Roadmap on Digital Holography-Based Quantitative Phase Imaging.
Quantitative Phase Imaging (QPI) provides unique means for the imaging of biological or technical microstructures, merging beneficial features identified with microscopy, interferometry, holography, and numerical computations. This roadmap article reviews several digital holography-based QPI approaches developed by prominent research groups. It also briefly discusses the present and future perspectives of 2D and 3D QPI research based on digital holographic microscopy, holographic tomography, and their applications.


Laboratory control of heparin therapy.
The effect of heparin therapy was followed in 50 patients treated for thrombo-embolic disease. Individual response to a standard dose of 40,000 units of heparin daily showed a considerable variation and the effect was not constant on subsequent days. Five of the 50 patients developed a serious haemorrhage. It is proposed that to ensure the adequacy of treatment detectable levels of heparin should be obtained but because of the high risk of bleeding these levels should not be excessive. The results suggest that control of heparin therapy can be based on the thrombin clotting time. Using this test it is advised that treatment is monitored daily in order to achieve a plasma heparin level of up to 1 mg per 100 ml.


Inflammatory, lipid, and body composition responses to interval training or moderate aerobic training.
The goal of this study was to compare the effect of work- and duration-matched interval training (HIIT) versus moderate aerobic endurance training (ET) on acute and chronic inflammation, along with changes in the lipid profile, to determine which may be more beneficial for improving cardiovascular health. Twelve sedentary males (maximal oxygen consumption = 41.6 ± 5.4 mL kg(-1) min(-1)) completed 8 weeks of aerobic interval training or moderate aerobic training, with variables including C-reactive protein (CRP) for chronic inflammation, interleukin-6 (IL-6) response for the acute inflammatory response, plasma concentrations of high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TRG), and low-density lipoprotein, and body composition measured before and after the training period. HIIT decreased plasma TRG from 92 ± 32 to 61 ± 12 mg dL(-1), which was significantly different from ET, while ET improved the TC:HDL ratio from 4.67 ± 0.85 to 4.07 ± 0.96 and reduced the percentage of android fat from 36.78 ± 9.60 to 34.18 ± 11.39 %. Neither training protocol resulted in an acute IL-6 response on the first nor the last day of exercise, a change in chronic levels of CRP, or a significant increase in HDL, despite previous research finding these changes. It seems that in order to maximize the health outcomes from physical activity, both HIIT and ET should be included. The acute inflammatory response and reductions in chronic inflammation resulting from exercise training may not be as common as the literature suggests.


Application Value of Antimicrobial Peptides in Gastrointestinal Tumors.
Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate immune defense of many organisms, antimicrobial peptides not only have broad-spectrum antibacterial activity but also can specifically kill tumor cells. The positive charge of antimicrobial peptides under neutral conditions determines their high selectivity to tumor cells. In addition, antimicrobial peptides also have unique anticancer mechanisms, such as inducing apoptosis, autophagy, cell cycle arrest, membrane destruction, and inhibition of metastasis, which highlights the low drug resistance and high specificity of antimicrobial peptides. In this review, we summarize the related studies on antimicrobial peptides in the treatment of digestive tract tumors, mainly oral cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. This paper describes the therapeutic advantages of antimicrobial peptides due to their unique anticancer mechanisms. The length, net charge, and secondary structure of antimicrobial peptides can be modified by design or modification to further enhance their anticancer effects. In summary, as an emerging cancer treatment drug, antimicrobial peptides need to be further studied to realize their application in gastrointestinal cancer diseases.


Detection of multiple mycotoxin occurrences in soy animal feed by traditional mycological identification combined with molecular species identification.
Soy products are a main component of animal feed. Because mycotoxins may harm farm animals, undermining productivity and health, a mycological and toxigenic screening was carried out on 36 batches used in animal feed, collected in 2008, 2009 and 2010 in Italy. The investigated mycoflora of a subset of soy seed (n = 6) suggested that Aspergillus spp. and Fusarium spp. frequently colonize soy seeds. Aflatoxins, fumonisins and deoxynivalenol were detected in 88.9%, 72.2% and 30.6% of samples, respectively. Co-occurrence of at least two toxins was observed in 72% of cases. The molecular analysis of the Fusarium spp. population identified Fusarium verticillioides as potential producers of fumonisins, but no known deoxynivalenol producers were detected. It is suggested that the widespread presence of toxins can be due to non-optimal storing conditions of the feed. Moreover, our results suggest that mycotoxin thresholds should be adapted to consider the frequent case of toxin co-occurrence. This approach would better reflect the real toxigenic risk of feedstuffs.


NH2-terminal inactivation peptide binding to C-type-inactivated Kv channels.
In many voltage-gated K(+) channels, N-type inactivation significantly accelerates the onset of C-type inactivation, but effects on recovery from inactivation are small or absent. We have exploited the Na(+) permeability of C-type-inactivated K(+) channels to characterize a strong interaction between the inactivation peptide of Kv1.4 and the C-type-inactivated state of Kv1.4 and Kv1.5. The presence of the Kv1.4 inactivation peptide results in a slower decay of the Na(+) tail currents normally observed through C-type-inactivated channels, an effective blockade of the peak Na(+) tail current, and also a delay of the peak tail current. These effects are mimicked by addition of quaternary ammonium ions to the pipette-filling solution. These observations support a common mechanism of action of the inactivation peptide and intracellular quaternary ammonium ions, and also demonstrate that the Kv channel inner vestibule is cytosolically exposed before and after the onset of C-type inactivation. We have also examined the process of N-type inactivation under conditions where C-type inactivation is removed, to compare the interaction of the inactivation peptide with open and C-type-inactivated channels. In C-type-deficient forms of Kv1.4 or Kv1.5 channels, the Kv1.4 inactivation ball behaves like an open channel blocker, and the resultant slowing of deactivation tail currents is considerably weaker than observed in C-type-inactivated channels. We present a kinetic model that duplicates the effects of the inactivation peptide on the slow Na(+) tail of C-type-inactivated channels. Stable binding between the inactivation peptide and the C-type-inactivated state results in slower current decay, and a reduction of the Na(+) tail current magnitude, due to slower transition of channels through the Na(+)-permeable states traversed during recovery from inactivation.


Quantitation of monosaccharide isotopic enrichment in physiologic fluids by electron ionization or negative chemical ionization GC/MS using di-O-isopropylidene derivatives.
The aldonitrile pentaacetate and other derivatives lack ions in the electron ionization (EI) spectra possessing an intact hexose structure and thus must be analyzed by chemical ionization GC/MS in order to study multiple isotopomers. We report methods for quantitation of hexose di-O-isopropylidene acetate (IPAc) or pentafluorobenzoyl (PFBz) esters. These were prepared in a two-step procedure using inexpensive reagents that do not adversely impact the isotopomer structure of the sugar. The acetate derivative possesses an abundant [M - CH3] ion in the EI spectrum which is suitable for quantitative analysis of isotopomers. The negative chemical ionization (NCI) spectrum of the corresponding pentafluorobenzoyl derivative has a dominant molecular anion. Moreover, the PFBz derivative is about 100-fold more sensitive than the acetate, which offers some advantages for analysis of minor hexoses found in plasma. Isotopic calibration curves of [U-13C]glucose are linear over the 0.1-60% tracer/tracee range tested. The useful range for isotopic tracer studies is 25-2500 pmol for EI analysis of the acetate derivative and 0.1-55 pmol for NCI analysis of PFBz derivative (sample amount injected). For most studies where sample size is not limited, EI-GC/MS analysis of the IPAc derivative is preferred. NCI-GC/MS analysis is reserved when sample size is limiting or when studies involve hexoses other than glucose that are normally present at low concentration.


Congenital Cataract and Its Genetics: The Era of Next-Generation Sequencing
Congenital cataract is a challenging ophthalmological disorder which can cause severe visual loss. It can be diagnosed at birth or during the first year of life. Early diagnosis and treatment are crucial for the visual prognosis. It can be associated with various ocular and systemic abnormalities. Determining whether congenital cataract is isolated or associated with other pathology is an indispensable step for the prediction of potential vision as well as early diagnosis and treatment of conditions that can cause morbidity or mortality. Many genes have been identified in the molecular etiology of congenital cataract. Most mutations have been reported in the crystallin genes. Determination of the genetic cause may not only enable individualized genetic counseling but also help to identify concomitant ocular and/or systemic disorders depending on the characteristics of the genetic test used. Recently, next-generation sequencing in particular has become an evolving technology for determining the molecular etiology of congenital cataract and furthering our knowledge of the disease.


Heterogeneity of anti-PR3 associated disease in Hong Kong.
Thirty seven patients tested positive for antibody against proteinase 3 (anti-PR3) using either one of the two in-house ELISA methods at the Immunology Laboratory, University of Hong Kong. All except three were Chinese. Systemic vasculitis was diagnosed in 13 patients. However, the positive predictive value of anti-PR3 for Wegener's granulomatosus was low (22%). The commonest presenting feature was respiratory (32%). Both respiratory and renal symptoms were commonly reported in anti-PR3 positive patients as in previous studies. In this largely Chinese population, there is marked variability in the spectrum of diseases associated with anti-PR3; though many had vasculitic diseases, some were diagnosed with other conditions such as inflammatory bowel diseases and respiratory infection. In contrast with series in white people, antimyeloperoxidase rather than anti-PR3 associated disease is more prevalent in Chinese patients.


