Genotype-Guided Warfarin Dosing in Patients With Mechanical Valves: A Randomized Controlled Trial.
The clinical utility of genotype-guided warfarin dosing remains controversial. The objective of this trial was to evaluate the efficacy and safety of genotype-guided warfarin dosing in East Asians. A double-blind, randomized control trial was performed to compare a genotype-guided dosing algorithm (CYP2C9, VKORC1, and CYP4F2) with a clinical-guided one in the initiation treatment for patients with mechanical heart valves. The primary outcomes included the time to reach a stable dose and the percentage of time in the therapeutic range (TTR). Two hundred one patients were randomly assigned to treatment, 101 to control and 100 to study. The major bleeding and thromboembolic event-free rate in the study group was 97.0% (95% confidence interval: 90.9% to 99.2%). Compared with the control group, the study group shortened the time to reach a stable dose (mean: 42.09 ± 23.655 days versus 33.52 ± 20.044 days, p = 0.009). The TTRs were 47.257% and 47.461% in the control and study group (p = 0.941), respectively. Patients with the CYP2C9 *1/*3 genotype had higher international normalized ratio (INR) variability than patients with the CYP2C9 *1/*1 genotype (p = 0.024). Compared with normal and sensitive responders, the highly sensitive responders were at increased risk of an INR of 4.0 or greater (p < 0.05). The genotype-guided warfarin dosing was safe and might be more efficient for the time to reach a stable dose. Pharmacogenomic testing might be beneficial to identify the patients with the CYP2C9 *1/*3 genotype and the highly sensitive responders, who were in the high-risk subgroup of patients with mechanical heart valves. An appropriately powered study is needed to further confirm these findings.


Treatment of pustulosis palmaris et plantaris with colchicine. A double-blind cross-over trial.
27 patients with pustulosis palmaris et plantaris were treated daily with colchicine 0.5 mg X 3 for four weeks in a double-blind study. Only ten patients experienced a halt of pustule formation, whereas redness, scaling, and subjective symptoms were unchanged. Colchicine seems of limited value in patients with pustulosis palmaris et plantaris.


Pronuclear morphology and chromosomal abnormalities as scoring criteria for embryo selection.
To verify whether a correlation exists between pronuclear zygote morphology and the chromosomal condition of preimplantation embryos. Prospective analysis of pronuclear zygote morphology and preimplantation genetic diagnosis (PGD) for aneuploidy of the resulting embryos. Reproductive medicine unit, day surgery clinic. Seventy-seven patients undergoing 107 PGD cycles because of advanced maternal age (77 cycles) or previous IVF failures (30 cycles). Evaluation of pronuclear zygote morphology and chromosomal condition of the resulting embryos. Rate of embryo development, proportion of euploid embryos, and distribution of chromosomal abnormalities. The position of pronuclei within the ooplasm, the size and distribution of nucleoli, and the orientation of polar bodies with respect to pronuclei were highly predictive for the presence of complex chromosomal abnormalities in the developing embryos; zygotes with juxtaposed pronuclei, large-size nucleoli, and polar bodies with small angles subtended by pronuclei and polar bodies were the configurations associated with the highest rates of euploidy. The combination of the patterns related to pronuclear zygote morphology indicated four configurations where the proportion of chromosomally normal embryos was significantly higher compared with the other configurations, suggesting the validity of this scoring system for the selection of embryos generated by PGD patients.


Mid-term results after thoracoscopic transmyocardial laser revascularization.
Transmyocardial revascularization is a surgical therapy for the relief of severe angina in patients who are not suitable candidates for coronary artery bypass graft surgery or percutaneous coronary interventions. Historically, surgical techniques employed a left thoracotomy with or without thoracoscopic assist for visualization. This study evaluated the feasibility and midterm outcomes after transmyocardial laser revascularization performed using a completely thoracoscopic, closed chest approach. Patients (9 men [90%] and 1 woman [10%]) at a mean age of 66 +/- 10 years who were ineligible for coronary artery bypass graft surgery or percutaneous coronary intervention underwent sole therapy transmyocardial laser revascularization using a completely thoracoscopic surgical approach using a holmium:yttrium-aluminum-garnet laser system. Preoperatively, patients had a mean ejection fraction of 0.51 +/- 0.09 and a mean angina class of 3.7 +/- 0.5. A mean of 30 +/- 2.4 channels were created during mean laser and operative procedure times of 14 +/- 2.9 and 133 +/- 32 minutes, respectively. Patients were extubated at a mean of 7.6 +/- 12 hours and were discharged from the hospital at a mean of 5.4 +/- 3.4 days. There were no hospital deaths or major complications. At a mean of 8.4 +/- 5.5 months postoperatively, all patients survived and significant clinical improvement with a mean angina class of 1.3 +/- 0.5 (p < 0.001). A completely thoracoscopic surgical approach is feasible for sole therapy transmyocardial revascularization that affords improved visualization over a limited thoracotomy approach. Limited complications and significant clinical improvement after the procedure were observed. With minimal port manipulation, there is an opportunity for decreased postoperative pain; however, larger studies are warranted to verify this hypothesis.


Two birds with one stone: integrated assessment of coronary physiology and plaque vulnerability from a single angiographic view-a case report.
Physiology-guided coronary revascularization was shown to improve clinical outcomes in multiple patient subsets, whilst in those presenting with acute coronary syndromes, it seems to be associated with an excess of cardiovascular events. One of the major drawbacks in this setting is the potential deferral of non-flow-limiting but 'vulnerable' coronary plaques. A 40-year-old patient presented with a myocardial infarction without ST-segment elevation (NSTEMI). At the invasive coronary angiography (ICA) a sub-occlusive stenosis on his left circumflex artery was detected and treated with percutaneous coronary intervention (PCI). The treatment of a concomitant intermediate eccentric focal stenosis on the right coronary artery (RCA) was deferred after a negative pressure wire-based physiological assessment. The patient was re-admitted 9 months later due to a recurrent NSTEMI, and a severe progression of the deferred RCA lesion was found at the ICA. In retrospect, an angiography-based assessment of physiological severity and plaque vulnerability of the non-culprit RCA stenosis by means of Murray's law-based QFR (μQFR) and radial wall strain (RWS) was performed. At baseline, μQFR value (0.90) corroborated the non-ischaemic findings of wire-based assessment. However, RWS analysis showed a marked hotspot (maximum RWS value 27.7%), indicating the presence of a vulnerable plaque. Radial wall strain is a novel biomechanical deformation index derived from coronary angiography. Segments with high RWS are associated with lipid-rich plaques that are prone to progression and plaque rupture. Therefore, the identification of RWS hotspots might potentially improve the risk stratification of non-culprit lesions and empower secondary prevention strategies.


Antibiotic-treated Streptococcus sanguinis intracranial mycotic aneurysm.
We report the case of a woman 33 years of age with infective endocarditis-related intracranial mycotic aneurysm (IMA) caused by a Streptococcus sanguinis infection. The clinical diagnosis was confirmed by the findings of magnetic resonance imaging, magnetic resonance angiographic (MRA) studies, echocardiographic studies, and a positive blood culture result. She underwent antimicrobial treatment only (ceftriaxone intravenously for 8 weeks and penicillin V orally for 6 weeks). The regression and disappearance of IMA were demonstrated by a series of MRA follow-up studies.


The Influence of SLC22A3 Genetic Polymorphisms on Susceptibility to Type 2 Diabetes Mellitus in Chinese Population.
Solute carrier family 22 member 3 (SLC22A3) gene had been reported to be associated with the efficacy of metformin in type 2 diabetes mellitus (T2DM). However, few studies reported the relationship between SLC22A3 polymorphism and T2DM. The aim of this study was to investigate the association of SLC22A3 polymorphism and susceptibility to T2DM in Chinese population. We identified SLC22A3 rs555754, rs3123636, rs3088442 genotypes of 450 T2DM patients and 220 healthy controls from the Chinese population. The association between SNPs of SLC22A3 and susceptibility of T2DM was evaluated. The clinical characteristics were significantly different between T2DM patients and healthy controls. The polymorphisms of SLC22A3 rs555754 and rs3123636 were obviously associated with the susceptibility of T2DM which was adjusted for age, sex and BMI, while rs3088442 did not. And there was haplotype association of SLC22A3 rs3088442-rs3123636 with T2DM susceptibility. SLC22A3 rs555754 and rs3123636 polymorphisms were associated with the susceptibility to T2DM in Chinese Han population. Large sample size studies would be required to verify this association.


Augmentation of pulmonary foreign body granulomatous inflammation in mice by lipopolysaccharide: involvement of macrophage activation and tumor necrosis factor-alpha.
We examined the effect of lipopolysaccharide (LPS) on dextran bead-induced lung granulomas using LPS responder (C3H/HeN) and nonresponder (C3H/HeJ) mice. LPS augmented granuloma sizes, TNF-alpha and N-acetyl-beta-D-glucosaminidase levels of lung extracts in C3H/HeN, but not in C3H/HeJ mice. Granuloma macrophages of C3H/HeN mice produced higher levels of superoxide anion and TNF-alpha than those of C3H/HeJ mice. Taken together with our previous report that macrophages and macrophage-derived cytokines are essential for the development of lesions, the present results suggest that activation of macrophages plays an important role in the development and augmentation of pulmonary granulomas.


A non-classical ISRE/ISGF3 pathway mediates induction of RANTES gene transcription by type I IFNs.
RANTES (regulated upon activation normal T cell expressed and secreted) is a chemoattractant cytokine important in the generation of inflammatory responses and human immunodeficiency virus resistance. In hematopoietic cells, RANTES is over-expressed by type I interferons (IFN-alpha and IFN-beta). The upstream region of the RANTES gene promoter contains a distal low affinity IFN-stimulated response element (ISRE). Specific mutagenesis in this ISRE-like motif abolished the activation of RANTES transcription by type I IFNs. Examination of the ISRE binding factors strongly suggested that signal transducer and activator of transcription (Stat)-2 and p48/IFN-stimulated gene factor 3gamma (ISGF3gamma) are not required for the induction of RANTES by type I IFNs. The specific requirement of Stat-1 was demonstrated using Stat-1-deficient U3A cells. These results revealed a non-classical ISRE/ISGF3 signal transduction pathway for the induction of RANTES by type I IFNs.


