Retention of mandibular advancement devices in the treatment of obstructive sleep apnea: an in vitro pilot study.
In order for a mandibular advancement device (MAD) to be efficacious, it must remain seated on the teeth during sleep. Quantitative data on the retentive characteristics of MADs are currently unavailable. The present pilot study is the first to describe an in vitro setup testing the retentive characteristics of different monobloc MADs. A hydraulic cyclic test machine was used with MADs seated on dental casts to measure retention forces upon removal of the MADs. A custom-made monobloc (CM-mono), a thermoplastic monobloc (TP-mono), and a thermoplastic duobloc (TP-duo) configured as a monobloc were tested. Two protrusions were investigated, representing 25 and 65% of the maximal protrusion. The effects of the type of MAD, duration of the test, and amount of protrusion on removal forces were measured. The measured removal forces of all three MADs tested differed significantly, with the TP-duo showing the highest values (P < 0.0001). The effects of wear due to the repetitive cyclic loading became obvious by the production of wear particles in all MADs tested. However, only the TP-duo showed a significant reduction in time in removal forces for both protrusion positions (P < 0.0001; P = 0.0011). The effect of the amount of protrusion on the removal forces differed significantly between all three MADs tested (P = 0.0074). This in vitro pilot study reveals significant differences in retention forces for the MADs tested. The findings are consistent with clinical effects of nightly loss of MADs as reported in the literature and are within the range of reported physiological mouth-opening forces. Future research is needed to determine the key design features of MADs that explain these differences.


Successive changes of the cellular composition in lymphoid organs of MRL-Mp/lpr-lpr mice during the development of lymphoproliferative disease as investigated in cryosections.
To analyze the tissue distribution of lymphocyte subsets of autoimmune MRL/Mp-lpr/lpr mice, we have studied cryostat sections of the lymphoid organs at different stages of the disease using monoclonal antibodies directed against Ly 1 (MAb 53-7.3), Ly 2 (MAb 53-6.7), B 220 (MAb 14.8), and mu heavy chain (MAb b.7.6). We have observed an increase of a characteristic subpopulation of lymphocytes (Ly 1+ (dull), Ly 2-, B 220+, sIgM-), first seen at age of 8 weeks. In lymph nodes, these cells are first organized follicle-like with sIgM+ cells in the center. Later (20th-29th weeks), mu+ cells are found almost exclusively in small areas between the follicles. In the spleen, the cells first appear in the outer periarteriolar lymphatic sheath. Later, they are distributed within the follicles. sIgM+ cells disappear from the follicles; few remain within the marginal zone. In the thymus, some mice show a highly increased number of mu+ cells in the medulla. In Peyer's Patches, these Ly 1+ (dull) B 220+ cells are found predominantly in the interfollicular zone.


Nonlocal anomaly of the axial-vector current for bound states.
We argue that the amplitude <rho(gamma)/delta(nu)(q(gamma)(nu)gamma(5)q)/0> does not vanish in the limit of zero quark masses. This represents a new kind of violation of the classical equation of motion for the axial current and should be interpreted as the axial anomaly for bound states. The anomaly emerges in spite of the fact that the one loop integrals are ultraviolet finite as guaranteed by the finite size of bound-state wave functions. As a result, the amplitude behaves like approximately 1/p(2) in the limit of a large momentum p of the current. The observed effect requires the modification of the classical equation of motion of the axial-vector current by nonlocal operators.


Free cytosolic Ca2+ measurements with fluorine labelled indicators using 19FNMR.
Characterisation by 19F NMR of fluorine-labelled indicators of cytosolic free Ca2+ concentration (by 5FBAPTA) and pH (by Fquene) is described, together with the techniques used to load the cell suspensions with the indicators for NMR spectroscopy. Useful features of the 19F NMR indicators include direct identification of the intracellular cation bound to the indicators, internal calibration of [Ca]i and pHi from the spectra, and simultaneous measurements of two or more indicators in the same cell suspension. Perturbations of cellular functions by 5FBAPTA and quin 2 are very similar, but vary widely in different cell systems. The [Ca]i and pHi responses of normal and transformed cells to mitogens and growth factors in serum are compared with data from similar experiments using fluorescence indicators. The only major discrepancy in [Ca]i measurements using the two independent assays was observed in Ehrlich ascites tumour cells. These cells have a high intracellular Zn2+ content which substantially quenches the quin 2 fluorescence, but does not affect [Ca]i measurements by 5FBAPTA. The Zn2+ present in the cells is detected as a separate response in the 5FBAPTA spectrum. The time course of the Ca signal in 2H3 cells stimulated by antigen to release histamine by exocytosis has been defined using 5FBAPTA and quin 2. Extension of the 19F NMR technique to [Ca] i and pHi measurements in perfused organs is illustrated in rat heart and responses to pharmacological agents are demonstrated. Developments in prospect to improve sensitivity and to measure [Na]i with a new family of indicators are outlined.


Xanthogranulomatous pyelonephritis in children.
We report on a child with xanthogranulomatous pyelonephritis--an uncommon entity in children. A review of the literature revealed that in only 18 per cent was the diagnosis made correctly preoperatively. In children the disease is of a focal nature rather than a diffuse one, suggesting that possibly radical surgery would be less necessary for adequate treatment.


Photobiomodulation preconditioned human semen protects sperm cells against detrimental effects of cryopreservation.
The biological consequences of semen samples preconditioning with photobiomodulation (PBM) were studied on human sperm cells post cryopreservation. Donated semen samples were collected from 22 married men with normal sperm parameters according to World Health Organization (WHO) criteria. Included samples were divided into control and PBM-preconditioning (one session, 810 nm, diode laser, and 0.6 J/cm2) groups before cryopreservation procedure. Progressive sperm motility (PSM), morphology, viability, sperm mitochondrial membrane potential(MMP), intracellular reactive oxygen species (ROS) and lipid peroxidation of sperm cells were assessed post thawing. PBM preconditioning of cryopreserved semen samples most prominently increased the PSM percentage 30 min post thawing (p = 0.000).Application of PBM before cryopreservation significantly increased the number of viable spermatozoa (p = 0.000), increased significantly the number of spermatozoa with high MMP (p = 0.004) and decreased significantly the number of spermatozoa with low MMP post-thawing(P = 0. 007)compared to control group. Cryopreserved human sperm cells with PBM preconditioning showed significant decrease in the levels of intracellular ROS (47.66 ± 2.14 versus 60.42 ± 3.16, p = 0.002) and lipid peroxidation (3.06 ± 0.13 versus 3.68 ± 0.27, p = 0.05)compared to control group. Our findings, as the first evidence, indicated that PBM-preconditioning of human semen before cryopreservation provides a real and substantial advantage. This might lead to a novel strategy in improving PBM application in the procedures of assisted reproductive technologies.


Cyanamide mediated syntheses under plausible primitive earth conditions. IV. The synthesis of acylglycerols.
The synthesis of palmitoylglycerols in good yields occurs when a solution of glycerol, ammonium palmitate, cyanamide and imidazole is dried and heated at ambient humidity at temperatures ranging from 60 degrees--100 degrees C for 16 h. Much less product is formed in the absence of either or both cyanamide or imidazole. This work suggests that acylglycerols could have been synthesized on the primitive Earth under plausible prebiotic conditions which were similar but not identical to those which have been shown to condense deoxynucleotides into oligodeoxynucleotides and amino acids into peptides.


Neural activation underlying cognitive control in the context of neutral and affectively charged pictures in children.
The neural correlates of cognitive control for typically developing 9-year-old children were examined using dense-array ERPs and estimates of cortical activation (LORETA) during a go/no-go task with two conditions: a neutral picture condition and an affectively charged picture condition. Activation was estimated for the entire cortex after which data were exported for four regions of interests (ROIs): ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), and orbitofrontal/ventromedial prefrontal cortex (OFC/VMPFC). Results revealed faster reaction times, greater N2 activation, and greater prefrontal activation for the affectively charged picture condition than the neutral picture condition. The findings are discussed in reference to the impact of affective stimuli on recruitment of specific brain regions involved in cognitive control.


Females display relatively preserved muscle quality compared with males during the onset and early stages of C26-induced cancer cachexia.
Cancer cachexia is clinically defined by involuntary weight loss >5% in <6 mo, primarily affecting skeletal muscle. Here, we aimed to identify sex differences in the onset of colorectal cancer cachexia with specific consideration to skeletal muscle contractile and metabolic functions. Eight-weeks old BALB/c mice (69 males, 59 females) received subcutaneous C26 allografts or PBS vehicle. Tumors were developed for 10-, 15-, 20-, or 25 days. Muscles and organs were collected, in vivo muscle contractility, protein synthesis rate, mitochondrial function, and protein turnover markers were assessed. One-way ANOVA within sex and trend analysis between sexes were performed, P < 0.05. Gastrocnemius and tibialis anterior (TA) muscles became atrophic in male mice at 25 days, whereas female mice exhibited no significant differences in muscle weights at endpoints despite presenting hallmarks of cancer cachexia (fat loss, hepatosplenomegaly). We observed lowered muscle contractility and protein synthesis concomitantly to muscle mass decay in males, with higher proteolytic markers in muscles of both sexes. mRNA of Opa1 was lower in TA, whereas Bnip3 was higher in gastrocnemius after 25 days in male mice, with no significant effect in female mice. Our data suggest relative protections to skeletal muscle in females compared with males despite other canonical signs of cancer cachexia and increased protein degradation markers; suggesting we should place onus upon nonmuscle tissues during early stages of cancer cachexia in females. We noted potential protective mechanisms relating to skeletal muscle contractile and mitochondrial functions. Our findings underline possible heterogeneity in onset of cancer cachexia between biological sexes, suggesting the need for sex-specific approaches to treat cancer cachexia.NEW & NOTEWORTHY Our study demonstrates biological-sex differences in phenotypic characteristics of cancer cachexia between male and female mice, whereby females display many common characteristics of cachexia (gonadal fat loss and hepatosplenomegaly), protein synthesis markers alterations, and common catabolic markers in skeletal muscle despite relatively preserved muscle mass in early-stage cachexia compared with males. Mechanisms of cancer cachexia appear to differ between sexes. Data suggest need to place onus of early cancer cachexia detection and treatment on nonmuscle tissues in females.


