Pneumatosis intestinalis and portal venous gas in mechanical small bowel obstruction: Is it worrisome?
The purpose of this study was to evaluate the clinical significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) in patients with mechanical small bowel obstruction (SBO), using surgical findings or clinical follow-up as standard of reference. Fourteen patients with mechanical SBO associated with PI and PVG were retrospectively included. There were 7 men and 7 women with a mean age of 59±19 (SD) (range: 25-93 years). CT examinations were reviewed by two radiologists to confirm the diagnosis of mechanical SBO and make a description of PI. Interobserver agreement was calculated. The reference standard was intraoperative appearance of the bowel wall (10/14; 71%) or the recovery of a normal bowel function in patients who were managed conservatively (4/14; 29%). Among the 10 patients who underwent surgery, a normal appearance of the bowel in association with PI on CT was found intraoperatively in 8/10 (80%) patients and a reversible ischemia in the remaining 2/10 (20%) patients. The four patients who were managed conservatively recovered normal bowel function. Two patients died within two weeks following SBO. PI and PVG are not specific signs of bowel necrosis in mechanical SBO.


[Patient experience, epistemic authority and health challenges: the example of long COVID].
Since February 2020, hundreds of thousands of patients have been left with persistant symptoms after their infection. Along with their clinicians, these patients are exposed to a high degree of uncertainty and the urgent need to produce conceptual frameworks aimed at recognising, treating and validating their experience as patients suffering from new and protracted symptoms and witnessing debates as to how these symptoms should be qualified. In this respect, long covid illustrates the need to combine the collective experiential knowledge of patients and scientific knowledge for the benefit of the patients, clinicians and research.


Transitions between tobacco and cannabis use among adolescents: a multi-state modeling of progression from onset to daily use.
Use of a given substance may follow a stage process leading from onset to regular use, and use of one substance can be strongly associated with use of another. The aim of this study was to describe the transitions between tobacco and cannabis use. Data was derived from a French nationwide survey involving 29,393 teenagers. A homogenous Markov multi-state model (MSM) was fitted. The substance use pattern modeled was: no lifetime use→1 (2) substance(s) initiation→1 (2) daily substance(s) use, with pathways between tobacco and cannabis. The likelihood of first initiating tobacco appeared 17.6 times greater than the likelihood of initiating cannabis. Once a subject has experimented with one substance, the risk of another substance experiment was much greater. Transition intensity from tobacco initiation to daily use was 4.8 times higher than that from cannabis. Our results are compatible with a process mixing the gateway theory, the reverse gateway theory and the route of administration model, but do not explore a common liability to addictions, which could be explored by using a MSM on a prospective cohort with initial collection of some explanatory factors.


Acute abdomen in patients with SARS-CoV-2 infection or co-infection.
Patients with an acute abdomen require emergency surgery. SARS-CoV-2 infection can affect multiple organ systems, including the digestive tract. Little is known about the consequences of COVID-19 infection in emergency surgical patients. Perioperative data for COVID-19 patients undergoing emergency surgery from March 1, 2020, to May 23, 2020 were collected prospectively (NCT04323644). During this period, 215 patients underwent surgery, including 127 patients in an emergency setting, of whom 13 (10.2%) had COVID-19. Two scenarios were identified: (a) patients who were admitted to a hospital for an acute surgical condition with a concomitant diagnosis of COVID-19, and (b) patients with severe COVID-19 developing acute abdominal pathologies during their hospital stay. When compared with those in group B, patients in group A globally recovered better, with a lower mortality rate (14.3% vs. 33.3%), lower ARDS rate (28.5% vs. 50.0%), less rates of preoperative invasive ventilation (14.3% vs. 50.0%) and postoperative invasive ventilation (28.5% vs. 100.0%), and a shorter duration of invasive ventilation. No causality between SARS-CoV-2 infection and gastrointestinal affliction was found. Our observations underline that mild co-infection with COVID-19 did not result in more complications for emergency abdominal surgery. Howe, an acute abdomen during severe COVID-19 infection was part of an unfavorable prognosis.


Efficient extraction of uranium from environmental samples using phosphoramide functionalized magnetic nanoparticles: Understanding adsorption and binding mechanisms.
Phosphoramide functionalized Fe3O4 nanoparticles (NPs) were synthesized by a three step procedure and its application for uranium extraction from different enviornmental matrices has been demonstrated. A maximum adsorption capacity of 95.2 mg of U/g of the sorbent has been achieved which is higher as compared to many reported magnetic NPs. pH dependent adsorption studies were performed at 1 ppm uranium concentrations which suggests more than 80% adsorption in pH range of 4-8 with maximum adsorption at pH 6. Interestingly this is the pH range of most naturally occurring water bodies suggesting the potential of this material to extract uranium from real environmental samples. Adsorption studies were carried out with tap water, drinking water and sea water and more than 90% uranium extraction was observed. Desorption studies were performed with different reagents suggesting that the material can be reused again. EXAFS studies have been carried out which suggests that the uranium binds with oxygens of three PO group at the surface of phosphoramide functionalized NPs and based on this, binding mode of uranium with the synthesized sorbent is proposed.


Molecular structure, vibrational spectral assignments, HOMO-LUMO, MESP, Mulliken analysis and thermodynamic properties of 2,6-xylenol and 2,5-dimethyl cyclohexanol based on DFT calculation.
The FT-IR and FT-Raman spectra of 2,6-xylenol and 2,5-dimethyl cyclohexanol are recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively. The spectral data obtained are assigned to different normal modes by using of comparison with the theoretical values obtained by applying density functional theory (DFT/B3LYP) method with 6-31+G and 6-31++G basis set. The total energy distribution contributions of vibrations modes are distinguished through scaling factors. The calculated HOMO and LUMO energies shows that the charge transfers occur within the molecules. The harmonic frequencies obtained from these two methods are compared. The Mulliken, molecular electrostatic potentials analysis are calculated theoretically.


Genetic determination of sibship and twin zygosity in a case of an alleged double infant homicide.
A 32 year-old woman was hospitalised with severe septic symptoms. The examination of the patient revealed placenta residues in the woman's uterus as cause of the infection. The police was called and investigated her apartment in search of the missing baby. Finally, the bodies of two newborn babies were found in the freezer. According to the mother, the babies were stillborn twins. The autopsy revealed that the smaller, moderately putrefied child was stillborn, while the larger infant showed typical signs of drowning and only slight putrefaction. The placenta was judged by gynaecologists to be that of a single pregnancy. Thus the prosecution suspected that the woman had had two independent pregnancies and ordered an additional genetic analysis. A genetic analysis clearly revealed that the babies were monozygotic twins, supporting the mother's statement of a twin pregnancy.


An artificial chromosome ylAC enables efficient assembly of multiple genes in Yarrowia lipolytica for biomanufacturing.
The efficient use of the yeast Yarrowia lipolytica as a cell factory is hampered by the lack of powerful genetic engineering tools dedicated for the assembly of large DNA fragments and the robust expression of multiple genes. Here we describe the design and construction of artificial chromosomes (ylAC) that allow easy and efficient assembly of genes and chromosomal elements. We show that metabolic pathways can be rapidly constructed by various assembly of multiple genes in vivo into a complete, independent and linear supplementary chromosome with a yield over 90%. Additionally, our results reveal that ylAC can be genetically maintained over multiple generations either under selective conditions or, without selective pressure, using an essential gene as the selection marker. Overall, the ylACs reported herein are game-changing technology for Y. lipolytica, opening myriad possibilities, including enzyme screening, genome studies and the use of this yeast as a previous unutilized bio-manufacturing platform.


Development of a homogeneous fluorescence anisotropy assay to monitor and measure FtsZ assembly in solution.
We present here a fluorescence anisotropy method for the quantification of the polymerization of FtsZ, an essential protein for cytokinesis in prokaryotes whose GTP-dependent assembly initiates the formation of the divisome complex. Using Alexa 488 labeled wild-type FtsZ as a tracer, the assay allows determination of the critical concentration of FtsZ polymerization from the dependence of the measured steady-state fluorescence anisotropy on the concentration of FtsZ. The incorporation of the labeled protein into FtsZ polymers and the lack of spectral changes on assembly were independently confirmed by time-resolved fluorescence and fluorescence correlation spectroscopy. Critical concentration values determined by this new assay are compatible with those reported previously under the same conditions by other well-established methods. As a proof of principle, data on the sensitivity of the assay to changes in FtsZ assembly in response to Mg(2+) concentration or to the presence of high concentrations of Ficoll 70 as crowding agent are shown. The proposed method is sensitive, low sample consuming, rapid, and reliable, and it can be extended to other cooperatively polymerizing systems. In addition, it can help to discover new antimicrobials that may interfere with FtsZ polymerization because it can be easily adapted to systematic screening assays.


Effect of ladostigil treatment of aging rats on gene expression in four brain areas associated with regulation of memory.
Episodic and spatial memory decline in aging and are controlled by the hippocampus, perirhinal, frontal and parietal cortices and the connections between them. Ladostigil, a drug with antioxidant and anti-inflammatory activity, was shown to prevent the loss of episodic and spatial memory in aging rats. To better understand the molecular effects of aging and ladostigil on these brain regions we characterized the changes in gene expression using RNA-sequencing technology in rats aged 6 and 22 months. We found that the changes induced by aging and chronic ladostigil treatment were brain region specific. In the hippocampus, frontal and perirhinal cortex, ladostigil decreased the overexpression of genes regulating calcium homeostasis, ion channels and those adversely affecting synaptic function. In the parietal cortex, ladostigil increased the expression of several genes that provide neurotrophic support, while reducing that of pro-apoptotic genes and those encoding pro-inflammatory cytokines and their receptors. Ladostigil also decreased the expression of axonal growth inhibitors and those impairing mitochondrial function. Together, these actions could explain the protection by ladostigil against age-related memory decline.


