Physiological responses in two populations of Andropogon glomeratus Walter B.S.P. to short-term salinity.
Andropogon glomeratus is a C4 nonhalophytic grass which exhibits population differentiation for tolerance to short-term salinity exposure. To investigate possible physiological mechanisms whch enable salt-tolerant individuals to survive short-term inundation, gas exchange and water relations parameters were measured before and during a 5-day watering treatment of half-strength synthetic seawater in plants from a tolerant and a non-tolerant population. Photosynthetic recovery was followed for 10 days after the salinity treatment. Photosynthetic CO2 uptake was substantially inhibited in both populations. Stomatal conductances decreased and intercellular CO2 concentrations increased, indicating non-stomatal factors were primarily responsible for the decrease in CO2 uptake. After termination of the salinity treatment photosynthetic capacity increased more rapidly in the tolerant population and reached the pretreatment level after 6 days, whereas the nontolerant population did not recover fully after 10 days. A-Ci curves measured before and after the salinity treatment indicated a decrease in the carboxylation efficiency, and suggested a proportionately greater metabolic inhibition relative to the increase in the stomatal limitation. Osmotic adjustment occurred in a 2-day period in the tolerant population, but there was no change in the osmotic potentials or the water potential at the point of turgor loss in the nontolerant population. Thus short-term salt tolerance in the marsh population is associated with rapid osmotic adjustment and recovcry of photosynthetic capacity shortly after the end of the salinity exposure, rather than maintenance of greater photosynthesis during the salinity treatment.


Further validation and reliability testing of the Attitudes and Beliefs about Living with Epilepsy (ABLE) components of the CDC Epilepsy Program Instrument on Stigma.
The aim of this study was to conduct additional validation and reliability testing of the Attitudes and Beliefs about Living with Epilepsy (ABLE) components of the CDC Epilepsy Program Instrument on Stigma. Thirteen items were tested using a representative sample of U.S. adults (n=4345). Confirmatory factor analyses confirmed two underlying constructs as hypothesized that accounted for 61% of the variance in the factor analysis: Negative Stereotypes (alpha=0.86) and Risk and Safety Concerns (alpha=0.88). As expected, participants differed on scale scores by demographic characteristics. Test-retest reliability was acceptable. The results of these analyses extend those from our previous study suggesting that the negative stereotypes and risk and safety concern scales demonstrate acceptable validity and reliability, and can be used to measure attitudes toward epilepsy related to these two domains.


Ceramic transition metal diboride superlattices with improved ductility and fracture toughness screened by ab initio calculations.
Inherent brittleness, which easily leads to crack formation and propagation during use, is a serious problem for protective ceramic thin-film applications. Superlattice architectures, with alternating nm-thick layers of typically softer/stiffer materials, have been proven powerful method to improve the mechanical performance of, e.g., cubic transition metal nitride ceramics. Using high-throughput first-principles calculations, we propose that superlattice structures hold promise also for enhancing mechanical properties and fracture resistance of transition metal diborides with two competing hexagonal phases, [Formula: see text] and [Formula: see text]. We study 264 possible combinations of [Formula: see text], [Formula: see text] or [Formula: see text] MB[Formula: see text] (where M [Formula: see text] Al or group 3-6 transition metal) diboride superlattices. Based on energetic stability considerations, together with restrictions for lattice and shear modulus mismatch ([Formula: see text], [Formula: see text] GPa), we select 33 superlattice systems for further investigations. The identified systems are analysed in terms of mechanical stability and elastic constants, [Formula: see text], where the latter provide indication of in-plane vs. out-of-plane strength ([Formula: see text], [Formula: see text]) and ductility ([Formula: see text], [Formula: see text]). The superlattice ability to resist brittle cleavage along interfaces is estimated by Griffith's formula for fracture toughness. The [Formula: see text]-type TiB[Formula: see text]/MB[Formula: see text] (M [Formula: see text] Mo, W), HfB[Formula: see text]/WB[Formula: see text], VB[Formula: see text]/MB[Formula: see text] (M [Formula: see text] Cr, Mo), NbB[Formula: see text]/MB[Formula: see text] (M [Formula: see text] Mo, W), and [Formula: see text]-type AlB[Formula: see text]/MB[Formula: see text] (M [Formula: see text] Nb, Ta, Mo, W), are suggested as the most promising candidates providing atomic-scale basis for enhanced toughness and resistance to crack growth.


Molecular evidence for new foodways in the early colonial Caribbean: organic residue analysis at Isla de Mona, Puerto Rico.
Ceramic objects account for over 90% of the cultural material recovered from archaeological sites in the Caribbean. However, little research has been conducted on molecular evidence for past food production from these same vessels. Forty ceramic sherds from Isla de Mona have been analysed by GC-MS and GC-C-IRMS in order to address questions surrounding foodways in the Greater Antilles prior to and post European arrival. We evaluate evidence for dietary changes to illuminate aspects of cultural exchange between Indigenous populations and the first generations of Spanish colonists. Here, we show that plant residues are found in a variety of pottery forms, with some evidence for non-ruminant and ruminant fats. The dearth of marine biomarkers is curious given the volume of fish bones found in archaeological contexts on Isla de Mona and may offer evidence for spit-roasting, pit-roasting, or the use of a 'barbacoa' to cook fish on the island. The ubiquity of plant residues in a variety of pottery forms may relate to the large-scale cultivation and export of cassava (Manihot esculenta) from the island. A Spanish olive jar revealed evidence of wine residues, which may constitute the earliest detection of wine residues in pottery found in the Americas. The online version contains supplementary material available at 10.1007/s12520-023-01771-y.


Utilizing of Ag@AgCl@graphene oxide@Fe3O4 nanocomposite as a magnetic plasmonic nanophotocatalyst in light-initiated H2O2 generation and chemiluminescence detection of nitrite.
A simple and sensitive chemiluminescence (CL) procedure was developed for the quantification of nitrite in aqueous solutions. The method is based on light-initiated generation of H2O2 by a magnetic Ag@AgCl@Graphene oxide nanocomposite and its subsequent redox reaction with nitrite ion in acidic medium. During the carbonate-catalyzed decomposition of produced peroxynitrite and energy transferring to uranine, a CL emission was observed at λ=534n m. Several factors affecting the CL intensity were investigated and optimized. Under optimum conditions, the CL intensity was directly proportional to the nitrite concentration in the range of 5-200 ng mL(-1). The limit of detection and relative standard deviation (for n=5; at a nitrite concentration of 70 ng mL(-1)) were 1.15 ng mL(-1) and 2.57%, respectively. The method was successfully applied to determine nitrite in food stuffs with recoveries in the range of 95.0-103.0% for the spiked samples. The accuracy of the method was evaluated by comparing the results with those obtained by analyzing the samples using a standard method.


Extreme thermal stability of the antiGFP nanobody - GFP complex.
The green fluorescent protein (GFP) and its derivatives are widely used in biomedical research. The manipulation of GFP-tagged proteins by GFP-specific binders, e.g. single-domain antibodies (nanobodies), is of increasing significance. It is therefore important to better understand the properties of antiGFP-GFP interaction in order to establish methodological applications. In this work the interaction of superfolder GFP (sfGFP) and its enhancer nanobody (aGFPenh) was characterized further. Previous calorimetric experiments demonstrated that the aGFPenh nanobody binds strongly to sfGFP with a nanomolar affinity. Here we show that this interaction results in a substantial structural stabilization of aGFPenh reflected in a significant increase of its melting temperature by almost 30 °C. The thermal stability of the sfGFP-aGFPenh complex is close to 85 °C in the pH range 7.0-8.5. For therapeutic applications thermoresistance is often an essential factor. Our results suggest that methodologies based on GFP-aGFP interaction can be applied under a wide range of physicochemical conditions. The aGFPenh nanobody seems to be suitable for manipulating sfGFP-labeled targets even in extreme thermophilic organisms.


The current state of studies of malaria vectors and the antivectorial campaign in west Africa.
Most malaria transmission in West Africa is by Anopheles funestus and An. gambiae s.l. An. funestus is not very polymorphic and is generally susceptible to currently used insecticides. An. gambiae in contrast is very polymorphic. On the basis of chromosomal polymorphism An. gambiae can be divided into forest and savannah forms. The savannah forms in turn exist as several types, viz. Bissau, Mopti and Bamako. Insecticide susceptibility does not correlate with chromosomal type in most cases; nevertheless, correct identification of vectors is necessary if a successful antimalarial campaign is to be developed. It is particularly important to determine which of the mosquitoes in the region under study are the important vectors of malaria. In the light of the difficulties encountered in mass vector control programmes, individual control measures such as home spraying and use of impregnated bed nets and curtains may be considered for malaria control.


[Yoghurt-induced Lactobacillus bacteremia in a patient with Crohn's disease on therapy with ustekinumab and concomitant HIV-Infection].
Probiotics are live microorganisms that are often used as adjunctive therapy in patients with inflammatory bowel disease. Although there is a lack of evidence for their benefit, the use of probiotics is encouraged by the perceived lack of adverse events. However, in rare instances, probiotics can cause systemic infections through bacteremia. We report about a patient with Crohn's disease and HIV-infection, who developed a septicemia. A Lactobacillus-bacteremia was diagnosed, the causative agents could be traced back to the consumption of self-made yoghurt. The utility of probiotics in IBD patients with underlying immune-compromising diseases is a risk which is difficult to predict, therefore their use in these patients should be discouraged.


Unexpected thermo-responsiveness of bisurea-functionalized hydrophilic polymers in water.
Thermoresponsive polymers are important materials for various applications. However, the number of polymers that exhibit this property in the temperature range of interest remains limited. The development of novel rational design strategies through the understanding of the thermal transition's origin is therefore of utmost importance. Bisurea-functionalized water-soluble polymers were synthesized by RAFT polymerization. After direct dissolution in water, the supramolecular assemblies were analyzed by cryo-TEM and SANS. Their temperature-dependent water-solubility was characterized by various techniques, namely DLS, SANS, DSC, IR, to understand the origin of the temperature sensitivity. The supramolecular assemblies exhibit an unexpected temperature-dependent solubility. For instance, a cloud point of only 39 °C was measured for poly(N,N-dimethylacrylamide) assemblies. This property is not restricted to one specific polymer but is rather a general feature of bisurea-functionalized polymers that form supramacromolecular bottlebrushes in water. The results highlight the existence of two distinct transitions; the first one is a visually perceptible cloud point due to the aggregation of individual micelles, presumably driven by the hydrophobic effect. The second transition is related to the dissociation of intermolecular bisurea hydrogen bonds. Finally, we show that it is possible to widely tune the cloud point temperature through the formation of co-assemblies.


