Correlation of plasma von Willebrand factor levels, an index of endothelial damage/dysfunction, with two point-based stroke risk stratification scores in atrial fibrillation.
To test the hypothesis that the new CHADS2 and Framingham point-based risk stratification scores could be related to plasma vWf (a plasma index of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation) levels in a large cohort of AF patients, we studied 200 consecutive patients (101 male; 72+/-9 years) attending our anti-coagulation clinic for the initiation of anticoagulation treatment with acenocoumarol. AF patients had a median CHADS2 score of 2 (1-2) and a median Framingham point-based risk score of 14 (9-21). Results of research indices in our AF patients were as follows: vWf 142.8+/-41.8 IU/dL and sE-sel 44 (31-62) ng/mL. There were significant correlations between plasma vWf levels and both risk CHADS2 and Framingham risk scores (vWf-CHADS2 risk score: Spearman, r=0.249, p<0.001; vWf-Framingham risk score: r=0.294, p<0.001). sE-sel did not show any significant correlation with both risk scores (sE-sel-CHADS2 risk score: r=-0.054, p=0.460; sE-sel-Framingham risk score: r=0.062, p=0.460). There were no statistically significant correlations between vWf and sE-sel (r=-0.127, p=0.081). Both CHADS2 and Framingham risk scores were significantly correlated with each other, r=0.627, p<0.001. In conclusion, in a wide cohort of non-selected and consecutive AF patients, endothelial damage/dysfunction (assessed by plasma vWf levels) but not endothelial activation (sE-sel) correlated with two new risk stratification scores for stroke in AF. Further prospective studies are needed to assess the prognostic role of prothrombotic indices in AF in relation to stroke and thromboembolic events, and their role in complementing clinical risk stratification schemas.


Isolation of two cDNA sequences which encode cytotoxic cell proteases.
Two cDNAs which cross-hybridized with cytotoxic cell protease genes were identified in a library generated from a cytotoxic T cell line. Sequence analysis revealed that the two new members of the family contained the three catalytic triad residues which characterize the active sites of serine proteases. A comparison of the protein sequences revealed not only a high degree of homology but also the conservation of some unusual structural features. These include the lack of a disulphide bond which spans the active site serine, the presence of a signal sequence and the inference of a dipeptide activation sequence.


Who Should Do Data Ethics?
Who decides what good data science looks like? And who gets to decide what "data ethics" means? The answer is all of us. Good data science should incorporate the perspectives of people who create and work with data, people who study the interactions between science and society, and people whose lives are affected by data science.


Quantitative description of upper extremity function and activity of people with spinal muscular atrophy.
Therapeutic management of the upper extremity (UE) function of people with spinal muscular atrophy (SMA) requires sensitive and objective assessment. Therefore, we aimed to measure physiologic UE function of SMA patients with different functional abilities and evaluate the relation between these physiologic measures and functional UE scales. 12 male and 5 female SMA patients (mean age 42 years; range 6-62 years) participated in this explorative study. Concerning the physiologic level, the maximal muscle torque, the maximal and normalized surface electromyography (sEMG) amplitudes, and the maximal passive and active joint angles were measured. Concerning the activity level, the Performance of the Upper Limb (PUL) scale was used, and hand function was examined using the Nine-Hole Peg Test and the Timed Test of In-Hand Manipulation (TIHM). Outcome measures that significantly related to the functional ability were: the PUL score (all dimensions); the finger to palm task of the Timed TIHM; biceps, triceps, and forearm extensor strength; and the active range of motion of shoulder abduction, shoulder flexion, and wrist extension. In addition, the following physiologic variables were related to the activity level (PUL score): hand function (the Nine-Hole Peg Test; Rs = - 0.61), the Timed TIHM (Rs = - 0.53), the maximal muscle torque (Rs = 0.74), the maximal sEMG amplitude (Rs = 0.79), and the maximal active joint angle (Rs = 0.88). Muscle functions in SMA patients are already affected before activity limitations are noticeable. Consequently, monitoring the maximal muscle strength and the normalized muscle activity during task performance could play a role in the early detection of UE limitations. The mechanism behind the loss of arm activities due to SMA is primarily caused by decreasing muscle capacity, which influences the ability to move an arm actively. In clinical practices, these dimensions should be considered separately when monitoring disease progression in order to better evaluate the need for interventions.


Alternative splicing of lola generates 19 transcription factors controlling axon guidance in Drosophila.
The Drosophila melanogaster transcription factor Lola (longitudinals lacking) is a pivotal regulator of neural wiring that sets the precise expression levels of proteins that execute specific axon guidance decisions. Lola has a zinc finger DNA binding domain and a BTB (for Broad-complex, Tramtrack and Bric a brac) dimerization motif. We now show that alternative splicing of the lola gene creates a family of 19 transcription factors. All lola isoforms share a common dimerization domain, but 17 have their own unique DNA-binding domains. Seven of these 17 isoforms are present in the distantly-related Dipteran Anopheles gambiae, suggesting that the properties of specific isoforms are likely to be critical to lola function. Analysis of the expression patterns of individual splice variants and of the phenotypes of mutants lacking single isoforms supports this idea and establishes that the alternative forms of lola are responsible for different functions of this gene. Thus, in this system, the alternative splicing of a key transcription factor helps to explain how a small genome encodes all the information that is necessary to specify the enormous diversity of axonal trajectories.


An unusual auricular malformation accompanied by accessory tragus: macrotragus.
Definition of malformations of the tragus is important for terminology and treatment. Most common entities are the skin tag, accessory tragus, preauricular sinus, and cyst, whereas macrotragus is an uncommon and unaddressed deformity that should be distinguished from these. In this report, three cases with diagnosis of the macrotragus are presented. The tragus was uniformly large and displaced anteriorly, and external auditory meatus was not obliterated in all cases. For correction, excision of the excess tragal cartilage and skin was performed. In all cases, bilaterally symmetric tragus was achieved. There were no complications in the early postoperative period and there was no enlargement after 6months of observation. Macrotragus and accessory tragus are different entities that should be distinguished for accurate diagnosis. They have similar histopathological but distinct anatomical characteristics. Although both are treated by a simple excision, in the case of macrotragus, special effort should be taken to leave enough cartilage to restore normal tragal contours.


Whole-body autoradiography of 63Ni in mice throughout gestation.
Whole-body autoradiography was used to study nickel uptake and retention in mice throughout gestation. After an intraperitoneal injection of 50 muCi 63NiCl2 into a 16-day-pregnant mouse, nickel appeared rapidly in connective tissues. Prominent sites of radioactivity 72 h after injection included the visceral yolk sac, lung, gastrointestinal tract and kidney. Nickel crossed the placental barriers throughout gestation, i.e. the visceral yolk sac during early gestation, the visceral yolk sac and chorioallantoic placenta during late gestation. A marked uptake of nickel was seen already in the 5- and 6-day embryo. Fetal accumulation of nickel took place up to 16 days gestation. Whereas nickel was distributed throughout the early embryo, distribution became more differentiated with increasing gestation, imitating that in the mother. Penetration of nickel into the mouse conceptus makes possible a similar ability in the human conceptus.


Diversity and disparities in research studies and career trajectories in psychiatry.
It is well recognized that underrepresented and systematically minoritized groups do not have balanced access to clinical trials as study participants or as research Investigators. However, comprehensive data on the perspective of expert clinicians is largely lacking in the current literature. In this pilot exploration, we collected the opinions of 33 subject matter experts (SME) to identify and explore potential barriers to diversification in clinical trials. The majority of respondents live in North America or Central or Western Europe and identified as not a member of an underrepresented or marginalized group (UMB), with about 15% of respondents being a member of a UMB. Overall, about a quarter of respondents reported making an intentional effort to recruit members of UMB as study participants and identified recruitment challenges linked to two areas: psycho-social barriers and practical barriers. A variety of strategies were employed to improve recruitment including engagement with community leaders, targeted advertising, utilizing databases, and social media campaigns. About half of respondents reported difficulties recruiting Investigators from UMB backgrounds, stating culture and language barriers, perceived lack of interest in the field among individuals from UMB, and lack of information as possible reasons for the challenges.


The 'Industrial Enlightenment' and technological paradigms of the modern steel industry.
Scientific knowledge is crucial to opening up new possibilities for major technological advances. When did science become important for economic development? The steam engine was the earliest major science-based invention. Conversely, the role of science has not been regarded as important in the innovations leading to modern steelmaking. In addition, how did science begin to play an important role? Mokyr focuses on the 'Industrial Enlightenment', which has its origins in the Baconian program of the seventeenth century. However, the role of science is often not regarded as important in the emergence of modern steelmaking technology. This paper examines the process through which modern steelmaking emerged and clarifies the role of science and 'Industrial Enlightenment'. This discussion is also important in determining how to view the role of science in economic development and in considering 'the Great Divergence' and 'the Great Knowledge Transcendence'. In addition, the examination of this paper will show how to create radical innovations that are completely different from existing paradigms, and how to create new technological paradigms to overcome difficulties such as the recent Covid-19 pandemic and environmental problems. When much time elapses between scientific and technological advances, the role of science is often not regarded as important and sensational innovations such as the Bessemer process are emphasized. However, this is not a proper evaluation. The role of 'Industrial Enlightenment' on the supply side must also be recognized as significant in the emergence of modern steelmaking technology.


The neurohypophysial axons in normal and dehydrated rats: an electron microscopic study including ZIO-staining method.
The neurohypophysial axons from normal rats and those dehydrated for 4 and 12 days were investigated by means of conventional glutaraldehyde fixation and the zinc-iodide-osmium (ZIO) staining technique. Conventionally fixed axons from dehydrated rats revealed depletion of dense core of neurosecretory granules, more frequent occurrence of microvesicles, proliferation of smooth endoplasmic reticulum or accumulation of lysosomes. It has been disclosed that the ZIO reaction product has the ability to stain microvesicles (normal rats) and smooth endoplasmic reticulum, lysosomes, some neurosecretory granules and some parts of stromal inclusion at the release site (dehydrated rats). Quantitative data are also presented. They indicate a significantly decreased number of both neurosecretory granules (NSG) and ZIO-positive microvesicles (MV) in dehydrated rats. Equally, the value of the median of the MV/NSG ratio was significantly increased from 1.38 in normal rats to 5.50 and 7.50 in rats dehydrated for 4 and 12 days, respectively. Thus, the possible involvement of ZIO-positive microvesicles in a process associated with neurosecretion is suggested. While in normal rats a correlation was found between the number of neurosecretory granules and the area of sectioned profiles of the axons, no evidence was obtained for it in 12-day dehydrated rats. Conversely, no evidence for a relationship between the axon area and the number of ZIO-positive microvesicles was obtained in normal rats, while in rats dehydrated for 12 days a correlation was found.