Use of HIV Post-Exposure Prophylaxis Among Men Who Have Sex With Men in Shenzhen, China: A Serial Cross-Sectional Study.
HIV postexposure prophylaxis (PEP) has been prescribed to non-occupational people in recent years, but the implementation of PEP in China is still unclear. This study sought to examine the PEP use rate and factors associated with PEP in Men who have sex with men (MSM). We recruited HIV-negative MSM through offline methods from 2018 to 2020 in Shenzhen, China. Overall, PEP use increased from 3.92% to 2018, 5.73% in 2019, and 10.29% in 2020. Among 2833 participants who reported their most recent questionnaire, factors associated with PEP use included residence in Shenzhen less than 1 year, sexual intercourse with women, preferred way of finding sexual partners in MSM venues, multiple sexual partners (≥ 2), condom use, lubricant use, viagra use, less use of rush popper, HIV-related services and interest in initiating Pre-exposure prophylaxis (PrEP). The implementation of the PEP plan should focus on the groups that may be at risk of HIV infection and their continued risky behaviours. For the inappropriate use of PEP, PEP publicity should guide MSM to choose regular hospitals and strengthen HIV testing before and after PEP.


[6A8 alpha-mannosidase catalyzes p-nitrophenyl-alpha-D-mannopyranoside].
To confirm the alpha-mannosidase nature of the protein encoded by 6A8 cDNA. 1) To construct a full-length 6A8 cDNA based on the three cloned DNA fragments by means of gene recombinant technique; 2) To insert the 6A8 cDNA into eukaryotic expression vector pCDI; 3) To transfect the recombinant pCDI-6A8 into COS-7 cells; 4) To characterize the nature of the protein encoded by 6A8 cDNA by means of enzymic activity assay and Western blotting assay. The constructed 6A8 cDNA was the right cDNA in sequence. The enzymetic activity of the homogenate of COS-7 cells transfected with pCDI-6A8 was 3-4 times higher than that of the cells transfected with the mock or the wild cells. The enzymetic reaction could not be inhibited by swainsonine. Western blot showed a band of 120,000 recognized by mAb 6A8. The band in the cells transfected with pCDI-6A8 cDNA was much darker than that in the cells transfected with the mock or in the wild cells. The protein encoded by 6A8 cDNA is a kind of alpha-mannosidase, which belongs to type II alpha-mannosidase.


Potentiation of the hyporeactivity induced by in vivo endothelial injury in the rat carotid artery by chronic treatment with fish oil.
1. The present study investigates whether or not chronic feeding of rats with a diet enriched in fish oil affects the reactivity of balloon-injured carotid arteries. The left carotid arteries were injured in vivo by the repeated passage of a balloon catheter. Both the right (control artery) and the left carotid arteries were excised 24 h after the injury, and suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. 2. Phenylephrine evoked similar concentration-contraction curves in the right (control) carotid arteries without endothelium from control and fish oil-fed rats. Balloon injury decreased the contractility of carotid arteries to phenylephrine in both types of rats and the pEC50 for phenylephrine was significantly decreased in balloon-injured arteries from control rats compared to those obtained in arteries from fish oil-fed rats (pEC50 7.59 +/- 0.1 and 7.28 +/- 0.06, respectively) while maximal contractions were similar (1.93 +/- 0.15 g and 1.79 +/- 0.12 g, respectively). 3. The treatment of control right carotid arteries without endothelium with either NG-nitro-L-arginine (an inhibitor of nitric oxide synthase) or superoxide dismutase (which protects nitric oxide from degradation) did not affect significantly the contractions to phenylephrine in either group. In these preparations, methylene blue (an inhibitor of soluble guanylate cyclase) decreased slightly but significantly maximal contractions to phenylephrine in both groups. The treatment of balloon-injured carotid arteries with NG-nitro-L-arginine or methylene blue partly restored contractions to phenylephrine in arteries from both types of rat. Superoxide dismutase further depressed the contractility to the alpha l-adrenoceptor agonist in balloon-injured arteries from control diet-fed rats but had no effect in balloon-injured preparations from fish oil-fed rats.4. 3-Morpholino-sydnonimine (SIN-1, a donor of nitric oxide) evoked similar concentration-dependent relaxations in control and balloon-injured carotid arteries from both types of rat.5. Balloon injury caused an increase in the tissue content of cyclic GMP in carotid arteries from control diet-fed rats. This production of cyclic GMP was abolished by N0-nitro-L-arginine. Superoxide dismutase potentiated significantly the production of cyclic GMP caused by balloon injury in control but not in fish oil-fed rats.6 These observations confirm that in vivo balloon injury causes the production of nitric oxide in the injured blood vessel wall. This production of nitric oxide from L-arginine accounts for the decreased contractility to phenylephrine and the accumulation of cyclic GMP in balloon-injured arteries. They further indicate that chronic feeding of rats with fish oil potentiates the L-arginine-nitric oxide pathway in the injured vessel leading to an enhanced hyporeactivity to phenylephrine.


Modeling radiofrequency responses of realistic multi-electrode leads containing helical and straight wires.
To present a modeling workflow for the evaluation of a lead electromagnetic model (LEM) consisting of a transfer function (TF) and a calibration factor. The LEM represents an analytical relationship between the RF response of a lead and the incident electromagnetic field. The study also highlights the importance of including key geometric details of the lead and the electrode when modeling multi-electrode leads. The electrical and thermal responses of multi-electrode leads with helical and straight wires were investigated using 3D electromagnetic (EM) and thermal co-simulations. The net dissipated power (P) around each lead electrode and the net temperature increase at the electrodes (ΔT) were obtained for a set of incident EM fields with different spatial distributions. A reciprocity approach was used to determine a TF for each electrode based on the results of the computational model. The evaluation of the calibration factors and the TF validation were performed using the linear regression of P versus the LEM predictions. P and ΔT were investigated for four multi-electrode leads and four single-electrode leads containing either helical or straight wires. All electrodes of the multi-electrode lead were found to be points of high power deposition and temperature rise. The LEMs for the individual electrodes varied substantially. A significant dependence of the calibration factors on the surrounding tissue medium was also found. Finally, the model showed that the TF, the calibration factor, P and ΔT for multi-electrode leads differ significantly from those for single-electrode leads. These results highlight the need to evaluate a LEM for each electrode of a multi-electrode lead as well as for each possible surrounding medium. It is also shown that the results derived from simulations based on simplified single-electrode leads can significantly mislead multi-electrode lead analyses.


Involvement of glomerular SREBP-1c in diabetic nephropathy.
The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGFbeta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47phox, p67phox, and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-1c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MES13 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy.


Altered transsulfuration pathway enzymes and redox homeostasis in inherited retinal degenerative diseases.
Retinal degenerative diseases result from apoptotic photoreceptor cell death. As endogenously produced gaseous molecules such as hydrogen sulfide (H2S) and nitric oxide (NO) play a key role in apoptosis, we compared the expression levels of genes and proteins involved in the production of these molecules in the retina of normal dogs and three canine models (rcd1, crd2, and xlpra2) of human inherited retinal degeneration (IRD). Using qRT-PCR, Western blot, and immunohistochemistry (IHC), we showed that mRNA and protein levels of cystathionine β-synthase (CBS), an enzyme that produces H2S in neurons, are increased in retinal degeneration, but those of cystathionine γ-lyase (CSE), an enzyme involved in the production of glutathione (GSH), an antioxidant, are not. Such findings suggest that increased levels of H2S that are not counterbalanced by increased antioxidant potential may contribute to disease in affected retinas. We also studied the expression of neuronal and inducible nitric oxide synthase (nNOS and iNOS), the enzymes responsible for NO production. Western blot and IHC results revealed increased levels of nNOS and iNOS, resulting in increased NO levels in mutant retinas. Finally, photoreceptors are rich in polyunsaturated fatty acids (PUFAs) that can make these cells vulnerable to oxidative damage through reactive oxygen species (ROS). Our results showed increased levels of acrolein and hydroxynonenal (4HNE), two main toxic products of PUFAs, surrounding the membranes of photoreceptors in affected canines. Increased levels of these toxic products, together with increased NO and ROS, likely render these cells susceptible to an intrinsic apoptotic pathway involving mitochondrial membranes. To assess this possibility, we measured the levels of BCL2, an anti-apoptotic protein in the mitochondrial membrane. Western blot results showed decreased levels of BCL2 protein in affected retinas. Overall, the results of this study identify alterations in the expression of enzymes directly involved in maintaining the normal redox status of the retina during retinal degeneration, thereby supporting future studies to investigate the role of H2S and NO in retinal degeneration and apoptosis.


Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation.
Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation.


Identification of Simple Compounds with Microtubule-Binding Activity That Inhibit Cancer Cell Growth with High Potency.
We analyzed more than 1 million small molecules with the goal of finding simple synthetic compounds that potently inhibit cancer cell growth. We identified three such compounds with unknown mechanisms of action. Subsequent studies revealed that all three of these small molecules target microtubules. These three scaffolds can serve as templates for developing new microtubule-targeted agents, overcoming the limits of existing microtubule-inhibiting drugs derived from complex natural products.


Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK.
Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. UK National Health Service. After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.