Sunburns among beachgoers in the northern coast of Peru: frequency and factors associated.
Overexposure to ultraviolet (UV) radiation has increased skin cancer incidence and the risk of sunburns, especially during the summer months. Identify the frequency and factors associated with sunburns in a sample of beachgoers in the northern coast of Peru. We conducted a secondary data analysis of a previous study that assessed the awareness, behavior and attitudes concerning sun exposure among beachgoers. We included adults between 18 and 59 years who went to a beach in northern Peru during summer (March 2018). Three generalized linear models of the Poisson family were constructed to evaluate the factors associated with having had at least one sunburn last summer. All regression models reported the adjusted prevalence ratio (aPR) with their respective 95% confidence interval (95% CI). Of a total of 402 participants, 225 (56.0%) had one to five sunburns and 25 (6.2%) had six or more. Beachgoers who were 1-15 days (aPR: 1.16, 95% CI [1.05-1.27]) or more than 15 days (aPR: 1.22, 95% CI [1.09-1.36]) exposed to the sun on the beach had a higher frequency of at least one sunburn. The non-regular wearing of a hat or cap also increased the frequency of sunburns (aPR: 1.06, 95% CI [1.01-1.12]). In contrast, those who had Skin Phototype III (aPR: 0.94, 95% CI [0.88-0.99]) or IV (aPR: 0.69, 95% CI [0.63-0.75]) had a lower frequency of sunburns. Three out of five beachgoers had one or more sunburns in the last summer. The factors associated with a higher frequency were the time of sun exposure at the beach and the non-regular use of a hat or cap. Type III-IV skin phototypes were associated with a lower sunburn frequency.


Monophyly of class I aminoacyl tRNA synthetase, USPA, ETFP, photolyase, and PP-ATPase nucleotide-binding domains: implications for protein evolution in the RNA.
Protein sequence and structure comparisons show that the catalytic domains of Class I aminoacyl-tRNA synthetases, a related family of nucleotidyltransferases involved primarily in coenzyme biosynthesis, nucleotide-binding domains related to the UspA protein (USPA domains), photolyases, electron transport flavoproteins, and PP-loop-containing ATPases together comprise a distinct class of alpha/beta domains designated the HUP domain after HIGH-signature proteins, UspA, and PP-ATPase. Several lines of evidence are presented to support the monophyly of the HUP domains, to the exclusion of other three-layered alpha/beta folds with the generic "Rossmann-like" topology. Cladistic analysis, with patterns of structural and sequence similarity used as discrete characters, identified three major evolutionary lineages within the HUP domain class: the PP-ATPases; the HIGH superfamily, which includes class I aaRS and related nucleotidyltransferases containing the HIGH signature in their nucleotide-binding loop; and a previously unrecognized USPA-like group, which includes USPA domains, electron transport flavoproteins, and photolyases. Examination of the patterns of phyletic distribution of distinct families within these three major lineages suggests that the Last Universal Common Ancestor of all modern life forms encoded 15-18 distinct alpha/beta ATPases and nucleotide-binding proteins of the HUP class. This points to an extensive radiation of HUP domains before the last universal common ancestor (LUCA), during which the multiple class I aminoacyl-tRNA synthetases emerged only at a late stage. Thus, substantial evolutionary diversification of protein domains occurred well before the modern version of the protein-dependent translation machinery was established, i.e., still in the RNA world.


A new tool for measuring hand preference in non-human primates: adaptation of Bishop's Quantifying Hand Preference task for Olive baboons.
As non-human primates are phylogenetically close to humans, they are ideal models to investigate the precursors of human brain hemispheric specialisation. However, in spite of hundreds of reports investigating hand preference, empirically based theories generating valuable predictions are still lacking, mainly because of a disappointing deficiency in comparability between studies and even more so between species. Therefore, we propose here to adapt, for the first time, the Quantifying Hand Preference (QHP) task, devised for humans, to non-human primates. This test could be a very useful standard measure of hand preference for simple reaching in non-human primates because of its simplicity to set up and of the parameters (e.g., subject's posture; position of the item) it can control. Our test subjects were 42 baboons of various ages and both sexes. Our results highlight the crucial influence of item position on hand preference for simple reaching, even when the item is positioned close to the subjects' body midline. Both sex and age influence baboons' handedness index but this effect varies according to the position of the item to be grasped. We discuss our results within the theoretical framework concerning hemispheric specialisation for object manipulation and with the perspective of replicating this experiment with other non-human primate species and genera.


Protein restriction for children with chronic renal failure.
Protein restriction has been prescribed for some time for patients with chronic kidney disease (CKD). The effect of a low protein diet on delaying the progression to end-stage kidney disease (ESKD) in children and its impact on growth and nutrition remains unresolved. To determine the efficacy of protein restricted diet in delaying the start of maintenance dialysis and maintaining nutrition in children. Cochrane Renal group trials register, the Cochrane Central register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of nephrology textbooks, review articles and relevant trials. Randomised control trials (RCTs) comparing un-restricted protein diet versus a protein restricted diet (to safe amounts recommended by WHO), with follow-up period of at least six months were included. Two authors independently selected studies. Statistical analysis were performed using the random effects model. For dichotomous outcome results are expressed as relative risk (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment, the mean difference (WMD) was used. Two studies (250 children) were identified, 124 received a protein restricted diet and 126 a control diet. No significant differences was found in the number of renal deaths (RR 1.12, 95% CI 0.54 to 2.33), progression of kidney disease (creatinine clearance at two years: WMD 1.47, 95% CI -1.19 to 4.14) or growth (weight - WMD -0.13, 95% CI -1.10 to 0.84; height - WMD -1.99, 95% CI -4.84 to 0.86). Reducing protein intake does not appear to have significant impact in delaying the progression to ESKD in children.


Cerium chloride as a histochemical marker of hydrogen peroxide in reperfused ischemic hearts.
Hydrogen peroxide (H2O2) has been implicated in cardiac damage due to ischemia and reperfusion. We adapted an electron microscopic, histochemical method for demonstrating H2O2 produced by isolated cells to isolated, buffer-perfused rabbit hearts. The method involves formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). We perfused hearts retrograde via the aorta with well-oxygenated bicarbonate-buffered solution, followed by one in which bicarbonate was replaced with imidazole (IPSS) to prevent precipitation of bicarbonate and CeCl3. Some hearts were made globally ischemic (30 min, 37 degrees C), reperfused 5 min with well-oxygenated IPSS containing 1 mM CeCl3, then processed for electron microscopy. Others were perfused with IPSS containing catalase (300 U/ml) or albumin before ischemia and upon reperfusion, followed by CeCl3 administration. Nonischemic control hearts perfused with IPSS (+/- catalase) were also studied. Electron micrographs were assessed visually and by computer for precipitate localization and amount. There was abundant precipitate on the luminal face of the coronary vascular endothelium in ischemic-reperfused, cerium-treated hearts, including those treated with albumin. There was significantly less in reperfused catalase-treated or nonischemic control hearts. X-ray microbeam analysis of the endothelial precipitate indicated the presence of Ce. This appears to be the first visual demonstration of a CeCl3-H2O2-dependent reaction product in intact isolated ischemic hearts. The data indicate that at the time of reperfusion some H2O2 is accessible to the vascular space, and that its amount can be reduced by perfused catalase. Further modifications this technique may be useful for assessing the sites and pathways by which H2O2 is generated by hearts or other buffer-perfused organs subjected to stresses such as ischemia or hypoxia.


Hyperprolactinemia in postmenopausal women.
To study the clinical cause and course of hyperprolactinemia in postmenopausal women. Retrospective case-note study. Tertiary care hospital. Six postmenopausal women with hyperprolactinemia. Clinical history and physical examination, serum levels of PRL, LH, FSH, computed tomography (CT) of the pituitary gland before and after treatment with bromocriptine. At presentation, the mean age was 57.5 +/- 7.5 SD years. The mean level of PRL was 1,427 +/- 1,599 ng/mL (1,427 +/- 1,599 micrograms/L). All women suffered from secondary amenorrhea for a mean duration of 31.8 +/- 5.6 years. Five of six had galactorrhea at some time in the past. Pituitary imaging revealed a pituitary macroadenoma in four women, an enlarged sella suggestive of a pituitary macroadenoma in one woman, and a microadenoma in one. After treatment with bromocriptine, the PRL level decreased in all women to within normal limits. Five of six women developed hot flushes after the PRL level returned to normal. Most cases of hyperprolactinemia in postmenopausal women are due to macroadenoma rather than microadenoma, the common finding in younger women. The clinical course is suggestive of a prolonged disease that was not detected earlier, although clinical signs were present. These findings are suggestive of an enlargement of microadenomas to macroadenomas as time passes.


Balanced structural changes involving the human X: effect on sexual phenotype.
Reports of 107 cases (89 females and 18 males) with balanced X-autosome translocations and 11 cases with pericentric inversions (and their families) have been reviewed. Of the 78 informative females, 36 were infertile and had an X-breakpoint in the segment Xq13-26. Thus the existence of the critical segment has been amply confirmed by this review. However the finding of three normal fertile females with deletion of a part or the whole of this segment suggests that it is not the break in the critical segment, as was first thought, but rather the contact between loci in the critical segment and loci external to it that is responsible for the abnormal sexual phenotype. Six females were exceptions to the critical region hypothesis. The X-breakpoints in these were in the critical region and yet each had had one or more children. Three of the six women (two inversions and one translocation carriers) were not wholly normal as they suffered from menstrual cycle disorder, secondary sterility and/or early menopause. Four of the six (including the three true exceptions) had a breakpoint in band Xq22. It is possible that there are two critical segments within Xq13-26 separated by a small segment in band Xq22. Seven of the nine adult male carriers of the balanced X-autosome translocations were infertile. Even from this limited number of cases it appears that male carriers of X-autosome translocations are likely to suffer from a disturbance of spermatogenesis as is the case in mouse and drosophila. Male carriers of X-inversions do not necessarily suffer from infertility. Results from one family with X-inversion suggest that some sort of a position effect in the X affecting the sexual phenotype may also be operating in the male.


