].
We report two cases of the so-called adenomatoid tumor of the uterus, which have been detected in patients who underwent surgery for leiomyomas. The clinical signs, origin and immunohistochemical characteristics of the adenomatoid tumor are described. Adenomatoid tumors are slow growing epithelioid neoplasias with a co-expression of vimentin and cytokeratins. The characteristic cytokeratins are numbered 7, 8, 18, 19 and 5. The mesothelial histogenesis of the tumor can be confirmed. Our results rule out origins from Müllerian or mesonephrogenous ducts and angioma or adenoma. Considering our experiences, adenomatoid and leiomyoma cannot be distinguished macroscopically. The hysterectomy or salpingo-oophorectomy, primarily performed under other diagnoses, are the therapies of choice.


[Effects of splenectomy on long-term results of the surgical treatment of stomach cancer].
The long-term results of surgery including splenectomy as treatment for stomach cancer were evaluated in 321 such cases. Tumor- and surgical procedure--related splenectomies were considered separately. Splenectomy did not influence long-term results of treatment in the study group. The effect of splenectomy on cell-mediated immunity within six postoperative months is discussed.


Hepatic infarction. A clinicopathologic study of seven cases.
Five of the seven cases of hepatic infarction that compose this study were encountered in a series of 442 consecutive autopsies, giving an incidence of one in 88 autopsies. The clinical and laboratory features were suggestive of hepatocellular dysfunction, although in only three cases was the diagnosis considered prior to death. Morphologically, in four of the seven patients, the infarcts were regarded as massive or of submassive proportions and were directly responsible for the patients' death. The majority of infarcts were of recent origin, with the estimated ages ranging from 18 to 72 hours. One was of about two weeks' duration and was the only example in this series associated with cirrhosis.


CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway.
Hypoxia induces protective autophagy in advanced glioblastoma cells, and targeting this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastoma cells in response to extensive hypoxia. Here, we describe a novel tumor suppressor in glioblastoma cells, whereby hypoxia downregulated CREBRF expression and acts as a potent inhibitor of autophagy in glioblastoma cells via the CREB3/ATG5 pathway. Our results demonstrate that CREBRF expression negatively correlates with autophagic and HIF-1α levels in different grade gliomas. Given that CREBRF is a negative regulator of CREB3, CREB3 knockdown also repressed hypoxia-induced autophagy in glioblastoma cells in vitro. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression.


[Value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal carcinoma].
To evaluate the value of EBNA1-IgA and EA-IgG in serological diagnosis of nasopharyngeal carcinoma (NPC). The serum EBNA1-IgA and EA-IgG of 56 patients with NPC and 58 healthy adults were detected by ELISA. The sensitivity, specificity, positive predictive value, accuracy rate and odds ratio of the two tests used singly or in combination were compared with each other. The sensitivity of EBNA1-IgA (91.07%) was higher than that of EA-IgG (87.50%), while the specificity of EA-IgG (87.93%) was higher than that of EBNA1-IgA (84.48%). The combination of EBNA1-IgA and EA-IgG could enhance the specificity (94.83%), positive predictive value (0.9375), likelihood ratio (15.5435) and odds ratio (75.0000) for serological diagnosis of NPC. Forty-five patients showed both positive EBNA1-IgA and positive EA-IgG. A positive EA-IgG was detected in 4 out of 5 patients with negative EBNA1-IgA and a positive EBNA1-IgA was founded in 6 out of 7 patients with negative EA-IgG. Although relatively high sensitivity and specificity could be obtained by either EBNA1-IgA or EA-IgG test alone, the combination of these two tests with a complementary effect is able to enhance the reliability of serological diagnosis of NPC as most patients have positive ENBA1-IgA and EA-IgG concurrently.


[Intracerebroventricular administration of adenosine A1 receptor antisense oligodeoxynucleotide inhibites the neuroprotective effect of the cerebral ischemic preconditioning in rats].
To further explore the role of adenosine A1 receptor in the neuroprotective effect of cerebral ischemic preconditioning, the present study was undertaken to observe the effect of inhibiting expression of adenosine Al receptor with adenosine A1 receptor antisense oligodeoxynucleotide (ARA1 As-ODN) on the neuroprotective effect of cerebral ischemic preconditioning against delayed neuronal death (DND) normally induced by lethal brain ischemia. The rat 4-vessel occlusion global cerebral ischemic model was used. Forty-eight male Wistar rats with permanent occlusion of the bilateral vertebral arteries were divided into 8 groups: Sham, CIP, brain ischemic insult, CIP + brain ischemic insult, Distilled water + CIP + brain ischemic insult, ARA1 As-ODN, ARA1 As-ODN +CIP, ARA1 As-ODN+ CIP + brain ischemic insult(two doses of 10 nmol/5 microl and 20 nmol/5 microl were used) groups. ARA1 As-ODN was dissolved in distilled water and injected into the right lateral cerebral ventricle. To illustrate the profile of DND, histological grade (HG) and neuronal density (ND) in the CA1 region of the hippocampus were examined 7 d after the sham operation or the last time of ischemia under thionin staining. The HG and ND in CIP group were similar to those in sham group. Brain ischemic insult induced obvious DND as represented with the increase in HG and decrease in ND significantly (P < 0.05 vs. sham and CIP groups). In CIP + ischemic insult group,no obvious DND was observed,which indicated that CIP protected pyramidal neurons against the ischemic insult.While the administration of ARA1 As-ODN in ARA1 As-ODN + CIP + brain ischemic insult group caused obvious increase in HG and decrease in ND compared with CIP + brain ischemic insult group (P < 0.05) in a dose dependent manner,which indicated that the neuroprotective effect of CIP against DND of hippocampal pyramidal neurons normally induced by ischemic insult was inhibited by the administration of ARA1 As-ODN. The results further demonstrate the association of up-regulation of adenosine A1 receptors with the induction of CIP-mediated BIT.


