The Effects of sodium bicarbonate Ringer's solution on acute kidney injury and the clinical outcomes after liver transplantation: A randomized controlled trial.
Background: Acute kidney injury is the most common complication after liver transplantation. Sodium bicarbonate Ringer's solution is a new type of crystalloid solution that has been recently used in the clinical setting. Whether sodium bicarbonate Ringer's solution reduces the occurrence of postoperative AKI and improves the clinical outcomes of liver transplantation patients is not clear. Objective: To compare the effects of sodium bicarbonate Ringer's solution versus normal saline on acute kidney injury and clinical outcomes following classic orthotopic liver transplantation. Methods: Sixty-four participants were randomly assigned to the sodium bicarbonate Ringers (BRS) group or the normal saline (NS) group. The primary outcomes were the incidence and severity of acute kidney injury after liver transplantation. The secondary outcomes included the rate of renal replacement therapy, length of mechanical ventilation, stay in the ICU, stay in the hospital after surgery and 30-day mortality. Other outcomes included the concentration of sodium, chloride, bicarbonate, anion gap, lactate concentration and changes in chloride preoperatively and postoperatively. Result: Sixty-two patients completed the trial and were analyzed, with 31 patients in each group. There was a significantly lower rate of postoperative acute kidney injury in the BRS group (14/31, 45.2%) than in the NS group (24/31, 77.4%), with a relative risk of 0.58 (95% CI, 0.38-0.90; p = 0.009). The severity of AKI in the BRS group was lower than that in the NS group (Z = -2.932, p = 0.003). There was no significant difference observed in the secondary outcomes. For other outcomes, the concentration of preoperative sodium was lower than postoperative sodium in the NS group (137.2 vs. 140.4, p = 0.009). The concentration of preoperative chloride was lower than that of postoperative chloride in the NS group (102.9 vs. 106.2, p < 0.001). The change in the concentration of chloride in the BRS group was lower than that in the NS group (1.6 vs. 4.7, p = 0.006). Conclusion: Sodium bicarbonate Ringer's solution reduced the incidence and severity of acute kidney injury after classic orthotopic liver transplantation.


Current status of white coat hypertension: where are we?
White coat hypertension (WCH) is characterised by an elevated clinic blood pressure (BP) with normal ambulatory or home BP. It is well recognised in clinical practice and occurs in approximately one-third of untreated patients with elevated clinic BP. Current evidence suggests that WCH is associated with cardiovascular risk factors, including the development of sustained hypertension and the presence of target organ damage. However, its effects on cardiovascular outcomes remain a matter of debate. There is also insufficient evidence from randomised controlled trials to determine whether WCH warrants treatment. This narrative review aims to provide an update on the current understanding of WCH. It focuses on the clinical characteristics and potential implications of WCH, its relationship to cardiovascular risk and the evidence regarding treatment. Gaps in existing research are also highlighted.


Conformation-determined through-bond versus through-space electronic communication in mixed-valence systems with a cross-conjugated urea bridge.
Bis-triarylamine 2 and cyclometalated diruthenium 6(PF6)2 with a linear trans,trans-urea bridge have been prepared, together with the bis-triarylamine 3 and cyclometalated diruthenium 8(PF6)2 with a folded cis,cis-N,N-dimethylurea bridge. The linear or folded conformations of these molecules are supported by single-crystal X-ray structures of 2, 3, and other related compounds. These compounds display two consecutive anodic redox waves (N(·+/0) or Ru(III/II) processes) with a potential separation of 110-170 mV. This suggests that an efficient electronic coupling is present between two redox termini through the cross-conjugated urea bridge. The degree of electronic coupling has been investigated by using spectroelectrochemical measurements. Distinct intervalence charge-transfer (IVCT) transitions have been observed for mixed-valent (MV) compounds with a linear conformation. The IVCT transitions can also be identified for the folded MV compounds, albeit with a much weaker intensity. DFT results support that the electronic communication occurs by a through-bond and through-space pathway for the linear and folded compounds, respectively. The IVCT transitions of the MV compounds have been reproduced by TDDFT calculations. For the purpose of comparison, a bistriarylamine and a diruthenium complex with an imidazolidin-2-one bridge and a urea-containing mono-triarylamine and monoruthenium complex have been synthesized and studied.


[Retroperitoneal Cellular Angiofibroma: A Rare Gynecological Entity].
Cellular angiofibroma is a mesenchymal tumor, described in 1997, without gender preference, that usually appears at age 40. The vulvovaginal area is the most common site in women, mimicking vulvar benign tumors, like Bartholin gland cyst. However, there are a few described cases of a deep or extra-pelvic angiofibroma. Excision is the treatment of choice and the recurrence rate appears to be low. We present the case of a woman with a heterogeneous tumor in the right adnexial region. At the surgery, a retroperitoneal tumor was excised and the histopathological tissue analysis revealed a cellular angiofibroma.


Assessing tremor severity.
A clinical rating scale which measured the severity of tremor in 20 patients (12 with essential tremor and 8 with "dystonic" tremor) was assessed at specific anatomical sites for both inter and intra-rater reliability using four raters. The scores obtained with the scale were compared with the results of upper limb accelerometry, an activity of daily living self-questionnaire and estimates of the tremor induced impairment in writing and drawing specimens. The results show that, for the purposes of routine assessment and therapeutic trials, a clinical rating scale can produce reliable results which are a more valid index of tremor induced disability than standard postural accelerometry.


Parallel carbon nanotube stripes in polymer thin film with remarkable conductive anisotropy.
In our previous study ( Mao et al. J. Phys. Chem. Lett. 2013 , 4 , 43 - 47 ), we proposed a novel method, that is, the shear-flow-induced hierarchical self-assembly of two-dimensional fillers (octadecylamine-functionalized graphene) into the well-ordered parallel stripes in a polymer matrix, to fabricate the anisotropic conductive materials. In this study, we extend this method to one-dimensional multiwalled carbon nanotubes (MWCNTs). Under the induction of shear flow, the dispersed poly(styrene ethylene/butadiene-styrene) (SEBS) phase and MWCNTs can spontaneously assemble into well-ordered parallel stripes in the polypropylene (PP) thin film. The electrical measurements indicate that the electrical resistivity in the direction parallel to the stripes is almost 6 orders of magnitude lower than that in the perpendicular direction, which is by far the most striking conductive anisotropy for the plastic anisotropic conductive materials. In addition, it is found that the size of the MWCNT stripe as well as the electrical property of the resulting anisotropic conductive thin film can be well-controlled by the gap of the shear cell.


Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease.
The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis of published GWA studies. We propose that dysregulation of monocyte adaptation to the environment of the gastrointestinal mucosa is the key process leading to inflammatory bowel disease.


Amplified Expansion Stimulated Emission Depletion Microscopy.
Expansion microscopy (ExM) enhances spatial resolution by using a swellable polymer that expands the sample volume by a factor of ≈4 in one dimension and a factor of ≈64 in volume. Combining ExM with stimulated emission depletion (STED) microscopy, referred to as ExSTED, increases the resolution to up to 10 nm. However, photobleaching is a critical issue in ExSTED because the sample expansion lowers the fluorophore density whereas high-resolution STED requires high depletion intensity. To overcome these issues, we developed extremely bright expansion nanoscopy by using biotin-avidin signal amplification to increase the labeling density. Our method provides up to sevenfold increases in fluorescence signal intensity in expanded samples, thus enabling the use of STED imaging with maximum depletion intensities of a commercial microscope in the order of GW cm-2 . We demonstrated the method by using biotinylated antibodies and genetic incorporation approaches that allow localization of biotin in a specific molecule or organelle.


Role of Digital Economy in Rebuilding and Sustaining the Space Governance Mechanisms.
The need for sustainable corporate governance has gained the interests of researchers for a while now and it has been found as a very significant component of successful organizational operations. The current paper has examined the role of sustainable corporate governance in achieving sustainable economic space along with measuring the indirect impact of technological innovation and IT governance on the whole process. This paper has followed the quantitative-positivism approach to measure the hypotheses developed in the study. The population considered in this study are the managers currently employed in the corporate sector in China (N = 310). The data is analyzed using the Smart-PLS 3.3.3 software for checking the data for preliminary screening and the measurement of hypotheses. The findings of the study show that the three components of sustainable corporate governance, i.e., concern for employees, sustainable corporate governance awareness, and the environmental aspects have a significant as well as a positive effect on technological innovation and hence on the sustainable economic space. Similarly, the study has recorded a significant moderating effect of IT governance on the relationship of technological innovation and the sustainable economic space. Overall, it can be seen that corporate governance, innovative technology, and a sustainable digital economy share a reciprocal relationship. Where corporate governance helps as a supporting force to keep both innovation and sustainability in action. Whereas IT governance provides enhanced communication and delivery of public services, business, and advanced human capital. The study will be of high advantage for the corporate sector in China for devising and modifying their policies that consider the employee's concerns for the governance mechanisms prevailing at priority in the organizations. Further, it will be interesting for the organizations to incorporate the IT governance mechanism in their technological innovations for achieving a sustainable economic space.