[Initial disorders and premorbid personality characteristics in delusional psychoses].
In compliance with a special list of standartized signs, the nozological and typical differences in initial and premorbid personality traits were studied. These symptoms were correlated in 407 patients with delusional psychoses in the framework of schizophrenia, symptomatic disorders and epilepsy. The signs were assessed in accordance to the degree of their probability. The report contains a description of the most probable traits having a prognostical and differential diagnostical significance.


Extensive remodeling of the photosynthetic apparatus alters energy transfer among photosynthetic complexes when cyanobacteria acclimate to far-red light.
Some cyanobacteria remodel their photosynthetic apparatus by a process known as Far-Red Light Photoacclimation (FaRLiP). Specific subunits of the phycobilisome (PBS), photosystem I (PSI), and photosystem II (PSII) complexes produced in visible light are replaced by paralogous subunits encoded within a conserved FaRLiP gene cluster when cells are grown in far-red light (FRL; λ = 700-800 nm). FRL-PSII complexes from the FaRLiP cyanobacterium, Synechococcus sp. PCC 7335, were purified and shown to contain Chl a, Chl d, Chl f, and pheophytin a, while FRL-PSI complexes contained only Chl a and Chl f. The spectroscopic properties of purified photosynthetic complexes from Synechococcus sp. PCC 7335 were determined individually, and energy transfer kinetics among PBS, PSII, and PSI were analyzed by time-resolved fluorescence (TRF) spectroscopy. Direct energy transfer from PSII to PSI was observed in cells (and thylakoids) grown in red light (RL), and possible routes of energy transfer in both RL- and FRL-grown cells were inferred. Three structural arrangements for RL-PSI were observed by atomic force microscopy of thylakoid membranes, but only arrays of trimeric FRL-PSI were observed in thylakoids from FRL-grown cells. Cells grown in FRL synthesized the FRL-specific complexes but also continued to synthesize some PBS and PSII complexes identical to those produced in RL. Although the light-harvesting efficiency of photosynthetic complexes produced in FRL might be lower in white light than the complexes produced in cells acclimated to white light, the FRL-complexes provide cells with the flexibility to utilize both visible and FRL to support oxygenic photosynthesis. This article is part of a Special Issue entitled Light harvesting, edited by Dr. Roberta Croce.


Human single chain antibody to vascular endothelial growth factor: gene cloning, high-level expression, affinity maturation and bioactivity.
Using antibody phage display technique, a human single chain antibody to vascular endothelial growth factor (VEGF) has been cloned. The antibody expression reached 45% of the total bacterial proteins. The purification and refolding of the antibody were completed in one step by using gel filtration chromatograph. ELISA analysis showed that the antibody not only specifically bound to human VEGF, but also competitively inhibited VEGF reacting with its receptors. In order to raise the affinity of the single chain antibody, its heavy chain variable region was randomly mutated using error-prone PCR and an antibody mutant library was constructed, from which a mutant with higher affinity was screened out. The three-dimensional structure and binding affinity of wild type and mutant antibody were compared. Our study provided a potential reagent for tumor angiogenic therapy and a significant model for antibody high-level expression and affinity maturation.


Unveiling the chemistry of 1,3,4-oxadiazoles and thiadiazols: A comprehensive review.
Oxadiazoles and thiadiazoles are malleable heterocycles that have recently generated major interest in the field of medicinal chemistry. Compounds based on these moieties have versatile biological applications such as anticonvulsant, anticancer, antidiabetic, and antioxidant agents. Due to the versatile nature and stability of the oxadiazole and thiadiazole nucleus, medicinal chemists have changed the structural elements of the ring in numerous ways. These compounds have shown significant anticonvulsant effects, demonstrating their potential in the management of epileptic disorders. In this review, we have covered numerous biological pathways and in silico targeted proteins of oxadiazole and thiadiazole derivatives for treating various biological disorders. The data compiled in this article will be helpful for researchers, research scientists, and research chemists who work in the field of drug discovery and drug development.


Speech-language therapy educator reflections on the planning and implementation of education and training during the COVID-19 pandemic.
Universities across the world experienced lockdown and closure of all learning institutions around March 2020 because of the advent of the coronavirus disease 2019 (COVID-19). This lockdown and closure presented challenges to the traditional pedagogical approaches in the health sciences, which typically include both campus-based and clinical site-focused activities involving face-to-face interactions and work integrated learning. The onset of the COVID-19 pandemic resulted in a shift to emergency remote teaching (ERT) and learning. This study aimed to explore speech-language pathology (SLP) educators' experiences of the planning and implementation of ERT and learning during the COVID-19 pandemic. A qualitative, descriptive narrative design was adopted to meet the objectives of the study. Seven SLP educators from a single university in South Africa participated in this study by constructing narratives on their experiences. The narratives were analysed using thematic analysis. Five themes emerged from the data analysis, and these included (1) uncertainty, (2) educator feelings, (3) capacity development, (4) influence of circumstances on teaching, learning and assessment and (5) troubleshooting. Current findings provide insight into the challenges encountered and strategies utilised by educators in planning and implementing ERT and learning. Beyond the COVID-19 pandemic, most educators believe that a hybrid model would address some concerns identified, such as that of missing face-to-face contact, but that it would still allow for the full exploitation of online activities for teaching, learning and assessment required during clinical training.


Origami tubes with reconfigurable polygonal cross-sections.
Thin sheets can be assembled into origami tubes to create a variety of deployable, reconfigurable and mechanistically unique three-dimensional structures. We introduce and explore origami tubes with polygonal, translational symmetric cross-sections that can reconfigure into numerous geometries. The tubular structures satisfy the mathematical definitions for flat and rigid foldability, meaning that they can fully unfold from a flattened state with deformations occurring only at the fold lines. The tubes do not need to be straight and can be constructed to follow a non-linear curved line when deployed. The cross-section and kinematics of the tubular structures can be reprogrammed by changing the direction of folding at some folds. We discuss the variety of tubular structures that can be conceived and we show limitations that govern the geometric design. We quantify the global stiffness of the origami tubes through eigenvalue and structural analyses and highlight the mechanical characteristics of these systems. The two-scale nature of this work indicates that, from a local viewpoint, the cross-sections of the polygonal tubes are reconfigurable while, from a global viewpoint, deployable tubes of desired shapes are achieved. This class of tubes has potential applications ranging from pipes and micro-robotics to deployable architecture in buildings.


Comparative bioavailability study of two atenolol tablet preparations.
A study was conducted to compare the bioavailability of a generic product of atenolol (Normaten FC) with the innovator product, Tenormin. Twelve healthy adult volunteers participated in the study conducted according to a randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was obtained between the Tmax values and the logarithmic transformed AUC0-infinity and Cmax values of the two products. Moreover, the 90% confidence interval for the ratio of the logarithmically transformed AUC0-infinity values of Normaten FC over those of Tenormin was found to lie between 0.82 and 0.98, while that of the logarithmically transformed Cmax values was between 0.82 and 1.09, both being within the bioequivalence limit of 0.80-1.25. The values of elimination half-life t1/2 between the two products were also found comparable and not significantly different statistically. The t1/2 values obtained in our study were slightly longer than those reported in the literature for other population groups.


Influence of salivary secretory immunoglobulin A level on the pain experienced by orthodontic patients.
Pain, a common experience reported by patients under orthodontic treatment, results from force application to the teeth and trauma caused by attrition of brackets and wires against the underlying oral mucosa. The main protection of the mucosa is secretory immunoglobulin A (sIgA), which may play a fundamental role in integrity maintenance and whose production may be reduced as a result of the stress of orthodontic treatment. The aim of this study was to assess sIgA levels in the saliva and their correlation with oral pain intensity in adults and children after the installation of fixed orthodontic appliances. Twenty patients (10 children, age 11-13 years; 10 adults, age 18-37 years) were assessed before treatment, after bracket bonding, and after initial arch wire insertion. Saliva was sampled for sIgA analysis, and oral pain was assessed through a visual analog scale. Although there was a trend toward reduction of the salivary sIgA levels during the initial arch phase in the children, and during the bonding and initial arch phases in the adults, this finding was not significant. There was a trend toward a negative correlation of oral pain intensity and salivary sIgA levels in the children, which may indicate the importance of sIgA for oral protection during orthodontic treatment, interfering with the pain experienced by the patients.


Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths.
Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology. Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests. Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either. Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.


Isolated Thoracoschisis: Case Report and Review of Literature.
A full-term male baby presented at day 2 postnatal with Riedel liver lobe, stomach, and much of the bowel herniating through a thoracic wall defect located just above and lateral to the left nipple. Operative conversion into a gastroschisis-like defect with construction of a silo bag was done. On thorough review of literature, it was found that this is only the second male infant reported with isolated thoracoschisis.


