Comparative study measuring the dilatory effect of a mydriatic device (Mydriasert(®)) versus topical drops.
To compare the mydriatic efficacy of an ophthalmic insert (Mydriasert, MY) versus phenylephrine and tropicamide (PT) eye drops. Two controlled, prospective, randomized, single-blind studies were performed. In the first study, a total of 80 eyes from 40 outpatient-clinic patients were analyzed. PT drops were applied to the right eye, and a MY device was inserted in the left eye for 30min. Time until maximal pupil dilation for each eye was then assessed. In the second study, 80 eyes from 80 patients undergoing cataract surgery were analyzed. Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery (40 patients), or a MY device was inserted one hour prior to surgery (40 patients). In the first study, MY achieved superior mydriasis compared to PT eye drops at 90min (9.04±1.33mm vs 8.78±1.37mm, P=0.012). However MY took longer than PT drops to achieve maximal dilation, and mydriasis was inferior in eyes with MY compared to PT drops at 30min (7.21±1.73mm vs 8.22±1.43mm, P<0.001), the two groups only becoming similar by 60min (8.85±1.44mm vs 8.71±1.27mm, P=0.236). In the second study, both MY and PT achieved similar levels of mydriasis at the beginning of surgery (8.75±0.76mm with MY vs 8.77±0.63mm with PT), and also at the end of surgery (7.96±1.06mm with MY vs 8.32±0.72mm with PT), with no significant difference between groups (P=0.08). MY was well tolerated and cardiovascular effects were not influenced by dilation method. MY could be a safe and efficacious alternative for mydriasis. The mydriatic effect of MY is as good as conventional PT eye drops after 60min, and is superior after 90min. MY also maintains good pupil dilation during cataract surgery.


Factors associated with speed of diagnosis, referral, and treatment in colorectal cancer.
Delay in the presentation of symptoms and in referral of patients for surgical opinion remains an important problem in colorectal cancer. Factors influencing patients to consult early include advice from close family or other associates and abdominal pain or vomiting, or both, as one of the early symptoms. More localised rectal symptoms and loss of weight are often associated with long delay. The "classic" symptom pictures are not often seen in the early stages of the disease. Few identifiable factors were associated with delay in referral for surgical opinion. Doctors who examine their patients (rectally or otherwise) refer them sooner. In the districts studied delay in instituting definitive treatment after consultant referral does not seem to be a major problem. There is some evidence that delay is associated with stage of the disease at presentation.


[Use of phisiotens for the treatment of arterial hypertension in elderly patients].
To study effectiveness and safety of physiotens in elderly patients with essential hypertension (degree 1-2). The trial enrolled 10 patients (6 males and 4 females) at the age of 60 to 75 years (mean age 66.4 +/- 3.7 years) with untreated or ineffectively treated essential hypertension (degree I-II by WHO classification). The disease stood for 17 +/- 5.3 years. Physiotens was given for 2 weeks in a single daily dose 0.2-0.4 mg. 24-h blood pressure monitoring, standard neuropsychological examination, echoCG, assessment of quality of life (Visual Analog Scale, Disability Scale) were performed before and after the treatment. Physiotens significantly reduced systolic and insignificantly diastolic pressure in daytime and at night; improved memory and thinking; 24 weeks of the treatment led to a decrease in left ventricular myocardium mass (by 13%, on the average) and in the thickness of left ventricular walls (by 7% on the average) as well as in life quality. Long-term physiotens treatment of elderly patients with mild and moderate hypertension provides a fall in day and night arterial pressure, regression of left ventricular myocardium mass, improves quality of life, memory and thinking.


[Detoxifying effect of RNA].
The documented facts are presented concerning the detoxifying effect of NaRNA when injected together with adsorbed DPT vaccine, TAB-tetanus vaccine and typhoid vaccine with sextitoxoid. The intraperitoneal and oral administration of the preparation of RNA was shown to protect rodents from the toxic effect of the vaccines. In these experiments the tests were made to determine the following characteristics: LD50 of the vaccine, survival time, the change of body weight, the spleen index, efficiency, food and water consumption. A decrease in the toxicity of the prophylactic preparations was not accompanied by a decrease in vaccinal immunity.


Recruitment of additional brain regions to accomplish simple motor tasks in chronic alcohol-dependent patients.
Chronic alcohol-dependent patients (ALC) exhibit neurocognitive impairments attributed to alcohol-induced fronto-cerebellar damage. Deficits are typically found in complex task performance, whereas simple tasks may not be significantly compromised, perhaps because of little understood compensatory changes. We compared finger tapping with either hand at externally paced (EP) or maximal self-paced (SP) rates and concomitant brain activation in ten pairs of right-hand dominant, age-, and gender-matched, severe, uncomplicated ALC and normal controls (NC) using functional magnetic resonance imaging (fMRI). Mean tapping rates were not significantly different in ALC and NC for either task, but SP tapping variances were greater in ALC for both hands. SP tapping was more rapid with dominant hand (DH) than non-dominant hand (NDH) for both groups. EP and SP tapping with the non-dominant hand demonstrated significantly more activation in ALC than NC in the pre and postcentral gyri, inferior frontal gyrus, inferior parietal lobule, and the middle temporal gyrus. Areas activated only by ALC (not at all by NC) during NDH tapping included the inferior frontal gyrus, middle temporal gyrus, and postcentral gyrus. There were no significant group activation differences with DH tapping. No brain regions activated more in NC than ALC. SP tapping in contrast to EP activated fronto-cerebellar networks in NC, including postcentral gyrus, anterior cingulate, and the anterior lobe and vermis of the cerebellum, but only parietal precuneus in ALC. These findings with NDH finger tapping support previous reports of neurocognitive inefficiencies in ALC. Inferior frontal activation with EP in ALC, but not in NC, suggests engagement of regions needed for planning, organization, and impulse regulation; greater contralateral parietal lobe activation with SP in ALC may reflect right hemispheric impairments in visuospatial performance. Contrasting brain activation during SP and EP suggests that ALC may not have enlisted a fronto-cerebellar network as did NC but rather employed a higher order planning mode by recruiting parietal lobe functions to attain normal mean finger tapping rates. Elucidation of the compensatory neural mechanisms that allow near normal performance by ALC on simple tasks can inform functional rehabilitation of patients in recovery.


Development of an Early Prediction Model for Subarachnoid Hemorrhage With Genetic and Signaling Pathway Analysis.
Subarachnoid hemorrhage (SAH) is devastating disease with high mortality, high disability rate, and poor clinical prognosis. It has drawn great attentions in both basic and clinical medicine. Therefore, it is necessary to explore the therapeutic drugs and effective targets for early prediction of SAH. Firstly, we demonstrate that LCN2 can effectively intervene or treat SAH from the perspective of cell signaling pathway. Next, three potential genes that we explored have been validated by manually reviewed experimental evidences. Finally, we turn out that the SAH early ensemble learning predictive model performs better than the classical LR, SVM, and Naïve-Bayes models.