Surface tension induced by dipalmitoyl lecithin in vitro under physiological conditions.
1. The surface tension of 161 films of DPL have been measured on a Langmuir trough using a Wilhelmy balance under conditions controlled to simulate the state of the alveolar lining in vivo.2. The parameters controlled were temperature (maintained at 37 degrees C), humidity (100% at 37 degrees C), surfactant concentrations (encompassing the best available estimates), area changes (consistent with normal respiration), frequency adaptation to continuous cycling and composition and pH of the aqueous hypophase.3. Simultaneously maintaining all of these parameters within the best estimates of physiological limits, the relationships between surface tension and surface area showed appreciable differences from previous studies, our results showing higher minimum values of surface tension, appreciably less change in surface tension with compression and far less hysteresis between surface tension and surface area.4. The higher minimum values are consistent with original estimates of alveolar surface tension made by von Neergaard, namely 35-41 dyne cm(-1).5. Although appreciably smaller than hitherto reported, the change in surface tension with change in area is still adequate to impart alveolar stability.6. The reversibility between surface tension and surface area under physiological conditions is discussed in connection with compliance hysteresis which is considered to be more dependent upon geometric irreversibility of the alveolar surface than upon any intrinsic property of the surfactant.


A multi-dimensional examination of the positive reinforcing properties of acetaldehyde.
The suggestion that acetaldehyde may be endowed with positive reinforcing properties and may in fact mediate some of the psychopharmacological actions of ethanol has been examined by us and other investigators using a variety of paradigms. We first reported that non-dependent animals would self-administer acetaldehyde through an intra-cerebroventricular route. In addition, we have demonstrated that central infusion induced a conditioned place preference. We have also shown that an animal's propensity to self-administer acetaldehyde directly into the brain was related to its subsequent voluntary intake of ethanol. Lastly, we have reported that inhibition of acetaldehyde metabolism resulted in an enhancement of alcohol-induced euphoria in man. The data collected to date from four different paradigms strongly support the notion that acetaldehyde is endowed with positive reinforcing properties which may play a critical role in the mediation of ethanol euphoria.


An explant of heifer mammary gland to study the immune response of the organ.
Continuous or primary epithelial cell lines have been extensively used to study the mammary gland immune response, but they are constituted by a single cell population. Our aim was to test whether an explant of heifer gland, where the tissue structure is maintained, might be a valid model to investigate the innate immune response to infection. The study was carried out on 2mm3-sections of heifer udders, in 2 consecutive trials, using LPS or LTA in the first trial and two different concentrations of Staphylococcus aureus (Staph. aureus) in the second. Treated and untreated sections were collected after 1h, 3h and 6h incubation; in the first trial, a final time-point at 18h was considered. The mRNA expression of TNFα, IL-1β, IL-6, IL-8 and LAP was analyzed by quantitative real-time PCR. Histological examination showed well-preserved morphology of the tissue, and apoptosis only showed a slight, not significant increase throughout the experiment. IL-1β and IL-6 were significantly up-regulated, in response to LPS or Staph. aureus, while TNF-α and IL-8 significantly increased only under LPS treatment. LAP expression showed a significant late increase when stimulated by LPS. The immunochemical staining of the sections demonstrated a higher number of T lymphocytes within the alveolar epithelium, in comparison with interstitial localization. Since the explants belonged to pubertal non-pregnant heifers, T cells may be regarded as resident cells, suggesting their participation in the regulation of mammary homeostasis. Therefore, applying our model would give new insights in the investigation of udder pathophysiology.


Progranulin protects against cerebral ischemia-reperfusion (I/R) injury by inhibiting necroptosis and oxidative stress.
Ischemic stroke is a leading cause of mortality and disability worldwide. Nevertheless, its molecular mechanisms have not yet been adequately illustrated. Progranulin (PGRN) is a secreted glycoprotein with pleiotropic functions. In the present study, we found that PGRN expression was markedly reduced in mice after stroke onset through middle cerebral artery occlusion (MCAO). We also showed that necroptosis was a mechanism underlying cerebral I/R injury. Importantly, PGRN knockdown in vivo significantly promoted the infarction volume and neurological deficits scores in mice after MCAO surgery. Necroptosis induced by MCAO was further accelerated by PGRN knockdown, as evidenced by the promoted expression of phosphorylated receptor-interacting protein (RIP) 1 kinase (RIPK1), RIPK3 and mixed lineage kinase domain-like (MLKL), which was accompanied with increased expression of cleaved Caspase-8 and Caspase-3. However, PGRN over-expression was neuroprotective. Additionally, PGRN-regulated ischemic stroke was related to ROS accumulation that MCAO-mice with PGRN knockdown exhibited severe oxidative stress, as proved by the aggravated malondialdehyde (MDA) and lipid peroxidation (LPO) contents, and the decreased superoxide dismutase (SOD) activity. However, PGRN over-expression in mice with cerebral ischemia showed anti-oxidative effects. Finally, PGRN was found to attenuate oxidative damage partly via its regulatory effects on necroptosis. Therefore, promoting PGRN expression could reduced cerebral I/R-induced brain injury by suppressing neroptosis and associated reactive oxygen species (ROS) production. These data elucidated that PGRN might provide an effective therapeutic treatment for ischemic stroke.


Ciliate cryptobiosis: a microbial strategy against environmental starvation.
This review outlines the main features of ciliate resting-cyst formation or encystment. It represents a strategy against several environmental stresses (such as starvation), which involves a highly gene-regulated cell differentiation process and originates a more resistant, differentiated form or resting cyst. This process is mainly characterized by drastic cytoplasmic dehydration that induces a general metabolic rate decrease, intense autophagic activity, the formation of a permeable cyst wall protecting the cell against the adverse environmental conditions, and a gene-silencing mechanism after opening the specific encystment genes.


Rapid adaptation of primate LGN neurons to drifting grating stimulation.
The visual system needs to dynamically adapt to changing environments. Much is known about the adaptive effects of constant stimulation over prolonged periods. However, there are open questions regarding adaptation to stimuli that are changing over time, interrupted, or repeated. Feature-specific adaptation to repeating stimuli has been shown to occur as early as primary visual cortex (V1), but there is also evidence for more generalized, fatigue-like adaptation that might occur at an earlier stage of processing. Here, we show adaptation in the lateral geniculate nucleus (LGN) of awake, fixating monkeys following brief (1 s) exposure to repeated cycles of a 4-Hz drifting grating. We examined the relative change of each neuron's response across successive (repeated) grating cycles. We found that neurons from all cell classes (parvocellular, magnocellular, and koniocellular) showed significant adaptation. However, only magnocellular neurons showed adaptation when responses were averaged to a population response. In contrast to firing rates, response variability was largely unaffected. Finally, adaptation was comparable between monocular and binocular stimulation, suggesting that rapid LGN adaptation is monocular in nature.NEW & NOTEWORTHY Neural adaptation can be defined as reduction of spiking responses following repeated or prolonged stimulation. Adaptation helps adjust neural responsiveness to avoid saturation and has been suggested to improve perceptual selectivity, information transmission, and predictive coding. Here, we report rapid adaptation to repeated cycles of gratings drifting over the receptive field of neurons at the earliest site of postretinal processing, the lateral geniculate nucleus of the thalamus.


Halochromic generation of white light emission using a single dithienophosphole luminophore.
A new dithienophosphole-based donor-acceptor conjugated luminophore shows a large halochromic effect on its emission color that changes from red to green upon addition of acid. White light emission can be generated upon partial protonation resulting in a broad emission band.


Effects of information asymmetries in contests between net spinning caddis larvae (Plectrocnemia conspersa).
During five days prior to the introduction of potential intruder larvae, residents were treated in four different ways. In one treatment the residents were unfed and their nets were taken away at daily intervals. Nets were not taken away in the other treatments, and residents were unfed, fed 2 or 4 items per day, respectively. Small intruders were equally successful as large ones in taking over low energy demanding nets of unfed, disturbed residents whose nets were taken away daily. Take overs of high ranked nets of larvae fed four prey items per day were mainly performed by large intruders. Low investment nets of unfed, disturbed resident larvae were often taken over during the first day upon the implantation of intruder larvae. On the contrary, unfed undisturbed larvae defending a five times as energy demanding net only suffered a slight net loss. Nets of unfed, undisturbed larvae were taken over somewhat more often than those from residents fed two prey per day. The results indicate prior treatment to inform these three resident categories of their resource values. Owners of high ranked nets fed two prey per day were most keen on defence during the first day upon introduction of potential intruders. Residents fed four prey per day suffered from a significantly higher number of take overs during the first day compared with larvae only fed two prey per day. The residents fed four prey per day stored some of the food in their nets making this resource more valuable also to intruders. After five days the number of take overs was about the same irrespective of previous treatment.