Protective effect of Amomi semen extract on alloxan-induced pancreatic beta-cell damage.
The protective effect of Amomi semen extract (ASE) on alloxan-induced pancreatic beta-cell damage was investigated in HIT T-15 cells, a Syrian hamster pancreatic beta-cell line. Alloxan caused pancreatic beta-cell damage through the generation of reactive oxygen species (ROS), the elevation of cytosolic free Ca2+, DNA fragmentation and the decrease of cellular NAD+ and ATP levels. All these effects of alloxan were significantly prevented by pretreatment with a water-soluble extract of Amomi semen. Pretreatment with ASE in pancreatic islets isolated from mice, also significantly abolished the inhibition of glucose-stimulated insulin secretion by alloxan. The results of this study provide evidence that ASE may have a protective activity on alloxan-induced beta-cell damage, and that the protective effect is primarily due to the inhibition of ROS generation by alloxan.


Lateral hernia secondary to colorectal submucosal resection repaired by robotic-assisted approach: Case report.
Lateral abdominal wall defects are a rare event and commonly result from iatrogenic causes and trauma. We report the first known case of flank hernia after endoscopic submucosal resection of a colonic polyp complicated by colonic perforation. This is a case of a 50-year-old male who underwent endoscopic colonic resection complicated by perforation of the colon. Eight months later, he presented with an enlarging, asymptomatic left flank bulge. CT showed a large flank hernia which was successfully repaired using a robotic transabdominal preperitoneal (TAP) approach. The hypothesis is that the endoscopic resection with colonic perforation caused an iatrogenic injury to the abdominal wall creating a lateral abdominal hernia. Injury to abdominal wall musculature may take months to develop into a clinically apparent hernia. Flank hernias can be successfully repaired using a robotic minimally invasive approach. Flank bulge and hernias must be included or at least be considered as consequence of a potential complication from endoscopic colonic perforation. Surgeons and endoscopists must be aware of this potential complication and its latent presentation. This case stresses the importance of long-term outcomes monitoring, particularly with innovative procedures.


Early fibrosis inhibits hepatocellular carcinoma mediated by free radical effects.
We studied the in-vitro/in-vivo interactions between HCC/HSCs in early and advanced fibrosis-models. Hep3B-mono-cultures secreted high levels of αFetoProtein (αFP). Human-HSCs co-cultured with Hep3B-cells significantly decreased αFP and increased their apoptosis. Confocal-microscopy demonstrated Hep3B-phagocytosis inside the HSCs suggesting a direct cellular-contact mediating anti-tumor effect. Leptin-activated HSCs further suppressed Hep3B-cells with increased ROS and decreased GSH. Following intrahepatic-Hep3B-cell injections, mice with established "advanced liver-fibrosis"; had higher tumor-size and αFP serum-levels as compared to non-fibrotic livers. Mice with "early liver-fibrosis", which initiated post tumor induction had a significant decrease in tumor and high Malondialdehyde (MDA) serum levels compared to advanced-fibrosis animals. At early-fibrosis stages, activated-HSCs express direct anti-tumor effects by phagocytosis and apoptosis of tumor-cells mediated by oxidative stress.


Tautomerization Effect of Histidines on Oligomer Aggregation of β-Amyloid(1-40/42) during the Early Stage: Tautomerism Hypothesis for Misfolding Protein Aggregation.
As the intrinsic origin of the hypothesis for β-amyloid (Aβ) from Alzheimer's disease, histidine behaviors were found to play a crucial role in Aβ aggregation. To investigate the histidine behaviors during the early stage of aggregation, Aβ40/42 pentamers with different histidine isomer states were simulated at the atomic level. Results show that five Aβ40 (δδδ) and Aβ42 (εδδ) monomers can rapidly decrease the aggregation threshold, promote stable pentamer formation, and increase pentamer contents by 51.8% and 56.7%, respectively, as compared with the values of their wild-type (εεε) counterparts. Additionally, pentamers of Aβ40 (δδδ) and Aβ42 (εδδ) have different aggregation pathways and disassembly species, Tr+D and Te+M, during the growth of the pentamer. This work discloses the significance of histidine tautomerization in Aβ aggregation, implying a potential way to control Aβ aggregation and develop the assembly inhibitors.


Optimization for ultrasonic-microwave synergistic extraction of polysaccharides from Cornus officinalis and characterization of polysaccharides.
Ultrasonic-microwave synergistic extraction (UMSE) of polysaccharides from Cornus officinalis was optimized by response surface methodology (RSM). The effect of four different factors on the yield of C. officinalis polysaccharides (COP) was studied. RSM results showed that the optimal conditions were extraction time of 31.49823 min, microwave power of 99.39769 W, and water-to-raw material ratio of 28.16273. The COP yield was 11.38±0.31% using the modified optimal conditions, which was consistent with the value predicted by the model. The crude COP was purified by DEAE-Cellulose 52 chromatography and Sephadex G-100 chromatography. Five fractions, namely, crude COP, COP-1, COP-2, COP-3, and COP-4, were obtained. Monosaccharide composition analysis revealed that the COP was composed of glucose, arabinose, fucose, xylose, mannose, and rhamnose. Preliminary structural characterizations of COP were conducted by scanning electron microscopy and Fourier transform infrared spectroscopy.


An ileo-colic intussusception reaching down to the descending colon - A case report.
Intussusception in healthy adults is rare and often associated with oncologic diseases. This case report presents a case of an ileo-colic intussusception reaching down to the descending colon in a healthy adult that required ileo-colic resection. We present a case of a 78-year-old male patient with acute onset unspecific abdominal pain. The medical history was unremarkable. Preoperative radiologic assessments showed an invagination of the small intestine into the colon without any signs of polyps or tumours. An emergency laparotomy with resection of the affected intestine was performed. The pathologist described a 49 cm length of intussuscepted colon and an additional 7 cm intussusception of the terminal ileum. A circular area with multiple polyps extending over 8 cm in the colon could be identified. The microscopic findings showed a low-grade dysplasia within this area. Following surgery, the patient was discharged to rehabilitation after a ten-day hospitalization. Intussusception in adults is rare and the clinical presentation includes unspecific symptoms making the diagnosis challenging. In 90% of the cases, a pathologic lesion is found (two-thirds are neoplasms). An intussusception involving the colon should be treated surgically without prior reduction due to the high incidence of a neoplasm and the risk for perforation and tumour dissemination. In the literature, neoplastic disease represents the major cause for intussusception in adults. This report presents a rare case of an ileo-colic intussusception reaching down to the descending colon treated successfully with a subtotal colectomy.


Numerical modeling of the temperature distribution within a bonded paper web when undergoing microwave heating in a waveguide
In this paper, a numerical technique is used to study the temperature distribution within the heated bonded paper web placed in a waveguide. The parameters of the problem were selected so as to best locate the test sample that would generate the desired absorbed power. The method of false transient was utilized to accelerate the numerical convergence and the equations were discretized with central difference in both time and space. The resulting system of equations was solved using an Alternating Direction Implicit scheme. Good agreement was achieved between the numerical solutions and the experimental validations.


The relation between plasma testosterone levels and the lengths of phases of the menstrual cycle.
Plasma testosterone levels were measured in 331 women of reproductive age. The incidence of clinical signs of hyperandrogenism (hirsutism, acne) was recorded. Ovulatory activity was evaluated clinically by basal body temperature and frequent observation of changes in the appearance of the cervical os and cervical mucus. Plasma testosterone levels were abnormally elevated in patients with clinical signs of hyperandrogenism. The highest mean testosterone levels were noted in the group of hyperandrogenic women with amenorrhea. Significant prolongation of the follicular phase and shortening of the luteal phase were demonstrated to be associated with clinical signs of hyperandrogenism and elevated plasma testosterone levels. Statistically significant correlations between plasma testosterone levels and duration of phases of the menstrual cycle were observed. Testosterone levels were directly related to the length of the follicular phase and inversely related to the length of the luteal phase. A significant inverse correlation between the lengths of the two phases of the menstrual cycle was also demonstrated. These results suggest an association between hyperandrogenism and prolongation of the follicular phase and shortening of the luteal phase of the menstrual cycle, possibly related to the high incidence of infertility and menstrual irregularity reported for hyperandrogenic women.


Acute decompensated heart failure.
This article defines acute decompensated heart failure. Additionally, it lists common precipitating factors and the clinical presentation. Proper diagnostic technique is highlighted, as are possible treatments.


Zuo1, a ribosome-associated J protein, is involved in glucose repression in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the J-protein Zuo1 and the nonconventional Hsp70 homologue Ssz1 stimulate the ATPase activity of the chaperone proteins Ssb1 and Ssb2 (Ssb1/2), which are associated with the ribosomes. The dephosphorylation of sucrose nonfermenting 1 (Snf1) on Thr210 is required for glucose repression. The Ssb1/2 and 14-3-3 proteins Bmh1 and Bmh2 appear to be responsible for the dephosphorylation of Snf1 on Thr210 and glucose repression. Here, we investigated the role of Zuo1 in glucose repression. The zuo1∆ strain as well as the ssb1∆ssb2∆ strain exhibited a glucose-specific growth defect during logarithmic growth on glucose. Many of the respiratory chain genes examined were statistically significantly upregulated, but less than 2-fold, in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain on glucose. In addition, excessive phosphorylation of Snf1 on Thr210 was observed in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain in the presence of glucose. The mRNA levels of SSB1/2 and BMH1 were statistically significantly reduced by approximately 0.5- to 0.8-fold relative to the wild-type level in the zuo1∆ strain on glucose. These results suggest that Zuo1 is responsible for glucose repression, possibly by increasing the mRNA levels of SSB1/2 and BMH1 during growth on glucose.