Public health restrictions, directives, and measures in Arctic countries in the first year of the COVID-19 pandemic.
Beginning January of 2020, COVID-19 cases detected in Arctic countries triggered government policy responses to stop transmission and limit caseloads beneath levels that would overwhelm existing healthcare systems. This review details the various restrictions, health mandates, and transmission mitigation strategies imposed by governments in eight Arctic countries (the United States, Canada, Greenland, Norway, Finland, Sweden, Iceland, and Russia) during the first year of the COVID-19 pandemic, through 31 January 2021s31 January 2021. We highlight formal protocols and informal initiatives adopted by local communities in each country, beyond what was mandated by regional or national governments. This review documents travel restrictions, communications, testing strategies, and use of health technology to track and monitor COVID-19 cases. We provide geographical and sociocultural background and draw on local media and communications to contextualise the impact of COVID-19 emergence and prevention measures in Indigenous communities in the Arctic. Countries saw varied case rates associated with local protocols, governance, and population. Still, almost all regions maintained low COVID-19 case rates until November of 2020. This review was produced as part of an international collaboration to identify community-driven, evidence-based promising practices and recommendations to inform pan-Arctic collaboration and decision making in public health during global emergencies.


Concentrations of cefpirome in cerebrospinal fluid of children with bacterial meningitis after a single intravenous dose.
A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) microg/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.


Passive Air Samplers As a Tool for Assessing Long-Term Trends in Atmospheric Concentrations of Semivolatile Organic Compounds.
Many attempts have been made to quantify the relationship between the amount of persistent organic pollutants sequestered by passive air sampling devices and their actual concentrations in ambient air. However, this information may not be necessary for some applications. In this study, two sets of 30 ten-year-long time series of simultaneous passive and high-volume active air sampling carried out at the Košetice observatory in the Czech Republic were used for a comparison of temporal trends. Fifteen polyaromatic hydrocarbons, seven polychlorinated biphenyls and eight organochlorine pesticides were investigated. In most cases, a good agreement was observed between the trends derived from passive and active monitoring with the exception of several compounds obviously affected by sampling artifacts. Two sampling artifacts were observed: breakthrough of high-volume sampler filters for penta- and hexachlorobenzene and semiquantitative values for PAHs with a high molecular weight. It has been suggested before that annually aggregated results of passive air monitoring may be used directly for the assessment of the long-term behavior of these compounds. The extensive set of long-term data used in this study allowed us to confirm this finding and to demonstrate that it is also possible to derive temporal trends and the compounds' half-lives in air from the passive-sampling time series.


Cross-link formation at the head-tail junction of mammalian spermatozoa during aging is dependent on sperm motility.
A high percentage of the heads of mouse, hamster, and rabbit spermatozoa were detached from their tails by vortexing a suspension of spermatozoa that had been incubated with dithiothreitol (DTT), a sulfhydryl reagent. Similar treatment of spermatozoa that had been aged under physiologic conditions for several hours and were still motile before reaction with DDT gave a much lower percentage of head detachment. This stabilization of the sperm head-tail junction developed only if spermatozoa were motile during aging. n-Butylamine also induced head detachment of mouse spermatozoa. Motile and immotile mouse spermatozoa became resistant to n-butylamine when aged in physiologic medium and buffer, respectively. However, stabilization developed much faster if spermatozoa were motile. Stabilization of the head-tail junction of motile spermatozoa to the reagents occurred over the time periods required for capacitation and the development of hyperactivated motility. Development of resistance to the two reagents may be biochemical events associated with capacitation.


Enhancing Antitumor Efficacy of Nucleoside Analog 5-Fluorodeoxyuridine on HER2-Overexpressing Breast Cancer by Affibody-Engineered DNA Nanoparticle.
Chemotherapy, as an adjuvant treatment strategy for HER2-positive breast cancer, can effectively improve clinical symptoms and overcome the drug resistance of therapeutic monoclonal antibodies. Nucleoside analogues are a class of traditional chemotherapeutic drugs that are widely applied in adjuvant therapy. However, there are many critical issues that limit their clinical efficiency, including poor selectivity and stability, severe side effects and suboptimal therapeutic efficacy. Hence, this work aims to develop a new DNA nanocarrier for targeted drug delivery to solve the above problems. Four 41-mer DNA strands were synthesized and 10 FUdR molecules were attached to 5' end of each DNA strand by DNA solid-phase synthesis. An affibody molecule was connected to the end of polymeric FUdR through a linker in one of the four strands. The affibody-FUdR-tetrahedral DNA nanostructures (affi-F/TDNs) were self-assembled through four DNA strands, in which one vertex was connected to an affibody at the end of a polymeric FUdR tail and three vertices were only polymeric FUdR tails. In vitro cellular uptake of affi-F/TDNs was examined visually with confocal fluorescence microscopy and flow cytometry, and the cytotoxicity of affi-F/TDNs against cancer cells was investigated with MTT assay. Cell apoptosis was detected by Annexin V-FITC/PI double staining method. Using NOD/SCID (Mus Musculus) mice model, the targeted killing efficacy of affi-F/TDNs was also evaluated. The drug-loading of FUdR in affi-TDNs was 19.6% in mole ratio. The in vitro results showed that affi-F/TDNs had high selectivity and inhibition (81.2%) for breast cancer BT474 cells overexpressing HER2 and low toxicity in MCF-7 cells with low HER2 expression. During the in vivo application, affi-F/TDNs displayed good stability in the blood circulation, achieved specific accumulation in tumor region and the best antitumor efficacy (inhibition ratio of 58.1%), and showed excellent biocompatibility. The affibody-DNA tetrahedrons, as a simple and effective active targeting delivery nanocarrier, provided a new avenue for the transport of nucleoside antitumor drugs.


Acute Kidney Injury and Fluid Resuscitation in Septic Patients: Are We Protecting the Kidney?
Acute kidney injury (AKI) is a common complication in critically ill patients, especially among septic patients. Sepsis and hypovolemia are the 2 most frequent etiologies of AKI in intensive care units and frequently coexist in critically ill patients. Effective fluid resuscitation is crucial for the stabilization of sepsis-induced tissue hypoperfusion or septic shock. However, the lack of a goal-directed therapy targeting kidney oxygenation prevents from optimization of the fluid therapy with regard to improvement of renal oxygen delivery and extraction. Similarly, fluid administration as all therapeutic actions carries adverse effects such as the activation of cytokines, disruption of the capillary glycocalyx, and adverse effects on kidney metabolism and oxygenation. Moreover, a positive fluid balance is associated with an increased risk of AKI and is a negative predictor for recovery of renal function. The role of fluid resuscitation on kidney injury stems from the high renal vulnerability to hypoxemic injury. Indeed, fluids have a poor oxygen solubility and hemodilution decreases blood viscosity both promoting intrarenal shunting and heterogeneity with a decreased capillary density and enhanced intrarenal cortex and medullary hypoxia. The development of physiological biomarkers that are able to detect the early development of AKI specifically aimed at the identification of renal microcirculatory dysfunctions should form a valuable contribution to monitoring therapeutic modalities.


Middle fossa approach to a temporosphenoidal encephalocele -technical note-.
Temporosphenoidal encephalocele (TSE) is a rare entity caused by herniation of the anteromedial temporal lobe into the sphenoid sinus (SS) through a middle fossa (MF) defect. A 45-year-old woman presented with a spontaneous TSE manifesting as a 4-year history of recurrent cerebrospinal fluid rhinorrhea and meningitis. Coronal computed tomography showed a skull defect in the superior wall of the right lateral recess of the SS. This homogeneous intrasphenoidal lesion appeared hypointense on T(1)-weighted magnetic resonance (MR) imaging and hyperintense on T(2)-weighted MR imaging. The patient underwent a frontotemporal craniotomy and extradural MF exploration. The encephalocele was amputated and the temporal base dura primarily sutured and reinforced with fat graft. The MF hole was plugged with temporalis fascia and a calvarial graft layered over the bone defect. Histological examination confirmed meningoencephalocele. Rhinorrhea resolved and the patient remained asymptomatic. Resection of an anteromedial TSE and closure of the craniodural defect in the MF floor via a less invasive extradural skull base approach is effective.


Combined fracture and mortality risk evaluation for stratifying treatment in hip fracture patients: A feasibility study.
This study aims to test the feasibility of the Fracture and Mortality Risk Evaluation (FAME) Index. Two academic centers in Lithuania and Turkey participated in this retrospective study conducted between November 2018 and July 2019. A total of 100 consecutive patients (22 males, 78 females; mean age 78.9 years; range, 45 to 100 years) with low energy proximal femur fractures admitted for surgery were included in the study. Fracture Risk Assessment tool (FRAX) and the Sernbo scores were calculated and patients were classified into one of the nine subcategories of the FAME Index. Demographics and FAME Index classifications were similar between centers. Patients with high risk of fracture and low risk of mortality accounted for 18% of all patients, which is the FAME Index subcategory to theoretically benefit from cancellous bone augmentation during internal fixation of a fragility hip fracture the most. The FAME Index was successfully applied in clinical emergency setting utilizing a simple form, and demonstrated promising potential in stratification of hip fractures most suitable for screw and device augmentation. Larger studies with at least one-year of follow-up are warranted to verify the validity of FAME Index.


Implication of conjugated linoleic acid (CLA) in human health.
Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its variety of biologically beneficial effects. CLA reduces body fat, cardiovascular diseases and cancer, and modulates immune and inflammatory responses as well as improves bone mass. It has been suggested that the overall effects of CLA are the results of interactions between two major isomers, cis-9,trans-11 and trans-10,cis-12. This review will primarily focus on current CLA publications involving humans, which are also summarized in the tables. Along with a number of beneficial effects of CLA, there are safety considerations for CLA supplementation in humans, which include effects on liver functions, milk fat depression, glucose metabolism, and oxidative stresses.


