Dynamics of DNA duplexes containing internal G.T, G.A, A.C, and T.C pairs: hydrogen exchange at and adjacent to mismatch sites.
We have undertaken high-resolution NMR studies to elucidate the conformation and dynamics of the d(C1-G2-C3-G4-A5-A6-T6-T5-C4-G3-C2-G1) 12-mer duplex and its analogs where the symmetrically related dG.dC base pairs in position 3 are replaced by dG.dT, dG.dA, dA.dC, and dT.dC mismatch pairs. The pairing schemes for the dG.dA and dA.dC mismatch interactions have been elucidated from intra- and inter-base pair nuclear Overhauser effect measurements. The replacement of two dG.dC pairs by two dG.dA or two dG.dT pairs results in an approximately 20 C destabilization of the 12-mer; replacement by two dA.dC or two dT.dC pairs results in an approximately 30 C destabilization of the 12-mer. The hydrogen exchange kinetics of the resolved and assigned imino protons in the 12-mer duplex and its mismatch analogs in 0.1 M phosphate have been monitored by saturation recovery measurements. We observe kinetic destabilization at dG.dC base pair 4 adjacent to the mismatch site, which increases in the order 12-mer less than 12-mer GT less than 12-mer GA less than 12-mer AC less than 12-mer TC. By contrast, the kinetic destabilization at dA.dT base pairs 5 and 6 increases in the order 12-mer approximately 12-mer GT approximately 12-mer GA less than 12-mer AC less than 12-mer TC. These results demonstrate that the introduction of dG.dT and dG.dA mismatches results in dynamic perturbations that are localized at the adjacent base pairs, whereas introduction of dA.dC and dT.dC mismatches results in perturbations that extend several base pairs into the duplex. Both base pair opening and preequilibrium pathways contribute to the imino proton hydrogen exchange rates in the 12-mer GA, 12-mer AC, and 12-mer TC duplexes, which is in contrast to earlier studies that demonstrated that the imino proton hydrogen exchange rates were a direct measure of the base pair opening rates in the 12-mer and 12-mer GT duplexes.


Patient Blood Management after Hematopoietic Stem Cell Transplantation in a Pediatric Setting: Starting Low and Going Lower.
Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL; p = 0.010), whereas it remained the same in 2017, 2018, and 2019 (7.3, 7.2, and 7.2 g/dL, respectively). Similarly, the PLT threshold decreased significantly from 2016 to 2017 (from 18,000 to 16,000/μL; p = 0.026) and further decreased in 2019 (15,000/μL). In patients without severe hemorrhagic complications, the number of RBC and PLT transfusions remained very low over time. No increase in 100-day and 180-day non-relapse mortality or adverse events was observed during the study period. No patient died due to hemorrhagic complications. Our preliminary observations support robust studies enrolling HSCT patients in patient blood management programs.


Normative visual acuity in Chinese preschoolers aged 36 to <48 months as measured with the linear HOTV chart: the Yuhuatai Pediatric Eye Disease Study.
To document population-based normative data for uncorrected visual acuity (UCVA) in Chinese preschoolers aged 36 to <48 months without any sight-affecting abnormalities and to evaluate its effectiveness for vision referral. In a population-based cohort of children in the Yuhuatai Pediatric Eye Disease Study, UCVA was measured by using the linear HOTV chart, followed by other ocular examinations. Reference population was defined as children without ophthalmic abnormalities or refractive error. Normative UCVA was obtained from the reference population. The UCVA referral cut-off was defined as the lowest fifth percentile of the normative distribution of UCVA. The analysis cohort consisted of 1606 Chinese preschoolers aged 36 to <48 months. Among them, a total of 791 children were included in the reference population. The 5th, 50th and 95th percentiles of the UCVA distribution in the reference population were 20/40, 20/32 and 20/25, respectively. UCVA improved with increasing age (p<0.0001), but worsen if prematurity was presented (p=0.041). Using the fifth percentile, UCVA cut-off from the reference population generated referral rates of 26.9% in the general population, and detected more than 86% of amblyopia cases. We propose that UCVA no better than 20/40 measured by linear HOTV chart should be a referral cut-off for Chinese preschoolers aged 36 to <48 months. Most amblyopia cases can be identified with this age-specific and chart-specific UCVA cut-off.


Evaluation of electrical impedance tomography in the measurement of PEEP-induced changes in lung volume.
A new noninvasive practical technique called electrical impedance tomography (EIT) was examined for the measurement of alveolar recruitment. Prospective clinical study. ICU of a general hospital. Acute respiratory failure (ARF) patients. The ventilation-induced impedance changes (VICs) of the nondependent and the dependent part of the lung were determined by EIT as a measure of tidal volume distribution. By the use of an impedance ratio (IR), defined as the VIC of the nondependent part of the lung divided by the VIC of the dependent part of the lung, the ventilation performances in both parts of the lung were compared to each other. Between patients, the VIC of the nondependent part of the lung was significantly lower in the patients with a level of positive end-expiratory pressure (PEEP) of > 10 cm H2O than in patients with a PEEP of < 5 cm H2O (p < 0.05). A significantly lower IR (-/+ SD) was found in the group with PEEP of > 10 cm H2O than in the group with PEEP between 0 and 5 cm H2O (1.28+/-0.58 vs 2.99+/-1.24, respectively; p < 0.01). In individual patients, the VIC of the whole lung increased when the PEEP level was increased. The VICs of the nondependent part of the lung and of the dependent part of the lung showed significant increases at a PEEP of 10 cm H2O compared to a PEEP of 0 cm H2O (p < 0.05). Also the IR decreased in individual patients when the PEEP was increased; a significant decrease was found at 10 cm H2O compared to 0 cm H2O (1.67+/-1.24 vs 2.23+/-1.47, respectively; p < 0.05). The decrease in IR indicates an increase in VIC in the dependent part of the lung above the nondependent part of the lung. The increase in VIC can be regarded as an increase in lung volume, implying alveolar recruitment in the dependent part of the lung. The same results also have been shown in earlier reports by CT scan. Since EIT is far more practical than CT scanning and also is a bedside method, EIT might help in the adjustment of ventilator settings in ARF patients.


Autoantibodies to thyroglobulin are encoded by diverse V-gene segments and recognize restricted epitopes.
Murine experimental autoimmune thyroiditis has been used as a model for human autoimmune thyroiditis. Experimental autoimmune thyroiditis is induced in mice by immunization with mouse thyroglobulin (Tg) in CFA. To characterize the antibodies to this autoantigen, we have studied the binding specificities and determined the nucleotide sequences of monoclonal anti-Tg antibodies. The specificities of the mAb for determinants on Tg varied extensively. Seven of 16 mAb showed reactivity to only mTg, 4 reacted to Tg from more than one species and four reacted to a variety of Ag. Many of the mAb were competitively inhibited by thyroid hormones, suggesting that they recognize the hormonogenic sites on the Tg molecule. The mAb could be divided into at least seven reactivity patterns based on reciprocal competitive inhibition studies, indicating that mTg contains at least seven antigenic regions. DNA sequence analysis of the mAb showed that a large number of V region gene segments encoded the H and L chains. No evidence for preferential use of any V region family or gene segment was found. Gene segments from the VH 7183, Q52, J558, and VH10 families were used by heavy chains, and the V kappa 1, 4, 8, 9, 19, and 21 families were used by kappa-chains. The results indicate that the antigenic epitopes on mTg elicit a very diverse autoantibody response that is derived from a large number of V region gene segments. Many of these autoantibodies show specific reactivity with mTg indicating they recognize species specific epitopes. The results suggest that clonal deletion of autoreactive Ab to certain self-epitopes may not occur.


Circadian clock, cancer, and chemotherapy.
The circadian clock is a global regulatory system that interfaces with most other regulatory systems and pathways in mammalian organisms. Investigations of the circadian clock-DNA damage response connections have revealed that nucleotide excision repair, DNA damage checkpoints, and apoptosis are appreciably influenced by the clock. Although several epidemiological studies in humans and a limited number of genetic studies in mouse model systems have indicated that clock disruption may predispose mammals to cancer, well-controlled genetic studies in mice have not supported the commonly held view that circadian clock disruption is a cancer risk factor. In fact, in the appropriate genetic background, clock disruption may instead aid in cancer regression by promoting intrinsic and extrinsic apoptosis. Finally, the clock may affect the efficacy of cancer treatment (chronochemotherapy) by modulating the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs as well as the activity of the DNA repair enzymes that repair the DNA damage caused by anticancer drugs.


Mechanisms of stabilization of the insulin hexamer through allosteric ligand interactions.
The insulin hexamer is an allosteric protein capable of undergoing transitions between three conformational states: T6, T3R3, and R6. These transitions are mediated by the binding of phenolic compounds to the R-state subunits, which provide positive homotropic effects, and by the coordination of anions to the bound metal ions, which act as heterotropic effectors. Since the insulin monomer is far more susceptible than the hexamer to thermal, mechanical, and chemical degradation, insulin-dependent diabetic patients rely on pharmaceutical preparations of the Zn-insulin hexamer, which act as stable forms of the biologically active monomeric insulin. In this study, the chromophoric chelator 2,2',2"-terpyridine (terpy) has been used as a kinetic probe of insulin hexamer stability to measure the effect of homotropic and heterotropic effectors on the dissociation kinetics of the Zn2+- and Co2+-insulin hexamer complexes. We show that the reaction between terpy and the R-state-bound metal ion is limited by the T3R3 <==> T6 or R6 <==> T3R3 conformational transition steps and the dissociation of one anionic ligand, or one anionic ligand and three phenolic ligand molecules, respectively, for T3R3 and R6. Consequently, because the activation energies of these steps are dominated by the ground-state stabilization energy of the R-state species, the kinetic stabilization of the insulin hexamer toward terpy-induced dissociation is linked to the thermodynamic stabilization of the hexamer. The mass action effect of anion binding and, foremost, of phenolic ligand binding provides the major mechanism of stabilization, resulting in the tightening of the tertiary and quaternary hexamer structures. Using this kinetic method, we show that the R6 conformation of Zn-insulin in the presence of Cl- ion and resorcinol is > 1.5 million-fold more stable than the T3 units of T6 and T3R3 and > 70,000-fold more stable than the R3 unit of T3R3. Furthermore, the stabilization effect is correlated with the affinity of the ligands: the tighter the binding, the slower the reaction between terpy and R-state-bound metal ion. These concepts provide a new basis for the pharmaceutical improvement of the physicochemical stability of formulations both for native insulin and for fast-acting monomeric insulin analogues through ligand-mediated allosteric interactions.