Comparison efficiency of the artificial intelligence methods for the diagnosis of Acid - base and anion gap disorders.
Diagnosis of the most complicated disorders in acid-base status and accompanying electrolyte balance creates a lot of troubles for practicing physicians. The purpose of our study was to create and compare: 1) an artificial neural network, 2) genetic program, 3) fuzzy-neural system that can diagnose acid-base disorders, based on a set of laboratory gasometric and electrolyte measurements. We took into account 7 single acid-base disorders, 11 double acid-base disorders and 6 triple complicated disorders with accompanying anion gap alterations. We prepared a set laboratory measurements consisting of 250 results for training and the same number of results for testing the program. Finally, the efficiency of presented artificial intelligence (AI) methods has been described and compared.


Cytotoxic ent-kaurane diterpenoids from Isodon henryi.
Chromatographic fractionation of the extract of Isodon henryi resulted in the isolation of seven new ENT-kaurane diterpenoids, named minheryins A-G (1-7), together with the six known ENT-kaurane diterpenoids leukamenin F (8), excisoidesin (9), leukamenin E (10), wangzaozin A (11), pseurata A (12), and racemosin A (13), which were elucidated by spectroscopic analysis. Compounds 7-13 were tested for their cytotoxicity against K562 and HepG2 cell lines, and they all exhibited significant activities with IC50 values<0.50 microg/mL. Isolates 1-5 were evaluated against the K562 cell line, and only 3 showed weak activity.


Phosphorous acid and urea: valuable sources of phosphorus and nitrogen in the hydrothermal synthesis of ammonium-thorium phosphates.
Microcrystals of the first ammonium-thorium phosphates, (NH 4) 2Th(PO 4) 2.H 2O (tetragonal, I4 1/ amd, a = 7.0192(4) A, c = 17.9403(8) A) and NH 4Th 2(PO 4) 3 (monoclinic, C2/ c, a = 17.880(6) A, b = 6.906(1) A, c = 8.152(2) A, beta = 104.39(2) degrees ) were hydrothermally obtained from a Th(NO 3) 4-CO(NH 2) 2-H 3PO 3-H 2O system ( T = 180 degrees C). In both cases, the structure consists of a three-dimensional framework with PO 4 tetrahedra coordinated to Th atoms (ThO n polyhedra, where n = 8 or 9, for the tetragonal or monoclinic phase, respectively). The ammonium ions (and water molecules) are located in the tunnels.


Charge separation promoted activation of molecular oxygen by neutral gold clusters.
Gold nanoparticles and sub-nanoparticles famously act as highly efficient and selective low-temperature oxidation catalysts with molecular oxygen, in stark contrast to the nobility of the bulk phase. The origins of this activity and the nature of the active species remain open questions. Gas-phase studies of isolated gold clusters hold promise for disentangling these problems. Here we address the interaction of neutral gold clusters (Au(n); 4 ≤ n ≤ 21) with molecular oxygen by probing the highly characteristic O-O vibrational stretch frequencies. This reveals that for selected cluster sizes the oxygen is highly activated with respect to the free moiety. Complementary quantum chemical calculations provide evidence for substantial electron transfer to the O(2) unit and concomitant rearrangement of the parent gold cluster structure upon binding and activation. This gives evidence for a model of the interaction between neutral gold clusters and molecular oxygen.


The function of the ACE2/Ang(1-7)/Mas receptor axis of the renin-angiotensin system in myocardial ischemia reperfusion injury.
Angiotensin-converting enzyme 2(ACE2) is a critical element of the renin-angiotensin system (RAS), which can convert angiotensin (Ang)II to Ang(1-7), followed by binding Mas receptor (MasR) and subsequently produces cardioprotective effects through various signal transduction pathways. It has been discovered in research that activation of the RAS contributes a crucial influence during the myocardial ischemia reperfusion injury (MIRI) development. The features of ACE2, Ang(1-7), and MasR, as well as the function of the ACE2/Ang(1-7)/MasR axis in MIRI, are discussed in our review, with the therapeutic potential of this axis as a new treatment option for MIRI patients shown. To retrieve a thorough collection of studies, we performed a search in PubMed using the following combination of keywords: (ACE2) or (Ang1-7) or (Mas receptor) and (Myocardial Ischemia reperfusion injury). The time limits used for the search were 1986 to 2021. In total, 367 articles were included. Titles and abstracts of articles were screened for relevance, and all relevant articles published in English were included. ACE2, a prominent member of the RAS, performs a crucial regulatory function in the cardiovascular system. ACE2 regulates the RAS inversely mainly by hydrolyzing the harmful AngII to the beneficial Ang(1-7). Increasing or activating ACE2 or Ang(1-7) may help prevent and treat MIRI. However, additional research into the specific processes behind the ACE2/Ang(1-7)/MasR axis in MIRI is necessary, as well as the performance of additional in-depth studies to go from basic research to clinical translation.


Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia.
Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm l-1 when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis (CASA). When transferred from an isotonic solution (330 mOsm l-1 ) to a hypotonic solution (290 mOsm l-1 ), cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4'-diisothiocyanatostilbene-2,2'- isulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed ClC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and ClC-3 expression levels (especially in the neck) than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia.


Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Attenuates the Development of Right Ventricular Dysfunction in Monocrotaline-induced Pulmonary Hypertensive Rats.
Highly concentrated carbon dioxide (GO2) is useful for treating ischemic diseases. Therefore, we investigated whether treatment with a few micrometers of CO2 molecules, atomized by two fluid nozzles (CO2 mist), could attenuate the development of right ventricular (RV) dysfunction in pulmonary hypertensive rats. Six-week-old male Wistar rats were divided into three groups: one that received injected saline; a second that received subcutaneous monocrotaline (MCT; 60 mg/kg) without treatment (PH-UT) group; and a third that received MCT with CO2 mist treatment (PH-CM) after MCT administration. The lower body of each rat was encased in a polyethylene bag, filled with the designated gaseous agent via a gas mist generator, for 30 minutes daily. Hemodynamics and cardiac function were measured at 28 days after beginning MCT administration. Protein levels were measured by western blotting. Rats that received MCT without treatment began to die within 3-4 weeks of the initial administration. However, treatment with CO2 mist extended the survival period of rats in that group. At 28 days after MCT administration, the hemodynamic status, such as the blood pressure and heart rate, involved with left ventricular function, of rats in the PH-UT group were similar to those of rats in the PH-CM group. However, MCT-induced RV weight and RV dysfunction were significantly attenuated by treatment with CO2 mist. Both RV phosphorylated endothelial nitric oxide synthase and heat shock protein 72 levels increased significantly in the PH-CM group, compared to the PH-UT group. Percutaneous CO2 mist therapy may alleviate RV dysfunction in patients with pulmonary hypertension.