Phenylalanine-24 in the N-terminal region of ammodytoxins is important for both enzymic activity and presynaptic toxicity.
Ammodytoxins (Atxs) are group II phospholipases A(2) (PLA(2)s) with presynaptic toxicity from venom of the snake Vipera ammodytes ammodytes. The molecular basis of their neurotoxicity, and that of similar PLA(2) toxins, is still to be explained. To address this problem, a surface-exposed aromatic residue, Phe(24), in the N-terminal region of the most potent Atx, AtxA, was replaced by other aromatic (tyrosine, tryptophan), hydrophobic (alanine) and polar uncharged (serine, asparagine) residues. The mutants were produced in the bacterial expression system, refolded in vitro and purified to homogeneity. All but the Trp(24) mutant, whose activity was similar to that of the wild type, showed a considerable decrease (40-80%) in enzymic activity on a micellar phosphatidylcholine substrate. This result indicates an important role for the aromatic side chains of phenylalanine or tryptophan, but not tyrosine, in PLA(2) activity, very likely at a stage of interfacial adsorption of the enzyme to zwitterionic aggregated substrates. The substitutions of Phe(24) also significantly decreased toxicity in mice, with the most prominent decrease, of 130-fold, observed in the case of the Asn(24) mutant. The results with the mutants show that there is no correlation between enzymic activity, lethality and binding affinity for three AtxA neuronal receptors (R180, R25 and calmodulin). Our results suggest a critical involvement of Phe(24) in the neurotoxicity of AtxA, apparently at a stage which does not involve the interaction with the known Atx-binding neuronal proteins and catalytic activity.


Herbal pre-conditioning induces proliferation and delays senescence in Wharton's Jelly Mesenchymal Stem Cells.
Mesenchymal Stem Cells (MSCs) are multipotent stem cells which are being explored for various clinical applications. Isolation and in-vitro expansion of MSCs remain important in achieving desired cell number for the therapy. However, in-vitro proliferation of MSCs is often associated with senescence and early onset of apoptosis which limits its therapeutic ability and long term clinical use. Tinospora cordifolia and Withania somnifera are used widely in Ayurveda: the traditional Indian system of medicine and are reported to have rejuvenating and anti-aging potential. In the present study, we investigated the effect of Tinospora cordifolia and Withania somnifera on proliferation and senescence of wharton's jelly MSCs (WJMSCs) in-vitro. WJMSCs were treated in culture medium with Tinospora cordifolia leaf and Withania somnifera root extracts to examine their effect on proliferation and senescence properties of WJMSCs. Proliferation of WJMSCs was assayed by cell count, MTT, BrdU incorporation assay, cell cycle analysis and Ki67 mRNA expression. Senescence was demonstrated using β-galactosidase senescence assay and associated mRNA markers. Culture medium supplemented with Tinospora cordifolia leaf and Withania somnifera root extracts exhibited significant increase in proliferation of WJMSCs as evidenced by cell count and MTT assay. Cell cycle analysis using propidium iodide showed increase in G2/M phase and decrease in apoptotic cells. BrdU incorporation and upregulation of proliferation marker ki67 by RT PCR showed increased DNA synthesis/proliferation in Tinospora cordifolia and Withania somnifera extract treated MSCs. Delayed senescence was confirmed by β-galactosidase senescence assay and down regulation of senescence marker p21. Our results demonstrate for the first time that Tinospora cordifolia and Withania somnifera extracts support proliferation and inhibit senescence in WJMSCs making them suitable candidates as supplements for in-vitro expansion without affecting the cell viability indicating its non-toxic nature.


A Mixed-Methods Study of Veterans Affairs Providers' Experiences Communicating With Patients About the Affordable Care Act.
The provisions under the Affordable Care Act (ACA) can potentially increase insurance options for Veterans. Veterans must be informed about their options, and potential benefits and challenges associated with use of multiple health care systems. This study aimed to assess VA providers' perceptions of how they contributed to Veterans' health care decision-making within the health care context established by the ACA. A mixed-methods approach including an online survey and semi-structured interviews was used to assess the experiences of health care providers (e.g., physicians, nurses, and social workers) communicating with Veterans about the ACA. Closed-ended survey questions were analyzed using descriptive statistics. Qualitative analysis of open-ended responses to the survey and semi-structured interview entailed thematic analysis, which involved identifying themes and patterns within and across participants until reaching saturation. A total of 251 providers completed the survey (20% response rate), and 26 providers completed a semi-structured interview (23% participation rate). Most providers (75.3%) reported being only "a little" or "somewhat" knowledgeable about the overall provisions of the ACA, and 90.8% of providers reported needing more information about the ACA. Key themes that emerged from the qualitative analyses included a variety of issues related to the ACA. According to providers, Veterans raised concerns about: signing up for the ACA, retaining VA benefits, knowledge about VA benefits and the ACA, understanding implications of insurance coverage through the ACA, and affordability of the ACA. Providers expressed the need for provider and patient educational resources. Our findings suggest that Veterans and their providers encounter challenges comprehending recent policy changes and navigating ongoing dual health care use. According to providers, Veterans' knowledge about the ACA can affect their ability to make informed health care decisions. Equipping patients and providers with more information about the ACA, and promoting communication between patients and providers may foster shared decision-making processes with regard to health care and treatment options. Strategies to improve knowledge transfer and patient-provider communication about policy changes warrant further investigation.


Dependence of Chs2 ER export on dephosphorylation by cytoplasmic Cdc14 ensures that septum formation follows mitosis.
Cytokinesis, which leads to the physical separation of two dividing cells, is normally restrained until after nuclear division. In Saccharomyces cerevisiae, chitin synthase 2 (Chs2), which lays down the primary septum at the mother-daughter neck, also ensures proper actomyosin ring constriction during cytokinesis. During the metaphase-to-anaphase transition, phosphorylation of Chs2 by the mitotic cyclin-dependent kinase (Cdk1) retains Chs2 at the endoplasmic reticulum (ER), thereby preventing its translocation to the neck. Upon Cdk1 inactivation at the end of mitosis, Chs2 is exported from the ER and targeted to the neck. The mechanism for triggering Chs2 ER export thus far is unknown. We show here that Chs2 ER export requires the direct reversal of the inhibitory Cdk1 phosphorylation sites by Cdc14 phosphatase, the ultimate effector of the mitotic exit network (MEN). We further show that only Cdc14 liberated by the MEN after completion of chromosome segregation, and not Cdc14 released in early anaphase by the Cdc fourteen early anaphase release pathway, triggers Chs2 ER exit. Presumably, the reduced Cdk1 activity in late mitosis further favors dephosphorylation of Chs2 by Cdc14. Thus, by requiring declining Cdk1 activity and Cdc14 nuclear release for Chs2 ER export, cells ensure that septum formation is contingent upon chromosome separation and exit from mitosis.


Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus.
Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the accumulation of inflammatory factors in the lesions in venous thrombus. Matrix metalloproteinase (MMP) expression and activity were downregulated in rivaroxaban-treated rats with deep venous thrombus. Rivaroxaban inhibited the elasticity of the extracellular matrix and collagen-elastin fibers. On the whole, these results indicate that rivaroxaban attenuates deep venous thrombus through MMP-9-mediated NF-κB signaling pathway.


Review of Current Evidence for Minimally Invasive Posterior Sacroiliac Joint Fusion.
The sacroiliac joint (SIJ) is a large, irregularly shaped, serpentine joint structure bordered anteriorly and posteriorly by the sacroiliac ligaments. With increased recognition of the SIJ as a pain source, treatments have been historically nonsurgical in nature. Common treatments include bracing, medications, activity modification, manual therapy, chiropractic manipulation, physical therapy, and intra-articular SIJ injections. Surgical stabilization and/or fusion of the SIJ may be considered when a patient has persistent moderate to severe pain, functional impairment, and failed conservative management. Surgical stabilization and fusion has traditionally been by way of the transiliac approach. More recent SIJ fusion systems have proposed not only a posterior approach but one that stabilizes the joint space by placing an allograft within the SIJ. Anatomically, a posterior approach is able to avoid neurovascular structures that otherwise are encountered with the transiliac approach and may be performed percutaneously. Preliminary evidence reports consistent pain reduction with minimal complications. This paper is purposed to detail the present evidence of minimally invasive posterior SIJ fusion, as well as highlight the need for further research moving forward.


Association of 24-Hour Intraocular Pressure Fluctuation With Corneal Hysteresis and Axial Length in Untreated Chinese Primary Open-Angle Glaucoma Patients.
The purpose of this study was to evaluate the association of 24-hour intraocular pressure (IOP) fluctuation with corneal biomechanics and ocular biometric parameters in Chinese patients with primary open angle glaucoma (POAG) before initial treatment. Forty-nine Chinese patients with POAG (98 eyes) were recruited in this study before start of any POAG treatment. The 24-hour IOP was measured with a 2-hour interval by a noncontact tonometer. Corneal biomechanical properties and biometric parameters were measured once during 8 AM to 6 PM before 24-hour IOP measurement. The 24-hour IOP fluctuation was defined as the differences between the peak and trough IOP measurement and was significantly associated with axial length (AL) in the multivariate analysis. The POAG subjects with AL ≤ 26 mm had significantly larger 24-hour IOP fluctuation but lower corneal hysteresis, compared to those with AL > 26 mm. In addition, subgroup analysis showed that high tension glaucoma subjects had larger 24-hour IOP fluctuation and higher corneal resistance factor than patients with normal tension glaucoma. This study revealed the association of 24-hour IOP fluctuation with office hour corneal biomechanical properties and AL in patients with POAG. Their contributions to IOP fluctuation should be considered in the risk analysis of glaucoma development and progression. Ocular biometric parameters are related with 24-hour IOP fluctuation in patients with POAG, which is potentially helpful in explaining different progression patterns in different types of patients.