Specific neuronal subpopulations in the amygdala of macaque monkeys express high levels of nonphosphorylated neurofilaments.
Pyramidal neurons in the neocortex that express nonphosphorylated neurofilaments (NPNFs) are especially vulnerable to degeneration in Alzheimer's disease. Since the basolateral nuclear complex of the amygdala (BNC) and cortical nuclear complex of the amygdala (CNC) are cortex-like structures, containing both pyramidal (PNs) and nonpyramidal neurons (NPNs), it is of interest to determine which cell types in the primate BNC and CNC are NPNF+. We also studied NPNF expression in the non-cortex-like nuclei of the amygdala (central and medial nuclei). Digitized images of sections through fetal, newborn, infant, and adult macaque brains stained for NPNFs, obtained from the Macaque Brain Resource (MacBrainResource, MBR), were analyzed. The pattern of NPNF immunoreactivity (NPNF-ir) in the BNC, CNC, and medial nucleus was essentially identical in all four age groups, but there were some age-dependent differences in the central nucleus. All BNC and CNC nuclei contained a moderate density of NPNF+ NPNs. Both the somata and the entire dendritic arborizations of these NPNs were stained. PNs with robust NPNF-ir in their somata and proximal dendrites were only seen in the basal magnocellular nucleus, where it appeared that virtually every PN was NPNF+. This pattern of NPNF expression is distinct from that seen in the mammalian neocortex, where NPNF+ neurons are almost entirely PNs, but is very similar to that seen in a recent study of the rat BNC. These findings, in conjunction with the cortical data, suggest the possibility that NPNF+ neuronal subpopulations in the BNC and CNC might be especially vulnerable in Alzheimer's disease.


Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.
Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.


Using unstimulated urinary lead excretion to assess the need for chelation in the treatment of lead poisoning.
To determine whether unstimulated urine samples could be used to identify children needing chelation therapy for lead poisoning, we compared urinary lead excretion with and without chelation. A convenience sample of 39 children was admitted to a pediatric clinical research center for therapeutic chelation. Urine was collected for 24 hours on 2 consecutive days. Edetate disodium calcium, 1000 mg/m2, was given intramuscularly in two divided doses on the second day. Significant correlations existed between urinary lead excretion (PbU) on the control day at 12- and 24-hour collection intervals and on the first day of chelation (p less than 0.0001). Published criteria for positive edetate disodium calcium provocative tests were used to calculate corresponding cutoff points for unstimulated 24-hour PbU. Resultant PbU values ranged from 10.4 to 35.6 micrograms (0.05 to 0.17 mumol). When PbU was expressed in terms of creatinine excretion, cutoff points of 0.06 and 0.19 microgram PbU/mg creatinine were determined, making possible the use of random unstimulated samples to assist in the identification of children in need of chelation.


Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography-UV-mass spectrometry methodology.
A standardised LC-UV-MS micro-scale method for screening of fungal metabolites and mycotoxins in culture extracts is presented. The paper includes data for detection and dereplication of > 400 fungal metabolites to facilitate detection and identification when standards are not available. The data also shows the types of components that can be analysed by positive electrospray (ESI+) mass spectrometry (MS) along with common fragments and adducts of these, as well as giving suggestions on whether UV or ESI+-MS methods should be used. Examples of dereplication of penitrems and macro-cyclic ichothecenes, and detection of several novel compounds are shown. This was done by UV spectroscopy combined with accurate mass determination of adduct and fragment ions obtained by high-resolution orthogonal time-of-flight MS.


A method for the rapid detection of urinary tract infections.
To determine the reliability of a rapid detection method compared with the reference standard streaked agar plate in diagnosing the presence of urinary tract infection (UTI). De-identified clean catch urine specimens from 980 office visit patients were processed during a 30-day period. Classic 1-μL and 10-μL streaked agar plates were used in parallel with the new CultureStat Rapid UTI Detection System (CSRUDS). Urine results were evaluated using the CSRUDS at 30 and 90 minutes after collection. A comparative analysis of the subsequent plate results versus the CSRUDS results was achieved for 973 of these samples. Positive UTI conditions were accurately identified by both CSRUDS and agar streak plate methods. CSRUDS accurately identified UTI negative conditions with 99.3% reliability at 90 minutes. The negative predictive value of CSRUDS was 99.2% at 30 minutes. Current agar plating for first-round UTI screening has substantial documented problems that can negatively affect an accurate and timely UTI diagnosis. A novel rapid detection system, the CSRUDS provides UTI negative/positive same-day results in ≤ 90 minutes from the start of test. Such rapidly available results will enable more accurate and timely clinical decisions to be made in the urology office, particularly regarding infection status before urologic instrumentation.


Ventilation homogeneity improves with growth early in life.
Some studies have suggested that lung clearance index (LCI) is age-independent among healthy subjects early in life, which implies that ventilation distribution does not vary with growth. However, other studies of older children and adolescents suggest that ventilation becomes more homogenous with somatic growth. We describe a new technique to obtain multiple breath washout (MBWO) in sedated infants and toddlers using slow augmented inflation breaths that yields an assessment of LCI and the slope of phase III, which is another index of ventilation inhomogeneity. We evaluated whether ventilation becomes more homogenous with increasing age early in life, and whether infants with chronic lung disease of infancy (CLDI) have increased ventilation inhomogeneity relative to full-term controls (FT). FT (N = 28) and CLDI (N = 22) subjects between 3 and 28 months corrected-age were evaluated. LCI decreased with increasing age; however, there was no significant difference between the two groups (9.3 vs. 9.5; P = 0.56). Phase III slopes adjusted for expired volume (S(ND)) increased with increasing breath number during the washout and decreased with increasing age. There was no significant difference in S(ND) between full-term and CLDI subjects (211 vs. 218; P = 0.77). Our findings indicate that ventilation becomes more homogenous with lung growth and maturation early in life; however, there is no evidence that ventilation inhomogeneity is a significant component of the pulmonary pathophysiology of CLDI.


Reduced delta power and synchrony and increased gamma power during the P3 time window in schizophrenia.
Event-related potential studies in schizophrenia have demonstrated amplitude reduction of the P3 in oddball tasks. The P3 has been linked to attention and memory brain functions. In 24 schizophrenia patients and 28 control subjects, wavelet transform was used to reveal event-related modulations of the EEG signal during target trials in delta, theta, alpha, beta, and gamma frequency bands. Patients showed reductions in P3 amplitude accompanied by reduced low frequency delta-theta and increased beta-gamma band EEG activity. These results indicate abnormalities in the synchronization and/or efficiency of neural processes involved in memory and attention networks in schizophrenia.


(E)-4-[(3,5-Dimethyl-phen-yl)imino-meth-yl]-2-meth-oxy-3-nitro-phenol.
The mol-ecule of the title compound, C(16)H(16)N(2)O(4), exists in the E configuration with respect to the central C=N double bond. The dihedral angle between the two benzene rings is 2.17 (9) Å. In the crystal, mol-ecules are linked via O-H⋯N hydrogen bonds into chains that propagate along the b-axis direction. There is also π-π stacking of inversion-related mol-ecules, with inter-planar spacings of 3.479 (5) Å and ring centroid-centroid distances of 3.876 (4) Å.


Syphilitic proctitis.
Two adult male homosexuals with syphilitic proctitis and without any detectable anal lesions are reported. There was no history or evidence of an external primary chancre in either patient. Of note, one had extensive rectal involvement of the first 20 cm and the other had multiple sites involved. One patient developed severe rectal bleeding following biopsy and a Jarisch-Herxheimer reaction after the first penicillin injection. Salient features of the literature are reviewed and discussed.


Abdominal sacrocolpopexy: anatomic outcomes and complications with Pelvicol, autologous and synthetic graft materials.
The purpose of this study was to compare anatomic outcomes and graft-related complications (GRCs) for abdominal sacrocolpopexy (ASC) with Pelvicol (CR BARD, Murray Hill, NJ), autologous fascia, and synthetic grafts. This is a retrospective cohort study of ASC from 2001-2005. We reviewed anatomic outcomes and GRCs. Apical failure was defined as >stage 0. Of 259 ASC procedures, Pelvicol was used in 102 procedures (39%); synthetic mesh in 134 procedures (52%), and autologous fascia in 23 procedures (9%). Mean postoperative follow up was 1.1 years. Apical failure by graft group were Pelvicol 10 (11%), synthetics 1 (1%), and autologous 1 (7%; P = .011). All 7 reoperations for apical prolapse were in the Pelvicol group. GRCs occurred in 16% of the cases, with a higher proportion of erosions in the Pelvicol group (11% vs 3% and 4%; P = .045). Reoperations as a result of GRC were similar between groups. ASC is more likely to fail with Pelvicol than with synthetic or autologous grafts. The use of Pelvicol did not reduce graft-related complications in this population.


Enhancement of anaerobic digestibility of waste activated sludge using photo-Fenton pretreatment.
Biological treatments, such as activated sludge process, are common methods to treat municipal and industrial wastewaters. However, they produce huge amounts of waste activated sludge (WAS). The excess sludge treatment and disposal are a challenge for wastewater treatment plants due to economic, environmental, and regulatory factors. In this study, photo-Fenton pretreatment (oxidation using hydrogen peroxide and iron catalyst aided with UV light) was optimized using response surface methodology (RSM) and central composite design (CCD) to determine the effects of three operating parameters (H2O2 dosage, H2O2/Fe2+ molar ratio, and irradiation time) on disintegration and dewaterability of WAS. MLVSS removal, capillary suction time (CST) reduction, sCOD, and EPS were obtained as 70%, 25%, 12,000 mg/L, and 500 mg/L, respectively, at the optimal conditions, i.e., 725 g H2O2/kg TS, H2O2/Fe2+ molar ratio 80, and irradiation time 40 min. Two batch-fed completely mixed mesophilic anaerobic digesters were then operated at 15-day solid retention time (SRT) and 37 ± 0.5 °C to compare the digestibility of untreated and photo-Fenton pretreated sludge in terms of volatile solids (VS) reduction, COD removal, and biogas production at steady-state operations. Photo-Fenton pretreatment followed by anaerobic digestion of WAS was very effective and yielded 75.7% total VS reduction, 81.5% COD removal, and 0.29-0.31 m3/kg VSfed·d biogas production rate, compared to 40.7% total VS solid reduction, 54.7% COD removal, and 0.12-0.17 m3/kg VSfed·d biogas production rate for control. Thus, photo-Fenton can be a useful pretreatment step in sludge management.