Mitochondrial-generated ROS down regulates insulin signaling via activation of the p38MAPK stress response pathway.
Impairment of insulin signaling and hepatic insulin resistance has been attributed to ROS-mediated activation of p38MAPK stress response signaling. Our research focused on whether (a) ROS generated by mitochondrial electron transport chain complex I (ETC-CI) dysfunction, via the use of Rotenone, inactivates insulin signaling; and (b) the p38MAPK pathway is involved in the ROS-induced impairment of insulin signaling. Our results show that in primary mouse hepatocytes the CI inhibitor, Rotenone, (a) induces IRS-1 Ser(307) phosphorylation that is blocked by the anti-oxidant NAC or by the p38MAPK inhibitors, SB203580 and SB202190; (b) inhibits insulin-stimulated AKT-Ser(473) and GSK3β-Ser(9) phosphorylations, in a manner that is not responsive to reversal by the anti-oxidant NAC or by the p38MAPK inhibitors, SB203580 and SB202190. We conclude that rotenone-induced insulin resistance involves a p38MAPK-dependent mechanism for the inhibition of the proximal end of insulin signaling (IRS1), and a p38MAPK-independent mechanism for the inhibition of the distal end (AKT and GSK3β). Our study suggests that ROS generated by inhibition of ETC CI, promotes hepatic insulin resistance partly via activation of the p38MAPK stress-response pathway.


The past, present, and future of experimental methods in the social sciences.
In the midst of the current causal revolution, experimental methods are increasingly embraced across the social sciences. We first document the growth in the use of the experimental method and then overview the current state of the field along with suggestions for future research. Our review covers the core features of experiments that facilitate causal inference, and we offer numerous examples of different experimental designs and the types of research questions they are well-suited to test. We then harmonize popular but differing perspectives on validity in regard to experiments focused on theoretical considerations. Next, we detail a new framework of purposive sampling for social science experiments, suggesting researchers could benefit from moving beyond only two stock choices of representativeness or convenience. We then discuss issues of analysis unique to experimental data before ending with a critical discussion of null findings, open-science practices, social desirability, and other open debates in the experimental methods literature.


Factors Affecting Quality of Life for People Living with Albinism in Botswana.
People with albinism (PWA) in Africa suffer many challenges, including higher risk of skin cancers and deeply embedded stigma. We conducted interviews with PWA to determine factors influencing their quality of life (QOL) in Botswana. Physical concerns expressed included skin/eye health issues and limited access to health care. Psychosocial concerns included stigma/discrimination and myths/superstitions. Environmental concerns included barriers to personal development of education and employment, safety concerns, financial insecurity, and disability rights issues. Pervasive difficulty in obtaining equal rights to physical, psychosocial, and environmental health affected QOL. Education around albinism and disability rights are needed to improve QOL for PWA.


WNK1 kinase signaling in metastasis and angiogenesis.
With-no-lysine kinases (WNKs) are a novel family of serine/threonine protein kinases participating in ion homeostasis via the WNK-OSR1/SPAK-NKCC cascade. Recent studies of WNK1 have revealed that its related signaling pathways mediated tumor-induced angiogenesis and carcinogenesis and uncovered novel roles of WNK1 in endothelial cell migration and proliferation, tumor cell proliferation, and metastasis. Herein, we review the functions of WNK1 in cancer metastasis and angiogenesis and propose WNK1 targeting as an anti-cancer strategy.


Improved angiogenic response in pig heart following ischaemic injury using human skeletal myoblast simultaneously expressing VEGF165 and angiopoietin-1.
To achieve angiogenic interaction between VEGF(165) and angiopoietin-1 (Ang-1) using a novel adenoviral bicistronic vector (Ad-Bic) encoding the two factors and delivered ex vivo using sex-mismatched human skeletal myoblasts. A myocardial infarction model was developed in 29 female pigs; randomised into four groups: DMEM (group-1, n=6); Adenovirus null (Ad-null) vector-myoblast (group-2, n=5); Ad-Ang-1 myoblast (group 3, n=7) and Ad-Bic-myoblast (group-4, n=11). Three weeks later, 5 ml DMEM without myoblasts or containing 3 x 10(8) myoblasts carrying lac-z gene and transduced with Ad-null, Ad-Ang-1 or Ad-Bic were injected intra-myocardially in and around the infarct. 2D-echocardiography and fluorescent microsphere studies 6- and 12-weeks post-treatment revealed significantly improved cardiac performance and regional blood flow in groups 3 and 4. Histological studies and Y-chromosome analysis revealed extensive survival of lac-z positive myoblasts staining positive for human proteins in the pig heart. ELISA, immunostaining and RT-PCR revealed that Ad-Bic transduced myoblasts concomitantly but transiently expressed hVEGF(165) and Ang-1 both in vitro and in vivo. Double fluorescent immunostaining of the tissue sections for vWFactor-III and smooth muscle actin showed significantly higher vascular density of mature blood vessels per low power microscopic field in groups 3 and 4 at 6- and 12-weeks. Our combined approach led to enhanced angiogenesis with a greater percentage of functionally mature blood vessels in a porcine heart.


Porcine malignant hyperthermia. IX: Changes in the concentrations of intramuscular high-energy phosphates, glycogen and glycolytic intermediates.
A technique of obtaining muscle biopsies with a liquid nitrogen cryoprobe was used to study intramuscular metabolites in MH-susceptible and unsusceptible pigs. There was no significant difference in muscle metabolite values obtained from susceptible and unsusceptible pigs in the resting state. During MH the changes in metabolites were a result of rapid glycogenolysis and no abnormality of glycolytic control was observed.


Simultaneous analysis of filgrastim and pegfilgrastim aggregates by size-exclusion chromatography.
A new size-exclusion high-performance liquid chromatographic (SE-HPLC) method for the simultaneous analysis of filgrastim and pegfilgrastim aggregates was developed and validated. A cross-linked agarose and dextran column was used at ambient temperature and an alkaline sodium phosphate buffer as mobile phase eliminated non-ideal interactions with the stationary phase. The robustness of the method was assessed by varying injection volumes, flow rates and sample vehicles. Other reliability assessments include calibration curve, intra and inter-day precision and accuracy, repeatability of retention times, application to real in-process production samples and column lifetime. The method exhibited linearity over the concentration of 0.02-4 mg/ml range for filgrastim and pegfilgrastim monomer with a correlation coefficient of greater than 0.999. The lower limit of quantification was 0.02 mg/ml and the limit of detection was 0.005 mg/ml. This SE-HPLC technique has been successfully used for several years and more than 10,000 samples.


Performance of an immunochromatographic test for the rapid diagnosis of malaria.
The immunochromatographic test (ICT) for the rapid diagnosis of malaria has been marketed for several years. In a study in which three Centres of Tropical Medicine participated and data were pooled, performance of the test varied considerably when comparing the results between each centre. The sensitivity of ICT in 2,343 patients tested in our services was 100% and the specificity 99.74%. Moreover, two patients with a positive ICT would initially have been missed by expert microscopy, with Plasmodium falciparum malaria being confirmed microscopically some hours later. The principal reasons for the better performance of the test in our series appear to be blood collection in EDTA vials and considerable experience with handling and interpreting the ICT test.


Neurodevelopmental outcomes of premature infants with intraventricular hemorrhage across a lifespan.
Neurodevelopmental impairment rates remain high among extremely preterm and very low birth weight infants. This review describes the rates of brain injury and neuro-developmental impairment at 2,3 years, early school age, adolescence, and young adulthood for survivors with intraventricular hemorrhage (IVH). Former preterm infants with a history of high-grade IVH are at the greatest risk of adverse neurodevelopmental outcomes. There is variability, however, in definitions of brain injury, methods for assessing brain injury, and definitions of adverse outcomes among multicenter networks. Despite differences in methods described in publications, perinatal grade III-IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and white matter injury are consistently associated with increased rates of adverse motor and cognitive outcomes in the first 2,3 years of life, at early school age, in adolescence and early adulthood. Effects of socioeconomic status on outcomes, however, increase with the increasing age of the child. In summary, although preterm survivors of IVH are at an increased risk of adverse outcomes across a lifetime, there is evidence that social and environmental factors contribute to recovery over time.


Inhibitors Targeting the F-BOX Proteins.
F-box proteins are involved in multiple cellular processes through ubiquitylation and consequent degradation of targeted substrates. Any significant mutation in F-box protein-mediated proteolysis can cause human malformations. The various cellular processes F-box proteins involved include cell proliferation, apoptosis, invasion, angiogenesis, and metastasis. To target F-box proteins and their associated signaling pathways for cancer treatment, researchers have developed thousands of F-box inhibitors. The most advanced inhibitor of FBW7, NVD-BK M120, is a powerful P13 kinase inhibitor that has been proven to bring about apoptosis in cancerous human lung cells by disrupting levels of the protein known as MCL1. Moreover, F-box Inhibitors have demonstrated their efficacy for treating certain cancers through targeting particular mutated proteins. This paper explores the key studies on how F-box proteins act and their contribution to malignancy development, which fabricates an in-depth perception of inhibitors targeting the F-box proteins and their signaling pathways that eventually isolate the most promising approach to anti-cancer treatments.


An efficient amplification pulse sequence for measuring chemical shift anisotropy under fast magic-angle spinning.
A two-dimensional experiment for measuring chemical shift anisotropy (CSA) under fast magic-angle spinning (MAS) is presented. The chemical shift anisotropy evolution is amplified by a sequence of π-pulses that repetitively interrupt MAS averaging. The amplification generates spinning sideband manifolds in the indirect dimension separated by the isotropic shift along the direct dimension. The basic unit of the pulse sequence is designed based on the magic-angle turning experiment and can be concatenated for larger amplification factors.