Factors controlling the spatial distribution of soil organic carbon in Daxing'anling Mountain.
Daxing'anling Mountain, in the northeastern part of China, contains a large amount of soil organic carbon (SOC). Using data including topography, climate, and vegetation, the spatial distribution of SOC content was modeled using classical and geography-based statistics, as well as a geographically weighted kriging model. The study findings include: (1) SOC content generally ranges 40-70 g/kg, with high SOC content in the southwest and low SOC content in the southeast; (2) Results of principal component analysis suggested the normalized difference vegetation index is the best predictor of patterns in SOC; and (3) The geo-weighted regression Kriging model well reflects factors influencing spatial distribution of SOC content. This study provides important baseline information for environmental protection in the Daxing'anling Mountain area, as well as general information as to important factors that mediate this important reservoir of soil carbon.


The effects of non-attendance information therapy on the control of glycosylated hemoglobin (HbA1C) in type 2 diabetic patients.
Patient education plays an important role in the control of diabetes. Nonattendance education, enabling elimination of limitations caused by time and space and facilitating the relationship between patient and care liaison is an effective, simple, and cheap method. The aim of this study is determination of the effects of nonattendance information therapy on the control of glycosylated hemoglobin (HbA1C) in type 2 diabetic patients in Isfahan. The present study was an interventional semi experimental study with pretest and post-test and control groups. Statistical population were type 2 diabetics patients of the Isfahan Endocrine and Metabolism Research Center, of whom 64 people were randomly selected and divided into intervention and control groups. First, the preliminary data were collected using the HbA1c test in patients. Then, the intervention group received training package and Short Message Service (SMS) for eight weeks. After one-month incubation period, HbA1c was again determined in both groups. Data were analyzed using t-test, paired t-test and Mann-Whitney U and Chi-square tests. Results showed that diabetes patients' HbA1c in the intervention group was significantly lower after the intervention through training packages and SMS service compared to before the intervention (P < 0.001). Comparison of the two groups showed that there was a significant difference in the HbA1C between the intervention and control groups (P = 0.048). Follow-up of education of patients with type 2 diabetes through training packages and SMS services had significant effects on the control of the patients' HbA1C. Also due to the low cost and high effectiveness of this method, it is recommended to health-care providers and treatment groups. This study also showed that having medical librarians along with treatment group can have a positive effect on the type 2 diabetic patients' health.


Nutritional influences during pregnancy.
Maternal nutrition represents one of the important influences on the course and outcome of pregnancy and attention to nutritional factors (i.e., assessment of nutritional status, dietary advice, and follow-up evaluation) properly constitute an essential component of prenatal care. Nearly all nutrients are required in increased amounts during gestation but the magnitude of the increase varies from nutrient to nutrient. Caloric needs increase by 300 kcal per day, representing an addition of 15 per cent, and should be sufficient to support a weight gain averaging 350 to 400 gm per week during the last two trimesters. Total protein intake during pregnancy should be 1.3 gm per kg for the mature woman and somewhat higher for the adolescent. Gestational needs for iron cannot be met by diet and supplementation (in the form of simple ferrous salts, 30 to 60 mg daily) should be provided. Folate requirements are doubled during pregnancy and, while these can be met by diet, supplementation may be considered as an option. Provision of the gestational calcium allowance from food sources is readily possible if (and only if) daily products are consumed. The generally increased need for other nutrients can be provided readily by the properly selected diet. Thus, with respect to supplements, iron and perhaps folate should be advised routinely while other vitamin-mineral supplements are probably neither helpful nor harmful. Prescription of vitamin-mineral supplements cannot be expected to compensate for poor dietary habits. Dietary restriction of nutrients in general, and energy and sodium in particular, has the potential for impairing the maternal capacity to make the required physiologic adjustments of pregnancy and interfering with fetal development. Restriction of any nutrient to levels below the guidelines provided by the Recommended Dietary Allowances is rarely if ever advisable.


RBPmap: A Tool for Mapping and Predicting the Binding Sites of RNA-Binding Proteins Considering the Motif Environment.
RNA-binding proteins (RBPs) play a key role in post-transcriptional regulation via binding to coding and non-coding RNAs. Recent development in experimental technologies, aimed to identify the targets of RBPs, has significantly broadened our knowledge on protein-RNA interactions. However, for many RBPs in many organisms and cell types, experimental RNA-binding data is not available. In this chapter we describe a computational approach, named RBPmap, available as a web service via http://rbpmap.technion.ac.il/ and as a stand-alone version for download. RBPmap was designed for mapping and predicting the binding sites of any RBP within a nucleic acid sequence, given the availability of an experimentally defined binding motif of the RBP. The algorithm searches for a sub-sequence that significantly matches the RBP motif, considering the clustering propensity of other weak matches within the motif environment. Here, we present different applications of RBPmap for discovering the involvement of RBPs and their targets in a variety of cellular processes, in health and disease states. Finally, we demonstrate the performance of RBPmap in predicting the binding targets of RBPs in large-scale RNA-binding data, reinforcing the strength of the tool in distinguishing cognate binding sites from weak motifs.


Bile acids in glucose metabolism and insulin signalling - mechanisms and research needs.
Of all the novel glucoregulatory molecules discovered in the past 20 years, bile acids (BAs) are notable for the fact that they were hiding in plain sight. BAs were well known for their requirement in dietary lipid absorption and biliary cholesterol secretion, due to their micelle-forming properties. However, it was not until 1999 that BAs were discovered to be endogenous ligands for the nuclear receptor FXR. Since that time, BAs have been shown to act through multiple receptors (PXR, VDR, TGR5 and S1PR2), as well as to have receptor-independent mechanisms (membrane dynamics, allosteric modulation of N-acyl phosphatidylethanolamine phospholipase D). We now also have an appreciation of the range of physiological, pathophysiological and therapeutic conditions in which endogenous BAs are altered, raising the possibility that BAs contribute to the effects of these conditions on glycaemia. In this Review, we highlight the mechanisms by which BAs regulate glucose homeostasis and the settings in which endogenous BAs are altered, and provide suggestions for future research.


Structural and Molecular Dynamics of Mycobacterium tuberculosis Malic Enzyme, a Potential Anti-TB Drug Target.
Tuberculosis (TB) is the most lethal bacterial infectious disease worldwide. It is notoriously difficult to treat, requiring a cocktail of antibiotics administered over many months. The dense, waxy outer membrane of the TB-causing agent, Mycobacterium tuberculosis (Mtb), acts as a formidable barrier against uptake of antibiotics. Subsequently, enzymes involved in maintaining the integrity of the Mtb cell wall are promising drug targets. Recently, we demonstrated that Mtb lacking malic enzyme (MEZ) has altered cell wall lipid composition and attenuated uptake by macrophages. These results suggest that MEZ contributes to lipid biosynthesis by providing reductants in the form of NAD(P)H. Here, we present the X-ray crystal structure of MEZ to 3.6 Å. We use biochemical assays to demonstrate MEZ is dimeric in solution and to evaluate the effects of pH and allosteric regulators on its kinetics and thermal stability. To assess the interactions between MEZ and its substrate malate and cofactors, Mn2+ and NAD(P)+, we ran a series of molecular dynamics (MD) simulations. First, the MD analysis corroborates our empirical observations that MEZ is unusually flexible, which persists even with the addition of substrate and cofactors. Second, the MD simulations reveal that dimeric MEZ subunits alternate between open and closed states, and that MEZ can stably bind its NAD(P)+ cofactor in multiple conformations, including an inactive, compact NAD+ form. Together the structure of MEZ and insights from its dynamics can be harnessed to inform the design of MEZ inhibitors that target Mtb and not human malic enzyme homologues.


The mechanism of self-recognition in humans.
Recognizing oneself as the owner of a body and the agent of actions requires specific mechanisms which have been elucidated only recently. One of these mechanisms is the monitoring of signals arising from bodily movements, i.e. the central signals which contribute to the generation of the movements and the sensory signals which arise from their execution. The congruence between these two sets of signals is a strong index for determining the experiences of ownership and agency, which are the main constituents of the experience of being an independent self. This mechanism, however, does not account from the frequent cases where an intention is generated but the corresponding action is not executed. In this paper, it is postulated that such covert actions are internally simulated by activating specific cortical networks or representations of the intended actions. This process of action simulation is also extended to the observation and the recognition of actions performed or intended by other agents. The problem of disentangling representations that pertain to self-intended actions from those that pertain to actions executed or intended by others, is a critical one for attributing actions to their respective agents. Failure to recognize one's own actions and misattribution of actions may result from pathological conditions which alter the readability of these representations.


Etravirine-based highly active antiretroviral therapy in HIV-1-infected paediatric patients.
We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1. A multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data. The median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log(10) ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/μL (range 221-655 cells/μL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirine-associated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNA<400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNA<50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks (IQR 35.7-63.4 weeks); four patients (17%) were exposed to etravirine for >120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure. We observed a sustained antiviral response and improved immunological parameters in multidrug-resistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.


Cephalometric comparisons of dentofacial parameters between Egyptian and North American adolescents.
The purpose of this study was to develop cephalometric standards for the Egyptian adolescent boys and girls and to compare them to a matched Iowa adolescent sample. The Egyptian sample consisted of 39 boys and 51 girls with a mean age of 12.5 years. The Iowa sample consisted of 33 boys and 22 girls with a mean age of 13.0 years. Basic descriptive statistics were calculated for 35 cephalometric dentofacial parameters. The general linear models procedure, analysis of variance, was used for the comparisons between the groups. F values were calculated for the overall group comparisons, and the statistical significance was predetermined at the 0.05 level of confidence. Comparisons between the boys and girls in both populations indicated that the boys were larger in the linear dimensions of the cranial base and face heights than the girls. Comparisons between the Egyptians and the Iowans indicated that Egyptian boys have a tendency toward bimaxillary dental protrusion and a decreased overbite as compared with Iowa boys. Egyptian girls have a relatively more convex profile and a tendency toward mandibular dental protrusion. When the overall findings are evaluated, it could be concluded that, in general, there is a great similarity in the overall facial morphology between the Egyptian and Iowa populations.