Prevalence and risk factors for gastrointestinal parasitism in traditionally maintained goat flocks of South Gujarat.
A total of 360 faecal samples of goat belonging to Ahir community were collected randomly from eight villages on monthly basis. On same day, collected samples were subjected to qualitative faecal examination and positive samples were categorized into mild, moderate and heavy infected groups. The risk factors considered for study were age, pregnancy, lactation, seasons, wet land grazing and hygiene in housing. Overall 41.11 % animals were found positive for helminth eggs and among them 24.17, 10.56 and 6.39 % of goats were mildly, moderately and heavily infected, respectively. The helminths recorded were strongyles (26.9 %), amphistomes (18.1 %), Trichuris spp. (8.1 %) and Nematoidirus spp. (3.9 %). Similarly, 72 (20 %) animals were found positive for presence of coccidia oocysts in which 13.06, 4.17 and 2.78 % were having mild, moderate and heavy infection. The Chi square test revealed that the housing quality, seasons and body condition scores (BCS) were having significant effects on helminths prevalence. The Chi square values indicated that age, hygiene of houses, seasons and BCS have significantly associated with prevalence of coccidiosis. The helminths prevalence was having significant positive correlation with lactation status and housing quality whereas it was significantly negatively correlated with prevalence of coccidia. Kendall's Correlation coefficients among various risk factors reveals that age and housing quality has significant negative correlations with coccidia infection. The gastro-intestinal (GI) parasites incidence was significantly high during the monsoon than the summer/winter season. The correlation of GI- parasitic prevalence with pregnancy status and age was not found.


Sparse representation of parametric dictionary based on fault impact matching for wheelset bearing fault diagnosis.
Wheelset bearing is one of the crucial rotating elements in the train bogie. Detection of wheelset bearing defect comes with many challenges due to complex wheel/rail excitation and the horrible working condition. The parametric dictionary sparse representation provides a practical path to detect the weak fault of wheelset bearing. However, the parametric dictionary obtained by the classical correlation filtering algorithm (CFA) is hard to match the analyzed signal's underlying fault impact characteristic. A novel parametric dictionary design algorithm named fault impact matching algorithm (FIMA) combining Orthogonal matching pursuit (OMP) is proposed to address the problem in this paper. The core of the FIMA mainly comprises two stages: partial segmentation and global analysis. Two indexes, correlation function (CF) and kurtosis, are used to comprehensively evaluate the partial and global matching degree between the Laplace wavelet and the signal. The proposed method's effectiveness is verified by the fault simulation analysis and the practical wheelset bearing fault signals (outer and inner race fault). Some comparison studies demonstrate that the proposed method outperforms the CFA-OMP, the K-SVD-OMP and some time-frequency decomposition methods, such as EWT and VMD, in detecting the bearing weak defects.


Potential Bias of Patient Payer Category on CG-CAHPS Scores and Its Impact on Physician Reimbursement.
Patient satisfaction scores play an ever increasing role in physician reimbursement. Positive scores contribute to a physician earning up to 9% reimbursement bonuses, while negative scores may contribute up to 9% reduction in reimbursement. This method of reimbursement modification is already standard within the Centers for Medicare and Medicaid Services and is quickly catching on with commercial payers. We suspect patient satisfaction scores will eventually influence reimbursement for all payers. Incentivizing patient satisfaction calls into question whether patient-specific variables exist that inherently impact survey scores without any physician input. This review specifically assesses the effect insurance status has on CG-CAHPS® scores since the survey was first implemented in 2007. Peer-reviewed articles that met inclusion criteria were graded on a scale of 0-3 according to significance of patient bias observed. Commercial insurance and Medicare are associated with higher patient satisfaction survey scores, while Medicaid and Workers' Compensation are associated with lower scores. Because most physicians have no control over the type of insurance that covers their patients, we recommend augmenting reimbursement models to account for payer mix.


Long-Term Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19 Subunit of Interleukin-23, Through Two Years: Results From a Phase III, Randomized, Double-Blind, Placebo-Controlled Study Conducted in Biologic-Naive Patients With Active Psoriatic Arthritis.
To assess long-term efficacy and safety of guselkumab, an interleukin-23 p19 subunit (IL-23p19) inhibitor, in patients with active psoriatic arthritis (PsA) from the phase III DISCOVER-2 trial. In the DISCOVER-2 trial, patients with active PsA (≥5 swollen joints and ≥5 tender joints; C-reactive protein level ≥0.6 mg/dl) despite prior nonbiologic therapy were randomized to receive the following: guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4 and then every 8 weeks; or placebo with crossover to guselkumab 100 mg every 4 weeks, beginning at week 24. Efficacy assessments included American College of Rheumatology ≥20%/50%/70% improvement criteria (ACR20/50/70), Investigator's Global Assessment (IGA) of psoriasis score of 0 (indicating complete skin clearance), resolution of enthesitis (Leeds Enthesitis Index) and dactylitis (Dactylitis Severity Score), and changes in the Sharp/van der Heijde modified radiographic scores for PsA. Clinical data (imputed as no response/no change from baseline if missing) and observed radiographic data were summarized through week 100; safety assessments continued through week 112. Of the 739 randomized and treated patients, 652 (88%) completed treatment through week 100. Across groups of guselkumab-treated patients (including those in the placebo-guselkumab crossover group), the following findings at week 100 indicated that amelioration of arthritis signs/symptoms and extraarticular manifestations was durable through 2 years: ACR20 response (68-76%), ACR50 response (48-56%), ACR70 response (30-36%), IGA score of 0 (55-67%), enthesitis resolution (62-70%), and dactylitis resolution (72-83%). Mean changes in the Sharp/van der Heijde modified score for PsA from weeks 52 to week 100 (range 0.13-0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100. Through week 112, 8% (5.8 per 100 patient-years) and 3% (1.9 per 100 patient-years) of the 731 guselkumab-treated patients had a serious adverse event or serious infection, respectively; 1 death occurred (road traffic accident). In biologic-naive PsA patients, guselkumab provided durable improvements in multiple disease domains with no unexpected safety findings through 2 years.


Mechanism of action of benzodiazepines - the GABA hypothesis.
Benzodiazepines influence on a number of neurotransmitters such as acetylcholine, catecholamines, serotonin, glycine and gamma-aminobutyric acid (GABA), but during recent years the major interest has been focused on the inhibitory transmitter GABA. This paper reviews the hypothesis that benzodiazepines act via GABA-ergic mechanisms in the central nervous system. At NIMH in Washington D.C. a novel method to measure the turnover rate of GABA in rat brain nuclei has been developed (Bertilsson et al., J. Pharmacol. Exp. Therap. 200: 277, 1977). The incorporation of 13C from glucose into glutamic acid and GABA was quantitated in stereomicroscopically isolated nuclei. Using this technique it was shown that the GABA agonist muscimol and diazepam have a similar action. Both drugs decreased the turnover rate of GABA in N. caudatus and accumbens, but not in globus pallidus (Mao et al., Biol. Psychiatry 12: 395, 1977). This gives further support to the theory that diazepam acts as a GABA-mimetic drug.


Endothelial progenitor cells and thrombosis.
The remodelling of existing vessels (i.e. angiogenesis) and the "de novo" vessel formation (i.e. vasculogenesis) occur not only during the embryonic development but also over the entire postnatal life. In 1997, the Asahara group first reported that endothelial progenitor cells circulate in peripheral blood and that they are recruited at sites of ischemia, thus proving that these cells are able to promote vasculogenesis. Since then, several different approaches have been set up to investigate endothelial progenitor cells. This review summarizes the different modalities utilized to enumerate these cells, delineates their involvement in the haemostatic pathways, and depicts their altered trafficking during cardiovascular diseases. Finally, recent observations suggesting a primary role for endothelial progenitors in particular situations such as pulmonary arterial hypertension or Philadelphia negative-myeloproliferative neoplasms are discussed.


Proteomic analysis of SUMO1-SUMOylome changes during defense elicitation in Arabidopsis.
Rapid adaptation of plants to developmental or physiological cues is facilitated by specific receptors that transduce the signals mostly via post-translational modification (PTM) cascades of downstream partners. Reversible covalent attachment of SMALL UBIQUITIN-LIKE MODIFIER (SUMO), a process termed as SUMOylation, influence growth, development and adaptation of plants to various stresses. Strong regulatory mechanisms maintain the steady-state SUMOylome and mutants with SUMOylation disturbances display mis-primed immunity often with growth consequences. Identity of the SUMO-substrates undergoing SUMOylation changes during defenses however remain largely unknown. Here we exploit either the auto-immune property of an Arabidopsis mutant or defense responses induced in wild-type plants against Pseudomonas syringae pv tomato (PstDC3000) to enrich and identify SUMO1-substrates. Our results demonstrate massive enhancement of SUMO1-conjugates due to increased SUMOylation efficiencies during defense responses. Of the 261 proteins we identify, 29 have been previously implicated in immune-associated processes. Role of others expand to diverse cellular roles indicating massive readjustments the SUMOylome alterations may cause during induction of immunity. Overall, our study highlights the complexities of a plant immune network and identifies multiple SUMO-substrates that may orchestrate the signaling. SIGNIFICANCE: In all eukaryotes, covalent linkage of the SMALL UBIQUITIN-LIKE MODIFIER (SUMOs), a process termed as SUMOylation, on target proteins affect their fate and function. Plants display reversible readjustments in the pool of SUMOylated proteins during biotic and abiotic stress responses. Here, we demonstrate net increase in global SUMO1/2-SUMOylome of Arabidopsis thaliana at induction of immunity. We enrich and identify 261 SUMO1-substrates enhanced in defenses that categorize to diverse cellular processes and include novel candidates with uncharacterized immune-associated roles. Overall, our results highlight intricacies of SUMO1-orchestration in defense signaling networks.


[Giant calculus in a diverticulum of the anterior urethra].
A case of lithiasis in a front diverticulum of the urethra in male is presented. The unusual presentation it had together with the lack of frequency was pointed out, commenting briefly the diagnostic methods and ways of treatment.