Concomitant up-regulation of proopiomelanocortin and dopamine D2-receptor gene expression in the pituitary intermediate lobe of the spontaneously hypertensive rat.
Alterations in central dopaminergic mechanisms in the Spontaneously Hypertensive Rat (SHR) have been previously implicated in the development of the hypertensive phenotype in this rat strain. We have examined the expression and regulation of the dopamine-responsive gene proopiomelanocortin (POMC) in the neurointermediate lobe (NIL) of the pituitary in both SHR and normotensive Wista Kyoto (WKY) rats. Solution hybridization/nuclease protection analysis showed that adult SHR express POMC mRNA in the NIL at approximately 2-4 times the level seen in normotensive WKY controls, associated with a concomitant 2-fold increase in dopamine D2-receptor (D2-R) mRNA expression. Despite the obvious difference in D2-R gene expression, NIL POMC mRNA in both rat strains was regulated in an identical manner following 4 d in vivo bromocriptine or haloperidol treatment. In contrast, though D2-R mRNA expression in the WKY NIL was significantly up-regulated by D2-R blockade with haloperidol, the elevated levels of D2-R mRNA in the NIL of the hypertensive strain were not altered by D2-R antagonism. Following isolation from all hypothalamic input by 5 d in vitro culture, SHR melanotrophs exhibited a 2-3 fold higher rate of beta EP secretion and POMC mRNA expression than melanotrophs derived from normotensive WKY rats, though beta EP secretion was inhibited in a similar fashion by the D2-R agonist quinpirole in both cultures. The current data demonstrate changes in expression of both POMC and D2-R mRNA in the SHR NIL which may be a consequence of altered dopaminergic input and/or alterations in D2-R regulation in this tissue, possibly enabling other factors in addition to dopamine to maintain the NIL of the SHR in a relatively hyperactive state. Whether or not POMC-derived peptides or other factors secreted from the melanotroph cell play any role in the development or maintenance of hypertension in this strain is yet to be established.


Lipoxin A4 levels in asthma: relation with disease severity and aspirin sensitivity.
Lipoxin (LX) A4, an endogenous anti-inflammatory eicosanoid, has been found to be low in patients with severe asthma. However, few studies also suggested more diminished LX A4 levels in aspirin-exacerbated respiratory disease (AERD) when compared with aspirin-tolerant asthma (ATA). It is, therefore, currently not clear whether the asthma severity or the presence of AERD has a primary role in the disturbed LX metabolism. To detect LX A4 and 15-epi-LX A4 levels in asthma patients with and without AERD of comparable severity. The study groups consisted of 22 subjects with AERD, 22 subjects with ATA and 10 volunteers without asthma and aspirin sensitivity. Whole-blood samples were stimulated with calcium ionophore, A23187 (5 x 10(-5) m) and A23187 (5 x 10(-5) m)+aspirin (10(-4) m). LX A4 and 15-epi-LX A4 levels were analysed by the enzyme immune assay method. Severe asthma patients in both AERD [0.5 (0.8)] ng/mL and ATA [0.5 (0.45) ng/mL] groups showed diminished generation for LX A4 to stimulation with A23187 in comparison with other severity degrees in their groups (P=0.02 and 0.046, respectively). LX A4 generation in both severe groups was comparable with each other (P>0.05). Although severe cases with AERD showed a diminished capacity to generate 15-epi-LX A4, this did not reach statistical significance. This study indicated that diminished LX A4 generation was unique to severe asthma phenotype regardless of comorbid aspirin sensitivity. Clinical Implications Lower LX A4 levels in severe asthma would suggest a possibility for LX analogues as future treatment options in these patients.


Influence of wearing a scuba diving mouthpiece on the stomatognathic system - considerations for mouthpiece design.
Although diver's mouth syndrome (DMS) has long been recognized by scuba divers, little attention has been paid to the influence of wearing a scuba diving mouthpiece on the stomatognathic system. In this review, DMS-related stomatognathic events (DMS-SE) while wearing a mouthpiece, the relationship between components of the mouthpiece and those events, and design considerations to reduce the risk of those events are discussed based on evidence from 32 articles concerning scuba diving mouthpieces. Forward movement of the mandible, loss of molar occlusal support, and continuous jaw clenching while wearing a mouthpiece are considered to be pathogenic for DMS-SE. Several experimental studies have suggested a relationship between incidence of those events and the design of mouthpiece components such as the connector, labial flange, platform, and occlusal rug, and the possibility of reducing risk of those events through design customization of these components. Improvement of the shape of commercially available mouthpieces and creation of custom-made mouthpieces may thus contribute to the prevention and treatment of DMS-SE and the provision of a comfortable diving environment.


Hemin as a General Static Dark Quencher for Constructing Heme Oxygenase-1 Fluorescent Probes.
The development of small-molecule probes suitable for live-cell applications remains challenging yet highly desirable. We report the first fluorescent probe, RBH, for imaging the heme oxygenase-1 (HO-1) activity in live cells after discovering hemin as a universal dark quencher. Hemin works via a static quenching mechanism and shows high quenching efficiency (>97 %) with fluorophores across a broad spectrum (λex =400-700 nm). The favorable properties of RBH (e.g. long excitation/emission wavelengths, fast response rate and high magnitude of signal increase) enable its use for determining HO-1 activity in complex biological samples. As HO-1 is involved in regulating antioxidant defence, iron homeostasis and gasotransmitter carbon monoxide production, we expect RBH to be a powerful tool for dissecting its functions. Also, the discovery of hemin as a general static dark quencher provides a straightforward strategy for constructing novel fluorescent probes for diverse biological species.


[Benign postural vertigo and nystagmus of the horizontal semicircular canal].
Benign paroxysmal vertigo and nystagmus are induced not only by the posterior but also by the horizontal semicircular canal. Benign positional nystagmus of the horizontal canal is more often observed than was previously thought. In 10 patients we analyzed the characteristics and the variability of nystagmus which accompanies positional vertigo of the horizontal canal. There are two forms of nystagmus: primary-geotropic, most often paroxysmal nystagmus (7 patients), and primary-apogeotropic, non-paroxysmal nystagmus (3 patients). Interestingly, in 2 patients with the primary-apogeotropic form the nystagmus converted during the examination into the primary-geotropic form. The reverse was not observed. We discuss the possible pathophysiological mechanisms which could be relevant for provoking manoeuvres.


Dominant lethality by expression of a catalytically inactive class I tRNA synthetase.
Alignment-guided mutagenesis was used to create an inactive, but toxic, aminoacyl-tRNA synthetase. An Asp-96-->Ala (D96A) replacement in the nucleotide binding fold of the class I Escherichia coli isoleucyl-tRNA synthetase inactivates the enzyme without disrupting its competence for binding isoleucine tRNA. Expression of plasmid-encoded mutant enzyme in a cell with a wild-type ileS chromosomal allele resulted in cell death. Introduction of a second K732T substitution previously shown to weaken tRNA binding gives an inactive D96A/K732T double mutant. Expression of the double mutant is not lethal to E. coli. D96A but not the double mutant significantly inhibited in vitro charging of isoleucine tRNA by the wild-type enzyme. The results suggest a dominant tRNA binding-dependent arrest of cell growth caused by a reduction in the pool of a specific tRNA. Specific tRNA binding drugs may have therapeutic applications for treatment of microbial pathogens.


Urethral stricture repair: results in 179 patients.
From 1977 till April 1990 169 operative reconstructions of urethral strictures were carried out in this clinic. 49 patients with a short stricture (less than 2 cm) underwent excision and end to end anastomosis. In 18 patients with a long stricture (2-6 cm) one stage urethroplasty with a transverse distal penile or preputial island of skin flap was used. 102 patients with extensive or otherwise problematic strictures were subjected to two-stage mesh skin graft urethroplasty. In 10 patients with a short stricture we have recently implanted a new urethral stent in the strictured area after visual urethrotomy. During a long-time follow-up a good anatomical and functional result was achieved in all but 2 patients who underwent an excision and end to end anastomosis. In the island flap urethroplasty group a restricture occurred in one patient, and mesh graft urethroplasty was successful in all but 3 patients. In the urethral stent patients the primary results are excellent.


The Genome of Nitrospina gracilis Illuminates the Metabolism and Evolution of the Major Marine Nitrite Oxidizer.
In marine systems, nitrate is the major reservoir of inorganic fixed nitrogen. The only known biological nitrate-forming reaction is nitrite oxidation, but despite its importance, our knowledge of the organisms catalyzing this key process in the marine N-cycle is very limited. The most frequently encountered marine NOB are related to Nitrospina gracilis, an aerobic chemolithoautotrophic bacterium isolated from ocean surface waters. To date, limited physiological and genomic data for this organism were available and its phylogenetic affiliation was uncertain. In this study, the draft genome sequence of N. gracilis strain 3/211 was obtained. Unexpectedly for an aerobic organism, N. gracilis lacks classical reactive oxygen defense mechanisms and uses the reductive tricarboxylic acid cycle for carbon fixation. These features indicate microaerophilic ancestry and are consistent with the presence of Nitrospina in marine oxygen minimum zones. Fixed carbon is stored intracellularly as glycogen, but genes for utilizing external organic carbon sources were not identified. N. gracilis also contains a full gene set for oxidative phosphorylation with oxygen as terminal electron acceptor and for reverse electron transport from nitrite to NADH. A novel variation of complex I may catalyze the required reverse electron flow to low-potential ferredoxin. Interestingly, comparative genomics indicated a strong evolutionary link between Nitrospina, the nitrite-oxidizing genus Nitrospira, and anaerobic ammonium oxidizers, apparently including the horizontal transfer of a periplasmically oriented nitrite oxidoreductase and other key genes for nitrite oxidation at an early evolutionary stage. Further, detailed phylogenetic analyses using concatenated marker genes provided evidence that Nitrospina forms a novel bacterial phylum, for which we propose the name Nitrospinae.