An advanced method for quantitative measurements of cholesterol crystallization.
Cholesterol crystallization within an atherosclerotic plaque significantly contributes to the acceleration of plaque rupture - a problematic event due to the current lack of specific treatments to prevent such formations. Modelling this pathogenic process is also difficult due to the lack of suitable experimental models that enable quantitative analysis of crystal formation and bioactivity screening of potential therapeutic compounds. To develop an in vitro human cell model of cholesterol crystallization combined with an imaging system that incorporates both quantitative analysis and real-time continuous imaging of cholesterol crystal formation. An enhanced in vitro model of cholesterol crystallization was developed through the use of acetylated low-density lipoprotein (AcLDL) and 7-ketocholesterol as agents of foam cell induction within a human THP-1 monocytic cell line. Advanced confocal and polarizing microscopies were incorporated into the model so as to allow for quantitation of cholesterol crystallization, with the lipid-loaded group producing significantly greater numbers of cholesterol crystals than the untreated group. The utility of this system was also demonstrated by investigating the effects of the cholesterol-lowering drug lovastatin and therapeutic bile compound ursodeoxycholic acid (UDCA), showing that these drugs influence different aspects of cholesterol crystal formation. The in vitro human THP-1 monocyte model of cholesterol crystallization provides an effective and efficient means of quantitating cholesterol crystallization in the pre-clinical stage of research. The model also allows for the screening of potentially therapeutic compounds that may be used in attenuating or preventing cholesterol crystallization.


The pharmacokinetics of esmolol in pediatric subjects with supraventricular arrhythmias.
Esmolol is often used in the acute management of children with arrhythmias and/or hypertension; however, pharmacokinetic studies of the drug in children have been limited. The objective of this study was to determine the pharmacokinetics of esmolol in children with a history of supraventricular arrhythmias (SVT) who were scheduled for diagnostic electrophysiology study or a catheter ablation procedure. Subjects were stratified into two age groups: 2-11 and 12-16 years. After an episode of stimulated or spontaneous SVT, esmolol was administered intravenously as a 1,000 microg/kg bolus followed by continuous infusion at 300 microg/kg/min. Blood samples were collected before, at 5, 10 and 15 min after the loading dose, and 3, 6, 9, 12, 15 and 20 min after the end of the infusion. Plasma concentration of esmolol was quantitated by a specific LC/MS assay. Pharmacokinetic data were available for 25 subjects. Arterial esmolol concentrations were approximately five times greater than venous concentrations. Esmolol had an extremely short distribution half-life (0.6 min), a rapid terminal elimination half-life (6.9 min), and a rapid clearance (119 +/- 51 mL/min/kg) which was not related to subject age or weight. Seventeen of the subjects (63%) converted to normal sinus rhythm in an average of 2 min (range 0-5 min). The pharmacokinetics of esmolol and its efficacy in terminating SVT in children is similar to that observed in adults.


[Osteosis and calcinosis in scleroderma circumscripta linearis].
In a female patient suffering from linear morphea of long duration, we observed ossification and calcification of the affected tissue. There were no other abnormalities that might have been responsible for these symptoms.


Highly chelating stellate mesoporous silica nanoparticles for specific iron removal from biological media.
In this work, the design of a new generation of functionalized large pore silica nanoparticles is addressed for the specific removal of iron from biological environments. Herein, mesoporous silica with a large pore stellate morphology, denoted STMS, were grafted with the highly specific iron chelating agent desferrioxamine B, DFoB. The challenge of this work was the step by step elaboration of the nanoplatform and the evaluation of its chelating efficiency and selectivity. Hence, the controlled covalent grafting of DFoB specific iron chelator, was successfully achieved ensuring a high grafting rate of chelating ligand of 730 nmol·mg-1 (i.e., 0.85 ligand·nm-2). Furthermore, these highly chelating STMS silica were able to capture iron(III) stabilized with nitrilotriacetic acid (NTA) in solution at physiological pH with a fast kinetics (less than 30 min). For a stoichiometry 0.85:1 (FeNTA : DFoB), the STMS-DFoB nanoparticles allowed reaching capture capacity and efficiency of 480 nmolFe3+/mg SiO2 and 78%, respectively. Regarding the selectivity features of the removal process, studies were performed with two different media composed of various metal ions: (i) an equimolar solution of various metal cations and (ii) a Barth's buffer mimicking the brain solution composition. In both cases, the chelating STMS-DFoB showed a high selectivity for iron versus other ions at the same (Al3+) or different valency (Na+, K+…). Finally, this work paves the way for new nanosystems for metal overload treatments as well as for future highly chelating nanoplatforms that can be used at the interface between depollution and nanomedecine.


From Architecture to Evolution: Multisensory Evidence of Decentralized Emotion.
Emotional appraisal in humans is often considered a centrally mediated process by which sensory signals, void of emotional meaning, are assessed by integrative brain structures steps removed from raw sensation. We review emerging evidence that the emotional value of the environment is coded by nonvisual sensory systems as early as the sensory receptors and that these signals inform the emotional state of an organism independent of sensory cortical processes. We further present evidence for cross-species conservation of sensory projections to central emotion-processing brain regions. Based on this, we argue not only that emotional appraisal is a decentralized process, but that all human emotional experience may reflect the sensory experience of our ancestors.


Real-world data of clazosentan in combination therapy for aneurysmal subarachnoid hemorrhage: a multicenter retrospective cohort study.
Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0-6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge.


Bi-directional interconversion of brite and white adipocytes.
Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereby increasing energy expenditure. In addition to classical brown adipocytes, adult rodents-like adult humans-harbour brown-like adipocytes in the predominantly white adipose tissue. The formation of these brite (brown-in-white) adipocytes is a physiological response to chronic cold and their cellular origin is under debate. We show here that cold-induced formation of brite adipocytes in mice is reversed within 5 weeks of warm adaptation, but the brite adipocytes formed by cold stimulation are not eliminated. Genetic tracing and transcriptional characterization of isolated adipocytes demonstrates that they are converted into cells with the morphology and gene expression pattern of white adipocytes. Moreover, these white-typical adipocytes can convert into brite adipocytes on additional cold stimulation. Shifting the balance of this interconversion from the white towards the brite phenotype might provide a new means of counteracting obesity by increasing energy expenditure.


Extracellular modulation of Fibroblast Growth Factor signaling through heparan sulfate proteoglycans in mammalian development.
Fibroblast Growth Factor (FGF) signaling plays crucial roles in multiple cellular processes including cell proliferation, differentiation, survival, and migration during mammalian embryogenesis. In the extracellular matrix, as well as at the cell surface, the movement of FGF ligands to target cells and the subsequent complex formations with their receptors are positively and negatively controlled extracellularly by heparan sulfate proteoglycans (HSPGs) such as syndecans, glypicans, and perlecan. Additionally, spreading of HSPGs by cleavage with sheddases such as proteinases and heparanases, and the overall length and sulfation level of specific heparan sulfate structures further generate a great diversity of FGF signaling outcomes. This review presents our current understanding of the regulatory mechanisms of FGF signaling in extracellular spaces through HSPGs in mammalian development.


Interaction of support surface stability and Achilles tendon vibration during a postural adaptation task.
Orchestration of sensory-motor information and adaptation to internal or external, acute or chronic changes is one of the fundamental features of human postural control. The postural control system is challenged on a daily basis, and displays a remarkable ability to adapt to both long and short term challenges. To explore the interaction between support surface stability and Achilles tendon vibration during a period of adaptation we used both a linear measure and a non-linear measure derived from center-of-pressure (COP) data. An equilibrium score (ES), based upon peak amplitude of anterior-posterior sway towards theoretical limits of stability was the linear measure used to assess postural performance. We observed early effects of vibration on postural stability, depending on support characteristics. Participants were able to decrease sway with extended practice over days, independent of support surface stability. Approximate entropy analysis of COP data provided additional information about control adaptation processes.


The effects of the antirheumatic agents N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium (CCA) and D-penicillamine on the NK and ADCC activities and interferon production of lymphocytes.
CCA and D-penicillamine enhanced the NK activity of human lymphocytes in vitro incubation. ADCC activity of the lymphocytes was increased slightly by D-penicillamine but not by CCA. CCA enhanced interferon production from lymphocytes but D-penicillamine did not.


[Transforming growth factor-beta1 induced cultured human trabecular cells to produce elastin].
To understand transforming growth factor-beta(1) (TGF-beta(1)) inducing cultured human trabecular cells (HTCs) to produce elastin and to approach the effect of resistance of aqueous outflow in the pathogenesis and mechanism of primary open angle glaucoma (POAG). Trabecular meshwork's specimens were collected from twelve normal eyeballs of six human donors under six years of age within 24 hours after death. HTCs were primarily cultured and subcultured. Cultured cells were observed under light and electron microscopes. Laminin (LN) and IV collagen (IV C) in extracellular matrix (ECM) were immunohistochemically stained by S-P method. The third passage confluent cells after two weeks were divided into three groups: control group, TGF-beta(1) group and neutralizing antibody of TGF-beta(1) group. Concentration of neutralizing antibody of TGF-beta(1) was 30 microg/ml. After culturing for two weeks, elastin in the media of three groups was respectively determined by western blotting from sodium dodecylsulfate-polyacrylamide gel electrophoresis using anti-human aortic alpha-elastin rabbit serum, biotin conjugated goat anti-rabbit IgG and anti-biotin conjugated horse radish peroxidase. Cultured HTCs were identified from cultured cell's growing characteristics, morphological features under light and electron microscopes, and stained peculiarities of LN and IV C in ECM. With western blotting, elastin in the control group was not detected, elastin in TGF-beta(1) group was detected, and elastin in neutralizing antibody of TGF-beta(1) group was not detected. TGF-beta(1) induces cultured HTCs to produce elastin, which the neutralizing antibody of elastin can antagonize; the increase of the amount of elastin may aggravate its stacking in ECM and increase the resistance of aqueous outflow in trabecular meshwork, leading to the occurrence of glaucoma.