Prone-lateral access to the lumbar spine: single-level corpectomy with approach discussion.
The lateral lumbar interbody fusion has evolved as newly envisioned access corridors become feasible with technological advances. Prone lateral access has evolved as a single-access approach to combine the benefits of minimally invasive surgery with direct and indirect decompression of the neural elements with synergistic anterior and posterior column correction. In this video, the authors discuss the pearls, pitfalls, and adjuvant technologies they use in a high-volume prone lateral center via case demonstration of a prone lateral corpectomy. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2216.


Outcomes of parenting interventions for child conduct problems: a review of differential effectiveness.
This review integrates findings from studies formally testing moderators of parenting interventions targeting child conduct problems from ages 1 to 10 with a focus on baseline child problem behavior, sociodemographic risks, and family process risks as moderators. The review examines whether differential effectiveness has been found for individuals at higher versus lower risk across the body of moderator studies of parenting interventions. We conclude that greater problematic child behavior at baseline may, in some cases, be associated with greater benefit from parenting interventions. None of these studies reviewed found reduced effects for those with higher baseline child problem behavior. With regard to sociodemographic and family process risks as moderators, findings are less consistent; however, on the whole, the collection of studies suggests equal effectiveness across levels of risk, with reduced effects for those at higher risk rarely demonstrated. Implications of these conclusions for future research and intervention efforts are discussed.


Different programs of gene expression are associated with different phases of the 24h and sleep-wake cycles.
The Fos and Jun proteins are encoded by proto-oncogenes acting as immediate early genes in that they are rapidly induced by different kinds of stimuli in the nervous system. These two proteins bind to DNA regulating gene transcription, and thus determining the specificity of the neuronal response to the applied stimulation. We investigated whether the expression of these genes undergoes a variation during 24h in the absence of exogenous stimulation. Male Wistar adult (200 gr. body weight) rats, kept under a 12h/12h light-dark cycle, were sacrificed every 4h starting at 0700. The expression of c-fos, c-jun and jun B mRNAs was studied in six different brain areas by means of Northern blot hybridization, c-fos expression was also studied with in situ hybridization and immunohistochemistry. In basal conditions c-fos expression displayed a highly significant spontaneous oscillation, with the highest level during the darkness hours and the lowest during the light hours. Parallel levels of jun B expression were found in the cortex and striatum, whereas c-jun mRNA remained constantly high throughout 24 h. The periodicity of c-fos and jun B oscillation persisted also when the animals were exposed for 6 days to constant (24h/24h) light or darkness. Such oscillation could instead be inverted by manipulating the rest-activity cycle, i.e. keeping the animals awake during the light hours and allowing them to sleep during the dark hours. We then verified whether the expression of fos and jun could be correlated with states of wakefulness (W) and sleep (S), monitored with EEG recording under behavioral control.(ABSTRACT TRUNCATED AT 250 WORDS)


Attitudes toward orthorexia nervosa relative to DSM-5 eating disorders.
A pattern of disordered eating involving a pathological fixation with healthy food consumption, labeled orthorexia nervosa (ON), has recently generated attention; however, research has not yet investigated perceptions of ON-related behaviors. This study examined potential stigmatization of ON, compared with DSM-5 ED diagnoses. Participants (N = 505) were randomly assigned to read a vignette depicting a woman with anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), or ON. They then answered questions about the individual depicted in the vignette. A series of MANOVAs investigated whether opinions and beliefs about the person depicted varied as a function of the disorder described in the vignette. Individuals with ON were perceived as less likely to "improve with treatment" than individuals with BN, and less likely to "pull themselves together," than individuals with BED. Individuals with ON and AN were viewed as "hard[er] to talk to" and more of a "danger to others" compared with individuals with BED. ON was viewed as less distressing, less likely to evoke sympathy, and more acceptable than the other disorders. Finally, "poor living choices" were perceived as contributing more substantially to ON. Participants' attributions of various personality characteristics did not differ based on ED diagnosis. Results suggest that ON is viewed as less severe, more desirable, and more often the result of personal life choices. However, findings also imply that ON is associated with stigma, similar to DSM-5 EDs. These negative attitudes might reinforce ON behaviors, and limit awareness of their potential complications.


The Influence of Epicardial Fat and Nonalcoholic Fatty Liver Disease on Heart Rate Recovery in Metabolic Syndrome.
Epicardial adipose tissues reflecting visceral fat accumulations of the heart are associated with metabolic syndrome (MetS) and can be a predictor of other cardiometabolic diseases. It can adversely influence autonomic nervous system (ANS) of heart. Heart rate recovery (HRR) is an easy method for measuring ANS dysfunction. The purpose of this study was to determine whether epicardial fat thickness (EFT) and nonalcoholic fatty liver disease (NAFLD) are related to HRR in patients with MetS. We enrolled 772 consecutive patients from a health-screening center who underwent abdominal ultrasonography, treadmill test, and cardiac echocardiography. EFT using echocardiography and HRR by symptom-limited exercise testing was assessed. According to the presence of MetS and NAFLD, patients were classified into the four groups. In NAFLD patients, EFT was higher and HRR was lower, especially in patients with MetS and NAFLD, compared to non-MetS participants without NAFLD (MetS with NAFLD, EFT 7.5 ± 4.4 mm, HRR 31.9 ± 12.7; MetS without NAFLD, EFT 4.9 ± 3.0 mm, HRR 39.5 ± 11.1; non-MetS with NAFLD, EFT 5.9 ± 3.6 mm, HRR 36.6 ± 12.7; and non-MetS without NAFLD, EFT 4.4 ± 3.5 mm, HRR 43.4 ± 14.5, p < 0.001). Patients with severe liver steatosis (LS) showed significantly higher EFT than those with moderate LS (14.2 ± 2.0 vs. 7.5 ± 3.1 mm, P < 0.001), and EFT was positively correlated with severity of LS (r = 0.431, P < 0.001). HRR was significantly correlated with EFT (r = -0.386, P < 0.001) and severity of LS (r = -0.324, P < 0.001). EFT and NAFLD were significantly correlated with HRR in patients with MetS and they may be highly related to increased cardiovascular risk. These results suggest a cross-link among EFT, NAFLD, and cardiac autonomic dysfunction in patients with MetS.


