Reliability of Free Inflation and Dynamic Mechanics Tests on the Prediction of the Behavior of the Polymethylsilsesquioxane-High-Density Polyethylene Nanocomposite for Thermoforming Applications.
Numerical modeling of the thermoforming process of polymeric sheets requires precise knowledge of the viscoelastic behavior under conjugate effect pressure and temperature. Using two different experiments, bubble inflation and dynamic mechanical testing on a high-density polyethylene (HDPE) nanocomposite reinforced with polymethylsilsesquioxane HDPE (PMSQ-HDPE) nanoparticles, material constants for Christensen's model were determined by the least squares optimization. The viscoelastic identification relative to the inflation test seemed to be the most appropriate for the numerical study of thermoforming of a thin PMSQ-HDPE part. For this purpose, the finite element method was considered.


Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.
T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.


VGLUT3-immunoreactive afferents of the lateral septum: ultrastructural evidence for a modulatory role of glutamate.
Through its extensive connections with various brain regions, the lateral septum (LS) participates in the processing of cognitive, emotional and autonomic information. It is decisively involved in the generation of behavioral responses according to environmental demands. Modulatory afferents reaching the LS from the brain stem (e.g. dopaminergic, serotonergic) play a role in the adjustment of these behavioral responses. Recently, a population of vesicular glutamate transporter 3-immunoreactive (VGLUT3-ir) fibers forming prominent pericellular basket-like structures (PBLS) was described in the rat LS. These VGLUT3-ir PBLS are distributed in a layer-like pattern, which is very typical for modulatory afferents of the LS. There is meanwhile broad evidence that glutamate can act as a modulatory or co-transmitter and that those neurons, which make use of this transmission mode, primarily express VGLUT3. Thus, the VGLUT3-ir fibers within the LS could also display features typical for non-canonical glutamatergic transmission. Employing pre-embedding electron microscopy for VGLUT3 in rats, we show now that the VGLUT3-ir fibers outlining LS neurons represent axonal terminals, which primarily form symmetric synapses with somata and proximal dendrites of their target neurons. Occasionally, we also found VGLUT3-ir terminals that make canonical asymmetric synapses on distal dendrites and spines. Thus, VGLUT3-ir boutons in the LS form two different, disproportionate, populations of synaptic contacts with their target neurons. The larger one of them is indicative of employing glutamate as a modulatory transmitter.


Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells.
The effects of microiontophoretic applications of equivalent doses (ejection times and currents) of noradrenaline, amphetamine, octopamine and p-hydroxynorephedrine on the spontaneous firing of Purkinje and unidentified cells in the cerebellum of rats were examined. In addition, the effects of amphetamine of Purkinje cells were examined in animals pretreated with the tyrosine hydroxylase inhibitor, alpha-methyltyrosine (alpha-MpT) or with a combination of reserpine plus alpha-MpT. The results indicate that the "false transmitters" are weak agonists when compared to noradrenaline in inhibiting the firing of Purkinje cells. The results of the iontophoretic studies with amphetamine are not consistent with a pre-synaptic releasing effect by amphetamine at noradrenergic synapses in the cns since the efficacy of amphetamine on Purkinje cells was unaltered after pretreatment with alpha-MpT or alpha-MpT plus reserpine.


Neurogenetic mechanisms of learning: a phylogenetic perspective.
Common psychiatric disorders often involve abnormal patterns of adaptive response to environmental stimuli. Thus, an understanding of the pathophysiology and inheritance of such maladaptation requires specification of the underlying neural mechanisms involved in learning, which is broadly defined as the modification of behavior as a result of individual experience. The phylogenetic development of learning ability in animals is shown to proceed by a sequence of discrete steps in which non-associative learning is augmented successively by classical conditioning to aversive stimuli, followed by classical conditioning to food and other rewarding stimuli, then exploratory learning about novel habitats and operant conditioning of behavioral responses, and finally conceptual learning ability. As a result of this complex phylogenetic history, adaptive responses to the environment in mammals including human beings is multidimensional. A model of the structure of stimulus-response and cognitive-processing characteristics in human beings is described. The model is discussed in terms of its evolutionary advantages for survival and reproductive fitness as well as its importance in understanding susceptibility to psychiatric disorders, including personality and anxiety disorders.


Molecular Pathways, Targeted Therapies, and Proteomic Investigations of Colorectal Cancer.
According to the GLOBOCAN 2020 data, colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death. The risk factors for colorectal cancer include a diet abundant with fat, refined carbohydrates, animal protein, low fiber content, alcoholism, obesity, long-term cigarette smoking, low physical activity, and aging. Colorectal carcinomas are classified as adenocarcinoma, neuroendocrine, squamous cell, adenosquamous, spindle cell, and undifferentiated carcinomas. In addition, many variants of colorectal carcinomas have been recently distinguished based on histological, immunological, and molecular characteristics. Recently developed targeted molecules in conjunction with standard chemotherapeutics or immune checkpoint inhibitors provide promising treatment protocols for colorectal cancer. However, the benefit of targeted therapies is strictly dependent on the mutational status of signaling molecules (e.g., KRAS) or mismatch repair systems. Here it is aimed to provide a comprehensive view of colorectal cancer types, molecular pathways associated, recently developed targeted therapies, as well as proteomic investigations applied to colorectal cancer for the discovery of novel biomarkers and new targets for treatment protocols.


Observations on 320 infertile patients treated with human gonadotropins (human menopausal gonadotropin/human chorionic gonadotropin).
From 1964 to 1975, 320 patients with failure of ovulation were treated with human gonadotropins (human menopausal gonadotropin [HMG]/human chorionic gonadotropin [HCG]). Estimation of the pituitary and ovarian function of each patient rather than classification into clinical groups contributed positively to the selection of patients. The dosage schedules used for the patients should be considered conservative, insofar as the amount of HMG and HCG administered per treatment cycle is concerned. The response to human gonadotropins was evaluated mainly according to excretion levels of estrogen and pregnanediol. Of the 320 patients, 256 ovulated at least once during treatment with gonadotropins (80%). Ovarian hyperstimulation syndrome was encountered in 22 patients (6.8%). Pregnancy occurred in 163 patients (50.9%) and in some of them twice, so that the total number of pregnancies was 206. Fifteen pregnancies were multiple (all of them twins). Of 197 pregnancies followed, 43 ended in abortion and 36 in premature labor. Cesarian section was performed in 21 cases.


Schizophrenia and substance use comorbidity: a genome-wide perspective.
Dual diagnosis with substance use disorders (SUDs) consistently contributes to the premature mortality and increased disability observed in schizophrenia. Large genome-wide association studies are providing the information needed to investigate the genetic architecture of psychiatric disorders. Here, we discuss recent genetic investigations of dual diagnosis (i.e., schizophrenia plus a SUD) and how these findings can inform public health messages.


Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia.
Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c-fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.


[The megastigman glycosides from herb of Potentilla multifida].
To investigate the chemical constituents of Potentilla multifida. Various chromatographic techniques were employed for isolation and purification of the constituents. The structures were elucidated by spectral analysis. Four megastigmane glycosides were isolated from P. multifida and their structures were identified as citroside A (1), icariside B1 (2), (6S,7E,9R)-roseoside (3), (6S,7E,9R)-vomifoliol-9-O-beta-D-xylopyranosyl-(1-->6)-O-beta-D-glucopyranoside (4), respectively. All compounds were obtained from the genus Potentilla for the first time.


GlutaMAX prolongs the shelf life of the culture medium for porcine parthenotes.
In vitro porcine embryo production systems have been established and well characterized. However, the efficiency of embryo development during IVC is still very low. In the present study, we have investigated the development of parthenogenetic porcine embryos in the well-known PZM-5 medium for porcine embryos, which was modified by replacing glutamine with the GlutaMAX supplement. We revealed that blastocyst apoptosis was significantly lower in the presence of GlutaMAX, which reduced the release of mitochondrial cytochrome c. Furthermore, the expression of apoptosis genes was significantly lower during GlutaMAX treatment (P < 0.05). The modified medium was also examined for the eventual loss of its efficacy in the presence of GlutaMAX. Three, 6, and 12 months after medium preparation, blastocyst formation in the GlutaMAX-supplemented medium was significantly higher than the number of blastocysts in the medium containing glutamine. After a long period of storage, ammonia concentration was significantly increased in the glutamine medium, whereas it was not statistically different in the GlutaMAX medium. Elevated ammonia concentrations reduced the mitochondrial membrane potential and ATP content of blastocysts in the glutamine medium. These results demonstrate that GlutaMAX can reduce blastocyst apoptosis via inhibition of the cytochrome c pathway and significantly extend the shelf life of the culture medium to at least 1 year.


Adrenal neuroblastoma with metastatic mandibular mass: An unusual presentation.
Neuroblastoma very rarely presents as a mandibular mass. We report the case of a 3-year-old female child who presented to us with a right mandibular mass of 3 months duration. She was investigated and diagnosed as a case of stage 4 right adrenal neuroblastoma with mandibular and skull metastasis.