Collagen arthritis in rats, arthritogenic lymphokines and other aspects.
This review will mainly highlight data from selected, independent studies which collectively implicate a primary role for T cells in the pathogenesis of collagen arthritis in rats. Conferring insusceptibility to this experimental disease with the use of polyclonal, T cell specific antiserum provided direct initial evidence for this conclusion. Substantiation for the theory of a dominant T cell role in collagen arthritis was afforded by T cell line vaccination; scrutiny showed that the mechanism accounting for this protection was a specific down-regulation of the cellular response to collagen. Additional support came from experiments which showed that as few as 10(3) type II collagen specific T line cells were capable of provoking a sustained proliferative synovitis when instilled into the knee joint cavity of syngeneic naive rats. Further analysis of this phenomenon revealed that the arthritogenic capacity of various collagen-reactive line cells correlated with their ability to release a 65-Kd, collagen-binding lymphokine. This antigen-specific lymphokine was designated arthritogenic factor, based on an arthritogenic activity in the knee joint bioassay similar to that of the cells. A functional and physicochemically identical rat arthritogenic factor has also been identified in the adjuvant model of arthritis. These data support the premise that a major effector mechanism in experimental rat arthritis is the release of arthritogenic factor by expanded clones of autoreactive T cells; they also indicate that substantive efforts should be undertaken to seek to identify arthritogenic factor-like lymphokines in patients with chronic inflammatory synovial disease. As an equally plausible alternative hypothesis, the review will close with a brief discussion of recent findings supporting the possible involvement of cartilage-binding, complement-fixing anti-type II collagen antibodies in the pathogenesis of rheumatoid arthritis.


Wireless local area networking for linking a PC reporting system and PACS: clinical feasibility in emergency reporting.
Although local area networks (LANs) are commonplace in hospital-based radiology departments today, wireless LANs are still relatively unknown and untried. A linked wireless reporting system was developed to improve work throughput and efficiency. It allows radiologists, physicians, and technologists to review current radiology reports and images and instantly compare them with reports and images from previous examinations. This reporting system also facilitates creation of teaching files quickly, easily, and accurately. It consists of a Digital Imaging and Communications in Medicine 3.0-based picture archiving and communication system (PACS), a diagnostic report server, and portable laptop computers. The PACS interfaces with magnetic resonance imagers, computed tomographic scanners, and computed radiography equipment. The same kind of functionality is achievable with a wireless LAN as with a wired LAN, with comparable bandwidth but with less cabling infrastructure required. This wireless system is presently incorporated into the operations of the emergency and radiology departments, with future plans calling for applications in operating rooms, outpatient departments, all hospital wards, and intensive care units. No major problems have been encountered with the system, which is in constant use and appears to be quite successful.


Speciation and rapid phenotypic differentiation in the yellow-rumped warbler Dendroica coronata complex.
The relative importance of the Pleistocene glacial cycles in driving avian speciation remains controversial, partly because species limits in many groups remain poorly understood, and because current taxonomic designations are often based on phenotypic characteristics of uncertain phylogenetic significance. We use mtDNA sequence data to examine patterns of genetic variation, sequence divergence and phylogenetic relationships between phenotypically distinct groups of the yellow-rumped warbler complex. Currently classified as a single species, the complex is composed of two North American migratory forms (myrtle warbler Dendroica coronata coronata and Audubon's warbler Dendroica coronata auduboni), and two largely sedentary forms: Dendroica coronata nigrifrons of Mexico, and Dendroica coronata goldmani of Guatemala. The latter are typically considered to be races of the Audubon's warbler based on plumage characteristics. However, mtDNA sequence data reveal that sedentary Mesoamerican forms are reciprocally monophyletic to each other and to migratory forms, from which they show a long history of isolation. In contrast, migratory myrtle and Audubon's warblers form a single cluster due to high levels of shared ancestral polymorphism as evidenced by widespread sharing of mtDNA haplotypes despite marked phenotypic differentiation. Sedentary and migratory forms diverged in the early Pleistocene, whereas phenotypic differentiation between the two migratory forms has occurred in the Holocene and is likely the result of geographical isolation and subsequent range expansion since the last glaciation. Our results underscore the importance of Quaternary climatic events in driving songbird speciation and indicate that plumage traits can evolve remarkably fast, thus rendering them potentially misleading for inferring systematic relationships.


Large-scale analysis of gene expression profiles.
The accumulation of DNA microarray data has now made it possible to use gene expression profiles to analyse expression data. A gene expression profile contains the expression data for a given gene over various samples, and can be contrasted with an expression signature, which contains the expression data for a single sample. Gene expression profiles are most revealing when samples are grouped appropriately, either by standard clinical or pathological categories or by categories discovered through cluster analysis techniques. Expression profiles can exist at various levels of abstraction, yielding information across various tissues or across diseases within a particular tissue. Hypothesis tests may be applied to expression profiles on a large scale to identify candidate genes of interest.


Computer-assisted molecular modeling of tumor promoters: rationale for the activity of phorbol esters, teleocidin B, and aplysiatoxin.
In the two-stage model of skin carcinogenesis, it is believed that initiators bind to DNA and that tumor promoters such as phorbol 12-tetradecanoate 13-acetate (TPA) bind noncovalently to membrane-associated high-affinity receptors, probably protein kinase C. Two other types of potent tumor-promoting substances, aplysiatoxin and teleocidin, appear to act also by binding to and activating protein kinase C, even though their chemical structures are quite different. Therefore, we have undertaken computer modeling of the special relationship of various functional groups in these three chemical classes of tumor promoters in an attempt to explain how these diverse structures bind to the same receptor molecule. We propose a stereochemical model in which the oxygens in TPA at C-3, C-4, C-9, and C-20 (O-3, O-4, O-9, and O-20) correspond to the O-11, N-13, N-1, and O-24 positions in teleocidin and the O-27, O-3, O-11, and O-30 oxygens in aplysiatoxin, respectively. In this model all distances with respect to overlap of the corresponding atoms are less than 1 A. In addition, all three types of molecules have their hydrophobic moieties oriented in a similar position. This model is further discussed with respect to other compounds showing various degrees of activity as tumor promoters, including mezerein, ingenol, and 4 alpha-TPA. The model explains how chemically diverse structures can have similar biological activity as tumor promoters and provides a basis for designing both agonists and antagonists of tumor promoters.


Repurposing the anti-epileptic drug sodium valproate as an adjuvant treatment for diffuse intrinsic pontine glioma.
Targeting epigenetic changes in diffuse intrinsic pontine glioma (DIPG) may provide a novel treatment option for patients. This report demonstrates that sodium valproate, a histone deacetylase inhibitor (HDACi), can increase the cytotoxicity of carboplatin in an additive and synergistic manner in DIPG cells in vitro. Sodium valproate causes a dose-dependent decrease in DIPG cell viability in three independent ex vivo cell lines. Furthermore, sodium valproate caused an increase in acetylation of histone H3. Changes in cell viability were consistent with an induction of apoptosis in DIPG cells in vitro, determined by flow cytometric analysis of Annexin V staining and assessment of apoptotic markers by western blotting. Subsequently, immunofluorescent staining of neuronal and glial markers was used to determine toxicity in normal rat hippocampal cells. Pre-treatment of cells with sodium valproate enhanced the cytotoxic effects of carboplatin, in three DIPG cell lines tested. These results demonstrate that sodium valproate causes increased histone H3 acetylation indicative of HDAC inhibition, which is inversely correlated with a reduction in cell viability. Cell viability is reduced through an induction of apoptosis in DIPG cells. Sodium valproate potentiates carboplatin cytotoxicity and prompts further work to define the mechanism responsible for the synergy between these two drugs and determine in vivo efficacy. These findings support the use of sodium valproate as an adjuvant treatment for DIPG.


Using deviance regulation theory to target marijuana use intentions among college students.
Several large epidemiological studies have shown increasing trends on a number of indices of marijuana use among college age samples. This may be due to changing attitudes about marijuana use linked to legalization efforts. Interventions that can target problematic use on a broad scale are lacking. Recent research has shown that deviance regulation theory (DRT) can be used to design effective web-based substance use interventions. DRT relies on the interplay between perceived norms and an appropriately framed message about the given behavior. The current study examines the use of DRT to change marijuana use intentions. Participants (n = 694 college students) completed measures of marijuana use and marijuana use norms. They were then assigned to receive a positively framed message about marijuana abstainers or a negatively framed message about marijuana users. Following the manipulation, participants rated intentions to use marijuana over the next three months. Consistent with DRT, there was an interaction between message frame and marijuana use norms. The positive frame attenuated the association between marijuana use norms and use intentions. A negative frame resulted in the lowest levels of use intentions among those with low use norms. Results suggest that DRT may be used to modify use intentions in college students, a population that has shown increasing rates of use. (PsycINFO Database Record


An inhibitory epitope of human Toll-like receptor 4 resides on leucine-rich repeat 13 and is recognized by a monoclonal antibody.
Lipopolysaccharide (LPS)-induced activation of Toll-like receptor 4 (TLR4) elicits the innate immune response and can trigger septic shock if excessive. Two antibodies (HT4 and HT52) inhibit LPS-induced human TLR4 activation via novel LPS binding-independent mechanisms. The HT52 epitope resides on leucine-rich repeat 2 (LRR2) and is a feature of many inhibitory antibodies; antigen specificity of HT4 does not reside in LRR2. Here, we identified an HT4 epitope on LRR13 located close to the TLR4 dimerization interface that plays a role in NFκB activation. HT4 and HT52 mutually enhanced TLR4 inhibition. LRR13 is a novel inhibitory epitope and may be useful for developing anti-TLR4 antibodies. Combination therapy with LRR2 and LRR13 may effectively inhibit TLR4 activation.