Transformation of cholic acid by Arthrobacter simplex.
Fermentation of cholic acid with Arthrobacter simplex (IICB 227) under aerobic conditions yielded 3,12-dioxo-23,24-dinorchola-4,6-dienoic acid, 7 alpha-hydroxy-3,12-dioxo-23,24-dinorchol-4-enoic acid, 3 alpha, 7 alpha-dihydroxy-12-oxo-5 beta-cholan-24-oic acid, 3 alpha, 7 alpha-dihydroxy-12-oxo-5 beta-23,24-dinorcholan-22-oic acid, 7 alpha, 12 alpha-dihydroxy-3-oxo-5 beta-cholan-24-oic acid, 7 alpha-12 alpha-dihydroxy-3-oxo-4-cholenoic acid, 7 alpha, 12 alpha-dihydroxy-3-oxo-23,24-dinorchol-4-enoic acid, and methyl-3 alpha-7 alpha, 12 alpha-trihydroxy-5 beta-cholan-24-oate in addition to a new metabolite 2 beta-hydroxy-3,12-dioxo-23,24-dinorchola-4,6-dienoic acid. Each microbial metabolite was characterized by the application of various spectroscopic methods. The availability of some of the metabolites' enabled complete elucidation of their 13C NMR spectra.


The folded, bipaddled pectoralis major composite flap in oral cancer reconstruction.
We report on the pectoralis major composite (musculocutaneous or rib osteomusculocutaneous) flap used in bipaddled fashion for one-stage immediate reconstruction in 53 patients with oral cancer. Of these, 44 patients had lesions of buccal mucosa and lateral lower alveolus, and 9 patients had lesions of floor of mouth and middle third of lower alveolus. In one patient this flap was used as a free composite tissue transfer in bipaddled fashion. The flap can be used either before or after radiotherapy in oral cancer and provides both lining mucosa and skin cover. If necessary, a rib (vascularised bone graft) incorporated with this composite flap can give skeletal support for mandibular arch reconstruction.


Structure-activity characterization of sulfide:quinone oxidoreductase variants.
Sulfide:quinone oxidoreductase (SQR) is a peripheral membrane protein that catalyzes the oxidation of sulfide species to elemental sulfur. The enzymatic reaction proceeds in two steps. The electrons from sulfides are transferred first to the enzyme cofactor, FAD, which, in turn, passes them onto the quinone pool in the membrane. Several wild-type SQR structures have been reported recently. However, the enzymatic mechanism of SQR has not been fully delineated. In order to understand the role of the catalytically essential residues in the enzymatic mechanism of SQR we produced a number of variants of the conserved residues in the catalytic site including the cysteine triad of SQR from the acidophilic, chemolithotrophic bacterium Acidithiobacillus ferrooxidans. These were structurally characterized and their activities for each reaction step were determined. In addition, the crystal structures of the wild-type SQR with sodium selenide and gold(I) cyanide have been determined. Previously we proposed a mechanism for the reduction of sulfides to elemental sulfur involving nucleophilic attack of Cys356 on C(4A) atom of FAD. Here we also consider an alternative anionic radical mechanism by direct electron transfer from Cys356 to the isoalloxazine ring of FAD.


[Intracellular potassium in normal and pathological pregnancy. I. Regulation of transport and concentration].
Potassium is the most represented intracellular cation. Its concentration is regulated by active and passive mechanisms: cellular capacity, diffusion, channels and active transport. The relationships among Potassium and other cell cations may be involved in the pregnancy adaptation, and in the pathogenesis of some diseases, among which hypertension and diabetes.


Analysis of free fractions for chiral drugs using ultrafast extraction and multi-dimensional high-performance affinity chromatography.
A multi-dimensional chromatographic approach was developed to measure the free fractions of drug enantiomers in samples that also contained a binding protein or serum. This method, which combined ultrafast affinity extraction with a chiral stationary phase, was demonstrated using the drug warfarin and the protein human serum albumin.


Patterns of covert speech behavior and phonetic coding.
In previous research a discriminative relationship has been established between patterns of covert speech behavior and the phonemic system when processing continuous linguistic material. The goal of the present research was to be more analytic and pinpoint covert neuromuscular speech patterns when one processes specific instances of phonemes. Electromyographic (EMG) recording indicated that the lips are significantly active when visually processing the letter "P"(an instance of bilabial material), but not when processing the letter "T" or a nonlinguistic control (C) stimulus. Similarly, the tongue is significantly active when processing the letter "T" (an instance of lingual-alveolar material), but not when processing the letters "P" or "C". It is concluded that the speech musculature covertly responds systematically as a function of class of phoneme being processed. These results accord with our model that semantic processing ("understanding") occurs when the speech (and other) musculature interacts with linguistic regions of the brain. In the interactions phonetic coding is generated and transmitted through neuromuscular circuits that have cybernetic characteristics.


Retinoic acid and dexamethasone interact to regulate S14 gene transcription in 3T3-F442A adipocytes.
We have examined the effects of retinoic acid (RA) on S14 gene expression in 3T3-F442A preadipocytes and adipocytes. RA induced mRNAS14 14-fold in adipocytes, but had no effect on S14 gene expression in preadipocytes. Northern analysis of retinoic acid receptor (RAR) isoforms revealed the presence of RAR alpha, but not RAR beta, in both preadipocytes and adipocytes. These results suggest that adipocyte-specific factors expressed during differentiation may be required for RA control of S14 gene expression in cultured adipocytes. When compared to dexamethasone (DEX), RA was a weak inducer of S14 gene expression. However, when added together, RA and DEX acted synergistically to induce S14 gene expression. Since changes in S14 gene transcription paralleled changes in mRNAS14 levels, the principal target for RA and DEX action on S14 gene expression was at the level of gene transcription. In the presence of DEX (0.1 nM), RA effects on S14 gene expression were dose-dependent (ED50 = 5 nM) and rapid (within 4 h). In contrast to S14, RA inhibited glycerol 3-phosphate dehydrogenase (GPD) gene transcription and mRNAGDP abundance by 75%. The effects of RA on S14 and GPD gene transcription in cultured adipocytes suggest that RA action may extend beyond growth and differentiation to include effects on lipid metabolism.


Sludge disinfection using electrical thermal treatment: The role of ohmic heating.
Electrical heating has been proposed as a potential method for pathogen inactivation in human waste sludge, especially in decentralized wastewater treatment systems. In this study, we investigated the heat production and E. coli inactivation in wastewater sludge using electrical thermal treatment. Various concentrations of NaCl and NH4Cl were tested as electrolyte to enhance conductivity in sludge mixtures. At same voltage input (18V), sludge treated with direct current (DC) exhibited slower ascent of temperature and lower energy efficiencies for heat production comparing to that using alternate current (AC). However, DC power showed better performance in E. coli inactivation due to electrochemical inactivation in addition to thermal inactivation. Greater than 6log10 removal of E. coli was demonstrated within 2h using 0.15M of NaCl as electrolyte by AC or DC power. The heat production in sludge was modeled using Maxwell-Eucken and effective medium theory based on the effective electrical conductivity in the two-phase (liquid and solid) sludge mixtures. The results showed that the water and heat loss is a critical consideration in modeling of sludge temperature using ohmic heating. The experimental data also suggested that the models are less applicable to DC power because the electrochemical reactions triggered by DC reduce the concentration of NH4+ and other ions that serve as electrolyte. The results of this study contribute to the development of engineering strategies for human waste sludge management.


Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives.
N-Methyl-D-aspartate receptors (NMDARs) composed of different splice variants display distinct pH sensitivities and are crucial for learning and memory, as well as for inflammatory or injury processes. Dysregulation of the NMDAR has been linked to diseases like Parkinson's, Alzheimer's, schizophrenia, and drug addiction. The development of selective receptor modulators, therefore, constitutes a promising approach for numerous therapeutical applications. Here, we identified (R)-OF-NB1 as a promising splice variant selective NMDAR antagonist. We investigated the interaction of (R)-OF-NB1 and NMDAR from a biochemical, bioinformatical, and electrophysiological perspective to characterize the downstream allosteric modulation of NMDAR by 3-benzazepine derivatives. The allosteric modulatory pathway starts at the ifenprodil binding pocket in the amino terminal domain and immobilizes the connecting α5-helix to the ligand binding domain, resulting in inhibition. In contrast, the exon 5 splice variant GluN1-1b elevates the NMDARs flexibility and promotes the open state of its ligand binding domain.


The predictive value of inflammatory markers for pathological response of ipsilateral supraclavicular lymph nodes and for prognosis in breast cancer after neoadjuvant chemotherapy.
Inflammatory tumor microenvironment is closely related to cancer. In this study, we mainly explore the predictive value of inflammatory markers for pathological response of ipsilateral supraclavicular lymph nodes (ISLN) and for prognosis in breast cancer with ISLN metastasis after neoadjuvant chemotherapy (NAC). In this study, 117 breast cancer patients with ISLN metastasis were collected from the Affiliated Hospital of Zhengzhou University. The best cut-off value was determined by using the receiver operating characteristics (ROC) curve. Chi-square test and binary Logistic regression were used to analyze the correlation between clinical pathological data and pathological response of ISLN and to determine independent predictors. Correlation analysis between inflammatory markers and prognosis used time-dependent COX regression. The pathological complete response (pCR) rate of ISLN after NAC was 64.4%. Multivariate analysis showed that breast pCR (OR 9.67, 95% CI: 2.64-35.31, P<0.01) was an independent predictor of ISLN pathological response after NAC. After a median follow-up of 25 months, multivariate time-dependent COX results showed that higher platelet levels were correlated with poor disease-free survival (DFS) (HR 1.008, 95% CI: 1.001-1.015, P=0.028). Meanwhile, menopausal status (HR 0.35, 95% CI: 0.15-0.79, P=0.01) and supraclavicular pCR (HR 0.33, 95% CI: 0.15-0.77, P=0.01) were also independent predictors of DFS. Peripheral blood inflammatory markers have limited predictive value for pathological response of ISLN after NAC for breast cancer. High platelet count is associated with poor prognosis of breast cancer patients with ISLN metastasis.