Valgus alignment of the femoral component is associated with higher revision rates 10 years after TKA.
Appropriate positioning and alignment of tibial and femoral component in primary total knee arthroplasty (TKA) are factors of major importance directly related to patient satisfaction and implant survival. Most literature works elaborate on overall post-operative alignment and its correlation to implant survival. However, less is known about the impact of individual component alignment. The purpose of this study was to investigate the effect of undercorrection of overall alignment as well as the effect of individual tibial and femoral component alignment on the post-operative failure rate after total knee arthroplasty. Clinical and radiographic data of primary TKA cases from 2002 to 2004, with a minimum of 10-year follow-up, were retrospectively reviewed. The pre- and post-operative hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA) and mechanical medial proximal tibial angle (mMPTA) were measured on weight-bearing, full-length antero-posterior lower limb radiographs. Statistical analysis was performed to establish the correlation between both overall and implant alignment and revision rate. In total, 379 primary TKA cases were evaluated. The mean time of follow-up was 12.9 years (range 10.3-15.9 years, SD = 1.8). Nine out of 379 cases were revised due to aseptic loosening; the mean time to revision was 5.5 years (range 1.0-15.5 years, SD = 4.6). Varus undercorrection of overall alignment was not associated with a higher rate of revision (p = 0.316). Post-operative valgus femoral alignment (mLDFA < 87°) contributed to a significant decreased prosthesis survival in contrast to neutral femoral alignment (revision rate valgus group: 10.7% and neutral group: 1.7%; p = 0.003). Post-operative tibial mechanical alignment was not identified as a significant predictor for implant survival (revision rate varus group: 2.9% and neutral group: 2.4%; p = 0.855). Primary TKA showed significantly higher revision rates when the femoral component was placed in > 3° of valgus (mLDFA < 87°). In contrast, postoperative overall residual varus alignment (HKA) and varus alignment of the tibial component were not related to higher revision rates at a minimum 10-year follow-up after TKA. These findings should be considered when choosing component position in individualised TKA. III.


Identification of a unique 1,4-β-D-glucan glucohydrolase of glycoside hydrolase family 9 from Cytophaga hutchinsonii.
Cytophaga hutchinsonii is an aerobic cellulolytic soil bacterium that rapidly digests crystalline cellulose. The predicted mechanism by which C. hutchinsonii digests cellulose differs from that of other known cellulolytic bacteria and fungi. The genome of C. hutchinsonii contains 22 glycoside hydrolase (GH) genes, which may be involved in cellulose degradation. One predicted GH with uncertain specificity, CHU_0961, is a modular enzyme with several modules. In this study, phylogenetic tree of the catalytic modules of the GH9 enzymes showed that CHU_0961 and its homologues formed a new group (group C) of GH9 enzymes. The catalytic module of CHU_0961 (CHU_0961B) was identified as a 1,4-β-D-glucan glucohydrolase (EC 184.108.40.206) that has unique properties compared with known GH9 cellulases. CHU_0961B showed highest activity against barley glucan, but low activity against other polysaccharides. Interestingly, CHU_0961B showed similar activity against ρ-nitrophenyl β-D-cellobioside (ρ-NPC) and ρ-nitrophenyl β-D-glucopyranoside. CHU_0961B released glucose from the nonreducing end of cello-oligosaccharides, ρ-NPC, and barley glucan in a nonprocessive exo-type mode. CHU_0961B also showed same hydrolysis mode against deacetyl-chitooligosaccharides as against cello-oligosaccharides. The kcat/Km values for CHU_0961B against cello-oligosaccharides increased as the degree of polymerization increased, and its kcat/Km for cellohexose was 750 times higher than that for cellobiose. Site-directed mutagenesis showed that threonine 321 in CHU_0961 played a role in hydrolyzing cellobiose to glucose. CHU_0961 may act synergistically with other cellulases to convert cellulose to glucose on the bacterial cell surface. The end product, glucose, may initiate cellulose degradation to provide nutrients for bacterial proliferation in the early stage of C. hutchinsonii growth. KEY POINTS: • CHU_0961 and its homologues formed a novel group (group C) of GH9 enzymes. • CHU_0961 was identified as a 1,4-β-d-glucan glucohydrolase with unique properties. • CHU_0961 may play an important role in the early stage of C. hutchinsonii growth.


Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation.
In an attempt to differentiate between nociceptive group IV muscle receptors and "ergoceptive" ones, the discharges of single group IV fibres from skeletal muscle in response to local pressure, sustained stretch, repetitive contraction and intra-arterial injections of bradykinin, 5-hydroxytryptamine (5-HT), potasssium, phosphate, and lactate were studied in anesthetized cats.


Increasing Mechanical Properties of 2-D-Structured Electrospun Nylon 6 Non-Woven Fiber Mats.
Tensile strength, Young's modulus, and toughness of electrospun nylon 6 non-woven fiber mats were improved by increasing individual nanofiber strength and fiber-fiber load sharing. Single-walled carbon nanotubes (CNTs) were used as reinforcement to increase the strength of the electrospun nylon 6 nanofibers. Young's modulus, tensile strength, and toughness of the nylon 6 non-woven fiber mats electrospun from 20 wt % solutions increased 51%, 87%, and 136%, respectively, after incorporating 1 wt % CNTs into the nylon 6 nanofibers. Three methods were investigated to enhance fiber-fiber load sharing: increasing friction between fibers, thermal bonding, and solvent bonding. The addition of beaded nylon 6 nanofibers into the non-woven fiber mats to increase fiber-fiber friction resulted in a statistically significantly increase in Young's modulus over comparable smooth non-woven fiber mats. After annealing, tensile strength, elongation, and toughness of the nylon 6 non-woven fiber mats electrospun from 20 wt % + 10 wt % solutions increased 26%, 28%, and 68% compared to those from 20 wt % solutions. Solvent bonding with formic acid vapor at room temperature for 30 min caused increases of 56%, 67%, and 39% in the Young's modulus, tensile strength, and toughness of non-woven fiber mats, respectively. The increases attributed to increased individual nanofiber strength and solvent bonding synergistically resulted in the improvement of Young's modulus of the electrospun nylon 6 non-woven fiber mats.


NT3 expressed in skin causes enhancement of SA1 sensory neurons that leads to postnatal enhancement of Merkel cells.
To determine the role of NT3 in the postnatal maturation of Merkel cell (MC) sensory neurite complexes (touch domes), we examined the development of their neural and end-organ components in wild-type and transgenic mice that overexpress NT3 (NT3-OE). Touch domes are sensory complexes of the skin that contain specialized MCs innervated by slowly adapting type 1 (SA1) neurons. Touch domes are dependent on NT3 and, though formed in newborn mice that lack NT3, are severely depleted during postnatal maturation. Mice that overexpress NT3 in the skin have larger touch domes characterized by enhanced neural innervation and MC number. In this study, we asked how this NT3-mediated enhancement occurs, whether through stimulatory effects of NT3 on the SA1 neuron, or the MC, or both. The innervation density and number of MCs associated with each touch dome were measured in wild-type and transgenic animals at postnatal times. In newborn NT3-OE mice, touch dome innervation was enhanced. Surprisingly, however, the number of MCs was lower in newborn NT3-OE animals than in wild-type littermates, and equivalent numbers were not reached until postnatal day 8 (PN8). Not until the PN12 and PN16 time points did MCs increase in NT3-OE mice. To examine the neural dependence of MCs in NT3-OE mice, touch domes were chronically denervated by resecting dorsal cutaneous nerves. Both wild-type and NT3-OE animals showed similar depletion in the number of MCs associated with touch domes. These data indicate that NT3 is not a survival factor for MCs and that the NT3-mediated enhancement of MC number is indirect and neurally dependent.


Virtual injections using 4D flow MRI with displacement corrections and constrained probabilistic streamlines.
Streamlines from 4D-flow MRI have been used clinically for intracranial blood-flow tracking. However, deterministic and stochastic errors degrade streamline quality. The purpose of this study is to integrate displacement corrections, probabilistic streamlines, and novel fluid constraints to improve selective blood-flow tracking and emulate "virtual bolus injections." Both displacement artifacts (deterministic) and velocity noise (stochastic) inherently occur during phase-contrast MRI acquisitions. Here, two displacement correction methods, single-step and iterative, were tested in silico with simulated displacements and were compared with ground-truth velocity fields. Next, the effects of combining displacement corrections and constrained probabilistic streamlines were performed in 10 healthy volunteers using time-averaged 4D-flow data. Measures of streamline length and depth into vasculature were then compared with streamlines generated with no corrections and displacement correction alone using one-way repeated-measures analysis of variance and Friedman's tests. Finally, virtual injections with improved streamlines were generated for three intracranial pathology cases. Iterative displacement correction outperformed the single-step method in silico. In volunteers, the combination of displacement corrections and constrained probabilistic streamlines allowed for significant improvements in streamline length and increased the number of streamlines entering the circle of Willis relative to streamlines with no corrections and displacement correction alone. In the pathology cases, virtual injections with improved streamlines were qualitatively similar to dynamic arterial spin labeling images and allowed for forward/reverse selective flow tracking to characterize cerebrovascular malformations. Virtual injections with improved streamlines from 4D-flow MRI allow for flexible, robust, intracranial flow tracking.


MFCC Parameters of the Speech Signal: An Alternative to Formant-Based Instantaneous Vocal Tract Length Estimation.
On the one hand, the relationship between formant frequencies and vocal tract length (VTL) has been intensively studied over the years. On the other hand, the connection involving mel-frequency cepstral coefficients (MFCCs), which concisely codify the overall shape of a speaker's spectral envelope with just a few cepstral coefficients, and VTL has only been modestly analyzed, being worth of further investigation. Thus, based on different statistical models, this article explores the advantages and disadvantages of the latter approach, which is relatively novel, in contrast to the former which arises from more traditional studies. Additionally, VTL is assumed to be a static and inherent characteristic of speakers, that is, a single length parameter is frequently estimated per speaker. By contrast, in this paper we consider VTL estimation from a dynamic perspective using modern real-time Magnetic Resonance Imaging (rtMRI) to measure VTL in parallel with audio signals. To support the experiments, data obtained from USC-TIMIT magnetic resonance videos were used, allowing for the 2D real-time analysis of articulators in motion. As a result, we observed that the performance of MFCCs in case of speaker-dependent modeling is higher, however, in case of cross-speaker modeling, which uses different speakers' data for training and evaluating, its performance is not significantly different of that obtained with formants. In complement, we note that the estimation based on MFCCs is robust, with an acceptable computational time complexity, coherent with the traditional approach.