Expression Changes of Structural Protein Genes May Be Related to Adaptive Skin Characteristics Specific to Humans.
Human skin is morphologically and physiologically different from the skin of other primates. However, the genetic causes underlying human-specific skin characteristics remain unclear. Here, we quantitatively demonstrate that the epidermis and dermis of human skin are significantly thicker than those of three Old World monkey species. In addition, we indicate that the topography of the epidermal basement membrane zone shows a rete ridge in humans but is flat in the Old World monkey species examined. Subsequently, we comprehensively compared gene expression levels between human and nonhuman great ape skin using next-generation cDNA sequencing (RNA-Seq). We identified four structural protein genes associated with the epidermal basement membrane zone or elastic fibers in the dermis (COL18A1, LAMB2, CD151, and BGN) that were expressed significantly greater in humans than in nonhuman great apes, suggesting that these differences may be related to the rete ridge and rich elastic fibers present in human skin. The rete ridge may enhance the strength of adhesion between the epidermis and dermis in skin. This ridge, along with a thick epidermis and rich elastic fibers might contribute to the physical strength of human skin with a low amount of hair. To estimate transcriptional regulatory regions for COL18A1, LAMB2, CD151, and BGN, we examined conserved noncoding regions with histone modifications that can activate transcription in skin cells. Human-specific substitutions in these regions, especially those located in binding sites of transcription factors which function in skin, may alter the gene expression patterns and give rise to the human-specific adaptive skin characteristics.


Retrovirus RNA trafficking: from chromatin to invasive genomes.
Full-length retroviral RNA has three well-established functions: it constitutes the genomic RNA that is packaged into virions and is transmitted to target cells by infection, it is the messenger RNA (mRNA) template for viral Gag and Pol protein synthesis and it serves as the pre-mRNA for the production of subgenomic spliced mRNAs that encode additional viral proteins such as Env. More recent work indicates that these full-length RNAs also play important roles in the assembly of virus particles, not only as a structural scaffold that facilitates viral core formation but also as a potential regulator of the assembly process itself. Here, we discuss how these assorted activities may be coupled with each other, paying particular attention to the importance of RNA trafficking and subcellular localization in the cytoplasm, possible points of regulation, and the role(s) played by cellular RNA-binding proteins.


Postoperative Carbohydrate Antigen 19-9 Level as a Good Indicator of Ineffective Response to the Currently Recommended S-1 Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma: A Single-Center, Retrospective Study.
The intensity of adjuvant treatment for pancreatic ductal adenocarcinomas (PDACs) has not been stratified according to the risk after resection. This study was designed to identify patients with PDACs in whom the current S-1 adjuvant treatment is ineffective. This single-center, retrospective study included patients who underwent pancreatectomy for PDACs from 2009 to 2020 at Sendai Open Hospital and were receiving S-1 adjuvant treatment. The independent risk factors for recurrence and survival were determined by using a Cox proportional hazards regression model. The effects of S-1 adjuvant treatment and detailed patterns of recurrence were evaluated in patients with high-risk factors. Overall, 118 patients with PDAC received S-1 adjuvant treatment. Postoperative nonnormalized carbohydrate antigen (CA19-9) was a predictive risk factor for recurrence (p < 0.010; hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.26-6.62) and survival (p = 0.008; HR, 2.25; 95% CI, 1.24-4.11) after S-1 adjuvant treatment. In 24 patients with nonnormalized postoperative CA19-9, S-1 monotherapy was ineffective in preventing recurrence, even during the treatment period, compared with that noted in patients who did not receive adjuvant treatment. The recurrence rate during adjuvant treatment was 41.7%; in all cases, recurrence was caused by distant metastasis. The total recurrence rate was up to 95.8%, and distant recurrence was especially frequent. The current S-1 adjuvant treatment regimen is ineffective for patients with postoperative nonnormalized CA19-9. The postoperative CA19-9 level may be a good indicator for further aggressive treatment. This study may lead to further discussions on intensity stratification of adjuvant treatments for PDAC.


A themed collection in memory of Petr Nachtigall.
Professor RNDr. Petr Nachtigall, PhD passed away on 28 December 2022. He was an internationally recognized expert in computational materials science; working at Charles University in the Department of Physical and Macromolecular Chemistry. We honor his memory.


Identification of potential antioxidant compounds in the essential oil of thyme by gas chromatography with mass spectrometry and multivariate calibration techniques.
Thyme species are used in traditional medicine throughout the world and are known for their antiseptic, antispasmodic, and antitussive properties. Also, antioxidant activity is one of the interesting properties of thyme essential oil. In this research, we aim to identify peaks potentially responsible for the antioxidant activity of thyme oil from chromatographic fingerprints. Therefore, the chemical compositions of hydrodistilled essential oil of thyme species from different regions were analyzed by gas chromatography with mass spectrometry and antioxidant activities of essential oils were measured by a 1,1-diphenyl-2-picrylhydrazyl radical scavenging test. Several linear multivariate calibration techniques with different preprocessing methods were applied to the chromatograms of thyme essential oils to indicate the peaks responsible for the antioxidant activity. These techniques were applied on data both before and after alignment of chromatograms with correlation optimized warping. In this study, orthogonal projection to latent structures model was found to be a good technique to indicate the potential antioxidant active compounds in the thyme oil due to its simplicity and repeatability.


Perceived social presence reduces fact-checking.
Today's media landscape affords people access to richer information than ever before, with many individuals opting to consume content through social channels rather than traditional news sources. Although people frequent social platforms for a variety of reasons, we understand little about the consequences of encountering new information in these contexts, particularly with respect to how content is scrutinized. This research tests how perceiving the presence of others (as on social media platforms) affects the way that individuals evaluate information-in particular, the extent to which they verify ambiguous claims. Eight experiments using incentivized real effort tasks found that people are less likely to fact-check statements when they feel that they are evaluating them in the presence of others compared with when they are evaluating them alone. Inducing vigilance immediately before evaluation increased fact-checking under social settings.


Subperiosteal Osteoid Osteoma in the Coronoid Fossa Mimicking Early Elbow Arthropathy: A Case Report.
The elbow pain and restricted movement is a nagging problem and elbow arthropathies need to be excluded. On rare instances, uncommon etiology like a benign lesion is the culprit and the diagnosis would require judicious clinicoradiological correlation. Osteoid osteoma in the intra- or juxta-articular region is reported in the literature as rare, sporadic report. A 23-year-old, Indian male patient presented with a provisional diagnosis of early elbow arthropathy on account of unexplained pain and restricted elbow movement without a history of trauma. He was subjected to appropriate investigations revealing synovial hypertrophy, effusion, and bone edema suggestive of early arthropathy. Additional imaging led to an uncommon definitive diagnosis. An intra-articular osteoid osteoma was found over the medial aspect of the coronoid fossa with a thin rim of cortical rim projecting anteriorly. The lesion was diagnosed and delineated on computerized tomography and an open excision of the lesion and synovectomy was done for histopathological evaluation. Histology confirmed the presence of an osteoid osteoma at an uncommon location. The careful appreciation of radiological images is critical to not miss significant etiology that may mimic non-specific elbow pain. High index of suspicion coupled with appropriate diagnostic imaging results in early diagnosis and appropriate management. Osteoid osteoma should be a differential diagnosis in cases with pain and restricted elbow movement and excision of which results in recovery of painless range of motion.


One-stage breast reconstruction using McGhan Style 150 biodimensional expanders: a review of 107 implants with six years experience.
Permanent expanders have revolutionised breast reconstructive surgery, allowing one-stage procedures and the development of increasingly sophisticated implants (textured, anatomically shaped) has played an important role in enhancing the aesthetic outcomes. It is important to evaluate the tolerability of the implant. The aim of this present study was to evaluate the survival curves for McGhan Style 150 permanent expanders, in a consecutive series of breast reconstructions. Complications rates were also examined. Between April 1997 and May 2003, 107 McGhan Style 150 expanders (either full height or short height depending on patients' requirements) were used in 97 consecutive patients for a variety of breast reconstructive procedures. Overall, 46 devices were used for immediate reconstruction, 15 for delayed reconstruction and 46 for implant exchange, respectively. The mean age at implantation was 48 years (min: 26; max: 71). The mean follow-up was 60 months (min: 12; max: 72). Explantation was considered the most objective outcome variable, therefore this parameter was carefully monitored and then analysed using the Kaplan-Meier method of survival analysis. Different curves were compared using the log-rank test. Long term complications were also recorded. Among complications the most frequent finding was Baker 3-4 capsular contracture, occurring in 26% of immediate reconstructions at six years. Explantations increased in an almost linear fashion, with an overall rate of 25%, with a statistically significant difference among immediate reconstruction group and the implant exchange group. The rate of explantations was high, if compared with other series, because the sample included patients undergoing strong adjuvant therapies, particularly in the immediate group (locally advanced disease). The overall rate of explantations and of capsular contracture was found to be significantly lower in the delayed and substitution groups, than the immediate group (p<0.05). In our hands, the McGhan Style 150 anatomically shaped permanent expanders were associated with acceptable results, especially when used as 'permanent prostheses' for second stage procedures.