Fine mapping of the tiller inhibition gene TIN4 contributing to ideal plant architecture in common wheat.
A tiller inhibition gene, TIN4, was mapped to an approximately 311 kb genomic interval on chromosome arm 2DL of wheat. The tiller is one of the key components of plant morphological architecture and a central agronomic trait affecting spike number in wheat. Low tiller number has been proposed as a major component of crop ideotypes for high yield potential. In this study, we characterized the development of tillering in near-isogenic lines (NIL7A and NIL7B), indicating that the TIN4 gene inhibited the growth of tillering buds and negatively regulated tiller number. Low-tillering was controlled by a single gene (TIN4) located on chromosome 2DL by genetic analysis and bulked segregant RNA-seq analysis. A total of 17 new polymorphic markers were developed in this study, and 61 recombinants were identified in the secondary F2 population containing 4,266 individuals. TIN4 was finally mapped on a 0.35 cM interval, co-segregated with molecular marker M380, within a 311 kb genomic interval of the wheat cultivar Chinese Spring reference genome sequence that contained twelve predicted genes. Yield experiments showed that the yield of low-tillering lines was higher than that of high-tillering lines at a higher density. Overall, this study provides a foundation for the construction of a low-tillering ideotype for improving wheat yield and further cloning TIN4 by map-based cloning approach.


Continuous renal replacement therapy with an automated monitor is superior to a free-flow system during extracorporeal life support.
To determine whether integrated continuous renal replacement therapy provides more accurate fluid management than IV pump free-flow ultrafiltration in pediatric patients on extracorporeal life support. Retrospective study. PICU and neonatal ICU in a tertiary academic center. Infants and children less than 18 years old. Extracorporeal membrane oxygenation and continuous renal replacement therapy. Clinical data collected on patients who received free-flow or integrated renal replacement therapy while on extracorporeal life support. Normalized ultrafiltration error was calculated as: (physician specified fluid loss per 24-hr period - actual fluid loss per 24-hr period) divided by patient body weight (kg). Mixed linear regression analyses were used to model longitudinal ultrafiltration error trajectories within each mode of ultrafiltration. Based on an analysis of 458 serial ultrafiltration fluid balance measurements, integrated ultrafiltration was significantly more accurate than free-flow ultrafiltration (normalized ultrafiltration error of 1.2 vs 13.1 mL; p < 0.001). After adjusting for patient factors and time, integrated ultrafiltration was associated with a significantly lower normalized ultrafiltration error (variable estimate, -24 ± 6; p < 0.001). The use of integrated ultrafiltration was associated with shorter duration of extracorporeal life support (384 vs 583 hr, p < 0.001) and renal replacement therapy (185 vs 477 hr, p < 0.001) than free-flow patients. Overall ICU and hospital length of stay and in-hospital mortality were similar between the groups. While free-flow ultrafiltration has the advantages of simplicity and low cost, integrated renal replacement therapy provides more accurate fluid management during extracorporeal life support. Better fluid status management with integrated renal replacement therapy may contribute to shorter duration of extracorporeal life support.


Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study.
Changes in cognitive function have been identified in and reported by many cancer survivors. These changes have the potential to impact patient quality of life and functional ability. This prospective longitudinal study was designed to quantify the incidence of change in cognitive function in newly diagnosed ovarian cancer patients throughout and following primary chemotherapy. Eligible patients had newly diagnosed, untreated ovarian cancer and had planned to receive chemotherapy. Web-based and patient reported cognitive assessments and quality of life questionnaires were conducted prior to chemotherapy, prior to cycle four, after cycle six, and six months after completion of primary therapy. Two-hundred-thirty-one evaluable patients entered this study between May 2010 and October 2011. At the cycle 4 time point, 25.2% (55/218) of patients exhibited cognitive impairment in at least one domain. At the post-cycle 6 and 6-month follow up time points, 21.1% (44/208) and 17.8% (30/169) of patients, respectively, demonstrated impairment in at least one domain of cognitive function. There were statistically significant, but clinically small, improvements in processing speed (p<0.001) and attention (p<0.001) but not in motor response time (p=0.066), from baseline through the six-month follow up time period. This was a large, prospective study designed to measure cognitive function in ovarian cancer. A subset of patients had evidence of cognitive decline from baseline during chemotherapy treatment in this study as measured by the web-based assessment; however, changes were generally limited to no more than one domain.


Crystal engineering of high explosives through lone pair-π interactions: Insights for improving thermal safety.
In this high-risk/high-reward study, we prepared complexes of a high explosive anion (picrate) with potentially explosive s-tetrazine-based ligands with the sole purpose of advancing the understanding of one of the weakest supramolecular forces: the lone pair-π interaction. This is a proof-of-concept study showing how lone pair-π contacts can be effectively used in crystal engineering, even of high explosives, and how the supramolecular architecture of the resulting crystalline phases influences their experimental thermokinetic properties. Herein we present XRD structures of 4 novel detonating compounds, all showcasing lone pair-π interactions, their thermal characterization (DSC, TGA), including the correlation of experimental thermokinetic parameters with crystal packing, and in silico explosion properties. This last aspect is relevant for improving the safety of high-energy materials.


Neural mechanisms of spatial- and feature-based attention: a quantitative analysis.
Attentional selection can be based on spatial locations, non-spatial stimulus features, or entire objects as integrated feature ensembles. Several studies reported attentional modulations in those regions that process the constituent features of the presented stimuli. Here we employed functional magnetic resonance imaging (fMRI) to directly compare the magnitude of space- and/or feature-based attentional modulations while subjects directed their attention to a particular color (red or green) of a transparent surface and at the same time to a spatial location (left or right visual field). The experimental design made it possible to disentangle and quantify the hemodynamic activity elicited by identical physical stimuli when attention was directed to spatial locations and/or stimulus features. The highest modulations were observed when the attentional selection was based on spatial location. Attended features also elicited a response increase relative to unattended features when their spatial location was attended. Importantly, at unattended locations, a response increase upon feature-based selection was observed in motion-sensitive but not in color-related areas. This suggests that compared to color, motion stimuli are more effective in capturing attention at unattended locations leading to a competitive advantage. These results support the idea of a high biological relevance of the feature motion in the visual world.


Cardiovascular risk factors: differences between ethnic groups.
to compare the metabolic, anthropometric, tobacco and alcohol consumption indicators considered as risk factors for cardiovascular diseases, as well as the demographic and socioeconomic characteristics between indigenous from Rio Negro, Sateré-Mawé, mixed-race/black and white people living in the city of Manaus. a cross-sectional observational study guided by the STROBE tool. There was a sample of 191 adults of both sexes. Anthropometric measurements, blood pressure and biochemical analyzes were performed. Statistical test was applied to cross color/race/ethnicity variable with the investigated variables. indigenous had better metabolic and anthropometric indicators related to cardiovascular diseases than mixed-race/black and white, as well as Sateré-Mawé in relation to Rionegrinos (from Rio Negro). the main differences were obesity, dyslipidemia, pre-systemic arterial hypertension/systemic arterial hypertension, and increased circumferences, with a worse situation for mixed-race/black people. The findings indicate differences in risk factors between race/color and ethnicity groups evaluated.


Coumarin accumulation and trafficking in Arabidopsis thaliana: a complex and dynamic process.
Iron (Fe) is a major micronutrient and is required for plant growth and development. Nongrass species have evolved a reduction-based strategy to solubilize and take up Fe. The secretion of Fe-mobilizing coumarins (e.g. fraxetin, esculetin and sideretin) by plant roots plays an important role in this process. Although the biochemical mechanisms leading to their biosynthesis have been well described, very little is known about their cellular and subcellular localization or their mobility within plant tissues. Spectral imaging was used to monitor, in Arabidopsis thaliana, the in planta localization of Fe-mobilizing coumarins and scopolin. Molecular, genetic and biochemical approaches were also used to investigate the dynamics of coumarin accumulation in roots. These approaches showed that root hairs play a major role in scopoletin secretion, whereas fraxetin and esculetin secretion occurs through all epidermis cells. The findings of this study also showed that the transport of coumarins from the cortex to the rhizosphere relies on the PDR9 transporter under Fe-deficient conditions. Additional experiments support the idea that coumarins move throughout the plant body via the xylem sap and that several plant species can take up coumarins present in the surrounding media. Altogether, the data presented here demonstrate that coumarin storage and accumulation in roots is a highly complex and dynamic process.


Immune responses during recovery from protein-energy malnutrition.
Protein-energy malnutrition (PEM) is a worldwide problem. Infants and children from developing countries and elderly people from all around the world are the two main groups suffering from PEM. PEM induces profound immunodeficiency, characterized mainly by decreased cell-mediated immunity, and also by decreased humoral and non-specific immunity. Non-specific immune deficiency is of particular importance for defences against infections and its decrease in PEM may further deteriorate nutritional and immune status, pushing patients into a vicious and dramatic circle. Refeeding such patients and the restoration of their nutritional status lead to improvement in all immune responses: a strong association between the evolution of these two responses is always observed during refeeding. The need for specific nutrients to restore immune functions during refeeding of PEM patient has been extensively studied in the past years. This review describes the pathophysiological mechanisms of immune consequences of PEM and of immune restoration with refeeding, and in addition focuses upon some nutrients of particular importance, namely glutamine, zinc and vitamin E. Particular attention is directed at the elderly patients with PEM, a growing population for which the importance of undernutrition on prognosis is not yet fully recognized.


Androgens stimulate coordinated lipogenic gene expression in normal target tissues in vivo.
In prostate cancer cell lines in culture androgens cause a marked and coordinated upregulation of the expression of several lipogenic genes. Here, using castrated male Wistar rats as an experimental paradigm, we investigated whether coordinated androgen stimulation of lipogenic gene expression represents a more general physiological regulation in non-cancerous androgen-responsive cells as well. In typical target tissues for androgen action such as the ventral prostate and the lacrimal gland, androgen deprivation resulted in a marked reduction in the mRNA and protein levels of genes involved in fatty acid (fatty acid synthase and acetyl-CoA-carboxylase) and cholesterol synthesis (HMG-CoA-reductase and farnesyl diphosphate synthase). Readministration of testosterone immediately following orchidectomy restored the expression of all four genes. Substitution of testosterone by the non-aromatizable androgen dihydrotestosterone gave rise to comparable changes in the mRNA and protein levels of the lipogenic genes under investigation, confirming the involvement of the androgen receptor in the observed effects. In support of the coordinate nature of this regulation, androgen-induced upregulation of lipogenic gene expression is accompanied by an increase in the nuclear content of SREBP, a key lipogenic transcription factor. Taken together, these findings provide evidence for a coordinate regulation of lipogenic gene expression not only in prostate cancer cell lines in culture but also in non-cancerous androgen-responsive tissues in vivo.