Industrial hearing conservation.
Hearing conservation programs, when appropriate in industry, are now a necessity. Even though one may not wish to adopt an altruistic attitude toward the conservation of hearing, one must, like it or not, initiate a hearing conservation program because of both federal and state regulations. Since industrial noise exposure produced more hearing loss in more people than all other causes of hearing loss combined, it is incumbent on all industries with noise makers to do something about protecting human hearing. The tragedy is that nearly all industrial hearing loss can be prevented with proper hearing conservation measures. The cost of hearing conservation is far less than the cost of hearing loss in terms of human suffering and dollars in the compensation courts. Proper education of both managment and labor can result in successful hearing conservation programs. The method of choice is reduction of the noise at the source, but in many cases this is infeasible both technically and economically and therefore protection at the ear must be used. Experience has shown that with proper supervision ear protection programs can prevent the majority of instances of hearing loss in the majority of individuals exposed.


Tethered cord after spina bifida aperta: a longitudinal study of somatosensory evoked potentials.
Progressive neurological deterioration may occur after meningomyelocele repair. Magnetic resonance imaging almost invariably demonstrates a conus medullaris in an abnormally low position, whether neurological symptoms develop or not. Surgery of a secondary tethered cord is indicated when progression of neurological symptoms is documented. We performed a longitudinal study of posterior tibial nerve somatosensory evoked potentials (SSEPs) in children and adolescents after neonatal meningomyelocele repair. All patients were able to walk. Declining or negative posterior tibial nerve SSEPs were recorded in 15 patients; 14 of these had clinical signs of a secondary tethered cord. After surgery of the tethered cord, the SSEPs improved in 8 of 10 patients. Posterior tibial nerve SSEPs may contribute to the diagnosis of secondary tethered cord. After untethering, the evoked potentials demonstrate recovery of spinal cord function and might help to delineate prognosis.


[Lethal pulmonary involvement of neutrophilic dermatosis following erythropoietin therapy].
Neutrophilic disease is characterized by aseptic visceral infiltration by normal polymorphonuclear leukocytes that can occur in any organ. Association with an underlying systemic disease, particularly haematological malignancy or inflammatory bowel disease, is frequent. This may produce a multisystem disorder, but diagnosis is usually based on skin lesions because of their clinical and histological accessibility. Pulmonary manifestations are the most common extracutaneous symptoms but may be misdiagnosed, as in our case report. A 77-year-old woman with IgA myeloma presented with an inflammatory bullous plaque of the leg coupled with fever lasting one week. The clinical and histological examinations were evocative of a neutrophilic dermatosis such as Sweet's syndrome. Significant improvement was initially obtained with systemic corticosteroids and colchicine. The course became complicated by necrotic neutrophilic papulopustular lesions of the upper limbs and pulmonary manifestations, with fever and decline in overall condition occurring the day after administration of erythropoietin. A hypothesis of septic aetiology prompted antibiotic and antifungal therapy, which remained ineffective. The patient died the day after the second erythropoietin injection. This case involved late identification of the aseptic neutrophilic aetiology of pulmonary manifestations. Several factors favouring their appearance and the fatal outcome may be suggested: the existence of a myeloma, association with myelodysplastic syndrome and the possible iatrogenic action of erythropoietin. To the best of our knowledge, this is the first reported case of extracutaneous neutrophilic infiltrate occurring in a patient treated with this haematopoietic hormone.


Co-contraction of cervical muscles during sagittal and coronal neck motions at different movement speeds.
Muscle co-contraction is important in stabilizing the spine. The effects of movement speed and direction on the cervical co-contraction were, however, not yet investigated. Surface electromyographies of three paired cervical muscles were measured in 17 young healthy subjects. The subjects performed voluntary neck movements in sagittal and coronal plane at fast, medium, and slow speeds. The co-contraction ratio was defined as the normalized integration of antagonistic electromyographic activities divided by that of total muscle activities. The results showed that the co-contraction ratio at fast speed (0.42 +/- 0.21) was smaller than that at medium (0.45 +/- 0.20) and slow (0.46 +/- 0.19) speeds (P </= 0.001). The co-contraction ratio was different between flexion and extension, but was similar between left and right lateral bending. The implications of co-contraction patterns include: (1) agonistic activities increase with speed but antagonistic activities do not increase accordingly; (2) neck extensors are highly activated during sagittal motions; and (3) muscular activations are symmetric during coronal motions. In conclusion, the co-contraction patterns from young healthy subjects demonstrate normal neuromuscular control in regulating the stiffness of cervical spine, and may further be references to assess the neck disorders in elderly or patients.


Patient satisfaction with random assignment to extended early intervention for psychosis vs regular care: Relationship with service engagement.
We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later. Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow-up with service providers was recorded monthly. Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ2 = 49.96, P < .001). In the extended EI group, those happy with their assigned group were likelier to continue seeing their case manager for the entire five-year period than those who were unhappy/indifferent (χ2 = 5.61, P = .030). Perceptions about EI, indicated by satisfaction with being assigned to extended EI, may have lasting effects on service engagement.


LEAFY COTYLEDON2 (LEC2) promotes embryogenic induction in somatic tissues of Arabidopsis, via YUCCA-mediated auxin biosynthesis.
The LEAFY COTYLEDON2 (LEC2) transcription factor with a plant-specific B3 domain plays a central role in zygotic and somatic embryogenesis (SE). LEC2 overexpression induced in planta leads to spontaneous somatic embryo formation, but impairs the embryogenic response of explants cultured in vitro under auxin treatment. The auxin-related functions of LEC2 appear during SE induction, and the aim of the present study was to gain further insights into this phenomenon. To this end, the effect of LEC2 overexpression on the morphogenic responses of Arabidopsis explants cultured in vitro under different auxin treatments was evaluated. The expression profiles of the auxin biosynthesis genes were analysed in embryogenic cultures with respect to LEC2 activity. The results showed that LEC2 overexpression severely modifies the requirement of cultured explants for an exogenous auxin concentration at a level that is effective in SE induction and suggested an increase in the auxin content in 35S::LEC2-GR transgenic explants. The assumption of an LEC2 promoted increase in endogenous auxin in cultured explants was further supported by the expression profiling of the genes involved in auxin biosynthesis. The analysis indicated that YUCCAs and TAA1, working in the IPA-YUC auxin biosynthesis pathway, are associated with SE induction, and that the expression of three YUCCA genes (YUC1, YUC4 and YUC10) is associated with LEC2 activity. The results also suggest that the IAOx-mediated auxin biosynthesis pathway involving ATR1/MYB34 and CYP79B2 does not seem to be involved in SE induction. We conclude that de novo auxin production via the tryptophan-dependent IPA-YUC auxin biosynthesis pathway is implicated in SE induction, and that LEC2 plays a key role in this mechanism.


Metabolomics: An emerging potential approach to decipher critical illnesses.
Critical illnesses contribute to the maximum morbidity and mortality of hospitalized patients. Acute respiratory distress syndrome (ARDS) and sepsis/septic shock are the two most common acute illnesses associated with intensive care unit (ICU) admission. Once triggered, both have an identical underlying mechanism, portrayed by inflammation and endothelial dysfunction. The diagnosis of ARDS is based on clinical findings, laboratory tests, and radiological imaging. Blood cultures remain the gold standard for the diagnosis of sepsis, with the limitation of time delay and low positive yield. A combination of biomarkers has been proposed to diagnose and prognosticate these acute disorders with strengths and limitations, but still, the gold standard has been elusive to clinicians. In this review article, we illustrate the potential of metabolomics to unravel biomarkers that can be clinically utilized as a rapid prognostic and diagnostic tool associated with specific patient populations (ARDS and sepsis/septic shock) based on the available scientific data.


Plants and earthworms control soil carbon and water quality trade-offs in turfgrass mesocosms.
Understanding how plants and earthworms regulate soil-based ecosystem services can guide design and management of built environments to improve environmental quality. We tested whether plant and earthworm activity results in trade-offs between soil carbon (C) retention and water quality. In a 2 × 2 factorial random block design, we introduced shrubs (Aronia melanocarpa) and earthworms (Lumbricus terrestris) to turfgrass (Lolium perenne) sandy loam mesocosms in a greenhouse. We measured soil respiration and soil microclimate every two weeks and leachate every two months. After 15 months, we assessed C and nitrogen (N) in bulk soil and aggregates (> 2000, 2000-250, 250-53 μm). Turfgrass mesocosms with earthworms retained less soil C (6.10 ± 0.20 kg/m2), especially when warmer. Soils planted with shrubs were drier and had 7% lower mean respiration rates than soils without shrubs. Turfgrass mesocosms with both shrubs and earthworms retained more soil C (6.66 ± 0.25 kg/m2), even when warmer, and held ~1.5 times more C in >2 mm aggregates than turfgrass-only mesocosms. Turfgrass mesocosms with shrubs and earthworms leached nitrate-N with increased respiration and retained phosphate-P and dissolved organic carbon (DOC) when wetter. In contrast, turfgrass mesocosms with only shrubs had the opposite response by leaching less nitrate-N with increased respiration, and more phosphate-P and DOC when wetter. Overall, shrub and earthworm activity in turfgrass mesocosms led to soil C-nutrient retention trade-offs. Our results reveal potential challenges in managing built environments to both retain soil C and improve water quality.