Diagnosis and clinical features of small hepatocellular carcinoma with emphasis on the utility of real-time ultrasonography. A study in 51 patients.
The clinical features and usefulness of various methods for diagnosis of small hepatocellular carcinoma, no greater than 5 cm in diameter, were studied in 51 patients. The diagnosis was verified in 28 patients by hepatic resection and in 4 patients at autopsy. The tumor was less than 3 cm in diameter in 23 patients. In 37 patients (72.5%), the tumor was first discovered by real-time linear scan ultrasonography, generally during a routine periodic follow-up examination of patients with chronic liver disease, mostly cirrhosis. Clinically, 62.7% of the patients were asymptomatic, and symptoms in the remainder were not suggestive of carcinoma. Most patients showed only mildly abnormal liver function tests that did not suggest the diagnosis. Serum alpha-fetoprotein level was normal in 25.5%, and it was elevated above 200 ng/ml in only 33.3%. Among the various imaging modalities, ultrasonography had the highest detection rate (92.2%) for these small hepatocellular carcinomas compared with computed tomography (73.2%), scintigraphy (50.0%), and angiography (86.0%). False-positive lesions, however, were also found frequently by ultrasonography, requiring ultrasonography-guided biopsy for differential diagnosis in some of the patients. Routine examination at regular intervals of patients with chronic liver disease using a combination of real-time ultrasonography and alpha-fetoprotein measurement is currently the most effective approach to detecting small hepatocellular carcinoma.


Household Expenditure on Diarrhea Treatment among Under Five Children in Godawari Municipality of Nepal.
Diarrheal disease is a global public health problem. In Nepal, diarrhea is still the leading cause of waterborne disease, which constitutes 48% among all hospitalized disease cases who come to health center for treatment. Despite low treatment cost of diarrhea, out-of-pocket expenditure required at the time of treatment is a major barrier to seek health care. This study, therefore, aims to explore household expenditure for the diarrheal treatment in under five children and its financial burden in households. A community based cross sectional study was carried out in 14 wards of Godawari Municipality among under five children with diarrhea from June 2018 to September 2018. We conducted financial burden survey among 371 household with diarrhea cases. Prevalence rate of diarrhea was found 50% among under five children. The average out-of-pocket expenditure was NRs 568.62 (US $5.06) per episode for diarrhea treatment. The total average direct cost for diarrheal treatment was NRs 183.58 (US $1.63). The two major cost driver during each episode were loss of wage by parents NRs 360.97 (US $3.21) and medicine costs NRs 114.15 (US $1.01). The Diarrheal prevalence rate in the study area was found higher than the National. The indirect cost of each diarrheal episode is more than three times of the direct cost.


Prognosis of hypercalcemia in aerodigestive tract cancers: study of 136 recent cases.
Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002-January 2004). Hypercalcemia was defined by calcemia level above 2.55 mmol/l. Univariate analysis for prognosis was performed with Mann-Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18-86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2-553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2-553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07-6.82), age inferior to 50 (OR=2.67 CI 95% 1.23-5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8-11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73-17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99-13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02-10.52), male gender (OR=38.22 CI 95% 12.2-89), calcemia level superior to 2.7 mmol/l (OR=3.08 CI 95% 1.42-6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01-4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.


Circular dichroism of cephalopod rhodopsin and its intermediates in the bleaching and photoregeneration process.
In the bleaching process of cephalopod rhodopsin, a new intermediate was found in the conversion process from lumirhodopsin to metarhodopsin. This intermediate of octopus has an absorption peak at about 475 nm and has been named as M475. The circular dichroism value of M475 is too small to be evaluated. On the other hand, lumirhodopsin shows a negative CD at 470 nm, a positive CD at 350 nm and a large positive CD band with three peaks at 280, 287 and 295 nm. Such a large CD band in the ultraviolet region is not observed in rhodopsin, M475 and metarhodopsin. This CD seems to be mainly due to tryptophan and tyrosine residues restricted in free rotation in the protein moiety of lumirhodopsin. The intermediate in the photoregeneration process of cephalopod rhodopsin, P380, has a positive CD band at the main peak, 380 nm, and also a large positive CD band in the ultraviolet region like lumirhodopsin.


Bacteriophage T4 Dda helicase translocates in a unidirectional fashion on single-stranded DNA.
The T4 bacteriophage Dda helicase is believed to be involved in early events in T4 DNA replication and has been shown to stimulate genetic recombination processes in vitro. Dda unwinds double-stranded DNA with 5' to 3' polarity but its ability to translocate on DNA has not been established. The DNA stimulated ATPase activity of Dda helicase has been used to probe translocation on single-strand DNA (ssDNA). Dda exhibits higher ATPase activity in the presence of poly(dT) than oligo(dT)16, indicating that Dda translocates on ssDNA. Oligonucleotides containing biotin/streptavidin blocks on the 5' or 3' end were used to probe directionality of translocation. The Kact (Km for DNA) for Dda ATPase activity was reduced in the presence of a streptavidin block on the 3' end, whereas a streptavidin block on the 5' end had only a small effect on the steady-state ATPase parameters. These results suggest that Dda translocates unidirectionally in a 5' to 3' manner and upon encountering the block remains bound to the oligonucleotide rather than sliding off the 3' end. The direction of translocation on ssDNA is consistent with the direction in which Dda unwinds duplex DNA and is not dependent on duplex structure.


Neuroimaging in early-treated phenylketonuria patients and clinical outcome: A systematic review.
Lacking direct neuropathological data, neuroimaging exploration has become the most powerful tool to give insight into pathophysiological alterations of early-treated PKU (ETPKU) patients. We conducted a systematic review of neuroimaging studies in ETPKU patients to explore 1) the occurrence of consistent neuroimaging alterations; 2) the relationship between them and neurological and cognitive disorders; 3) the contribution of neuroimaging in the insight of neuropathological background of ETPKU subjects; 4) whether brain neuroimaging may provide additional information in the monitoring of the disease course. Thirty-eight studies met the inclusion criteria for the full-text review, including morphological T1/T2 sequences, diffusion brain imaging (DWI/DTI) studies, brain MRI volumetric, functional neuroimaging studies, neurotransmission and brain energetic imaging studies. Non-progressive brain white matter changes were the most frequent and precocious alterations. As confirmed in hundreds of young adults with ETPKU, they affect over 90% of ETPKU patients. Consistent correlations are emerging between microstructural alteration (as detected by DWI/DTI) and metabolic control, which have also been confirmed in a few interventional trials. Volumetric studies detected later and less consistent cortical and subcortical grey matter alterations, which seem to be influenced by the patient's age and metabolic control. The few functional neuroimaging studies so far showed preliminary but interesting data about cortical activation patterns, skill performance, and brain connectivity. Further research is mandatory in these more complex areas. Recurrent methodological limitations include restricted sample sizes concerning the clinical variability of the disease, large age-range, variable measures of metabolic control, and prevalence of cross-sectional rather than longitudinal interventional studies.


Composition and Tissue-Specific Distribution of Stilbenoids in Grape Canes Are Affected by Downy Mildew Pressure in the Vineyard.
Grape canes are byproducts of viticulture containing valuable bioactive stilbenoids including monomers and oligomers of E-resveratrol. Although effective contents in stilbenoids are known to be highly variable, the determining factors influencing this composition remain poorly understood. As stilbenoids are locally induced defense compounds in response to phytopathogens, this study assessed the impact of downy mildew infection during the growing season on the stilbenoid composition of winter-harvested grape canes. The spatial distribution between pith, conducting tissues, and cortex of E-piceatannol, E-resveratrol, E-ε-viniferin, ampelopsin A, E-miyabenol C, Z/E-vitisin B, hopeaphenol, and isohopeaphenol in grape canes from infected vineyards was strongly altered. In conducting tissues, representing the main site of stilbenoid accumulation, E-ε-viniferin content was higher and E-resveratrol content was lower. These findings suppose that the health status in vineyards could modify the composition of stilbenoids in winter-harvested grape canes and subsequently the potential biological properties of the valuable extracts.


Leaf specific mass confounds leaf density and thickness.
We explored the relationship between leaf specific mass (LSM) and its two components, leaf density and thickness. These were assessed on the leaves of (a) the moderately sclerophyllous tree Arbutus menziesii distributed along a natural nutrient/moisture gradient in California, (b) eight sclerophyllous shrub species on four substrates in south-western Australia, and (c) seedlings of two morphologically contrasting Hakea species grown under varying soil nutrient, moisture and light regimes in a glasshouse experiment. Leaf area, mass, LSM, density and thickness varied greatly between leaves on the same plant, different species, and with different nutrient, moisture and light regimes. In some cases, variations in LSM were due to changes in leaf density in particular or thickness or both, while in others, density and thickness varied without a net effect on LSM. At lower nutrient or moisture availabilities or at higher light irradiances, leaves tended to be smaller, with higher LSM, density and thickness. Under increased stress, the thickness (diameter) of needle leaves decreased despite an increase in LSM. We concluded that, while LSM is a useful measure of sclerophylly, its separation into leaf density and thickness may be more appropriate as they often vary independently and appear to be more responsive to environmental gradients than LSM.


Solubilization and reconstitution of hepatic System A-mediated amino acid transport. Preparation of proteoliposomes containing glucagon-stimulated transport activity.
System A-mediated amino acid transport activity from rat liver plasma membrane vesicles has been solubilized and reconstituted into proteoliposomes using a freeze-thaw-dilution technique. The presence of cholate, at a cholate to protein ratio of 1:1, during the freeze-thaw step resulted in an enhancement in recoverable transport activity. The carrier required both phosphatidylcholine and phosphatidylethanolamine for optimal activity, but the addition of cholesterol to the reconstitution procedure appeared to have no significant effect on the resulting activity. A lipid to protein ratio of 20:1 yielded maximal transport activity. Sonication of the proteoliposomes provided some improvement in the accuracy of replicate assays for a given proteoliposome preparation. Isolated liver plasma membrane vesicles prepared from rats treated in vivo with glucagon in combination with dexamethasone contained stimulated System A activity. This enhanced transport activity could be solubilized and recovered in proteoliposomes generated from these plasma membranes. The data support the proposal that hormone regulation of the hepatic System A gene results in the de novo synthesis and plasma membrane insertion of the carrier protein itself.