Rotator cuff degeneration of the healthy shoulder in patients with unilateral arm amputation is not worsened by overuse.
In order to evaluate whether overuse has a significant role in rotator cuff tear (RCT) aetiology, we evaluated both shoulders of patients with old unilateral arm amputation expecting a higher rate of RC degeneration in the healthy side. Nineteen males and six females (mean age: 57.3 ± 10.1) with an old (>20 years) unilateral arm amputation were submitted to an MRI of both shoulders. Tendon status and muscle tropism were evaluated according to Sugaya and Fuchs classifications, respectively; the acromion humeral distance was measured. Statistical analysis was performed to verify the prevalence of Sugaya and Fuchs categories in each sides. A significant prevalence of Sugaya type II in the amputated side (p = 0.02) and of type I in the healthy side (p < 0.001) was found. Rotator cuff was healthy in 28 and 52% of amputated and non-amputated side, respectively. The mean acromio-humeral distances of the amputated and healthy side were 0.8 cm (SD: 0.1) and 0.9 cm (SD: 0.1), respectively, (p = 0.02). A significant prevalence of Fuchs type II category in the healthy side (p < 0.001) was found. Fuchs III/IV were observed in 40 and 12% of amputated and healthy side, respectively. The present study resizes the role of overuse on the aetiology of RCT. Cuff tear prevalence in not amputated shoulders, inevitably submitted to functional overload, was not higher than that of coetaneous subjects with two functional upper limbs. Shoulder non-use is a risk factor for rotator cuff tear. As the prevalence of rotator cuff degeneration/tear is higher in the amputee side, non-use is a more relevant risk factor than overuse. In the daily clinical practice, patients with rotator cuff tear should be encouraged to shoulder movement because rotator cuff tendon status could be worsened by disuse. III.


Cloning, Expression Analysis and Functional Characterization of Squalene Synthase (SQS) from Tripterygium wilfordii.
Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs. To obtain soluble protein, the truncated TwSQS without the last 28 amino acids of the carboxy terminus was inductively expressed in Escherichia coliTransetta (DE3). The purified protein was detected by SDS-PAGE and Western blot analysis. Squalene was detected in the product of in vitro reactions by gas chromatograph-mass spectrometry, which meant that TwSQS did have catalytic activity. Organ-specific and inducible expression levels of TwSQS were detected by quantitative real-time PCR. The results indicated that TwSQS was highly expressed in roots, followed by the stems and leaves, and was significantly up-regulated upon MeJA treatment. The identification of TwSQS is important for further studies of celastrol biosynthesis in T. wilfordii.


Dynamics in the costs of criminality among opioid dependent individuals.
Research into the avoided crime-related costs associated with methadone maintenance treatment (MMT) is sparse. Our objective was to characterize the dynamics in crime-related costs associated with MMT effectiveness among opioid dependent individuals in Vancouver, Canada. We considered individuals enrolled in a prospective study between December, 2011 and May, 2013. Monthly crime-related costs (2013 CAD) were derived from self-reported criminal activity. On the basis of MMT receipt and illicit opioid use, individuals were classified in mutually exclusive health states: (i) MMT high effectiveness; (ii) MMT low effectiveness; (iii) opioid abstinence; or (iv) relapse. We classified individuals as daily, non-daily or non-stimulant users and controlled for demographic and socio-economic characteristics. A two-part multiple regression model was constructed; the first part modeled non-zero cost probability, the second estimated the level of costs. Avoided costs were estimated for each health state and stratified by stimulant use intensity. Our study included 982 individuals (median age 47, 38% female) for 2232 observations. Individuals on MMT with high effectiveness incurred lower monthly costs of criminality (avoided costs of $6298; 95% C.I. ($1578, $11,017)), as did opioid abstinent individuals ($6563 ($1564, $11,561)). Avoided costs for daily stimulant users were greater than for non-daily users, both for individuals on MMT with high effectiveness ($12,975 vs. $4125) and opioid abstinent ($12,640 vs. $4814). Using longitudinal data on individuals with a history of MMT, we found substantially lower costs of criminality associated with high effect to MMT. Avoided costs were highest among daily stimulant users that were on MMT with high effectiveness or those opioid abstinent.