Candidate loci reveal genetic differentiation between temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha).
Local adaptation is a dynamic process driven by selection that can vary both in space and time. One important temporal adaptation for migratory animals is the time at which individuals return to breeding sites. Chinook salmon (Oncorhynchus tshawytscha) are excellent subjects for studying the genetic basis of temporal adaptation because their high seasonal homing fidelity promotes reproductive isolation leading to the formation of local populations across diverse environments. We tested for adaptive genetic differentiation between seasonal runs of Chinook salmon using two candidate loci; the circadian rhythm gene, OtsClock1b, and Ots515NWFSC, a microsatellite locus showing sequence identity to three salmonid genes central to reproductive development. We found significant evidence for two genetically distinct migratory runs in the Feather River, California (OtsClock1b: F(ST)=0.042, P=0.02; Ots515NWFSC: F(ST)=0.058, P=0.003). In contrast, the fall and threatened spring runs are genetically homogenous based on neutral microsatellite data (F(ST)=-0.0002). Similarly, two temporally divergent migratory runs of Chinook salmon from New Zealand are genetically differentiated based on polymorphisms in the candidate loci (OtsClock1b: F(ST)=0.083, P-value=0.001; Ots515NWFSC: F(ST)=0.095, P-value=0.000). We used an individual-based assignment method to confirm that these recently diverged populations originated from a single source in California. Tests for selective neutrality indicate that OtsClock1b and Ots515NWFSC exhibit substantial departures from neutral expectations in both systems. The large F(ST )estimates could therefore be the result of directional selection. Evidence presented here suggests that OtsClock1b and Ots515NWFSC may influence migration and spawning timing of Chinook salmon in these river systems.


Pediatric onset spinal cord injury: implications on management of the upper limb in tetraplegia.
This article focuses on the pediatric upper limb after spinal cord injury and highlights the obstacles during reconstruction.


Density-dependent response to mycorrhizal infection in Abutilon theophrasti Medic.
One purpose of this study was to determine whether an increase in plant density would result in a decrease in response to mycorrhizal infection (particularly as measured by phosphorus content). Increases in plant density generally result in increases in root density in the volume of soil occupied by the plants. Root density, in turn, largely determines phosphorus uptake. If mycorrhizal plants had significantly higher effective root densities than non-mycorrhizal plants due to the fungal hyphae and thus were more thorough in exploiting a given volume of soil for phosphorus, then a given increase in root density might result in a greater proportional increase in phosphorus uptake for non-mycorrhizal plants than for mycorrhizal plants. Two experiments were performed in which mycorrhizal infection and available soil volume per plant were manipulated; one in which the number of plants within a given pot size was varied (experiment 1), and another in which single plants were grown in pots of differing volume (experiment 2). The two experiments yielded similar results but for apparently different reasons. In the first experiment, for a given increase in root density, non-mycorrhizal plants had a greater proportional increase in phosphorus uptake than mycorrhizal plants. Thus, as predicted, response to mycorrhizal infection was greatest at the lowest planting density (highest available soil volume per plant, lowest root density). In experiment 2, response to infection was also greatest at the highest available soil volume per plant (largest pot), but pot size did not influence root density. These results show that the benefit from mycorrhizal infection may be partly determined by root density and they suggest that plants either occurring in patches of contrasting root density in a given community, or occurring in different communities with inherently different root densities may differ in their reliance upon mycorrhizal fungi for phosphorus uptake.


Half-sandwich ruthenium(II), rhodium(III) and iridium(III) fluorescent metal complexes containing pyrazoline based ligands: DNA binding, cytotoxicity and antibacterial activities.
A series of nine new complexes of ruthenium(II), rhodium(III), and iridium(III) incorporated with pyrazoline-based ligands were synthesized and characterized by various spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, UV-Vis spectroscopy, ESI-MS spectrometry and X-ray crystallographic studies. All the synthesized compounds were assessed for their antibacterial abilities against Gram-positive and Gram-negative bacterial strains. The compounds showed better antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus Thuringiensis), with activities superior to standard kanamycin. Antioxidant studies revealed the mild radical scavenging proficiency of the compounds. DNA binding studies using fluorescence spectroscopy showed that the compounds could bind to Salmon Milt DNA electrostatically via external contact and groove surface binding with moderate affinity. The synthesized complexes were tested for anticancer activity using cell cytotoxicity and apoptosis assays in Dalton's lymphoma (DL) cell lines. The findings were compared to cisplatin (the standard drug) under identical experimental conditions. The cell viability results showed that complex 7 induced higher cytotoxicity in the DL cell line than the other tested compounds. The results of the molecular docking analysis further suggest that selective complexes have complete contact with the active amino acids sites of anti-apoptotic Bcl-2 family protein.


Disposable polydimethylsiloxane/silicon hybrid chips for protein detection.
This paper presents disposable protein analysis chips with single- or four-chamber-constructed from poly(dimethylsiloxane) (PDMS) and silicon. The chips are composed of a multilayer stack of PDMS layers that sandwich a silicon microchip. This inner silicon chip features an etched array of micro-cavities hosting polymeric beads. The sample is introduced into the fluid network through the top PDMS layer, where it is directed to the bead chamber. After reaction of the analyte with the probe beads, the signal generated on the beads is captured with a CCD camera, digitally processed, and analyzed. An established bead-based fluorescent assay for C-reactive protein (CRP) was used here to characterize these hybrid chips. The detection limit of the single-chamber protein chip was found to be 1 ng/ml. Additionally, using a back pressure compensation method, the signals from each chamber of the four-chamber chip were found to fall within 10% of each other.


It's all about position: the basal layer of human epidermis is particularly susceptible to different types of sunlight-induced DNA damage.
In this issue, Tewari et al. show that although UVB most effectively causes cyclobutane pyrimidine dimers (CPDs) at the human epidermal surface, UVA-induced CPDs predominate in the basal layer. Previous studies found higher accumulation of UVA-induced 8-oxo-7,8-dihydro-2'-deoxyguanosine and mutations in the basal layer. Therefore, the epidermal basal layer is particularly sensitive to UVA-induced genetic damage and the formation of mutations.


Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.


Nanomaterials for cancer immunotherapy.
Cancer immunotherapy is quickly growing to be the fourth most important cancer therapy, after surgery, radiation therapy, and chemotherapy. Immunotherapy is the most promising cancer management strategy because it orchestrates the body's own immune system to target and eradicate cancer cells, which may result in durable antitumor responses and reduce metastasis and recurrence more than traditional treatments. Nanomaterials hold great promise in further improving the efficiency of cancer immunotherapy - in many cases, they are even necessary for effective delivery. In this review, we briefly summarize the basic principles of cancer immunotherapy and explain why and where to apply nanomaterials in cancer immunotherapy, with special emphasis on cancer vaccines and tumor microenvironment modulation.


Seasonally fluctuating resources and temporal variability of interspecific competition.
The influence of seasonal availability of two critical resources (food and substrates from which food was harvested) on interspecific competition between striped surfperch (Embiotoca lateralis) and black surfperch (Embiotoca jacksoni) was examined. There was a strong depth-related gradient in density of prey and in cover of foliose algae; both declined with increasing bottom depth. Density of prey was reduced 5-10 fold during the winter season, but cover of substrates remained constant throughout the year. Although both fishes co-occurred throughout the same depth range, striped surfperch were more common in shallow habitats and black surfperch were more abundant deeper. Local abundance and distribution patterns of both surfperch species did not change seasonally. Stepwise regression analyses suggested that availability of favored substrates was a proximate influence on local patterns of surfperch distribution and abundance, and that interspecific competition depressed abundance of the two species to the same degree. Removal experiments conducted during the cold-water season revealed that interspecific competition influenced depth distribution of black surfperch but not striped surfperch. Seasonal change in density of prey was accompanied by marked changes in overlap in use of foraging substrates by the surfperches. The pattern of change in interspecific overlap suggested that surfperch competed for food only when prey were seasonally scarce. There was no difference in the agonistic tendencies of the two fishes, and the absolute and relative frequency of interspecific chases was independent of food level. These results have important implications regarding the impact of temporal variability of interspecific competition in natural communities. In the surfperch system, competition was characterized by constant and time-varying elements that had symmetrical and asymmetrical effects and involved both interference and exploitation mechanisms.


Size dependent changes in tumor phosphate metabolism after radiation therapy as detected by 31P NMR spectroscopy.
In Vivo 31P NMR spectroscopy was used to study changes in phosphate metabolism that occur after irradiation of the C3H fibrosarcoma, FSaII. Previously, we have shown that small FSaII tumors (less than 250 mm3) have a greater phosphocreatinine/inorganic phosphate (PCr/Pi) ratio and a lower hypoxic cell fraction (HCF) than large FSaII tumors (greater than 250 mm3). Six small tumors (113 +/- 26 mm3) were treated with radiation doses chosen to induce local control in greater than 50% of animals, (70-100 Gy, single fraction). Minimal changes in the tumor 31P NMR spectrum were seen over eight days of monitoring. During this interval, tumor regression began a minimum of 36 hours after radiation. This contrasted with large tumors (650-1000 mm3) wherein a significant increase in the Pcr/Pi ratio was seen 44 hr after irradiation. In tumors of this size range, a tumor growth delay of 4 to 7 days is obtained after a single 70 Gy fraction of radiation. Since small FSaII tumors have a minimal HCF (approximately equal to 4%), radiation induced reoxygenation would not be expected to have a large effect on their average cellular metabolism. Large tumors of this histology have a high HCF (greater than or equal to 40%), and may therefore be expected to have a significant average change in tumor cell metabolism with reoxygenation. The 31P NMR observations of small and large tumors after irradiation are compatible with radiation induced reoxygenation in the larger tumors.