Separation of exfoliated tumor cells from viscoelastic pleural effusion using a microfluidic sandwich structure.
A microfluidic device with a sandwich structure is proposed to achieve label-free and size-selective separation of tumor cells from pleural effusion. The sandwich structure is a co-flow system incorporating an initial sample layer, an isolation layer and the target sample layer. The isolation layer is used to provide a size-selective interface between the initial sample layer and the isolation layer. The relative magnitude of the inertial lift force and the interfacial lift force at the interface only allows exfoliated tumor cells to migrate out of the sample layer. The high interfacial elastic lift force of the isolation layer also enables the device to be used for pleural effusion samples, whose properties usually vary across a wide range. The target sample layer is used for large migration distances of exfoliated tumor cells in the contraction-expansion array (CEA) channel and high separation efficiency. Cell washing is also achieved with the target sample layer, demonstrating the integration of our device. Experimentally, an optimal flow rate ratio of 1:1:6 was obtained to ensure the stability of the sandwich structure, and the collected fluid was all from the target sample layer. A critical polyethylene oxide (PEO) concentration of the isolation layer (500 ppm, η0 = 1.37 mPa·s) was then obtained by particle tests. Twenty-micrometer particles were efficiently separated from different viscoelastic samples (PEO concentration changes from 0 to 400 ppm) at this concentration. For the cell test, exfoliated tumor cells from different pleural effusion samples were successfully separated and washed. The separation efficiency of exfoliated tumor cells and blood cells was about 100% and over 90%, respectively. Compared with a conventional co-flow system of two fluids, this device has great advantages in 1) wide applicability for pleural effusion samples of various viscoelasticity and 2) focusing performance. It shows potential for use in medical research and clinical diagnosis of cancer.


PABPN1L assemble into "ring-like" aggregates in the cytoplasm of MII oocytes and is associated with female infertility†.
Infertility affects 10-15% of families worldwide. However, the pathogenesis of female infertility caused by abnormal early embryonic development is not clear. A recent study showed that poly(A)binding protein nuclear 1-like (PABPN1L) recruited BTG anti-proliferation factor 4 (BTG4) to mRNA 3'-poly(A) tails and was essential for maternal mRNA degradation. Here, we generated a PABPN1L-antibody and found "ring-like" PABPN1L aggregates in the cytoplasm of MII oocytes. PABPN1L-EGFP proteins spontaneously formed "ring-like" aggregates in vitro. This phenomenon is similar with CCR4-NOT catalytic subunit, CCR4-NOT transcription complex subunit 7 (CNOT7), when it starts deadenylation process in vitro. We constructed two mouse model (Pabpn1l-/- and Pabpn1l tm1a/tm1a) simulating the intron 1-exon 2 abnormality of human PABPN1L and found that the female was sterile and the male was fertile. Using RNA-Seq, we observed a large-scale up-regulation of RNA in zygotes derived from Pabpn1l-/- MII oocytes. We found that 9222 genes were up-regulated instead of being degraded in the Pabpn1l-♀/+♂zygote. Both the Btg4 and CCR4-NOT transcription complex subunit 6 like (Cnot6l) genes are necessary for the deadenylation process and Pabpn1l-/- resembled both the Btg4 and Cnot6l knockouts, where 71.2% genes stabilized in the Btg4-♀/+♂ zygote and 84.2% genes stabilized in the Cnot6l-♀/+♂zygote were also stabilized in Pabpn1l-♀/+♂ zygote. BTG4/CNOT7/CNOT6L was partially co-located with PABPN1L in MII oocytes. The above results suggest that PABPN1L is widely associated with CCR4-NOT-mediated maternal mRNA degradation and PABPN1L variants on intron 1-exon 2 could be a genetic marker of female infertility.


Long-Term Metal PM2.5 Exposures Decrease Cardiac Acceleration and Deceleration Capacities in Welders.
The aim of the study was to clarify whether long-term metal particulates affect cardiac acceleration capacity (AC), deceleration capacity (DC), or both. We calculated chronic exposure index (CEI) for PM2.5 over the work life of 50 boilermakers and obtained their resting AC and DC. Linear regression was used to assess the associations between CEI PM2.5 exposure and each of AC and DC, controlling for age, acute effects of welding exposure, and diurnal variation. Mean (standard deviation) CEI for PM2.5 exposure was 1.6 (2.4) mg/m-work years and ranged from 0.001 to 14.6 mg/m-work years. In our fully adjusted models, a 1 mg/m-work year increase in CEI for PM2.5 was associated with a decrease of 1.03 (95% confidence interval: 0.10, 1.96) ms resting AC, and a decrease of 0.67 (95% confidence interval: -0.14, 1.49) ms resting DC. Long-term metal particulate exposures decrease cardiac accelerations and decelerations.


Is acetaminophen safe in pregnancy?
Acetaminophen is thought to be the safest analgesic and antipyretic medicine for pregnant women, and it is widely used all over the world. However, prenatal acetaminophen was reported to be associated with asthma, lower performance intelligence quotient (IQ), shorter male infant anogenital distance (predicting poor male reproductive potential), autism spectrum disorder, neurodevelopmental problems (gross motor development, communication), attention-deficit/hyperactivity disorder, poorer attention and executive function, and behavioral problems in childhood. Each article has poor power to show risks of acetaminophen, however, the integration of the articles that showed adverse effects of acetaminophen may have power to show them. Acetaminophen use in childhood was associated with autism spectrum disorder, asthma symptoms, wheezing, and allergic disease. Acetaminophen is the safest medicine as analgesics for nociceptive pain and antipyretics in childhood and pregnancy. There is no alternative medication of acetaminophen. Acetaminophen should not be withheld from children or pregnant women for fears it might develop adverse effects. Acetaminophen should be used at the lowest effective dosage and for the shortest time. When we know the possible, rare but serious complications, we should use acetaminophen in pregnancy only when needed and no safer option for pain or fever relief is available. Health care providers should help inform the general lay public about this difficult dilemma.


Impact of pruritus on quality of life in sulfur mustard-exposed Iranian veterans.
Sulfur mustard, a chemical warfare agent, has various verified chronic effects on the skin. One of the foremost negative impacts of this agent is chronic pruritus, which plagues chemically injured veterans for life and can downgrade their quality of life. To assess the association between the quality of life and pruritus severity in chemically injured veterans. One hundred and twenty-five consecutive chemically injured veterans suffering from pruritus were assessed via the Dermatology Life Quality Index (DLQI) and pruritus score. Pruritus scores less than 15, between 16 and 30, and more than 30 were considered as mild, moderate, and severe pruritus, respectively. Patients with different levels of pruritus were compared with respect to their DLQI and its subscores. All subjects were male with a mean age of 44.3 +/- 8.0 years; 11.2% had mild, 35.2% moderate, and 53.6% severe itching. The DLQI median scores in the mild, moderate, and severe cases were 16, 20, and 21, respectively (P = 0.014). The DLQI subscores of symptoms and feelings (P = 0.015), personal relationships (P = 0.002), and daily activities (P = 0.036) were worst in patients with severe itching. Chemically injured veterans suffering from severe itching have a significantly poorer quality of life than do patients with milder symptoms.


Sulfate radical based advanced oxidation processes for agro-industrial effluents treatment: A comparative review with Fenton's peroxidation.
Agro-industrial wastewater management becomes a major task while environmental regulations are becoming stricter worldwide. Agro-industrial wastewaters are known by high content of organic pollutants that cause an adverse effect on the water bodies. Industries are looking for efficient, easy-to-use and affordable treatment processes. Sulfate radical based advanced oxidation processes (S-AOPs) are arising as suitable alternatives for agro-industrial effluents treatment. In this review, the major findings regarding the application of this technology for real agro-industrial wastewater depuration are discussed. Moreover, these technologies are compared as an alternative to Fenton's process, which is a widely studied advanced oxidation process and with high efficiency in the treatment of agro-industrial effluents. The studies already carried out are promising, but there is still a great lack of studies in this area and using this technique.


Pelizaeus-Merzbacher disease, easily misdiagnosed as cerebral palsy: a report of a three-generation family.
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder affecting myelination of the central nervous system, and is caused by mutations of the proteolipid protein 1 (PLP1) gene. Clinical manifestations of PMD are variable and major features include progressive nystagmus, spasticity, tremor, ataxia, and psychomotor delay. We describe a classical PMD patient who had been misdiagnosed as cerebral palsy. He had nystagmus and psychomotor delay since infancy and tremor with ataxia developing gradually. Brain MRI revealed demyelination over white matter of the cerebral hemispheres and posterior limbs of the internal capsules. Positive family history led to subsequent mutation analysis, which identified a novel mutation (c.88G>C) in PLP1 in the proband, as well as his affected brother and maternal uncle, and asymptomatic maternal grandmother, mother and two sisters. Therefore, PMD should be considered in a cerebral palsy-like patient with or without positive family history. Mutation analysis is crucial for early diagnosis and further genetic counseling.