Heritability of milk casein and genetic and phenotypic correlations with production traits.
Individual milk samples were obtained monthly from November 1979 to November 1981 from approximately 2,800 Holstein cows in 63 herds enrolled in the Quebec Dairy Herd Analysis Service. These milk samples were analyzed for fat, total protein, casein, and serum protein. After editing, the data comprised 2,813 lactations representing 109 sires. By approximate maximum likelihood procedures, the model included herd (absorbed), year-month, and parity fixed effects, and sire and error random effects. Lactation casein yield increased with advancing parity to parity five and then decreased slightly. Lactation casein percent and number (percent casein in protein) declined until parities four and three, respectively, and essentially remained constant thereafter. Lactation casein yield was high for lactations initiated during winter months as opposed to summer months. No seasonal trend was apparent for casein percent or number. Heritabilities for lactation casein yield, percent, and number were .11, .26, and .08. Genetic and phenotypic correlations of casein yield with milk, fat, and protein yields were large and positive. Genetic correlation of casein percent with milk yield was negative (-.76) but positive (.96) with protein percent. Genetic correlations involving casein number tended to be small.


Core substructure of the hemiellipsoidal phycobilisome from the red alga Porphyridium cruentum.
The allophycocyanin core of hemiellipsoidal phycobilisomes from the red alga, Porphyridium cruentum, was isolated by chromatography on hydroxylapatite and subsequent density gradient centrifugation. Electron microscopy of negatively stained core complexes revealed a tricylindrical structure with a width of 21 to 23 nm in face view and a depth of 12 to 14 nm in side view. Fluorescence emission spectra of these complexes were similar to those of whole phycobilisomes confirming the presence of the two "terminal energy acceptors" allophycocyanin B (APB) and the high molecular linker polypeptide LCM. The polypeptide composition analyzed by SDS-PAGE showed the "anchor" polypeptide LCM, alpha AP, alpha APB, beta AP subunits, a low molecular weight linker with M(r) 13,500 and a blue-colored polypeptide of M(r) 19,800. A complex containing APB could be isolated from a "trimeric" allophycocyanin fraction of the density gradient by agarose gel electrophoresis in the presence of ampholytes. This complex shows a polypeptide composition of (alpha APB alpha AP2 beta AP3).L13.5C and contributes to the core with 30 to 35% of total "trimers". In comparison to the allophycocyanin cores from hemidiscoidal phycobilisomes of cyanobacteria and red algae, all data concerning the core of the hemiellipsoidal phycobilisomes from Porphyridium cruentum strongly suggest that there is no increase in size but an increase in its APB content. A model comprising the allophycocyanin core and the membrane integral photosystem II particles presents the structural and possible functional consequences of the results.


Secure top most significant genome variants search: iDASH 2017 competition.
One of the 3 tracks of iDASH Privacy & Security Workshop 2017 competition was to execute a whole genome variants search on private genomic data. Particularly, the search application was to find the top most significant SNPs (Single-Nucleotide Polymorphisms) in a database of genome records labeled with control or case. In this paper we discuss the solution submitted by our team to this competition. Privacy and confidentiality of genome data had to be ensured using Intel SGX enclaves. The typical use-case of this application is the multi-party computation (each party possessing one or several genome records) of the SNPs which statistically differentiate control and case genome datasets. Our solution consists of two applications: (i) compress and encrypt genome files and (ii) perform genome processing (top most important SNPs search). We have opted for a horizontal treatment of genome records and heavily used parallel processing. Rust programming language was employed to develop both applications. Execution performance of the processing applications scales well and very good performance metrics are obtained. Contest organizers selected it as the best submission amongst other received competition entries and our team was awarded the first prize on this track.


Focal fatty infiltration of the liver: analysis of prevalence and CT findings in children and young adults.
Focal fatty infiltration of the liver, a benign entity that can be confused with a malignant lesion, is well characterized in adults but not in children. The goal of this study was to determine by CT the prevalence and characteristics of focal fatty infiltration in children and young adults. We retrospectively analyzed 305 consecutive contrast-enhanced abdominal CT examinations of 218 children and young adults with no known liver disease, performed during 2 years at our institution, to identify focal fatty infiltration of the liver. The imaging criterion for focal fatty infiltration of the liver on helical CT was a geometric or ovoid low-attenuation area adjacent to the falciform ligament, gallbladder fossa, or porta hepatis. If a patient's findings met the CT criterion for focal fatty infiltration of the liver, all previous abdominal CT and MR imaging examinations performed for that patient were reviewed to assess the evolution of focal fatty infiltration of the liver. Of 218 children and young adults, 20 (9.2%) met the CT criterion for focal fatty infiltration of the liver. In our population, focal fatty infiltration of the liver was identified only adjacent to the falciform ligament. The prevalence of focal fatty infiltration of the liver increased significantly with advancing age: 0% for ages 1 month-4 years; 7.3% for 5-9 years; 10.2% for 10-14 years, and 25.6% for 15-19 years (p < 0.0001). Focal fatty infiltration of the liver was identified in 9.2% of patients in our population, and occurrence of this lesion in children increases significantly with advancing age. However, focal fatty infiltration of the liver is uncommon in infants and young children and should be a diagnosis of exclusion.


The Influence of Health Equity on Patient Outcomes in Orthopaedics.
Health equity has become both a national and international health priority when addressing health disparities that influence health outcomes across all patient populations. Orthopaedic nurses play a critical role in advancing health equity among orthopaedic patients when it comes to ensuring orthopaedic patients have fair and just opportunities to achieve their best state of musculoskeletal health. For health equity to be realized by the specialty of orthopaedics and the orthopaedic patient populations being served, it is important for the orthopaedic nurse to be involved in community-based partnerships, research opportunities, and health policy initiatives that focus on the advancement of health equity for all populations.


[The innate antiretroviral defense of human cells, based on the DNA editing].
The editing process may play an essential role in the antiviral cell defense. The human cytidine deaminase APOBEC3G, that catalyses the deoxycytidine to deoxyuridine deamination reaction in the reverse transcript of the HIV-1 genome, leads to instability of the viral DNA, if only HIV-1 virion is defective and lacks the Vif protein. This mechanism has an affect on G-A hipermutation appearing in the provirus DNA and defective HIV-1 viral RNA, yielded in infected cell. Such hipermutation has previously been discovered in the viral HIV-1 genome, produced in peripheral blood mononuclears that were long-term cultured after collection from infected patient. Probably, the deamination reaction that is inhibited in the wild type HIV-1 by the Vif protein, occurs rarely during infection and thus increases viral diversity and drug's resistance. In this review, we present the results of latest studies concerning the mechanism of viral DNA deamination, specifity of this process and APOBEC3G - HIV-1 Vif interactions, that may be useful in designing the new anti-HIV therapies.