[Results of 10 years of performing abortions at the Gynecologic Clinic of the Dresden Medical Academy].
Since the abortion law of March, 9th 1972, 8456 interruptions of pregnancy were performed at the Medical School up to 1981. 649 patients were treated in two steps because of the use of prostaglandins. Age, frequency of abortions, relation to previous births and socio-gynecological questions are object of investigations. The analysis is based on computerized data.


Impact of Age and Sex on α-Syn (α-Synuclein) Knockdown-Mediated Poststroke Recovery.
Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age. Adult and aged male and female mice were subjected to transient middle cerebral artery occlusion. α-Syn small interfering RNA (siRNA) was administered intravenous at 30 minutes or 3 hour reperfusion. Poststroke motor deficits were evaluated between day 1 and 7 and infarct volume was measured at day 7 of reperfusion. α-Syn knockdown significantly decreased poststroke brain damage and improved poststroke motor function recovery in adult and aged mice of both sexes. However, the window of therapeutic opportunity for α-Syn siRNA is very limited. α-Syn plays a critical role in ischemic brain damage and preventing α-Syn protein expression early after stroke minimizes poststroke brain damage leading to better functional outcomes irrespective of age and sex.


[Prevalence of asthma in Cuban adolescents by different clinical criteria].
Despite of the knowledge about asthma, its diagnosis is clinical and its prevalence depends on the case criterion. Several methodologies have been applied to determine its prevalence; the International Study of Asthma and Allergies in Childhood (ISAAC) is the newest, although some inconsistencies have been attributed to their results. To estimate the prevalence of asthma according to five diagnostic criteria and according to respiratory symptoms in order to contribute to improve the diagnosis quality. Data of the first phase of the ISAAC study made at the Centro Cubano Playa-Marianao in 2003 were collected. Three thousand twenty-six children of 13 to 14 years of age answered a survey, and prevalence of established criteria was estimated; confidence intervals were used to compare them. Estimations were presented with 95% of confidence; the chi square test and the odds ratio were applied for prevalence rates by gender. When comparing all the prevalences among different criteria, those corresponding to criteria I and II were statistically significant. Criterion I was the least discriminatory and criterion V had the highest power to discriminate. Criterion III offered an intermediate value of prevalence, with a proper level to discern. The first three criteria had higher prevalences in women, with statistically significant values among genders (p = 0.002, p = 0.045 and p = 0.008, respectively). Using a criterion that could include several symptoms, especially in low income-countries, where hospitals do not have current and expensive diagnostic methods, would be useful and would contribute to diminish the diagnostic error.


Oncologic outcomes and technical considerations of nipple-sparing mastectomies in breast cancer: experience of 425 cases from a single institution.
Nipple-sparing mastectomy (NSM) is an advantageous treatment option, providing a complete cure and good cosmetic results. We tested whether NSM is a surgically and oncologically safe technique. We evaluated the oncological outcome of 425 breasts in 413 patients who underwent NSM between January 2000 and March 2013. We retrospectively reviewed patient data and analyzed all patient characteristics as potential risk factors of recurrence at the nipple-areola complex (NAC). To confirm the oncological safety of NSM, we compared outcomes of NSM and conventional total mastectomy. The median follow-up time after surgery was 46.8 months (range 6-158 months). Nipple necrosis was observed in 6 cases (1.4 %). The cumulative local recurrence rate after NSM was 5.8 % (25/425 cases), similar to that of conventional total mastectomy in the same period (5.6 %, 49/878 cases). Furthermore, the cumulative local recurrence rate at the NAC was 2.3 % (10 cases). HER2-enriched tumors and young age (<40 years) were significant risk factors for recurrence at the NAC. In patients with recurrence, the site of recurrence was easily excised, and good cosmetic results were achieved in breast reconstruction cases. NSM is safe with a low complication rate. No significant difference was observed in cumulative local recurrence rate, cumulative distant disease recurrence rate, and overall survival between patients who underwent NSM or conventional total mastectomy, confirming that NSM was surgically and oncologically safe.


Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction.
The cardiac isotype of the myofibrillar contractile protein, troponin-I, is located specifically in the mammalian heart. A sensitive radioimmunoassay has been developed to detect human and nonhuman primate cardiac troponin-I in serum down to 10 ng/ml. Immunochemical cross reactivity with skeletal troponin-I was only 2% and was species nonspecific. Normal patient levels of cardiac troponin-I are about 10 ng/ml. In patients with acute myocardial infarction (n = 32), serum cardiac troponin-I was elevated within 4 to 6 hours, reached a mean peak level of 112 ng/ml (range 20 to 550 ng/ml) at 18 hours, and remained above normal for up to 6 to 8 days following infarction. Peak cardiac troponin-I correlated with peak creatine kinase (CK) MB isoenzyme (r = 0.75). In subjects (n = 34) with skeletal muscle damage (total CK = 338 to 5384 IU/L), cardiac troponin-I levels were not elevated above normal, although CK-MB isoenzyme was elevated in some patients. Cardiac troponin-I levels were normal or slightly elevated in patients with ischemic heart disease and were normal in patients with chest pain of noncardiac origin. Immunoassay of cardiac troponin-I could be a valuable diagnostic aid in the cardiac-specific detection of cell necrosis.


Hydatid cysts of the lung: lesion size in relation to clinical presentation and therapeutic approach.
The aim of this study was to assess the relationship between the pulmonary hydatid cyst size and the clinical presentation, surgical approach, and postoperative outcome. We review the problems encountered in treating large pulmonary hydatid cysts and highlight the risks associated with the rupture of the cyst and a delay of the surgical treatment. The medical records of 169 patients surgically treated for lung hydatid cysts were reviewed. Patients were divided into two groups based on cyst size: group 1 (n = 128) with small (<10 cm) cysts and group 2 (n = 41) with giant (≥10 cm) cysts. Data related to symptoms, preoperative complications, surgical procedures performed and postoperative morbidity were analyzed and compared. In both groups, the most common symptom was chest pain, followed by dyspnea and cough, respectively. There were no differences between the two groups with respect to cyst-associated parenchymal or pleural complications before surgery (p = 0.80). In the large majority of cases, the surgical treatment was cystotomy, removal of the cystic membrane and capitonnage. Wedge resection was performed in nine patients in total (seven in group 1, two in group 2) and one patient in group 2 required a lobectomy. Decortication was required significantly more frequently in group 2 than in group 1 (p = 0.001). Sixteen patients in group 1 and 10 patients in group 2 developed postoperative complications (p = 0.19). There was no peri or postoperative mortality. There was no difference between the groups with respect to the duration of hospitalization (p = 0.17). Two patients with complicated hydatid cysts in group 1 had recurrent lesions during follow-up, whereas there was no recurrence in group 2. All pulmonary hydatid cysts should be surgically treated as soon as possible after their diagnosis in order to avoid complications. Most of these lesions, regardless of size, can be surgically managed with procedures that preserve the maximal lung parenchyma and yield excellent outcomes.


Retention of metals in periprosthetic tissues of patients with metal-on-metal total hip arthroplasty is reflected in the synovial fluid to blood cobalt transfer ratio in the presence of a pseudotumour.
Modern metal-on-metal (MOM) arthroplasties were performed for over a decade before alarming reports of adverse metal reactions dramatically reduced their use. Failures are seen more often with high-wearing implants, but also well-positioned components with more favourable wear patterns can cause problems. There are no specific clinical indicators that could help us to predict the prognosis of these implants. For this reason, we still need more information on the effect of underlying factors that contribute to this process. In this prospective cohort study, we investigated how cup orientation and type of pseudotumour determined by the Hart classification effect the distribution of metals in blood, synovial fluid and tissues surrounding the metal-on-metal hip prosthesis in revision surgery patients. One thousand two hundred twenty-nine metal-on-metal hip patients were screened and of those, 60 patients that had a revision surgery due to adverse metal reaction were included. Whole blood, synovial fluid and synovial/pseudotumour tissue samples were analysed for metal ion concentrations (Co, Cr, Mo and Ti). The lowest metal concentrations were found when both cup anteversion and inclination were optimal, and the highest when both were suboptimal. Suboptimal anteversion alone raised Cr-ion concentrations more than suboptimal inclination. The concentrations of metals in blood, synovial fluid or synovial soft tissue were the same in patients with and without a pseudotumour, but the relative transfer percentage of cobalt from synovial fluid to blood was higher in patients with a pseudotumour. The implant orientation alone does not explain the metal concentrations found in tissues or distribution of metals between different tissues. The accumulation of metals in periprosthetic soft tissues increase the total metal load, and in the presence of a pseudotumour this is reflected in the transfer ratio of Co from synovial fluid to the blood. The total metal load of the pseudotumour tissue should be defined in future studies to determine if this will provide new insights for clinical practice.


Implementing an Evidence-Based COPD Hospital Discharge Protocol: A Narrative Review and Expert Recommendations.
Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation.