Poly[hexa-aqua-bis-(μ(3)-hepta-nedioato-κO:O':O'')dimagnesium].
In the title compound, [Mg(2)(C(7)H(10)O(4))(2)(H(2)O)(6)](n), the Mg(II) ion is coordinated by three aqua ligands and three O atoms from three heptanedioato ligands in a distorted octa-hedral geometry. Each heptanedioato ligand bridges three Mg atoms, generating polymeric layers parallel to the bc plane. The polymeric layers related by translation along the a axis inter-act further via O-H⋯O hydrogen bonds, which consolidate the crystal packing.


Pharmacoinformatics studies of coenzyme Q10 and potassium polyacrylate on angiotensin-converting enzyme associated with hypertension.
Coenzyme Q10's (CoQ10) favorable impact on cardiovascular diseases risk factors like hypertension and atherosclerosis is linked to the antioxidant action of CoQ10 in these conditions. This study showed the possible effects of CoQ10, potassium polyacrylate (PCK), and valsartan, a reference drug, on the angiotensin-converting enzyme (ACE), a crucial component of the renin-angiotensin system. The Glide tool on Maestro 11.1 was used to calculate the respective binding affinity and binding energy of these compounds towards ACE. The Schrödinger suite was used to run molecular dynamic simulations for 100 ns. The pkCSM tool was used to forecast the pharmacokinetic characteristics and toxicological effects. The SwissADME server was used to estimate the drug-like properties of these compounds. Based on their corresponding scoring values and the negative values of the binding free energies, molecular docking analysis of CoQ10 and PCK revealed that both exhibited favorable binding affinities towards the ACE, with CoQ10 having the highest binding scores. The results showed that both CoQ10 and PCK and the reference drug, valsartan, have some amino acids in common (at the pocket site of ACE) as the key residues for binding to ACE. Both CoQ10 and PCK demonstrated drug-like qualities and were not harmful, according to the predicted pharmacokinetics and toxicology studies. The results of this study suggest that because of its inhibitory interactions with ACE, CoQ10 in particular could be useful in regulating and reducing hypertension.Communicated by Ramaswamy H. Sarma.


Competition Between Different Social Ranked Rams has Similar Effects on Testosterone and Sexual Behaviour Throughout the Year.
Dominant rams have preferential access to females, as they frequently interrupt sexual behaviour from subordinated. Testosterone concentrations are directly linked to sexual and aggressive behaviour and have important variations along the year. Therefore, it may be expected that the effects of dominance relationships on reproductive behaviour differ according to testosterone concentrations, and thus to the period of the year. The aim of this study was to compare the effects of dominance relationships on testosterone and sexual behaviour in different moments of the year in rams. Twelve rams were maintained in a single group. Social rank was determined in January (maximum reproductive development), May (regression of the reproductive status) and August (lowest reproductive activity), and the four rams with higher (HR) and the four with lower (LR) success index were used. Testosterone serum concentration was weekly measured four times during each experimental period. Sexual behaviour was evaluated in each period with an oestrous ewe, and with the oestrous ewe and another ram from the other social rank (each HR with each LR ram). Testosterone concentration was greater in HR than LR rams in January (p = 0.03), and all the behaviours were displayed more frequently in non-competitive than in competitive tests (p < 0.05). Rams modified their sexual strategy in competitive environments decreasing the display of sexual behaviour independently of their social status. This effect was observed consistently throughout the year: high-ranked rams have greater testosterone concentrations than LR rams only during the pre-rut, when they naturally compete to join the groups of ewes.


Structural analysis of a helical peptide unfolding pathway.
The analysis of the folding mechanism in peptides adopting well-defined secondary structure is fundamental to understand protein folding. Herein, we describe the thermal unfolding of a 15-mer vascular endothelial growth factor mimicking alpha-helical peptide (QK(L10A)) through the combination of spectroscopic and computational analyses. In particular, on the basis of the temperature dependencies of QK(L10A) H(alpha) chemical shifts we show that the first phase of the thermal helix unfolding, ending at around 320 K, involves mainly the terminal regions. A second phase of the transition, ending at around 333 K, comprises the central helical region of the peptide. The determination of high-resolution QK(L10A) conformational preferences in water at 313 K allowed us to identify, at atomic resolution, one intermediate of the folding-unfolding pathway. Molecular dynamics simulations corroborate experimental observations detecting a stable central helical turn, which represents the most probable site for the helix nucleation in the folding direction. The data presented herein allows us to draw a folding-unfolding picture for the small peptide QK(L10A) compatible with the nucleation-propagation model. This study, besides contributing to the basic field of peptide helix folding, is useful to gain an insight into the design of stable helical peptides, which could find applications as molecular scaffolds to target protein-protein interactions.


Chloroxyanion Residues in Cantaloupe and Tomatoes after Chlorine Dioxide Gas Sanitation.
Chlorine dioxide gas is effective at cleansing fruits and vegetables of bacterial pathogens and(or) rot organisms, but little data are available on chemical residues remaining subsequent to chlorine gas treatment. Therefore, studies were conducted to quantify chlorate and perchlorate residues after tomato and cantaloupe treatment with chlorine dioxide gas. Treatments delivered 50 mg of chlorine dioxide gas per kg of tomato (2-h treatment) and 100 mg of gas per kg of cantaloupe (6-h treatment) in sealed, darkened containers. Chlorate residues in tomato and cantaloupe edible flesh homogenates were less than the LC-MS/MS limit of quantitation (60 and 30 ng/g respectively), but were 1319 ± 247 ng/g in rind + edible flesh of cantaloupe. Perchlorate residues in all fractions of chlorine dioxide-treated tomatoes and cantaloupe were not different (P > 0.05) than perchlorate residues in similar fractions of untreated tomatoes and cantaloupe. Data from this study suggest that chlorine dioxide sanitation of edible vegetables and melons can be conducted without the formation of unwanted residues in edible fractions.


Walnut Oil Alleviates Intestinal Inflammation and Restores Intestinal Barrier Function in Mice.
Ulcerative colitis belongs to inflammatory bowel diseases, which is a group of chronic disorders of the gastrointestinal tract. It is a debilitating condition with a wide range of symptoms including rectal bleeding, diarrhea, and visceral pain. Current dietary habits often lead to imbalance in n-6/n-3 polyunsaturated fatty acids (PUFA) in favor of n-6 PUFA. Recent data showed the potential anti-inflammatory advantage of n-3 PUFA. Walnut oil (WO) is rich in those fatty acids and mainly consists of linoleic and linolenic acids that may act via free fatty acids receptors (FFARs). We assessed the anti-inflammatory effect of WO in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Moreover, we examined changes in the expression of tight junction proteins (TJ), pro-inflammatory cytokines, and FFAR proteins in the inflamed mouse colon. WO improves the damage score in inflamed tissue, significantly restoring ion transport and colonic wall permeability. Inflammation caused changes in TJ, FFAR, and pro-inflammatory gene proteins expression, which WO was able to partially reverse. WO has anti-inflammatory properties; however, its exact mechanism of action remains unclear. This stems from the pleiotropic effects of n-3 PUFA ligands associated with receptor distribution and targeted signaling pathways.


Lack of time and dependence on significant others: Occupational therapists´ experiences of prescribing time assistive technology for persons with dementia.
Background: There is lack of knowledge on how occupational therapists (OTs) assess daily time management (DTM) for persons with dementia (PwDs) and on which aspects affect prescription of time assistive technology (AT).Aim: To explore OTs' experiences of assessing the need for and prescribing time AT for PwDs.Material and methods: Focus group interviews with OTs that prescribe time AT for PwDs analyzed via qualitative content analysis.Results: A main category and four categories were identified. The categories illustrated a complex and time-consuming prescription process, which was facilitated if the PwD was supported by a significant other (SO). Support from a SO was especially important during implementation and follow-up. OTs had to take individual responsibility for staying informed about time AT. Organizational limitations and time constraints were barriers for OTs striving to work according to national prescription guidelines.Conclusions and significance: High demands are made on SO's participation during the prescription process. PwDs with no support from SOs are at risk not receiving or fully benefitting from time AT. To avoid inequalities, specific forms of support need to be developed and targeted at PwDs without SOs to ensure that they have sufficient opportunities to access and use time AT.


Unconscious fantasy in context: The work of Jacob A. Arlow.
For Jacob A. Arlow, understanding unconscious fantasies was central to his clinical work. These fantasies are to be found at the core of those eruptions that break without warning into our ordinary lives, whether in the form of hysterical symptoms, daydreams or nightmares. What, however, could an unconscious fantasy be on a theoretical level, beyond a vehicle for discharge? Although partly unconscious, such fantasies are sometimes composed of fixed verbal content with a high degree of internal organisation. Unconscious fantasies therefore pose many challenges to understanding.


Kinetic studies and unstructured models of lymphocyte metabolism in fed-batch culture.
The growth of two lymphocyte cell lines, a hybridoma cell line and a human cutaneous T cell lymphoma (HuT78), was studied in fed-batch culture, and unstructured models of growth developed. A criteria was established to insure that the growth rate varied by less than a specified tolerance throughout the culture period. Glutamine and serum were growth-limiting nutrients for both cell lines with half-maximal growth rates at 0. 53 mM glutamine and 0. 55%(v/v) serum for the hybridoma cells and 0. 21 mM glutamine and 1. 5% serum for the HuT-78 cells. Over the range of glucose concentrations from 5. 5 mM to 28 mM, the specific growth rate of hybridoma cells was independent of glucose concentration, whereas glucose concentrations above 5. 5 mM inhibited HuT-78 growth. For both cell lines, the growth rate was significantly inhibited by the addition of ammonium, although the hybridoma cell line was more affected by ammonia than was the HuT-78 cell line. Growth of HuT-78 cells increased in the presence of interleukin-2. Unstructured models for the hybridoma cells were similar to other models presented in the literature. Applications of these models to adoptive immunotherapy are discussed.