Isolation and protein MdtQ analysis of outer membrane vesicles released by carbapenem-resistant Klebsiella pneumoniae.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a leading public health problem, and is increasingly being reported worldwide with resistance to a wide spectrum of antibiotics. Recent reports have demonstrated that the outer membrane vesicles (OMVs) of gram-negative bacteria are potent resistance factors, but their role in the drug resistance of CRKP has not been elucidated. In order to investigate the effects of OMV components on drug resistance and to explore the mechanism of antimicrobial resistance in CRKP, we isolated the OMVs through ultracentrifugation, separated the OMV proteins through mass spectrometry (MS), and performed bioinformatics analysis. A total of 3,192 proteins were detected by nano LC-MS/MS analysis, with 108 (61.4%) cytoplasmic proteins, 50 (28.4%) cytoplasmic membrane proteins, nine (5.1%) periplasmic proteins, six (3.4%) outer membrane proteins, two (1.1%) extracellular proteins, and one (0.6%) other protein detected in the vesicles. MdtQ was detected as the only multidrug resistance outer membrane protein. Further experiments confirmed that MdtQ included the 1440 BP sequence and had a unique three-dimensional structure. To superimpose MdtQ with KPC-2 resistant proteins, I7ACB1, I7AKP2, and Q93LQ9, the root mean square deviation (RMSD) values were calculated (0.379, 0.671, and 1.35, respectively). I7ACB1 had the lowest RMSD value, indicating that it had the best superimposition effect. Furthermore, MdtQ had 20 biological pocket structures, and the four most important pockets were evenly distributed around the inner perimeter of its three-dimensional structure. These findings may provide a theoretical basis for controlling the spread of bacterial resistance in the future.


Lipolytic activities of freshly isolated rat liver parenchymal cells.
By using a specific collagenase preparation preserving lipolytic enzymes, we could isolate intact rat liver cells with monoester lipase (MEL) and, for the first time, substantial amounts of endogenous neutral triester lipase (TEL) activities assayable as cell-bound enzymes. TEL and MEL activities were found exclusively in parenchymal cells. Virtually all TEL was located on plasma membrane from which it was rapidly released at 37 degrees C in the absence of any additive. MEL was distributed almost equally inside the cell and in the membrane, to which it was firmly attached. Infusion of heparin to the whole animal before liver exposure decreased by 80% the TEL content of parenchymal cells (a property typical of hepatic lipase) whilst MEL was unchanged. These results question the concept that heparin-releasable hepatic lipase acts at the surface of endothelial liver cells and further suggest that TEL and MEL refer to distinct catalytic entities.


Anticipatory phase correction in sensorimotor synchronization.
Studies of phase correction in sensorimotor synchronization often introduce timing perturbations that are unpredictable with regard to direction, magnitude, and position in the stimulus sequence. If participants knew any or all of these parameters in advance, would they be able to anticipate perturbations and thus regain synchrony more quickly? In Experiment 1, we asked musically trained participants to tap in synchrony with short isochronous tone sequences containing a phase shift (PS) of -100, -40, 40, or 100 ms and provided advance information about its direction, position, or both (but not about its magnitude). The first two conditions had little effect, but in the third condition participants shifted their tap in anticipation of the PS, though only by about ±40 ms on average. The phase correction response to the residual PS was also enhanced. In Experiment 2, we provided complete advance information about PSs of various magnitudes either at the time of the immediately preceding tone ("late") or at the time of the tone one position back ("early") while also varying sequence tempo. Anticipatory phase correction was generally conservative and was impeded by fast tempo in the "late" condition. At fast tempi in both conditions, advancing a tap was more difficult than delaying a tap. The results indicate that temporal constraints on anticipatory phase correction resemble those on reactive phase correction. While the latter is usually automatic, this study shows that phase correction can also be controlled consciously for anticipatory purposes.


Long-term serial cultivation and growth requirements for human umbilical vein endothelial cells.
Human umbilical vein endothelial cells (HUV-EC) grew rapidly in vitro in medium supplemented with epidermal growth factor, fetal bovine serum (FBS) and human diploid fibroblast-conditioned medium. The effect of FBS could be replaced partially by bovine serum albumin, cholesterol, and vitamin E, and completely by further addition of serum dialysate or refeeding every other day. Among these components, fibroblast-conditioned medium is essential for HUV-EC growth. The HUV-EC were cultured serially for over 50 population doublings in the 10% FBS containing fibroblast-conditioned medium and for over 40 population doublings in the serum-free medium. Mitogenic factor(s) present in the medium conditioned by fibroblasts may be related to endothelial cell growth factor and play an important role in angiogenesis and regeneration of vascular endothelium in vitro.


Developmental pattern of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat.
The activity, protein concentration and catalytic efficiency of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase was determined in rats aged 1 to 199 days. Microsomal enzyme total activity peaked on day 24, during weaning, and again on day 63, during the onset of puberty. Increased enzyme activity during weaning resulted primarily from an increase in the catalytic efficiency of the enzyme with a slight reduction in enzyme protein content. The rise in enzyme activity during the onset of puberty, however, was primarily the result of an increase in enzyme protein concentration. Thus, the activity of reductase in mammalian livers reflects, at different stages in development, the modulating influence of both the total number of reductase molecules and the catalytic efficiency of the enzyme.


Contraband: the hidden risk.
In a 28-month retrospective study of contraband possession in an inpatient psychiatric setting, 54 incidents of contraband confiscation were identified. Incidents were analyzed according to day and shift of occurrence, nature of contraband, patient diagnoses and characteristics, and patient outcome of contraband possession. Study findings stress the importance of clearly stated contraband policies and procedures, especially in light of patient and staff rights and responsibilities.


Detection of 14q32 rearrangements in multiple myeloma, using simultaneous FISH analysis combined with immunofluorescence.
14q32 rearrangement has been identified as a recurrent hotspot of translocations in multiple myeloma (MM). The Fluorescence Immunophenotyping and Interphase Cytogenetics as a tool for the Investigation of Neoplasms (known as FICTION technique) for evaluation of chromosomal changes in MM. The aim of this work is to detect 14q32 rearrangement, using FICTION technique, on archival bone marrow (BM) slides of MM patients, and to study its prognostic value. This study was conducted at Ain Shams University Hospital. The FICTION technique, which uses CD138 and dual color, and the break-apart 14q32 rearrangement probe, was performed on archived smears of BM slides for 50 MM patients at the time of diagnosis. A significantly higher percentage of cases were positive for 14q32 rearrangement by FICTION (32%) compared to fluorescence in situ hybridization (FISH) (12%) (p=0.04). Cases positive by FICTION for the rearrangement were designated as Group A, while negative cases were designated as Group B. Significantly lower Hb and CRP levels were found among Group B when compared to Group A patients (p=0.001 and 0.01, respectively). Serum albumin level and Bence Jones protein (BJP) significantly affect overall survival (OS) (p=0.01, 0.007, respectively). However, a statistically non-significant shorter mean survival time was found in positive cases through FICTION versus negative cases. FICTION technique provides a sensitive tool for establishing clonal plasma cells (PC) infiltration of BM aspirates, and is amenable for use on archived as well as fresh smears.


Latent dimensions of social anxiety disorder: A re-evaluation of the Social Phobia Inventory (SPIN).
The Social Phobia Inventory (SPIN; Connor et al., 2000) is a well-validated instrument for assessing severity of social anxiety disorder (SAD). However, evaluations of its factor structure have produced inconsistent results and this aspect of the scale requires further study. Primary care patients with SAD (N=397) completed the SPIN as part of baseline assessment for the Coordinated Anxiety Learning and Management study (Roy-Byrne et al., 2010). These data were used for exploratory and confirmatory factor analysis of the SPIN. A 3-factor model provided the best fit for the data and factors were interpreted as Fear of Negative Evaluation, Fear of Physical Symptoms, and Fear of Uncertainty in Social Situations. Tests of a second-order model showed that the three factors loaded strongly on a single higher-order factor that was labeled Social Anxiety. Findings are consistent with theories identifying Fear of Negative Evaluation as the core feature of SAD, and with evidence that anxiety sensitivity and intolerance of uncertainty further contribute to SAD severity.


Parent Ratings of Health Insurance Adequacy for Children with Emotional, Behavioral, or Developmental Problems.
Parents of children with special health care needs (CSHCN) report that private insurance is less adequate than public health coverage. Parents of CSHCN with emotional, behavioral, or developmental problems (EBDPs) may perceive private insurance to be especially inadequate due to higher need for a wider array of non-medical services and supports. This study's objective is to assess differences in parent ratings of insurance adequacy for public versus private health coverage between non-CSHCN, CSHCN, and CSHCN with EBDPs. This study pooled publicly available data from the 2016 through 2019 National Survey of Children's Health. Multivariable fixed effects logistic regression models estimated the association between insurance type, CSCHN and EBDP status, and parent ratings of their child's insurance adequacy. Marginal effects were calculated for insurance type, CSHCN and EBDP status, and their interactions to estimate the size of the association. Among all subgroups, consistently more parents with publicly insured children rated their insurance as adequate compared to those with private insurance. Parents of privately insured CSHCN with EBDPs rated their insurance as adequate at significantly lower rates than any other group of parents (55%)-including those with privately insured children without EBDPs (non-CSHCN= 67%; CSHCN = 63%) and all other parents with publicly insured children (non-CSHCN = 87%; CSHCN = 83%; CSHCN with EBDPs = 84%). Future research should investigate if perceptions of insurance adequacy among families whose CSHCN has an EBDP aligns with reports of service access and unmet health care needs.


Delayed versus early hepatic resection among patients with severe traumatic liver injuries undergoing damage control laparotomy.
We aimed to assess the effect of time to hepatic resection on the outcomes of patients with high-grade liver injuries who underwent damage control laparotomy (DCL). This is a 4-year (2017-2020) analysis of the ACS-TQIP. Adult trauma patients with severe liver injuries (AAST-OIS grade ≥ III) who underwent DCL and hepatic resection were included. We excluded patients with early mortality (<24 h). Patients were stratified into those who received hepatic resection within the initial operation (Early) and take-back operation (Delayed). Of 914 patients identified, 29% had a delayed hepatic resection. On multivariable regression analyses, although delayed resection was not associated with mortality (aOR:1.060,95%CI[0.57-1.97],p = 0.854), it was associated with higher complications (aOR:1.842,95%CI[1.38-2.46],p < 0.001), and longer hospital (β: +0.129, 95%CI[0.04-0.22],p = 0.005) and ICU (β:+0.198,95%CI[0.14-0.25],p < 0.001) LOS, compared to the early resection. Delayed hepatic resection was associated with higher adjusted odds of major complications and longer hospital and ICU LOS, however, no difference in mortality, compared to early resection.