Reference power values for the jump squat exercise in elite athletes: A multicenter study.
The present study aimed to provide reference values for lower-limb muscle power assessed during the incremental jump squat (JS) test in elite athletes (i.e., professional athletes competing at international level). We pooled data from all JS tests performed by elite athletes of different sports in two high-performance centres between 2015 and 2019, and computed reference values (i.e., terciles) for mean power (MP), mean propulsive power (MPP), and peak power (PP). Reference values were obtained from 684 elite athletes (458 male and 226 female) of 16 different sports (boxing, judo, karate, fencing, taekwondo, wrestling, basketball, soccer, futsal, handball, rugby union, badminton, tennis, long distance running, triathlon, and sprinting). Significant differences (p < 0.001) were found between male and female athletes for MP (7.47 ± 1.93 and 6.15 ± 1.68 W·Kg-1, respectively), MPP (10.50 ± 2.75 and 8.63 ± 2.43 W·Kg-1), and PP (23.64 ± 6.12 and 19.35 ± 5.49 W·Kg-1). However, the velocity at which these power measures was attained seemed to be independent of sex (~0.95, 1.00 and 2.00 m·s-1 for mean, mean propulsive, and peak velocity, respectively) and homogeneous across different sport disciplines (coefficient of variation <10%). These data can be used to classify athletes' power capabilities, and the optimum velocity ranges provided here could be useful for training purposes.


Cellular concentrations of protein kinase A modulate prostaglandin and cAMP induction of alkaline phosphatase.
The relationship between the concentration of cAMP-dependent protein kinase (PKA) activity and the induction of alkaline phosphatase (AP) was examined in transfected L cell lines with altered PKA levels. C alpha 12 cells were generated by transfecting mouse L cells with an expression vector coding for the mouse C alpha catalytic subunit of PKA and were shown to contain 2.5-fold more PKA activity than L cells. RAB10 cells were generated by transfection with an expression vector for a mutant regulatory subunit and had 10-fold lower levels of PKA activity than L cells. AP induction by 8-chlorophenylthio-cAMP (CPT-cAMP) was found to be 2-fold greater in C alpha 12 cells than in L cells, while RAB10 cells lacked any induction of AP in response to CPT-cAMP. Northern blot and solution hybridization analyses of AP mRNA showed that induced AP mRNA levels were comparable in C alpha 12 and in L cells. Western blot analysis demonstrated that AP protein levels were greater in C alpha 12 cells and suggested that the increased AP protein level resulted from either increased stability of the AP protein or increased rate of translation of the AP mRNA. In contrast, Northern blot analysis of the RAB10 cells failed to detect AP mRNA after CPT-cAMP treatment and suggested that PKA is required for induction of AP mRNA. Stimulation of endogenous cAMP levels by treatment with prostaglandin E1 gave similar effects on AP activity as those seen with CPT-cAMP. These results indicate that cellular levels of PKA can determine the magnitude of cellular response to hormonal stimulation and also suggest that PKA can regulate AP gene expression at both the level of the AP mRNA and AP protein.


The relationship between latent heating, vertical velocity, and precipitation processes: The impact of aerosols on precipitation in organized deep convective systems.
A high-resolution, two-dimensional cloud-resolving model with spectral-bin microphysics is used to study the impact of aerosols on precipitation processes in both a tropical oceanic and a midlatitude continental squall line with regard to three processes: latent heating (LH), cold pool dynamics and ice microphysics. Evaporative cooling in the lower troposphere is found to enhance rainfall in low cloud condensation nuclei (CCN) concentration scenarios in the developing stages of a midlatitude convective precipitation system. In contrast, the tropical case produced more rainfall under high CCN concentrations. Both cold pools and low-level convergence are stronger for those configurations having enhanced rainfall. Nevertheless, latent heat release is stronger (especially after initial precipitation) in the scenarios having more rainfall in both the tropical and midlatitude environment. Sensitivity tests are performed to examine the impact of ice and evaporative cooling on the relationship between aerosols, LH and precipitation processes. The results show that evaporative cooling is important for cold pool strength and rain enhancement in both cases. However, ice microphysics play a larger role in the midlatitude case compared to the tropical. Detailed analysis of the vertical velocity governing equation shows that temperature buoyancy can enhance updrafts/downdrafts in the middle/lower troposphere in the convective core region; however, the vertical pressure gradient force (PGF) is the same order and acts in the opposite direction. Water loading is small but on the same order as the net PGF-temperature buoyancy forcing. The balance among these terms determines the intensity of convection.


Early and late CNS-effects of corona virus infection in rats.
The mouse hepatitis virus strain JHM was injected intracerebrally into newborn and weanling rats. Three types of diseases were observed: 1. Acute panencephalitis: Almost all suckling rats became moribund within 6 days. Histologically severe panencephalitis with demyelinating foci was noticed; the foci were similar to those found in mice. Virus was easily detectable in the oligodendroglial cells and neurons both by immunofluorescence and electron microscopy. Infectious virus could be isolated. 2. Subacute demyelinating encephalomyelitis (SDE): Three weeks after infection of weanling rats, about 35% of the animals developed paralysis. Neuropathologically, demyelination with a striking predilection for white matter was observed in the brain stem, optic nerve and spinal cord. Virus was detectable by electron microscopy in degenerating oligodendroglial cells only, which corresponded to the results obtained by the immunofluorescent techniques. Infectious virus could be recovered. 3. Chronic progressive paralysis: Inoculated weanling rats without SDE developed 6 to 8 months later a slowly progressing paralysis of the legs. Hydrocephalus and myelomalacia were present. Viral "footprints" could not be detected.


Expression of BORIS in melanoma: lack of association with MAGE-A1 activation.
Several genes with specific expression in germ cells show aberrant activation in different types of tumors. These genes, termed cancer-germline (CG) genes, encode tumor-specific antigens, which represent potential targets for therapeutic vaccination against cancer. The germline-specific gene BORIS (Brother Of the Regulator of Imprinted Sites), which encodes an 11-zinc-fingers transcriptional regulator, was recently qualified as a new CG gene, as it was found to be activated in a variety of tumor samples. Moreover, it was suggested that BORIS might be responsible for the activation of most other CG genes, including gene MAGE-A1, in tumors. In the present study, we evaluated the frequency of BORIS activation in melanoma by quantitative RT-PCR. BORIS activation was detected in 27% (n = 63) melanoma tissue samples. Surprisingly, many melanoma samples expressed MAGE-A1 and other CG genes in the absence of BORIS activation, suggesting that BORIS is not an obligate factor for activation of these genes in melanoma. Consistently, forced expression of BORIS in melanoma cell lines did not induce expression of MAGE-A1. Our results indicate that BORIS may serve as a useful target for immunotherapy of melanoma. However, it appears that BORIS is neither necessary nor sufficient for the activation of other CG genes.


Glucose variability, blood pressure and arterial stiffness in type 1 diabetes.
Evidence suggests that chronic hyperglycaemia predicts not only microvascular disease but also macrovascular disease, however it is not known whether it is the glucose variability per se or the total glucose exposure that confers risk. The objective of this study was to investigate whether daily glucose variability influence blood pressure and arterial stiffness, an early sign of macrovascular disease, at baseline and during a hyperglycaemic clamp in patients with type 1 diabetes. Twenty-two non-smoking male patients with type 1 diabetes without any diabetic complications, participated in the study. The patients were monitored for 72-h using a continuous glucose monitoring system. Before and during a 2-h hyperglycaemic clamp, blood pressure as well as pulse wave analysis and pulse wave velocity (PWV) were performed to assess arterial stiffness. No correlation was observed between mean amplitude of glycaemic excursions (MAGE) and arterial stiffness at baseline. There was a correlation between mean daily glucose and aortic PWV even after adjusting for BMI, HbA(1c), and duration of diabetes in a multiple regression analysis (r=0.48; P<0.01). MAGE (r=0.52; P<0.01) correlated independently with the change in aortic DBP during the clamp. This study suggests that high mean daily blood glucose but not glucose variability per se is associated with arterial stiffness in patients with T1D. Daily glucose variability is positively associated with the change in central blood pressure during a hyperglycaemic clamp.


Quantification of the Dynamic Interface Evolution in High-Efficiency Working Li-Metal Batteries.
Lithium (Li) metal has been considered a promising anode for next-generation high-energy-density batteries. However, the low reversibility and intricate Li loss hinder the widespread implementation of Li metal batteries. Herein, we quantitatively differentiate the dynamic evolution of inactive Li, and decipher the fundamental interplay among dynamic Li loss, electrolyte chemistry, and the structure of the solid electrolyte interphase (SEI). The actual dominant form in inactive Li loss is practically determined by the relative growth rates of dead Li0 and SEI Li+ because of the persistent evolution of the Li metal interface during cycling. Distinct inactive Li evolution scenarios are disclosed by ingeniously tuning the inorganic anion-derived SEI chemistry with a low amount of film-forming additive. An optimal polymeric film enabler of 1,3-dioxolane is demonstrated to derive a highly uniform multilayer SEI and decreased SEI Li+ /dead Li0 growth rates, thus achieving enhanced Li cycling reversibility.


Blockade of dopamine receptors in the renal vasculature by isomers of flupenthixol and sulpiride.
We studied the renal vascular effects of flupenthixol and sulpiride isomers in the isolated perfused rat kidney in the presence of phenoxybenzamine (10(-5) M) and sotalol (10(-5) M). The vascular bed was contracted with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M) and dose-dependently relaxed with dopamine. Cis-flupenthixol (10(-9)-10(-7) M) antagonized competitively the response to dopamine (apparent pA2 = 8.34 +/- 0.09; mean +/- SD) without affecting papaverine-induced relaxation. Trans-flupenthixol was without effect at 10(-7) M. The dopamine receptor antagonist activities of the sulpiride isomers are low and d-sulpiride is twice as active as 1-sulpiride. Thus, the renal vascular dopamine receptor can be further characterized by the relative antagonist activities of cis-flupenthixol and sulpiride and by a rather low stereospecificity in favor of d-sulpiride.