Aerobic Exercise Prescription in Stroke Rehabilitation: A Web-Based Survey of US Physical Therapists.
Best practice recommendations indicate that aerobic exercise (AEX) should be incorporated into stroke rehabilitation. However, this may be challenging in clinical settings. The purpose of this study was to assess physical therapist (PT) AEX prescription for patients with stroke, including AEX utilization, barriers to AEX prescription, dosing parameters, and safety considerations. A cross-sectional Web-based survey study was conducted. Physical therapists with valid e-mail addresses on file with the state boards of Florida, New Jersey, Ohio, Texas, and Wyoming were eligible to participate. Survey invitations were e-mailed to all licensed PT in these states. Analysis focused on respondents who were currently involved with clinical stroke rehabilitation in common practice settings. Results from 568 respondents were analyzed. Most respondents (88%) agreed that AEX should be incorporated into stroke rehabilitation, but 84% perceived at least one barrier. Median prescribed AEX volume varied between practice settings from 20- to 30-minute AEX sessions, 3 to 5 days per week for 2 to 8 weeks. Prescribed intensity was most commonly light or moderate; intensity was determined by the general response to AEX and patient feedback. Only 2% of respondents reported that the majority of their patients with stroke had stress tests. Most US PTs appear to recognize the importance of AEX for persons poststroke, but clinical implementation can be challenging. Future studies and consensus are needed to clarify best practices and to develop implementation interventions to optimize AEX utilization in stroke rehabilitation.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A167).


Chemistry, pharmacology, pharmacokinetics, and clinical applications of mesalamine for the treatment of inflammatory bowel disease.
Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled-release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion-dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left-sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment-related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid-sparing agent for patients with either active or quiescent Crohn's disease.


High frequency of CYP1A1*2C allele in Brazilian populations.
The genetic variability of the CYP1A1 I462V polymorphism (CYP1A1*2C) was investigated in four Brazilian populations: three groups of African descent and one group of European descent. The CYP1A1 polymorphism was analyzed by two different procedures, first by the allele-specific polymerase chain reaction (PCR) method and then by the PCR-restricted fragment length polymorphism (PCR-RFLP) method before digestion with BsrDI. The frequency of CYP1A1 *2C was 11% in Brazilians of European descent, a frequency that is slightly higher but not statistically different from that observed in European populations. In Brazilians of African ancestry this value was very high (12% to 15%). This allele was not observed in the only two African populations investigated thus far. By themselves, the two factors of interethnic admixture (with populations of European descent and/or Amerindian populations) and genetic drift cannot explain the high values observed here. Our findings suggest that the CYP1A1 *2C allele may possibly be present in Africa, but restricted to some ethnic groups not yet investigated. Environmental factors in South America might also have acted as selective factors increasing the CYP1A1 *2C gene frequency. Our data also suggest that the CYP1A1 *2C allele might possibly have originated in Africa.


Association of anti-citrullinated vimentin and anti-citrullinated α-enolase antibodies with subsets of rheumatoid arthritis.
To determine whether the anti-citrullinated vimentin peptide 60-75 (anti-Cit-vimentin) and the immunodominant anti-citrullinated α-enolase peptide 1 (anti-CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti-cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA. The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA-DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models. A differential, particularly strong, and independent association was observed between the presence of anti-Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti- Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti-CEP-1 positivity and the presence of HLA-DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti-CCP status. Our results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.


The Implementation of Screening for Adverse Childhood Experiences in Pediatric Primary Care.
To assess the implementation of screening, screening rates, and prevalence of adverse childhood experiences (ACEs) in a large integrated healthcare system. Kaiser Permanente Southern California is a large integrated healthcare system with 15 medical centers/hospitals and 233 medical office buildings that serve approximately 1.5 million children. Screening for ACEs began in July 2018 at 1 medical center (Downey, Bellflower medical office) for 3- and 5-year-old well-child visits (yearly physical examination). It quickly expanded to 3 other medical centers (6 clinics in total) and now also includes the 10- and 13-year-old well-child visits. Since July 2018 we have screened 3241 3-year-olds (53% of the target population), 2761 5-year-olds (53%), 545 10-year-olds (37%), and 509 13-year-olds (13%). Of the 3-year-olds who were screened, 15% had an ACEs score of 1 or higher. Of the 5-year-olds that were screened, 17.5% had an ACEs score of 1 or higher. Of the 10-year-olds, 30.5% had an ACEs score of 1 or higher and of the 13-year-olds, 33.8% had an ACEs score of 1 or higher. Although we have encountered some challenges, particularly with follow-up for those screening positive for ACEs, screening was feasible. The data show an increasing trend of ACEs in 3- to 13-year-old children, highlighting the need for early education about ACEs to mitigate the effects of toxic stress.


[Successful endovascular repair of isolated iliac aneurysm and reserving the internal iliac artery with fenestrated covered stent].
Isolated iliac aneurysm is rare and difficult for surgery repair because it locates in the deep pelvis. Endovascular repair is preferred currently, and internal iliac artery is generally embolized in order to avoid the endoleak. Embolization of the internal iliac artery can lead to the complications such as buttock claudication, colon ischaemia and erectile dysfunction. Therefore, the antegrade flow of internal iliac artery should be reserved. One seventy-seven-year-old male patient with isolated left common iliac aneurysm, 30 mm in diameter, was successful endovascular repaired using fenestrated covered stent. At 1-month follow up, the patient was asymptomatic. Computed tomography scan shows the iliac aneurysm was completely excluded, and the antegrade flow of the left common, internal and external iliac arteries were normal.


Combined Oxidative Phosphorylation Deficiency Type-13 with Perinatal Presentation: A Case Report.
Polynucleotide phosphorylase is involved in RNA processing in mitochondria. Biallelic variants in PNPT1 cause mitochondrial RNA import protein deficiency and heterogeneous clinical manifestations. The patiest was the first child of remote consanguineous parents, born at 35 weeks by caesarean section due to fetal growth restriction. Apgar index was 9/10/10. Birth weight, length and head circumference were at 3rd, <3rd and 10th percentiles, respectively. In the first hours of life, respiratory distress, hypoglycaemia and seizures ensued. She started invasive mechanic ventilation, phenobarbital and was transferred to ICU. Physical examination showed minor facial dysmorphisms, brief eye-opening, hypotonia and hyporeflexia. Electroencephalogram showed immature pattern and multifocal paroxysmal activity. MRI at D8 of life showed severe reduced brain volume. Normal aminoacid screen was also observed. Expanded newborn screening was negative. Mitochondrial organic aciduria was seen. WES showed a homozygotic likely pathogenic variant in the PNPT1 gene. MRI at 6-months showed brain atrophy, thin corpus callosum, reduced brainstem volume. Bilateral and symmetrical lesions in globi pallidi, compatible with Leigh síndrome were observed. Currently, at 14 months, no neurodevelopment progress, dystonia, visual deficit, sensorineural deafness, hypertrophic cardiomyopathy and microcephaly are observed. The early and severe Leigh-like presentation of our patient expands the phenotype spectrum of this disease. As far as we know, this is the first reported case of PNPT1 mutation with onset in the perinatal period. Moreover, hypertrophic cardiomyopathy has not yet been described in association with mutation of the PNPT1 gene. WES was the key for early diagnosis in this patient. It should be done in all children with severe clinical presentation of unknown origin.


The effect of functional knee bracing on the anterior cruciate ligament in the weightbearing and nonweightbearing knee.
We investigated the effect of functional bracing on anterior cruciate ligament strain in humans by arthroscopic implantation of a differential variable reluctance transducer on the ligament and measurement of its strain behavior. Strains were measured while "injury mechanism" loads were applied to the weightbearing and nonweightbearing knees for both braced and unbraced conditions. For the unbraced knee, there was a significant increase in ligament strain values when subjects went from a seated position (minimal shear and compressive loads across the knee) to a standing posture (substantial shear and compressive loads across the knee). Similar strain values were found between these same seated and standing postures when a 140-N anterior-directed load was applied to the tibia. This indicates that the ligament is strained during weightbearing and demonstrates that the compressive load across the knee produced during weightbearing does not significantly reduce ligament strain values in comparison with the unweighted joint with relaxed muscles for the 140-N load limit of our anterior shear test. Bracing produced a protective effect on the ligament by significantly reducing the strain values for anterior-directed loading of the tibia up to 140 N with the knee in both weightbearing and nonweightbearing conditions. Likewise, bracing produced a protective effect on the ligament by significantly reducing strain values in response to internal-external torque of the tibia up to 6 N-m with the knee nonweightbearing. The brace strap that contacts the tibia just distal to the insertion of the patellar tendon was instrumented with a load sensor, allowing us to measure the posterior-directed loads applied by the brace to the tibia. Adjustment of strap tension between low and high settings did not modulate the protective effect of the brace on the ligament.