Sociodemographic Factors and Intestinal Microbiome Development in Preterm, Very Low Birth Weight Infants.
Preterm very low birth weight (VLBW) infants are at risk for intestinal morbidities and dysbiotic development of the intestinal microbiome. Despite the influence of sociodemographic factors on premature infant health outcomes, whether they shape the intestinal microbiome early in life is not clear. The objective was to explore the associations between race, sex, and socioeconomic status and the intestinal microbiome of VLBW infants during the first 4 weeks of life. This was a secondary analysis of data from an ongoing randomized trial of 79 infants ≤30 weeks' gestation and ≤1,500 g. Stool samples were collected at week 1 through week 4, frozen to -80°C and analyzed by 16S rRNA sequencing of the V4 region using Illumina MiSeq. Reads were analyzed to measure α and β diversity as well as relative abundance of bacteria in the intestinal microbiome. Of the 79 infants, 63 had at least one sample available. Twenty-three (37%) of infants were African American, 30 (48%) were male, and 44 (71%) had Medicaid insurance. There were no statistically significant (<0.05) differences in α diversity or β diversity, and the differential abundance analysis suggests limited patterns of distinction in the intestinal microbiome between non-African American and African American infants, male and female infants, and infants with maternal private or Medicaid insurance. Our results suggest race, sex, and socioeconomic status shape colonization of specific microorganisms to a limited extent. Future studies should confirm these findings and determine clinical relevance through further study of differentially abundant microorganisms and additional factors contributing to colonization patterns. · Diversity of the gut microbiome was similar between infants of varying race, sex, and socioeconomic status.. · We observed sociodemographic-linked differences in colonization of individual taxa.. · Further study is required to confirm these results and the clinical relevance of these findings..


Estimating the welfare gains from anti-retroviral therapy in Sub-Saharan Africa.
Since the start of the century, many countries in Sub-Saharan Africa have experienced large gains in life expectancy and average consumption levels. Around the same time, an unprecedented international effort has taken place to combat HIV/AIDS mortality with the expansion of anti-retroviral therapy (ART) across many of the hardest hit countries. In this paper, I estimate the impact of ART on average welfare over time in 42 countries using the equivalent consumption approach. I decompose the change in welfare to isolate the relative contribution of ART-driven improvements in life expectancy and consumption. The results indicate that ART has accounted for around 12% of total welfare growth in SSA between 2000 and 2017. In those countries most affected by HIV/AIDS, this figure rises to around 40%. Moreover, the estimates suggest that welfare in some of the worst-hit countries would have declined over time without the ART expansion.


Infectious keratitis after lamellar keratoplasty.
Infectious keratitis after lamellar keratoplasty is a potentially devastating complication that may severely limit the visual and anatomical outcomes. The deep-seated location of the infiltrates, sequestration of the pathogenic microorganisms and limited penetration of the currently available antimicrobial agents often results in delayed diagnosis that may jeopardize the management in these cases. Fungal keratitis is more common as compared with bacterial or viral keratitis and classically presents as white interface infiltrates that may not be associated with significant inflammation. Confocal microscopy may help to establish a rapid diagnosis in such cases, and anterior segment optical coherence tomography may be used to determine the extent of infection and monitor its progression. Conservative measures such as topical antimicrobials and interface irrigation with antimicrobial agents may be done. Surgical intervention in the form of partial excision/removal of the graft in endothelial keratoplasty or a full-thickness keratoplasty is often required for the effective management of deep-seated infections. Timely diagnosis and intervention may result in complete resolution of infection in both anterior lamellar and endothelial keratoplasty. Infections after anterior lamellar keratoplasty have a fair prognosis, and a clear graft with functional visual acuity may be achieved in most cases. By contrast, infections after endothelial keratoplasty have a guarded prognosis, and the presence of concomitant endophthalmitis may further complicate the graft survival and visual outcomes.


Expression of Toll-like receptors and their detection of nuclear self-antigen leading to immune activation in JSLE.
Toll-like receptors (TLRs) essential in the functioning of the immune system have been implicated in the development of autoimmunity. TLR3, 7, 8 and 9 are capable of recognizing nucleic autoantigens typical of SLE. Their expression correlates positively with disease activity in adult-onset SLE. This study aimed to determine the role of TLRs in JSLE and whether apoptotic neutrophils are a source of nuclear autoantigen being detected through TLR3, 7, 8 and 9, leading to an inflammatory response. TLR3, 7, 8 and 9 mRNA and protein expression were measured in peripheral blood mononuclear cells (PBMCs) in JSLE patients compared with JIA and non-inflammatory controls. Activation of the TLRs by JSLE serum-induced apoptotic neutrophils was detected by measuring IFN-α mRNA and protein expression, and confirmed using myeloid differentiation factor 88 (MyD88) and TIR domain-containing adapter-inducing IFN-β (TRIF) inhibitors. JSLE patients have increased TLR3, 8 and 9 mRNA and protein expression compared with controls (P < 0.05). Incubation of PBMCs with apoptotic neutrophils demonstrated a dose-response relationship for IFN-α mRNA expression. Inhibition of TLR signalling by blocking MyD88 and TRIF signalling decreased IFN-α mRNA expression in PBMCs incubated with apoptotic neutrophils (P < 0.05). This study demonstrated significantly increased TLR expression in JSLE compared with controls. Our data indicate that apoptotic neutrophils trigger TLR activation through their presentation of autoantigens. The role of TLRs in this inflammatory response was demonstrated by a dose-response relationship to apoptotic neutrophil concentration and confirmed by a decrease in IFN-α production after inhibition of TLR signalling.


[Electron microscopic investigations on the influence of lymphocytes of sensitized and non-sensitized guinea pigs on the visceral yolk sac epithelium of the rat (author's transl)].
Rats on day 19 of pregnancy were intrauterinely injected lymphocytes from guinea-pigs, sensitized or not sensitized to trophoblast antigens of the rat placenta. In the first case locally severe cytolytic effects were observed on the yolk-sac surface, in the second case--the controls--no immune reaction was evident.


The effect of increasing honey concentration on the properties of the honey/polyvinyl alcohol/chitosan nanofibers.
The effect of increasing honey concentrations from 10% to 30% within the Honey (H)/polyvinyl alcohol (P)/chitosan (CS) nanofibers was investigated. Changes in the electrospun nanofiber diameters, crystallinity, thermal behavior, porosity and antibacterial activity have been assessed using SEM, XRD, DSC, TGA, mercury porosimeter and viable cell count technique. The HPCS nanofibers were cross-linked and tested for their swelling abilities and degradation behavior. The mean diameter of HPCS nanofibers increased from 284±97nm to 464±185nm upon increasing the honey concentration from 10% to 30%. Irrespective the honey concentrations, the nanofibers have demonstrated enhanced porosity. Increasing the honey concentration resulted in a reduction in the swelling of the 1h cross-linked HPCS nanofibers containing 10% and 30% H from 520% to 100%; respectively. Degradation after 30days was reduced in the 3h cross-linked HPCS nanofibers compared to the non-crosslinked HPCS nanofibers. Enhanced antibacterial activity was achieved against both Staphylococcus aureus and Escherichia coli upon increasing the honey concentration. Changing the honey concentration and the extent of nanofiber crosslinking can be used to adjust different parameters of the HPCS nanofibers to suit their applications in wound healing and tissue engineering.


Morphological characteristics of the acromion in Fosbury flop tears and their clinical outcomes after arthroscopic rotator cuff repair.
Rotator cuff tears that have flipped upon itself and adhered medially have been recently described as Fosbury flop tears (FFT). However, there are no reports on the cause and clinical outcomes of FFT. We investigated the preoperative anatomical factors and clinical outcomes related to the occurrence of FFT. Among patients with more than two years of follow-up, 33 patients with FFT who underwent arthroscopic rotator cuff repair (ARCR) for a small-to-medium sized tear of the supraspinatus tendon alone (Group F: mean age, 63.4 ± 8.9 years) and 52 patients without FFT who underwent ARCR (Group C: mean age, 62.1 ± 7.0 years) were included. Presence of diabetes mellitus, critical shoulder angle (CSA), lateral acromial angle (LAA), acromiohumeral distance (AHD), sagittal and coronal morphologies of the acromion, JOA score, and rate of rotator cuff re-tear were evaluated. There were significantly more males in Group F (P = 0.017). There were no significant differences in age or rate of diabetic complications. The mean CSA, LAA, and AHD in the Groups F and C were respectively as follows: CSA, 33.7 ± 4.0° and 34.5 ± 3.4°; LAA, 82.1 ± 9.9° and 82.1 ± 6.9°; AHD, 10.2 ± 1.4 mm and 9.8 ± 1.4 mm. There were no significant differences between groups. The acromial morphology showed no significant difference in the sagittal plane; however, significantly more double-floor type acromia were found in the coronal plane (P < 0.001). Although the JOA score significantly improved in both groups, there was no significant difference between groups. The re-rupture rate was significantly higher in Group F than Group C (15.2% versus 1.9%; P = 0.02). Double-floor type acromia in the coronal plane was common in Group F. The location of osteophytes on the inferior surface of the acromion was believed to be associated with the occurrence of FFT. Furthermore, a high re-tear rate was observed in group F.


Preparation and anticancer actions of CuET-nanoparticles dispersed by bovine serum albumin.
Diethyldithiocarbamate-copper complex (CuET) shows promising anticancer effect; nonetheless, preclinical evaluations of CuET are hindered due to poor solubility. We prepared bovine serum albumin (BSA)-dispersed CuET nanoparticles (CuET-NPs) to overcome the shortcoming. Results from a cell-free redox system demonstrated that CuET-NPs reacted with glutathione, leading to form hydroxyl radical. Glutathione-mediated production of hydroxyl radicals may help explain why CuET selectively kills drug-resistant cancer cells with higher levels of glutathione. CuET-NPs dispersed by autoxidation products of green tea epigallocatechin gallate (EGCG) also reacted with glutathione; however, the autoxidation products eradicated hydroxyl radicals; consequently, such CuET-NPs exhibited largely compromised cytotoxicity, suggesting that hydroxyl radical is a crucial mediator of CuET anticancer activity. In cancer cells, BSA-dispersed CuET-NPs exhibited cytotoxic activities equivalent to CuET and induced protein poly-ubiquitination. Moreover, the reported powerful inhibition of CuET on colony formation and migration of cancer cells could be replicated by CuET-NPs. These similarities demonstrate BSA-dispersed CuET-NPs is identical to CuET. Thus, we advanced to pilot toxicological and pharmacological evaluations. CuET-NPs caused hematologic toxicities in mice and induced protein poly-ubiquitination and apoptosis of cancer cells inoculated in mice at a defined pharmacological dose. Given high interest in CuET and its poor solubility, BSA-dispersed CuET-NPs pave the way for preclinical evaluations.