Combination of dispersive solid phase extraction with solidification organic drop-dispersive liquid-liquid microextraction based on deep eutectic solvent for extraction of organophosphorous pesticides from edible oil samples.
A dispersive solid phase extraction method was combined with deep eutectic solvent-based solidification of floating organic drop-dispersive liquid-liquid microextraction and used for the extraction/preconcentration of some organophosphorus pesticides residues from edible oil samples. The extracted analytes were quantified with gas chromatography-nitrogen phosphorous detector. In this procedure, the sample lipids are saponified with a sodium hydroxide solution and then the analytes are adsorbed onto a primary secondary amine sorbent. After that the analytes are desorbed with acetone as an elution/dispersive solvent and mixed with choline chloride: 3,3-dimethyl butyric acid deep eutectic solvent and the mixture is rapidly dispersed into deionized water. Then, the obtained cloudy solution is centrifuged and placed into an ice bath. The extraction solvent is solidified on the top of the solution. Finally, it is removed and dissolved in acetonitrile, and 1 µL of the solution is injected into the separation system. Validation of the method showed that limits of detection and quantification were in the ranges of 0.06-0.24 and 0.20-0.56 ng mL-1, respectively. Enrichment factors and extraction recoveries of the analytes ranged from 170-192 and 68-77%, respectively. The method had an acceptable precision with relative standard deviations less than ≤9.2% for intra- (n=6) and inter-day (n=6) precisions at four concentrations (3, 10, 50, and 250 ng mL-1, each analyte). Finally the method was used for determination of the analytes in five edible oil samples.


Effects of α-conotoxin ImI on TNF-α, IL-8 and TGF-β expression by human macrophage-like cells derived from THP-1 pre-monocytic leukemic cells.
α7 nicotinic acetylcholine receptors (nAChRs) are ubiquitous in the nervous system and ensure important neurophysiological functionality for many processes. However, they are also found in cells of the immune system, where their role has been less studied. Here we report the pro-inflammatory effect of ImI, a well characterized conotoxin that inhibits α7 nAChRs, on differentiated THP-1 pre-monocyte macrophages (MDM) obtained by phorbol 12-myristate 13 acetate (PMA) treatment. Enzyme-linked immunosorbent assay (ELISA) performed on supernatant fluids of LPS challenged MDM showed ImI-mediated upregulation of pro-inflammatory cytokine TNF-α in an ImI concentration-dependent manner from 0.5 to 5.0 µmol/L and for IL-8 up to 1.0 µmol/L. Levels of anti-inflammatory cytokine TGF-β remained practically unaffected in ImI treated MDMs. Nicotine at 10 µmol/L significantly downregulated the release of TNF-α, but showed a lesser effect on IL-8 secretion and no effect on TGF-β. Fluorescent competitive assays involving ImI, α-bungarotoxin and nicotine using MDM and the murine macrophage RAW 264.7 suggest a common binding site in the α7 receptor. This work extends the application of conotoxins as molecular probes to non-excitatory cells, such as macrophages and supports the involvement of the α7 nAChR in regulating the inflammatory response via the cholinergic anti-inflammatory pathway (CAP).


Transient structure and SH3 interaction sites in an intrinsically disordered fragment of the hepatitis C virus protein NS5A.
Understanding the molecular mechanisms involved in virus replication and particle assembly is of primary fundamental and biomedical importance. Intrinsic conformational disorder plays a prominent role in viral proteins and their interaction with other viral and host cell proteins via transiently populated structural elements. Here, we report on the results of an investigation of an intrinsically disordered 188-residue fragment of the hepatitis C virus non-structural protein 5A (NS5A), which contains a classical poly-proline Src homology 3 (SH3) binding motif, using sensitivity- and resolution-optimized multidimensional NMR methods, complemented by small-angle X-ray scattering data. Our study provides detailed atomic-resolution information on transient local and long-range structure, as well as fast time scale dynamics in this NS5A fragment. In addition, we could characterize two distinct interaction modes with the SH3 domain of Bin1 (bridging integrator protein 1), a pro-apoptotic tumor suppressor. Despite being largely disordered, the protein contains three regions that transiently adopt α-helical structures, partly stabilized by long-range tertiary interactions. Two of these transient α-helices form a noncanonical SH3-binding motif, which allows low-affinity SH3 binding. Our results contribute to a better understanding of the role of the NS5A protein during hepatitis C virus infection. The present work also highlights the power of NMR spectroscopy to characterize multiple binding events including short-lived transient interactions between globular and highly disordered proteins.


Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice.
The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'


Biological underpinnings of psychogenic nonepileptic seizures: directions for future research.
Psychogenic nonepileptic seizures (PNES) are relatively common occurrences in epilepsy centers, but their pathophysiology is still poorly understood. Research that elucidates the pathophysiology of PNES, including their neurobiological basis and biomarkers, may have important clinical implications. The literature provides some evidence that genetic factors, intrinsic factors, and environmental factors probably play a significant role as the biological underpinnings of PNES. Researchers may be able to learn more about the pathophysiology of PNES by investigating the effects of each of these factors on functional and structural brain connectivity.


Further evidence of a right hand advantage in motor skill by chimpanzees (Pan troglodytes).
Asymmetries in motor skill when grasping small food items was evaluated in a sample of captive chimpanzees. In two experiments, error rates in grasping food were assessed when controlling for individual differences in grip morphology. In both experiments, chimpanzees were found to make more errors with the left compared to the right hand. Male chimpanzees were also found to make more errors compared to females. These results are discussed in the context of a presumed disassociation between hand preference and performance as indicators of cerebral dominance in motor functions.


Synthesis and development of new 2-substituted 1-[3-(4-arylpiperazin-1-yl)propyl]-pyrrolidin-2-one derivatives with antiarrhythmic, hypotensive, and alpha-adrenolytic activity.
A series of new 1-[3-(4-arylpiperazinyl-1-yl)-2-(N-alkylcarbamoyloxy)propyl]-pyrrolidin-2-one derivatives (4a-12a) were synthesised and tested for their electrocardiographic, antiarrhythmic and antihypertensive activity, as well as for the alpha1- and alpha2-adrenoceptor binding affinities. Of the newly synthesised derivatives, 1-{2-(N-2-methylethylcarbamoiloxy)-3-[4-(2-methoxyphenyl)piperazin-1-yl)]propyl}pyrrolidin-2-one dihydrochloride (10a) was the most active in prophylactic antiarrhythmic tests, its ED50 value equalling 2.7 mg kg(-1), and the therapeutic index being 75.2; moreover, compound 10a was also found to possess hypotensive activity. A preliminary molecular modelling study suggested that the selected alpha1-AR antagonist distances and angles between pharmacophoric features, estimated for the tested compounds, were in good agreement with the parameters evaluated for ligands.


Mumps virus-specific immune response outcomes and sex-based differences in a cohort of healthy adolescents.
Despite high levels of MMR-II usage in the US, mumps outbreaks continue to occur. Evidence suggests that mumps vaccine-induced humoral immunity wanes over time. Relatively few studies have examined cell-mediated immunity or reported on sex-based differences. To better understand sex-based differences in the immune response to mumps vaccine, we measured neutralizing antibody titers and mumps-specific cytokine/chemokine responses in a cohort of 748 adolescents and young adults after two doses of MMR vaccine. We observed significantly higher neutralizing antibody titers in females than in males (120.8 IU/mL, 98.7 IU/mL, p = 0.038) but significantly higher secretion levels of MIP-1α, MIP-1β, TNFα, IL-6, IFNγ, and IL-1β in males compared to females. These data demonstrate that sex influences mumps-specific humoral and cell-mediated immune response outcomes, a phenomenon that should be considered during efforts to improve vaccines and prevent future outbreaks.


Interaction of triethyl lead chloride with microtubules in vitro and in mammalian cells.
The effects of triethyl lead chloride (TriEL) on the in vitro assembly and disassembly of microtubules (MTs) from porcine brain were studied by turbidometry at 350 nm and by electron microscopy. TriEL inhibited MT assembly at 50 microM concentration and caused an almost complete disassembly of preformed MTs. The drug depolymerized MTs more effectively than colchicine. Concentrations higher than 50 microM TriEL caused an aberrant assembly process. Fibers about 10 nm width were formed in addition to aggregates of amorphous material. In vivo TriEL also caused MT depolymerization in interphase and mitotic PtK-1 and Ehrlich ascites tumor (EAT) cells as monitored by indirect immuno-fluorescent staining of tubulin and electron microscopy. The extent of MT depolymerization was concentration- and time-dependent. Recovery occurred as early as 5 min after removal of the drug. The fluorescent actin pattern in PtK-1 cells typical of stress fibers and subcortical filaments seemed not to be altered by the presence of TriEL. The vimentin intermediate filament system was, however, rearranged as a juxtanuclear complex after TriEL treatment. Furthermore, TriEL effected the inhibition of cellular growth (100% inhibition at about 10(-5) M). Cytokinesis is prevented to a great extent, resulting in the formation of binucleate cells which can additionally possess some micronuclei.