Headspace determination of evolved carbon dioxide in a biodegradability screening test.
A headspace method to measure the carbon dioxide evolved in a screening biodegradability test is described. Use was made of conventional serum bottles, sealed with butyl rubber septa, through which headspace samples were taken after acidification and equilibration of the test solution. For each determination a serum bottle was sacrificed. The gas samples were injected directly into the reaction chamber of a carbon analyzer. Eighteen chemicals varying in solubility and biological properties were submitted to the test. Where possible, mineralization of test compounds was monitored through dissolved organic carbon analysis in addition to CO2 analyses. The reliability of the method was verified by comparing the measured concentration of dissolved inorganic carbon of a standard sodium carbonate solution with values calculated from measured concentrations of carbon dioxide in the headspace after acidification. Results of biodegradability testing are discussed in view of the suitability of the method to poorly soluble compounds.


Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease.
Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.


Rat post-implantation embryo culture using heterologous serum.
In the present study sera from twelve species have been compared to rat serum and ascitic fluid for their ability to support the growth of post-implantation rat embryos. No alternative to rat serum or rat ascitic fluid was found. The basis for this apparent species specificity was further analysed. A marked improvement in embryonic growth was seen when rat serum was added to the heterologous serum prior to culture, whereas replenishment of a heterologous serum several times during culture had no effect. The experiments suggested that heterologous sera were nutritionally inadequate but not simply in energy source. Possible mechanisms for the specificity are discussed.


Keyhole craniectomy for correction of sagittal synostosis.
A modification of the technique combining sagittal strip, circular occipital and biparietal wedge craniectomies (Albright's procedure) for the treatment of sagittal synostosis, with prominent occipital bossing, is described. "Keyhole," as opposed to wedge, parietal craniectomies allow improvement in the shape of the skull, beginning intraoperatively, while eliminating the outbending of the parietal bone that occurs at the apex of a wedge craniectomy.


Evidence-based early clinical detection of emerging diseases in food animals and zoonoses: two cases.
If diseases of food-producing animals or zoonoses (re-)emerge, early clinical decision making is of major importance. In this particular condition, it is difficult to apply a classic evidence-based veterinary medicine process, because of a lack of available published data. A method based on the partition of field clinical observations (evidences) could be developed as an interesting alternative approach. The classification and regression tree (CART) analysis was used to improve the early clinical detection in two cases of emerging diseases: bovine spongiform encephalopathy (mad cow disease) and bluetongue due to the serotype 8-virus in cattle.


Glial fibrillary acidic protein in chronic relapsing experimental allergic encephalomyelitis in SJL/J mice.
The gliotic scar in the demyelinated plaque is a prominent feature of the pathology of multiple sclerosis. Chronic relapsing experimental allergic encephalomyelitis (EAE) in the SJL/J mouse has many characteristics in common with multiple sclerosis in the human, including the development of intense gliosis during the course of the demyelinating disease. With the use of antibody to the astrocyte marker glial fibrillary acidic protein (GFAP) we have measured the increase of GFAP over an 11-month course of chronic EAE. Intense staining of astrocyte fibers was seen around EAE lesions, which were most frequently observed in the cerebellum, periventricular areas, and in the spinal cord. The relative amount of GFAP was estimated by preparation of cytoskeletal proteins from the affected CNS areas, separation of proteins by polyacrylamide gel electrophoresis, and quantitation of GFAP in relation to the 70-kD neurofilament protein (NF) in gel scans. The ratio GFAP/70-kD NF protein in control animals did not change significantly over 11 months, whereas this ratio gradually increased to 2.54 in animals with chronic relapsing EAE 6 months after immunization. Although some decrease of neural fibers may have contributed partially to this change in ratio, the amounts of GFAP were greatly increased. These results indicate that the SJL/J mouse with chronic relapsing EAE provides an excellent model with which to investigate the formation and development of the gliotic plaque analogous to that seen in demyelinated areas in multiple sclerosis tissue.


Development of the peripheral and central venous catheter-related bloodstream infection prevention knowledge and attitudes scale.
Because of the necessities of modern medicine, catheters are frequently used for patients today. Mistakes made in catheter implementation frequently cause nosocomial infections. The purpose of this study was to develop a scale to be used for the evaluation of nurses' knowledge and attitudes about peripheral and central venous catheter-related bloodstream infection prevention. This methodological study was conducted between July 2016 and December 2017, with 150 nurses who worked in intensive care units and surgical, internal and paediatric clinics in hospitals located in two different cities in the eastern part of Turkey and who consented to participate in the study. Item total correlation values of the scale ranged between 0.515 and 0.703. Correlation coefficient between the two measurements as a result of the test-retest reliability was found to be 0.64, and there was a linear relationship between the measurements. The Kaiser-Meyer-Olkin (KMO) value was found to be0.875, which indicates the adequacy of the sample. Barlett's test results indicated a correlation between the items (P < .01). Cronbach's alpha value of the scale was found to be 0.86. Results showed that the 5-point Likert scale was formed with 14 items and two factors, which included "general precautions" and "catheter care." Scale total score is obtained by collecting all the items. Higher scores indicate higher knowledge and attitudes. This scale could be used for assessing the knowledge and attitudes of nurses about peripheral and central venous catheter-related bloodstream infection prevention precautions. The Peripheral and Central Venous Catheter-Related Bloodstream Infection Prevention Knowledge and Attitudes Scale could be used for infection prevention in the assessment of the knowledge and attitudes of nurses with a view of preventing infections. The scale can be used in intensive care units and surgical, internal and paediatric clinics in order to assess nurses' knowledge and attitudes.


A simple and rapid immunocytochemical technique for detection of cytokeratin, vimentin, and S-100 protein in veterinary diagnostic cytology.
The objective of this study was to establish a simple and rapid immunocytochemical technique that can be used in veterinary diagnostic cytology. Air-dried impression smears were collected from canine tumors. Samples of epithelial tumors, mesenchymal tumors, and malignant peripheral nerve sheath tumors and melanomas were used for detection of cytokeratin, vimentin, and S-100 protein, respectively. The labeled streptavidin-biotin system was used in the present study. Optimal fixation was determined using standard immunocytochemical procedures, and acetone fixation was found to be the most effective. Optimal concentrations of primary and secondary antibodies were determined at a preset 5-min incubation. Omission of H2O2 treatment, shortening the time for blocking and labeled-streptavidin incubation, and simplifying washing did not decrease immunopositive intensities or enhance false-positive reactions. The described rapid protocol requires approximately 45 min without the use of any special equipment.


Resistance of Salmonella typhi to chloramphenicol. I. A preliminary report.
Resistance of Salmonella typhi to chloramphenicol has not been reported so far except in strains made resistant in the laboratory. While examining 52 smooth strains of S. typhi and three smooth strains of S. paratyphi A 10 strains of S. typhi were found to be resistant to 50 to 500 mug. chloramphenicol. Of these 10 strains, eight appeared to be tolerant of the antibiotic, but the remaining two strains appeared to produce a substance that antagonizes or destroys chloramphenicol.


Changes in the contralateral eye in uncomplicated persistent hyperplastic primary vitreous in adults.
In two adults (a 62-year-old man and a 71-year-old woman) uncomplicated full-blown unilateral persistent hyperplastic primary vitreous was diagnosed on the basis of characteristic clinical features and ultrasonography. In the contralateral uninvolved eyes, we found open-angle glaucoma, anomalous blood vessels along the entire circumference of the anterior chamber angle, band keratopathy, and heterochromia iridis. The axial length of one involved eye was about 0.85 mm larger than that of the uninvolved eye.


Cationic liposomes suppress intracellular calcium ion concentration increase via inhibition of PI3 kinase pathway in mast cells.
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca2+ concentration ([Ca2+]i) via inhibition of store-operated Ca2+ entry (SOCE). Here we study the mechanism underlying an impaired [Ca2+]i increase by cationic liposomes in mast cells. We show that cationic liposomes inhibit the phosphorylation of Akt and PI3 kinases but not Syk and LAT. As a consequence, SOCE is suppressed but Ca2+ release from endoplasmic reticulum (ER) is not. Cationic liposomes inhibit the formation of STIM1 puncta, which is essential to SOCE by interacting with Orai1 following the Ca2+ concentration decrease in the ER. These data suggest that cationic liposomes suppress SOCE by inhibiting the phosphorylation of PI3 and Akt kinases in mast cells.


[Rebound tonometry with sterilized probes].
Intraoperative measurement of intraocular pressure (IOP) opens up possibilities to investigate the influence of IOP on the stability of the eyeball during the performance of surgical maneuvers. Few techniques have been described, none of which are commercially available. This study investigated the use of sterilized probes for rebound tonometry, which could be used intraoperatively. Tonometry was performed on 30 eyes using a noncontact tonometer and rebound tonometry with the iCare 100 and iCare 200 (iCare Finland Oy, Vantaa, Finland) in a sitting and in a supine position. When performing rebound tonometry probes from the package were used sequentially with sterilized probes. The comparability of sterilized and nonsterilized probes was investigated using different rebound tonometers and different settings. Measurements on a sitting subject were comparable with sterilized and nonsterilized probes. Statistically significant comparability was also found in a supine position. Measurements with identically sterilized probes on identically positioned subjects were comparable with iCare 100 und iCare 200 (T2 vs. T4, p = 0.003 und T3 vs. T5 p < 0.001). The comparison of measurements of the original probe with the sterilized probe in a sitting and in a supine position were possible with statistical significance (p < 0.005). Measuring with the iCare 200 in a sitting position showed a slightly lower IOP with the sterilized probe with the difference being statistically significant. Single autoclaving does not alter the probes' ability to measure IOP. The use of probes which have been sterilized according to the regulations for other surgical instruments opens up new possibilities for the intraoperative measurement of IOP. This facilitates the use in scientific studies on surgical techniques. In the postoperative period the use of sterilized probes can reduce the risk of infection.