Molecular design of aquaporin-1 water channel as revealed by electron crystallography.
The electron crystallographic structure of the aquaporin-1 water channel, determined at approximately 6A, reveals that the protein has six transmembrane alpha-helices forming a trapezoid-like cylinder. There is a branched rod-like structure within the cylinder that traverses the membrane and likely contains at least one alpha-helix.


Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in the brain.
The effects of yohimbine (3 mg/kg i.p.), phenoxybenzamine (20 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) on the synthesis and the utilization of dopamine and noradrenaline in the central nervous system of rats were investigated. Dopa accumulation following decarboxylase inhibition and the alpha-methyltyrosine-induced disappearance of the amines were used as the measure of these effects. The synthesis and the utilization of dopamine and noradrenaline were accelerated by yohimbine. Clonidine plus phenoxybenzamine inhibited the synthesis and utilization of dopamine and the combination also partly antagonized the effects of yohimbine on the trunover of dopamine. The effects of the three drugs on the synthesis and utilization of dopamine might be secondary to their actions on alpha-adrenoreceptors of noradrenaline synapses since, at the doses used, yohimbine increases the release of noradrenaline, phenoxybenzamine blocks postsynapptic noradrenaline receptors and clonidine reduces the release of noradrenaline. This hypothesis is supported by the findings that yohimbine and phenoxybenzamine did not change the increased synthesis of dopamine in reserpine-treated rats and that clonidine did not inhibit the increased synthesis of dopamine after axotomy or treatment with reserpine.


Comparison of the Therapeutic Effects of Sodium Valproate and Levetiracetam on Pediatric Epilepsy and the Effects of Nerve Growth Factor and γ-Aminobutyric Acid.
We aimed to investigate the therapeutic effect of sodium valproate combined with levetiracetam on pediatric epilepsy and the effects of nerve growth factor and γ-aminobutyric acid. Eighty-three epileptic children admitted to Xuzhou Municipal Hospital of Xuzhou Medical University (Xuzhou, China) from Jan 2018 to Nov 2019 were collected and divided into a control group (40 cases, treated with sodium valproate alone) and an observation group (43 cases, treated with sodium valproate combined with levetiracetam). The therapeutic effect and incidence of adverse reactions were observed. The levels of nerve growth factor (NGF), γ-aminobutyric acid (GABA) and serum neuron-specific enolase (NSE) of children were compared. Changes of cognitive function and the total effective rate were evaluated. Logistic regression analysis was used to analyze the risk factors affecting the therapeutic effect. After treatment, NGF, GABA and NSE in the observation group were significantly improved compared with those before treatment. The cognitive function of the observation group was significantly improved after treatment when compared with the control group. The total effective rate in the observation group was higher than that in the control group. Adverse reactions in the observation group were less than those in the control group. Seizure type, NGF, GABA, NSE and treatment methods were independent risk factors affecting the therapeutic effect of pediatric epilepsy. The application of sodium valproate combined with levetiracetam in the treatment of pediatric epilepsy is helpful to improve the overall therapeutic effect, significantly improve the cognitive function of children, and improve the levels of NGF, GABA and NSE.


VIP (vasoactive intestinal polypeptide)-like immunoreactive amacrine cells in the retina of the rat.
Vasoactive intestinal polypeptide (VIP)-like immunoreactivity was demonstrated in the rat retina, using the peroxidase anti-peroxidase (PAP) method. VIP-like immunoreactivity was observed in the cytoplasm of amacrine cells of the inner nuclear layer (INL) and their varicose processes ramifying in the inner plexiform layer (IPL). VIP-like immunoreactive amacrine cells were present in both central and peripheral retinal regions. In some sections fine ramifications of varicose processes in the IPL could be clearly traced. VIP-like immunoreactivity was detected in both 'stratified' and 'diffuse' amacrine cells. VIP-like immunoreactive amacrine cells were classified into four types.


Nanobody-Dependent Detection of Microcystis aeruginosa by ELISA and Thermal Lens Spectrometry.
Nanobodies against cell surface antigens of toxic cyanobacteria Microcystis aeruginosa were recovered by whole-cell biopanning of a naïve phage display library of nanobodies. Six unique sequences were identified and three sub-cloned and purified as fusion immunoreagents together with either green fluorescent protein or AviTag to be used for diagnostics. The yields of nanobody constructs were in the range of 5-10 mg/l and their specificity and sensitivity was initially evaluated by immunofluorescence and by fluorescent enzyme-linked immunosorbent assay (ELISA) using fluorescent nanobodies. The ELISA data confirmed the nanobody specificity but showed that the saturation of the fluorescence signal already in the presence of few hundreds of cells limited the dynamic range of the method. As an alternative, Avi-tagged nanobodies were used in combination with streptavidin-linked horseradish peroxidase for developing a diagnostic colorimetric cell ELISA, the limit-of-detection of which was 3.2 and 4.5 cells/ml for the two tested cyanobacteria strains, whereas the linear range of the assay was expanded from 10 to 10,000 cells. The fluorescent nanobodies were finally exploited for quantifying cyanobacteria by thermal lens spectrometry (TLS) that enabled to reach a limit-of-detection of 1.2 cells/ml and provided a linear range of measurement between 0 and 10,000 cells. No cross-reactivity with unrelated microalgae was detected and both colorimetric ELISA and TLS provided a linear range of detection of few logs. The data indicate that nanobodies are suitable capture reagents and that both TLS and colorimetric ELISA are reliable to monitor variations of cyanobacteria populations.


A Comparison of Topical Corticosteroids and Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis.
Topical corticosteroids (TCS) are a mainstay of treatment for atopic dermatitis (AD). There are shared physician and patient concerns that TCS use can result in skin atrophy and systemic absorption. The clinical use of topical calcineurin inhibitors (TCI) for AD is relatively limited despite evidence that TCI are safe and effective. Understanding the differences in efficacy and adverse effects between TCS and TCI can help shape prescription practices to the benefit of patients. The objective of this review is to characterize the difference in efficacy and adverse effects between TCS and TCI. A review of the literature between 2002 and 2022 was performed using the PubMed, EMBASE, and Cochrane Library databases. Ten studies comparing TCS of varying potencies with TCI approved for AD treatment were included in the review. Outcome measures were qualified using percent reductions on the modified Eczema Area and Severity Index score and decreases in physician's global evaluation of AD severity. Tacrolimus had statistically significant (P < .05) improvement in disease severity compared with TCS in 4 of the 5 studies that compared tacrolimus with weak TCS. The data suggest greater treatment efficacy of tacrolimus over weak TCS, and inferior efficacy of pimecrolimus (TCI) compared with both tacrolimus and weak TCS. It is difficult to draw conclusions between moderate, potent, and very potent TCS and TCI due to the small number of available studies. TCI can improve disease severity, especially on thin or intertriginous skin regions most vulnerable to adverse events with TCS treatment, and their use may help overcome adherence issues due to patient bias against TCS.


Increased respiratory morbidity associated with exposure to a mature volcanic plume from a large Icelandic fissure eruption.
The 2014-15 Holuhraun eruption in Iceland was the largest fissure eruption in over 200 years, emitting prodigious amounts of gas and particulate matter into the troposphere. Reykjavík, the capital area of Iceland (250 km from eruption site) was exposed to air pollution events from advection of (i) a relatively young and chemically primitive volcanic plume with a high sulphur dioxide gas (SO2) to sulphate PM (SO42-) ratio, and (ii) an older and chemically mature volcanic plume with a low SO2/SO42- ratio. Whereas the advection and air pollution caused by the primitive plume were successfully forecast and forewarned in public advisories, the mature plume was not. Here, we show that exposure to the mature plume is associated with an increase in register-measured health care utilisation for respiratory disease by 23% (95% CI 19.7-27.4%) and for asthma medication dispensing by 19.3% (95% CI 9.6-29.1%). Absence of public advisories is associated with increases in visits to primary care medical doctors and to the hospital emergency department. We recommend that operational response to volcanic air pollution considers both primitive and mature types of plumes.


The lipF promoter of Mycobacterium tuberculosis is upregulated specifically by acidic pH but not by other stress conditions.
The lipF gene of Mycobacterium tuberculosis has been implicated in pathogenesis and its promoter has been shown to be upregulated by acidic stress. To further define the acidic pH that upregulates the lipF promoter from M. tuberculosis and to establish that it is specifically upregulated by acid stress and not by other environmental stresses, promoter expression levels were measured under a variety of conditions. The conditions measured were pH, temperature, oxidative stress, and hypoxic stress.


Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis.
The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.


[Prognostic significance of isolated local recurrences in breast cancer following mastectomy and axillary node excision. Apropos of 77 recurrences in 2362 patients].
During the years 1958-1984, 2 362 patients presenting with breast carcinoma were treated at the Fondation Bergonié by modified radical mastectomy and followed or not by radiotherapy or adjuvant chemotherapy. A retrospective analysis of this series showed that 77 patients (3.3%) presented an isolated locoregional recurrence as the first sign of treatment failure. A chest wall recurrence alone was noted in 47 patients, while 30 presented an involvement of the lymph nodes, sometimes associated with chest wall disease. The prognosis' factors of isolated locoregional recurrence, studied by multidimensional analysis by Cox's model are by decreasing order the disease free interval and the Scarf and Bloom's histologic grade. The median survival is 29 months after isolated locoregional recurrence and the survival curve is very similar to that of patients with isolated bone metastatic recurrences (median survival of 26 months) and slightly better than the median survival of patients with non osseous metastasis (median survival of 16 months).