Influence of experimental Anaplasma marginale infection and splenectomy on NTPDase and 5'nucleotidase activities in platelets of cattle.
The objective of this paper was to evaluate NTPDase and 5'-nucleotidase activities in platelets of bovine with and without spleen and infected by Anaplasma marginale. Our results demonstrate that infection along with splenectomy is able of inducing a profile of cellular protection, which showed an increase in the degradation of the nucleotides ATP and ADP by NTPDase, in addition to AMP by 5'nucleotidase to form the nucleoside adenosine in platelets, i.e., the enzymatic activities of platelets were increased in splenectomized animals when compared to non-splenectomized group. It notes that adenosine is a molecule with anti-inflammatory function. But this profile is related to a deficiency in immune signaling triggered by nucleotide ATP, which may be related to the increase in bacteremia and disability in combating the parasite in splenectomized host.


A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020.
Sentinel node biopsy is a surgical technique to explore lymph nodes for surgical staging of endometrial cancer, which has replaced full retroperitoneal lymph node dissection. However, the effectiveness of sentinel node biopsy, its value to patients, and potential harms compared with no-node dissection have never been shown in a randomized trial. Stage 1 will test recovery from surgery. Stage 2 will compare disease-free survival at 4.5 years between patients randomized to sentinel node biopsy versus no retroperitoneal node dissection. The primary hypothesis for stage 1 is that treatment with sentinel node biopsy will not cause detriment to patient outcomes (lymphedema, morbidity, loss of quality of life) and will not increase treatment-related morbidity or health services costs compared with patients treated without a retroperitoneal node dissection at 12 months after surgery. The primary hypothesis for stage 2 is that disease-free survival at 4.5 years after surgery in patients without retroperitoneal node dissection is not inferior to those receiving sentinel node biopsy. This phase III, open-label, two-arm, multistage, randomized non-inferiority trial (ENDO-3) will determine the value of sentinel node biopsy for surgical management of endometrial cancer. Patients with endometrial cancer are randomized to receive: (1) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy with sentinel node biopsy or (2) laparoscopic/robotic hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection. In stage 1, 444 patients will be enrolled to demonstrate feasibility and quality of life. If this is demonstrated, we will enroll another 316 patients in stage 2. Inclusion criteria include women aged 18 years or older with histologically confirmed endometrial cancer; clinical stage 1, who meet the criteria for laparoscopic or robotic total hysterectomy and bilateral salpingo-oophorectomy. Patients with uterine mesenchymal tumors are excluded. The endpoint for stage 1 is surgical recovery, with the proportion of patients returning to usual daily activities at 3 months post-surgery as measured with the EQ-5D. Stage 2 is disease-free survival at 4.5 years. 760 participants (both stages). Stage 1 commenced in January 2021 and is planned to be completed in December 2024 when 444 participants have completed 12 months' follow-up. Stage 2 will enroll a further 316 participants for a total of 760 patients. NCT04073706.


Components of predation intensity in the low zone of the New England rocky intertidal region.
Predation intensity often increases along local gradients of decreasing environmental rigor. Assuming factors such as productivity and heterogeneity do not change along such gradients, potential factors responsible for this pattern include: (1) increased effectiveness per individual predator, (2) increased numbers of individual predators, (3) increased numbers of predator species of the same general morphological attributes, and (4) increased numbers of predator species of different general morphological attributes. I term these factors the components of predation intensity.In relatively protected low rocky intertidal regions of northern New England, community structure depends in part on the foraging activities of up to six species (three general types) of predators (Lubchenco and Menge 1978). These include three species of crab, two species of seastars, and one thaidid gastropod. This predator guild prevents mussel and barnacle populations from outcompeting Chondrus crispus. This red alga dominates space when predators are present, but is outcompeted by mussels when predators are excluded.Prey consumption rates (mg per predator individual per hr or mg g-1 hr-1) in field experiments indicate that the rank from most to least effective predator type is crabs, seastars, and the gastropod. Statistically significant variations occur between predator types (largest differences), species of a given type, and individuals of a species (smallest differences). Estimates of the relative contribution of each species to total predation intensity in the low zone at several sites indicate that each predator species is a major predator at one or more sites. Thus, if one predator species in this guild becomes scarce, the other predators may increase their effects and reduce variation in the total predation intensity exerted by the guild. Comparisons with other systems suggest that increased diversity of types of foraging characteristics in predatory guilds is an important component of increased predation intensity along gradients of decreased environmental rigor.


Macular structure parameters as an automated indicator of paracentral scotoma in early glaucoma.
To evaluate the predictive ability of macular parameters defined in the significance map created using spectral-domain optical coherence tomography (SD-OCT) for paracentral visual field defects in early glaucoma. Prospective comparative study. We studied 78 early-glaucomatous eyes of 78 patients, who underwent SD-OCT and standard automated perimetry 10-2. Macular layer parameters included the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) + inner plexiform layer (IPL), and RNFL + GCL + IPL. The minimal distance between the area with abnormal (P < 1%) thickness and foveal center was defined as the shortest distance. A wider area of an abnormally thinned (<1%) region, within either an inferior or a superior hemicircle with a diameter of 6 mm centered at the fovea, was defined as the macular abnormal area. A circumpapillary RNFL parameter was defined in its 36 sectors. Areas under the receiver operating characteristic curves (ROCs) were calculated to discriminate between eyes with (n = 39) and without (n = 39) paracentral visual field defects in the central 5 degrees. Measurement reproducibility was almost perfect in the macular parameters at P < 1% (intraclass correlation, 0.907-0.942). Areas under the ROC were significantly higher (P ≤ 0.01) in the macular parameters (0.870-0.930), including the shortest distance of GCL + IPL/RNFL + GCL + IPL, and the macular abnormal area of RNFL/GCL + IPL/RNFL + GCL + IPL than in the circumpapillary RNFL parameter (0.676). When specificity was fixed at ≥90%, the shortest distance of GCL + IPL (area under the ROC = 0.874) and the macular abnormal area of RNFL (area under the ROC = 0.894) showed sensitivities greater than 50%. Macular structural parameters defined on an SD-OCT significance map may be potentially useful predictors of the presence of paracentral scotoma.


Breakthrough of lignin valorization: A novel alcohol-dichoromethane binary mixture solvent for lignin dissolution with excellent properties.
A novel binary solvent system consisting of alcohols (e.g., methanol, ethanol, isopropanol) and dichloromethane was developed as an efficient dissolution system for dissolving various types of lignin. It was found that in this dissolution system, adjusting the volume ratio of alcohol and dichloromethane will significantly affect the solubility of lignin. At the same time, this study proposed that the reason why the solvent can dissolve lignin was the hydrophobic skeleton and hydrophilic groups can be solvated by dichloromethane and alcohols respectively, which significantly promoted the dissolution of lignin. Furthermore, the solvent did not significantly alter the structure of the lignin. The proposed novel solvent is simple, efficient, versatile and flexible, can adapt to the high diversity of lignin, and has broad application prospects.


Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study.
Objectives: Non-alcoholic fatty liver disease (NAFLD) currently affects a quarter of the global population. Systemic inflammation, metabolic syndrome, and coronary artery disease, all conditions associated with NAFLD, have also been related to cognitive dysfunction in older age. The present study aimed to investigate the relationship between NAFLD risk and a dementia diagnosis in a large population-based sample aged > 65 years. Methods: We selected 1,542 participants (723 men) from the Salus in Apulia Study. To assess the risk of fat distribution in the liver, we used the Fatty Liver Index (FLI). Dementia was diagnosed according to the American Psychiatric Association criteria (DSM-5). Results: The overall prevalence of dementia was 8.5% [95% confidence interval (CI): 7-10%]. Subjects with dementia were older [effect size (ES): -0.89, 95% CI: -1.07 to -0.70], had a lower level of education (ES:0.88, 95% CI:0.69-1.06), higher levels of gamma-glutamyl transferase (ES: -0.21, 95% CI: -0.39 to -0.03), lower levels of total cholesterol (ES: -0.24, 95% CI: -0.42 to -0.06) and low-density lipoprotein cholesterol (ES: -0.20, 95% CI: -0.38 to 0.02), and a higher FLI (ES: -0.22, 95% CI: -0.39 to -0.04). In the logistic regression model adjusted for age, sex, education, hypertension, diabetes mellitus, alcohol consumption, smoking habits, stroke, cholesterol, and Apo-E, a dementia diagnosis was positively associated with FLI > 60 [odds ratio (OR):1.81; standard error (SE): 0.53; 95% CI: 1.02-3.21]. Conclusion: Our findings suggested that an increased NAFLD risk may be associated to dementia and cognitive decline in older age. Considering the high NAFLD prevalence, the possible adverse disease effects on cognitive performance pose a health problem with significant social and economic implications.


Long-term results of a staged approach: continent urinary diversion in preparation for renal transplantation.
We provide the long-term results of renal transplantation into continent urinary intestinal reservoirs as a planned 2-stage procedure. Between November 1990 and January 2009, 18 patients underwent cadaveric or living related renal transplantation into continent urinary reservoirs (continent cutaneous diversion 16, orthotopic substitution 2). All patients were prospectively followed. Of these patients 15 are currently free of dialysis. At a mean followup of 89.2 months (range 2 to 188) 13 patients had a serum creatinine ranging from 0.6 to 3.1 mg/dl (mean 1.49) after the first transplantation. Two patients underwent a second transplantation 12 and 122 months after loss of the transplant for renal vein thrombosis and chronic allograft dysfunction, respectively. Two additional patients had to resume hemodialysis 62 and 109 months after renal transplantation. The second transplantation was delayed mainly due to compliance problems. One patient died of fulminant septicemia after laparotomy elsewhere for bowel obstruction with normal renal function before that episode. The continence mechanism needed correction in 3 patients, and 2 further revisions were required for ureteral kinking and lymphocele. The patients with orthotopic substitution (2) voided to completion and showed complete continence. All patients with cutaneous diversion were continent day and night with easy catheterization. This study is among the largest single series to date of renal transplantation into continent urinary diversions. Long-term followup confirms that this approach is a safe and socially well accepted treatment option in carefully selected patients.


Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle.
Complementary DNA clones corresponding to human brain nitric oxide (NO) synthase have been isolated. The deduced amino acid sequence revealed an overall identity with rat brain NO synthase of about 93% and contained all suggested consensus sites for binding of the co-factors. The cDNA transfected COS-1 cells showed significant NO synthase activity with the typical co-factor requirements. Unexpectedly, messenger RNA levels of this isoform of NO synthase was more abundant in human skeletal muscle than human brain. Moreover, we detected high NO synthase activity and the expressed protein in human skeletal muscle by Western blot analysis, indicating a possible novel function of NO in skeletal muscle.


Humoral stimulation of cell proliferation in small bowel after transection and resection in rats.
Possible humoral involvement in the control of postresectional intestinal adaptation was tested in individual rats and in pairs of rats connected in vascular parabiosis for 48 hr. In individual rats, transection of the jejunum produced transient mucosal hyperplasia in the mid and distal small intestine, independent of the effect of laparotomy and of handling the bowel. Jejunal resection caused more intense and sustained distal hyperplasia, with increases in midbowel RNA content (38%), DNA content (16%), and DNA specific activity (68%) over values 48 hr after transection. In parabiotic rats, both transection and resection of the jejunum in one partner stimulated mucosal uptake of [H]TdR in the intact parabiont; increments of 59 to 128% in total radioactivity and in specific activity of DNA were found in the mid and distal small intestine of the intact parabiont. Because only rats actually undergoing abdominal operations had higher mucosal nucleic acid contents than their parabiotic partners, the transmitted response was weaker than the direct response. Systemic factors as well as local (topical) stimulators appear to be involved in adaptation of the shortened gut.


Spectroscopic investigations on the simulated solar light induced photodegradation of 4-nitrophenol by using three novel copper(II) porphyrin-TiO2 photocatalysts.
Three porphyrins containing different functional groups (-OH, C-O2C2H5, -COOH), 5-(4-hydroxy) phenyl-10,15,20-triphenyl porphyrin (1a), 5-(4-ethylacetatatomethoxy) phenyl-10,15,20-triphenyl porphyrin (1b), 5-(4-carboxylatomethoxy) phenyl-10,15,20-triphenyl porphyrin (1c), were synthesized and characterized spectroscopically. The CuPp(2a, 2b, 2c)-TiO2 photocatalysts were then prepared and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis-DRS), Fourier-transform infrared spectroscopy (FT-IR). The photocatalytic activities of the photocatalysts were investigated by carrying out the photodegradation of 4-nitrophenol in aqueous solution under simulated solar irradiation. It was found that the CuPp(2a, 2b, 2c)-TiO2 enhanced the photocatalytic efficiency of bare TiO2 in photodegrading the 4-NP due to the interaction between CuPp(2a, 2b, 2c) and TiO2, resulted in the enhancement of the photogenerated electron-hole separation. The reasons of this enhanced photocatalytic activity were also discussed. Based on the present study, it could be considered as a promising photocatalyst for the further industrial application.


Impact of SGLT2 inhibitors on the mechanisms of myocardial dysfunction in type 2 diabetes: A prospective non-randomized observational study in patients with type 2 diabetes mellitus without overt heart disease.
This prospective observational study evaluated the possible mechanisms of action of SGLT2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2DM) without overt heart disease. The study was designed to verify whether SGLT2i impact biomarkers of: myocardial stress-NT-proBNP, inflammation-high sensitivity C-reactive protein, oxidative stress -myeloperoxidase, functional and structural echocardiographic parameters, in patients with T2DM on metformin (heart failure stages A and B) who needed treatment intensification with a second antidiabetic agent. The patients were divided in two groups - the ones planned to receive SGLT2i or DPP-4 inhibitor (except saxagliptin). At baseline, and after six months of therapy, 64 patients underwent blood analysis, physical and echocardiography examination. There were no significant differences between the two groups in terms of biomarkers of myocyte and oxidative stress, inflammation and blood pressure. Body mass index, triglycerides, aspartate aminotransferase, uric acid, E/E', deceleration time and systolic pressure in the pulmonary artery significantly decreased, while stroke volume, indexed stroke volume, high-density lipoprotein, hematocrit and hemoglobin significantly increased in the group on SGLT2i. According to the results, SGLT2i mechanisms of action comprise rapid changes in body composition and metabolic parameters, reduced cardiac load and improvement in diastolic and systolic parameters.


Validity of the motor observation questionnaire for teachers as a screening instrument for children at risk for developmental coordination disorder.
This study investigates validity of the Motor Observation Questionnaire for Teachers (MOQ-T) in 182 children aged 5-10years, 91 children referred for motor problems to a rehabilitation center and 91 comparison children. Performance on the MOQ-T was compared to performance on the Movement Assessment Battery for Children (M-ABC) and the Developmental Coordination Disorder Questionnaire (DCD-Q). Significant correlations were obtained between the MOQ-T and the DCD-Q (r=-.63), and the MOQ-T and the M-ABC (r=.57). The MOQ-T discriminated between children at risk for DCD and comparison children. Sensitivity of the MOQ-T was 80.5%, specificity 62% with the M-ABC as 'gold standard'. These results support the validity of the MOQ-T as a screening instrument for identification of children at risk for DCD.


Size-segregated source identification of water-soluble and water-insoluble metals and trace elements of coarse and fine PM in central Los Angeles.
In this study, the water-solubility and sources of metals and trace elements in both fine and coarse particulate matter (PM) were investigated in Central Los Angeles. Sampling was performed in the winter, spring, and summer of 2022 at the Particle Instrumentation Unit (PIU) of the University of Southern California located in the proximity of I-110 freeway. Both fine and coarse PM samples were collected using Personal Cascade Impactors (PCIS) and chemically analyzed to determine their water-soluble and water-insoluble metal content. Principal Component Analysis (PCA) and Multiple Linear Regression (MLR) were used to determine the sources of soluble and insoluble metals and obtain their contributions to total metal concentration. Our results indicate that the water-solubility of most of the metals is higher in the fine size fraction compared to the coarse fraction. Seasonal variations in the water solubility of selected metals for both coarse and fine fractions were observed, with higher water-soluble metal concentrations in summer for several species (e.g., Fe, S, Pb, Cu, La, Ni, and Al), possibly due to higher photochemical processing, while in winter, almost all species exhibited higher insoluble fraction concentrations. The PCA and MLR analyses results showed that tire and brake wear was the most significant contributor to the total metals for both fine soluble and insoluble portions, accounting for 35% and 75% of the total metals, respectively. Combustion sources also contributed substantially to water-soluble metals for fine and coarse size ranges, representing 40% and 32% of the total metal mass, respectively. In addition, mineral dust and soil and re-suspended dust were identified as the highest contributors to coarse metals. The MLR analysis also revealed that secondary aerosols contributed 11% to the fine water-soluble metals. Our results suggest that non-tailpipe emissions significantly contribute to both coarse and fine PM metals in the Central Los Angeles region.


Analysis of the biological and molecular properties of phencyclidine-like compounds by chemometrics.
The quantitative structure-activity relationships (QSAR's) of 3 series of arylcyclohexylamines have been investigated using computational chemistry and multivariate statistics. Principal component analysis of the aromatic ring data set demonstrated some clustering of activity categories. Biological activity of the cyclohexane ring data set was correlated with molar refractivity. These findings may be useful for predicting the activity of novel neuroprotective agents.


Impact of Socioeconomic Status on Major Amputation in Patients with Peripheral Vascular Disease and Diabetes Mellitus.
Both peripheral vascular disease (PVD) and diabetes mellitus (DM) are leading causes of lower extremity amputation. The Area Deprivation Index (ADI) is a tool used to estimate socioeconomic status (SES) based off a person's 9-digit zip code, and this value has been shown to correlate with poor health outcomes. We sought to understand the effect of SES on major amputation in diabetic patients with PVD in a single healthcare system. All patients presenting to a single healthcare system with dual diagnosis of PVD and DM from January 2012 to December 2017 were identified using International Classification of Diseases (ICD) 9/10 codes. Patients undergoing major amputation (below-knee and above-knee) were identified by Current Procedural Terminology (CPT) codes and compared to those who did not have amputation. The ADI score and comorbid disease processes were identified. The Mann-Whitney U-test was performed to compare ADI scores between the amputation and nonamputation groups. Categorical variables were analyzed using the Chi-squared or Fisher's exact test, and t-tests were used for continuous variables. A logistic regression was performed to test the association between SES and amputation status. A total of 2,009 patients were identified, of which 85 underwent major amputation. After adjusting for comorbidities, patients in the amputation group had higher ADI scores as compared to those who did not have amputation (median ADI score 8 vs. 6, P < 0.05). Logistic regression modeling demonstrated an Odds Ratio of 1.10 (95% confidence interval: 1.01-1.19), indicating the odds of being in the amputation group are increased by 10% for every 1-point increase in the ADI score. After controlling for comorbidities, patients with PVD and DM residing in neighborhoods with lower SES have increased odds of undergoing major lower-limb amputation than those from neighborhoods with higher SES despite receiving care at the same healthcare system. Further study is warranted to determine factors contributing to this difference.


Veterans Administration Cooperative Studies Project No. 147. Part IX: A comparison of the mechanical properties of several alternative metal ceramic alloys cast in clinical and research laboratories.
Comparison of mechanical properties of five metal ceramic alloys cast in clinical and research laboratories resulted in significant differences. Tested alloys included one Au-Pd (control), one Pd-Ag, and three Ni-Cr. Mechanical properties included strength, elongation, and microhardness. Tensile bars were torch cast simultaneously with restorations in the clinical laboratory and induction cast by using a preformed design in the research laboratory. Mechanical properties of most alloys showed larger variations when cast in the clinical laboratory. In the clinical laboratory the Au-Pd alloy showed significantly higher values for all properties. One Ni-Cr alloy was not significantly affected by environment for all properties. The remaining alloys were significantly affected for some properties by environment. The different laboratories had no greater or lesser effect on the base metals as a group than on the noble metals. Variation in handling, spruing, casting, and specimen size may account for some of the differences between laboratories.