Comparison of the serum neutralization test and a competitive enzyme-linked immunosorbent assay for the detection of antibodies to vesicular stomatitis virus New Jersey and vesicular stomatitis virus Indiana.
A competitive enzyme-linked immunosorbent assay (C-ELISA) for the detection of antibodies against vesicular stomatitis virus New Jersey (VSV-NJ) and vesicular stomatitis virus Indiana (VSV-IN) was compared with the serum neutralization test (SNT) using 1,106 serum samples obtained from dairy cattle on sentinel study farms in the Poás region of Costa Rica. Kappa coefficients between the C-ELISA and the SNT were 0.8871 (95% confidence interval [CI]: 0.8587-0.9155) and 0.6912 (95% CI: 0.6246-0.7577) for the VSV-NJ and VSV-IN tests, respectively. These results indicate good to excellent agreement between the 2 tests under these conditions.


Polymorphisms in the transcription factor NRF2 and forearm vasodilator responses in humans.
Oxidative stress is integral to the development of endothelial dysfunction and cardiovascular disease. As NRF2 is a key transcription factor in antioxidant defense, we aimed to determine whether polymorphisms within the promoter region of the gene encoding NRF2 (NFE2L2) would significantly modify vasodilator responses in humans. Associations between the -653A/G (rs35652124), -651G/A (rs6706649), and -617C/A (rs6721961) polymorphisms within the NFE2L2 promoter and vascular function were evaluated in healthy African-American (n=64) and white (n=184) individuals. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography at baseline and in response to incremental doses of bradykinin or sodium nitroprusside. Forearm vascular resistance (FVR) was calculated as the mean arterial pressure/FBF. In African Americans, -653G variant allele carriers had significantly lower FBF and higher FVR under basal conditions as well as in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). In whites, although no significant associations were observed with the -653A/G genotype, -617A variant allele carriers had significantly higher FVR at baseline and in response to bradykinin or sodium nitroprusside compared with wild-type individuals (P<0.05 for each comparison). The -651G/A polymorphism was not associated with vasodilator responses in either racial group. Polymorphisms within the NFE2L2 promoter were associated with impaired forearm vasodilator responses in an endothelial-independent manner, suggesting an important role of NRF2 in the regulation of vascular function in humans.


Phenolic compounds as α-glucosidase inhibitors: a docking and molecular dynamics simulation study.
Phenolic compounds possess significant biological activity. Several pieces of research emphasize the medicinal importance of phenolic compounds, including diabetes. The present study investigated the α-glucosidase inhibitory activity of phenolic compounds reported from several plants. The phenolic compounds reported in different literature were collected. Molecular docking was carried out using AutoDock Vina. Various physicochemical properties such as size, LogP, molecular complexity, hydrogen bonding properties of phenolic compounds were correlated with the binding affinities. Furthermore, MD simulation was carried out to study the structural stability of the docking complexes. A total of 155 phenolic compounds were reported from different plants. Amentoflavone showed the strongest binding affinity with α-glucosidase, much more potent than reference acarbose. The binding energy showed a good correlation with the molecular complexity, hydrogen bond donor and acceptor property and heavy atom counts of the compounds. The polarity of the surface area also showed a positive correlation with the binding affinity of the compounds. The best docking phenolic compound, amentoflavone, showed stable binding affinity and conformation during the simulation period compared to apoprotein and acarbose-docking complex. The top ten phenolic compounds, including amentoflavone, showed considerable drug-likeness properties with fewer toxicity effects. The study suggests that the amentoflavone could be a potential therapeutic drug as an α-glucosidase inhibitor and help control postprandial hyperglycemia.Communicated by Ramaswamy H. Sarma.


Prevalence of malnutrition in free living elderly people in Iran: a cross-sectional study.
The elderly are a particularly vulnerable group. Malnutrition is common and increases an old person's vulnerability to disease. We determine the prevalence of malnutrition in free living elderly people and its relationship with nutritional status and some socioeconomic conditions. Nutritional status and its relationship with socioeconomic conditions were evaluated using Mini Nutritional Assessment in free-living elderly people (n=1962 using cluster sampling, 917 male/1045 female, aged>60). Among the population, 42.7% were well nourished, 12.0% malnourished and 45.3% at risk of malnutrition. There was more malnutrition in females compared to males (13% vs. 10.8%; p<0.001), rural than urban (14.8% vs. 9.9%; p<0.001), non educated than educated (13.3% vs 6.9%; p<0.001), lonely than living with family (17.5% vs. 10.3%; p<0.001), unemployed than employed (13.3% vs. 6.3%; p<0.05), elderly on income support (Behsisty charity) compared with elderly on retirement salary, (41.7% vs. 3.3%; p<0.05). Total Mini Nutritional Assessment scores correlated significantly with length of education, age, waist circumference, and body mass index (r =0.426, -0.142, 0.355 and 0.269 respectively). This study revealed a 12% malnutrition prevalence in this elderly group, with higher percentages in special socioeconomic conditions. Health care providers need to be aware of this problem and its scope. These results reinforce the need to screen, monitor and support elderly people.


The mechanical effects of rhinoceros horned viper (Bitis nasicornis) venom on the isolated perfused guinea-pig heart.
In the guinea-pig Langendorff heart preparation, addition of 0.1 mg Bitis nasicornis venom to the perfusion solution caused transient increases in heart rate (HR) and left ventricular systolic pressure (LVSP) with peak increases at 2 min. With higher doses (0.6 and 1.4 mg), these increases were followed by the return of HR to normal, significant decreases in LVSP below control values and marked increases in left ventricular diastolic pressure. Histaminergic blockade with ranitidine reduced the positive responses. The results suggest that a venom component, possibly acting on intracellular calcium movement, could be responsible for both positive and negative effects.


Tuberculosis cure rates and the ETR.Net: investigating the quality of reporting treatment outcomes from primary healthcare facilities in Mpumalanga province, South Africa.
Tuberculosis control programs rely on accurate collection of routine surveillance data to inform program decisions including resource allocation and specific interventions. The electronic TB register (ETR.Net) is dependent on accurate data transcription from both paperbased clinical records and registers at the facilities to report treatment outcome data. The study describes the quality of reporting of TB treatment outcomes from facilities in the Ehlanzeni District, Mpumalanga Province. A descriptive crossectional study of primary healthcare facilities in the district for the period 1 January - 31 December 2010 was performed. New smear positive TB cure rate data was obtained from the ETR.Net followed by verification of paperbased clinical records, both TB folders and the TB register, of 20% of all new smear positive cases across the district for correct reporting to the ETR.Net. Facilities were grouped according to high (>70%) and low cure rates (≤ 70%) as well as high (> 20%) and low (≤ 20%) error proportions in reporting. Kappa statistic was used to determine agreement between paperbased record, TB register and ETR.Net. Of the100 facilities (951 patient clinical records), 51(51%) had high cure rates and high error proportions, 14(14%) had a high cure rate and low error proportion whereas 30(30%) had low cure rates and high error proportions and five (5%) had a low cure rate with low error proportion. Fair agreement was observed (Kappa = 0.33) overall and between registers. Of the 473 patient clinical records which indicated cured, 383(81%) was correctly captured onto the ETR.Net, whereas 51(10.8%) was incorrectly captured and 39(8.2%) was not captured at all. Over reporting of treatment success of 12% occurred on the ETR.Net. The high error proportion in reporting onto the ETR.Net could result in a false sense of improvement in the TB control programme in the Ehlanzeni district.