A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute.
Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B. In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.


Similar mutant frequencies observed between pairs of monozygotic twins.
The relative contribution of both genetic and environmental factors to spontaneous mutation frequency in humans is unknown. We have investigated the contribution of genetic factors to this phenomenon by determining the in vivo mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in circulating T-lymphocytes obtained from pairs of monozygotic twins. hprt mutant frequencies were determined three times over fourteen days in six sets of monozygotic male twins (mean age 30) taking part in a Russian Space Program inclined bed rest experiment. Blood samples were obtained prior to, during, and immediately following the experiment. Mononuclear cells were separated, frozen, and flown to Canada for analysis using the hprt T-lymphocyte clonal assay. There is no evidence within this data set to demonstrate that the period of inclined bed rest to simulate the effects of weightlessness had any effect on the observed mutant frequency. However, the average mutant frequency for the six sets of Russian twins was found to be three times higher than that of Western counterparts. More surprisingly, the spontaneous mutant frequency of monozygotic twins was found to be much more similar within pairs than between pairs of twins. These data suggest that the contribution of genetics in the determination of mutation frequency is substantial. However, whether high concordance within twin pairs reflects shared environmental experience as well as common genetic factors is not entirely clear. More data will be required to distinguish genetic from environmental factors and to determine the degree to which mutant frequency is genetically determined.


RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.
The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers commonly arise in colorectal adenomas already bearing the APC mutation, whereas sporadic microsatellite unstable colorectal cancers arise from serrated polyps typically lacking APC mutation, decreasing the selection pressure on other WNT signaling related loci in Lynch syndrome.


A formula for the minimal coordination number of a parallel bundle.
An exact formula for the minimal coordination numbers of the parallel packed bundle of rods is presented based on an optimal thickening scenario. Hexagonal and square lattices are considered.


Astroglial-mediated remodeling of the interhemispheric midline during telencephalic development is exclusive to eutherian mammals.
The corpus callosum forms the major interhemispheric connection in the human brain and is unique to eutherian (or placental) mammals. The developmental events associated with the evolutionary emergence of this structure, however, remain poorly understood. A key step in callosal formation is the prior remodeling of the interhemispheric fissure by embryonic astroglial cells, which then subsequently act as a permissive substrate for callosal axons, enabling them to cross the interhemispheric midline. However, whether astroglial-mediated interhemispheric remodeling is unique to eutherian mammals, and thus possibly associated with the phylogenetic origin of the corpus callosum, or instead is a general feature of mammalian brain development, is not yet known. To investigate this, we performed a comparative analysis of interhemispheric remodeling in eutherian and non-eutherian mammals, whose lineages branched off before the evolution of the corpus callosum. Whole brain MRI analyses revealed that the interhemispheric fissure is retained into adulthood in marsupials and monotremes, in contrast to eutherians (mice), in which the fissure is significantly remodeled throughout development. Histological analyses further demonstrated that, while midline astroglia are present in developing marsupials, these cells do not intercalate with one another through the intervening interhemispheric fissure, as they do in developing mice. Thus, developing marsupials do not undergo astroglial-mediated interhemispheric remodeling. As remodeling of the interhemispheric fissure is essential for the subsequent formation of the corpus callosum in eutherians, our data highlight the role of astroglial-mediated interhemispheric remodeling in the evolutionary origin of the corpus callosum.


Biotemplate Replication of Novel Mangifera indica Leaf (MIL) for Atmospheric Water Harvesting: Intrinsic Surface Wettability and Collection Efficiency.
Water shortage has become a global crisis that has posed and still poses a serious threat to the human race, especially in developing countries. Harvesting moisture from the atmosphere is a viable approach to easing the world water crisis due to its ubiquitous nature. Inspired by nature, biotemplate surfaces have been given considerable attention in recent years though these surfaces still suffer from intrinsic trade-offs making replication more challenging. In the design of artificial surfaces, maximizing their full potential and benefits as that of the natural surface is difficult. Here, we conveniently made use of Mangifera indica leaf (MIL) and its replicated surfaces (RMIL) to collect atmosphere water. This research provides a novel insight into the facile replication mechanism of a wettable surface made of Polydimethylsiloxane (PDMS), which has proven useful in collecting atmospheric water. This comparative study shows that biotemplate surfaces (RMIL) with hydrophobic characteristics outperform natural hydrophilic surfaces (DMIL and FMIL) in droplet termination and water collection abilities. Water collection efficiency from the Replicated Mangifera indica leaf (RMIL) surface was shown to be superior to that of the Dry Mangifera indica leaf (DMIL) and Fresh Mangifera indica leaf (FMIL) surfaces. Furthermore, the wettability of the DMIL, FMIL, and RMIL was thoroughly investigated, with the apices playing an important role in droplet roll-off.