De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma.
Mutations affecting isocitrate dehydrogenase (IDH) enzymes are prevalent in glioma, leukemia, and other cancers. Although mutant IDH inhibitors are effective against leukemia, they seem to be less active in aggressive glioma, underscoring the need for alternative treatment strategies. Through a chemical synthetic lethality screen, we discovered that IDH1-mutant glioma cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We developed a genetically engineered mouse model of mutant IDH1-driven astrocytoma and used it and multiple patient-derived models to show that the brain-penetrant DHODH inhibitor BAY 2402234 displays monotherapy efficacy against IDH-mutant gliomas. Mechanistically, this reflects an obligate dependence of glioma cells on the de novo pyrimidine synthesis pathway and mutant IDH's ability to sensitize to DNA damage upon nucleotide pool imbalance. Our work outlines a tumor-selective, biomarker-guided therapeutic strategy that is poised for clinical translation.


[The effect of the antibiotic edeine on tRNA interaction with A, P and E sites of Escherichia coli 70S ribosomes].
Edeine inhibits poly(U)-dependent binding of tRNAPhe to the P and A sites simultaneously, both on 30S subunits and 70S ribosomes. Hence, edeine cannot be considered as antibiotic, "complementary" to tetracycline for selective adsorption of tRNA only to the P or to the A site. Further, edeine decreases the affinity constant of tRNAPhe for the P-site by more than two orders of magnitude, no matter poly(U) is present or not. Neither edeine nor tetracycline affect interaction of deacylated tRNAPhe with the E-site of E. coli 70S ribosomes.


COV-MobNets: a mobile networks ensemble model for diagnosis of COVID-19 based on chest X-ray images.
The medical profession is facing an excessive workload, which has led to the development of various Computer-Aided Diagnosis (CAD) systems as well as Mobile-Aid Diagnosis (MAD) systems. These technologies enhance the speed and accuracy of diagnoses, particularly in areas with limited resources or remote regions during the pandemic. The primary purpose of this research is to predict and diagnose COVID-19 infection from chest X-ray images by developing a mobile-friendly deep learning framework, which has the potential for deployment in portable devices such as mobile or tablet, especially in situations where the workload of radiology specialists may be high. Moreover, this could improve the accuracy and transparency of population screening to assist radiologists during the pandemic. In this study, the Mobile Networks ensemble model called COV-MobNets is proposed to classify positive COVID-19 X-ray images from negative ones and can have an assistant role in diagnosing COVID-19. The proposed model is an ensemble model, combining two lightweight and mobile-friendly models: MobileViT based on transformer structure and MobileNetV3 based on Convolutional Neural Network. Hence, COV-MobNets can extract the features of chest X-ray images in two different methods to achieve better and more accurate results. In addition, data augmentation techniques were applied to the dataset to avoid overfitting during the training process. The COVIDx-CXR-3 benchmark dataset was used for training and evaluation. The classification accuracy of the improved MobileViT and MobileNetV3 models on the test set has reached 92.5% and 97%, respectively, while the accuracy of the proposed model (COV-MobNets) has reached 97.75%. The sensitivity and specificity of the proposed model have also reached 98.5% and 97%, respectively. Experimental comparison proves the result is more accurate and balanced than other methods. The proposed method can distinguish between positive and negative COVID-19 cases more accurately and quickly. The proposed method proves that utilizing two automatic feature extractors with different structures as an overall framework of COVID-19 diagnosis can lead to improved performance, enhanced accuracy, and better generalization to new or unseen data. As a result, the proposed framework in this study can be used as an effective method for computer-aided diagnosis and mobile-aided diagnosis of COVID-19. The code is available publicly for open access at https://github.com/MAmirEshraghi/COV-MobNets .


Epicardial adipose tissue is associated with extent of pneumonia and adverse outcomes in patients with COVID-19.
We sought to examine the association of epicardial adipose tissue (EAT) quantified on chest computed tomography (CT) with the extent of pneumonia and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). We performed a post-hoc analysis of a prospective international registry comprising 109 consecutive patients (age 64 ± 16 years; 62% male) with laboratory-confirmed COVID-19 and noncontrast chest CT imaging. Using semi-automated software, we quantified the burden (%) of lung abnormalities associated with COVID-19 pneumonia. EAT volume (mL) and attenuation (Hounsfield units) were measured using deep learning software. The primary outcome was clinical deterioration (intensive care unit admission, invasive mechanical ventilation, or vasopressor therapy) or in-hospital death. In multivariable linear regression analysis adjusted for patient comorbidities, the total burden of COVID-19 pneumonia was associated with EAT volume (β = 10.6, p = 0.005) and EAT attenuation (β = 5.2, p = 0.004). EAT volume correlated with serum levels of lactate dehydrogenase (r = 0.361, p = 0.001) and C-reactive protein (r = 0.450, p < 0.001). Clinical deterioration or death occurred in 23 (21.1%) patients at a median of 3 days (IQR 1-13 days) following the chest CT. In multivariable logistic regression analysis, EAT volume (OR 5.1 [95% CI 1.8-14.1] per doubling p = 0.011) and EAT attenuation (OR 3.4 [95% CI 1.5-7.5] per 5 Hounsfield unit increase, p = 0.003) were independent predictors of clinical deterioration or death, as was total pneumonia burden (OR 2.5, 95% CI 1.4-4.6, p = 0.002), chronic lung disease (OR 1.3 [95% CI 1.1-1.7], p = 0.011), and history of heart failure (OR 3.5 [95% 1.1-8.2], p = 0.037). EAT measures quantified from chest CT are independently associated with extent of pneumonia and adverse outcomes in patients with COVID-19, lending support to their use in clinical risk stratification.


Validation of the simplified Chinese version of PROMIS Parent Proxy-25 Profile in parents of children with cancer.
To determine the psychometric properties of the Patient-reported Outcomes Measurement Information System Parent Proxy-25 Profile (PROMIS-25) in a sample of Chinese parents of children with cancer. A cross-sectional sample (N = 148) of parents with children aged 5-17 years living with cancer was recruited. Each participant completed sociodemographic and clinical questionnaires and PROMIS-25. The flooring and ceiling effects were calculated. Reliability was determined by the Cronbach's alpha and split-half coefficient. Factor structure was examined by factor analysis. Model fit and graphical plots were assessed to test the assumptions of Rasch model-based item response theory (IRT). Differential item functioning (DIF) was assessed in terms of gender, age, and treatment stage. PROMIS-25 demonstrated some flooring and ceiling effect, excellent reliability (Cronbach's α > 0.7 for all six domains), and the six-domain factor structure was supported. The IRT assumptions were met in terms of unidimensionality, local independence, monotonicity, and measurement equivalence with acceptable DIF in terms of gender, age, diagnosis, and treatment stage. PROMIS-25 is a highly reliable and valid instrument for evaluating children with cancer that assesses important health-related quality of life domains of child cancer. Chinese parents of children with cancer and healthcare providers could use PROMIS-25 to assess the symptoms of children.


Orbital meningioma with a granular cell component in a dog, with extracranial metastasis.
A meningioma with a significant component of granular cells is described in the left ocular orbit of a 5-year-old male Golden retriever dog that presented with exophthalmos. The neoplastic mass surrounded the optic nerve. Microscopically, the tumour was characterized by nests of large, round to polygonal cells, variable in size, with eccentric nuclei and abundant eosinophilic cytoplasm, containing PAS-positive granules. In focal areas, cells were smaller and occasionally formed whorl-like structures. Immunohistochemical analysis revealed that neoplastic cells reacted positively for vimentin and, with less intensity, for neuron specific enolase and S-100, whereas they were negative for glial fibrillary acidic protein and cytokeratins. Metastatic growths, formed by similar cells, were seen in the lung and heart.


Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia.
Treatments for hematological malignancies have improved considerably over the past decade, but the growing therapeutic arsenal has not benefited adult T-cell leukemia (ATL) patients. Oncolytic viruses such as vesicular stomatitis virus (VSV) have recently emerged as a potential treatment of solid tumors and leukemias in vitro and in vivo. In the current study, we investigated the ability of VSV to lyse primary human T-lymphotropic virus type 1 (HTLV-1)-infected T-lymphocytes from patients with ATL. Ex vivo primary ATL cells were permissive for VSV and underwent rapid oncolysis in a time-dependent manner. Importantly, VSV infection showed neither viral replication nor oncolysis in HTLV-1-infected, nonleukemic cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and in naive CD4(+) T-lymphocytes from normal individuals or in ex vivo cell samples from patients with chronic lymphocytic leukemia (CLL). Interestingly, activation of primary CD4(+) T-lymphocytes with anti-CD3/CD28 monoclonal antibody, and specifically with anti-CD3, was sufficient to induce limited viral replication and oncolysis. However, at a similar level of T-cell activation, VSV replication was increased fourfold in ATL cells compared to activated CD4(+) T-lymphocytes, emphasizing the concept that VSV targets genetic defects unique to tumor cells to facilitate its replication. In conclusion, our findings provide the first essential information for the development of a VSV-based treatment for ATL.


Roles for neuregulins in human cancer.
The human epidermal growth factor (EGF) receptor (HER) family of receptor tyrosine kinases has frequently been implicated in cancer. Apart from overexpression or mutation of these receptors, also the aberrant autocrine or paracrine activation of HERs by EGF-like ligands may be important in cancer progression. Neuregulins constitute a family of EGF-like ligands that bind to HER3 or HER4, preferably forming heterodimers with the orphan receptor HER2. Mesenchymal neuregulin typically serves as a pro-survival and pro-differentiation signal for adjacent epithelia. Disruption of the balance between proliferation and differentiation, because of autocrine production by the epithelial cells, increased sensitivity to paracrine signals or disruption of the spatial organization, may lead to constitutive receptor activation, in the absence of receptor overexpression. Consequently, the analysis of ligand expression and/or activated receptors in tumor samples may broaden the group of patients that can benefit from targeted therapies.