Incidence and factors associated with chronic chikungunya arthritis following chikungunya virus infection.
Chikungunya virus infection is a mosquito-borne illness. First-phase symptoms include fever, malaise, rash, and arthritis (self-limiting). Some patients can have chronic-phase symptoms, including chronic tenosynovitis, bursitis, and arthritis. This study aimed to determine the incidence and risk factors of chronic arthritis in patients with chikungunya infection. This retrospective cohort study analysed all adults diagnosed with chikungunya infection between 2015 and 2020 at our centre. Baseline and follow-up symptoms were evaluated in serologically confirmed cases. Chronic chikungunya arthritis was persistent arthritis >3 months after the onset. Patients who had preexisting chronic inflammatory arthritis and were lost to follow-up before 3 months from diagnosis were excluded. This study enrolled 120 patients. The median age was 51 (IQR 14) years, and 78% were female. The median number of joints with arthritis was 4 (IQR 8). The initial visual analog scale (VAS) score was 50 mm (IQR 40). Small joints of the hands, wrist, and knee (44.2%, 43.3%, and 42.3%, respectively) were the most affected. The incidence of chronic chikungunya arthritis was 40.4%. From the multivariable logistic regression, the initial number of joints with arthritis, initial VAS scores, and female sex were independently associated with chronic chikungunya arthritis with odds ratios of 1.09 (95% confidence interval [CI] 1.01-1.18), 1.03 (95% CI 1.01-1.06), and 4.17 (95% CI, 1.05-16.67), respectively. Chronic chikungunya arthritis is common in patients with chikungunya virus infection. Its predictive factors include the initial number of joints with arthritis, initial VAS scores, and female sex.


Synthesis, anti-mycobacterial activity and DNA sequence-selectivity of a library of biaryl-motifs containing polyamides.
The alarming rise of extensively drug-resistant tuberculosis (XDR-TB) strains, compel the development of new molecules with novel modes of action to control this world health emergency. Distamycin analogues containing N-terminal biaryl-motifs 2(1-5)(1-7) were synthesised using a solution-phase approach and evaluated for their anti-mycobacterial activity and DNA-sequence selectivity. Thiophene dimer motif-containing polyamide 2(2,6) exhibited 10-fold higher inhibitory activity against Mycobacterium tuberculosis compared to distamycin and library member 2(5,7) showed high binding affinity for the 5'-ACATAT-3' sequence.


Novel indolizine derivatives lowers blood glucose levels in streptozotocin-induced diabetic rats: A histopathological approach.
Diabetes mellitus is a deadly disorder in human which induce chronic complications. The streptozotocin (STZ)-induced diabetes in rat is the most common animal model of human diabetes. The present study investigated the effects of novel indolizine derivatives (1-16) on plasma blood glucose concentrations in STZ-diabetic rats. In vitro experiments were performed on 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide free radicals, α-glucosidase enzyme and in vivo studies on normal, oral glucose loaded and STZ-induced diabetic rats. Among all synthetic derivatives, compound 12 showed good inhibitory profile against DPPH, superoxide free radicals and α-glucosidase enzyme with half maximal inhibitory concentration (IC50) values of 56.2, 33.5 and 26.5 μg/mL, respectively. The lethal dosage of indolizine derivatives was found to be above 1000 mg/kg body weight (b.w.). From the in vivo studies, it can be determined that the compound 12 depicted pronounced protective hypoglycemic effects in normal, glucose-loaded and STZ-induced diabetic rats with respect to the standard. Furthermore, 21 days of successive treatment with compound 12 in diabetic rats exhibited better recovery of body weight and considerable variations in biochemical parameters as that of the standard drug. Moreover, the histopathological section of pancreas and testes justifies the rehabilitation and regeneration of islets, acini and Sertoli cells in animals treated with compound 12. Our data suggest that the indolizine derivatives can be a benchmarks for designing potent oral antidiabetic agents.


Inulinase production in a batch bioreactor using agroindustrial residues as the substrate: experimental data and modeling.
The production of inulinase employing agroindustrial residues as the substrate is a good alternative to reduce production costs and to minimize the environmental impact of disposing these residues in the environment. This study focused on the use of a phenomenological model and an artificial neural network (ANN) to simulate the inulinase production during the batch cultivation of the yeast Kluyveromyces marxianus NRRL Y-7571, employing a medium containing agroindustrial residues such as molasses, corn steep liquor and yeast extract. It was concluded that due to the complexity of the medium composition it was rather difficult to use a phenomenological model with sufficient accuracy. For this reason, an alternative and more cost-effective methodology based on ANN was adopted. The predictive capacity of the ANN was superior to that of the phenomenological model, indicating that the neural network approach could be used as an alternative in the predictive modeling of complex batch cultivations.


The impact of clean intermittent catheterization on students and families in the school environment.
Clean intermittent catheterization (CIC) is often used for bladder emptying in children with lower urinary tract dysfunction. Until recently, the emphasis in assessing the effects of CIC has been on preserving kidney function, reducing urinary tract infection, and achieving urinary continence. Few studies have investigated the impact of CIC on students and families in a school setting. This study sought to examine what students and caregivers experienced when CIC was required during the school day and how schools adjusted to a student needing to perform it. A phenomenological approach utilizing semistructured interviews was performed to understand the impact of CIC on students. Purposeful sampling identified eligible families. A guide was developed from expert opinion validated by a pilot sample with feedback collated into a family/provider codesigned questionnaire. Interviews emphasized the impact and challenges students faced at school. Transcripts were coded using Dedoose software with emerging themes identified and a code book was created for closed coding that led to thematic analysis. A total of 40 families (52 caregivers and children > 12 years) were interviewed. Emergent themes included: Caregivers and students felt (1) school personnel were not always aware of nor prepared regarding the implications of CIC; (2) school bathrooms were often less than ideal (e.g., location, size, cleanliness, privacy, and availability); and (3) student participation in extracurricular activities was challenging. This study identifies potential areas of intervention in meeting the needs of students who require CIC and the importance of having collaborative efforts of caregivers, health care providers, and school personnel in addressing and meeting CIC needs. Care coordination that involves consistent communication and careful planning between health care teams, school personnel, students, and caregivers can optimize a student's educational experience.


Hepatic cavernous hemangioma: a potential pitfall during evaluation of gastrointestinal bleeding with 99mTc-labeled erythrocytes.
The purpose of this report is to underscore one previously unreported hepatic parenchymal lesion detected during evaluation of occult lower gastrointestinal hemorrhage. In more than 90% of the patients harboring the lesion, the individual remains asymptomatic, requires no intervention, and closed biopsy is contraindicated: hepatic cavernous hemangioma. Whereas the list is expanding of normal and abnormal structures which can interfere with the interpretation of scintigraphic gastrointestinal bleeding studies accomplished with 99mTc-labeled erythrocytes, it is absolutely necessary to demonstrate intestinal transit of the activity, in order to discount detected activity in either nonhemorrhagic lesions or normal structures as the nidus of suspected bleeding.


What was the impact of tobacco taxes on smoking prevalence and coronary heart disease mortality in the United States -2005-2016, and did it vary by race and gender?
Tobacco taxes have reduced smoking and coronary heart disease (CHD) mortality, yet few studies have examined heterogeneity of these associations by race and gender. We constructed a yearly panel (2005-2016) that included age-adjusted cigarette smoking prevalence and CHD mortality rates across all 50 U.S. States and the District of Columbia using the Behavioral Risk Factor Surveillance System and Wide-ranging Online Data for Epidemiological Research. We examined associations between changes in total cigarette excise taxes (i.e., federal and state) and changes in smoking prevalence and CHD mortality, using linear regression models with state and year fixed effects. Each dollar of tobacco tax was associated with a reduction in age-adjusted smoking prevalence 1 year later of -0.4 [95% CIs: -0.6, -0.2] percentage points; and a relative reduction in the rate of CHD mortality 2 years later of -2.0% [95% CIs: -3.7%, -0.3%], or -5 deaths/100,000 in absolute terms. Associations between tobacco taxes and smoking prevalence were statistically significantly different by race and gender and were strongest among Black non-Hispanic women (-1.2 [95% CIs: -1.6, -0.8] percentage points). Associations between tobacco taxes and CHD mortality were not statistically significantly different by race and gender, but point estimates for percent changes were highest among Black non-Hispanic men (-2.9%) and Black non-Hispanic women (-3.5%) compared to White non-Hispanic men (-1.8%) and White non-Hispanic women (-1.5%). These findings suggest that tobacco taxation is an effective intervention for reducing smoking prevalence and CHD mortality among White and Black non-Hispanic populations in the United States.


A gene-specific effect of an internal deletion in the Bdp1 subunit of the RNA polymerase III transcription initiation factor TFIIIB.
The Saccharomyces cerevisiae RPR1 gene encodes the RNA subunit of its RNase P, which processes RNA polymerase (pol) III primary transcripts. RPR1, which is transcribed by pol III, has been isolated as a multicopy suppressor of a specific small internal deletion (amino acids 253-269) in the Bdp1 subunit of transcription factor TFIIIB, the core pol III transcription factor. The selective effect of this Bdp1 deletion on RPR1 transcription has been analyzed in vitro. It is shown that TFIIIC-dependent assembly of TFIIIB on the RPR1 promoter is specifically sensitive to this Bdp1 deletion, leading to gene-specifically defective single-round and multiple-round transcription.