Bilateral acute epidural hematoma with good outcome.
Epidural haematomas are one of the most common complicated closed-head injuries, but they, rarely show any bilateral localization. We are reporting here a case of a man found unconscious with Glasgow Coma Scale score; 8/15. Computed tomography of skull revealed bilateral epidural hematoma. Two emergency craniotomies were performed simultaneously, with satisfactory radiological control and neurological outcome. We discussed the aspects of a etiology and treatment about this unusual condition.


Amplifying Older Aboriginal and Torres Strait Islander Women's Perspectives to Promote Digital Health Equity: Co-Designed Qualitative Study.
Digital health is becoming ubiquitous, and we must ensure equity in access. Indigenous people across most high-income countries typically have not benefited as much as other citizens from usual health care systems and technologies. Despite Aboriginal and Torres Strait Islander people's clear interest in, and enthusiastic use of, new technologies, little research has examined the needs or interests of older Aboriginal and Torres Strait Islander women. This study prioritizes the perspectives of older Aboriginal and Torres Strait Islander women, tapping into their expertise associated with Indigenous ways of knowing, being, and doing, as well as their unique position within their families and communities, to design a model for using digital technologies to improve health for themselves and their families as well as their communities. Older Aboriginal and Torres Strait Islander women from 4 partner organizations were recruited for this study. This co-designed qualitative research included citizen scientists in shaping the protocol as well as collecting, analyzing, and interpreting data. We used yarning, an Indigenous research method validated for use in health research with Indigenous people and seen as respectful and culturally safe, as a primary research tool. The use of Indigenous methodologies and our iterative process enabled us to deeply explore and incorporate perspectives from all participants and ensure that the perspectives of Indigenous citizen scientists with lived experience were privileged. The data-checking methods also used a yarning methodology, which ensured that the findings and translational model derived from the findings were validated by the participants. Participants comprised 24 Aboriginal and Torres Strait Islander women aged ≥41 years and including 3 generations that did not grow up with the internet: seniors, baby boomers, and Generation X. The key findings in this research were that older women use various digital technologies to improve health and well-being for themselves and their families as well as their communities. Older Aboriginal women want a culturally sensitive cyberspace that caters specifically to their needs and includes relevant content and functionality that are accessible and efficient. Our translational model highlights the conditions necessary for anyone to use digital health technologies, summarizes the essential elements needed to promote equity in digital health, and illuminates the unmet needs and requirements for older Aboriginal and Torres Strait Islander women to fully benefit from digital health technologies. Health is a fundamental right. As we move toward greater reliance on digital health solutions, we must recognize and address the concerns of the smaller populations of people who differ in their needs. We must urgently address the financial, connectivity, and other limiting factors highlighted by older Aboriginal and Torres Strait Islander women in this study that limit equitable access to digital health tools. RR2-10.1177/20552076221084469.


Switchable supermode emission in a doubly-coupled-ring system for multifunctional integrated photonic devices.
Effective integration of optical modes within chip-scale devices is critical to realize functional light emission, as it offers abundant physics and a versatile ability to control the mode evolution. Here, we present an efficient approach to achieve switchable emission by flexibly controlling supermode states in a doubly-coupled-ring system with four guided modes. The lasing conditions, which rely on the system's Hamiltonian, are revealed to yield multiple supermode states, including an exceptional-point state, a (quasi-)dark state, and a bright state. By freely engineering the coupling rate via phase-change material, the proposed system allows the generation of any desired states, enabling switchable and multifunctional emissions in fixed on-chip structures. Beyond the manipulation of various supermode emission states, our work presents a promising path toward the development of multifunctional integrated photonic devices, which may have applications in light storage, optical isolation, sensing, and so on.


Reconstruction of digit images from human brain fMRI activity through connectivity informed Bayesian networks.
Newly emerged developments in decoding of stimulus images from fMRI measurements have shown promising results. Decoding-classification has been the main concern of decoding studies, whereas the matter of reconstruction (decoding) of stimulus images from fMRI data, especially natural images, lacks adequate examination and it requires plenty of efforts to improve. The present study employs Bayesian networks for decoding-reconstruction which is a novel application of this tool. Moreover, as a novel approach, we exploit the brain connectivity information in decoding-reconstruction procedure through Bayesian networks. The proposed method was applied to reconstruct 100 images of digits 6 and 9 from the fMRI measurements obtained when showing some handwritten images of 6 and 9 to the subject. The information of only 10 brain voxels were exploited and an average (standard deviation) city-block distance error of 0.1071(0.0134) was obtained for all stimuli's reconstruction. In comparison with current common methods: The results reveal that Bayesian networks are successful in decoding-reconstruction of handwritten digits and inclusion of brain connectivity information makes them perform even more efficiently and improves decoding-reconstruction as well (reducing average error by almost 5%). In the task of decoding-reconstruction, the models including brain connectivity appear significantly superior to other existing models.