Long-Term Outcomes of Total Hip Arthroplasty With Transverse Subtrochanteric Shortening Osteotomy and Modular Stem in Crowe IV Developmental Dysplasia.
The reconstruction of high dislocation related to developmental dysplasia of the hip (DDH) remains challenging for joint surgeons. The aim of this study is to evaluate the rate of union, the revision rate, functional scores, and complications in patients with Crowe IV DDH treated with total hip arthroplasty, transverse subtrochanteric shortening osteotomy, and modular stem in an average 10-year follow-up. Twenty-eight patients (33 hips) with Crowe IV DDH who were operated on between 2008 and 2013 were followed. All patients underwent uncemented total hip arthroplasty with transverse subtrochanteric shortening osteotomy and anatomical acetabular cup implantation. The mean age was 36.6 years, and the mean follow-up period was 121 months. Clinical and radiological outcomes were evaluated. The mean Harris Hip Score significantly improved from 47.0 preoperatively to 89.6 postoperatively. The mean limb length discrepancy was significantly reduced from 3.8 to 0.8 cm. The mean osteotomy union time was 6.8 months. At the mean follow-up of 121 months, there were 3 cases of postoperative dislocation, 2 cases of intraoperative fracture, and 1 case of posterior tibial venous thrombosis. No revision occurred, and no signs of component loosening or migration were observed at the last follow-up. Crowe IV DDH patients treated with transverse subtrochanteric shortening osteotomy, modular stem, and anatomic acetabular component insertion can have satisfactory and reliable 10-year clinical outcomes.


Outcomes of esophagectomy for esophageal achalasia in the United States.
While the outcomes after Heller myotomy have been extensively reported, little is known about patients with esophageal achalasia who are treated with esophagectomy. This was a retrospective analysis using the Nationwide Inpatient Sample over an 11-year period (2000-2010). Patients admitted with a primary diagnosis of achalasia who underwent esophagectomy (group 1) were compared to patients with esophageal cancer who underwent esophagectomy (group 2) during the same time period. Primary outcome was in-hospital mortality. Secondary outcomes included length of stay, postoperative complications, and total hospital charges. A propensity-matched analysis was conducted comparing the same outcomes between group 1 and well-matched controls in group 2. Nine hundred sixty-three patients with achalasia and 18,003 patients with esophageal cancer underwent esophagectomy. The propensity matched analysis showed a trend toward a higher mortality in group 2 (7.8 vs. 2.9 %, p = 0.08). Postoperative length of stay and complications were similar in both groups. Total hospital charges were higher for the achalasia group ($115,087 vs. $99, 654.2, p = 0.006). This is the largest study to date examining outcomes after esophagectomy in patients with achalasia. Based on our findings, esophagectomy can be considered a safe option, and surgeons should not be hindered by a perceived notion of prohibitive operative risk in this patient population.


Elevated creatine kinase and malignancy.
Increased serum levels of CK isoenzymes variously signal heart, brain, or skeletal muscle damage. They may also be markers for advanced tumors with poor prognosis.


The excess volatility puzzle explained by financial noise amplification from endogenous feedbacks.
The arguably most important paradox of financial economics-the excess volatility puzzle-first identified by Robert Shiller in 1981 states that asset prices fluctuate much more than information about their fundamental value. We show that this phenomenon is associated with an intrinsic propensity for financial markets to evolve towards instabilities. These properties, exemplified for two major financial markets, the foreign exchange and equity futures markets, can be expected to be generic in other complex systems where excess fluctuations result from the interplay between exogenous driving and endogenous feedback. Using an exact mapping of the key property (volatility/variance) of the price diffusion process onto that of a point process (arrival intensity of price changes), together with a self-excited epidemic model, we introduce a novel decomposition of the volatility of price fluctuations into an exogenous (i.e. efficient) component and an endogenous (i.e. inefficient) excess component. The endogenous excess volatility is found to be substantial, largely stable at longer time scales and thus provides a plausible explanation for the excess volatility puzzle. Our theory rationalises the remarkable fact that small stochastic exogenous fluctuations at the micro-scale of milliseconds to seconds are renormalised into long-term excess volatility with an amplification factor of around 5 for equity futures and 2 for exchange rates, in line with models including economic fundamentals explicitly.


Beneficial effects of ventromedial hypothalamus (VMH) lesioning on function and morphology of the liver after hepatectomy in rats.
Liver has a high regenerative capacity and restores its mass and function shortly after partial hepatectomy through increased proliferation and metabolic modification of hepatocytes. The proliferation of hepatocytes can be triggered by its mass reduction after hepatectomy or by the neural factors including lesioning of the ventromedial hypothalamus (VMH). In the present study, we examined the effect of VMH lesioning on liver regeneration in hepatectomized rats by evaluating liver function and morphology. We found that functional deficits caused by partial hepatectomy [prolonged prothrombin time (PT), increased indocyanine green (ICG) retention, and decrease in PAS (periodic Acid-Schiff staining)-positive hepatocytes] were restored by VMH lesioning at 1 week after the surgery, whereas these alterations disappeared at 4 weeks. Morphologically, lipid microdroplets, which are considered to be important for maintaining contiguous liver function via supplying fuel for cell proliferation, were found to accumulate in hepatocytes of the hepatectomized rats at early period (1 day) after partial hepatectomy. Interestingly, such lipid microdroplets were also detected in the VMH lesioned rats and the more abundantly in the VMH lesioned, hepatectomized rats up to 1 week after the surgery. In conclusion, our results suggest that VMH lesioning in rats promotes recovery of liver anatomically and functionally after partial hepatectomy by promoting cell proliferation process.


Interaction between adenosine A 2B-receptors and alpha2-adrenoceptors on the modulation of noradrenaline release in the rat vas deferens: possible involvement of a group 2 adenylyl cyclase isoform.
In the prostatic portion of rat vas deferens, activation of adenosine A 2B-receptors, beta2-adrenoceptors, adenylyl cyclase or protein kinase A caused a facilitation of noradrenaline release. Blockade of alpha2-adrenoceptors with yohimbine (1 microM) attenuated the facilitation mediated by adenosine A 2B-receptors and by direct activation of adenylyl cyclase with forskolin but not that mediated by beta2-adrenoceptors or by direct activation of protein kinase A with 8-bromoadenosine-3',5'-cyclicAMP. The adenosine A 2B- and the beta2-adrenoceptor-mediated facilitation was prevented by the adenylyl cyclase inhibitors, 2',5'-dideoxy-adenosine (3 microM) and 9-cyclopentyladenine (100 microM), at concentrations that also attenuated the release enhancing effect of forskolin, but were not changed by the phospholipase C inhibitor 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U-73122, 1 microM). Facilitation of noradrenaline release mediated by adenosine A 2B-receptors was also attenuated by activation of protein kinase C with the phorbol ester 12-myristate 13-acetate (1 microM) and by inhibition of Gbetagamma subunits with an anti-betagamma peptide; facilitation mediated by beta2-adrenoceptors was mainly attenuated by the calmodulin inhibitor calmidazolium (10 microM) and by the calmodulin kinase II inhibitor (N-[2-[N-(4-chlorocinnamyl)-N-methylaminomethyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzene-sulfonamide phosphate (KN-93, 5 microM). The results suggest that adenosine A 2B- but not beta2-adrenoceptor-mediated facilitation of noradrenaline release is enhanced by an ongoing activation of alpha2-adrenoceptors. They further suggest that adenosine A 2B-receptors and beta2-adrenoceptors are coupled to distinct adenylyl cyclase isoforms what may explain the different influence of alpha2-adrenoceptor signalling pathway on the facilitatory effects mediated by the two adenylyl cyclase coupled receptors.


Impact of AccuLevel on treatment of acute asthma.
Study of the impact of rapid availability of theophylline concentrations on emergency treatment of acute asthma disclosed use of AccuLevel in 50 children significantly shortened the time required to reach concentrations of at least 10 micrograms/mL and shortened time spent in the emergency room as compared with 50 children in whom serum concentrations were measured only by EMIT.


Tanycyte specific ablation of diacylglycerol lipase alpha stimulates the hypothalamic-pituitary-thyroid axis by decreasing the endocannabinoid mediated inhibition of TRH release.
In addition to the hypophysiotropic thyrotropin-releasing hormone (TRH)-synthesizing neurons, a glial cell type, the tanycytes, also play a role in the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. Tanycytes modulate the feedback regulation of the axis by regulating the local thyroid hormone availability in the median eminence where the hypophysiotropic axons terminate. Recently, we showed that tanycytes produce diacylglycerol lipase alpha (DAGLα), the synthesizing enzyme of the endocannabinoid 2-arachidonoylglycerol (2-AG) that inhibits the release of TRH from the hypophysiotropic terminals in median eminence explants. To determine the importance of the endocannabinoid production of tanycytes, adult male Rax-CreERT2//DAGLαfl/fl mice were treated with tamoxifen to induce a tanycyte specific decrease of DAGLα expression (T-DAGLα KO). The effect of this genetic manipulation on the activity of the HPT axis was determined. Tanycyte specific decrease of DAGLα expression resulted in an approximately 2-fold increase of TSHβ mRNA level that was accompanied by increased levels of circulating free T4. The TRH mRNA level was, however, not influenced by the genetic manipulation. In addition to the effects on the HPT axis, the T-DAGLα KO mice showed increased fat mass ratio and decreased blood glucose levels. These data indicate that when endocannabinoid release of tanycytes is decreased, the disinhibition of the TRH release induces increased TSH synthesis and higher circulating T4 levels. Thus it suggests that in wild-type mice, tanycytes exert a tonic inhibitory effect on the TRH release of hypophysiotropic axons. Furthermore, the endocannabinoid release of tanycytes also influences glucose homeostasis and fat deposition.


Senior obstetric-gynecologic residents' perceptions of their surgical training, experiences and skill.
Senior obstetric and gynecologic residents' self-perceptions of surgical skill seem to be unrelated to the kinds of didactic experiences received or to the number of basic gynecologic procedures performed during training. These data offer further support for the need for a comprehensive reevaluation of the components of gynecologic surgical curricula; the cognitive, behavioral and psychomotor educational objectives of such training; and the methods by which the outcomes for these objectives are measured.


Mechanochemically Induced Controlled Glycation of Lysozyme and Its Effect on Enzymatic Activity and Conformational Changes.
Protein glycation through heating of a mixture of protein and reducing sugars is one of the most commonly used methods of protein modification; however, in most cases, this approach can lead to uncontrolled glycation. The hypothesis that mechanical energy supplied through ball milling can induce glycation of proteins was tested using a well-characterized enzyme lysozyme. The Q-TOF/MS analysis of the milled samples has indicated that the milling of sugar-protein mixtures in stainless steel jars for 30 min and at a frequency of 30 Hz generated mainly monoglycated proteins even with the highly reactive ribose. Increasing the sugar concentration or the milling time did not influence the overall yield or generate more glycoforms. Enzymatic activity measurements, FTIR, and fluorescence spectroscopic studies have indicated that milling of lysozyme alone leads to a significant loss in enzymatic activity and structural integrity in contrast to milling in the presence of sugars.