Toxic response of the freshwater green algae Chlorella pyrenoidosa to combined effect of flotation reagent butyl xanthate and nickel.
Butyl Xanthate (BX) is a typical flotation reagent used to extract non-ferrous nickel ores, discharged into the surrounding environment of mining areas in large quantities. However, few studies have focused on the toxicity of combined pollution of BX and nickel (Ni) on aquatic plants, especially phytoplankton, the main producer of aquatic ecosystems. The toxicity and potential mechanism of single and combined pollution of BX and Ni at different concentrations (0-20 mg L-1) on typical freshwater algae (Chlorella pyrenoidosa) were studied. BX slightly stimulated the growth of C. pyrenoidosa on the first day, but Ni and Ni/BX mixture significantly inhibited it during incubation. Results showed that the inhibition rate (I) of the pollutants on the growth of C. pyrenoidosa followed the order: Ni/BX mixture > Ni > BX. The 96-h 20% effective inhibitory concentrations (96h-EC20) of Ni and BX on C. pyrenoidosa growth were 3.86 mg L-1 and 19.25 mg L-1, respectively, indicating C. pyrenoidosa was sensitive to pollutants. The content of total soluble protein (TSP) and chlorophyll a (Chl-a) changed significantly, which may be caused by the damage of pollutants to cell structures (cell membranes and chloroplasts). In addition, the I of pollutants on C. pyrenoidosa growth was related to dose, superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA). The increasement of reactive oxygen species (ROS), antioxidant enzymes (SOD and CAT), and MDA content, suggested C. pyrenoidosa suffered from oxidative stress, leading to lipid oxidation. These results will help to understand the toxicity mechanism of pollutants in typical mining areas and assess the environmental risks of pollutants to primary producers in aquatic ecosystems.


High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle.
Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cε membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (-37%, P < .05) and AS160 Thr642 (-47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.


Non-Neuronal Acetylcholinesterase Activity Shows Limited Utility for Early Detection of Sepsis.
(1) Background: Sepsis is a severe systemic inflammatory condition characterized by rapid clinical deterioration and organ dysfunction. The cholinergic system has been implicated in modulating the inflammatory response. Acetylcholinesterase (AChE), an enzyme primarily responsible for the hydrolysis of acetylcholine, has been proposed as a potential early indicator of sepsis onset. However, the exact role of non-neuronal AChE activity in sepsis and its correlation with disease severity and patient outcomes remain unclear. This study aimed to investigate the involvement of AChE activity in sepsis and evaluate its association with disease severity and clinical outcomes. (2) Methods: A prospective study included 43 septic patients. AChE activity was measured at sepsis detection, as well as 7 and 28 days later. Inflammatory biomarkers, disease severity scores, and patient outcomes were evaluated. (3) Results: AChE activity remained stable for 7 days and decreased at 28 days. However, there was no correlation between initial AChE activity and inflammatory biomarkers, disease severity scores, ICU stay, or hospital stay. (4) Conclusions: Non-neuronal AChE activity may not reliably indicate early sepsis or predict disease severity.


ADHD comorbidity findings from the MTA study: comparing comorbid subgroups.
Previous research has been inconclusive whether attention-deficit/hyperactivity disorder (ADHD), when comorbid with disruptive disorders (oppositional defiant disorder [ODD] or conduct disorder [CD]), with the internalizing disorders (anxiety and/or depression), or with both, should constitute separate clinical entities. Determination of the clinical significance of potential ADHD + internalizing disorder or ADHD + ODD/CD syndromes could yield better diagnostic decision-making, treatment planning, and treatment outcomes. Drawing upon cross-sectional and longitudinal information from 579 children (aged 7-9.9 years) with ADHD participating in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), investigators applied validational criteria to compare ADHD subjects with and without comorbid internalizing disorders and ODD/CD. Substantial evidence of main effects of internalizing and externalizing comorbid disorders was found. Moderate evidence of interactions of parent-reported anxiety and ODD/CD status were noted on response to treatment, indicating that children with ADHD and anxiety disorders (but no ODD/CD) were likely to respond equally well to the MTA behavioral and medication treatments. Children with ADHD-only or ADHD with ODD/CD (but without anxiety disorders) responded best to MTA medication treatments (with or without behavioral treatments), while children with multiple comorbid disorders (anxiety and ODD/CD) responded optimally to combined (medication and behavioral) treatments. Findings indicate that three clinical profiles, ADHD co-occurring with internalizing disorders (principally parent-reported anxiety disorders) absent any concurrent disruptive disorder (ADHD + ANX), ADHD co-occurring with ODD/CD but no anxiety (ADHD + ODD/CD), and ADHD with both anxiety and ODD/CD (ADHD + ANX + ODD/CD) may be sufficiently distinct to warrant classification as ADHD subtypes different from "pure" ADHD with neither comorbidity. Future clinical, etiological, and genetics research should explore the merits of these three ADHD classification options.


A flexible formula for incorporating distributive concerns into cost-effectiveness analyses: Priority weights.
Cost effectiveness analyses (CEAs) are widely used to evaluate the opportunity cost of health care investments. However, few functions that take equity concerns into account are available for such CEA methods, and these concerns are therefore at risk of being disregarded. Among the functions that have been developed, most focus on the distribution of health gains, as opposed to the distribution of lifetime health. This is despite the fact that there are good reasons to give higher priority to individuals and groups with a low quality adjusted life expectancy from birth (QALE). Also, an even distribution of health gains may imply an uneven distribution of lifetime health. We develop a systematic and explicit approach that allows for the inclusion of lifetime health concerns in CEAs, by creating a new priority weight function, PW = α+(t-γ)·C·e-β·(t-γ), where t is the health measure. PW has several desirable properties. First, it is continuous and smooth, ensuring that people with similar health characteristics are treated alike. For example, those who achieve 50 QALE should be treated similarly to those who achieve 49.9 QALE. Second, it is flexible regarding shape and outcome measure (i.e., caters to other measures than QALE), so that a broad range of values may be modelled. Third, the coefficients have distinct roles. This allows for the easy manipulation of the PW's shape. In order to demonstrate how PW may be applied, we use data from a previous study and estimated the coefficients of PW based on two approaches. Equity concerns are important when conducting CEAs, which means that suitable PWs should be developed. We do not intend to determine which PW is the most appropriate, but to illustrate how a flexible general PW can be estimated based on empirical data.


[Differential diagnosis of rhinosinusogenic cerebral leptomeningitis and brain abscesses].
Analysis is made of the results of examination of 247 patients with cerebral leptomeningitis and 49 patients with brain abscesses. Owing to a comprehensive examination of that patients' group by means of a number of the current research methods, the immunocytochemical, roentgeno-radiological++ (computer-aided tomographic, MR tomographic, gamma-topographic) signs typical of each form of intracranial complications were delimited. This enables an early clinico-nosological + diagnosis to be established, which is of paramount practical importance for the choice of the appropriate treatment policy.


Subcortical volumetric changes across the adult lifespan: subregional thalamic atrophy accounts for age-related sensorimotor performance declines.
Even though declines in sensorimotor performance during healthy aging have been documented extensively, its underlying neural mechanisms remain unclear. Here, we explored whether age-related subcortical atrophy plays a role in sensorimotor performance declines, and particularly during bimanual manipulative performance (Purdue Pegboard Test). The thalamus, putamen, caudate and pallidum of 91 participants across the adult lifespan (ages 20-79 years) were automatically segmented. In addition to studying age-related changes in the global volume of each subcortical structure, local deformations within these structures, indicative of subregional volume changes, were assessed by means of recently developed shape analyses. Results showed widespread age-related global and subregional atrophy, as well as some notable subregional expansion. Even though global atrophy failed to explain the observed performance declines with aging, shape analyses indicated that atrophy in left and right thalamic subregions, specifically subserving connectivity with the premotor, primary motor and somatosensory cortical areas, mediated the relation between aging and performance decline. It is concluded that subregional volume assessment by means of shape analyses offers a sensitive tool with high anatomical resolution in the search for specific age-related associations between brain structure and behavior.