Micronized cellular adipose matrix as a therapeutic injectable for diabetic ulcer.
Despite the clinical potential of adipose-derived stem/stromal cells (ASCs), there are some clinical difficulties due to the regulation of cell therapies. Micronized cellular adipose matrix (MCAM) injectable was prepared through selective extraction of connective tissue fractions in fat tissue only through mechanical minimal manipulation procedures. It retained some capillaries and ASCs, but most adipocytes were removed. The presence of viable ASCs, vascular endothelial cells was confirmed and ASCs of MCAM kept intact mesenchymal differentiation capacity. In diabetic mice, skin wounds treated with MCAM showed significantly accelerated healing compared with phosphate-buffered saline-treated ones. The proven potential of MCAM to accelerate healing in ischemic diabetic ulcers may offer a simple, safe and minimally invasive means for tissue repair and revitalization.


The Cornell-Brown Scale for Quality of Life in dementia.
Quality of life (QOL) in patients diagnosed with dementia is of critical importance. Reliable and valid measurement of patient QOL is essential to evaluate the effectiveness of treatment interventions and to gain a better understanding of the detrimental impact of dementia on patients' lives. In this study, the psychometric properties of a new scale developed to measure QOL, the Cornell-Brown Scale for Quality of Life, were examined. Data were collected from 50 dementia clinic outpatients with a range of cognitive impairment. Scale ratings were based on a brief, joint interview with caregivers and patients. Findings indicated that the scale demonstrated adequate interrater reliability (intraclass r = 0.90) and internal consistency reliability (Cronbach alpha = 0.81). Criterion validity was indicated by a positive correlation between QOL scores and visual analogue positive mood ratings (Spearman rho = 0.63) and a negative correlation between QOL and dementia severity as measured by Clinical Dementia Ratings (Spearman rho = -0.35). Reliability and validity were not adversely affected by patient cognitive impairment. Thus, preliminary data indicate that the Cornell-Brown Scale for Quality of Life is a brief, easily administered, reliable, and valid measure of QOL.


The relationship between therapist behaviors and outcome for middle- and lower-class couples in marital therapy.
Treated a sample of 77 distressed middle- and lower-class couples by 19 therapists using conjoint therapy. Batteries of tests that assessed marital satisfaction and communications skills were given pre- and posttherapy plus 3 and 6 months later. Couple and therapist therapy behavior were assessed using audio tapes of interview sessions. A variety of sex and social class differences were found that correlated with therapy outcome. The overall thrust of the findings suggests that no one marital therapy technique will be appropriate for the different sexes and with those of different SES backgrounds.


Case Report: GPi DBS for Non-parkinsonian Midline Tremor: A Normative Connectomic Comparison to a Failed Thalamic DBS.
Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been heterogenous. Here, we present an atypical case with facial and palatal tremor treated with DBS. We aimed to show the difference between the fibers affected by stimulation of the two targets [globus pallidus interna (GPi) and ventral intermediate (Vim) thalamic nucleus] using a normative connectome analysis. Case Report: A 76-year-old woman with a 4-year history of severe facial and palatal tremor due to craniofacial dystonia. Following a failed bilateral Vim DBS, explantation of preexisting leads and implantation of bilateral GPi leads resulted in the resolution of tremor symptoms following a failed bilateral Vim DBS. We performed a normative connectome analysis using the volume of tissue activated (VTA) as a region of interest. The results revealed that the fiber tracts associated with VTA of GPi DBS had connections with the facial area of the motor cortex while the Vim DBS did not. Conclusion: This case study suggests the possibility that GPi DBS may be considered for midline tremor, and that the normative connectome analysis may possibly offer clues as to the structures underpinning a positive response. We may refine targets for some of the more difficult to control symptoms such as the midline tremor in this case.


Birth of cone bipolar cells, but not rod bipolar cells, is associated with existing RGCs.
Retinal ganglion cells (RGCs) play important roles in retinogenesis. They are required for normal retinal histogenesis and retinal cell number balance. Developmental RGC loss is typically characterized by initial retinal neuronal number imbalance and subsequent loss of retinal neurons. However, it is not clear whether loss of a specific non-RGC cell type in the RGC-depleted retina is due to reduced cell production or subsequent degeneration. Taking advantage of three knockout mice with varying degrees of RGC depletion, we re-examined bipolar cell production in these retinas from various aspects. Results show that generation of the cone bipolar cells is correlated with the existing number of RGCs. However, generation of the rod bipolar cells is unaffected by RGC shortage. Results report the first observation that RGCs selectively influence the genesis of subsequent retinal cell types.


Incidence of ulcerative colitis in the Cardiff region 1968-1977.
The incidence of ulcerative colitis in South Glamorgan during the decade 1968-77 remained steady with a mean of 7.2/10(5)/year. The disease was slightly more common in women, male:female ratio 1:1.2. Ulcerative colitis was rare in childhood but showed two peaks of incidence in adults, in the third and fourth decades and in the eighth decade.