Ecological and genetic impact of the 2011 Tohoku Earthquake Tsunami on intertidal mud snails.
Natural disturbances often destroy local populations and can considerably affect the genetic properties of these populations. The 2011 Tohoku Earthquake Tsunami greatly damaged local populations of various coastal organisms, including the mud snail Batillaria attramentaria, which was an abundant macroinvertebrate on the tidal flats in the Tohoku region. To evaluate the impact of the tsunami on the ecology and population genetic properties of these snails, we monitored the density, shell size, and microsatellite DNA variation of B. attramentaria for more than ten years (2005-2015) throughout the disturbance event. We found that the density of snails declined immediately after the tsunami. Bayesian inference of the genetically effective population size (Ne) demonstrated that the Ne declined by 60-99% at the study sites exposed to the tsunami. However, we found that their genetic diversity was not significantly reduced after the tsunami. The maintenance of genetic diversity is essential for long-term survival of local populations, and thus, the observed genetic robustness could play a key role in the persistence of snail populations in this region which has been devastated by similar tsunamis every 500-800 years. Our findings have significant implications for understanding the sustainability of populations damaged by natural disturbances.


Three isostructural one-dimensional Ln(III) chains with distorted cubane motifs showing dual fluorescence and slow magnetic relaxation/magnetocaloric effect.
Three new homometallic lanthanide complexes with mixed carboxylate-modified rigid ligands, [Ln(μ3-OH)(na)(pyzc)]n (na(-) = 1-naphtholate, pyzc(-) = 2-pyrazinecarboxylate, Ln = Dy (1), Yb (2), and Gd (3)), were solvothermally synthesized, and their structures and magnetic as well as photophysical properties were completely investigated. Complexes 1-3 are crystallographically isostructural, exhibiting linear chains with four bidentate bridging μ-COO(-) moieties encapsulated cubic {Ln4(μ3-OH)4}(8+) clusters repeatedly extended by 4-fold chelating-bridging-pyzc(-) connectors. Magnetically, the former two complexes with highly anisotropic Dy(III) and weak anisotropic Yb(III) ions in the distorted NO7 triangular dodecahedron coordination environment display field-induced slow relaxation of magnetization. Fitting the dynamic magnetic data to the Arrhenius law gives energy barrier ΔE/kB = 39.6 K and pre-exponential factor τo = 1.52 × 10(-8) s for 1 and ΔE/kB = 14.1 K and τo = 2.13 × 10(-7) s for 2. By contrast, complex 3 with isotropic Gd(III) ion and weak intracluster antiferromagnetic coupling shows a significant cryogenic magnetocaloric effect, with a maximum -ΔSm value of 30.0 J kg(-1) K(-1) at 2.5 K and 70 kOe. Additionally, the chromophoric na(-) and pyzc(-) ligands can serve as antenna groups, selectively sensitizing the Dy(III)- and Yb(III)-based luminescence of 1 and 2 in the UV-visible region by an intramolecular energy transfer process. Thus, complexes 1-3, incorporating field-induced slow magnetic magnetization and interesting luminescence together, can be used as composite magneto-optical materials. More importantly, these interesting results further demonstrate that the mixed-ligand system with rigid carboxylate-functionalized chromophores can be excellent candidates for the preparations of new bifunctional magneto-optical materials.


Progress and challenges in probing the human brain.
Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience.


Tomographic Mapping Analysis in the Depth Direction of High-Ge-Content SiGe Layers with Compositionally Graded Buffers Using Nanobeam X-ray Diffraction.
A high-Ge-content Si1-yGey/compositionally graded Si1-xGex-stacked structure grown on Si(001) is now considered to be an important platform for the realization of advanced nanometer-scale complementary metal oxide semiconductor devices with high-mobility channel materials, such as III-V materials and Ge, and monolithically integrated photonic modules. The performance of such advanced devices is critically influenced by crystalline inhomogeneity in the stacked structure; therefore, precise characterization of the crystallinity is important. In particular, the development of a characterization method not only for in-plane crystallinity but also for in-depth crystallinity is strongly required. This is because the crystalline quality of the constant composition Si1-yGey is sensitively dependent on that of the compositionally graded Si1-xGex layers underneath. Here, we have demonstrated in-depth tomographic mapping of a high-Ge-content Si1-yGey/compositionally graded Si1-xGex-stacked structure using position-dependent ω-2θ map measurement using nanobeam X-ray diffraction. This mapping technique is based on the correspondence of each 2θ value in the ω-2θ map to the lattice constant of stacked layers in the depth direction. Application of the proposed analytical procedure provides tomographic maps of the local variation in lattice plane tilting (VLPT) from the obtained ω-2θ maps. It is quantitatively verified that the local crystallinity in the layer at a certain depth is strongly influenced by that underneath the layer. The correlation between the local VLPT and real structural defects in the stacked structure is also discussed in detail.


Depressive Disorder Subtypes as Predictors of Incident Obesity in US Adults: Moderation by Race/Ethnicity.
We compared the relative importance of atypical major depressive disorder (MDD), nonatypical MDD, and dysthymic disorder in predicting 3-year obesity incidence and change in body mass index and determined whether race/ethnicity moderated these relationships. We examined data from 17,787 initially nonobese adults in the National Epidemiologic Survey on Alcohol and Related Conditions waves 1 (2001-2002) and 2 (2004-2005) who were representative of the US population. Lifetime subtypes of depressive disorders were determined using a structured interview, and obesity outcomes were computed from self-reported height and weight. Atypical MDD (odds ratio (OR) = 1.68, 95% confidence interval (CI): 1.43, 1.97; P < 0.001) and dysthymic disorder (OR = 1.66, 95% CI: 1.29, 2.12; P < 0.001) were stronger predictors of incident obesity than were nonatypical MDD (OR = 1.11, 95% CI: 1.01, 1.22; P = 0.027) and no history of depressive disorder. Atypical MDD (B = 0.41 (standard error, 0.15); P = 0.007) was a stronger predictor of increases in body mass index than were dysthymic disorder (B = -0.31 (standard error, 0.21); P = 0.142), nonatypical MDD (B = 0.007 (standard error, 0.06); P = 0.911), and no history of depressive disorder. Race/ethnicity was a moderator; atypical MDD was a stronger predictor of incident obesity in Hispanics/Latinos (OR = 1.97, 95% CI: 1.73, 2.24; P < 0.001) than in non-Hispanic whites (OR = 1.54, 95% CI: 1.25, 1.91; P < 0.001) and blacks (OR = 1.72, 95% CI: 1.31, 2.26; P < 0.001). US adults with atypical MDD are at particularly high risk of weight gain and obesity, and Hispanics/Latinos may be especially vulnerable to the obesogenic consequences of depressions.


Normal vitamin D and mineral metabolism in essential hypertension.
The effects of dietary sodium upon serum and urinary calcium and selected vitamin D metabolites were studied in two groups (n = 10 each) of age and gender matched, white normotensive subjects and patients with normal-renin hypertension. Isocaloric diets were consumed on a metabolic ward with sequential daily sodium intake of 109 meq for 5 days and 9 meq and 259 meq for 6 days each. Values for serum and urinary calcium, phosphorus, magnesium and electrolytes, creatinine clearance, plasma immunoreactive parathyroid hormone, and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar in both study groups on each diet. Measurements of plasma renin activity and serum aldosterone levels were higher in the hypertensive than in the normotensive group on each diet (p less than .05-.01). Serum 1,25-dihydroxyvitamin D and urinary calcium increased on the high sodium diet in the normotensive (p less than .05) and the hypertensive groups (p less than .01). When the data for normotensive subjects and hypertensive patients were pooled by gender, males had a 1 1/2 to 3 times the urinary calcium excretion than females, regardless of diet. The present study indicates that there are no differences in the selected components of calcium and vitamin D metabolism in response to sodium intake in patients with essential hypertension and normal plasma renin activity as compared to normal controls.


Belzutifan: A Narrative Drug Review.
Von Hippel-Lindau disease is an autosomal dominant disorder characterised by renal cell carcinomas, pancreatic neuroendocrine tumours, central nervous system hemangioblastomas, retinoblastomas, and tumours of the reproductive tract. This disease results from loss of function mutations in the tumour suppressor gene known as the Von Hippel-Lindau gene, located on chromosome 3. Loss of function mutation in the Von Hippel-Lindau gene results in the accumulation of a protein known as a hypoxia-inducible factor, which promotes cellular proliferation and angiogenesis, leading to cancer. Belzutifan inhibits the hypoxia-inducible factor by binding to the Per-ARNT -Sim-B binding pocket on the hypoxia-inducible factor -2α, inhibiting cellular proliferation and angiogenesis. In our thorough literature review, we identified 37 relevant articles. Belzutifan showed clinically meaningful response rates for both Von Hippel-Lindau disease-associated renal cell carcinomas and non-renal cell cancers. The pharmacokinetic profile of belzutifan was much better than its congener molecules due to the optimisation of its dihalide groups from germinal to vicinal. The pharmacodynamic effect of belzutifan was confirmed by its ability to decrease serum erythropoietin, which is a direct result of hypoxia-inducible factor- 2α inhibition. The significant side effects observed were anaemia, hypoxia, fatigue, hypertension, visual impairment and weight gain. Multiple clinical trials are currently underway to determine the role of beluztifan as part of combination regimens in treating Von Hippel-Lindau diseaseassociated malignancies.


Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials.
The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.