Pediatrician qualifications and asthma management behaviors and their association with patient race/ethnicity.
We sought to understand if pediatrician characteristics and asthma assessment and treatment varied in association with the proportion of African-American and Latino children in the pediatrician's practice. We conducted a cross-sectional survey of 500 American Academy of Pediatrics members between November 2005 and May 2006. Standardized vignettes were used to test how different indicators of a patient's asthma status affect pediatrician asthma assessments and recommendations. Linear and logistic regression models were used to examine the association of pediatrician assessments and treatment recommendations for these vignettes, respectively, with the proportion of reported African-American and Latino children seen in their practice. There were 270 respondents (response rate = 54%). Based on pediatrician-reported percentage of minority patients, there were no differences in board certification status, recognition of poorly controlled asthma nor in the likelihood of appropriately increasing long-term controller medications to treat poorly controlled asthma (p > 0.05 for all analyses). Caring primarily for minority children by AAP pediatricians appears unrelated to training qualifications or in their reported knowledge of how to appropriately assess and treat asthma. Therefore, studies of asthma care disparities should focus on understanding the knowledge-base of non-AAP pediatric providers who care for minority populations and exploring other potential contributory provider-level factors (e.g. communication skills).


Impact of pneumococcal vaccination in children on serotype distribution in adult community-acquired pneumonia using the serotype-specific multiplex urinary antigen detection assay.
The aim of the study was to compare the distribution of the vaccine-serotypes covered by pneumococcal conjugate vaccines (PCV7 and PCV13) in adult patients with pneumococcal community-acquired pneumonia in Germany between the periods 2002-2006 and 2007-2011 using a novel serotype-specific multiplex urinary antigen detection assay (SSUA). Vaccination of children started with PCV7 in 2007, which was replaced by PCV13 in 2010. Following confirmation of the accuracy of SSUA in long-term stored urine samples from 112 patients with confirmed pneumonia and known pneumococcal serotype, urine samples of 391 CAPNETZ patients with documented pneumococcal pneumonia (i.e. positive BinaxNOW) Streptococcus pneumoniae urine antigen test) but unknown serotype were tested for the 13 vaccine-serotypes using SSUA. The proportion of PCV7-serotypes significantly decreased in adult patients with pneumonia from 30.6% (2002-6) to 13.3% (2007-11, p < 0.001); in bacteremic pneumonia, PCV7-serotypes completely disappeared (3/14 versus 0/19, p = 0.058). Conversely, pneumococcal serotypes included by PCV13 remained stable during study period with a coverage of 61.5% (2002-06) and 59.7% (2007-11) in non-bacteremic pneumonia and 79% (for both periods) in bacteremic pneumonia, mainly due to an increase in pneumococcal serotypes 1, 3 and 7F during the second period. Thus, implementation of PCV7 in children in Germany in 2007 was associated with a significant decrease in vaccine-serotypes covered by PCV7 in adult patients with non-bacteremic pneumococcal pneumonia and with an elimination of PCV7 vaccine-serotypes in bacteremic pneumococcal pneumonia. PCV13 coverage remained high up to 2011, mainly due to an increase in serotypes 1, 3 and 7F.


Rotavirus nonstructural protein 1 suppresses virus-induced cellular apoptosis to facilitate viral growth by activating the cell survival pathways during early stages of infection.
Following virus infection, one of the cellular responses to limit the virus spread is induction of apoptosis. In the present study, we report role of rotavirus nonstructural protein 1 (NSP1) in regulating apoptosis by activating prosurvival pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt and NF-kappaB (nuclear factor kappaB) during early hours of infections (2 to 8 hpi). The NSP1 mutant strain A5-16 induces weak and transient activation of Akt (protein kinase B) and p65 NF-kappaB compared to the isogenic wild-type strain A5-13 in MA104 or HT29 cells. The weak NF-kappaB promoter activity or Akt phosphorylation after A5-16 infection could be complemented in cells transfected with plasmid expressing NSP1 after infection with the rotavirus A5-16 strain. In cells either infected with A5-13 or transfected with pcD-NSP1, coimmunoprecipitation of NSP1 with phosphoinositide 3-kinase (PI3K) was observed, indicating that strong activation of PI3K/Akt could be due to its interaction with NSP1. In addition, after infection with same multiplicity of infection, A5-16 showed reduced number of viral particles compared to the A5-13 strain at the end of the replication cycle. A lower growth rate could be due to weak induction of PI3K/Akt and NF-kappaB, since the A5-13 strain also showed reduced growth in the presence of PI3K or NF-kappaB inhibitors. This effect was interferon independent; however, it was partly due to significantly higher caspase-3 activity, poly-ADP ribose polymerase (PARP) cleavage, and apoptosis during earlier stages of infection with the NSP1 mutant. Thus, our data suggest that NSP1 positively supports rotavirus growth by suppression of premature apoptosis for improved virus growth after infection.


A Comprehensive Overview of IoT-Based Federated Learning: Focusing on Client Selection Methods.
The integration of the Internet of Things (IoT) with machine learning (ML) is revolutionizing how services and applications impact our daily lives. In traditional ML methods, data are collected and processed centrally. However, modern IoT networks face challenges in implementing this approach due to their vast amount of data and privacy concerns. To overcome these issues, federated learning (FL) has emerged as a solution. FL allows ML methods to achieve collaborative training by transferring model parameters instead of client data. One of the significant challenges of federated learning is that IoT devices as clients usually have different computation and communication capacities in a dynamic environment. At the same time, their network availability is unstable, and their data quality varies. To achieve high-quality federated learning and handle these challenges, designing the proper client selection process and methods are essential, which involves selecting suitable clients from the candidates. This study presents a comprehensive systematic literature review (SLR) that focuses on the challenges of client selection (CS) in the context of federated learning (FL). The objective of this SLR is to facilitate future research and development of CS methods in FL. Additionally, a detailed and in-depth overview of the CS process is provided, encompassing its abstract implementation and essential characteristics. This comprehensive presentation enables the application of CS in diverse domains. Furthermore, various CS methods are thoroughly categorized and explained based on their key characteristics and their ability to address specific challenges. This categorization offers valuable insights into the current state of the literature while also providing a roadmap for prospective investigations in this area of research.


Intragenic transposition of Ac generates a new allele of the maize P gene.
The maize P gene is required for the production of red phlobaphene pigments in the pericarp and cob. The P-vv allele, which specifies variegated pericarp and cob, contains an insertion of the transposable element Ac in the P gene. A new P-ovov allele (orange variegated pericarp and cob) was obtained as a single event mutation from P-vv. In contrast to the progenitor P-vv allele, P-ovov provides substantial pericarp and cob pigmentation and produces significant amounts of normal-sized P transcripts. The Ac element is not detectably altered in the P-ovov allele, but it has transposed to a new position within P that is 161 bp distant and inserted in the opposite orientation. This example provides molecular confirmation for the hypothesis that changes in expression of genes bearing insertions of transposable elements can occur via movement of the element to new sites within the gene.


Carbon metabolism regulates expression of the pfl (pyruvate formate-lyase) gene in Escherichia coli.
The anaerobic expression of pfl is reduced both in a strain mutated in the pgi gene and in a pfkA pfkB double mutant strain when cells are grown in medium supplemented with glucose. When cells are grown in medium supplemented with either fructose or pyruvate, no reduction is observed in these strains. The amount of pyruvate in the cells may be responsible for the reduced expression of pfl in the strains mutated in the genes encoding the glycolytic enzymes. Because of the lowered oxygen concentration in the medium, the expression of pfl is induced when an exponentially growing culture enters the stationary phase. This induction is increased when the Casamino Acid concentration is raised 10-fold or when the medium is supplemented with NaCl. Superhelicity of DNA is decreased in a pgi mutant strain grown in medium supplemented with glucose. The superhelicity is also changed, but the opposite way, in a wild-type strain grown in medium supplemented with Casamino Acids at a high concentration or 0.3 M sodium chloride. Our data show that changes in superhelicity do not affect the aerobic expression of pfl but might be important for the anaerobic induction of pfl.


[Combined therapy of trophic ulcers with protracted healing].
The results of treatment of 126 patients with trophic ulcers of the low extremities were analyzed. Trophic ulcers in 74 patients (58.7%) appeared due to postthrombophlebitic disease, in 25 patients (19.8%) due to primary varicose veins of lower limbs, in 15 (11.9%) patients due to obliterative diseases of peripheral vessels and in 12 (9.5%)--other diseases. The duration of the illness made up from 1 to 50 years. In 26 patients (group 1) low-intensity laser irradiation (LLI) was used together with combined conservative therapy; in 32 patients (group 2) hyperbaric oxygenation (HBO), in 21 (3 group)--combined application of LLI and HBO was used. The examination of regional macrohemodynamics and microcirculation in 39 patients showed decrease of rheographic index (RI) in the shin, increase of the arterioles tone and venous outflow disturbance. The use of LLI and HBO resulted in undoubtful increase of RI and improvement of microcirculatory indexes. As a result of combined application of LLI and HBO microflora of the ulcers lowered from 10 and 10 per 1 gr in patients of group 1 and 2, respectively, in patients of group 3 there was no growth of pathogenic microflora. The investigation of humoral and cellular immunity after the application of LLI and HBO demonstrated strong immunocorrective action.