[Congenital changes in the elbow joint].
Radio-ulnar synostosis is one of the congenital malformations of the elbow joint that can be severely disabling, especially if it is present bilaterally or there is marked hyperpronation. In the case of fixed pronation of 60 degrees or more corrective surgery is definitely indicated to reduce functional impairment. As yet, there is no standard operative procedure for restoration of useful supination/pronation function of the forearm. Derotational osteotomy at the site of synostosis seems to be the best procedure. As the postoperative aim we recommend fixed pronation at 15 degrees -35 degrees for the dominant hand and fixed supination at 15 degrees -30 degrees for the contralateral hand. Major derotational procedures should be performed in several stages to avoid neurovascular complications.


Alcohol and viral hepatitis: a mini-review.
Due to their high prevalence in the general population, alcohol use and abuse can be associated with hepatitis B and C virus infections and it has been demonstrated that alcohol plays a role as a co-morbid factor in the development of liver disease. There is evidence that alcohol abuse accelerates the progression of liver fibrosis and affects the survival of patients with chronic hepatitis C. The mechanism by which alcohol worsens hepatitis C virus-related liver disease has not been fully clarified, but enhanced viral replication, increased oxidative stress, cytotoxicity and impairment of immune response could play a relevant role. Alcohol abuse also seems to reduce both sensitivity to interferon and adherence to treatment. It sounds reasonable to presume that the mechanisms enhancing liver damage in patients affected by hepatitis B are similar to those involved in hepatitis C virus infection. However, more studies are warranted to improve our knowledge about the interaction between alcohol intake and hepatitis B virus infection. In conclusion alcohol abuse is associated with an accelerated progression of liver injury, leading to an earlier development of cirrhosis, higher incidence of hepatocellular carcinoma, and higher mortality. Abstinence could reverse some of these deleterious effects.


Extraordinary wave modes in purely imaginary metamaterials beyond the critical angle.
When waves are incident from a high-index medium to a low one, total reflection occurs commonly for the incidence beyond the critical angle. However, this common sense is broken by a purely imaginary metamaterial (PIM), which also supports a real refraction index yet with pure loss and gain elements in their permittivity and permeability. We find that even beyond the critical angle of a lower-index PIM slab, some extraordinary wave modes including laser, anti-laser, perfect attenuator and perfect amplifier can appear. The general conditions of these wave modes are theoretically given out and the underlying mechanisms are revealed. Also, we study the influence of incident polarizations, geometric thickness and the parameters of the PIM slab on these extraordinary wave modes, with more wave propagation behaviors discovered.


The Worringham and Beringer 'visual field' principle for rotary controls.
Worringham and Beringer (1989, 1998) developed a very important principle relating compatibility of movement of horizontally moving translational controls to display movements when the operator's view of the display is in a plane different to that of the control. On the basis of past data of the current authors, it is shown that the visual field principle also applies to the operation of vertically moving translational controls and to rotary controls. These additions make the Worringham and Beringer principle the most powerful design principle available for situations where the operator is viewing a display that is not in the same plane as the control. High compatibility between control input and display output is of great importance in machine design. This paper demonstrates that, for cases where the display is not in the same plane as the control, the visual field principle is operational for vertically moving translational controls and rotary controls as well as for horizontally moving translational controls.


Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning.
This study retrospectively analyzed data from 446 patients given hematopoietic cell transplants from HLA-matched related or unrelated donors after conditioning with 2 Gy total body irradiation with or without fludarabine and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine following grafting. Fifty-three of 446 patients received donor lymphocyte infusion (DLI) with a median CD3 dose of 1 x 10(7) cells/kg. Their diagnoses included myelodysplastic syndrome (n = 10), acute leukemia (n = 10), chronic leukemia (n = 11), multiple myeloma (n = 9), lymphoma (n = 9), and solid tumors (n = 4). Patients received DLI for persistent disease (n = 8), disease relapse (n = 17), progressive disease (n = 12), low donor chimerism with disease (n = 11), or low chimerism with disease remission (n = 5). Seventeen of the 53 patients (32%) are alive with a median follow-up of 30 months; 5 are in complete remission (CR), 2 are in partial remission (PR), and 10 have stable or progressive disease. Nine of 53 patients (17%) developed grades II to IV acute graft-versus-host disease. Of 48 patients receiving DLI for treatment of disease, 7 achieved CR and 5 PR, with an overall response rate of 25%. Six of 16 patients who received DLI for chimerism had increases in donor chimerism leading to sustained engraftment, whereas 10 eventually rejected their grafts. In conclusion, DLI is a potential treatment strategy, with acceptable toxicity, for patients with persistent, relapsed, or progressive disease after nonmyeloablative hematopoietic cell transplantation.


Water Consumption in European Children: Associations with Intake of Fruit Juices, Soft Drinks and Related Parenting Practices.
Background: High intake of fruit juices and soft drinks contributes to excessive weight gain and obesity in children. Furthermore, parenting practices play an important role in the development of children's dietary habits. The way parents play this role in the development of their children's choices of beverages is still unclear. Objectives: To study the associations: (1) of both fruit juices and soft drinks consumption with water consumption of children and (2) The associations between parenting practices towards fruit juices and soft drinks and water consumption of children. Design: Cross-sectional data from 6 to 8 year old children from seven European communities (n = 1187) were collected. Associations among fruit juices, soft drinks, the respective parenting practices and the child's water consumption were assessed by parental questionnaires. Results: The consumption of water was inversely associated with that of soft drinks but not with the consumption of fruit juices. The child's water intake was favorably influenced when stricter parenting practices towards soft drinks were adopted (e.g., less parental allowance, low home availability and high parental self-efficacy in managing intake). There was less influence observed of parenting practices towards fruit juices. Fruit juices were consumed more often than soft drinks. Conclusions: Low consumption of soft drinks-and not of fruit juices-was associated with high water consumption in children in the current study. Moreover, parenting practices towards both fruit juices and soft drinks were associated with the water intake of the children, irrespective of their socio-economic status.


Development of fetal gyri, sulci and fissures: a transvaginal sonographic study.
We aimed to determine the feasibility of imaging specific sulci, gyri and fissures using transvaginal sonography and to correlate their first sonographic recognition with gestational age. Retrospectively, 262 fetal brain scans were analyzed from a total of 337 scans. Scans were selected if any of the following structures were seen: in the coronal plane the lateral, callosal and cingulate sulcus and gyrus; in the median plane the parieto-occipital and calcarine fissures, and the cingulate gyrus and sulcus; and, in an oblique section, the lateral sulcus. The gestational age at which the fissures, sulci and gyri were first imaged was recorded and subsequently compared with similar anatomical studies from the literature. It was possible to identify all the targeted structures. The gestational ages at which the structures were first imaged were: the callosal sulcus, from 14 weeks; the lateral sulcus, from 18 weeks; the parieto-occipital sulcus and calcarine fissure, from 18 weeks; and the cingulate gyrus, from 26 weeks. We concluded that the developmental maturation of the normal fetal brain follows a predictable timetable, and that this maturation can be grossly followed with sonography. The sonographic recognition of the fissures, gyri and sulci lagged behind the observations by anatomical studies. The greatest discrepancy was the first appearance of the cingulate gyrus which, in the anatomical studies, could be seen by 18 postmenstrual weeks and, in our study, was seen after 26 postmenstrual weeks. The one exception was the callosal sulcus, which was first seen at 14 postmenstrual weeks in both the sonographic and anatomical studies. In conclusion, the recognition of specific structures of the cortical map is possible. Sonography may be used to image the developing cortical surface.


Promoting Health Literacy and Perceived Self-Efficacy in People with Chronic Obstructive Pulmonary Disease.
Chronic Obstructive Pulmonary Disease (COPD) is an irreversible condition and it is of great importance for the patients to practice self-care. Given the impact of inadequate health literacy on people's self-efficacy in a self-care program, the aim of this study was to improve health literacy and self-efficacy in people with COPD. The present quasi-experimental study was conducted on 70 patients with COPD admitted to Shahrekord educational hospitals in 2019. Using random allocation software, the samples were randomly divided into intervention and control groups. Data collection tools included three questionnaires including demographic, health literacy, and perceived self-efficacy questionnaires. A training program, with three weekly sessions of theoretical and practical trainings, was conducted for the intervention group in classes in the hospital. The time of each session was 40 min. Data were collected three times i.e., before, immediately after, and three months after the trainings. Data were analyzed by means of SPSS 21 statistical software using descriptive and inferential statistics. Before the intervention, the mean scores of perceived self-efficacy and health literacy did not differ significantly between the two groups, but after the intervention, the scores of the members in the intervention group increased significantly (f = 62.15, p < 0.05). The results of the study indicated an increase in the scores of perceived self-efficacy and health literacy in people with COPD. The use of targeted educational interventions can have a positive effect on the treatment and control of the disease.