Maternal plasma 25-hydroxyvitamin D levels, angiogenic factors, and preeclampsia.
The objective of the study was to examine the associations of maternal plasma levels of 25-hydroxyvitamin D [25(OH)D] with angiogenesis and endothelial dysfunction indicators: soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and risk of preeclampsia. In this prospective cohort study (n = 697), maternal plasma 25(OH)D levels were measured at 12-18 and 24-26 weeks; sFlt-1, PlGF, ICAM-1, and VCAM-1 levels were measured at 24-26 weeks. Maternal PlGF levels were significantly lower in women with 25(OH)D less than 50 nmol/L at 12-18 weeks (median, 449.5 vs 507.9 pg/mL, P = 0.04) and 24-26 weeks (median, 450.4 vs 522.5 pg/mL, P = 0.007). Both maternal 25(OH)D and PlGF levels were inversely associated with the risk of preeclampsia (both P < .05). However, based on a test of interaction, there was no evidence that the association between vitamin D and preeclampsia depended on the level of PlGF. Maternal vitamin D deficiency is associated with low PlGF levels and increased preeclampsia risk. However, our data do not support the hypothesis that the association between vitamin D deficiency and preeclampsia is mediated by impaired angiogenesis.


Tenofovir alafenamide plus dolutegravir as a switch strategy in HIV-infected patients: a pilot randomized controlled trial.
Currently, two-drug antiretroviral regimens are emerging fields in life-long treatment in people living with HIV. This randomized non-inferiority open-label controlled trial was designed to compare the 48-week efficacy and safety of tenofovir alafenamide plus dolutegravir versus the standard triple therapy in virologically suppressed people living with HIV. To the best of our knowledge this combination has not been studied before. This open-label randomized controlled trial was conducted in treatment-experienced people with HIV who had HIV-RNA < 47 copies/mL for at least two years. Patients received either tenofovir alafenamide plus dolutegravir combination (26 patients) or a standard three-drug regimen (29 patients). The primary outcome was the proportion of patients maintaining HIV-RNA < 47 copies/mL during 48 weeks, and the secondary outcomes were CD4 cell count changes, the adherence rate, and adverse drug reactions, all over 48 weeks of study. HIV viral load remained undetectable (HIV-RNA < 47 copies/mL) during the 48 weeks of the study in both arms. The absolute CD4 cell count change was not significant between the two groups. The overall proportion of adverse effects in each group was comparable. The rate of adherence to treatment was acceptable in both groups, and no significant difference was observed. Treatment simplification with tenofovir alafenamide plus dolutegravir regimen as maintenance therapy was non-inferior in terms of efficacy and safety compared to the standard triple therapy. Comparing efficacy of antiretroviral therapy.


Placental protein 10: levels in benign and malignant ovarian cyst fluids and pleural exudates.
Placental protein 10 (PP10) was measured in benign (n = 47) and malignant (n = 10) ovarian cyst fluids and in pleural fluid specimens from 19 patients with pleural metastases of various carcinomas (n = 15) or infectious pleurisy (n = 4). PP10 was found in 9 out of 18 follicular or luteal cyst fluids (range 2.0-42.0 micrograms/l) and in 24 out of 29 benign ovarian tumours (range 2.6-38.0 micrograms/l). Nine out of ten malignant ovarian cyst fluids contained detectable PP10 (range 4.0-55.2 micrograms/l). PP10 was found in all the pleural fluids from 15 patients with metastatic bronchial, pulmonary, breast or pancreatic carcinomas (range 5.1-100.2 micrograms/l), as well as from four patients with pleurisy (range 5.0-28.6 micrograms/l). Our results indicate that PP10 is tumour-associated, but not tumour-specific.


Identification of selenium-containing proteins in HEK 293 kidney cells using multiple chromatographies, LC-ICPMS and nano-LC-ESIMS.
Our previous studies using HeLa and HEK 293 cells demonstrated that selenomethionine, SeMet, exerts more of an antagonistic effect on arsenic than other selenium species. These studies attributed the antagonistic effect of SeMet to decreased levels of reactive oxygen species, ROS, changes in protein phosphorylation and possible incorporation of SeMet into proteins. The present study employs a metallomics approach to identify the selenium-containing proteins in HEK 293 cells raised with SeMet. The proteins were screened and separated using two dimensional high performance liquid chromatography (HPLC)-inductively coupled plasma mass spectrometry (ICPMS), size exclusion chromatography (SEC) and reversed-phase chromatography (RPC). The Se-containing proteins were identified by peptide mapping using nano-HPLC-Chip-electrospray ionization mass spectrometry (ESIMS).


Revisiting revitalization: exploring how structural determinants moderate pathways between neighborhood change and health.
Vacant housing can produce many issues that affect residents' quality of life, especially in historically segregated communities of color. To address these challenges, local governments invest in strategic, place-based revitalization initiatives focused on the regeneration of vacant housing. Yet, the outcomes of these efforts remain contested. To maximize health benefits of revitalization investments, a more nuanced understanding of pathways between neighborhood changes and residents' responses, adaptations, and ability to thrive is necessary, though, remains largely absent in the literature. Using the Vacants to Value initiative in Baltimore, MD as a case study, we explore (1) how health manifests among certain groups in the context of vacant housing revitalization; (2) how vacant housing and its regeneration engender social and cultural environmental change i.e., gentrification; and (3) what structural determinants (cultural norms, policies, institutions, and practices) contribute to the distribution of material resources and benefits of revitalization. Results suggest that vacant housing revitalization requires more than just physical remedies to maximize health. Our findings demonstrate how vacant housing revitalization influences the physical environment, social environment, and structural determinants of material resources and community engagement that can ultimately impact residents' physical, mental, and social health. This study recommends that because housing disparities are rooted in structural inequalities, how policies, practices, and processes moderate pathways for residents to adapt and benefit from neighborhood changes is consequential for health and health equity. Establishing shared governance structures is a promising approach to foster equitable decision-making and outcomes. Going forward in urban regeneration, pathways to retain and strengthen the social environment while revitalizing the physical environment may be promising to achieve healthy communities.


The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon.
The expression of a tight junction (TJ) component protein, claudin-4, in the enteric neurons was investigated in the rat distal colon by immunohistochemistry and RT-PCR. Claudin-4 immunoreactivity was detected in almost all neurofilament-positive enteric neurons both of the submucosal and the myenteric plexuses, and both of the cell bodies and the neurofibers. The immunoreactivity of enteric neurons for claudin-4 was divided into two types: strongly and weakly positive neurons. Especially in the myenteric plexus, the stained neurons were classified by Dogiel's morphological classification of enteric neurons. The strongly stained claudin-4 positive neurons show Dogiel type II morphology, while the weakly stained claudin-4 positive neurons show Dogiel type I morphology. These immunohistochemical data were supported by mRNA expression in the muscle plus submucosa preparation containing the submucosal and myenteric plexuses, as well as mucosa preparation. The physiological function of claudin-4 expressed on enteric neurons is unclear up to now. It is however suggested that claudin-4 expressed on enteric neurons might play roles for the neural activity, for example as insulation between neurofibers. In conclusion, the present study clearly shows that claudin-4 is expressed by enteric neurons. This is the first evidence that the neuron itself expresses the TJ component protein, claudin-4, in the nervous system.


The effect of gold sodium thiomalate and auranofin on lipopolysaccharide-induced interleukin-1 production by blood monocytes in vitro: variation in healthy subjects and patients with arthritis.
The anti-rheumatic gold compounds gold sodium thiomalate (GST) and auranofin (AF) have variable and often unpredictable effects in patients treated for arthritis. As inhibition of interleukin-1 (IL-1) production may be an important effect of these drugs, we investigated their effect on IL-1 production by lipopolysaccharide (LPS) stimulated monocytes in a serum-free, non-adherent culture system. A bi-modal effect was observed: low concentrations (GST 10-250 ng/ml and AF 1-100 ng/ml) potentiated IL-1 production, and higher concentrations (GST 200-1000 ng/ml and AF10-500 ng/ml) inhibited it. This bi-modal effect was observed for both secreted and cell-associated IL-1 activity with the exception that GST failed to inhibit cell-associated IL-1 generation. The potentiating effect was dependent on the continuous presence of gold for at least the first few hours after LPS stimulation. The inhibitory effect of GST was dependent on its presence after LPS stimulation while that of AF was evident even if cells were pretreated with AF and washed before exposure to LPS. There was considerable individual variation in IL-1 production in response to LPS as well as in the effects of gold on cells from both healthy individuals and patients with arthritis. There was also some overlap in the range of concentrations of gold that potentiated and inhibited IL-1 production, and there was relative insensitivity to the inhibitory effects of gold in certain individuals. These results may explain some of the variability in the response of patients to chrysotherapy and support further studies to see if these in vitro effects might predict clinical response to gold.


Functional extracellular matrix hydrogel modified with MSC-derived small extracellular vesicles for chronic wound healing.
Diabetic wound healing remains a global challenge in the clinic and in research. However, the current medical dressings are difficult to meet the demands. The primary goal of this study was to fabricate a functional hydrogel wound dressing that can provide an appropriate microenvironment and supplementation with growth factors to promote skin regeneration and functional restoration in diabetic wounds. Small extracellular vesicles (sEVs) were bound to the porcine small intestinal submucosa-based hydrogel material through peptides (SC-Ps-sEVs) to increase the content and achieve a sustained release. NIH3T3 cell was used to evaluate the biocompatibility and the promoting proliferation, migration and adhesion abilities of the SC-Ps-sEVs. EA.hy926 cell was used to evaluate the stimulating angiogenesis of SC-Ps-sEVs. The diabetic wound model was used to investigate the function/role of SC-Ps-sEVs hydrogel in promoting wound healing. A functional hydrogel wound dressing with good mechanical properties, excellent biocompatibility and superior stimulating angiogenesis capacity was designed and facilely fabricated, which could effectively enable full-thickness skin wounds healing in diabetic rat model. This work led to the development of SIS, which shows an unprecedented combination of mechanical, biological and wound healing properties. This functional hydrogel wound dressing may find broad utility in the field of regenerative medicine and may be similarly useful in the treatment of wounds in epithelial tissues, such as the intestine, lung and liver.