The estimated impact of the CCR-5 delta32 gene deletion on HIV disease progression varies with study design. Oslo HIV Cohort Study Group.
To study the impact of the genotype CCR-5 wild-type +/A32 on the progression rate to AIDS and death, and to discuss sources of bias according to study design. A prospective study of 310 HIV-positive subjects with follow-up time from study entry (prevalent cohort), and a prospective study of 105 HIV-positive subjects with well-defined time of HIV seroconversion, with follow-up time from the retrospectively assessed date of HIV seroconversion (retrospective incident cohort). Slower progression to AIDS among subjects with CCR-5 +/delta32 than those with CCR-5 +/+ genotype was estimated in the prevalent cohort (P=0.07, log-rank test). Slower progression to death from any cause was also estimated for subjects with CCR-5 +/delta32 (P < 0.05, log-rank test). No differences in survival after AIDS diagnosis were seen (P=0.89, log-rank test). No differences in the progression rate to AIDS (P=0.82, log-rank test) or death (P=0.78, log-rank test) were estimated in the retrospective incident cohort. The varying estimates of the impact of CCR-5 genotype on progression to AIDS in this and other studies, may be real and reflect differences in the dependence of HIV on the CCR-5 receptor, or may be due to systematic errors caused by study design. Several methodological difficulties occur when the factor studied, such as CCR-5 genotype, is associated both with the risk of being HIV-infected and the progression of disease.


Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial.
Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs. Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers (n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures. Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index (p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity. Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.


Social contagion of risk perceptions in environmental management networks.
An important requisite for improving risk communication practice related to contentious environmental issues is having a better theoretical understanding of how risk perceptions function in real-world social systems. Our study applied Scherer and Cho's social network contagion theory of risk perception (SNCTRP) to cormorant management (a contentious environmental management issue) in the Great Lakes Basin to: (1) assess contagion effects on cormorant-related risk perceptions and individual factors believed to influence those perceptions and (2) explore the extent of social contagion in a full network (consisting of interactions between and among experts and laypeople) and three "isolated" models separating different types of interactions from the full network (i.e., expert-to-expert, layperson-to-layperson, and expert-to-layperson). We conducted interviews and administered questionnaires with experts (e.g., natural resource professionals) and laypeople (e.g., recreational and commercial anglers, business owners, bird enthusiasts) engaged in cormorant management in northern Lake Huron (n = 115). Our findings generally support the SNCTRP; however, the scope and scale of social contagion varied considerably based on the variables (e.g., individual risk perception factors), actors (i.e., experts or laypeople), and interactions of interest. Contagion effects were identified more frequently, and were stronger, in the models containing interactions between experts and laypeople than in those models containing only interactions among experts or laypeople.


Prevalence of arthritis in older Mexican Americans.
This study examines the prevalence of self-reported physician-diagnosed arthritis and arthritis symptoms and their relationship to functional limitations in Mexican American elderly. We conducted a cross-sectional study using a probability sample of 2,873 non-institutionalized Mexican American men and women aged 65 or older, residing in the southwestern United States. Measures included self-reported physician-diagnosed arthritis, morning pain or stiffness, pain when standing, global health rating, activities of daily living (ADL), instrumental activities of daily living (IADL), depressive symptoms, presence of chronic diseases (diabetes mellitus, hypertension, heart attack, stroke), and body mass index. The Mantel-Haenszel chi-square statistic was used to test differences by arthritis status, and a logistic regression model was used to predict the odds of having arthritis. The overall prevalence of self-reported physician-diagnosed arthritis in the sample was 40.8 percent, 50.0 percent among women and 28.8 percent among men (P < 0.001). Morning pain or stiffness was reported by 37.7 percent of respondents and pain when standing or walking by 31.9 percent. All comorbid conditions, and both IADL and ADL limitations, were more prevalent in those with arthritis than in those without arthritis. Female sex and several medical conditions were independently associated with self-reported arthritis. Self-reported physician-diagnosed arthritis is common among older Mexican Americans. Functional limitation and disability are more prevalent among subjects with arthritis than among those without arthritis.


Selfishness as second-order altruism.
Selfishness is seldom considered a group-beneficial strategy. In the typical evolutionary formulation, altruism benefits the group, selfishness undermines altruism, and the purpose of the model is to identify mechanisms, such as kinship or reciprocity, that enable altruism to evolve. Recent models have explored punishment as an important mechanism favoring the evolution of altruism, but punishment can be costly to the punisher, making it a form of second-order altruism. This model identifies a strategy called "selfish punisher" that involves behaving selfishly in first-order interactions and altruistically in second-order interactions by punishing other selfish individuals. Selfish punishers cause selfishness to be a self-limiting strategy, enabling altruists to coexist in a stable equilibrium. This polymorphism can be regarded as a division of labor, or mutualism, in which the benefits obtained by first-order selfishness help to "pay" for second-order altruism.


MI-Common Data Model: Extending Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM) for Registering Medical Imaging Metadata and Subsequent Curation Processes.
The explosion of big data and artificial intelligence has rapidly increased the need for integrated, homogenized, and harmonized health data. Many common data models (CDMs) and standard vocabularies have appeared in an attempt to offer harmonized access to the available information, with Observational Medical Outcomes Partnership (OMOP)-CDM being one of the most prominent ones, allowing the standardization and harmonization of health care information. However, despite its flexibility, still capturing imaging metadata along with the corresponding clinical data continues to pose a challenge. This challenge arises from the absence of a comprehensive standard representation for image-related information and subsequent image curation processes and their interlinkage with the respective clinical information. Successful resolution of this challenge holds the potential to enable imaging and clinical data to become harmonized, quality-checked, annotated, and ready to be used in conjunction, in the development of artificial intelligence models and other data-dependent use cases. To address this challenge, we introduce medical imaging (MI)-CDM-an extension of the OMOP-CDM specifically designed for registering medical imaging data and curation-related processes. Our modeling choices were the result of iterative numerous discussions among clinical and AI experts to enable the integration of imaging and clinical data in the context of the ProCAncer-I project, for answering a set of clinical questions across the prostate cancer's continuum. Our MI-CDM extension has been successfully implemented for the use case of prostate cancer for integrating imaging and curation metadata along with clinical information by using the OMOP-CDM and its oncology extension. By using our proposed terminologies and standardized attributes, we demonstrate how diverse imaging modalities can be seamlessly integrated in the future.


Genetics of primary aldosteronism.
The American Association of Clinical Endocrinologists Adrenal Scientific Committee has developed a series of articles to update members on the genetics of adrenal diseases. Case presentation, discussion of literature, table, and bullet point conclusions. Primary aldosteronism (PA) is the most common form of secondary hypertension. Early detection, surveillance, and treatment of PA may mitigate future cardiovascular risk. The genetics of PA are rapidly evolving, and the consideration for genetic causes of PA are growing. Three inheritable forms of PA are now recognized: familial hyperaldosteronism type I (glucocorticoid-remediable aldosteronism), familial hyperaldosteronism type II, and familial hyperaldosteronism type III. The recent discovery of familial hyperaldosteornism type III spurred a flurry of international and collaborative research that is identifying more genetic and molecular causes of PA that relate to mutations in membrane electrolyte transport channels of zona glomerulosa cells. This article reviews the various genetic forms of PA, including a focus on the molecular mechanisms involved, diagnosis, and treatment.


Controlled comparison of conventional in-vitro fertilization and intracytoplasmic sperm injection in patients with asthenozoospermia.
A controlled comparison between conventional in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) has been carried out for patients with </=5% rapid progressive (type A) spermatozoa in their fresh semen. Twenty couples were allocated to the study. All semen samples fulfilled the minimum criteria to be allocated to the conventional IVF programme. The two pronuclear (2PN) fertilization rate per retrieved cumulus-oocyte complex was significantly higher after ICSI (63.4%) than after conventional IVF (22.9%), with complete fertilization failure after IVF in 10 out of the 20 cycles. Embryo quality was similar for both treatments. Sixteen patients received only ICSI embryos, two patients only IVF embryos and two patients received IVF and ICSI embryos. The ongoing clinical pregnancy rate was 45%, the implantation rate was 37%. Comparison of the characteristics of patients/cycles with and without 2PN fertilization revealed a higher proportion of progressively motile spermatozoa in the prepared sperm fraction for the group of patients with fertilization after conventional IVF. It can be concluded from this study that absence of or an extremely low proportion of rapid progressive motility in fresh semen indicates a high risk of complete fertilization failure with conventional IVF.


Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction.
Unilateral ureteral obstruction (UUO) is a well-established experimental model of renal injury leading to interstitial fibrosis. The molecular and cellular mechanism(s) of interstitial fibrosis in UUO kidney is beginning to be elucidated. Oxidative stress has been implicated in the pathogenesis of various forms of renal injury; however, little is known about its involvement in the setting of ureteral obstruction. To investigate the possible involvement of oxidative stress in the obstructive nephropathy, we studied the occurrence and distribution of Nepsilon-carboxymethyl-lysine (CML) in the kidneys after ureteral obstruction. CML is an integrative biomarker of the cumulative protein damage induced by glycoxidation. Heme oxygenase-1 (HO-1) mRNA and protein expression, which is a sensitive and reliable indicator of oxidative stress, were also examined. CML immunoreactivity was found in the interstitium of UUO kidneys 10 days after the onset ureteral obstruction. HO-1 mRNA was up-regulated as early as 12 hours after ureteral obstruction. HO-1 immunoreactivity was observed in the periglomerular and peritubular interstitium two days after ureteral obstruction. These results strongly suggested the presence of increased oxidative stress in the interstitium of UUO kidneys. The oxidative stress and the formation of various kind of biological active oxidative products in the interstitium are supposed to play significant roles in UUO kidney.