Patient comfort during pressure support and volume controlled-continuous mandatory ventilation.
Pressure-support ventilation (PSV) is more comfortable than volume controlled-continuous mandatory ventilation (VC-CMV) in acute hypercapnic respiratory failure, in patients undergoing noninvasive ventilation. Physiologic measurements of patient status have been compared in PSV and VC-CMV in endotracheally intubated patients, but patient perception of comfort has not been measured in this population. To determine if PSV is more comfortable than VC-CMV (volume-cycled, flow-limited) in intubated mechanically ventilated patients. In a randomized prospective trial, patients underwent PSV and VC-CMV for 30 min each, separated by a 30 min washout with the baseline ventilation mode (pressure-regulated volume-control ventilation [PRVC]). The level of pressure support was set as the plateau pressure on VC-CMV with a tidal volume of 8 mL/kg minus the end-expiratory pressure. After each mode the patient was asked to mark his or her comfort level on a visual analog scale. Eleven of the 14 patients were more comfortable during PSV. The baseline mean comfort score (during PRVC) was 62 +/- 18 (95% confidence interval 51.7-72.5). The mean comfort score for PSV was 83 +/- 11 (95% confidence interval 76.9-89.6). The mean comfort score for VC-CMV was 70 +/- 18 (95% confidence interval 59.4-79.9). PSV was significantly more comfortable than VC-CMV (p = 0.02) or PRVC (p = 0.009), whereas the comfort scores for VC-CMV and PRVC were not significantly different (p = 0.278). Respiratory rate, blood pressure, heart rate, minute ventilation, and blood oxygen saturation showed no difference between PRVC, VC-CMV, and PSV. On average the patients felt more comfortable during PSV than during VC-CMV or PRVC, so PSV may be the preferred mode for awake intubated patients.


An Introduction to Programming for Bioscientists: A Python-Based Primer.
Computing has revolutionized the biological sciences over the past several decades, such that virtually all contemporary research in molecular biology, biochemistry, and other biosciences utilizes computer programs. The computational advances have come on many fronts, spurred by fundamental developments in hardware, software, and algorithms. These advances have influenced, and even engendered, a phenomenal array of bioscience fields, including molecular evolution and bioinformatics; genome-, proteome-, transcriptome- and metabolome-wide experimental studies; structural genomics; and atomistic simulations of cellular-scale molecular assemblies as large as ribosomes and intact viruses. In short, much of post-genomic biology is increasingly becoming a form of computational biology. The ability to design and write computer programs is among the most indispensable skills that a modern researcher can cultivate. Python has become a popular programming language in the biosciences, largely because (i) its straightforward semantics and clean syntax make it a readily accessible first language; (ii) it is expressive and well-suited to object-oriented programming, as well as other modern paradigms; and (iii) the many available libraries and third-party toolkits extend the functionality of the core language into virtually every biological domain (sequence and structure analyses, phylogenomics, workflow management systems, etc.). This primer offers a basic introduction to coding, via Python, and it includes concrete examples and exercises to illustrate the language's usage and capabilities; the main text culminates with a final project in structural bioinformatics. A suite of Supplemental Chapters is also provided. Starting with basic concepts, such as that of a "variable," the Chapters methodically advance the reader to the point of writing a graphical user interface to compute the Hamming distance between two DNA sequences.


Mucormycotic infection in mice following prolonged incubation of spores in vivo and the role of spore agglutinating antibodies on spore germination.
Following intranasal inoculation of mice, Rhizomucor pusillus spores are gradually cleared from the lung, with the clearance complete at 30 days. Incubation of R. pusillus spores in vivo for up to 14 days after intranasal inoculation resulted in pulmonary mucormycosis when the mice were then treated with cortisone. Spore-agglutinating IgM antibodies were detected in normal adult mice and R. pusillus-inoculated but not cortisone-treated mice. There was no correlation between antispore antibody titers and spore germination in vitro. The absence of germinated R. pusillus in inoculated but non-cortisone-treated mice appears to be due to a reversible inhibition of spore germination rather than destruction of spores by the host. The factor(s) that restrict spore germination are reversible and do not appear to be spore agglutinating antibodies.


In vitro study of parasite elimination and endothelial protection by curcumin: adjunctive therapy for cerebral malaria.
Plasmodium falciparum infection can abruptly progress to severe malaria and cerebral malaria. Despite the current efficiency of antimalarial drugs in killing parasites, no specific effective treatment has been found for cerebral malaria. Thus, a new strategy targeting both parasite elimination and endothelial cell protection is urgently needed in this field. In this study, we determined whether curcumin, which has blood-brain permeability, antioxidative activity and/or immunomodulation property, provided a potential effect on both parasite elimination and endothelial protection. Murine brain microvascular endothelial cells (bEnd.3; ATCC) were cocultured with Plasmodium falciparum-infected red blood cells (Pf-IRBC), peripheral blood mononuclear cell (PBMC) and platelets. Apoptosis of endothelial cells was demonstrated by annexin V staining. Interestingly, curcumin exhibited high efficiency of antimalarial activity (IC50 ~10 µM) and decreased bEnd.3 apoptosis down to 60.0 % and 79.6 % upon pre-treatment and co-treatment, respectively, with Pf-IRBC, platelets and PBMC. Our findings open up a high feasibility of applying curcumin as a potential adjunctive compound for cerebral malaria treatment in the future.


[Elastases and pulmonary pathologies].
Various elastases classes normally reside in alveolar structure and are liable to degrade the elastin as well as the other macromolecular components of pulmonary extracellular matrix (collagen, proteoglycans, fibronectin...), during lung injury. The most are the polymorphonuclear or monocyte serine elastase and the macrophage metallo and cysteine elastases. Metalloelastase may also arise from pathogenic bacteria as Pseudomonas aeruginosa. In another part proteases elastase-type from fibroblasts, endothelial cells or alveolar macrophages might to be involved into the remodelling of lung connective tissue or pulmonary cells differentiation and activation. The regulation of elastolytic activities, is supported both by activators (as plasminogen activator...) and inhibitors (alpha 1 Pi, 2M, BrI, TIMP, bacterial inhibitors...). These inhibitors are mostly generated in situ from macrophages, monocytes or polymorphonuclear cells so allowing to control fast local elastolytic activity. Since alveolar macrophage can internalize leucocyte elastase, synthetize metalloelastases, and secrete their inhibitors and activators, it plays a complex role in the lung defense and during various pulmonary pathogenesis. In conclusion, the lung response to bacterial or viral infections, the intensity of alveolitis, the nature and the gravity of emphysematous or fibrotic lung lesions, as well as the tumour growth or metastatic pulmonary invasion may depend upon the lung elastolytic activities.


Pharmacy program for monitoring diabetic patients.
Pharmacist involvement in a program for monitoring and treating diabetic patients in a 58-bed Indian Health Service hospital is described. Using guidelines established in conjunction with the medical staff, pharmacists interviewed patients to determine the status of their disease, evaluated laboratory data, and decided whether to dispense refills or have the patient evaluated by a physician. The pharmacist also provided patient education concerning the disease, treatment and self-care. During a 19-month period, 50% of 193 diabetic patients were monitored primarily by pharmacists. The increased involvement of the pharmacists has resulted in better use of their abilities and has freed more time for physicians to spend with patients who have complications.


Necrotic oophoritis in gilts associated with experimental inoculation of a viral gene-deletion mutant pseudorabies vaccine.
Previous work on the reproductive effects of various herpesviruses has demonstrated adverse effects on reproductive function in several host species. Although herpesviral vaccines are used in several species to ameliorate the clinical effects of infection, pathogenicity for reproductive tissue, associated with diminished reproductive efficiency, has been reported to be retained in a live-attenuated vaccine strain of the herpesvirus, bovine herpesvirus-1. The objective of this study was to determine if a gene-deletion mutant, thymidine kinase negative, pseudorabies virus retained acute pathogenicity for the reproductive tract of swine following intravenous inoculation during estrus. Estrous cycles of nulliparous gilts were synchronized by administration of a gonadotropin and daily exposure to a boar. During estrus, six gilts were inoculated intravenously with twice the recommended intramuscular dose of a commercially available viral gene-deletion mutant pseudorabies vaccine. Six control gilts in estrus were sham inoculated intravenously with vaccine diluent during estrus. All animals were euthanatized 10 days postinoculation, and the ovaries and uterus were collected for histopathology following gross examination. All reproductive tracts were grossly normal. Histologically, four of six treated gilts had a mild to moderate, multifocal, necrotizing oophoritis, with the lesions limited to corpora lutea and the adjacent stroma. Ovaries of control gilts exhibited to necrotizing lesions. Both control and pseudorabies vaccine-inoculated gilts had occasional minimal focal mononuclear infiltrates in the ovaries. These data show that live attenuated viral gene-deletion mutant pseudorabies vaccine administered to swine during estrus can result in acute pathogenicity in ovarian corpora lutea. No endocrinologic data is available in these pigs, so the impact on pregnancy maintenance is unknown.


Evaluation of a newly developed quantitative heart-type fatty acid binding protein assay based on fluorescence immunochromatography using specific monoclonal antibodies.
To develop a rapid, sensitive and specific assay for quantification of serum heart-type fatty acid binding protein (H-FABP) based on immunofluorescence of specific monoclonal antibodies. We generated novel H-FABP-directed monoclonal antibodies by cloning of spleen cells of mice immunized with H-FABP. Epitopes were mapped and antigen affinity was assessed by surface plasmon resonance (SPR). The H-FABP specific monoclonal antibodies were coupled to fluorescent beads and sprayed onto a nitrocellulose membrane facilitating quantification of H-FABP by immunofluorescence. Reagent cross-reactivity, interference resistance, accuracy and sensitivity were examined. A total of 103 clinical samples were used to compare the sensitivity and specificity of the new assay to a commercially available Randox kit. This new assay could be finished within 15 min, with sensitivity reaching 1 ng/ml. In a trial of 103 clinical serum samples, the new testing kit results were highly correlated with those from the Randox kit (R(2) = 0.9707). Using the Randox kit as the reference kit, the sensitivity of the new assay was 98.25%, and specificity was 100%. An immunofluorescence-based H-FABP assay employing novel monoclonal antibodies could rapidly, specifically and sensitively detect H-FABP in serum samples, providing an effective method for rapid clinical assessment of H-FABP index in the clinic.


Computer-aided detection in oncologic imaging: screening mammography as a case study.
Accuracy of the imaging report is dependent on the observational and interpretive skills of the radiologist, which varies between observers. Over the past several decades, research programs have focused on the use of computer algorithms to address both the perception and the interpretation aspects of diagnostic imaging. Computer-based technology that analyzes images in order to detect features of disease is called computer-aided detection (CAD). This paper reviews the current status of CAD as used with screening mammography.