Pleomorphic spermatic cord liposarcoma: A case report and review of management.
Liposarcoma of the spermatic cord is very rare, representing about 7% of para testicular sarcomas. It is considered to be one of the highest malignancy grades. We present a case of a liposarcoma of the spermatic cord in a 45-year-old male complaining of a progressive painless swelling in the right inguinoscrotal region. Ultrasonography and computed tomography findings were compatible with liposarcoma of the spermatic cord. We performed a right radical orchiectomy with a wide resection of the mass. Histological examination confirmed the diagnosis and showed a pleomorphic subtype. The mainstay of management of spermatic cord liposarcoma is wide excision with radical orchiectomy. The most important factors for prognosis are the histologic subtype and surgical margin status. Adjuvant radiotherapy should be considered in cases at high risk for local recurrence. Long-term surveillance is mandatory. Liposarcoma of the spermatic cord is an uncommon para testicular tumor which should be part of the differential diagnosis of inguinoscrotal mass. A radical inguinal orchiectomy with wide resection of the soft tissue mass and the spermatic cord are the key to longest local and systemic disease-free survival.


Neither Skin Sutures nor Foam Dressing Use Affect Tracheostomy Complication Rates.
Tracheostomy is commonly used for managing the airway of trauma patients. Complications are common and result in increased length of stays and treatment cost. The aim of this study is to evaluate whether the utilization of skin sutures or foam barrier dressings affect tracheostomy complication rates. This is a single-center retrospective review of patients who underwent a tracheostomy by the trauma service between January 2014 and December 2017. Collected variables included demographics, patient history, treatment variables, complications, and outcomes. Univariate and multivariate analyses were constructed to identify significant predictors for the development of complications. A total of 268 patients were included. The median age was 43.5 y, 221 (82.5%) patients were men, and the median BMI was 28 (IQR 24.6, 32.2). Most (87.3%) of the procedures were performed in the operating room and 82.5% were open. Skin sutures were used in 46.3% and 53.4% had a foam barrier dressing placed. Current smoking [OR 8.1 (95% CI 1.5, 43.6)] and BMI [OR 1.1 (95% CI 1.03, 1.2)] significantly increased the risk of developing pressure necrosis. Use of sutures or foam dressings was not associated with pressure necrosis, bleeding, or surgical site infection. There were no unexpected tracheostomy decannulations regardless of the use of skin sutures. Suturing the tracheostomy or applying a foam barrier dressing was not associated with overall complications or decannulation rates. Based on our data, we suggest that skin sutures may be safely abandoned.


Enhancer detection in the ascidian Ciona intestinalis with transposase-expressing lines of Minos.
Germline transgenesis with a Tc1/mariner superfamily Minos transposon was achieved in the ascidian Ciona intestinalis. Transgenic lines that express transposases in germ cells are very useful for remobilizing transposon copies. In the present study, we created transposase-expressing lines of Minos in Ciona. A Ciona gene encoding protamine (Ci-prm) is expressed in the testes and sperm. Transgenic lines expressing Minos transposase in the testes and sperm were created with a cis-element of Ci-prm, and used for enhancer detection. Double-transgenic animals between transposase lines and a transgenic line with an enhancer detection vector passed on several independent enhancer detection events to subsequent progeny. This technique allowed us to isolate transgenic lines that express GFP in restricted tissues. This system provides an easy and efficient method for large-scale enhancer detection in Ciona intestinalis.


Deleterious effects of prostaglandin E2 in oesophageal carcinogenesis.
Oesophageal carcinoma is a devastating disease with a poor prognosis. This hypothesis shows how prostaglandin E2 exerts carcinogenic effects in the oesophagus. The contribution of prostaglandin E2 is related to other factors that predispose to oesophageal carcinoma. The implication of the hypothesis is that nonsteroidal anti-inflammatory drugs such as aspirin may be useful in the prevention of oesophageal carcinoma.


Successful segmental auxiliary liver transplantation from a non-heart-beating donor: implications for split-liver transplantation.
Liver transplantation (LT) using grafts from non-heart-beating donors (NHBDs) has been shown to be a successful practice. Recently reported primary nonfunction rates are similar to those of LT using grafts from brain-dead donors. We report the use of an NHBD liver, which was cut into a right-lobe graft and implanted as an auxiliary partial orthotopic liver transplant for acute liver failure in a 11-year-old child. The warm ischemia time was 21 minutes, and the cold ischemia was 8 hours. Initial graft function was excellent, and the child is well, with normal liver function 2 months posttransplant. Reduction and splitting of livers from NHBDs for transplantation is a realistic option, provided there is careful selection of the graft.


How I manage myeloproliferative neoplasm-unclassifiable: Practical approaches for 2022 and beyond.
Myeloproliferative neoplasm (MPN)-unclassifiable (MPN-U) or not otherwise specified represents a rare, poorly defined and heterogeneous group of MPNs. Disease incidence is difficult to define but likely represents close to 5% of all MPNs when strict World Health Organisation (WHO) criteria are applied. Dynamic review over time is required to assess if the disease can be re-classified into another MPN entity. A diagnosis of MPN-U leads to many challenges for both the patient and physician alike including lack of agreed monitoring and therapeutic guidelines, validated prognostic markers and licenced therapies coupled with exclusion from clinical trials. MPN-U has an inherent risk of an aggressive clinical course and transformation in some but who, and when to treat in the chronic phase, including identifying who may require more aggressive therapy at an earlier stage, remains elusive. Moreover, despite the significant thrombotic risk, there is no agreement on systematic primary thromboprophylaxis. We hereby provide a contemporary overview of MPN-U in addition to four illustrative cases providing our collective suggested approaches to clinical challenges.


Body fluid regulation in a simulated disabled submarine: effects of cold, reduced O2, and elevated CO2.
Survivors awaiting rescue aboard a disabled submarine (DISSUB) lacking power and/or environmental control would potentially be exposed to cold and reduced O2 and elevated CO2 levels. We hypothesized that elevated CO2 levels would lead to hormone changes that would mitigate cold and hypoxia-induced body fluid losses. Blood was drawn from seven men on three mornings: baseline (21% O2, 0.05% CO2), after 4 d of low O2, cold, and high CO2 (T101; 4 degrees C, 16.75% O2, 2.5% CO2), and following acute withdrawal of cold and high CO2 (T173, 16.75% O2, 0.05% CO2). Total body water (TBW) was measured using deuterium oxide dilution at baseline and at T148. Hormone analyses included atrial natriuretic peptide (ANP), aldosterone (ALDO), and plasma renin activity (PRA). TBW decreased by 0.4 +/- 0.4 L. Water turnover was 3.0 +/- 0.5 L x d(-1). ANP (pg x ml(-1)) was lower (p < 0.05) at T101 (3.46 +/- 1.17) and T173 (4.97 +/- 2.28) vs. baseline (8.19 +/- 3.40). PRA (pg x ml(-1)) was higher (p < 0.05) at T101 (10.43 +/- 4.90) and T173 (14.23 +/- 4.48) vs. baseline (6.81 +/- 3.43). ALDO, serum osmolality, and electrolytes were not different across time. Urine flow was lower at T101 and T173 vs. baseline, and urine osmotic clearance was lower at T173 vs. baseline. Free water clearance did not change across time. These data indicate that the combination of cold, low O2, and high CO2 for 5-7 d did not change total body water and hormone changes and urinary measures across the DISSUB were consistent with fluid retention.


Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche.
Senescent cells are responsible, in part, for tissue decline during aging. Here, we focused on CNS neural precursor cells (NPCs) to ask if this is because senescent cells in stem cell niches impair precursor-mediated tissue maintenance. We demonstrate an aging-dependent accumulation of senescent cells, largely senescent NPCs, within the hippocampal stem cell niche coincident with declining adult neurogenesis. Pharmacological ablation of senescent cells via acute systemic administration of the senolytic drug ABT-263 (Navitoclax) caused a rapid increase in NPC proliferation and neurogenesis. Genetic ablation of senescent cells similarly activated hippocampal NPCs. This acute burst of neurogenesis had long-term effects in middle-aged mice. One month post-ABT-263, adult-born hippocampal neuron numbers increased and hippocampus-dependent spatial memory was enhanced. These data support a model where senescent niche cells negatively influence neighboring non-senescent NPCs during aging, and ablation of these senescent cells partially restores neurogenesis and hippocampus-dependent cognition.


Migration of covered stents in thoracic central vein obstruction procedures in patients with hemodialysis: Case report and literature review.
The objective of the study is to present a case of hemodialysis in which the covered stent that had migrated into the right ventricle was retrieved by exploratory thoracotomy, and to review the literature on the diagnosis and treatment of stent migration in thoracic central vein obstruction (TCVO) procedures for hemodialysis patients. A systematic search of the PubMed database was performed to identify clinical presentations, imaging strategies, stent types, and treatment modalities for stent migration in hemodialysis patients. A total of 14 case reports on stent migration in TCVO procedures for hemodialysis patients were included and analyzed. Ten cases included migration to the cardiac chambers and the remainder migration to the pulmonary artery. The common symptoms of stent migration in TCVO procedures are reported to be chest pain and dyspnea, while three of the cases studied involved no symptoms. Echocardiography, chest X-ray, and computed tomography are the commonly used methods for the diagnosis of stent migration and identification of the precise positioning of the stent. Stent migration to the right subclavian or innominate veins was the most prevalent case (seven cases). All were bare stents. Seven cases involved retrieval by interventional surgery, while four cases involved retrieval by open heart surgery. However, there were three cases in which the "wait-and-see" approach was adopted since the patients were asymptomatic. Stent migration in TCVO procedures is a rare but extremely serious complication. The causes are not fully understood. The current treatment strategies include interventional surgery, open heart surgery, and the "wait-and-see" approach.