Evaluation of ceftiofur-PHBV microparticles in rats.
Despite the high number of antibiotics used for the treatment of infectious disease in animals, the development of slow release formulations presents a significant challenge, particularly in using novel biomaterials with low cost. In this report, we studied the pharmacokinetics, toxicity, and therapeutic activity of ceftiofur-PHBV (ceftiofur-poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) in rats. The pharmacokinetic study demonstrated a sustained release of ceftiofur into the bloodstream, with detectable levels over the minimum inhibitory concentration for at least 17 days after a single intramuscular injection of ceftiofur-PHBV (10 mg/kg weight). In addition, the toxicological evaluation of biochemical, hematological, and coagulation blood parameters at the therapeutic dose demonstrated the safety of ceftiofur-PHBV, with no adverse effects. In addition, ceftiofur-PHBV exhibited a therapeutic effect for a longer time period than the nonencapsulated ceftiofur in rats challenged with Salmonella Typhimurium. The slow release of ceftiofur from the ceftiofur-PHBV, its low toxicity in the blood parameters evaluated, and the efficacy in the rats infected with Salmonella Typhimurium make ceftiofur-PHBV a strong candidate for biotechnological applications in the veterinary industry.


Association of Lunate Morphology With Carpal Instability in Scapholunate Ligament Injury.
We examined the relationship between lunate morphology (type 1 without a medial facet; type II with a medial facet) and dorsal intercalated segmental instability (DISI) in patients with scapholunate ligament injuries. We tested the primary null hypothesis that there is no relationship between lunate morphology and development of DISI. Secondary analysis compared the agreement of classifying lunate morphology based on the presence of a medial lunate facet, capitate-to-triquetrum (CT) distance, and magnetic resonance imaging (MRI). We performed a retrospective chart review of patients with known scapholunate ligament injuries from 2001 to 2016. Posterior-anterior radiographs and MRI, when available, were evaluated. CT distances were measured as a secondary classification method. DISI and scapholunate instability were determined as radiolunate angle >15° and scapholunate angle >60°, respectively. Differences between groups were determined using chi-square analysis with significance set at P < .05. Agreement between plain radiographs, MRI, and CT distance was calculated using the kappa statistic. Our search found 58 of 417 patients who met inclusion criteria; 41 of 58 had type II and 17 of 58 had type I lunates. There was no significant difference between groups in regard to DISI or scapholunate instability. Subanalysis using MRI alone or correcting any discrepancy between plain film and MRI classification, using MRI as the standard, found no difference between groups in regard to DISI or scapholunate instability. In patients with scapholunate ligament injuries, there are no differences in the development of DISI or scapholunate instability between patients with type I and type II lunates.


Bibliometric network analysis of glaucoma.
Elevated intraocular pressure is recognized as the principal risk factor for development of optic nerve head (ONH) injury. Lamina cribrosa (LC) cells and astrocytes are two types of cells in the ONH. We attempted to identify more target genes and predict their underlying molecular mechanisms. In this study, we performed meta-analysis of the data from two microarray sets containing samples from LC cells and astrocytes each. Our analysis indicated that 47 differentially expressed genes (DEGs) had been identified, and 24 of them were used to construct a bibliometric network with other related genes, including GSTT1 ENO2, CPE, PTN, PTGDS, IL6, MMP1, and EGFR. Further, our results predicted these genes might be involved in glaucoma development through Toll-like receptor signaling pathway, ErbB signaling pathway, and glioma and other cancer-related pathways. Therefore our study provides potential target genes and pathways for future therapeutic studies of glaucoma.


P38α MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism.
Muscular dystrophies are a group of genetic diseases that lead to muscle wasting and, in most cases, premature death. Cytokines and inflammatory factors are released during the disease process where they promote deleterious signaling events that directly participate in myofiber death. Here, we show that p38α, a kinase in the greater mitogen-activated protein kinase (MAPK)-signaling network, serves as a nodal regulator of disease signaling in dystrophic muscle. Deletion of Mapk14 (p38α-encoding gene) in the skeletal muscle of mdx- (lacking dystrophin) or sgcd- (δ-sarcoglycan-encoding gene) null mice resulted in a significant reduction in pathology up to 6 months of age. We also generated MAPK kinase 6 (MKK6) muscle-specific transgenic mice to model heightened p38α disease signaling that occurs in dystrophic muscle, which resulted in severe myofiber necrosis and many hallmarks of muscular dystrophy. Mechanistically, we show that p38α directly induces myofiber death through a mitochondrial-dependent pathway involving direct phosphorylation and activation of the pro-death Bcl-2 family member Bax. Indeed, muscle-specific deletion of Bax, but not the apoptosis regulatory gene Tp53 (encoding p53), significantly reduced dystrophic pathology in the muscles of MKK6 transgenic mice. Moreover, use of a p38 MAPK pharmacologic inhibitor reduced dystrophic disease in Sgcd(-/-) mice suggesting a future therapeutic approach to delay disease.


Synthesis of mucous glycoproteins by rabbit tracheal cells in vitro. Modulation by substratum, retinoids and cyclic AMP.
One function of airway epithelium is the secretion of mucins, which comprise an important component of the mucous lining layer. We demonstrate that rabbit tracheal epithelial cells grown in primary culture incorporate [3H]glucosamine into material released into the medium which is characterized as mucin by the following criteria: high Mr, monosaccharide composition, ion-exchange behaviour different from that of glycosaminoglycans and oligosaccharides attached via N-acetylgalactosamine. The production of mucin by the cells requires growth on a substratum of collagen gel and is enhanced by retinoids in the extracellular medium. In the presence of retinoids, 8-bromo cyclic AMP and factors present in medium from 3T3 fibroblasts each further stimulate mucin production. These results indicate that an isolated epithelial-cell culture system, in the absence of nervous, mesenchymal or other tissue types, can be used to answer questions about the regulation of mucin production at the cellular level.


Deleted in Colorectal Cancer (DCC) gene polymorphism is associated with H. pylori infection among susceptible Malays from the north-eastern region of Peninsular Malaysia.
Using genome-wide case-control association approach, the current study aimed to determine whether genetic polymorphism(s) is/are associated with H. pylori infection among ethnic Malays from the north-eastern region of Peninsular Malaysia, a region with an exceptionally low prevalence for H. pylori infection and gastric cancer. Twenty-three Malay subjects positive for H. pylori confirmed with urease test and histology were enrolled as "cases" and 37 subjects negative for H. pylori were "controls". Both groups were matched for age and environmental risks. Extracted DNA samples (QIAGEN, Germany) from the venous blood of study subjects were genotyped using the Human Mapping 50k xbal array (Affymetrix, USA). High throughput downstream analyses were then used to determine the significant SNP(s) associated with H. pylori infection. Out of 20,361 SNPs filtered using the genotype association test, the top 1% (203) significant SNPs were selected for functional enrichment analysis. Of the 15 "enriched" SNPs, the rs10502974 which was located within the intronic region of Deleted in Colorectal Cancer (DCC) gene was the SNP most significantly associated with H. pylori infection (p=0.00549). Ethnic Malays is genetically susceptible to H. pylori infection and is possibly mediated through a genetic variation in the DCC gene.


Formononetin attenuates high glucose-induced neurotoxicity by negatively regulating oxidative stress and mitochondrial dysfunction in Schwann cells via activation of SIRT3.
High glucose induces Schwann cells death and neurotoxicity. Formononetin was originally found in Astragalus membranaceus and showed anti-tumor and anti-neuroinflammation properties. The aim of this study is to explore the molecular mechanism underlying the neuroprotective effects of formononetin and identify its direct protein target. The effects of formononetin on oxidative stress and mitochondrial dysfunction in Schwann cells induced by high glucose were investigated. High glucose treatment significantly induced oxidative stress, mitochondrial dysfunction and apoptosis in Schwann cells, while these effects were partially or completely prevented by co-treatment with formononetin. Mechanistically, we found that SIRT3/PGC-1α/SOD2 pathway was activated by formononetin under high glucose conditions as evidenced by western blotting. Knockdown of SIRT3 by siRNA delivery reversed the protective effects of formononetin on high glucose-induced Schwann cells injury and changes in expression profile of SIRT3 downstream target genes. Molecular docking, thermal shift assay and surface plasmon resonance assay revealed a direct binding between formononetin and SIRT3. Taken together, we identified a novel SIRT3 activator formononetin and revealed its beneficial effects on high glucose-induced neurotoxicity, suggesting that targeting SIRT3 in Schwann cells may be a new approach for treatment of peripheral nerve regeneration related diseases such as diabetic peripheral neuropathy.


The Development of a Quality of Life Scale for Informal Carers for Older Adults.
Background: The aim of the study was to develop a multidimensional quality of life instrument suitable for use among individuals across cultures who have an informal care role for older persons. Methods: Participants were informal carers of older adults in the United Kingdom (n = 308), United States (n = 164), and China (n = 131). We carried out exploratory and confirmatory factor analyses of 61 items derived from the eight-factor Adult Carers Quality of Life Questionnaire with newly added items to define both traditional and nontraditional informal care roles. Results: Findings suggest a 24-item quality of life scale with a six-factor structure to caring for older adults that assesses (a) exhaustion, (b) adoption of a traditional carer role, (c) personal growth, (d) management and performance, (e) level of support, and (f) financial matters. Conclusion: We present a new scale to assess the multidimensional aspects of quality of life among those caring for older adults.