A case of crescentic glomerulonephritis in a patient with COVID-19 infection: A case report and literature review.
Kidney involvement with COVID-19 infection is a well-known complication, and the majority of kidney involvement is related to ischemic injury/acute tubular injury. However, there are some cases of glomerulonephritis, the etiology of which is not yet known, but an immune process is likely to be the trigger. A 27-year-old man presented to our hospital with facial puffiness and lower-limb swelling. Laboratory assessment revealed features of impaired kidney function with proteinuria and hematuria; COVID-19 polymerase chain reaction was positive, which was consistent with pauci-immune crescentic focal segmental glomerulonephritis. After renal biopsy, the patient was started on methylprednisolone and rituximab. Due to worsening kidney parameters, he underwent intermittent hemodialysis as needed. Kidney function tests partially improved; he was discharged on oral steroids with follow-up in the nephrology clinic to observe for the need for further hemodialysis. We conducted a literature review of cases of glomerulonephritis associated with COVID-19 and described numerous types of glomerulonephritis. This report highlights the importance of recognizing emerging glomerulonephritis with COVID-19, the different pathological patterns of renal biopsies, and management interventions and responses.


[Pseudoterranovosis and sushi].
A case of accidental ingestión of Pseudoterranova decipiens is reported, on account of this patient we review main concepts related to this emerging pathology in Chile. Consumption of raw fish in different preparations such as sushi or sashimi, cebiche and seafood is becoming more and more popular. Through intermediary hosts used in the preparation, one can acquire the third stage larval of Anisakis simplex or P. decipiens. These parasites frequently cause gastritis, acutely after the consumption of raw fish, or more rarely intestinal involvement. It may also cause allergic symptoms such as urticaria, angioedema and anaphylactic shock. The larvae is eliminated spontaneously in most cases; others need to be removed by upper gastrointestinal endoscopio examination. In Chile, the most common species is P. decipiens, which are generally no invasive, rarely migrate beyond the stomach and cause mild or no symptoms. Prevention strategies include avoid eating raw fish or undercooked seafood containing the parasite, to cook food with high temperatures or to freeze raw fish prior to preparation of meals, which inactivates the larvae.


Migration of Dictyostelium discoideum to the Chemoattractant Folic Acid.
Dictyostelium discoideum can be grown axenically in a cultured media or in the presence of a natural food source, such as the bacterium Klebsiella aerogenes (KA). Here we describe the advantages and methods for growing D. discoideum on a bacterial lawn for several processes studied using this model system. When grown on a bacterial lawn, D. discoideum show positive chemotaxis towards folic acid (FA). While these vegetative cells are highly unpolarized, it has been shown that the signaling and cytoskeletal molecules regulating the directed migration of these cells are homologous to those seen in the motility of polarized cells in response to the chemoattractant cyclic adenosine monophosphate (cAMP). Growing D. discoideum on KA stimulates chemotactic responsiveness to FA. A major advantage of performing FA-mediated chemotaxis is that it does not require expression of the cAMP developmental program and therefore has the potential to identify mutants that are purely unresponsive to chemoattractant gradients. The cAMP-mediated chemotaxis can appear to fail when cells are developmentally delayed or do not up-regulate genes needed for cAMP-mediated migration. In addition to providing robust chemotaxis to FA, cells grown on bacterial lawns are highly resistant to light damage during fluorescence microscopy. This resistance to light damage could be exploited to better understand other biological processes such as phagocytosis or cytokinesis. The cell cycle is also shortened when cells are grown in the presence of KA, so the chances of seeing a mitotic event increases.


Ischemia-reperfusion injury and hypoglycemia risk in insulin-treated T1DM rats following different modalities of regular exercise.
While regular exercise is known to improve cardiovascular function, individuals with type 1 diabetes mellitus (T1DM) have an increased risk for exercise-induced hypoglycemia. Clinical data suggest that higher intensities of acute exercise may alleviate the onset of hypoglycemia; however, the cardiovascular benefit from these forms of exercise in patients with T1DM has yet to be established. The purpose of this study was to investigate the cardiovascular benefit of different regular exercise regimes, while monitoring blood glucose concentrations during the post-exercise period. Fifty rats (8-week-old Sprague-Dawley male) were equally divided into the following groups: nondiabetic sedentary (C), diabetic sedentary (DS), diabetic low-intensity aerobic exercise (DL), diabetic high-intensity aerobic exercise (DH) or diabetic resistance exercise (DR). Diabetes was induced using multiple streptozotocin injections (5×; 20 mg/kg) while subcutaneous insulin pellets maintained glycemia in a range typical for individuals that exercise with T1DM. Exercise consisted of six weeks of treadmill running (DL and DH) or weighted ladder climbs (DR). The cardiovascular benefit of each exercise program was determined by the myocardial recovery from ischemia-reperfusion injury. Exercise-related cardiovascular protection was dependent on the exercise modality, whereby DH demonstrated the greatest protection following an ischemic-reperfusion injury. Each exercise modality caused a significant decline in blood glucose in the post-exercise period; however, blood glucose levels did not reach hypoglycemic concentrations (<3.0 mmol/L) throughout the exercise intervention. These results suggest that elevating blood glucose concentrations prior to exercise allows patients with T1DM to perform exercise that is beneficial to the myocardium without the accompanying risk of hypoglycemia.