Equivalent Impact of Elevated Lipoprotein(a) and Familial Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease.
Genetically elevated plasma lipoprotein(a) and familial hypercholesterolemia each result in premature atherosclerotic cardiovascular disease (ASCVD); however, a direct comparison in the same population is needed of these 2 genetic traits on the risk of ASCVD. We determined the level of plasma lipoprotein(a) that is equivalent to low-density lipoprotein (LDL) cholesterol in clinically and genetically diagnosed familial hypercholesterolemia on risk of myocardial infarction and ASCVD. We examined the CGPS (Copenhagen General Population Study) with determination of lipoprotein(a) and familial hypercholesterolemia in 69,644 individuals followed for 42 years, during which time, 4,166 developed myocardial infarction and 11,464, ASCVD. For risk of myocardial infarction, the plasma lipoprotein(a) level equivalent to LDL cholesterol in clinical familial hypercholesterolemia was 67 mg/dL (142 nmol/L) for MEDPED (Make Early Diagnosis to Prevent Early Death), 110 mg/dL (236 nmol/L) for Simon Broome, 256 mg/dL (554 nmol/L) for possible DLCN (Dutch Lipid Clinic Network), and 402 mg/dL (873 nmol/L) for probable+definite DLCN, whereas it was 180 mg/dL (389 nmol/L) for genetic familial hypercholesterolemia. Corresponding values for ASCVD were 130 mg/dL (280 nmol/L), 150 mg/dL (323 nmol/L), 227 mg/dL (491 nmol/L), 391 mg/dL (849 nmol/L), and 175 mg/dL (378 nmol/L), respectively. Individuals with both elevated lipoprotein(a) and either familial hypercholesterolemia or a family history of premature myocardial infarction had a higher risk of myocardial infarction and ASCVD compared with individuals with only 1 of these genetic traits, with the highest HRs being for lipoprotein(a) upper 20% vs lower 50% of 14.0 (95% CI: 9.15-21.3) for myocardial infarction and 5.05 (95% CI: 3.41-7.48) for ASCVD. Lipoprotein(a) levels equivalent to LDL cholesterol in clinical and genetic familial hypercholesterolemia were 67 to 402 mg/dL and 180 mg/dL, respectively, for myocardial infarction and 130 to 391 mg/dL and 175 mg/dL, respectively, for ASCVD.


Synthesis, Structure, and Reactivity of 5-(Aryl)dibenzothiophenium Triflates.
A synthetic protocol for the preparation of 5-(aryl)dibenzothiophenium salts starting from inexpensive dibenzothiophene S-oxide and simple arenes is reported. The scope of the method regarding the nature of the arene is evaluated, intermediates along the reaction sequence have been trapped, and side-reactions identified. In addition, the X-ray structures of a complete set of these salts are reported and their reactivities studied. Specifically, chemoselective Suzuki coupling is observed at the dibenzothiophenium in the presence of iodides.


How machine learning can help select capping layers to suppress perovskite degradation.
Environmental stability of perovskite solar cells (PSCs) has been improved by trial-and-error exploration of thin low-dimensional (LD) perovskite deposited on top of the perovskite absorber, called the capping layer. In this study, a machine-learning framework is presented to optimize this layer. We featurize 21 organic halide salts, apply them as capping layers onto methylammonium lead iodide (MAPbI3) films, age them under accelerated conditions, and determine features governing stability using supervised machine learning and Shapley values. We find that organic molecules' low number of hydrogen-bonding donors and small topological polar surface area correlate with increased MAPbI3 film stability. The top performing organic halide, phenyltriethylammonium iodide (PTEAI), successfully extends the MAPbI3 stability lifetime by 4 ± 2 times over bare MAPbI3 and 1.3 ± 0.3 times over state-of-the-art octylammonium bromide (OABr). Through characterization, we find that this capping layer stabilizes the photoactive layer by changing the surface chemistry and suppressing methylammonium loss.


Untreated perinatal paternal depression: Effects on offspring.
Transition to parenthood represents an important life event which increases vulnerability to psychological disorders. Aim of this article is to analyze all studies which investigated the effects of untreated perinatal paternal depression in offspring. We searched pertinent, peer-reviewed articles published in English (January 1980 to April 2016) on MEDLINE, PsycINFO, and Science.gov. Twenty-three studies met the inclusion criteria. Most of the reviewed studies suffer from methodological limitations, including the small sample, the lack of a structured psychiatric diagnosis, and inclusion bias. Despite such limitations, paternal depression seems to be associated with an increased risk of developmental and behavioural problems and even psychiatric disorders in offspring. In particular, in infants and toddlers such problems vary from increased crying to hyperactivity and conduct problems to psychological and developmental impairment, and poor social outcomes. School-age children of depressed fathers have a doubled risk for suffering from specific psychiatric disorders. Hence, facilitating access to vigorous and evidence based treatments is a public health opportunity for improving the quality of life of depressed parents and their children. Evidences emerging from this review actually suggest that the traditional gender-focused approach to perinatal mood disorders should be completed by a family-centred approach, in order to improve the effectiveness of perinatal mental health programs.


A case of anti-VEGF therapy application in Takayasu arteries with retinopathy.
Takayasu arteritis (TA) is a systemic granulomatous large vessel vasculitis that involves mainly the aorta and its primary branches, and occurs most commonly in young females. Ocular manifestations of TA include small vessels dilation, microaneurysm, arteriovenous anastomosis, retinal ischemia and retinopathy. However, no specific and effective treatments for Takayasu retinopathy is applied. This case aimed to demonstrate the role of anti-VEGF (vascular endothelial growth factor) therapy in treating Takayasu retinopathy. We herein reported an 18-year-old Asian woman who presented with typical wreath-like arteriovenous anastomosis around the disc in the right eye and vitreous hemorrhage in the left eye. The stenosis and occlusion of bilateral subclavian arteries, carotid arteries and other proximal arteries on angiography confirmed the diagnosis of TA. Meanwhile, elevated ESR and CRP revealed that TA was in the active stage. We applied anti-VEGF therapy in treating Takayasu retinopathy specially to inhibit neovascularization. Additionally, vitreous extraction was conducted in the left eye after the treatment of anti-VEGF therapy. This is the first report of effective application of anti-VEGF therapy in inhibiting wreath-like arteriovenous anastomosis and improving vitrectomy in TA.


Examining Field Experiences of Teacher Candidates During COVID-19: Systemic Inequities Unveiled for Underserved English Learners in K-12 Grades.
The impact of coronavirus disease 2019 challenged schools and credential programs to adjust pedagogy, but rapid changes impeded equitable practices to K-12 grade English Learners (ELs). The framework stems from critical multicultural education. Data represented 81 credential candidates across three universities. Study confirmed that ELs lacked access to online learning, active engagement with peers/teachers, and differentiated instruction due to rapid changes and uncertainties to their programs.


Central-nervous-system stimulants: appraisal of use in geropsychiatric patients.
CNS stimulants such as methylphenidate and pentylenetetrazol are currently prescribed for the treatment of aged persons with symptoms of senility. A review of clinical studies conducted with these compounds indicates that firm evidence of efficacy is lacking. Because of the risks associated with high doses of such stimulants in the aged, it would seem that these compounds are of limited utility in geriatric psychiatry.


Thyroid disease and hypothyroidism are associated with poor COVID-19 outcomes: A systematic review, meta-analysis, and meta-regression.
Coronavirus disease (COVID-19) still becomes a global burden that affected people in different groups. The aim of this study was to evaluate the association between thyroid disease and the outcome of COVID-19 patients. This was a meta-analysis study from articles obtained through a systematic literature search to investigate the relationship between thyroid disease and COVID-19 outcomes. Composite poor outcomes comprised of severity, mortality, intensive care unit (ICU) admission, and hospitalization. A total of 31339 patients from 21 studies included in this study. Thyroid disorder was associated with increased composite poor outcome (risk ratio (RR) 1.87 [95% confidence interval (CI) 1.53, 2.27], p < 0.001; I2 = 84%, p < 0.01), this included higher disease severity (RR 1.92 [1.40, 2.63], p < 0.05; I2 = 86%, p < 0.01), ICU admission (RR 1.61 [1.12, 2.32], p > 0.05; I2 = 32%, p < 0.05), mortality (RR 2.43 [1.44, 4.13], p < 0.05; I2 = 83%, p < 0.01), and hospitalization (RR 1.28 [1.17, 1.39], p < 0.05; I2 = 0%, p < 0.96). Meta-regression analysis indicated that age (p = 0.002) was a significant influence that affects the association. Also, the presence of unspecified thyroid disease (RR 1.91 [1.38, 2.65], p < 0.05; I2 = 81%, p < 0.01) and hypothyroidism (RR 1.90 [1.45, 2.55], p < 0.05; I2 = 85%, p < 0.01) during admission were associated with poor outcomes. Thyroid abnormalities increased the risk of COVID-19 composite poor outcomes and were influenced by the patient's age. Abnormal thyroid and hypothyroidism, but not hyperthyroidism, were associated with poor COVID-19 outcomes.


Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge.
Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infectious doses of the CCR5 tropic SHIV(SF162p4). Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor T-cell responses, but rather with the Nab titer prior to exposure.