Influence of legal standards on the practice of industrial hygiene.
Prescriptive standards for the work environment affect the professional practice of industrial hygiene. Among the advantages are: legal requirements reinforce professional recommendations; penalties encourage abatement of hazards; compliance should ensure a safe and healthful environment; recordkeeping requirements will provide a basis for future action. Among the disadvantages are: rigid evaluation procedures, reporting format, etc., discourage professional judgment and development of new methods; professional reports become legal documents; single standards do not focus on the total environment.


[Extracellular ceroid in the adipose tissue of the field hare (Lepus europaeus Pall.)].
Routine histology of hares caught for ecological monitoring showed extracellular curvilamellar ceroid in a focal degeneration process of reserve adipose tissue in 19 animals. The defect was localized most frequently in parametrial adipose tissue, in mesovary, close to suprarenals and in spleen hilus. Discussion concerned an analogical process in men and other animal species and a possible role of vitamin E deficiency.


The treatment of decubitus ulcers with dextranomer.
Twenty-five patients with 35 bedsores were treated with dextranomer (Debrisan; Adcock Ingram) applied topically to the ulcers. Fourteen patients had ulcers which penetrated fascia, muscle and bone, 4 had superficial ulcers and 2 had discharging sinuses. Most of the severe ulcers healed rapidly and were cleansed and ready for surgery at an average of 14.6 days. The superficial ulcers were completely healed within 3 weeks. Treatment of the sinuses with dextranomer using a catheter/syringe technique resulted in wound closure within 28 days. In a representative sample of 12 patients in whom the surface area of the ulcers was measured by means of a planimeter, there was a median reduction in surface area of 44.8% by the 2nd week (P=0,0002) and 79% (P=0,001) at the end of the 4th week. The median percentage reduction in depth was 66.7% (P=0,008) at the end of the 4th week.


Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene.
The overall organization of the X-inactivation center (XIC/Xic) candidate region seems poorly conserved between human and mouse. The orientation of a region containing the X-inactive-specific transcript (Xist/ XIST) gene and three genes located 3' of Xist/XIST has been shown to be inverted between the two species, although the actual extent of this rearrangement is unknown. We have cloned and mapped the mouse homolog of the human XPCT (X-linked PEST-containing transporter) gene, which encodes a putative transmembrane transporter. Human XPCT is located about 200 kb outside of the XIC candidate region and 600 kb 5' of or telomeric to the XIST gene. The mouse Xpct gene, which lies approximately 300 kb 5' of and centromeric to Xist, displays 85% identity at the nucleotide level with the human gene, and the overall protein structure is conserved. The transcriptional orientation of mouse Xpct with respect to Xist is the opposite of that in human. Consequently, the evolution of the region between human and mouse appears to be highly complex, with structural rearrangements involving a region of up to 600 kb or more around the Xist gene.


Pulmonary responses of rats to ambient levels of ozone: effects of 7-day intermittent or continuous exposure.
Groups of Sprague-Dawley rats were exposed to ozone for either 8 or 24 hours a day for 7 consecutive days to evaluate morphologic changes of the respiratory system. Three levels of exposure (0.2, 0.5, and 0.8 p.p.m. of O3) were selected to simulate moderate to severe episodes of oxidant pollution in urban environments. Morphologic evaluation included light, scanning electron, and transmission electron microscopy. Biochemical parameters which were examined included succinate oxidase, glucose-6-phosphate dehydrogenase, and nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activities. The results indicated that (1) exposure to concentrations as low as 0.2 p.p.m. for 7 days induced pulmonary damage; (2) there was a dose-dependent pulmonary response to the three levels of ozone which was quantitated by alterations in biochemical marker enzyme activities and observed morphologically; (3) proportionate differences were not observed in morphologic characteristics of the lesions or detected in biochemical parameters between rats exposed continuously for 7 days and those exposed intermittently for 8 hours a day for 7 consecutive days; (4) alterations in surface height and granularity of the cytoplasmic luminal projection of Clara cells were subtle changes which were dose-dependent, occurring even at the lowest ozone concentration, and best detected by scanning electron microscopy; (5) alveolar macrophage accumulation within proximal alveoli of alveolar ducts was the most readily detectable morphologic indicator of pulmonary damage; and (6) although the brunt of ozone damage was borne by the centriacinar region, there was damage to cilia and increased ciliogenesis occurring in the trachea and larger conducting airways following exposure of 0.5 and 0.8 p.p.m. of ozone.


Kinking of carotid arteries is not a mechanism of cerebral ischemia: a functional evaluation by Doppler echography.
The aim of this paper was to evaluate the hemodynamic behavior of carotid kinking, as assessed by color Doppler ultrasonography at baseline and during neck movements, and their relation to neurological symptoms. In this cross-sectional study, 60 consecutive patients with non-atheromatous carotid kinking in whom diagnostic color Doppler ultrasonography investigation of neck vessels had been requested for clinical suspicion of atherosclerotic disease were evaluated. To evaluate if there were significant changes of blood velocities as a consequence of kinking, for each carotid artery we recorded systolic and diastolic velocities both in the segments proximal to kinking, as well as intra-kinking. The effects of postural changes and neck movements on carotid blood flow were also studied. Flow in carotid arteries with kinking was always normal, and no differences were found between flow velocity measured at the level of kinking compared to the normal tract of the vessel. During head rotation tests, flow remained largely unaffected, a substantial reduction in the velocities in the ophthalmic artery was found in 13.5% of the cases, while an increase was recorded in 27%; and no symptoms or events were recorded during the study. None of the patients referred symptoms, nor were neurological events or signs detected during the maneuvers. Our results show that carotid kinks are not a mechanism of acute cerebral ischemia, and therefore are unlikely to be a cause of neurological events or symptoms.


Synthesis and Electrochemical Reaction of Tin Oxalate-Reduced Graphene Oxide Composite Anode for Rechargeable Lithium Batteries.
Unlike for SnO2, few studies have reported on the use of SnC2O4 as an anode material for rechargeable lithium batteries. Here, we first introduce a SnC2O4-reduced graphene oxide composite produced via hydrothermal reactions followed by a layer-by-layer self-assembly process. The addition of rGO increased the electric conductivity up to ∼10-3 S cm-1. As a result, the SnC2O4-reduced graphene oxide electrode exhibited a high charge (oxidation) capacity of ∼1166 mAh g-1 at a current of 100 mA g-1 (0.1 C-rate) with a good retention delivering approximately 620 mAh g-1 at the 200th cycle. Even at a rate of 10 C (10 A g-1), the composite electrode was able to obtain a charge capacity of 467 mAh g-1. In contrast, the bare SnC2O4 had inferior electrochemical properties relative to those of the SnC2O4-reduced graphene oxide composite: ∼643 mAh g-1 at the first charge, retaining 192 mAh g-1 at the 200th cycle and 289 mAh g-1 at 10 C. This improvement in electrochemical properties is most likely due to the improvement in electric conductivity, which enables facile electron transfer via simultaneous conversion above 0.75 V and de/alloy reactions below 0.75 V: SnC2O4 + 2Li+ + 2e- → Sn + Li2C2O4 + xLi+ + xe- → LixSn on discharge (reduction) and vice versa on charge. This was confirmed by systematic studies of ex situ X-ray diffraction, transmission electron microscopy, and time-of-flight secondary-ion mass spectroscopy.


Meeting the needs of regional minority groups: the University of Washington's programs to increase the American Indian and Alaskan native physician workforce.
Minority populations in the United States are growing rapidly, but physician workforce diversity has not kept pace with the needs of underserved communities. Minorities comprised 26.4% of the population in 1995; by 2050, these groups will comprise nearly half. Medical schools must enlist greater numbers of minority physicians and train all physicians to provide culturally responsive care. The University of Washington School of Medicine (UWSOM) is the nation's only medical school that serves a five-state region (Washington, Wyoming, Alaska, Montana, and Idaho). Its mission addresses the need to serve the region, rectify primary care shortages, and meet increasing regional demands for underserved populations. The UWSOM Native American Center of Excellence (NACOE) was established as one important way to respond to this charge. The authors describe pipeline and minority recruitment programs at UWSOM, focusing on the NACOE and other activities to recruit American Indian/Alaskan Native (AI/AN) applicants to medical schools. These programs have increased the numbers of AI/AN medical students; developed the Indian Health Pathway; worked to prepare students to provide culturally responsive care for AI/AN communities; researched health disparities specific to AI/AN populations; provided retention programs and services to ensure successful completion of medical training; developed mentorship networks; and provided faculty-development programs to increase entry of AI/AN physicians into academia. Challenges lie ahead. Barriers to the pipeline will continue to plague students, and inadequate federal funding will have a significant and negative impact on achieving needed physician-workforce diversity. Medical schools must play a larger role in resolving these, and continue to provide pipeline programs, retention programs, and minority faculty development that can make a difference.


Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome.
The alveolar macrophages defend the lung against airborne pollutants and infectious microorganisms. Recent advances in the understanding of the role of macrophages in generation of immunological and inflammatory responses have established that alveolar macrophages could be used as targets for drug delivery. Enhanced uptake of particulate drug carriers by macrophages could be beneficial in pathological conditions such as tuberculosis and HIV where infectious microorganisms utilize macrophages as a safe haven and a vehicle to further infections. In contrary, to achieve prolonged residence time, extended drug release and in desired situations, increased systemic absorption, drug carrying particles that can avoid recognition and uptake by alveolar macrophages may prove to be significantly advantageous. Drug targeting to macrophages can achieve superior therapeutic efficacy for the treatment of medical conditions that involve tumorigenesis, inflammation and infections. Various particulate carriers containing therapeutic agents have been used to deliver drugs to the macrophages residing in the lung. Particulate systems have also been engineered to facilitate or avoid uptake by macrophages. But pathological conditions to be treated and drug delivery goals dictate the engineering approach for reducing or enhancing uptake by macrophages. In this review, we have summarized the influence of various physicochemical properties--composition, size, shape, pegylation and presence or absence of surface ligands--of particulate carriers on their uptake by macrophages. We have also described the macrophage biology and strategies that have been used to influence uptake and avoidance of particulate carriers by macrophages.