Unexpected Role of p-Toluenesulfonylmethyl Isocyanide as a Sulfonylating Agent in Reactions with α-Bromocarbonyl Compounds.
The reactions of p-toluenesulfonylmethyl isocyanide (TosMIC) with α-bromocarbonyl compounds leading efficiently to α-sulfonated ketones, esters, and amides were reported, in which an explicit new role of TosMIC as the sulfonylating agent was uncovered for the first time. Mechanistic study by control experiments and DFT calculations suggested that the reaction is initiated by Cu(OTf)2-catalyzed hydration of TosMIC to form a formamide intermediate, which undergoes facile C-S bond cleavage under the mediation of a Cs2CO3 additive.


Effectiveness of radiotherapy in myxoid sarcomas is associated with a dense vascular pattern.
Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularization pattern of MLS. Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns. Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all "pure" MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS. Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.


Effect of energy intake on nutritional status in maintenance hemodialysis patients.
Although maintenance hemodialysis (MHD) patients are often wasted, little is known about their dietary energy needs. We studied four men and two women in a clinical research center while they received diets providing 45, 35 and 25 kcal/kg desirable body weight/day; diets were fed, in random order, for 21 to 23 days each. Protein intake, 1.13 +/- 0.02 (SEM) g protein/kg/day, was similar with all three diets. Body weight rose with 45 and 35 kcal/kg/day (P less than 0.05) and fell with 25 kcal/kg/day (P less than 0.05). Nitrogen balance, adjusted for estimated unmeasured losses, was neutral with 45 and 35 kcal/kg/day and negative with 25 kcal/kg/day. Balance was neutral or positive in 6 of 6, 4 of 6, and 0 of 6 patients fed 45, 35, 25 kcal/kg/day, respectively. Nitrogen balance, many plasma amino acids and changes in body weight, mid-arm circumference, mid-arm muscle area and body fat each correlated with energy intake. Resting energy expenditure was normal. The energy intake estimated from regression equations to maintain neutral nitrogen balance was 38.5 kcal/kg desirable weight/day; for body fat and weight, it was 32 kcal/kg/day. These data suggest that MHD patients have normal energy expenditure and approximately normal requirements for maintenance of protein balance, body weight and body fat. An average energy intake of about 38 kcal/kg desirable weight/day may be necessary to maintain nitrogen balance in these patients.


Tumor distance from the mediastinum predicts N2 upstaging in clinical stage I lower-lobe non-small cell lung cancer.
Pulmonary lymphatic drainage of the lower lobe into the mediastinal lymph nodes includes not only the pathway via the hilar lymph nodes but also the pathway directly into the mediastinum via the pulmonary ligament. This study aimed to determine the association between the distance from the mediastinum to the tumor and the frequency of occult mediastinal nodal metastasis (OMNM) in patients with clinical stage I lower-lobe non-small cell lung cancer (NSCLC). Between April 2007 and March 2022, data of patients who underwent anatomical pulmonary resection and mediastinal lymph node dissection for clinical stage I radiological pure-solid lower-lobe NSCLC were retrospectively reviewed. In computed tomography axial sections, the ratio of the distance from the inner edge of the lung to the inner margin of the tumor within the lung width of the affected lung was defined as the inner margin ratio. Patients were divided into 2 groups based on whether the inner margin ratio was ≤0.50 (inner-type) or >0.50 (outer-type), and the association between inner margin ratio status and clinicopathological findings was assessed. In total, 200 patients were enrolled in the study. OMNM frequency was 8.5%. More inner-type than outer-type patients had OMNM (13.2% vs 3.2%; P = .012) and skip N2 metastasis (7.5% vs 1.1%; P = .038). Multivariable analysis revealed that the inner margin ratio was the only independent preoperative predictor of OMNM (odds ratio, 4.72; 95% CI, 1.31-17.07; P = .018). Tumor distance from the mediastinum was the most important preoperative predictor of OMNM in patients with lower-lobe NSCLC.


Quercetin inhibits transcriptional up-regulation of histamine H1 receptor via suppressing protein kinase C-δ/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells.
It has been reported that the histamine H1 receptor (H1R) gene is up-regulated in patients with allergic rhinitis and H1R expression level strongly correlates with the severity of allergy symptoms. Accordingly compounds that suppress the H1R gene expression are promising as useful anti-allergic medications. Recently, we demonstrated that histamine or phorbol-12-myristate-13-acetate (PMA) stimulation induced the up-regulation of H1R gene expression through the protein kinase Cδ (PKCδ)/extracellular signal-regulated kinase/poly(ADP-ribose) polymerase-1 signaling pathway in HeLa cells expressing H1R endogenously. Quercetin is one of the well-characterized flavonoids and it possesses many biological activities including anti-allergic activity. However, effect of quercetin on H1R signaling is remained unknown. In the present study, we examined the effect of quercetin on histamine- and PMA-induced up-regulation of H1R gene expression in HeLa cells. We also investigated its in vivo effects on the toluene-2,4-diisocyanate (TDI)-sensitized allergy model rats. Quercetin suppressed histamine- and PMA-induced up-regulation of H1R gene expression. Quercetin also inhibited histamine- or PMA-induced phosphorylation of Tyr(311) of PKCδ and translocation of PKCδ to the Golgi. Pre-treatment with quercetin for 3weeks suppressed TDI-induced nasal allergy-like symptoms and elevation of H1R mRNA in the nasal mucosa of TDI-sensitized rats. These data suggest that quercetin suppresses H1R gene expression by the suppression of PKCδ activation through the inhibition of its translocation to the Golgi.


Embryonic electrical connections appear to pre-figure a behavioral circuit in the leech CNS.
During development, many embryos show electrical coupling among neurons that is spatially and temporally regulated. For example, in vertebrate embryos extensive dye coupling is seen during the period of circuit formation, suggesting that electrical connections could pre-figure circuits, but it has been difficult to identify which neuronal types are coupled. We have used the leech Hirudo medicinalis to follow the development of electrical connections within the circuit that produces local bending. This circuit consists of three layers of neurons: four mechanosensory neurons (P cells), 17 identified interneurons, and approximately 24 excitatory and inhibitory motor neurons. These neurons can be identified in embryos, and we followed the spatial and temporal dynamics as specific connections developed. Injecting Neurobiotin into identified cells of the circuit revealed that electrical connections were established within this circuit in a precise manner from the beginning. Connections first appeared between motor neurons; mechanosensory neurons and interneurons started to connect at least a day later. This timing correlates with the development of behaviors, so the pattern of emerging connectivity could explain the appearance first of spontaneous behaviors (driven by a electrically coupled motor network) and then of evoked behaviors (when sensory neurons and interneurons are added to the circuit).


Hyperglycemia attenuates erythromycin-induced acceleration of liquid-phase gastric emptying of hypertonic liquids in healthy subjects.
Acute hyperglycemia has been associated with delayed gastric emptying in healthy controls. Erythromycin has recently been found to be a gastrointestinal prokinetic agent in both solids and hypertonic liquids. Our aim was to examine whether the acute steady-state hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of hypertonic liquids after a fasted state of the stomach in healthy subjects. In 12 healthy subjects scintigraphic measurement of gastric emptying of a hypertonic radiolabeled liquid meal, during normoglycemia (5-8.9 mmol/l glucose) or induced hyperglycemia (16-19 mmol/liter glucose) by intravenous glucose infusion after giving either placebo or 200 mg intravenous erythromycin, was performed on four separate days in random order. In the hyperglycemic state compared with normoglycemia, either after placebo administration or erythromycin, the gastric emptying of the hypertonic liquid was reduced. The lag-phase duration was significantly increased (17.5 +/- 5.5 min, and 7.2 +/- 4.5 min vs 10.5 +/- 3.4 min, and 3.5 +/- 2.5 min, respectively, P < 0.0001) as were the overall T1/2 (gastric emptying time of the half meal) (52.5 +/- 13 min and 24.5 +/- 5.5 min vs 42 +/- 10.5 min, and 16 +/- 6 min, respectively, P < 0.0001) and the percentage of liquid meal retained in the stomach at 60 and 100 min postprandially (P < 0.001). In conclusion, hyperglycaemia attenuates the acceleration effect of erythromycin and decreases the overall gastric emptying rate of hypertonic liquids in healthy subjects.


Impact of medium-chain triglycerides on gait performance and brain metabolic network in healthy older adults: a double-blind, randomized controlled study.
Nutritional supplementation with medium-chain triglycerides (MCTs) has the potential to increase memory function in elderly patients with frailty and dementia. Our aim was to investigate the effects of MCT on cognitive and gait functions and their relationships with focal brain metabolism and functional connectivity even in healthy older adults. Participants were blindly randomized and allocated to two groups: 18 g/day of MCT oil and matching placebo formula (control) administered as a jelly stick (6 g/pack, ingested three times a day). Gait analysis during the 6-m walk test, cognition, brain focal glucose metabolism quantified by 18F-fluorodeocyglucose positron emission tomography, and magnetic resonance imaging-based functional connectivity were assessed before and after a 3-month intervention. Sixty-three healthy, normal adults (females and males) were included. Compared with the control group, the MCT group showed better balance ability, as represented by the lower Lissajous index (23.1 ± 14.4 vs. 31.3 ± 18.9; P < 0.01), although no time × group interaction was observed in cognitive and other gait parameters. Moreover, MCT led to suppressed glucose metabolism in the right sensorimotor cortex compared with the control (P < 0.001), which was related to improved balance (r = 0.37; P = 0.04) along with increased functional connectivity from the ipsilateral cerebellar hemisphere. In conclusion, a 3-month MCT supplementation improves walking balance by suppressing glucose metabolism, which suggests the involvement of the cerebro-cerebellar network. This may reflect, at least in part, the inverse reaction of the ketogenic switch as a beneficial effect of long-term MCT dietary treatment.


Looking into the future of foods and health.
The health of the population is compromised by poor dietary choices. Resolving this situation will require a substantial investment at many levels of science, agriculture and food industrialisation. If such investments are undertaken they will provide the opportunity to change the food marketplace from a product centric, to a consumer centric, strategy competing to deliver health benefits to individuals.