A new species of the genus Dysommina (Teleostei: Anguilliformes: Synaphobranchidae: Ilyophinae) from the Western Pacific.
Dysommina orientalis, a new species of Ilyophine eel from off Taiwan and Japan is described and illustrated. The species had long been recognized as Dysommina rugosa in the western Pacific and is distinguished from D. rugosa by a lower number of predorsal vertebrae, a higher number of total vertebrae, shorter head length, smaller eye size, reduced vomerine dentition, and an increased number of both mandibular and maxillary teeth, as well as significant differences in DNA sequence in COI and 16S.


Efficacy of percutaneous cement-augmented screw fixation plus percutaneous kyphoplasty in the management of unstable osteoporotic vertebral compression fractures.
The present study was performed to compare the efficacy of percutaneous kyphoplasty (PKP) vs. percutaneous cement-augmented screw fixation plus PKP in the management of unstable osteoporotic vertebral compression fractures (OVCF). A total of 197 patients with unstable OVCF treated in the Department of Spine Surgery, Lianyungang First People's Hospital from September 2019 to September 2021 were recruited and assigned via random number table method 1:1 to receive either PKP (group A, n=106) or PKP plus percutaneous cement-augmented screw fixation (group B, n=91). The outcome measures for the evaluation of different surgical methods included visual analogue scale (VAS), the height of the anterior-posterior border of the injured spine, Cobb angle of the posterior convexity, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores. PKP exhibited shorter operative time and length of hospital stay and less intraoperative blood loss vs. PKP plus percutaneous cement-augmented screw fixation (p<0.05). Patients with PKP plus percutaneous cement-augmented screw fixation experienced milder postoperative pain vs. those with PKP alone at 7 days postoperatively, as evidenced by the lower VAS scores (p<0.05). PKP plus percutaneous cement-augmented screw fixation provided more restoration of anterior margin height and posterior convexity Cobb angle vs. PKP alone (p<0.05). Patients with PKP only showed slightly higher Japanese Orthopaedic Association (JOA) scores than those with combined surgery, while the postoperative clinical signs between the two arms were similar (p>0.05). Single PKP features the benefits of minimal trauma, simple operation, and rapid postoperative recovery in the treatment of OVCF. PKP plus percutaneous cement-augmented screw fixation for severe OVCF provided distinctly better performance than PKP alone in terms of early pain relief, restoration of vertebral body height, correction of posterior convexity deformity, and firm spinal stability.


High-performance electrochemical glucose sensing enabled by Cu(TCNQ) nanorod array.
It is highly attractive to construct stable enzyme-free glucose sensors based on three-dimensional direct electrochemical detection of glucose. In this paper, a copper 7,7,8,8-tetracyanoquinodimethane (Cu(TCNQ)) nanorod array on Cu foam (Cu(TCNQ) NA/CF) is proposed as an efficient catalyst for electrochemical glucose oxidation in alkaline conditions. When Cu(TCNQ) NA/CF was used as the enzyme-free sensory of glucose, the sensor showed a response time within 3 s, a wide linear detection in the range 0.001-10.0 mM, the minimum limit of detection was as low as 10 nM (S/N = 3), and it had a high sensitivity of 26 987 μA mM-1 cm-2. Moreover, this sensor also possesses long-term stability, high selectivity, reproducibility, and actual applications for fresh human serum sample analysis is also successfully accepted.


An industry update: what is the latest news in therapeutic delivery?
This Industry Update covers the period from 1 through 30 April 2017, and is based on information sourced from company press releases, scientific literature, patents and various news websites. Biogen expanded its portfolio of developmental drugs targeting neurological diseases by licensing a drug from Bristol-Myers Squibb which is currently under investigation for the treatment of progressive supranuclear palsy. Takeda announced a deal with NuBiyota focused on developing treatments for gastrointestinal disorders, based on the manipulation of microbes living in the gut. Novartis announced an expansion of its neuroscience collaboration with Amgen as well as licensing of a developmental compound to treat dry eye. EmulateBio announced a collaboration with the US FDA to explore and evaluate its organs-on-chip technology in toxicological testing of food products, but which has wider opportunities in drug development. In the treatment of pulmonary hypertension, Vectura announced the commercial launch of its Fox nebulizer technology to deliver a Bayer drug and Respira announced a deal in which it exclusively licensed an inhaled drug-device product to United Therapeutics. Published research suggested that the benefit of pumps over multiple injections in the treatment of diabetes maybe more due to training than technology, and a group from the University of Pennsylvania showed that electrical stimulation of the brain can improve memory function but only when applied at the right time. Alzheon published work that explains the mechanism behind its developmental Alzheimer's drug.


Why Some "Futile" Care Is "Appropriate": The Implications for Conscientious Objection to Contraceptive Services.
In response to the criticism of Schneiderman and colleagues (2017) that two recent policy statements of professional medical organizations referred to some medical treatment that were traditionally called "futile" by the terms "inappropriate" or "potentially inappropriate," this critique accepts their claim challenging these terms as being hopelessly ambiguous. However, this critique rejects the conclusion they all share that clinicians or hospitals should have the unilateral authority to refuse to provide treatments that will plausibly achieve the end that the patient or surrogate is pursuing. Although clinicians should be presumed authoritative in deciding to reject treatments that will not achieve the patient or surrogate's end, they should be obligated, provided five conditions are met, to provide those treatments that will achieve the patient or surrogate's end. The implications of honoring a physician's right to conscientious objection to treatments they deem "futile" are compared to physician claims of the right to refuse to provide contraceptive services on the same grounds.


Monte Carlo Simulation for Polychromatic X-Ray Fluorescence Computed Tomography with Sheet-Beam Geometry.
X-ray fluorescence computed tomography (XFCT) based on sheet beam can save a huge amount of time to obtain a whole set of projections using synchrotron. However, it is clearly unpractical for most biomedical research laboratories. In this paper, polychromatic X-ray fluorescence computed tomography with sheet-beam geometry is tested by Monte Carlo simulation. First, two phantoms (A and B) filled with PMMA are used to simulate imaging process through GEANT 4. Phantom A contains several GNP-loaded regions with the same size (10 mm) in height and diameter but different Au weight concentration ranging from 0.3% to 1.8%. Phantom B contains twelve GNP-loaded regions with the same Au weight concentration (1.6%) but different diameter ranging from 1 mm to 9 mm. Second, discretized presentation of imaging model is established to reconstruct more accurate XFCT images. Third, XFCT images of phantoms A and B are reconstructed by filter back-projection (FBP) and maximum likelihood expectation maximization (MLEM) with and without correction, respectively. Contrast-to-noise ratio (CNR) is calculated to evaluate all the reconstructed images. Our results show that it is feasible for sheet-beam XFCT system based on polychromatic X-ray source and the discretized imaging model can be used to reconstruct more accurate images.


Nonsense mediated decay induced by tethered human UPF3B is restricted to the cytoplasm.
The subcellular localization of the nonsense mediated decay (NMD) of mRNA transcripts bearing premature termination codons has been controversial. Recently, it has been demonstrated that RNA tethering of key mediators of NMD, including human UPF3B, accurately recreates NMD. Here, we have used tethered UPF3B, combined with regulation of nuclear mRNA export using the retroviral Rev/RRE system, to examine where UPF3B-mediated mRNA degradation occurs. Our data clearly demonstrate that nuclear mRNA export is required for UPF3B-mediated degradation and moreover show that this degradation is exclusively cytoplasmic, despite the fact that the UPF3B fusion protein used is a nucleocytoplasmic shuttle protein localized predominantly to the nucleus. Moreover, exclusively cytoplasmic NMD occurred whether the target mRNA was exported via the retroviral Rev/RRE pathway or via the Tap: Nxt pathway used by most cellular mRNAs. These data may suggest that truly nuclear NMD, if it occurs, is at least in part mechanistically distinct from cytoplasmic NMD.


The efficacy of cinacalcet combined with conventional therapy on bone and mineral metabolism in dialysis patients with secondary hyperparathyroidism: a meta-analysis.
Cinacalcet, the first calcimimetic to be approved for the treatment of secondary hyperparathyroidism (SHPT) in the chronic kidney disease patients, offers a novel therapeutic approach to SHPT. The aim of this meta-analysis is to access the efficacy and safety of cinacalcet on bone and mineral metabolism disorders in the dialysis patients with SHPT. Randomized controlled trials on cinacalcet combined with vitamin D and/or phosphate binders in the dialysis patients with SHPT were identified in Pubmed, Sciencedirect, and the Cochrane library. Data were analyzed with RevMan software. We compared the proportion of patients achieving the biochemical targets recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines and the incidence of adverse events between the cinacalcet and control groups. Six trials involving 2,548 patients were included. A greater proportion of patients in the cinacalcet group compared with the conventional group achieved the KDOQI targets. The relative risks (RRs) were parathyroid hormone (PTH) (RR = 3.51, 95 % CI: 2.38-5.17), calcium (RR = 2.04, 95 % CI: 1.76-2.37), phosphorus (RR = 1.15, 95 % CI: 0.83-1.60), and calcium-phosphorus product (Ca × P) (RR = 1.41, 95 % CI: 1.18-1.69), the number of patients simultaneously achieving the KDOQI targets for PTH + Ca × P was also greater (RR = 3.89, 95 % CI: 2.36-6.41), with p < 0.001 for each. The most common adverse events were nausea, vomiting, diarrhea, and hypocalcemia, which had a higher incidence in the cinacalcet group, but were usually mild to moderate in severity and transient. Compared with conventional therapy, treatment with cinacalcet results in more patients achieving KDOQI targets and offers an effective and safety therapeutic option for controlling mineral and bone disorders in the dialysis patients with SHPT.