Predictors and outcomes of early post-operative veno-arterial extracorporeal membrane oxygenation following infant cardiac surgery.
We aimed to determine predictors of, and outcomes after, veno-arterial extracorporeal membrane oxygenation instituted within 48 h after cardiac surgery (early ECMO) in young infants. Patients ≤ 6 weeks old having cardiac surgery from 2003 to 2012 were enrolled prospectively. Patients cannulated pre-operatively, intra-operatively, or ≥ 48 h post-operatively were excluded. Variables at p ≤ 0.1 on univariate regression were entered into multiple logistic regression to predict early ECMO. Early-ECMO cases were matched 1:2 for six demographic variables, and death by age 2 years old (determined using conditional logistic regression; presented as odds ratio (OR), 95% confidence interval (CI)) and General Adaptive Composite scores at age 2 years (determined using Wilcoxon rank sum) were compared; p ≤ 0.05 was considered statistically significant. Of 565 eligible patients over the 10-year period, 20 had early ECMO instituted at a mean (standard deviation) of 12.4 (11.4) h post-operatively, 10 of whom had extracorporeal cardiopulmonary resuscitation. Of early-ECMO patients, 8 (40%) were found to have residual anatomic defects requiring intervention with catheterization (n = 1) and/or surgery (n = 7). On multiple regression, the post-operative day 1 highest vasoactive-inotrope score (OR 1.02; 95%CI 1.06,1.08; p < 0.001), highest lactate (OR 1.2; 95%CI 1.06,1.35; p = 0.003), and lowest base deficit (OR 0.82; 95%CI 0.71,0.94; p = 0.004), CPB time (OR 1.01; 95%CI 1.00,1.02; p = 0.002), and single-ventricle anatomy (OR 5.35; 95%CI 1.66,17.31; p = 0.005) were associated with early ECMO. Outcomes at 2 years old compared between early-ECMO and matched patients were mortality 11/20 (55%) vs 11/40 (28%) (OR 3.22, 95%CI 0.98,10.63; p = 0.054) and General Adaptive Composite median 65 [interquartile range (IQR) 58, 81.5] in 9 survivors vs 93 [IQR 86.5, 102.5] in 29 survivors (p = 0.02). The identified risk factors for, and outcomes after, having early ECMO may aid decision making in the acute period and confirm that neurodevelopmental follow-up for these children is necessary. The hypothesis that earlier institution of ECMO may improve long-term outcomes requires further study.


Late results of surgical and medical therapy for patients with coronary artery disease and depressed left ventricular function.
Late survival and freedom from myocardial infarction were determined for 192 patients with coronary artery disease and depressed left ventricular ejection fraction at rest (less than or equal to 35%) determined by biplane angiography who were evaluated between 1970 and 1977. Seventy-seven patients had coronary artery bypass grafting and 115 patients were treated medically and were considered surgical candidates. The medical and surgical groups were comparable in all baseline characteristics examined except frequency of three vessel disease and angina pectoris, which occurred in a significantly greater percent of the surgically treated patients (p less than 0.01). Only three medically treated patients (2.6%) underwent coronary bypass grafting in the follow-up period. Seven year actuarial survival was 63% in the surgical and 34% in the medical group (p less than 0.001). Ninety-three percent of patients in the surgical group and 81% of those in the medical group were free of nonfatal myocardial infarction (p = 0.01), and 62 and 33%, respectively, were alive and free of myocardial infarction (p less than 0.001) at 7 years. Significant differences in survival favoring surgical treatment were observed for the subsets of patients with an ejection fraction of 25% or less (p = 0.0002) and 26 to 35% (p = 0.01), and for the subsets with three vessel coronary disease (p less than 0.001), normal left ventricular end-diastolic volume (less than or equal to 100 ml/m2) (p = 0.005) and elevated end-diastolic volume (greater than 100 ml/m2)(p = 0.001). After adjustment for other important prognostic variables, the type of treatment remained significant in predicting the relative risk (medical to surgical) of mortality at 5 and 7 years (2.58 and 2.12, respectively). These data corroborate the trends observed in several randomized trials of medical and surgical therapy in patients with abnormal left ventricular function. If hospital mortality for coronary artery bypass grafting is less than 5%, substantial benefit can be anticipated for the majority of patients with depressed ventricular function.


Plumbing mysterious RNAs in "dark genome" for the conquest of human diseases.
Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. We also discuss challenges and future directions for developing lncRNA treatments, aiming to bridge the gap between functional studies and clinical potential and inspire further exploration in the field.


Overexpression of Chimeric RNA by Retroviral Transduction.
Cloning the open reading frame (ORF) of a protein-coding chimeric RNA into a mammalian expression vector is a simple, practiced way to study the function of the chimeric RNA. Here, we provide procedures for the insertion of the RRM2-C2orf48 fusion ORF into a mammalian expression vector, achieving the overexpression of the RRM2-C2orf48 fusion protein in a colon cancer cell line by retroviral transduction.


The levels of five markers of hemostasis and endothelial status at different stages of normotensive pregnancy.
Urinary 11-dehydrothromboxane B(2)/creatinine (11-DTXB(2)/Cr) is a marker for in vivo platelet activation and vascular constriction, blood thrombomodulin (TM) for endothelial damage and associated thrombosis, thrombin-antithrombin complex (TAT) for thrombin formation, and beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) for in vivo platelet activation and releasing reaction. Little is known about the quantitative relationship among them during pregnancy. The present study investigated levels of five markers at different stages of normotensive pregnancy. Subjects were 17 healthy non-pregnant women (Group 1, control) and 67 women carrying single fetuses in normotensive pregnancy. Of the pregnant women, 17 were in the 20th week of gestation (Group 2), 20 were in their 30th week (Group 3), and 30 were in their 36th week (Group 4). Urinary and circulating blood levels of 11-DTXB(2)/Cr, TM, TAT, beta-TG, and PF-4 were measured simultaneously. The 11-DTXB(2)/Cr and TAT levels showed elevated values at the 20th and 30th weeks of gestation, and markedly elevated values at the 36th week, whereas the TM level remained constant throughout pregnancy. The beta-TG and PF-4 levels maintained stable values at the 20th week, but showed elevated values at the 30th and 36th weeks. Platelet aggregation, vascular constriction, and thrombin formation (detected by 11-DTXB(2)/Cr and TAT) appear to be enhanced as early as the 20th week of gestation, continuously enhanced by the 30th week, and markedly enhanced by the 36th week. Platelet activation and releasing reaction (determined by beta-TG and PF-4) gradually enhanced from the 30th to 36th weeks. In contrast, endothelial damage and associated thrombosis (detected by TM) were minimal throughout pregnancy. Investigating these markers of hemostasis and endothelial function in normotensive pregnancy may provide insights into related disease states.


C/D Ratio in Long-Term Renal Function.
Tacrolimus is an immunosuppressive drug. Its C0 concentration, commonly used for monitoring, does not always correspond to its pharmacologic effect. Thölking et al developed an indicator, the C/D ratio, that describes the drug's metabolism rate. Our purpose was to determine whether the points dividing the patients into fast, intermediate, and slow metabolizers that were assumed by those authors would be similar for long-term follow-up after renal transplantation (RTx). We examined the C/D ratio in 571 patients at their most recent appointments-1 year and more after renal transplantation. The mean time after RTx was 84 months. We studied kidney function both at the most recent appointment and early after RTx. The median C/D ratio for our group was 1.68. Our observations revealed a negative correlation between the C/D ratio and creatinine concentration and a positive correlation between the C/D ratio and eGFR concentration long term after RTx. We formulated a C/D ratio cutoff point between an eGFR < and ≥ 60 mL/min/1.73 m2 and came up with the value of 1.53. It was found that between the < 1.53 and ≥ 1.53 groups, there were significant differences in creatinine and eGFR concentrations at the most recent appointment, as well as differences in how creatinine and eGFR levels varied over time between RTx and the most recent observation. The C/D ratio is useful for assessing the effect of the tacrolimus metabolism rate on long-term renal function. We propose the C/D ratio value of 1.53 as the cutoff point below which the ratio provides a negative prognosis for long-term renal function.


Repeated surveillance of exposure to thallium in a population living in the vicinity of a cement plant emitting dust containing thallium.
From 1979 to 1981, several medical surveys were carried out among a population living in the vicinity of a cement plant that emitted dust containing thallium until August, 1979. Air, soil, plants, and domestic animals in the area were contaminated by thallium and this led to an increased intake of thallium in the population, mainly due to the consumption of home-grown vegetables and fruit. In order to assess the degree of the individuals' exposure to thallium, thallium levels in 24-h urine samples (TlU) were determined. Three surveys were carried out from September to December, 1979 to assess the degree of thallium exposure of different parts of the general population. Subjects with relatively high exposure, as indicated by the results of the above mentioned population surveys, or those suffering from health disorders that might be related to an increased intake of thallium, were reexamined several times from 1979-1981. Special attention was also given to children attending a kindergarten situated about 0.5 km from the cement plant. As compared to an "unexposed" reference population (mean TlU: 0.3 microgram/l), the majority of the population living in the cement plant area had significantly elevated urinary thallium levels (range: less than 0.1-76.5 micrograms/l) indicating a substantially increased environmental exposure. A reduction of the intake of thallium was mainly achieved by the fact that the population, as advised by the authorities, largely avoided the consumption of home-grown, potentially contaminated foodstuffs. Reports on the teratogenicity of thallium in certain animal species caused great concern that thallium might have exerted teratogenic effects on the newborn of women exposed to thallium during pregnancy. Therefore, an investigation of children born between January, 1978 and August, 1979 (n = 297) was carried out. Although the number of congenital malformations was greater than expected, we conclude, considering carefully all data available, that there is likely no causal relationship between thallium and the occurrence of congenital malformations in the children investigated.


Effects of climate variability changes on runoff and erosion in the Western European Loess Belt region (NW, France).
Runoff and soil erosion are very pronounced in the Western European Loess Belt. In this study, the distributed physically-based model CLiDE is calibrated, validated, and applied to a catchment of this area (Dun, NW, France) to assess the hydro-sedimentary impacts of climate change scenarios. Despite considerable progress over the last decade in the study of runoff and soil erosion in the context of climate change, the effects of changes in the temporal variability of precipitation remain poorly understood, especially at the scale of a river basin. To examine these relationships more closely, we developed a stochastic weather generator to individually adjust the components that structure the temporal variability of rainfall. The climate scenarios considered represent projections to the year 2100 of the temporal variability of rainfall over NW Europe. The scenarios are based on historical daily rainfall records (1990-2012) and 4 exploratory assumptions: a 50 % decrease in the interannual rainfall regime (scenario 6yD), a 100 % increase in the interannual rainfall regime (scenario 6yI), a 50 % increase in the seasonal rainfall regime (scenario 1yI) and a 50 % increase in the synoptic rainfall regime (scenario 3dI). Simulated daily water and sediment discharges and erosion/deposition maps for each scenario are compared to those simulated for the situation without changes in rainfall. The time series were aggregated over different time intervals to allow for a multi-scale analysis of the differences. The results indicate that the model provides a satisfactory prediction of the catchment's water and sediment discharges, especially over the calibration period. Increased climate variability, whether on a synoptic (3dI), seasonal (1yI) or interannual (6yI) scale, leads to increased runoff and erosion. Increasing the synoptic rainfall variability (3dI) leads to the largest increase in mean annual runoff and erosion. Only the reduction of the interannual rainfall variability (6yD) provokes the decrease of these values.