Case report: Tai Chi and Parkinsonism.
To describe the effects of an eight-week Tai Chi class on two patients: one with Parkinson's disease, the other with multiple system atrophy. Both patients demonstrated improved scores on the Activities-specific Balance Confidence Scale and the Functional Reach Test. One subject also demonstrated improved scores for the Timed Up and Go test. Both subjects reported subjective improvements in balance and balance awareness. Tai Chi may be a viable option for improving balance in patients with mild Parkinsonism.


Changes in regulatory phosphorylation of Cdc25C Ser287 and Wee1 Ser549 during normal cell cycle progression and checkpoint arrests.
Entry into mitosis is catalyzed by cdc2 kinase. Previous work identified the cdc2-activating phosphatase cdc25C and the cdc2-inhibitory kinase wee1 as targets of the incomplete replication-induced kinase Chk1. Further work led to the model that checkpoint kinases block mitotic entry by inhibiting cdc25C through phosphorylation on Ser287 and activating wee1 through phosphorylation on Ser549. However, almost all conclusions underlying this idea were drawn from work using recombinant proteins. Here, we report that in the early Xenopus egg cell cycles, phosphorylation of endogenous cdc25C Ser287 is normally high during interphase and shows no obvious increase after checkpoint activation. By contrast, endogenous wee1 Ser549 phosphorylation is low during interphase and increases after activation of either the DNA damage or replication checkpoints; this is accompanied by a slight increase in wee1 kinase activity. Blocking mitotic entry by adding the catalytic subunit of PKA also results in increased wee1 Ser549 phosphorylation and maintenance of cdc25C Ser287 phosphorylation. These results argue that in response to checkpoint activation, endogenous wee1 is indeed a critical responder that functions by repressing the cdc2-cdc25C positive feedback loop. Surprisingly, endogenous wee1 Ser549 phosphorylation is highest during mitosis just after the peak of cdc2 activity. Treatments that block inactivation of cdc2 result in further increases in wee1 Ser549 phosphorylation, suggesting a previously unsuspected role for wee1 in mitosis.


Time trends of some cardiovascular risk factors in Italy. Results from the Nine Communities Study. The Research Group ATS-RF2-OB43 of the Italian National Research Council.
Nine paired but independent population samples made up of men and women aged 20-59 years, located in nine areas of eight different regions of Italy, were examined in 1978-1979 (populations AB; n = 6,699) and in 1983-1984 (populations C; n = 5,548), and some cardiovascular risk factors were measured. Age-standardized mean levels of serum cholesterol were not different in the pools of populations AB and C; systolic blood pressure was lower in populations C, as compared with populations AB, by 0.9% in males and 3.0% in females; body mass index was unchanged in males and lower by 2.8% in females; the prevalence of smoking decreased 8.9% in males and increased 8.5% in females. A multivariate model including the above factors suggested, for males, a decline in the estimated coronary risk of 10.5%.


Robust registration of SAR and optical images based on deep learning and improved Harris algorithm.
Traditional algorithms can achieve good results when registering homologous images, but it cannot reach satisfying results for registration between synthetic aperture radar (SAR) and optical images. The difficulty is that the image texture information and structures of different modalities is very different which leads to poor registration results. To solve this problem, we present a robust matching framework for registration between SAR and optical images. First, a novel deep learning network is utilized to generate high quality pseudo-optical images from SAR images. Next, feature points are detected and extracted using the multi-scale Harris algorithm. Then the feature points are constructed through the gradient position orientation histogram method. Finally, the actual position of the feature points will be reconstructed through a feedback mechanism for matching. Experimental results demonstrate its superior matching performance with respect to the state-of-the-art methods.


Isolation and initial characterization of human glioblastoma cells resistant to photodynamic therapy.
Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma. The main problem with all oncological treatments, including PDT, is the presence of resistant cells. The objective of this study was to isolate and perform an initial characterization of human glioblastoma cells resistant to PDT employing methyl-5-aminolevulinic acid. We obtained resistant cells from the T98 G cell line. Resistant populations accumulated less photosensitizer, formed spheroids of higher number of cells, had higher tumorigenic capacity, and expressed higher mRNA levels of fibroblastic growth factor receptor (FGFR), epidermal growth factor receptor (EGFR) and β-platelet-derived growth factor receptor (βPDGFR) than parental cells. The studies of glioblastoma resistance to PDT would help to better understand the causes of tumor recurrence after PDT and to develop new therapeutic proposals in this field of oncology.


Adequacy of child anthropometric indicators for measuring nutritional stress at population level: a study from Niakhar, Senegal.
To compare the responsiveness of different anthropometric indicators for measuring nutritional stress among children in developing countries. Growth was studied within 6-month intervals in a rural Senegalese community during one dry and two rainy (hungry) seasons. Responsiveness was defined as the change divided by the standard deviation of each anthropometric indicator. Contrast was defined as the difference in responsiveness between dry and rainy seasons. The study was conducted in Niakhar, a rural area of Senegal under demographic surveillance, with contrasted food and morbidity situations between rainy and dry seasons. Some 5000 children under 5 years of age were monitored at 6-month intervals in 1983–1984. The present analysis was carried out on a sub-sample of children aged 6–23 months with complete measures, totalling 2803 children-intervals. In both univariate and multivariate analysis, mid-upper arm circumference was found to be more responsive to nutritional stress than the commonly used weight-for-height Z-score (contrast = -0.64 for mid-upper arm circumference v. -0.53 for weight-for-height Z-score). Other discriminant indicators were: muscle circumference, weight-for-height, BMI and triceps skinfold. Height, head circumference and subscapular skinfold had no discriminating power for measuring the net effect of nutritional stress during the rainy season. The use of mid-upper arm circumference for assessing nutritional stress in community surveys should be considered and preferred to other nutritional indicators. Strict standardization procedures for measuring mid-upper arm circumference are required for optimal use.


Surgical management of chylopericardium and chylothorax in a patient with Behçet's disease.
Behçet's syndrome is a chronic multisystem inflammatory disease characterised classically by recurrent oral and genital ulcers with ocular lesions. It can affect blood vessels of all sizes, but involves veins more commonly than arterie. The presence of chylothorax in Behçet's syndrome is rare, with only a few cases cited in the literature. The most likely pathogenesis is SVC thrombosis with obstruction of the orifice of the thoracic duct resulting in leakage of chyle from the pleural lymphatics into the pleural space. The majority of the previously reported cases were managed medically without surgical intervention. We believe that this report describes the first use of surgery to ligate the thoracic duct and create a pericardial window in a Behçet's syndrome with chylothorax and chylopericardium.


Comparison of hemostatic dressings for superficial wounds using a new spectrophotometric coagulation assay.
Due to demographical changes the number of elderly patients depending on oral anticoagulation is expected to rise. Prolonged bleeding times in case of traumatic injuries represent the drawback of these medications, not only in major trauma, but also in superficial wounds. Therefore, dressings capable of accelerating coagulation onset and shortening bleeding times are desirable for these patients. The hemostatic potential and physical properties of different types of superficial wound dressings (standard wound pad, two alginates, chitosan, collagen (Lyostypt(®)), oxidized cellulose, and QuikClot(®)) were assessed in vitro. For this purpose the clotting times of blood under the influence of the named hemostatics from healthy volunteers were compared with Marcumar(®) or ASS(®) treated patients. For that, a newly developed coagulation assay based on spectrophotometric extinction measurements of thrombin activity was used. The fastest coagulation onset was observed for oxidized cellulose (Ø 2.47 min), Lantor alginate-L (Ø 2.50 min) and QuikClot(®) (Ø 3.01 min). Chitosan (Ø 5.32 min) and the collagen Lyostypt(®) (Ø 7.59 min) induced clotting comparatively late. Regarding physical parameters, QuikClot(®) showed the lowest absorption capacity and speed while chitosan and both alginates achieved the highest. While oxidized cellulose displayed the best clotting times, unfortunately it also revealed low absorption capacity. All tested specimens seem to induce clotting independently from the administered type of oral anticoagulant, providing the possibility to neglect the disadvantage in clotting times arising from anticoagulation on a local basis. QuikClot(®), oxidized cellulose and unexpectedly alginate-L were superior to chitosan and Lyostypt(®). Due to its additional well-known positive effect on wound healing alginate-L should be considered for further investigations.


Ligand structure-function relationships in the vitamin D endocrine system from the perspective of drug development (including cancer treatment).
It has become readily apparent to many scientists and pharmaceutical companies that the vitamin D endocrine system offers a wide array of drug development opportunities. There are already successes, as noted by 1alpha,25(OH)2D3 (Roche, and Abbott) for renal osteodystrophy and osteoporosis and 1alpha(OH)D3 (Leo, Chugai, Teijin) for renal osteodystrophy and (in Japan) osteoporosis, 1alpha,24(OH)2-24-cyclopropyl-D3 (Dovonex) and 1alpha,24(OH)2D3 (Teijin) for psoriasis, and 19-nor-1alpha,25(OH)2D2 (Abbott) for renal osteodystrophy, as well as drugs under active development. Yet there are still many important and challenging drug development frontiers, particularly in the area of cancer treatment and immune system disorders where exploration is only in the initial early stages. In addition, the application of vitamin D-related drugs in neurology and brain pathology should not be overlooked. It is to be hoped that the cellular and molecular basis for the vexing problem of analog-induced hypercalcemia will be elucidated. Given that there are believed to be over 2000 analogs of 1alpha,25(OH)2D3 already available for consideration, it is to be expected that over the next decade a significant number of new vitamin D structure-function drug development projects will be brought to conclusion.