Differential effect of sodium arsenite during the activation of human CD4+ and CD8+ T lymphocytes.
Contamination of water with arsenic is a problem affecting several regions of the world. Peripheral blood mononuclear cells (PBMC) from chronically exposed individuals show a lower replicating activity than non-exposed individuals when stimulated with phytohemagglutinin (PHA). We have previously reported that PBMC from healthy donors treated in vitro with 1 muM sodium arsenite (NaAsO2) and stimulated with PHA showed a reduction in proliferation by a delay in cell cycle entry and a decrease in the rounds of cell division. In this paper we tested the effect of 1-5 muM NaAsO2 on the proliferation, viability, blast transformation, expression of the CD4 and CD8 molecules, and during the activation and proliferation of both CD4+ and CD8+ T lymphocytes. We found a reduction in cell proliferation and an increase in non-dividing cells with higher concentrations of NaAsO2 (2-5 microM) when proliferation was studied by 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution. The use of 7-aminoactinomycin D (7-AAD) in CFSE-labeled cells allowed us to detect an increase in percentage of non-dividing cells, and an increase in apoptotic/dead cells mainly in non-proliferating cells. Analysis of the expression of CD4 and CD8 molecules on these cells showed that concentrations > or = 2 microM NaAsO2 reduced the expression of the CD8 molecule and induced apoptosis/death in CD4+ cells. Analysis of blast transformation by flow cytometry showed an accumulation of CD8+ resting cells in the presence of NaAsO2. Analysis of CD25 and CD69 expression in kinetics experiments in both subtypes showed a delay in the expression of CD25 and a delay in the downregulation of the CD69 molecule, in both CD4+ and CD8+ cells. However, in the case of CD8+ cells, we detected an accumulation of a CD25- CD69- population in the presence of increasing concentrations of NaAsO2. Altogether, our results show that NaAsO2 alters the expression kinetics of the early activation molecules CD25 and CD69 similarly in both subtypes. In addition, activated and non-activated CD4+ cells die by apoptotic mechanisms and although a percentage of CD8+ cells also die by apoptosis, a subpopulation of these cells is unable to activate and thus accumulates as resting cells.


Biogeographical, ecological, and phylogenetic analyses clarifying the evolutionary history of Calibrachoa in South American grasslands.
Calibrachoa is a charismatic South American genus of Solanaceae, closely related to Petunia, which encompasses approximately 30 species. Studies that were based solely on plastid molecular markers indicated the monophyly of the genus and distributed its species in two subgenera; to date no phylogeny has included a broad morphological variants and nuclear markers. Here, we present a phylogenetic analysis based on eight plastid and eight nuclear markers that cover the most extensive geographic distribution for the genus. We use this phylogeny to infer the biogeographic history of the genus and to understand the primary drivers for species diversification. Our results yield a fully supported tree where monophyly is confirmed to genus and subgenera. The species of Stimomphis subgenus that were previously considered uncertain, here emerge in four highly supported clades. The hypothesis of niche conservatism is confirmed, and adaptive radiation explains the species diversification. The lowlands are the most likely ancestral area of the genus, subgenera, and two clades of Stimomphis subgenus. Our results constitute an excellent starting point for further evolutionary and taxonomic studies and explain several uncertain evolutionary relationships in the group and the evolution of their distribution.


Lithium dipotassium citrate monohydrate, LiK2C6H5O7(H2O).
The crystal structure of dilithium potassium citrate monohydrate, Li+·2K+·C6H5O7 3-·H2O or LiK2C6H5O7·H2O, has been solved by direct methods and refined against laboratory X-ray powder diffraction data, and optimized using density functional techniques. The complete citrate trianion is generated by a crystallographic mirror plane, with two C and three O atoms lying on the reflecting plane, and chelates to three different K cations. The KO8 and LiO4 coordination polyhedra share edges and corners to form layers lying parallel to the ac plane. An intra-molecular O-H⋯O hydrogen bond occurs between the hydroxyl group and the central carboxyl-ate group of the citrate anion as well as a charge-assisted inter-molecular O-H⋯O link between the water mol-ecule and the terminal carboxyl-ate group. There is also a weak C-H⋯O hydrogen bond.


Clinical behaviour of high-copper amalgams with time, site, size and class of cavity preparation.
In this study 767 amalgam restorations placed in the posterior permanent teeth of 122 patients were evaluated at 6-monthly intervals up to 2 years. Six commercially available high-copper alloy amalgams were assessed for surface roughness, surface tarnish, marginal staining and marginal fracture and the results were related to product, restoration age, restoration cavity class type, restoration size (normal or large Class II preparations) and tooth type (premolar or permanent molar). Dispersalloy (Johnson and Johnson, East Windsor, USA) gave restorations which were overall superior for the clinical characteristics examined. Large restorations on the occlusal surfaces of molar teeth showed more signs of deterioration over the study than did other restoration types. However, all restorations remained clinically satisfactory throughout the study.


Atomic and electronic structures of GaN/ZnO alloys.
A new model Hamiltonian is developed to describe the ab initio energy differences of the nonisovalent alloy configurations based on the semiconductor electron counting rule. Monte Carlo simulations using this Hamiltonian show strong short range order of the GaN/ZnO alloy, which has significant effects on its electronic structure. We also predict further reduction of the band gap by increasing the synthesis temperature.


Synovial sarcoma: diagnosis on fine-needle aspiration by morphology and molecular analysis.
Synovial sarcoma (SS) is characterized by the t(X; 18) (p11.2; q11.2) translocation resulting in the SYT-SSX fusion transcript, detectable by reverse transcriptase polymerase chain reaction (RT-PCR). Fine-needle aspiration (FNA) cytology diagnosis of SS is challenging. We evaluated the applicability of RT-PCR on FNAs and to perform a detailed cytomorphological analysis in unequivocal cases of SS. A prospective and retrospective analysis was performed over 4 years (2003-2007). Prospectively, FNAs positive for the SYT-SSX fusion transcript by RT-PCR (n = 6) and, retrospectively, cases proven on histopathology and immunohistochemistry (ICC; positivity for vimentin and epithelial membrane antigen [EMA]/cytokeratin) as SS (n = 10) were included in the study. A detailed cytomorphological analysis was carried out. There were 9 biphasic and 7 monophasic tumors. The aspirates from both biphasic and monophasic tumors were richly cellular in all cases with micro tissue fragments. Pericapillary arrangement of tumor cells was present in most cases. Attempted gland formation was seen in 7 of 9 biphasic tumors. The individual tumor cells were round, ovoid, or spindle shaped. Pleomorphism was mild; monophasic tumors displayed lesser pleomorphism as compared with the biphasic ones. Nuclear chromatin was bland in all cases except 1 and nucleolar prominence was seen in just 3 biphasic tumors. Mast cells were seen in 3 biphasic and 2 monophasic tumors. Scanty to moderate extracellular matrix material was seen in 5 cases. FNA cytology of SS shows a spectrum of cytomorphological features; the diagnosis is confirmed by RT-PCR on the aspirated material for the SYT-SSX fusion transcript.


Optimisation of a silicon/silicon dioxide substrate for a fluorescence DNA microarray.
This paper presents a comprehensive theory and experimental characterisation of the modulation of the fluorescence intensity by the construction of optical interferences on oxidised silicon substrates used for DNA microarrays. The model predicts a 90-fold variation of the fluorescence signal depending on the oxide thickness. For a Cy3 dye, the signal is maximal for a 90 nm oxide thickness corresponding to a 7.5-fold enhancement with respect to a standard glass substrate. For experimental validation of the model, we have prepared Si/SiO2 substrates with different parallel steps of decreasing oxide thicknesses on the same sample using a buffered oxide etch (BOE) etching process after thermal oxidation. The SiO2 surface has been functionalized by a silane monolayer before in situ synthesis of L185 oligonucleotide probes. After hybridisation with complementary targets, the variations of the fluorescence intensity versus oxide thickness are in very good accordance with the theoretical model. The experimental comparison against a glass substrate shows a 10-fold enhancement of the detection sensitivity. Our results demonstrate that a Si/SiO2 substrate is an attractive alternative to standard glass slides for the realisation of fluorescence DNA microarrays whenever detection sensitivity is an important issue.


Growing tumor vessels: more than one way to skin a cat - implications for angiogenesis targeted cancer therapies.
The establishment of a functional, integrated vascular system is instrumental for tissue growth and homeostasis. Without blood vessels no adequate nutrition and oxygen would be provided to cells, nor could the undesired waste products be efficiently removed. Blood vessels constitute therefore one of the largest and most complex body network whose assembly depends on the precise balance of growth factors acting in a complementary and coordinated manner with cells of several identities. However, the vessels that are crucial for life can also foster death, given their involvement in cancer progression towards malignancy and metastasis. Targeting tumor vasculature has thus arisen as an appealing anti-cancer therapeutic approach. Since the milestone achievements that vascular endothelial growth factor (VEGF) blockade suppressed angiogenesis and tumor growth in mice and prolonged the survival of cancer patients when administered in combination with chemotherapy, the clinical development of anti-VEGF(R) drugs has accelerated remarkably. FDA has approved the use of bevacizumab - a humanized monoclonal antibody against VEGF - in colorectal, lung and metastatic breast cancers in combination with standard chemotherapy. Additional broad-spectrum VEGF receptor tyrosine kinase inhibitors, such as sunitinib and sorafenib, are used in monotherapy for metastatic renal carcinoma, while sunitinib is also approved for imatinib resistant gastrointestinal stromal tumors and sorafenib for advanced stage hepatocellular carcinoma. Nevertheless, the survival benefit offered by VEGF(R) blockers, either as single agents or in combination with chemotherapy, is calculated merely in the order of months. Posterior studies in preclinical models have reported that despite reducing primary tumor growth, the inhibition of VEGF increased tumor invasiveness and metastasis. The clinical implications of these findings urge the need to reconcile these conflicting results. Anti-angiogenic therapy represents a significant step forth in cancer therapy and in our understanding of cancer biology, but it is also clear that we need to learn how to use it. What is the biological consequence of VEGF-blockade? Does VEGF inhibition starve the tumor to death - as initially postulated - or does it rather foster malignancy? Can anti-VEGF(R) therapy favor tumor vessel formation by VEGF-independent means? Tumors are very diverse and plastic entities, able to adapt to the harshest conditions; this is also reflected by the tumor vasculature. Lessons from the bench to the bedside and vice versa have taught us that the diversity of signals underlying tumor vessel growth will likely be responsive (or resistant) to distinct therapeutic approaches. In this review, we propose a reflection of the different strategies tumors use to grow blood vessels and how these can have impact on the (un)success of current anti-angiogenic therapies.