Efficacy and safety of robot-assisted versus fluoroscopy-assisted PKP or PVP for osteoporotic vertebral compression fractures: a systematic review and meta-analysis.
Percutaneous vertebral augmentation (PVA), which includes percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Robot-assisted (RA) and fluoroscopy-assisted (FA) are important methods for treating osteoporotic vertebral compression fractures (OVCFs), though it is still unclear which is superior. This analysis aimed to compare the efficacy and safety of RA and FA. PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure were systematically searched, the outcomes included surgical parameters (leakage rate, operation time, number of fluoroscopic, injection volume, inclination angle), and clinical indexes (hospital stays, Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Cobb angle, the midline height of vertebral). Thirteen articles involving 1094 patients were included. RA group produced better results than the FA group in the leakage rate (OR = 0.27; 95% CI 0.17-0.42; P < 0.00001), number of fluoroscopic (WMD = - 13.88; 95% CI - 18.47 to - 9.30; P < 0.00001), inclination angle (WMD = 5.02; 95% CI 4.42-5.61; P < 0.00001), hospital stays (WMD = - 0.32; 95% CI - 0.58 to - 0.05; P = 0.02), VAS within 3 days (WMD = - 0.19; 95% CI - 0.26 to - 0.12; P < 0.00001), Cobb angle within 3 days (WMD = - 1.35; 95% CI - 2.56 to - 0.14; P = 0.003) and Cobb angle after 1 month (WMD = - 1.02; 95% CI - 1.84 to - 0.20; P = 0.01). But no significant differences in operation time, injection volume, ODI, the midline height of vertebral, and VAS score after 1 month. Our analysis found that the RA group had lower cement leakage rates, number of fluoroscopic and hospital stays, a larger inclination angle, better short-term pain improvement, and Cobb angle improvement. It is worth acknowledging that robotic-assisted surgery holds promise for the development of spine surgery. The study was registered in the PROSPERO (CRD42023393497).


Decoding the molecular mechanisms of neuronal migration using in utero electroporation.
During the development of the cerebral cortex, excitatory neurons are produced in the ventricular zone lining the lateral ventricle or in the adjacent subventricular zone and migrate toward the brain surface in a process known as radial migration. During radial migration, neurons undergo multiple steps including a multipolar cell phase, a multipolar-bipolar transition, and a locomotion phase. Many genes tightly regulate the cell behavior in each phase. We have established an in utero electroporation method as a rapid in vivo gene transfer system, and this system has greatly contributed to recent advances in our knowledge of the molecular mechanisms underlying each migration phase. Here, we review the cell behaviors of neurons during each phase of radial migration and the molecular mechanisms involved in these phases. Knockdown or functional blocking of these genes using in utero electroporation results in various migration defects and abnormal cell morphologies. Here, we describe these phenotypes as much as possible so that this review can be used as a chart to evaluate the phenotypes of novel gene knockdown experiments. We also discuss the recent application of in utero electroporation in studies examining the functions of neurodevelopmental disorder-related genes.


Bone marrow runs the (bone) show.
In this issue of JEM, a paper by Kim et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211872), asking a simple question through a remarkable alliance of human and mouse genetics, demonstrates that a prevalent hematological condition can lead to osteoporosis. This work is important by virtue of the quality of its results and its implication for the relationship between bone and its marrow.


Assessment of the risks associated with the use of chemical carcinogens in biomedical research.
Estimates of occupational exposure to chemical carcinogens in biomedical research based on environmental monitoring data, efficiency of containment devices, and accident data suggest that workers may be exposed to a few tenths of a microgram of these carcinogens per work day. Environmental exposure to carcinogenic polycyclic aromatic hydrocarbons and N-nitroso compounds exceeds one microgram per day. Because occupational exposure to chemical carcinogens in the laboratory can be readily controlled and because environmental exposure appears to be greater than the occupational exposure that does occur, the relative risk of occupational exposure does not seem to constitute a major health problem.


Surgical treatment of severe blepharoptosis and facial palsy caused by oculopharyngodistal myopathy.
Oculopharyngodistal myopathy is an extremely rare disease characterised by slowly progressive blepharoptosis, facial and bulbar muscle weakness and distal leg myopathy. We report the case of a 72-year-old woman with severe bilateral blepharoptosis and facial palsy caused by oculopharyngodistal myopathy that was present for more than 29 years. The condition was successfully treated by simple surgical intervention.


Prognostic value of preoperative soluble interleukin 2 receptor α as a novel immune biomarker in epithelial ovarian cancer.
Epithelial ovarian cancer (EOC) is regarded as the deadliest gynecological cancer, and the demand for novel noninvasive prognostic biomarkers remains significant. This study aimed to investigate the prognostic value of preoperative blood biomarkers in EOC patients. In total, 73 patients who had undergone ovarian mass resection were enrolled. Serum concentration of biomarkers, including soluble interleukin 2 receptor α (sIL-2R), was measured 1-2 weeks before surgery. Independent prognostic factors for progression-free survival (PFS) were investigated with multivariate Cox regression analysis. A prognostic model was subsequently developed and evaluated by discrimination, calibration and clinical net benefit. Furthermore, transcriptome data of 376 EOC cases from The Cancer Genome Atlas (TCGA) were analyzed with ESTIMATE, CIBERSORT and Maftools algorithm to evaluate the correlation of IL2RA expression with tumor immune microenvironment and immunotherapeutic response. High sIL-2R concentration was found to be the only significant prognostic blood biomarker for PFS by multivariate Cox regression analysis in our center. A prognostic nomogram was developed with satisfactory discrimination, calibration and clinical net benefit. In addition, higher IL2RA expression was significantly associated with higher immune scores, activated CD4+ T cells, M2 macrophages and resting dendritic cells in TCGA data. Furthermore, IL2RA expression was closely related to TMB scores. sIL-2R is a potential prognostic immune biomarker for EOC patients, and a comprehensive prognostic model comprising sIL-2R with satisfactory discrimination and clinical appliance was developed. Therefore, we recommend routine sIL-2R testing in EOC patients.


Does Helicobacter pylori eradication reduce the long-term requirements for acid suppressants in patients with a history of peptic ulcer disease in general practice? Results from a four-year longitudinal study.
Acid suppressants, especially proton-pump inhibitors, are major contributors to the drug costs in primary care. Although Helicobacter pylori eradication reduces peptic ulcer relapse, some studies suggest that patients may remain symptomatic and continue to require acid-suppressant therapy. We identified all patients taking long-term acid suppressants in a large primary health care clinic to determine the proportion who had peptic ulcer disease and to examine the effect of H. pylori eradication on their long-term requirement for acid suppressants. 126/394 patients taking long-term acid suppressants had a definite diagnosis of peptic ulcer. Of these 126 patients, 60 were considered appropriate for the study. At Stage 1 (May 1994), all patients were tested for H. pylori infection and positive patients (60/66) received eradication therapy with omeprazole 20 mg bd and amoxycillin (1 gm bd) or clarithromycin (500 mg tds) for 2 weeks. Six weeks later (Stage 2) patients, requirements for continued acid-suppressant treatment were determined and previously positive subjects retested using the 13C urea breath rest. This showed that 70% (42/60) had been successfully eradicated. One year later (Stage 3), 44% (18/41) of the patients successfully eradicated still required acid suppressants. The majority of these patients (11/18; 61%) continued to remain on acid-suppressant treatment at 4 years (Stage 4) (95% CI 38%, 83%). We found that about 1/3 of all patients on long-term acid-suppressant therapy in General Practice had a confirmed diagnosis of peptic ulcer disease. Despite successful eradication treatment for H. pylori at the start of the study, about half of these patients still used acid suppressants after 1 year and 1/4 patients (11/41) in this group continued to remain on acid-suppressant treatment for another 3 years.


Bud selection and apoptosis-like degradation of nuclei in yeast heterokaryons: a KAR1 effect.
It has been shown that defects in cell fusion during mating can trigger programmed cell death in the yeast Saccharomyces cerevisiae. We wished to test whether defects in nuclear migration during cell fusion have the same effect. A partial pedigree analysis of nine kar1 x KAR1 crosses of two different types (four alpha KAR1 x a kar1 and five alpha kar1 x a KAR1 crosses) was carried out, and quantitative estimates of the frequencies of different mother/daughter (m/d) classes were obtained. The kar1 mutation affects nuclear congression and delays nuclear fusion. In each cross tested, the nucleus that entered the first bud tended to be the one contributed by the cell that carried the wild-type allele of KAR1. If budding was delayed by nutrient limitation, the kar1 nucleus could be rescued, indicating that the primary effect of the kar1 mutation is that it slows spindle action. Many m/d classes appear as a result of the degradation of one of the nuclei in the heterokaryon. Loss of nuclei in heterokaryons was accompanied by an accumulation of reactive oxygen species (ROS), and by abnormalities in nuclear structure revealed by TUNEL (terminal transferase-mediated dUTP nick end-labeling) analysis, DAPI staining and by histone-GFP fluorescence patterns which suggested an apoptosis-like process. Often only one nucleus was degraded, and ROS accumulation was restricted to one half of the zygote. We therefore suggest that the data obtained can be explained by apoptosis-like death of a half-cell (cell body).


Symmetrical lipomatosis of the tongue presenting as macroglossia. Report of two cases.
Symmetrical lipomatosis in the oral cavity is extremely rare. Two cases of symmetrical lipomatosis presenting as macroglossia are presented. Glossectomy was performed in order to reduce the size of the tongue and for diagnosis. Because of their multiplicity, non-encapsulation and invasiveness, the lesions were diagnosed histopathologically as symmetrical lipomatosis.