Prevalence, Clinical Criteria and Sociodemographic Predictors of Trichomonas vaginalis Infection in Suspected Egyptian Women, Using Direct Diagnostic Techniques.
The present study aimed to determine the prevalence and associated risk factors of vaginal trichomoniasis in women referred to gynecologic clinic in Benha University Hospital, Egypt. Two hundred female patients enrolled in the study. Vaginal samples were obtained from them and examined for T. vaginalis by wet mount, Giemsa stain, Acridine orange (AO) stain and culture on modified Diamond's medium. For analysis of accuracy of the methods used, the receiver operating characteristic (ROC) curve concept with culture as a gold standard was applied. Out of 200 patients, T. vaginalis was found in 22 (11%) patients by any of the diagnostic methods used. The accuracy of AO staining comes next to Diamond's culture (AUC 0.909, sensitivity 81.8%, specificity 100%, CI 0.81-1.0) followed by Giemsa staining (AUC 0.835, sensitivity 68.2%, specificity 98.9%, CI 0.72-0.95). The wet mount was the least accurate method (AUC 0.795, sensitivity 59.1%, specificity 100%, CI 0.67-0.92). There was no significant association between potentially supposed risk factors and trichomoniasis except patients complaining of either dysuria and dyspareunia or back pain and abdominal pain. Trichomoniasis is a common disease in our community. Sociodemographic factors do not seem to affect the prevalence among different Egyptian population. For accurate diagnosis, laboratory investigation is essential. A positive wet smear is diagnostic, but negative samples should be examined by methods that are more sensitive.


[Experimental prospective cognitive study on the evaluation of connection of fatigue perception and depression among caregivers and team treating cancer patients receiving oral chemotherapy to systemic chemotherapy. Equi-Car 10 study].
The Equi-Car 10 is an spontaneous, observational study. The objective was to assess the connection of fatigue perception and depression of caregivers, oncological team and oncological patients in oral chemotherapy to intravenous The study recruited 60 patients and 60 caregivers. The study was carried out on patients with lung, breast and colon cancer requiring chemotherapy, and family members were chosen as caregivers. Patients, caregivers and doctors filled in FACT-F and Zung questionnaires at the opening day of the medical record, after three and six cycles of chemotherapy, and three months after the end of the treatment. The Zung depression and Functional Assessment of Cancer therapy-Fatigue (FACT-F) showed: (a) on patients treated with intravenous therapy showed significantly higher levels of fatigue and depression than those of patients treated with oral therapy, even when the latter were treated for advanced disease; (b) on caregivers of patients treated with systemically administered therapies showed elevated levels of Fatigue and depression which proved to be significantly higher than those of caregivers of patients treated with oral therapies, even when treated for advanced disease; (c) on three oncologist has highlighted low levels of Fatigue and depression, for both types of patients, higher for patients with systemic therapy related to the management of side effects. The results showed that cancer patients and caregivers have high levels of fatigue and depression both related to the disease stage and to the mode of drug administration. It is necessary to provide cancer patients and caregivers with appropriate psychological support and preventive programs for secondary and relapse prevention.


Effect of phentolamine on perineal muscle EMG activity in paraplegia.
The effect of the alpha-adrenergic blocking agent, phentolamine, was studied on the perineal muscle EMG in 3 paraplegic patients. The drug reduced the EMG activity in these patients. This suggests that the normal suppression of external sphincter activity during micturition might be related to a reduction in the external sphincter activity supplied by the sympathetic system.


Comparative histological analysis of the alae nasi in French bulldogs with brachycephalic obstructive airway syndrome and unaffected non-brachycephalic dogs.
Brachycephalic dogs are characterised by a short and flat nose. This cranial conformation is associated with brachycephalic obstructive airway syndrome, a respiratory syndrome primarily characterised by stenotic nares, a hyperplastic soft palate and a hypoplastic trachea, among other malformations, with secondary abnormalities resulting in upper airway obstruction METHODS: In this study, we aimed to characterise and compare the histological features of tissue samples harvested from the alae nasi of French bulldogs and non-brachycephalic dogs. Samples from the alae nasi of 11 French bulldogs and 13 non-brachycephalic dogs were collected. Four-μm-thick, paraffin-embedded sections were obtained from each tissue sample and mounted on glass slides, followed by staining with haematoxylin and eosin, periodic acid-Schiff and toluidine blue for histological examination. The only variation observed between the samples obtained from French bulldogs and those obtained from non-brachycephalic dogs concerned the presence of cartilage in the specimens. Cartilage was absent in 10 of 11 French bulldogs but present in nine of 13 non-brachycephalic dogs; this difference was statistically significant (p < 0.05). The findings of this study need further validation in future prospective studies. It would be useful to examine the entire nostril wing, to include additional brachycephalic breeds, a larger number of subjects spanning a wider age range and degree of stenotic nares severity, a larger tissue sample, and a broadening of the control group to include dolichocephalic and mesaticephalic dogs. This study found an absence of cartilage in French bulldog nare specimens compared to those from non-brachycephalic dogs. This absence of cartilage may contribute to brachycephalic obstructive airway syndrome, although histological examination of the entire wing of the nostrils is needed to confirm this hypothesis.


Pulsing microwave energy: a method to create more uniform myocardial temperature gradients.
Microwave energy has been proposed as a possible technique to create large myocardial lesions. Achieving a uniform myocardial temperature gradient during microwave ablation may prevent excessive endocardial temperatures while maintaining temperatures at depth. The goal of the current study was to examine the ability of microwave (MW) pulsing to achieve a more uniform myocardial temperature gradient. Using an in-vitro ovine endocardial model, we measured tissue temperature at 0.5-mm, 2.0-mm, and 3.5-mm depths in a circulating saline bath. MW energy was delivered at 20 W at 915 MHz for 30 seconds. Pulse configurations of 1 second on-1 second off, 3 seconds on-3 seconds off, and 5 seconds on-5 seconds off, with 30 seconds of total MW time were compared with 30-seconds continuous. Maximum temperatures at 0.5 mm were significantly lower at 63.2 +/- 5.89 degrees C for the 1-second pulse compared with 83.5 +/- 7.31 degrees C for the continuous-energy delivery. Pulse configurations 3 seconds on-3 seconds off and 5 seconds on-5 seconds off also resulted in a significantly lower surface temperature than continuous-energy delivery. However, temperature at the 2.0-mm and 3.5-mm depth created by the pulsing delivery were similar to those achieved during continuous-energy delivery. Thus, microwave pulsing achieves a lower endocardial temperature and results in a more uniform temperature gradient. These techniques may prevent the excessive endocardial damage that may result in an increased risk of thrombus formation and embolization.


Incidence of atrial fibrillation among patients with an embolic stroke of undetermined source: Insights from insertable cardiac monitors.
Prophylactic use of direct oral anticoagulants for recurrent stroke prevention in patients with embolic strokes of undetermined source is currently being investigated. It is uncertain whether the bleeding risks associated with prophylactic direct oral anticoagulants use will outweigh any stroke prevention benefit in embolic strokes of undetermined source patients who lack underlying atrial fibrillation. We determined the proportion of cryptogenic stroke patients in the CRYSTAL atrial fibrillation trial who met inclusion criteria for the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials and their atrial fibrillation incidence. Both embolic strokes of undetermined source trials impose requirements on age, modified Rankin Score, antiplatelet use, and type of infarction. Insertable cardiac monitors were used to determine the atrial fibrillation detection rates at 30 days and 3 years using Kaplan-Meier's estimates. Among 441 patients enrolled in the CRYSTAL atrial fibrillation trial, 189 (42.9%) and 236 (53.5%) met the inclusion criteria of the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials, respectively. Atrial fibrillation detection rates at 3 years among insertable cardiac monitors patients eligible for the NAVIGATE embolic stroke of undetermined source and RE-SPECT embolic stroke of undetermined source trials were 35.8% and 33.6% while detection rates at 30 days were 5.6% and 3.5%, respectively. Only half of cryptogenic stroke patients in CRYSTAL atrial fibrillation met the inclusion criteria for the ongoing embolic strokes of undetermined source trials. Approximately, two-thirds of patients with embolic strokes of undetermined source do not have any atrial fibrillation despite continuous rhythm monitoring for up to three years. The benefits of prophylactic use of direct oral anticoagulants in the absence of atrial fibrillation is unknown and therefore embolic strokes of undetermined source patients could benefit from prolonged atrial fibrillation monitoring until more robust data are available. NCT00924638. https://clinicaltrials.gov/ct2/show/NCT00924638 .


An integrated approach to evaluate acetamiprid-induced oxidative damage to tRNA in human cells based on oxidized nucleotide and tRNA profiling.
Acetamiprid is poisonous to mammals due to severe acetamiprid-induced oxidative stress that could cause mitochondrial dysfunctions, lipid and protein oxidation, inflammation, apoptosis, and DNA damage. Evidence has accumulated for the role of oxidative stress in changing structures and functions of transfer RNAs (tRNAs) by inducing tRNA cleavage, reprogramming tRNA modifications and impairing aminoacyl-tRNA synthetase editing sites. However, the impact of acetamiprid-induced oxidative stress on tRNA is still unknown. Here, we investigated the effects of acetamiprid on cell viability, reactive oxygen species (ROS) levels, DNA damage, cellular oxidized nucleotide concentrations, and oxidative damage to tRNA in HepG2 cells and LO2 cells. Acetamiprid can cause the significant increment of ROS and DNA oxidative damage. In this study, an integrated approach was established to simultaneously study the network of oxidized nucleotides and explore the tRNA oxidative damage after acetamiprid exposure. A simple and high-throughput liquid chromatography with tandem mass spectrometry (LC-MS/MS) method coupled with (trimethylsilyl)diazomethane (TMSD) derivatization was successfully developed to quantify 12 cellular oxidized nucleotides that cannot be detected using traditional detection methods because of the huge interferences from naturally abundant nucleotides. Meanwhile, the accumulation rate and the locating sites of 8-oxo-2, 7-dihydro-guanine (8-oxo-G) in tRNA were inspected using the established N-(tert-Butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) labeling-based tRNA profiling method. After acetamiprid treatment, the increment of oxidized nucleoside triphosphates is smaller than that of their corresponding mono- and diphosphates, as well as the dephosphorylated nucleosides, on account of the existence of sanitization enzymes. Several tRNA fragments, CUC[m1A]Gp, CACGp, [Cm]C[m2G]p, and DDGp, are significantly downregulated in acetamiprid-treated HepG2 cells, while only [Cm]C[m2G]p in acetamiprid-treated LO2 cells. According to the profiling results, the significantly changed fragment CUC[m1A]Gp might be caused by the oxidation of guanine (G) to form 8-oxo-G at position 15 in human tRNAphe([Gm]AA), providing more information about the effect of oxidized nucleobases on tRNA's functions.