Altered consciousness and lethargy from compromised intestinal blood flow in children.
Altered state of consciousness and lethargy could be early and cardinal complaints in diseases that actually originate within the abdomen. Thirteen children were seen at our departments in whom impairment of the individual's mental state preceded the appearance of common gastrointestinal symptoms. Whereas in infants with intussusception of childhood neurological signs and symptoms have been rarely mentioned, references to an altered state of consciousness and lethargy in volvulus, strangulation or bowel incarceration have not been previously reported. Recognition of this possibility, however, should be taken into account in the diagnostic work-up of children presenting with inexplicable alterations of their mental state.


Nasal high-flow preoxygenation for endotracheal intubation in the critically ill patient: a randomized clinical trial.
Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bag-valve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU. Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO2) throughout the intubation procedure. Secondary outcomes included drop in SpO2, adverse events related to intubation, and outcome in the ICU. A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC n = 95; SMO n = 89), the median [IQR] lowest SpO2 was 100% [97; 100] for HFNC and 99% [95; 100] for the SMO group (P = 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26-0.99, P = 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13-0.76, P = 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15-0.95, P = 0.03). Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO2 during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events. Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. Clinicaltrials.gov identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry: https://clinicaltrials.gov/ct2/show/record/NCT02700321 .


Fourier transform-plasmon waveguide spectroscopy: a nondestructive multifrequency method for simultaneously determining polymer thickness and apparent index of refraction.
Fourier transform (FT)-plasmon waveguide resonance (PWR) spectroscopy measures light reflectivity at a waveguide interface as the incident frequency and angle are scanned. Under conditions of total internal reflection, the reflected light intensity is attenuated when the incident frequency and angle satisfy conditions for exciting surface plasmon modes in the metal as well as guided modes within the waveguide. Expanding upon the concept of two-frequency surface plasmon resonance developed by Peterlinz and Georgiadis [Opt. Commun. 1996, 130, 260], the apparent index of refraction and the thickness of a waveguide can be measured precisely and simultaneously by FT-PWR with an average percent relative error of 0.4%. Measuring reflectivity for a range of frequencies extends the analysis to a wide variety of sample compositions and thicknesses since frequencies with the maximum attenuation can be selected to optimize the analysis. Additionally, the ability to measure reflectivity curves with both p- and s-polarized light provides anisotropic indices of refraction. FT-PWR is demonstrated using polystyrene waveguides of varying thickness, and the validity of FT-PWR measurements are verified by comparing the results to data from profilometry and atomic force microscopy (AFM).


Chest computed tomography imaging utility for radiographically occult rib fractures in elderly fall-injured patients.
Previous studies demonstrate an association between rib fractures and morbidity and mortality in trauma. This relationship in low-mechanism injuries, such as ground-level fall, is less clearly defined. Furthermore, computed tomography (CT) has increased sensitivity for rib fractures compared with chest x-ray (CXR); its utility in elderly fall patients is unknown. We sought to determine whether CT-diagnosed rib fractures in elderly fall patients with a normal CXR were associated with increased in-hospital resource utilization or mortality. Retrospective analysis of emergency department patients presenting over a 3-year period. age, 65 years or older; chief complaint, including mechanical fall; and both CXR and CT obtained. We quantified rib fractures on CXR and CT and reported operating characteristics for both. Outcomes of interest included hospital admission/length of stay (LOS), intensive care unit (ICU) admission/LOS, endotracheal intubation, tube thoracostomy, locoregional anesthesia, pneumonia, in-hospital mortality. We identified 330 patients, mean age was 84 years (±SD, 9.4 years); 269 (82%) of 330 were admitted. There were 96 (29%) patients with CT-diagnosed rib fracture, 56 (17%) by CT only. Compared with CT, CXR had a sensitivity of 40% (95% confidence interval, 30-50%) and specificity of 99% (95% confidence interval, 97-100%) for rib fracture. A median of two additional radiographically occult rib fractures were identified on CT. Despite an increased hospital admission rate (91% vs. 78%) p = 0.02, there was no difference between patients with and without radiographically occult (CT+ CXR-) rib fracture(s) for: median LOS (4; interquartile range (IQR) 2-7 vs 4, IQR 2-8); p = 0.92), ICU admission (28% vs. 27%) p = 0.62, median ICU LOS (2, IQR 1-8 vs 3, IQR 1-5) p = 0.54, or in-hospital mortality (10.3% vs. 7.3%) p = 0.45. Among elderly fall patients, CT-identified rib fractures were associated with increased hospital admissions. However, there was no difference in procedural interventions, ICU admission, hospital/ICU LOS or mortality for patients with and without radiographically occult fractures. Diagnostic, level III.


Conserved structures exposed in HIV-1 envelope glycoproteins stabilized by flexible linkers as potent entry inhibitors and potential immunogens.
The HIV-1 envelope glycoprotein (Env) undergoes conformational changes while driving entry. We hypothesized that some of the intermediate Env conformations could be represented in tethered constructs where gp120 and the ectodomain of gp41 are joined by flexible linkers. Tethered Envs with long linkers (gp140-14 with 15 aa and gp140-24 with 26 aa) were stable and recognized by conformationally dependent anti-gp120 and anti-gp41 monoclonal antibodies (mAbs). Surprisingly, these proteins potently inhibited membrane fusion mediated by R5, X4, and R5X4 Envs with 5-100-fold lower IC50 than a tethered Env with short linker (gp140-4 with 4 aa), gp120, gp140, soluble CD4, or DP178 (T20). Compared to gp140, gp140-14,24 exhibited increased binding to anti-gp41 cluster II mAbs but not to cluster I mAbs. Cluster II mAbs but not cluster I, IV, or V mAbs reversed the inhibitory effect of gp140-14,24 suggesting a role of exposed conserved gp41 structures for the mechanism of inhibition. These findings suggest the existence of conserved gp41 structures that are important for HIV-1 entry and can be stably exposed in the native environment of the Env even in the absence of receptor-mediated activation. Thus, tethered Envs with long linkers may not only be important as HIV-1 inhibitors but also for elucidation of viral entry mechanisms and development of novel vaccine immunogens.


AMRI-59 functions as a radiosensitizer via peroxiredoxin I-targeted ROS accumulation and apoptotic cell death induction.
Previously, we identified AMRI-59 as a specific pharmaceutical inhibitor of peroxiredoxin (PRX) I enzyme activity. In this study, we examined whether AMRI-59 acts as a radiosensitizer in non-small cell lung cancer cells using clonogenic assays. The intracellular mechanisms underlying the radiosensitization effect of AMRI-59 were determined via immunoblotting in addition to measurement of ROS generation, mitochondrial potential and cell death. AMRI-59 activity in vivo was examined by co-treating nude mice with the compound and γ-ionizing radiation (IR), followed by measurement of tumor volumes and apoptosis. The dose enhancement ratios of 30 μM AMRI-59 in NCI-H460 and NCI-H1299 were 1.51 and 2.12, respectively. Combination of AMRI-59 with IR augmented ROS production and mitochondrial potential disruption via enhancement of PRX I oxidation, leading to increased expression of γH2AX, a DNA damage marker, and suppression of ERK phosphorylation, and finally, activation of caspase-3. Notably, inhibition of ROS production prevented ERK suppression, and blockage of ERK in combination with AMRI-59 and IR led to enhanced caspase-3 activation and apoptosis. In a xenograft assay using NCI-H460 and NCI-H1299, combined treatment with AMRI-59 and IR delayed tumor growth by 26.98 and 14.88 days, compared with controls, yielding enhancement factors of 1.73 and 1.37, respectively. Taken together, the results indicate that AMRI-59 functions as a PRX I-targeted radiosensitizer by inducing apoptosis through activation of the ROS/γH2AX/caspase pathway and suppression of ERK.


Nanoparticle-Based Activatable Probes for Bioimaging.
Molecular imaging can provide functional and molecular information at the cellular or subcellular level in vivo in a noninvasive manner. Activatable nanoprobes that can react to the surrounding physiological environment or biomarkers are appealing agents to improve the efficacy, specificity, and sensitivity of molecular imaging. The physiological parameters, including redox status, pH, presence of enzymes, and hypoxia, can be designed as the stimuli of the activatable probes. However, the success rate of imaging nanoprobes for clinical translation is low. Herein, the recent advances in nanoparticle-based activatable imaging probes are critically reviewed. In addition, the challenges for clinical translation of these nanoprobes are also discussed in this review.


Acoustics versus linguistics? Context is Part and Parcel to lateralized processing of the parts and parcels of speech.
The purpose of this review is to provide an accessible exploration of key considerations of lateralization in speech and non-speech perception using clear and defined language. From these considerations, the primary arguments for each side of the linguistics versus acoustics debate are outlined and explored in context of emerging integrative theories. This theoretical approach entails a perspective that linguistic and acoustic features differentially contribute to leftward bias, depending on the given context. Such contextual factors include stimulus parameters and variables of stimulus presentation (e.g., noise/silence and monaural/binaural) and variances in individuals (sex, handedness, age, and behavioural ability). Discussion of these factors and their interaction is also aimed towards providing an outline of variables that require consideration when developing and reviewing methodology of acoustic and linguistic processing laterality studies. Thus, there are three primary aims in the present paper: (1) to provide the reader with key theoretical perspectives from the acoustics/linguistics debate and a synthesis of the two viewpoints, (2) to highlight key caveats for generalizing findings regarding predominant models of speech laterality, and (3) to provide a practical guide for methodological control using predominant behavioural measures (i.e., gap detection and dichotic listening tasks) and/or neurophysiological measures (i.e., mismatch negativity) of speech laterality.