The development of myocardial changes during intermittent high altitude hypoxia in rats.
The initial phase and the development of myocardial focal necroses were studied in 50 rats adapted successively to intermittent high altitude. The altitude hypoxia was produced in a low pressure chamber (7000 m, five days a week, four hours daily). First-minute myocardial changes detected by histochemical methods were found after 4 exposures at a level of 3000 m and distinct ones after 8 exposures at a level of 4500 m. Histologically, acute focal necroses were found after 11 exposures at a level of 6000 m. Hypoxia and stress are suggested to account for these myocardial focal changes. During further adaptation no further acute focal necroses were observed.


Epidemiological and Virological Characterizations of the 2014 Dengue Outbreak in Guangzhou, China.
Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future.


Metagenomic analysis of the pygmy loris fecal microbiome reveals unique functional capacity related to metabolism of aromatic compounds.
The animal gastrointestinal tract contains a complex community of microbes, whose composition ultimately reflects the co-evolution of microorganisms with their animal host. An analysis of 78,619 pyrosequencing reads generated from pygmy loris fecal DNA extracts was performed to help better understand the microbial diversity and functional capacity of the pygmy loris gut microbiome. The taxonomic analysis of the metagenomic reads indicated that pygmy loris fecal microbiomes were dominated by Bacteroidetes and Proteobacteria phyla. The hierarchical clustering of several gastrointestinal metagenomes demonstrated the similarities of the microbial community structures of pygmy loris and mouse gut systems despite their differences in functional capacity. The comparative analysis of function classification revealed that the metagenome of the pygmy loris was characterized by an overrepresentation of those sequences involved in aromatic compound metabolism compared with humans and other animals. The key enzymes related to the benzoate degradation pathway were identified based on the Kyoto Encyclopedia of Genes and Genomes pathway assignment. These results would contribute to the limited body of primate metagenome studies and provide a framework for comparative metagenomic analysis between human and non-human primates, as well as a comparative understanding of the evolution of humans and their microbiome. However, future studies on the metagenome sequencing of pygmy loris and other prosimians regarding the effects of age, genetics, and environment on the composition and activity of the metagenomes are required.


Impact of education and support on the tolerability and quality of life in a cohort of HIV-1 infected patients treated with enfuvirtide (SURCOUF Study).
The aim of this study was to evaluate the quality of life and the intensity of the injection site reactions during the first 6 months of treatment with enfuvirtide according to the counseling and training provided by nurses and physicians. In this prospective, 6-month cohort, 61 HIV-1 infected adult patients starting enfuvirtide have been included. At baseline, 82% of the patients have either read information documents (23%) or received counseling (59%); 18% were self-injectors, 27.8% had a dual disposition (self-injector + third person), and 49.2% were injected by a third person. At month 6, among the 43 patients still on enfuvirtide, 59% have had no change in injection disposition, and 52% have the dual disposition. Quality of life and enfuvirtide acceptance improved during 6 months. With adequate education and choice of injection dispositions, treatment with enfuvirtide can lead to quality-of-life improvements.


The fruit fly Drosophila melanogaster favors dim light and times its activity peaks to early dawn and late dusk.
The light preferences of fruit flies were tested by 2 different means. First, flies were allowed to choose between different illuminations, and their favorite resting, grooming, and feeding places were determined with an infrared-sensitive camera. Second, the activity levels of the animals during their main daily activity period were determined photoelectrically (via infrared light beams) under different light intensities. Both methods revealed that the flies prefer dim light. They rested, groomed, and fed preferentially in places with a light intensity between 5 and 10 lux, and they showed the highest activity level when the light intensity during the day was kept at 10 lux. Furthermore, when dawn and dusk were simulated by logarithmically increasing/decreasing the light intensity during a 1.5-h interval, the flies' activity maxima occurred at about 7.5 lux during early dawn and late dusk. The results suggest that fruit flies time their clocks by early dawn and late dusk and avoid bright light during the day.


New crystal structure of the proteasome-dedicated chaperone Rpn14 at 1.6 Å resolution.
The 26S proteasome is an ATP-dependent protease responsible for selective degradation of polyubiquitylated proteins. Recent studies have suggested that proteasome assembly is a highly ordered multi-step process assisted by specific chaperones. Rpn14, an assembly chaperone for ATPase-ring formation, specifically recognizes the ATPase subunit Rpt6. The structure of Rpn14 at 2.0 Å resolution in space group P6(4) has previously been reported, but the detailed mechanism of Rpn14 function remains unclear. Here, a new crystal structure of Rpn14 with an E384A mutation is presented in space group P2(1) at 1.6 Å resolution. This high-resolution structure provides a framework for understanding proteasome assembly.