[Metabolism of drugs. II. The factors influencing metabolic reactions].
Among the factors influencing metabolic reactions leading to inactivation of the drugs the differences resulting from properties of the specific metabolic pathways, present in various species, alterations in hepatic enzymes activity, factors influencing the degree of xenobiotics binding to proteins (albumin, lipoproteins, and alphalacid glycoprotein) should be taken into consideration. Hepatic blood flow efficiency, age, sex and diseases, hormonal regulation (mainly glucocorticosteroids and thyroid) glanol are examples of factors exerting an influence on the metabolic reactions of the organism. Important role may also be assigned to lipid-free or low protein diet.


Development of a medication review tool for community-dwelling older adults in Korea.
With the aging population, older adults are more likely to receive outpatient care. Therefore, it is necessary to identify drug-related problems (DRPs) and potentially inappropriate medications (PIMs) associated with adverse clinical outcomes in community-dwelling older adults. This study aimed to develop a medication review tool for community-dwelling older adults in Korea. We developed the tool using three steps: (i) establishment of a preliminary list by reviewing 21 existing tools, (ii) a two-round Delphi survey to evaluate clinical appropriateness and (iii) a two-round Delphi survey to evaluate applicability. The list was categorized into 23 diseases/conditions with five types of DRPs. The interventions for each item have been described. The preliminary list contained 100 items. The final list contained 81 items, including 17 general PIMs, 26 PIMs under specific disease/conditions, 16 potential drug interactions, 20 potential omissions and 2 PIMs requiring dose adjustment. We developed a disease-based explicit medication review tool that can be used in primary care. This tool would assist primary care healthcare providers in identifying inappropriate medication use, which may help reduce adverse clinical consequences in older adults. Further studies are required to validate the clinical efficacy of this tool.


Prevalence of thrombophilia and central venous catheter-associated neck vein thrombosis in 41 children with cancer--a prospective study.
This study was designed to prospectively evaluate the prevalence of thrombophilia and central venous catheter-associated neck vein thrombosis in children with cancer. Children with cancer and central lines, treated at the National Hospital in Norway, were consecutively enrolled in the study. Biochemical analysis of thrombophilia and Doppler ultrasonography of neck veins were performed at inclusion, and ultrasonography was repeated 3-5 months later. We recorded systematically positive blood-cultures and days with intravenous antibiotics. In a subgroup of 13 patients with acute lymphoblastic leukaemia, the thrombophilia parameters were re-evaluated during asparaginase therapy. Forty-one children were included in the study and observed for a mean of 266 days (range 95-569 days). Eighteen patients (44%) developed venous thrombosis (VT), visualized by Doppler ultrasonography of the catheterized vein. Some clots were transient, but blood clots with diameters > 0.5 cm (n = 11) had a tendency to remain (P = 0.14). Twelve children (29%) were classified as thrombophilic at inclusion, with elevated serum levels of homocysteine and lipoprotein (a) as the most frequent alterations. Transient thrombophilia developed in all patients during asparaginase-therapy. Within the limitations of our study, we did not find any significant correlation between thrombophilia and development of VT, nor thrombosis and infectious disease. VT develops frequently in paediatric cancer patients with central lines, but the clinical implication of this observation remains to be clarified.


Hiccups and multiple sclerosis.
Hiccups is a rare and unfamiliar presenting symptom of multiple sclerosis. Patients admitted to Ramathibodi Hospital from 1969 to 1992 who had a clinical diagnosis of multiple sclerosis were reviewed The presenting symptoms and neurological signs were analysed. The clinical features and course of the disease of cases who initially presented with intractable hiccups were studied in detail. There were 4 cases out of a total of 47 cases (8.5%) who presented with hiccups. These patients all had relapse and remission and two of them had a rather fulminant course of illness. Therefore, multiple sclerosis should be seriously considered as a possible cause of intractable hiccups. It may be of benign or malignant form. In the latter, the patients may develop quadriparesis within hours or days and respiratory failure may ensue. They usually respond well to high dose intravenous corticosteroids especially pulse methylprednisolone.


Lymphocele after renal transplantation, a medical complication.
After 50 years, the incidence of lymphocele and lymphorrhea associated with renal transplantation remains substantially high in spite of more accurate surgical technique, reduction of other complications and improvement of general outcomes. The data from the literature point to the allograft as the source of increased lymph production, which in spite of an accurate hilar lymphatics ligature, can find a transcapsular outlet. Subclinical and clinical graft rejection and inflammation greatly enhance lymph production and leakage. This mechanism may partially mediate the effects of some immunosuppressive drugs on the incidence of lymphocele.


Pelvic endometriosis: MR imaging spectrum with laparoscopic correlation and diagnostic pitfalls.
Endometriosis is a common multifocal disease involving a number of anatomic sites in the pelvis. Although laparoscopy is the standard of reference for diagnosis, magnetic resonance (MR) imaging is a noninvasive method for evaluating areas inaccessible to laparoscopy. A large endometrioma (> or = 1 cm in diameter) appears as a homogeneously hyperintense mass on T1-weighted MR images and as a low-signal-intensity mass with areas of high signal intensity on T2-weighted images. A small endometrioma may be indicated when a pelvic mass less than 1 cm in diameter is hyperintense on T1-weighted images irrespective of its appearance on T2-weighted images. Endometriosis may also manifest as multiple, homogeneously hyperintense cysts on T1-weighted images. Involvement of the alimentary tract or bladder can appear as areas of high signal intensity. Although MR imaging is limited in its ability to depict small endometrial implants and adhesions, the advantages of MR imaging over laparoscopy include the ability to characterize endometriotic lesions and to evaluate extraperitoneal sites of involvement, contents of a pelvic mass, or lesions hidden by dense adhesions. The roles of the two modalities are therefore complementary. Knowledge of the variety of MR imaging appearances of endometriosis and organ involvement within the pelvis is important for guiding a subsequent laparoscopic examination.