Machine vision based detection of omega bends and reversals in C. elegans.
The behavior of the nematode Caenorhabditis elegans has proven increasingly useful for the genetic dissection of neurobiological signaling pathways and for investigating the neural and molecular basis of nervous system function. Locomotion is among the most complex aspects of C. elegans behavior, and involves a number of discrete motor activities such as omega bends (deep bends typically on the ventral side of the body which reorient the direction of forward locomotion) and reversals (changes in the direction of the locomotion wave that cause a switch from forward to backward crawling). Reliable methods for detecting and quantifying these movements are critical for escape reflexes and navigation behaviors. Here we describe a novel algorithm to automatically detect omega bends, which relies in part on a new method for obtaining a morphological skeleton describing the body posture of coiled worms. We also present an optimized algorithm to detect reversals, which showed improved performance over previously described methods. Together, these new algorithms have made it possible to reliably detect events that are time-consuming and laborious to detect by real-time observation or human video analysis. They have also made it possible to identify mutants with subtle behavioral abnormalities, such as those in which omega bends are dorsoventrally unbiased or uncorrelated with reversals. These methods should therefore facilitate quantitative analysis of a wide range of locomotion-related behaviors in this important neurobiological model organism.


Change in limb length after high tibial osteotomy using computer-assisted surgery: a comparative study of closed- and open-wedge osteotomies.
Limb length changes were evaluated after closed- and open-wedge high tibial osteotomies (HTOs) using computer-assisted surgery. A total of 78 closed- and 30 open-wedge HTOs were performed. The changes in limb length were evaluated on a navigation system and radiographs. The correction angle was defined as the difference between the pre and postoperative mechanical axis on the navigation system. The change in limb length with respect to the correction angle was analyzed. Following the closed-wedge HTOs, the mean changes in limb length based on the navigation system and radiographs were -1.3 ± 1.9 and -1.3 ± 10.7 mm, respectively, versus 6.2 ± 2.6 and 7.8 ± 2.9 mm after the open-wedge HTOs. The mean correction angle was 11.6 ± 3.2° for closed-wedge HTOs and 11.5 ± 1.9° for open-wedge HTOs. The correction angle did not affect the change in limb length after closed-wedge HTO, while the larger the correction angle required, the greater the increase in limb length after open-wedge HTO. The change in limb length was negligible after closed-wedge HTO, while the limb length was increased slightly after open-wedge HTO. The possibility of limb lengthening must be considered carefully when determining whom to perform open-wedge HTO on, especially when a large correction angle is required. III.


Controlled biosynthesis of gold nanoparticles with Coffea arabica using factorial design.
Green synthesis of metallic nanoparticles has become incredibly popular, mainly by minimizing problems of environmental contamination and by being able to reduce, stabilize and potentially functionalize nanomaterials. Such compounds have possible applications in various areas, e.g., pharmaceuticals (drug delivery systems, cosmetics), textile industry (clothing with antimicrobial properties), diagnostic medicine (imaging, high efficiency biosensors), energy (solar panels), bioremediation, among others. However, the lack of reproducibility and information on the control mechanisms during synthesis have made the application of green-synthesized nanoparticles unfeasible. Thus, this study proposed the investigation of the main mechanisms affecting synthesis control, using factorial design for the preparation of gold nanoparticles with extract of Coffea arabica. We obtained stable (Zeta Potential, UV-vis and DLS), monodisperse, and quasi-spherical (TEM) nanoparticles, which presented adsorbed aromatic molecules (FTIR and RAMAN) and defined crystal structure (XRD), proving that the plant extract acted as a reducing agent, as well as a stabilizer and functionalizer for the synthesized nanostructures. The factorial design employed here to obtain gold nanoparticles with Coffea arabica extract allowed for a controlled and reproducible synthesis, enabling new possibilities for the application in several fields.


Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction.
Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.


Discovery of a novel jellyfish venom metalloproteinase inhibitor from secondary metabolites isolated from jellyfish-derived fungus Aspergillus versicolor SmT07.
The major jellyfish stings that occur in China are caused by scyphozoan Nemopilema nomurai, whose venom exhibits significant metalloproteinase activity that contributes to the toxic effects of jellyfish envenomation. Researching effective inhibitors suppressing the metalloproteinase activity of jellyfish venom represents a new attempt to cure jellyfish envenomations. In the present study, secondary metabolites produced by the jellyfish-associated fungus Aspergillus versicolor SmT07 were isolated and evaluated for their anti-proteolytic activities. Two xanthones, sterigmatocystin (JC-01) and oxisterigmatocystin C (JC-06), and four alkaloids, cottoquinazoline A (JC-02), phenazine-1-carboxylic acid (JC-03), viridicatin (JC-04) and viridicatol (JC-05), were isolated and identified. Only phenazine-1-carboxylic acid (PCA) showed significant anti-proteolytic activity of jellyfish venom assayed on azocasein, and the IC50 value was 2.16 mM. PCA also significantly inhibited fibrinogenolytic activity, protecting the Bβ chain of fibrinogen from degradation when preincubated with jellyfish venom at a ratio of >1:0.6 (PCA:venom, w/w). Molecular docking with several well-characterized snake venom metalloproteinases suggested the venom metalloproteinases inhibitory property of PCA by forming complex interactions with the active site via hydrogen bonds, π-π stacking and salt bridges, which was distinct from the binding mode of batimastat. The present study represents the first study identifying natural jellyfish venom metalloproteinase inhibitors from marine natural products, which may provide an alternative to develop therapeutic agents for treating jellyfish envenomations.


Virus spread and immune response following anterior chamber inoculation of HSV-1 lacking the Beclin-binding domain (BBD).
The autophagy response induced by HSV-1 infection is antagonized by the Beclin-binding domain (BBD). The purpose of this study was to determine if lack of the BBD affects viral spread and immune response in the eyes and brain. Our results showed that lack of the BBD increases autophagy response and activation of NLRP3 inflammasome, which in turn induces a more rapid innate immune response mediated by macrophage/microglia and NK cells in the injected eye, limiting virus replication and retinal damage. We conclude that autophagy plays a role in controlling HSV-1 infection by more rapid induction of the innate immune response.


Remote sensing to detect harmful algal blooms in inland waterbodies.
Harmful algal blooms (HABs) are an issue of concern for water management worldwide. As such, effective monitoring strategies of HAB spatio-temporal variability in waterbodies are needed. Remote sensing has become an increasingly important tool for HAB detection and monitoring in large lakes. However, accurate HAB detection in small-medium waterbodies via satellite data remains a challenge. Current barriers include the waterbody size, the limited freely available high resolution satellite data, and the lack of field calibration data. To test the applicability of remote sensing for detecting HABs in small-medium waterbodies, three satellites (Planetscope, Sentinel-2 and Landsat-8) were used to understand how spatial resolution, the availability of spectral bands, and the waterbody size itself effect HAB detection skill. Different algorithms and a non-parametric method, Self-Organizing Map (SOM), were tested. Curvature Around Red and NIR minus Red had the best HAB detection skill of the 20 existing algorithms that were tested. Landsat 8 and Sentinel 2 were the best satellites for HAB detection in small to medium waterbodies. The most critical attribute for detecting HABs were the available satellite bands, which determine the detection algorithms that can be used. Importantly, algorithm performance was mostly unrelated to waterbody size. However, there remain some barriers in utilizing satellite data for HAB detection, including algae dynamics, macrophyte cover within the waterbody, weather effects, and the correction models for satellite data. Moreover, it is important to consider the match time between satellite overpass and sampling activities for calibration. Given these challenges, integrating regular sampling activities and remote sensing is recommended for monitoring and managing small-medium waterbodies.


Natural killer cells: functional differences in recurrent spontaneous abortion†.
Recurrent spontaneous abortion (RSA) is one of the major pregnancy disorders and poses a serious risk to both the mother and the fetus. Although a number of research efforts have been conducted, therapeutic advances for treating RSA have not lived up to their expectations. Hence, other treatments should be explored. The important role of natural killer (NK) cells in immunotherapy is attracting increasing attention, both as a pharmaceutical target and for cell therapies. NK cells are abundant in the endometrium and play a role in implantation and placentation in normal pregnancy. As research progresses, NK cells are increasingly regarded as playing essential roles in the emergence and development of RSA. In this article, I review recent findings on the role of uterine NK cells in the pathophysiology of RSA. These cells may become therapeutic NK cell-related targets. In conclusion, although several issues regarding NK cells in RSA remain unresolved and require further investigation, extensive evidence is available for the treatment of RSA.


Iron Speciation in Particulate Matter (PM2.5) from Urban Los Angeles Using Spectro-microscopy Methods.
The speciation, oxidation states, and relative abundance of iron (Fe) phases in PM2.5 samples from two locations in urban Los Angeles were investigated using a combination of bulk and spatially resolved, element-specific spectroscopy and microscopy methods. Synchrotron X-ray absorption spectroscopy (XAS) of bulk samples in situ (i.e., without extraction or digestion) was used to quantify the relative fractions of major Fe phases, which were corroborated by spatially resolved spectro-microscopy measurements. Ferrihydrite (amorphous Fe(III)-hydroxide) comprised the largest Fe fraction (34-52%), with hematite (α-Fe2O3; 13-23%) and magnetite (Fe3O4; 10-24%) identified as major crystalline oxide components. An Fe-bearing phyllosilicate fraction (16-23%) was fit best with a reference spectrum of a natural illite/smectite mineral, and metallic Fe(0) was a relatively small (2-6%) but easily identified component. Sizes, morphologies, oxidation state, and trace element compositions of Fe-bearing PM from electron microscopy, electron energy loss spectroscopy (EELS), and scanning transmission X-ray microscopy (STXM) revealed variable and heterogeneous mixtures of Fe species and phases, often associated with carbonaceous material with evidence of surface oxidation. Ferrihydrite (or related Fe(III) hydroxide phases) was ubiquitous in PM samples. It forms as an oxidation or surface alteration product of crystalline Fe phases, and also occurs as coatings or nanoparticles dispersed with other phases as a result of environmental dissolution and re-precipitation reactions. The prevalence of ferrihydrite (and adsorbed Fe(III) has likely been underestimated in studies of ambient PM because it is non-crystalline, non-magnetic, more soluble than crystalline phases, and found in complex mixtures. Review of potential sources of different particle types suggests that the majority of Fe-bearing PM from these urban sites originates from anthropogenic activities, primarily abrasion products from vehicle braking systems and engine emissions from combustion and/or wear. These variable mixtures have a high probability for electron transfer reactions between Fe, redox-active metals such as copper, and reactive carbon species such as quinones. Our findings suggest the need to assess biological responses of specific Fe-bearing phases both individually and in combination to unravel mechanisms of adverse health effects of particulate Fe.