Effect of isometric effort upon mitral regurgitation severity--echo Doppler study.
Isometric effort increases the severity of mitral regurgitation (MR) by augmenting the afterload and the regurgitant fraction. The worsening of MR may be different in various patients and can explain the differences in effort capacity of patients with identical rest mitral regurgitation. We studied 25 patients with MR of various etiologies, submitted to handgrip (maximal voluntary contraction), the severity of MR being evaluated by the determination of regurgitant area (colour Doppler). There was a 42% increase of the regurgitant area from 3.26 to 4.66 cm2 (p < 0.05). The increase was greater for ischemic MR (59%) than for MR in dilated cardiomyopathy (26%), the last value not being explained by a lower EF because rest EF was similar in patients with and without an increase of MR severity during maximal voluntary contraction. The individual analysis of the results showed an increase of the MR severity in 1/2 of the patients, in whom the left atrial dimension was greater, though the effort capacity was the same in the two subsets of patients. It is concluded that colour Doppler is a simple and valuable method for studying the influence of isometric exercise upon MR severity, this being increased in 1/2 of the patients, with a positive correlation with ischemic etiology of the disease, left atrial dimension, but not with the patients' effort capacity.


Magnetic discontinuities in magnetohydrodynamic turbulence and in the solar wind.
Recent measurements of solar wind turbulence report the presence of intermittent, exponentially distributed angular discontinuities in the magnetic field. In this Letter, we study whether such discontinuities can be produced by magnetohydrodynamic (MHD) turbulence. We detect the discontinuities by measuring the fluctuations of the magnetic field direction, Δθ, across fixed spatial increments Δx in direct numerical simulations of MHD turbulence with an imposed uniform guide field B(0). A large region of the probability density function (pdf) for Δθ is found to follow an exponential decay, proportional to exp(-Δθ/θ(*)), with characteristic angle θ(*)≈(14°)(b(rms)/B(0))(0.65) for a broad range of guide-field strengths. We find that discontinuities observed in the solar wind can be reproduced by MHD turbulence with reasonable ratios of b(rms)/B(0). We also observe an excess of small angular discontinuities when Δx becomes small, possibly indicating an increasing statistical significance of dissipation-scale structures. The structure of the pdf in this case closely resembles the two-population pdf seen in the solar wind. We thus propose that strong discontinuities are associated with inertial-range MHD turbulence, while weak discontinuities emerge from dissipation-range turbulence. In addition, we find that the structure functions of the magnetic field direction exhibit anomalous scaling exponents, which indicates the existence of intermittent structures.


Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.
More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality.


Narrative Review: Impairing Emotional Outbursts: What They Are and What We Should Do About Them.
Impairing emotional outbursts, defined by extreme anger or distress in response to relatively ordinary frustrations and disappointments, impact all mental health care systems, emergency departments, schools, and juvenile justice programs. However, the prevalence, outcome, and impact of outbursts are difficult to quantify because they are transdiagnostic and not explicitly defined by current diagnostic nosology. Research variably addresses outbursts under the rubrics of tantrums, anger, irritability, aggression, rage attacks, or emotional and behavioral dysregulation. Consistent methods for identifying and assessing impairing emotional outbursts across development or systems of care are lacking. The American Academy of Child and Adolescent Psychiatry Presidential Task Force (2019-2021) conducted a narrative review addressing impairing emotional outbursts within the limitations of the existing literature and independent of diagnosis. Extrapolating from the existing literature, best estimates suggest that outbursts occur in 4%-10% of community children (preschoolers through adolescents). Impairing emotional outbursts may respond to successful treatment of the primary disorder, especially for some children with attention-deficit/hyperactivity disorder whose medications have been optimized. However, outbursts are generally multi-determined and often represent maladaptive or deficient coping strategies and responses. Evidence-based strategies are necessary to address factors that trigger, reinforce, or excuse the behaviors and to enhance problem-solving skills. Currently available interventions yield only modest effect sizes for treatment effect. More specific definitions and measures are needed to track and quantify outbursts and to design and assess the effectiveness of interventions. Better treatments are clearly needed.


Smoking, nicotine and tar and risk of small for gestational age babies.
To assess the effect of maternal smoking and environmental tobacco smoke (ETS) on risk of small for gestational age infants (SGA). Case-control study of 844 cases and 870 controls. Maternal smoking in pregnancy was associated with an increased risk of SGA (adjusted odds ratio (OR)= 2.41; 95% confidence interval (CI) = 1.78, 3.28). We could not detect an increased risk of SGA with paternal smoking, or with other household smokers when the mother was a non-smoker, but did find an increased risk with exposure to ETS in the workplace or while socializing. Infants of mothers who ceased smoking during pregnancy were not at increased risk of SGA, but those who decreased but did not stop remained at risk of SGA. There was no evidence that the concentration of nicotine and tar in the cigarettes influenced the risk of SGA. Maternal smoking in pregnancy is a major risk factor for SGA. This study suggests that mothers should be advised to cease smoking completely during pregnancy, and that a reduction in the number of cigarettes smoked or smoking low tar or nicotine concentration cigarettes does not reduce the risk of SGA.