Use of paravertebral block anesthesia in the surgical management of breast cancer: experience in 156 cases.
To assess safety and efficacy of the regional anesthetic technique paravertebral block for operative treatment of breast cancer, and to compare postoperative pain, nausea, vomiting, and length of hospital stay in patients undergoing breast surgery using paravertebral block and general anesthesia. General anesthesia is currently the standard technique used for surgical treatment of breast cancer. Increasing hospital costs have focused attention on reducing the length of hospital stay for these patients. However, the side effects and complications of general anesthesia preclude ambulatory surgery for most patients undergoing breast surgery. In April 1994, the authors initiated the use of paravertebral block anesthesia for patients undergoing primary breast cancer surgery. A review of our early experience revealed that this regional anesthetic technique enables effective anesthesia for operative procedures of the breast and axilla, reduces postoperative nausea and vomiting, and provides prolonged postoperative sensory block that minimizes narcotic requirements. A retrospective analysis of 145 consecutive patients undergoing 156 breast cancer operations using paravertebral block and 100 patients undergoing general anesthesia during a 2-year period was performed. Anesthetic effectiveness and complications, inpatient experience with postoperative pain, nausea, vomiting, and length of stay were measured. Surgery was successfully completed in 85% of the cases attempted by using paravertebral block alone, and in 91% of the cases, surgery was completed by using paravertebral block supplemented with local anesthetic. There was a 2.6% incidence of complications associated with block placement. Twenty percent of patients in the paravertebral group required medication for nausea and vomiting during their hospital stay compared with 39% in the general anesthesia group. Narcotic analgesia was required in 98% of general anesthesia patients, as opposed to 25% of patients undergoing paravertebral block. Ninety-six percent of patients having paravertebral block anesthesia were discharged within the day of surgery, compared with 76% of patients who had a general anesthetic. Paravertebral block can be used to perform major operations for breast cancer with minimal complications and a low rate of conversion to general anesthesia. Paravertebral block markedly improves the quality of recovery after breast cancer surgery and provides the patient with the option of ambulatory discharge.


Surface finishing of glass ionomer.
To evaluate the surface roughness and staining of a glass ionomer cement when subjected to different finishing procedures. Sixty-four discs of Chem-Fil II glass ionomer cement were submitted to staining test with methylene blue by spectrophotometry and roughness test by profilometry. Four groups were evaluated: Mylar matrix (control). Sof-Lex discs, Enhance points, and diamond bur. Staining and roughness test, analyzed by ANOVA and Tukey's test, showed that the best surface was obtained when the material cured in contact with the Mylar matrix strip or when treated with Sof-Lex discs. The poorest results were obtained after using the diamond bur.


Anti-inflammatory properties of azelnidipine, a dihydropyridine-based calcium channel blocker.
Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect.


Vignettes of a pulmonary rehabilitation team.
A successful comprehensive pulmonary rehabilitation program depends on these key pieces: thorough planning, an experienced coordinator who is a patient advocate, a dedicated and supportive medical director, enthusiastic and committed team members, the use of program graduates as volunteers, and providing the essential components of pulmonary rehabilitation, which consist of assessment, patient training, exercise, psychosocial intervention, and follow-up. The patients are the most important members of the team. Their courage, dedication, and determination to make their quality of life the best it can be is truly an inspiration to all of us.


Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart.
It has been documented that dietary copper (Cu) deficiency impairs mitochondrial respiratory function, which is catalyzed by 5 membrane-bound multiple protein complexes. However, there are few reports on the simultaneous analysis of Cu effect on the subunit protein expression on all 5 protein complexes. The present study was undertaken to determine the effect of Cu deficiency on each mitochondrial respiratory complex's protein expression in rat heart tissue with western-blot analysis. Male Sprague-Dawley rats were fed diets that were either Cu adequate (6.0 microg Cu/g diet, n = 5) or Cu deficient (0.3 microg Cu/g diet, n = 5) for 5 wk. The monoclonal antibody-based western-blot analysis suggested that the protein levels of 39-kDa and 30-kDa subunits in complex I; 70-kDa and 30-kDa subunits in complex II; core I and core II subunits in complex III; and alpha and beta subunits of F1 complex in complex V in both high-salt buffer (HSB) and low-salt buffer (LSB) protein fractions from heart tissue of Cu-deficient rats did not differ from those of Cu-adequate rats. However, the protein level of cytochrome c oxidase (CCO) subunit (COX) I, COX Vb, and COX VIb subunits in complex IV (CCO) in both HSB and LSB protein fractions from heart tissue of Cu-deficient rats was lower than those of Cu-adequate rats. Collectively, these data demonstrate that Cu deficiency decreases each tested subunit protein expression of complex IV but not those of complex I, II, III, and V in mitochondrial respiratory complexes.


[Chemical destruction of sacral nerve roots by alcohol injection for the treatment of overactive bladder].
This study retrospectively reviewed the value of alcohol injection of sacral nerve roots after a lidocaine test in two indications: detrusor instability-detrusor hyperactivity syndrome and cystalgia. Single-centre retrospective study from January 1992 to March 2003. Twenty-eight patients (1 man, 27 women) were admitted to the urology department for lidocaine test injection because of detrusor hyperactivity 24 cases (idiopathic = 13, neurological = 11), and cystalgia in another 4 cases. After the lidocaine test, infiltration of the sacral nerve roots (bilateral S3) by 70% alcohol was performed in 24/28 cases. The therapeutic effect was assessed at 1 month: 14 out of 24 patients reported that they were globally improved by the alcohol injection. The mean duration of the therapeutic effect was 3.8 months. In the longer term, only one of the 14 patients initially improved did not subsequently experience deterioration of the clinical features (with a follow-up of 8 months). A second alcohol injection was performed in 5/28 patients, with a positive result in only one case (4%). 6/24 (25%) patients developed lower limb pain that resolved over 2 to 3 months; 3/24 (12%) presented immediate postoperative urinary retention (that persisted in the long term in 1 case); 1/24 (4%) presented cicatricial anal incontinence. Alcohol injection of sacral nerve roots is a simple and inexpensive technique, but is associated with morbidity, and has inconstant and only transient effects. It can only be considered exceptionally in highly selected cases when no more effective treatments are available, such as botulinum toxin injection or sacral nerve root neuromodulation.


The Diaza[184.108.40.206]fenestrane Skeleton-Synthesis of Leuconoxine Alkaloids.
Among the Aspidosperma-derived monoterpene indole alkaloids, the leuconoxine subgroup has drawn significant attention from the synthetic community during the past few years. This Minireview summarizes the hitherto six completed total syntheses of leuconoxines emphasizing the different strategies for assembling the key structural motif, an unprecedented diaza[188.8.131.52]fenestrane skeleton. In addition, the proposed biogenetic relationships within the group of these alkaloids are described.