Mortality and predictors of survival in patients with recent ventricular septal rupture.
Ventricular septal rupture (VSR) is a rare but fatal complication after acute myocardial infarction (AMI). However, the mortality in patients with recent VSR and appropriate timing of surgical repair have not been clarified. To examine the background characteristics and mortality of VSR patients as well as the usefulness and appropriate timing of surgery in this patient cohort. Among 3,947 consecutive patients with AMI at our hospital, 39 patients diagnosed with VSR from 2002 to 2020 were included in the analysis. All patients underwent transthoracic echocardiography to confirm VSR on admission. Coronary angiography (CAG) and measurement of pulmonary-systemic flow ratio were performed before emergent surgery. The use of mechanical support devices before or after procedures was considered for all patients who underwent CAG. Basically, we performed emergent or urgent operations to patients who were in a shock state or who needed mechanical support. The final decision of the timing of the operation was made by the cardiac team. Patients' mean age was 76.3 years, and 33.3% of them were males. Most culprit lesions were located in the left anterior ascending artery (81.3%). The mean pulmonary-systemic flow ratio after VSR onset was 3.07 ± 1.98. On admission, 48.7% of patients were in a shock state. Surgical repair was possible in 28 patients at a median of 1 day after admission, with a mortality rate of 25%. Among all patients, the mortality rate was 43.6%. Survivors were significantly younger (71.3 ± 11.3 vs. 82.7 ± 6.2 years, p < 0.01), had higher mean arterial blood pressure (75.6 ± 14.4 vs. 62.8 ± 16.2 mmHg, p = 0.0496) and lower ejection fraction (44.3 ± 11.7% vs. 54.8 ± 7.9%, p = 0.04), and underwent surgical repair more frequently (95.5% vs. 41.2%, p < 0.01) than the non-survivors. In multivariate analysis, younger age (odds ratio [OR] 1.18 95% confidence interval [CI] 1.01-1.38, p = 0.04) and surgical repair (OR 0.04, 95% CI 0.00-0.73, p = 0.03) were significant predictors of survival. In surgical repair cases, time from admission to operation did not differ significantly between survivors and non-survivors. Surgical repair and younger age are predictors of survival in patients with recent VSR, but the timing of surgery was not.


Requirements for clinical trials.
Significant progress and valuable contributions have been made by pioneers in the field of dental implantology during the past 20 years. The feasibility of clinical application of dental implants for specific prosthodontic conditions has been demonstrated by several reports based upon retrospective data or surveys of clinical experiences. However, there is a lack of reliable scientific information to determine the clinical efficacy of implant-supported prostheses or the physiological merits of the two types of implant-bone interface. Similarly, there are no known studies that have tested the relative efficacy of different implant systems. The claims of success rates for different implants can only be substantiated when controlled, independent studies are made, following research protocols that meet the requirements of clinical trials in terms of delineation of hypothesis, definition of treatment, entry and treatment allocations, exclusions and withdrawals, sample size, and a coordinated plan for the statistical analysis of data and interpretation of results. The study design of the VA Cooperative Study has followed the essential requirements of clinical trials in comparing the efficacies of the two treatment modalities--traditional removable partial dentures versus fixed partial dentures supported by implants.


[Sildenafil assumption and acute effects on the uroflowmetric parameters].
In the recent literature, great attention has been given to the evaluation of the real effectiveness of the phosphodiesterase type 5 inhibitors (PDE-5i), usually prescribed for the erectile dysfunction (ED), in the treatment of the lower urinary tracts symptoms (LUTS). The aim of this study was the evaluation of the acute effects of sildenafil on the uroflowmetric parameters. Within September 2011 and February 2012, twenty-seven patients, affected by ED with a IIEF-5 score ≤21 and a contextual IPSS within 8 e 19, have been selected and enrolled in this study. Two uroflowmetric measurements with suprapubic ultrasound valuation of the post voiding residual (PVR) were performed on each patient, 2 hours before and after the administration of sildenafil (50 mg). The average age of the patients came out within di 47.3±9.4 years. On the baseline, the average of the Qmax registered has been 15.6±3.3 mL/s, the average Qave has been 8.2±3.2 mL/s and the average resulted 32.5±11.4 mL. After the mono-administration of sildenafil 50 mg, the average Qmax value, the Qave one and the RPM one turned out into 17.7±5.1 mL/s, 10.1±3.5 mL/s and 22.6±9.6 mL. The differences within the standard values, were considered statistically relevant (P<0.05). Actually, the study shows that, in the acute phase, the administration of sildenafil 50 mg leads to effects on the uroflowmetric standards on men affected by LUTS and DE.


Surface activity of thymol: implications for an eventual pharmacological activity.
In the present work, we studied the ability of thymol to affect the organization of model membranes and the activity of an intrinsic membrane protein, the GABA(A) receptor (GABA(A)-R). In this last aspect, we tried to elucidate if the action mechanism of this terpene at the molecular level, involves its binding to the receptor protein, changes in the organization of the receptor molecular environment, or both. The self-aggregation of thymol in water with a critical micellar concentration approximately = 4 microM and its ability to penetrate in monomolecular layers of soybean phosphatidylcholine (sPC) at the air-water interface, even at surface pressures above the equilibrium, lateral pressure of natural bilayers were demonstrated. Thymol affected the self-aggregation of Triton X-100 and the topology of sPC vesicles. It also increased the polarity of the membrane environment sensed by the electrochromic dye merocyanine. A dipolar moment of 1.341 Debye was calculated from its energy-minimized structure. Its effect on the binding of [3H]-flunitrazepam ([3H]-FNZ) to chick brain synaptosomal membranes changed qualitatively from a tendency to the inhibition to a clear activatory regime, up on changing the phase state of the terpene (from a monomeric to a self-aggregated state). Above its CMC, thymol increased the affinity of the binding of [3H]-FNZ (K(d-control)= 2.9, K(d-thymol)= 1.7 nM) without changing the receptor density (B(max-control)= 910, B(max-thymol)= 895 fmol/mg protein). The activatory effect of thymol on the binding of [ [3H]-FNZ was observed even in the presence of the allosteric activator gamma-aminobutyric acid (GABA) at a concentration of maximal activity, and was blocked by the GABA antagonist bicuculline. Changes in the dipolar arrangement and in the molecular packing of GABA(A)-R environment are discussed as possible mediators of the action mechanism of thymol.


Expression and localization of delta-, kappa-, and mu-opioid receptors in human spermatozoa and implications for sperm motility.
Endogenous opioid peptides signal through delta-, kappa-, and mu-opioid receptors. Some of these peptides such as endorphins and enkephalins are present in the male reproductive tract, but the presence of the corresponding receptors in human sperm cells has not yet been reported. Our objective was to study the expression and localization of delta-, kappa-, and mu-opioid receptors on human spermatozoa and the implication in sperm motility. The expression of receptors was studied by RT-PCR, Western blot, and immunofluorescence techniques. We evaluated the effects of activation of each opioid receptor by specific agonist and antagonist. Human spermatozoa express delta-, kappa-, and mu-opioid receptors. These receptors were located in different parts of the head, in the middle region, and in the tail of the sperm. Progressive motility of spermatozoa, an important parameter to evaluate male fertility, was found to be significantly reduced after incubation with the mu-receptor agonist morphine, whereas this effect was antagonized in the presence of the corresponding antagonist naloxone. The delta-receptor antagonist naltrindole significantly reduced progressive motility immediately after its addition. However, the delta-receptor agonist DPDPE had no significant effect. Finally, neither the kappa-receptor agonist U50488 nor its antagonist nor-binaltorphimine significantly affected the progressive motility of human spermatozoa. We report for first time the presence of functional delta-, kappa-, and mu-opioid receptors in human sperm membranes. These findings are indicative of a role for the opioid system in the regulation of sperm physiology.


2-aroylindoles, a novel class of potent, orally active small molecule tubulin inhibitors.
2-Aroylindoles with 5-methoxy-1H-2-indolyl-phenylmethanone (D-64131) as the lead structure were discovered as a new class of synthetic, small molecule tubulin inhibitors. By competitively binding with [(3)H]colchicine to alphabeta-tubulin and inhibiting microtubule formation, cycling cells were arrested in the G(2)-M phase of the cell division cycle. The proliferation of tumor cells from 12 of 14 different organs and tissues was inhibited with mean IC(50)s of 62 nM and 24 nM by D-64131 and D-68144, respectively, comparable with the potency of paclitaxel with mean IC(50) of 10 nM. By measuring the cytotoxicity in a human colon carcinoma cell model with ectopic ecdysone-inducible expression of the cyclin-dependent kinase inhibitor p21(WAF1), specificity toward cycling cells was demonstrated. In contrast to microtubule inhibitors from natural sources, 2-aroylindoles did not alter the polymerization-dependent GTPase activity of beta-tubulin and are not substrates of the multidrug resistance/multidrug resistance protein efflux pump. No cross-resistance toward cell lines with multidrug resistance/multidrug resistance protein independent resistance phenotypes became evident. In animal studies, no signs of systemic toxicity were observed after p.o. dosages of up to 400 mg/kg of D-64131. In xenograft experiments with the human amelanoic melanoma MEXF 989, D-64131 was highly active with treatment resulting in a growth delay of 23.4 days at 400 mg/kg. Therefore, D-64131 and analogues have the potential to be developed for cancer therapy, replacing or supplementing standard therapy regimens with tubulin-targeting drugs from natural sources.


Variability in Damage Caused by the Mite Tetranychus urticae (Trombidiformes: Tetranychidae) Koch on Three Varieties of Strawberry.
The strawberry, Fragaria×ananassa Duchesne (Rosales: Rosaceae), is an important crop in Mexico. We evaluated the tolerance of three newly developed Mexican strawberry varieties (CP0615, CPLE-7, and CPJacona) to Tetranychus urticae Koch (Trombidiformes: Tetranychidae), the most important pest of strawberry. We evaluated the effect of three different initial mite densities on population growth, duration of each developmental stage and survival of T. urticae on the three strawberry varieties. We also compared the photosynthetic activity (Pn), sub-stomatal CO2 concentration (Ci), stomatal conductance (gs) and the area of leaf damaged in the three varieties. The largest final density of mites occurred on the variety CP0615, followed by the varieties CPLE-7 and CPJacona. There were no significant differences in the duration of T. urticae developmental stages amongst the varieties, except for larvae where the shortest duration was on variety CPLE-7. The proportion of eggs reaching the adult stage (survival) was significantly lower on the variety CPLE-7. The number and morphology of the trichomes did not play an important role in the outcomes, as they were similar in the three varieties. There were no significant differences in Pn, Ci, and gs values amongst the three varieties in the presence and absence of T. urticae. The area of leaf damaged in variety CPLE-7 was significantly smaller than for the other varieties. Based on these results, and with regard to spider mite tolerance, we believe that the variety CPLE-7 has the greatest potential for further development, and eventually, for use on a commercial scale in Mexico.