Serum carnitine levels in epileptic children before and during treatment with valproic acid, carbamazepine, and phenobarbital.
Serum levels of free, acyl, and total carnitine were determined in 32 patients with seizures, before and after 3, 6, and 12 months of treatment with valproic acid (17 patients), carbamazepine (10 patients), or phenobarbital (5 patients). In all three treated groups, both free and total carnitine levels showed a significant decline with respect to pretreatment levels. This decline was most marked and most consistent in patients treated with valproic acid. In 35% of the patients in this group, carnitine deficiency (ie, total carnitine < 30 micromol/L) was observed by month 12. In none of the three groups were serum carnitine levels significantly correlated with the serum concentration of the drug. These findings suggest a need to monitor serum carnitine levels in children treated with any of these drugs.


Apolipoprotein B48-membrane interactions. Absence of transmembrane localization in nonhepatic cells.
Apolipoprotein B (apoB) is essential for the hepatic assembly and secretion of triglyceride-rich very low density lipoproteins. Recent studies have revealed that in both hepatic and nonhepatic cells a large percentage of newly synthesized apoB polypeptides engage in transmembrane interactions with the endoplasmic reticulum (ER). These apoB-membrane interactions have been implicated in the processes of lipoprotein assembly and regulation. To identify domains of apoB that are responsible for its transmembrane localization, overlapping 300 amino acid segments of human apoB48 (amino-terminal 48% of apoB) and two control proteins, human complement component C3 and mouse CD4, were appended to the amino-terminal 77 amino acids of a soluble secretory precursor protein and expressed in COS-1 cells. While the integral membrane protein CD4 conferred predictable transmembrane orientation on the hybrid protein, as evidenced by its partial protease accessibility in intact microsomes, all of the apoB-containing proteins and the soluble secretory control, C3, were fully protease-resistant, consistent with their complete translocation into the ER. To determine if conformational properties of apoB are responsible for its transmembrane interactions with the ER, proteins containing the entire amino-terminal approximately 50% of apoB (apoB50) were expressed in COS-1 cells. Irrespective of whether targeting and translocation initiation were directed by a heterologous signal peptide or the native apoB signal peptide, apoB50 appeared to undergo complete membrane translocation into a protease-inaccessible compartment. These results demonstrate that the amino-terminal 50% of apoB lacks autonomous signals or properties that can fully block ER membrane translocation or promote any other form of stable transmembrane assembly in nonhepatic cells.


The Influence of Sex on Hippocampal Neurogenesis and Neurotrophic Responses on the Persistent Effects of Adolescent Intermittent Ethanol Exposure into Adulthood.
In the United States, approximately 90% of alcohol consumed by adolescents is binge drinking. Binge-like ethanol exposure during adolescence promotes dysregulation of neurotrophic responses and neurogenesis in the hippocampus. These effects include changes in proliferation, regulation, differentiation, and maturation of neurons, and there is indication that such effects may be disproportionate between sexes. This study determined whether sex impacts neurotrophic responses and neurogenesis in adulthood after adolescent intermittent ethanol (AIE) exposure. To determine this, adolescent rats underwent AIE with ethanol (5 g/kg). In adulthood, animals were euthanized, and immunohistochemical techniques and ELISAs were utilized to determine AIE effects on sex-specific neurogenesis factors and neurotrophic markers, respectively. AIE exposure led to a significant decrease in neurogenesis in the dentate gyrus of the hippocampal formation indicated by reductions in the numbers of DCX+, SOX2+ and Ki-67+ cells in male and female AIE-exposed rats. Additionally, AIE increased markers for the pro-inflammatory cytokines, TNF-α and IL-1β, in the hippocampus into adulthood in male AIE-exposed rats only. No significant AIE-induced differences were observed in the anti-inflammatory cytokines, IL-10 and TGF-β, nor in the neurotrophic factors BDNF and GDNF. Altogether, our findings indicate that although AIE did not have a persistent effect on hippocampal neurotrophic levels, there was still a reduction in neurogenesis. The neurogenic impairment was not sex specific, but the neurogenic deficits in males may be attributed to an increase in pro-inflammatory cytokine expression. A persistent impairment in neurogenesis may have an impact on both behavioral maladaptations and neurodegeneration in adulthood.


MacrophAging: a cellular and molecular review.
Aging is associated with the deterioration of several physiological functions, which leads to aged-related pathologies and, ultimately, to death. The immune system is affected by aging, causing an increased susceptibility to infections and mortality, as well as a major incidence of immune diseases and cancer in the elderly. Because macrophages are an essential component of both innate and adaptive immunity, altered function of these phagocytic cells with aging may play a key role in immunosenescence. Here we summarize data about the effects of aging on macrophages and we discuss the molecular events that could be involved in this process.


The demonstration of antibody specificity by a new technique. The gel electrophoresis-derived enzyme-linked immunosorbent assay (GEDELISA) and its application to antibodies specific for feline leukemia virus.
By combining the high resolution of sodium dodecylsulfate polyacrylamide gel electrophoresis with the sensitivity of enzyme-linked immunosorbent assay (ELISA) antibodies specific for different feline leukemia virus components are characterized. Based on the same principle, Concanavalin A binding sites of FeLV components are also detected.


Cytokine producing ability of peripheral blood cells from COVID-19 patients after unspecific in vitro stimulation.
Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed. The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit. Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner. Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.


Arthroscopic stabilization for Neer type 2 fracture of the distal clavicle fracture.
The distal clavicle fractures are divided into three types according to Neer's classification. Types 1 and 3 fractures are treated with a sling to immobilize the upper extremity. However, the treatment of type 2 fractures is controversial. We paid attention to the anatomic basis of type 2 fractures that the disruptions of the conoid ligament lead to the distraction between the two bony fragments. In this study, we describe the arthroscopic procedure to reconstruct the disrupted ligament and stabilize the fracture as a minimally invasive method. The subjects were seven patients with the distal clavicle fractures. According to Neer's or Rockwood's classification on plain radiographs, all seven patients were evaluated as type 2 or 2B, respectively. Our surgical procedure was performed with the patient in the beach chair position. We have used the artificial ligament with an EndoButton (Smith & Nephew Endoscopy, Andover, MA) as the substitute ligament to reconstruct the disrupted conoid ligament. The mean duration of postoperative follow-up was 2 years and 5 months. The bony union was achieved in all patients at a final follow-up. When concerning the range of motion at final examinations, mean forward flexion was 171°, mean abduction was 165°, mean internal rotation was Th11, and mean horizontal adduction was 132°. It is possible to treat the distal clavicle fractures by a minimally invasive arthroscopic procedure without opening the fracture site of clavicle.


Rice has two distinct classes of protein kinase genes related to SNF1 of Saccharomyces cerevisiae, which are differently regulated in early seed development.
We have isolated five cDNA clones (osk1-5) for protein kinases from rice which are related to SNF1 protein kinase of Saccharomyces cerevisiae. Based on the sequence homology, these cDNAs can be classified into two groups, group 1 (osk1) and group 2 (osk2-5). The products of these genes were demonstrated to be functional SNF1-related protein kinases by in vitro and in vivo experiments. Recombinant proteins expressed from both groups of genes were fully active as protein kinases and could phosphorylate SAMS peptide, a substrate specific for the SNF1/AMPK family, as well as themselves (autophosphorylation). Moreover, expression of osk3 cDNA in yeast snf1 mutants restored SNF1 function. Northern blot analyses showed differential expression of these two gene groups; group 1 is expressed uniformly in growing tissues (young roots, young shoots, flowers, and immature seeds), whereas group 2 is strongly expressed in immature seeds. SNF1-related protein kinases have been reported from different plant species, such as rye, barley, Arabidopsis, tobacco, and potato, while the type of gene strongly expressed in immature seeds is known only in cereals such as rye, barley, and, from our findings, in rice. Expression levels of the group 2 genes were further analyzed in seeds during seed maturation. Expression is transiently increased in the early stages of seed maturation and then decreases. The expression peak precedes those of the sbe1 and waxy genes, which are involved in starch synthesis in rice. Taken together, these findings suggest that group 2 OSK genes play important roles in the early stages of endosperm development in rice seeds.


Failure of noninvasive ventilation after lung surgery: a comprehensive analysis of incidence and possible risk factors.
Noninvasive ventilation has been successfully used after thoracic surgery. However, noninvasive ventilation fails in about 20% of patients. The aim of the study was to analyze episodes of noninvasive ventilation failure and to assess possible risk factors, while taking into account the performance of fiberoptic bronchoscopy for secretion management. From January 2006 to June 2008, the use of noninvasive ventilation was prospectively recorded after thoracic surgery. Data were retrospectively abstracted from charts, including the number of fiberoptic bronchoscopies performed. Risk factors associated with noninvasive ventilation failure were evaluated using logistic regression analysis to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). During the study period, 664 patients were admitted in the intensive care unit (ICU) after lung resection or pulmonary thromboendarterectomy. A total of 135 patients underwent noninvasive ventilation (20.3%). As many as 40 of these 135 patients needed to be intubated (29.6%) and represented the noninvasive ventilation failure group. Patients with noninvasive ventilation failure had more fiberoptic bronchoscopies performed compared with patients with noninvasive ventilation success: 3 (1-5) versus 1 (0-3); p = 0.0008. Four independent variables were associated with noninvasive ventilation failure during the first 48 h of appliance: increased respiratory rate (OR: 4.17 (1.63-10.67); increased Sequential Organ Failure Assessment (SOFA) score (OR: 3.05 (1.12-8.34); number of fiberoptic bronchoscopies performed (OR: 1.60 (1.01-2.54); and number of hours spent on noninvasive ventilation (OR: 1.06 (1.01-1.11). Nosocomial pneumonia was the leading cause of respiratory complications and occurred in 21 and 6 patients with and without noninvasive ventilation failure, respectively (53% vs 6%; p < 0.0001). Patients in the failure group had a higher mortality rate (20% vs 0%; p < 0.0001). Noninvasive ventilation failure is associated with higher mortality, but is merely a marker of progression of a more severe disease. This may at least indicate the need for caution in some patients. Interestingly, increased use of fiberoptic bronchoscopies during noninvasive ventilation appliance was identified as a risk factor of failure.