Brief report: A socio-demographic profile of multiparous teenage mothers.
Delineate a socio-demographic profile of multiparous teenage mothers at a public hospital in Brazil. This is a cross-sectional study consisting of 915 interviews with teenage girls, including 170 multiparous subjects whose babies were born alive. The multiparous teenage mothers had the following average characteristics: 17.8 years old; first pregnancy at 16 years; beginning of sexual life at 14.2 years; dropped out of school at 13.6 years; attended school for 6 years with only 10% still attending school when they were interviewed; 87.4% had prenatal exams; monthly income was reported to be 0.3% less than the national minimum salary. Teenage mothers are in need of better social, educational, and health care in order to have a greater chance of a positive motherhood experience, thereby creating a better, healthier environment for their children.


Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells.
In the bone marrow, MSCs reside in a hypoxic milieu (1-5% O2) that is thought to preserve their multipotent state. Typically, in vitro expansion of MSCs is performed under normoxia (~ 21% O2), a process that has been shown to impair their function. Here, we evaluated the characteristics and function of MSCs cultured under hypoxia and hypothesized that, when compared to normoxia, dedicated hypoxia will augment the functional characteristics of MSCs. Human and porcine bone marrow MSCs were obtained from fresh mononuclear cells. The first study evaluated MSC function following both long-term (10 days) and short-term (48 h) hypoxia (1% O2) culture. In our second study, we evaluated the functional characteristics of MSC cultured under short-term 2% and 5% hypoxia. MSCs were evaluated for their metabolic activity, proliferation, viability, clonogenicity, gene expression, and secretory capacity. In long-term culture, common MSC surface marker expression (CD44 and CD105) dropped under hypoxia. Additionally, in long-term culture, MSCs proliferated significantly slower and provided lower yields under hypoxia. Conversely, in short-term culture, MSCs proliferated significantly faster under hypoxia. In both long-term and short-term cultures, MSC metabolic activity was significantly higher under hypoxia. Furthermore, MSCs cultured under hypoxia had upregulated expression of VEGF with concomitant downregulation of HMGB1 and the apoptotic genes BCL-2 and CASP3. Finally, in both hypoxia cultures, the pro-inflammatory cytokine, IL-8, was suppressed, while levels of the anti-inflammatories, IL-1ra and GM-CSF, were elevated in short-term hypoxia only. In this study, we demonstrate that hypoxia augments the therapeutic characteristics of both porcine and human MSCs. Yet, short-term 2% hypoxia offers the greatest benefit overall, exemplified by the increase in proliferation, self-renewing capacity, and modulation of key genes and the inflammatory milieu as compared to normoxia. These data are important for generating robust MSCs with augmented function for clinical applications.


[Analysis of safety and effects on the oral whole cell/recombinant B subunit cholera vaccine in university students and workers].
To evaluate the safety, immunogenicity and protective efficiency of the oral whole cell/recombinant B subunit cholera vaccine in Beijing Olympic volunteers and workers. Analyzing the incidence rate of adverse reaction and Protective Rate (PR) after taking the vaccine in Olympic volunteers in 6 universities in Beijing; comparing the anti-cholera toxin (CT) detected with ELISA prior and after taking the vaccine in Olympic workers. The total rate of adverse reaction of Olympic volunteers was 0.38%; the main side effects were gastrointestinal symptoms, such as bellyache and diarrhea which were mild and temple; the acute diarrhea incidence rate of Olympic volunteers after taking the vaccine was significantly lower than those not taking it, the PR was 76.27%; the positive rate of anti-CT of Olympic workers after taking the vaccine was significantly higher than those before taking it, the levels of anti-CT titers declined after 6 months since they had taken the vaccine. The results from above two observed population indicate that the oral rBS-WC cholera vaccine is efficient and safe.


High-throughput MS-based protein phenotyping: application to haptoglobin.
A high-throughput affinity capture and reduction approach was developed for phenotype and post-translational modification analysis of a complexed globular protein, haptoglobin (Hp), directly from human plasma. Hp was selectively retrieved utilizing anti-Hp antibodies immobilized onto affinity pipette tips, eluted onto a formatted mass spectrometer target for reduction of Hp alpha-chains (Hpalpha1 and Hpalpha2) and subjected to subsequent MALDI-MS analysis. The affinity capture and reduction approach was originally developed from a pre-extraction reduction methodology that was optimized to an affinity capture post-reduction technique for intact Hp alpha-chain variant analysis, phenotype classification and ensuing post-translational variant detection. Three common Hp phenotypes (1-1, 2-1 and 2-2) were assigned according to detection of Hpalpha1 and/or Hpalpha2 reduced intact chain(s) average mass(es). The affinity capture post-reduction approach was scaled for high-throughput Hp alpha-chain phenotype analysis from a normal plasma cohort. The entire sample cohort was successfully analyzed and phenotyped using the developed approach. Additionally, Hp post-translational variants were detected and assigned via accurate MS analyses. The results of this study suggest use of the methodology in future analyses of other similarly complexed proteins and in normal versus disease cohort population proteomics studies.


Social Response to the Vaccine against COVID-19: The Underrated Power of Influence.
The Coronavirus Disease 2019 (COVID-19) pandemic has highlighted the need for preventive medicine and vaccinology to be paralleled to eliminate COVID-19 cases. A web-based questionnaire was disseminated through social media in the late November assessing the factors that may have influenced the final response to vaccination against COVID-19 in vaccinated and non-vaccinated Greek people. Women, the younger generations, and university graduates were more likely to accept vaccination, whereas men, those with a basic education level, and the older generation showed a hesitance to the vaccine against COVID-19. About half of the vaccinated participants were influenced in their final decision mainly by being informed from the internet (50.4%), their work (51.7%), and social life (53,1%) while half of the non-vaccinated individuals were mostly influenced by keeping updated from the internet (55.5%) and by government policies (51.3%). COVID-19 risk (OR 2.511; CI 2.149-2.934; p = 0.000), frequent vaccinations for emerging pathogens (OR 14.022; CI 11.998-16.389), and social life (OR 2.828; CI 2.417-3.309; p = 0.000) had a significant impact on people's positive response to vaccination against COVID-19. Monitoring and assessing the influence factors for the response to vaccination can be favourable strategies to further manage societal vaccination rates.


[Evaluation of vitamin status of workers of oil-processing enterprises (Samara Region) according to the data on vitamin consumption and blood serum level].
Vitamin status of 77 employees of oil refineries (39 men and 38 women aged 22 to 62 years, body mass index - 25.0±4.7 kg/m2) has been assessed in autumn. The sufficiency with vitamins A, E, D, B2, B12, folate and beta-carotene was evaluated by determination in blood plasma, daily intake of vitamins B1, B2, niacin, C, A and betacarotene was calculated by frequency of food consumption during previous month. All surveyed were sufficiently supplied with vitamins A, B12 and folate (reduced level was detected in 0-2.6%). The content of tocopherols referred to triglycerides was reduced in 33% of the workers, in men it was 2 fold more likely (p<0.05) than in women (43.6 vs 21.1%). Vitamin D insufficiency took place in 23.4% of individuals, vitamin B2 and beta-carotene - in 44.2%. A reduced blood plasma content of one vitamin was detected in 39.0% of the surveyed, while two vitamins - in 24.7% persons, 2.2 fold more often (p<0.05) in men than in women. Multivitamin insufficiency was detected in 10.4% of workers. Reduced blood plasma level of at least one vitamin-antioxidant was detected in 46.8% (in 61.5% of men and 31.6% of women, p<0.05). 26.0% of surveyed were provided with all 6 vitamins and beta-carotene. Reduced relative to RDA daily intake of antioxidant vitamins (ascorbic acid and beta-carotene) was observed in 64.9 and 100% of individuals, B group vitamins (niacin, B2 and B1) - in 48.1-64.9%, vitamin A - in 42.9%.


['Advanced triage' improves patient flow in the emergency department without affecting the quality of care].
To investigate whether 'advanced triage' improved patient flow among self-referred patients in the emergency department of a level 1 trauma centre and, most importantly, whether the quality of medical care was maintained. In advanced triage, the triage nurse initiates additional diagnostic investigations independently. Interventional study. After a baseline measurement had been carried out for eleven days (n = 506), the advanced triage protocol was tested during ten day or evening shifts (n = 198). The length of stay in the emergency department was measured. The attending emergency physician assessed the correctness and completeness of the additional diagnostics initiated by the triage nurse. Two traumatologists and two radiologists assessed the quality of x-ray imaging requests independently of each other. Average patient length of stay (LOS) was reduced by fourteen minutes (14%). The improvement was achieved primarily in patients who required additional diagnostic investigations. Their average LOS decreased by 27 minutes (18%). There was an 8% increase in the total number of diagnostic investigations requested. The triage nurse initiated the investigations correctly and fully in 93% of cases. The quality of x-ray imaging requests remained the same as before the introduction of advanced triage. The implementation of advanced triage improved patient flow for self-referred patients in the emergency department without affecting the quality of medical care. Advanced triage was successful in the Dutch system, too.


[The prevention of the hypercoagulation syndrome during the combined treatment of lung cancer patients using artificial hyperglycemia].
Status of hemostasis system and occurrence of postoperative thromboembolic complications were assessed in 246 lung cancer patients in whom combined treatment included artificial hyperglycemia. The latter condition contributed to higher blood coagulability resulting in lung artery thromboembolism in some cases. Administration of a combination of heparin, curantil and nicotinic acid was followed by a decrease in blood coagulability, increase in anticoagulation function, decrease in platelet aggregability, activation of fibrinolysis and regression of biochemical signs of DIC syndrome thereby assuring a drop in the occurrence of thromboembolic complications.