Fullerene Negative Ions: Formation and Catalysis.
We first explore negative-ion formation in fullerenes C44 to C136 through low-energy electron elastic scattering total cross sections calculations using our Regge-pole methodology. Then, the formed negative ions C44- to C136- are used to investigate the catalysis of water oxidation to peroxide and water synthesis from H2 and O2. The exploited fundamental mechanism underlying negative-ion catalysis involves hydrogen bond strength-weakening/breaking in the transition state. Density Functional Theory transition state calculations found C60- optimal for both water and peroxide synthesis, C100- increases the energy barrier the most, and C136- the most effective catalyst in both water synthesis and oxidation to H2O2.


Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala.
There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP), known as "Valeriana del monte", and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM), forced swimming (FST), strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5%) and time spent (44.7%) in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.


Rituximab in childhood and juvenile autoimmune bullous diseases as first-line and second-line treatment: a case series of 13 patients.
Little data are available concerning the outcome of rituximab (RTX) therapy in pediatric patients with autoimmune bullous diseases (AIBDs). We sought to evaluate safety and efficacy of RTX administration in pediatric patients with AIBDs and to assess first-line RTX therapy in pemphigus patients. AIBD patients consisting of 12 pemphigus patients and a patient with bullous pemphigoid who received RTX before the age of 18 were enrolled. Detailed information regarding patients' outcome after the first RTX cycle was assessed. The mean age of the patients at RTX infusion was 15 ± 2 years. Six patients in the pemphigus group received RTX as first-line therapy. In pemphigus patients: complete remission (on minimal therapy) was achieved by seven patients, partial remission (on minimal therapy) and complete remission (off therapy) were achieved by three patients and one, respectively. Relapse occurred in nine patients, which were mostly mild. Likewise, the BP patient received RTX with a good clinical response. The observed adverse events were mostly mild infusion reactions and a case of sepsis. Rituximab is safe and effective in childhood/juvenile patients with AIBDs. Furthermore, RTX can be used as first-line treatment in pediatric patients with pemphigus.


[Oxidized low density lipoproteins and their association with some atherosclerosis risk factors in a population of Novosibirsk men].
Lipid peroxidation products (LPP) and liposoluble antioxidants in low density lipoproteins (LDL), resistance of LDL to oxidation were determined in 305 male inhabitants of Novosibirsk aged 30-70 years. Other methods of examination included questionnaires, anthropometry, registration of blood pressure (BP) and ECG, measurement of total cholesterol (TCH), high density lipoprotein cholesterol (HDLCH), triglycerides (TG). Ten and 90% cut points of percentile distribution of LPP in LDL and parameters of their resistance to oxidation in male population of Novosibirsk were used as regional reference values. Interrelationships were found between LPP in LDL, parameters of LDL resistance to oxidation, levels of antioxidants in LDL, and TCH, TG, HDL CH, smoking, BP and body mass index. Associations between LPP in LDL, LDL resistance to oxidation and TCH, HDLCH, TG, smoking and systolic BP were independent.


Cardiac disease and cognitive impairment: a systematic review.
Cognitive impairment in cardiac patients may interfere with disease management. This review describes studies examining specific cognitive impairments in cardiac patients and studies that investigate the link between echocardiographic and cognitive measures. Executive function impairments were frequently reported in different patient groups. Also, lower cardiac output and worse left ventricular diastolic function are linked to executive function deficits. In cardiac patients, special attention should be paid to these executive function impairments in view of their role in disease management and independent living. Interventions that stimulate executive function should be encouraged and integrated in cardiac treatment protocols.


Anderson-Fabry disease: developments in diagnosis and treatment.
Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. The incidence has been estimated to 1 per 40,000-60,000 males and 1 per 117,000 in the general population. Symptoms usually occur during childhood or adolescence, occasionally in middle age (according to the level of the enzyme activity). Life-threatening complications often develop in untreated patients. In classic Fabry disease, they include cutaneous, renal, cardiac and cerebrovascular manifestations that lead to premature death. Early recognition of symptoms, enzyme activity levels, concentration of Gb3 levels in the blood, urine and skin biopsies, as well as genetic testing (GLA gene) enable establishment of early diagnosis and therapeutic intervention with enzyme replacement therapy. Early therapy initiation prior to significant disease manifestations or complications may improve patient outcome.


Genome Sequence of Lymphocystis Disease Virus 2 LCDV-JP_Oita_2018, Isolated from a Diseased Japanese Flounder (Paralichthys olivaceus) in Japan.
Here, we present the genome sequence of lymphocystis disease virus 2 LCDV-JP_Oita_2018 (genus Lymphocystivirus, family Iridoviridae), which was isolated from a diseased Japanese flounder (Paralichthys olivaceus) in Japan. The LCDV-JP_Oita_2018 genome was assembled into a circular contig of 186,627 bp, with 140 predicted protein-coding genes and a GC content of 27%.


Magnetic Properties of FeNi/Cu-Based Lithographic Rectangular Multilayered Elements for Magnetoimpedance Applications.
The rectangular elements in magnetoimpedance (MI) configuration with a specific nanocomposite laminated structure based on FeNi and Cu layers were prepared by lift-off lithographic process. The properties of such elements are controlled by their shape, the anisotropy induced during the deposition, and by effects associated with the composite structure. The characterizations of static and dynamic properties, including MI measurements, show that these elements are promising for sensor applications. We have shown that competition between the shape anisotropy and the in-plane induced anisotropy of the element material is worth taking into account in order to understand the magnetic behavior of multilayered rectangular stripes. A possibility of the dynamic methods (ferromagnetic and spin-wave resonance) to describe laminated planar elements having a non-periodic modulation of both structure and magnetic parameters of a system is demonstrated. We show that the multilayered structure, which was originally designed to prevent the development of a "transcritical" state in magnetic layers and to reach the required thickness, also induces the effects that hinder the achievement of the goal, namely an increase in the perpendicular magnetic anisotropy energy.


Efficacy and safety of preoperative transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.
The aim of the study was to compare preoperative transcatheter arterial chemotherapy (TACE) plus liver resection (LR) with liver resection (LR) alone for hepatocellular carcinoma (HCC). PubMed, Embase, Cochrane library, web of science and China National Knowledge Infrastructure (CNKI) were searched from their initiation until 24 August 2021. Eligible languages were English and Chinese. This study includes only RCT and cohort studies. The primary outcome was the prognostic factors including overall survival rate (OS), disease-free survival (DFS), recurrence-free survival (RFS), and we also research the operative time, intraoperative blood loss, and postoperative complication. Twenty-nine trials (2 RCTs and 27 cohorts) were included, containing a total of 22023 patients, compared with hepatic resection, preoperative TACE plus LR shows the benefit of RFS (Hazard Ratio (HR)=0.80, 95%CI = [0.73-0.88], p < .001), and the combined therapy was associated with a higher OS for patients with HCC in Barcelona Clinic Liver Cancer (BCLC) B stage (HR = 0.76, 95%CI = [0.60-0.96], p = .024). In terms of safety, combination therapy is related to less intraoperative blood loss (Weighted Mean Difference (WMD)=-11.17, 95%CI = [-21.79 to -0.54], p = .039); and there's no statistical significance in postoperative complication (Risk Ratio (RR)=0.99, 95%CI= [0.90-1.08], p = 0.771) and operative time (WMD = 7.57, 95%CI = [-5.07 to 20.20], p = .240). TACE prior to surgery should be recommended as a routine treatment for HCC patients, especially BCLC B stage HCC, in view of its benefits for RFS and OS. Large, multicenter, and blinded randomized trials should be performed to confirm these findings.


[Population's behaviour and expectations concerning malaria control in Ouidah, Benin, April 2006)].
The aim of this study conducted in April 2006 in Ouidah (Benin), was to measure some results indicators of the implementation of "Roll Back Malaria" in Benin. Impregnated bed nets are available in 25.6% of the households and are used by 21.2% of children under five years old and 26.7% of pregnant women. The main reasons for this use are protection against harmful effect of mosquitoes (74%) and prevention of the malaria transmission (51%). The cost of impregnated bed net purchased is in average 2115 FCFA. Malaria morbidity in household is very high (48%) among children under five years old. The percentage of feverish children correctly treated in household according to the National Malaria Control Program's protocol is 1%. The major expectations of the households are supply of impregnated bed nets free of charge (33%), reduction of its delivery price (18%), its availability in health facilities (15%) and free treatment of malaria cases (12%).


Combined primary hepatic neuroendocrine carcinoma and hepatocellular carcinoma: case report and literature review.
Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is rarely reported, and its clinical features, origin, diagnosis, and behavior have not been established. In the literature, mixed HCC-NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here, we report a patient with a combined-type HCC-NEC tumor. An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of the liver. Laboratory and radiologic examinations showed typical findings of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was treated by partial laparoscopic hepatectomy of segment 5. Pathological examination showed that the tumor was predominantly HCC, partly admixed with an NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC-HCC tumor. After the preoperative diagnosis, the patient underwent somatostatin receptor scintigraphy to detect the primary NEC lesion, but no accumulation was found in any other part of her body. She has been free of recurrence for 9 months since the surgery. Mixed HCC-NEC tumors are extremely rare, and correct diagnosis requires multidisciplinary collaboration. The accumulation of further cases is needed to help understand the exact pathology, diagnosis, and treatment of this disease.