Engineering bacterial toxin for the development of new vaccine against pertussis.
Bordetella pertussis is the causative agent of whooping cough. The cellular pertussis vaccine introduced in the forties is highly effective and is widely used, but its reactogenicity has led to public concern regarding its safety. The attempts to reduce the side effects associated with pertussis immunization have led to the preparation of acellular B. pertussis products: one composed of detoxified pertussis toxin (PT) and filamentous haemagglutinin (FHA), another one composed only of detoxified PT and a third vaccine composed of detoxified PT, FHA and serotypes 1, 3 of fimbriae. In our laboratories we have approached the study of pertussis toxin, the molecule present in all the proposed acellular pertussis vaccines and one of the main virulence factors of B. Pertussis, with the aim of producing new acellular pertussis vaccines by using recombinant DNA techniques.


Fetal Dysmorphology-Still an Essential Art. Analysis of the Limitations of Microarray in a Fetal Population and a Look Toward the Genome Sequencing Era.
Cytogenomic microarray allows assessment of the genome at higher resolutions than traditional karyotyping. The objective of this study is to evaluate the utility of microarray in a routine fetal autopsy setting before the advent of routine fetal exome/genome sequencing and the issues these technologies may generate. A systematic review of fetal postmortems at 12-24 weeks gestation between January 2011 and December 2014 was undertaken. Cases where there was no consent for audit, research, or genetic testing were excluded as were cases referred to the Procurator Fiscal, stillbirths, and neonatal deaths. Copy number variations were detected in 16 cases. In addition, there was 1 case of uniparental disomy; not all of these were related to the phenotype. There were a number of cases with phenotypic abnormalities and normal array results. Five of these underwent directed mutation analysis-3 were positive. Genetic laboratory investigations such as microarray and Quantitative Fluorescent-Polymerase Chain Reaction may increase the diagnostic yield in the assessment of fetal dysmorphology. However, this study shows that genetic results not only require careful review given the potential uncertain significance but also require phenotypic assessment of the fetus by a competent fetal dysmorphologist to determine the likely causative effect of any detected anomaly. This best practice will also extend to next generation sequencing and interpretation of variants of unknown significance. Fetal medicine teams should ideally include specialists well versed in assessment of fetal anomaly to provide families with the best possible information about the cause of their pregnancy loss and their options for future pregnancies.


Integrated analysis miRNA and mRNA profiling in patients with severe oligozoospermia reveals miR-34c-3p downregulates PLCXD3 expression.
Our previous research suggested that an integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions and to uncover the molecular mechanisms of male infertility. In this study, microarrays were used to compare the differences in the miRNA and mRNA expression profiles in the testicular tissues of severe oligozoospermia (SO) patients with obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs (miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN, WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using quantitative real-time PCR. Using statistical calculations and bioinformatics predictions, we identified 33 differentially expressed miRNAs and 1,239 differentially expressed mRNAs, among which one potential miRNA-target gene pair, miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), was identified. Immunohistochemical analysis indicated that PLCXD3 was located within the germ cells of the mouse and human testis. Moreover, we found that miR-34c-3p was able to decrease PLCXD3 expression in mouse (GC-1 and TM4) and human (NCM460) cell lines, presumably indicating the possibility that miR-34c-3p acts as an intracellular mediator in germinal lineage differentiation. Notably, we reported the expression of the PLCXD3 protein in a man with normal spermatogenesis and the lack of the PLCXD3 protein in a man with SO. Therefore, the identified miRNA and mRNA may represent a potentially novel molecular regulatory network and therapeutic targets for the study or treatment of SO, which might provide a better understanding of the molecular basis of spermatogenesis dysfunction.


[The use of International Classification for Nursing Practice (ICNP) in pediatric and neonatal settings: literature review].
Literature reports that the use of Standardized Nursing Terminology contributes to a better implementation of nursing care and patients' safety and to do research. ICNP is an international and combinatorial standard terminology proposal by ICN, adaptable to different settings, among which paediatric and neonatal. A literature review on different databases (Medline/Pubmed, CINAHL, Embase, Web of Science and Scopus) was conducted to investigate the use of ICNP in professional practice in paediatric and neonatal settings. 44 papers were included in the review; 33 of which focused on the paediatric setting while 11 on the neonatal setting. It is evident ICNP is usable in both settings, permitting to describe nursing care to different age groups, in-hospital, out-of-hospital and in specific clinical situations. ICNP is up to the task of describing nursing care, implementing nursing care plans, analysing types of nursing care for management aims, studying concepts or specific pediatric or neonatal situations. ICNP is adaptable to different nursing frameworks and models. Few studies analyses ICNP implementation or effectiveness in clinical settings. Additional research is needed to verify ICNP effectiveness in paediatric and neonatal settings and to implement contextual catalogues.


Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.
(68)Ga (T 1/2 = 68 min, a generator-produced nuclide) has great potential as a radionuclide for clinical positron emission tomography (PET). Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68)Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Asp)n (n = 2, 5, 8, 11, or 14) with easy-to-handle (67)Ga, with the previously described (67)Ga-DOTA complex conjugated bisphosphonate, (67)Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Asp)n by a Fmoc-based solid-phase method, complexes were formed with (67)Ga, resulting in (67)Ga-DOTA-(Asp)n with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of (67)Ga-DOTA-(Asp)n increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, (67)Ga-DOTA-(Asp)8, (67)Ga-DOTA-(Asp)11, and (67)Ga-DOTA-(Asp)14 showed high accumulation in bone (10.5 ± 1.5, 15.1 ± 2.6, and 12.8 ± 1.7% ID/g, respectively) but were barely observed in other tissues at 60 min after injection. Although bone accumulation of (67)Ga-DOTA-(Asp)n was lower than that of (67)Ga-DOTA-Bn-SCN-HBP, blood clearance of (67)Ga-DOTA-(Asp)n was more rapid. Accordingly, the bone/blood ratios of (67)Ga-DOTA-(Asp)11 and (67)Ga-DOTA-(Asp)14 were comparable with those of (67)Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of (68)Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases.


DATA SYNTHESIS AND METHOD EVALUATION FOR BRAIN IMAGING GENETICS.
Brain imaging genetics is an emergent research field where the association between genetic variations such as single nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is evaluated. Sparse canonical correlation analysis (SCCA) is a bi-multivariate analysis method that has the potential to reveal complex multi-SNP-multi-QT associations. We present initial efforts on evaluating a few SCCA methods for brain imaging genetics. This includes a data synthesis method to create realistic imaging genetics data with known SNP-QT associations, application of three SCCA algorithms to the synthetic data, and comparative study of their performances. Our empirical results suggest, approximating covariance structure using an identity or diagonal matrix, an approach used in these SCCA algorithms, could limit the SCCA capability in identifying the underlying imaging genetics associations. An interesting future direction is to develop enhanced SCCA methods that effectively take into account the covariance structures in the imaging genetics data.


Joint dynamics and intra-subject variability during countermovement jumps in children and adults.
The present study investigated lower limb joint work, lower limb joint energy transport and intra-subject variation of the joint dynamics during countermovement jumps in children and adults. Twelve healthy men and eleven healthy boys performed ten maximal countermovement jumps. Three dimensional kinematics and kinetics were recorded in synchrony. Hip, knee and ankle joint eccentric and concentric work, joint energy transfer, intra-subject variation of joint moment, joint power and joint moment components were calculated. The children had lower eccentric and concentric hip work and lower eccentric knee work but no group difference was observed in the concentric knee joint work and ankle joint work. Eccentric hip and knee joint energy transfer and concentric hip joint energy transfer were higher in adults. The children had higher intra-subject variation in the eccentric and concentric hip joint work, hip joint moment and hip and knee joint power. Higher intra-subject variation was observed in horizontal joint reaction force components for the children and higher intra-subject variation in the segment angular inertia components was observed for the adults. The joint dynamics of children during countermovement jumps were less efficient in producing proximal joint work, transferring energy through joint centres and characterized by a higher intra-subject variation.


Is It Time to Begin a Public Campaign Concerning Frailty and Pre-frailty? A Review Article.
Frailty is a state that encompasses losses in physical, psychological or social domains. Therefore, frail people demonstrate a reduced potential to manage external stressors and to respond to life incidents. Consequently, such persons are prone to various adverse consequences such as falls, cognitive decline, infections, hospitalization, disability, institutionalization, and death. Pre-frailty is a condition predisposing and usually preceding the frailty state. Early detection of frailty (i.e., pre-frailty) may present an opportunity to introduce effective management to improve outcomes. Exercise training appears to be the basis of such management in addition to periodic monitoring of food intake and body weight. However, various nutritional supplements and other probable interventions, such as treatment with vitamin D or androgen, require further investigation. Notably, many societies are not conscious of frailty as a health problem. In fact, people generally do not realize that they can change this unfavorable trajectory to senility. As populations age, it is reasonable to begin treating frailty similarly to other population-affecting disorders (e.g., obesity, diabetes or cardiovascular diseases) and implement appropriate preventative measures. Social campaigns should inform societies about age-related frailty and pre-frailty and suggest appropriate lifestyles to avoid or delay these conditions. In this article, we review current information concerning therapeutic interventions in frailty and pre-frailty and discuss whether a greater public awareness of such conditions and some preventative and therapeutic measures may decrease their prevalence.