Heterogeneity of human T lymphocytes to bind sheep red blood cells in multiple sclerosis patients and controls.
The present studies were performed as a result of the report that the human T-cells may be composed of heterogeneous subpopulation in the sense of their ability to bind SRBC. In this paper, the diversity of human peripheral lymphocytes in M.S. patients, other neurological diseases and controls were investigated by means of an interesting approach based on the heterogeneity of humnan T-lymphocytes examined by the rosette formation of SRBC (E rosette) in two different reaction media.


Interactions between Al₁₂X (X = Al, C, N and P) nanoparticles and DNA nucleobases/base pairs: implications for nanotoxicity.
The interactions between neutral Al(12)X(I ( h )) (X = Al, C, N and P) nanoparticles and DNA nucleobases, namely adenine (A), thymine (T), guanine (G) and cytosine (C), as well as the Watson-Crick base pairs (BPs) AT and GC, were investigated by means of density functional theory computations. The Al(12)X clusters can tightly bind to DNA bases and BPs to form stable complexes with negative binding Gibbs free energies at room temperature, and considerable charge transfers occur between the bases/BPs and the Al(12)X clusters. These strong interactions, which are also expected for larger Al nanoparticles, may have potentially adverse impacts on the structure and stability of DNA and thus cause its dysfunction.


SARS-CoV-2 Infection during the Omicron Surge among Patients Receiving Dialysis: The Role of Circulating Receptor-Binding Domain Antibodies and Vaccine Doses.
It is unclear whether circulating antibody levels conferred protection against SARS-CoV-2 infection among patients receiving dialysis during the Omicron-dominant period. We followed monthly semiquantitative SARS-CoV-2 RBD IgG index values in a randomly selected nationwide cohort of patients receiving dialysis and ascertained SARS-CoV-2 infection during the Omicron-dominant period of December 25, 2021 to January 31, 2022 using electronic health records. We estimated the relative risk for documented SARS-CoV-2 infection by vaccination status and by circulating RBD IgG using a log-binomial model accounting for age, sex, and prior COVID-19. Among 3576 patients receiving dialysis, 901 (25%) received a third mRNA vaccine dose as of December 24, 2021. Early antibody responses to third doses were robust (median peak index IgG value at assay limit of 150). During the Omicron-dominant period, SARS-CoV-2 infection was documented in 340 (7%) patients. Risk for infection was higher among patients without vaccination and with one to two doses (RR, 2.1; 95% CI, 1.6 to 2.8, and RR, 1.3; 95% CI, 1.0 to 1.8 versus three doses, respectively). Irrespective of the number of vaccine doses, risk for infection was higher among patients with circulating RBD IgG <23 (506 BAU/ml) (RR range, 2.1 to 3.2, 95% CI, 1.3 to 3.4 and 95% CI, 2.2 to 4.5, respectively) compared with RBD IgG ≥23. Among patients receiving dialysis, a third mRNA vaccine dose enhanced protection against SARS-CoV-2 infection during the Omicron-dominant period, but a low circulating RBD antibody response was associated with risk for infection independent of the number of vaccine doses. Measuring circulating antibody levels in this high-risk group could inform optimal timing of vaccination and other measures to reduce risk of SARS-CoV-2 infection.


Effect of secretin on serum trypsin-like immunoreactivity in alcoholics.
Serum trypsin-like immunoreactivity (TLI) was studied with a newly developed radioimmunoassay in human subjects. The intravenous administration of secretin was followed by an evident increase of serum TLI significantly greater in alcoholics as compared to controls.


Evaluation of segmental mandibular resection without microvascular reconstruction in patients affected by medication-related osteonecrosis of the jaw: a systematic review.
Medication-related osteonecrosis of the jaw (MRONJ) is a severe condition that affects the jaw in patients exposed to specific drugs. More often it has been described in association with bisphosphonates (BP), but nowadays it has been observed with the use of other medications, such as denosumab (a RANK ligand inhibitor and monoclonal antibody agent) and antiangiogenic drugs. Managing the condition has unfortunately proven difficult and still remains a major challenge for clinicians and surgeons. The aim of this systematic review was to identify and analyse the evidence on mandibular segmental resection in patients with advanced MRONJ. A multi-database (PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials) systematic search was performed. Any type of study on human patients treated with antiresorptive and antiangiogenic drugs was considered. The primary aim was to understand the success of mandibular segmental resection in the short, medium, and long term, and to understand its effects before, during, and after the operation. The search yielded 11 studies that were eligible for analysis with a total of 67 patients. Of the 11 studies, seven reported no complications, and overall, postoperative complications were seen in 16 cases. Recurrence of osteonecrosis was reported in one study. The most common postoperative complication was removal of hardware (n = 11). The mean (SD) follow-up time for eight studies was 35.57 (17.73) months. According to the limited data available in the literature, mandibular segmental resection is a viable treatment that has been used successfully in patients with various stages of MRONJ. The data show a relatively high percentage of recurrence. Additional data based on a larger cohort of patients or case-control studies are necessary to justify routine use of this type of intervention in patients affected by the condition.


MDCT of the airways: technique and normal results.
The new generation of multidetector CT (MDCT) has revolutionized noninvasive imaging of proximal and distal airways. Exquisite anatomic details of the airway lumen and airway wall on axial CT images benefit in routine practice from postprocessing tools in adequate orientation. This method ensures an excellent assessment of the morphology and location of any pathology. It may be combined with use of very low dose CT. Airway lumen and airway wall areas may be quantitatively assessed on MDCT images by using specific techniques that are reproducible and accurate.


Dimethyl sulfoxide maintains structure and function of cryopreserved equine endometrial explants.
Availability of viable frozen-thawed endometrial tissues could facilitate detailed studies into physiologic and disease processes influencing the endometrium. This study was designed to investigate the cryosurvival of equine endometrial tissue. Previous studies in the human and horse have focused on cryopreservation of dissociated endometrial cells. To our knowledge, there are no studies on cryopreservation of endometrial explants. Our objectives were to 1) determine the influence of differing concentrations of the permeating cryoprotectant dimethyl sulfoxide (Me2SO) on viability, structural integrity, and gene expression of cryopreserved equine endometrial tissues prior to and following a 5-day explant culture in vitro and 2) examine the influence of low (1000 mg/L dextrose) vs high (4500 mg/L dextrose) glucose medium during in vitro culture. Both 10% and 20% (v/v) concentrations of Me2SO maintained viability following cryopreservation and in vitro culture. In addition, gene expression remained unaltered following cryopreservation with either 10% or 20% Me2SO. However, tissue structural integrity was slightly reduced compared to the fresh control. Furthermore, there was no difference in structural integrity, cell viability, or gene expression between low and high glucose medium during in vitro culture. Although E-cadherin and Ki67 gene expression was not different among fresh, 10% Me2SO, and 20% Me2SO treatments prior to or following tissue culture, estrogen receptor-α and progesterone receptor gene expression were reduced in all groups after explant culture. This is the first report of successful cryopreservation of equine endometrial explants.


High-energy phosphate metabolism in the calf muscle during moderate isotonic exercise under different degrees of cuff compression: a phosphorus 31 magnetic resonance spectroscopy study.
The purpose of this study was to investigate phosphocreatine (PCr) and inorganic phosphate levels as well as pH changes in exercising muscle at a workload of 4.5 W under progressive cuff stenoses, whereby the flow reduction due to cuff compression was quantified by flow-sensitive magnetic resonance imaging. By using a whole-body 1.5-T magnetic resonance scanner and an exercise bench, serial phosphorus 31 (31P) magnetic resonance spectroscopy with a time resolution of 30 seconds was performed in 10 healthy men. Percentage changes in PCr, inorganic phosphate (Pi), and pH were statistically evaluated in comparison with baseline. The exercise protocol was characterized by a constant workload level of 4.5 W. Ischemic conditions were achieved by a cuff that was placed at the upper leg. Consecutively, increments of 0, 60, 90, 120, and 150 mm Hg were applied. Each increment lasted for 3 minutes. The following rest period was 10 minutes. Blood flow increased significantly immediately after the onset of muscle exercise. No significant changes in blood flow were detected as long as the air pressure of the pneumatic cuff was 60 to 90 mm Hg. Significant reductions in blood flow were observed immediately after inflation of the cuff to 120 and 150 mm Hg. PCr passed into a steady state during the first increment with 0 mm Hg and showed no substantial changes during the increment with 60, 90, and 120 mm Hg. PCr hydrolysis seemed progressive during the 150-mm Hg increment. Pi passed into a plateau level at the onset of exercise and increased significantly at the increment of 150 mm Hg. The pH turned into a steady state with no significant changes during the increments up to 120 mm Hg. At 150 mm Hg, pH decreased progressively. PCr levels at the end of the 150-mm Hg increment correlated significantly and moderately with the reduction in blood flow. Our study shows that the ischemic condition during constant muscle exercise is clearly characterized by PCr and Pi kinetics, as well as by pH changes. The correlation between the degree of blood flow reduction and PCr levels in the exercising muscle groups, which are supplied by the stenosed arteries, is the first essential of using 31P magnetic resonance spectroscopy in the assessment of the effect of arterial stenoses on muscle function in claudicants.


Human immunodeficiency viruses and drug therapy: resistance and implications for antiretroviral therapy.
Through a concerted effort to combat the human immunodeficiency virus (HIV) epidemic, researchers have made significant strides in molecular biology, virology, and immunology, which have resulted in an increased understanding of the complexities of this infection. The biggest obstacle to the success of current HIV therapy, however, is the emergence of viral resistance. Viral resistance is caused by mutations in the HIV-1 genome coding for structural changes in the target enzymes that can affect the binding or activity of the inhibitors. More information on the genetic basis of HIV resistance, mechanisms of viral variation, and therapeutic strategies for overcoming HIV resistance are needed. Sixty million people have been infected with HIV, 24 million have died, and it is projected that 200 million individuals will be infected by 2020.