HLA-DMB in Amerindians: Specific linkage of DMB*01:03:01/DRB1 alleles.
HLA-DMB proteins are important for intracellular microbial metabolism in order other major histocompatibility complex (MHC) molecules present peptides to lymphocytes. In addition, HLA-DMB alleles have been found linked to diseases in some ethnic groups and HLA-DMB molecules may be important to explain HLA disease association. To detect HLA-DMB alleles profile in Amerindians for the first time and compare them to other populations. This will establish the bases to study HLA-DMB linkage to disease in Amerindians. A group of 168 voluntary Amerindians have been typed for HLA-DMB alleles. They have been characterized both, by genetic and genealogical bases. Cloning and automated HLA-DMB DNA (exons 2, 3 and 4) sequencing have been performed for allele assignation. HLA-DMB*01:01:01 and HLA-DMB*01:03:01 show the highest frequencies. These have been compared to other World wide populations. HLA-DMB*01:03:01 is tightly associated to certain specific HLA-DRB1 alleles in Amerindians. The specific Amerindian HLA-DMB allele frequencies and their linkage disequilibrium with other MHC alleles may be crucial to determine HLA-DMB World wide variation, evolution and specific linkage to disease in Amerindians and other populations.


Survival of pathogenic microorganisms in an egg-nog-like product containing 7% ethanol.
A liquor consisting of whole egg, saccharose (25% w/v) and ethanol (7.0% w/v) was artificially contaminated with Salmonella enteritidis, S. typhimurium, Staphylococcus aureus (three different strains), Bacillus cereus and Listeria monocytogenes. After 3 weeks of incubation at 22 degrees C the numbers of Salmonella, S. aureus and L. monocytogenes decreased more than 3 log10 units. Under such conditions, however, the total number of microorganisms increased 3 log10 units. At 4 degrees C the decrease of pathogenic microorganisms was much slower and a decrease of 3 log10 units was observed only after 7 weeks of incubation. Egg-nog, without ethanol, incubated at 22 degrees C allowed growth of Salmonella and S. aureus, while the numbers of B. cereus spores remained unchanged. Vegetative cells of B. cereus as well as L. monocytogenes decreased in numbers. However, after prolonged incubation the numbers of L. monocytogenes increased significantly.


GAVCA Study: Randomized, Multicenter Trial to Evaluate the Quality of Ventricular Catheter Placement with a Mobile Health Assisted Guidance Technique.
Freehand ventricular catheter placement may represent limited accuracy for the surgeon's intent to achieve primary optimal catheter position. To investigate the accuracy of a ventricular catheter guide assisted by a simple mobile health application (mhealth app) in a multicenter, randomized, controlled, simple blinded study (GAVCA study). In total, 139 eligible patients were enrolled in 9 centers. Catheter placement was evaluated by 3 different components: number of ventricular cannulation attempts, a grading scale, and the anatomical position of the catheter tip. The primary endpoint was the rate of primary cannulation of grade I catheter position in the ipsilateral ventricle. The secondary endpoints were rate of intraventricular position of the catheter's perforations, early ventricular catheter failure, and complications. The primary endpoint was reached in 70% of the guided group vs 56.5% (freehand group; odds ratio 1.79, 95% confidence interval 0.89-3.61). The primary successful puncture rate was 100% vs 91.3% (P = .012). Catheter perforations were located completely inside the ventricle in 81.4% (guided group) and 65.2% (freehand group; odds ratio 2.34, 95% confidence interval 1.07-5.1). No differences occurred in early ventricular catheter failure, complication rate, duration of surgery, or hospital stay. The guided ventricular catheter application proved to be a safe and simple method. The primary endpoint revealed a nonsignificant improvement of optimal catheter placement among the groups. Long-term follow-up is necessary in order to evaluate differences in catheter survival among shunted patients.


Multifaceted understanding of human nerve implants to design optimized electrodes for bioelectronics.
Bioelectronic medicine is a promising venue for treatment of disabilities using implantable neural interfaces. Peripheral neurostimulation of residual nerves recently enabled multiple functional benefits in amputees. Despite the preliminary promising impact on patients' life, the over-time stability of implants and the related nerve reactions are unclear. To unveil the mechanisms and inform the design of better nerve-electrode interfaces, we engaged a multifaceted approach, merging functional responses from patients, their histological data, and corresponding computational modelling. Neurostimulation evoked different selective sensation locations and qualities over-time, with respective perceptual thresholds, that showed different degree of time stabilities dependent from the stimulating active sites. The histological analysis after explant showed mild tissue reactions, while electromechanically active sites and substrates remained conserved. Computational models, based on patients' histology, revealed the direct influence of the simulated tissue reaction to change of thresholds and type of perceived sensations. Novel insights of electrode biocompatibility was observed compared to animals and the increase of thresholds could be predicted computationally. This multifaced framework suggest that future intraneural implants should have easier implantation and higher biocompatibility counteracting the sensations changes through AI-based stimulations and electrode coatings.


Validation of age-specific survival prediction in pediatric patients with blunt trauma using trauma and injury severity score methodology: a ten-year Nationwide observational study.
In-hospital mortality in trauma patients has decreased recently owing to improved trauma injury prevention systems. However, no study has evaluated the validity of the Trauma and Injury Severity Score (TRISS) in pediatric patients by a detailed classification of patients' age and injury severity in Japan. This retrospective nationwide study evaluated the validity of TRISS in predicting survival in Japanese pediatric patients with blunt trauma by age and injury severity. Data were obtained from the Japan Trauma Data Bank during 2009-2018. The outcomes were as follows: (1) patients' characteristics and mortality by age groups (neonates/infants aged 0 years, preschool children aged 1-5 years, schoolchildren aged 6-11 years, and adolescents aged 12-18 years), (2) validity of survival probability (Ps) assessed using the TRISS methodology by the four age groups and six Ps-interval groups (0.00-0.25, 0.26-0.50, 0.51-0.75, 0.76-0.90, 0.91-0.95, and 0.96-1.00), and (3) the observed/expected survivor ratio by age- and Ps-interval groups. The validity of TRISS was evaluated by the predictive ability of the TRISS method using the receiver operating characteristic (ROC) curves that present the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the receiver operator characteristic curve (AUC) of TRISS. In all the age categories considered, the AUC for TRISS demonstrated high performance (0.935, 0.981, 0.979, and 0.977). The AUC for TRISS was 0.865, 0.585, 0.614, 0.585, 0.591, and 0.600 in Ps-interval groups (0.96-1.00), (0.91-0.95), (0.76. - 0.90), (0.51-0.75), (0.26-0.50), and (0.00-0.25), respectively. In all the age categories considered, the observed survivors among patients with Ps interval (0.00-0.25) were 1.5 times or more than the expected survivors calculated using the TRISS method. The TRISS methodology appears to predict survival accurately in Japanese pediatric patients with blunt trauma; however, there were several problems in adopting the TRISS methodology for younger blunt trauma patients with higher injury severity. In the next step, it may be necessary to develop a simple, high-quality prediction model that is more suitable for pediatric trauma patients than the current TRISS model.


Morphological variation in Echinorhynchustruttae Schrank, 1788 and the Echinorhynchusbothniensis Zdzitowiecki & Valtonen, 1987 species complex from freshwater fishes of northern Europe.
Echinorhynchustruttae and the Echinorhynchusbothniensis species complex are common parasites of salmoniform and other fishes in northern Europe. Echinorhynchusbothniensis and its sibling species Echinorhynchus 'bothniensis' are thought to be closely related to the Nearctic Echinorhynchusleidyi Van Cleave, 1924 based on morphological similarity and common usage of a mysid intermediate host. This study provides the first analysis of morphological and meristic variation in Echinorhynchustruttae and expands our knowledge of anatomical variability in the Echinorhynchusbothniensis group. Morphological variability in Echinorhynchustruttae was found to be far greater than previously reported, with part of the variance attributable to sexual dimorphism. Echinorhynchustruttae, the two species of the Echinorhynchusbothniensis group and Echinorhynchusleidyi displayed considerable interspecific overlap in the ranges of all conventional morphological characters. However, Proboscis profiler, a tool for detecting acanthocephalan morphotypes using multivariate analysis of hook morphometrics, successfully separated Echinorhynchustruttae from the other taxa. The Echinorhynchusbothniensis species group could not be reliably distinguished from Echinorhynchusleidyi (or each other), providing further evidence of the affinity of these taxa. Observations on the distribution of Echinorhynchustruttae in its definitive host population are also reported.


Bone marrow acid phosphatase in staging of prostatic cancer: how reliable is it?
To evaluate the reliability of bone marrow acid phosphatase in the staging of prostatic carcinoma we analyzed 50 bone marrow samples collected at random from the hematology service at this hospital. The samples were assayed for acid phosphatase content by a colorimetric method using sodium thymolphthalein monophosphate as a substrate and by 2 immunochemical assays developed at our laboratory (counter immunoelectrophoresis and radioimmunoassay). We found a high percentage (61 per cent) of falsely positive results in patients with various hematological diseases without evidence of prostatic carcinoma by the colorimetric evaluation. All of these patients except 1 had negative immunochemical assay. Until a specific assay for prostatic acid phosphatase is developed for clinical use we caution the use of a single elevation of bone marrow acid phosphatase as a parameter of metastatic disease.