Genotypic and phenotypic expression of vocal fold polyps and Reinke's edema: a preliminary study.
Although a great deal of research exists regarding lamina propria composition, no report exists that relates gene expression in benign laryngeal lesions to phenotypic markers. In this study, messenger RNA profiles for extracellular matrix proteins--procollagen I, collagenase, elastase, fibronectin, fibromodulin, decorin, hyaluronic acid synthase 2, and hyaluronidase--were completed on 5 polyps and 4 Reinke's edema specimens. These genotypic profiles were correlated to a videostroboscopic parameter of mucosal wave stiffness, which was used as a measurement of phenotypic expression. Polyps, characterized by stiffer mucosal waves, had higher levels of gene expression, whereas stiffer mucosal wave scores for Reinke's edema were associated with lower gene activity levels. This study supports the hypothesis that there is a relationship between genotypic expression found in polyps and Reinke's edema and phenotype as defined by a loss of or a decreased mucosal wave. The study also gives clues as to the proteins responsible for the phenotype.


Novel alternatives to extracellular vesicle-based immunotherapy - exosome mimetics derived from natural killer cells.
Exosomes are endogenous nanocarriers that can deliver biological information between cells. They are secreted by all cell types, including immune cells such as natural killer (NK) cells. However, mammalian cells release low quantities of exosomes, and the purification of exosomes is difficult. Here, nanovesicles were developed by extrusion of NK cells through filters with progressively smaller pore sizes to obtain exosome mimetics (NK-EM). The anti-tumour effect of the NK-EM was confirmed in vitro and in vivo. The morphological features of the NK-EM were revealed by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. In vitro, the cytotoxicity of the NK-EM to cancer cells (glioblastoma, breast carcinoma, anaplastic thyroid cancer and hepatic carcinoma) was assessed using bioluminescence imaging (BLI) and CCK-8 assay. For in vivo study, a xenograft glioblastoma mouse model was established. The anti-tumour activity of NK-EM was confirmed in vivo by the significant decreases of BLI, size and weight (all p < .001) of the tumour compared with the control group. Moreover, NK-EM cytotoxicity for glioblastoma cells that related with decreased levels of the cell survival markers p-ERK and p-AKT, and increased levels of apoptosis protein markers cleaved-caspase 3, cytochrome-c and cleaved-PARP was confirmed. All those results suggest that NK-EM exert stronger killing effects to cancer cells compared with the traditional NK-Exo, at the same time, the tumour targeting ability of the NK-EM was obtained in vivo. Therefore, NK-EM might be a promising immunotherapeutic agent for treatment of cancer.


CT-imaging of lesser known or seen anatomical structures of the temporal bone.
Temporal bone anatomy is complicated on CT with many normal variants, of which some are infrequently seen or lesser known. The unaware radiologist can confuse them with pathology. Other lesser known normal variations are important to report because they can cause pathology. This paper illustrates in detail how to avoid such misinterpretations of anatomical structures.


Incorporation of 14C-labelled fatty acids into the mammary-gland lipids of the lactating rabbit.
1. [1-(14)C]Stearic acid, [9-(14)C]stearic acid, [9-(14)C]palmitic acid and [9-(14)C]decanoic acid were fed to lactating rabbits, and the fatty acids of the mammary gland were separated and partially degraded. 2. Most of the (14)C recovered was located in the acids fed. Stearic acid was least efficiently absorbed; decanoic acid was the most extensively metabolized. 3. Resynthesis after degradation to C(2) units led to uniform alternate labelling in the C(2)-C(10) acids, whereas C(12)-C(18) acids had excess of (14)C at the carboxyl end. 4. Acids formed by beta-oxidation down to C(12), but not below, were also present in the mammary-gland lipids. Desaturation of the administered acids was a very minor reaction.


The amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component of American flamingo (Phoenicopterus ruber ruber).
The complete amino-acid sequence of alpha A- and beta-chains from the major hemoglobin component (HbA) of American Flamingo ( Phoenicopterus ruber ruber) is presented. The minor component (HbD) with alpha D-chains was detected in similar amounts (25%) as in chicken and pheasant hemoglobins. The comparison of American Flamingo and Greylag Goose (Anser anser) hemoglobins shows that alpha A-chains differ by 22 exchanges and beta-chains by only 4 exchanges. Two substitutions modify alpha 1 beta 1-contacts. Amino-acid replacements between American Flamingo and other bird hemoglobins are discussed.


(3,5,5,6,8,8-Hexamethyl-5,6,7,8-tetra-hydro-naphthalen-2-yl)methanol: a possible metabolite of the synthetic musk fragrance AHTN.
The title compound (AHTN-OH), C(17)H(26)O, was prepared in order to provide standard materials for the qualitative and quanti-tative analysis of environmental pollutants. The mol-ecule possesses a chiral C atom, although the structure determination was performed on racemic material, expressed in the structure as disordered chiral sites. The asymmetric unit consists of four AHTN-OH mol-ecules containing an hy-droxy group and forming a tetra-meric cyclic motif built up by four strong hydrogen bonds between these hy-droxy groups and additionally by two weak C-H⋯π inter-actions. Furthermore, these tetra-mers are linked via very weak C-H⋯π inter-actions, forming chains along the c axis.


Motherhood constellation and representational change in pregnancy.
The main aim of this study was to explore the prevalence and development of the motherhood constellation in pregnant women. The participants of the study were 162 pregnant women who were divided into three subgroups according to their gestation period (<6 months, 6-7 months, >7 months). The women were assessed using the Breakfast Interview, a microanalytic method devised by D.N. Stern (1995, 2004a). Two judges coded the transcripts of the interviews for the presence of the motherhood constellation themes using three-level rating scales. Results showed that the Life/Growth theme was the most frequent theme during pregnancy, and supported the hypothesis of a "peak" of the motherhood constellation themes around Month 6 to Month 7.


[Analysis of soil components along water channel of east route of South-to-North Water Diversion Project].
To explore the relationship between the soil components along the areas of the east route of the Southto-North Water Diversion Project and the survival situation of Oncomelania hupensis snails. Four study sites were selected along the project, and soil samples were collected to analyze the components. The amounts of components among the different study sites were compared statistically. Except zinc, sodium, and phosphorus, the contents of the soil components where the snails survived were different from those where snails were dead (t = -19.150 to 12.810, all P < 0.01). However, the logistic regression analysis did not obtain a model with statistical significance. O. hupensis snails live in the soil with adequate organic matter and neutral pH value. Along with the global warming and the operation of the South-toNorth Water Diversion Project, O. hupensis snails may survive in the northern area, and therefore, the surveillance work should be strengthened.


False aneurysm of the external iliac artery following hip endoprosthesis.
A false aneurysm developed from the external iliac artery within the pelvic cavity following total hip surgery when methylmethacrylate cement had been used to fix the cup. The aneurysm was probably caused by a cement spicule which had entered the pelvis and had come into contact with the external iliar artery.


Antidepressants and neuroplasticity.
We review the literature on the cellular changes that underlie the structural impairments observed in brains of animals exposed to stress and in subjects with depressive disorders. We discuss the molecular, cellular and structural adaptations that underlie the therapeutic responses of different classes of antidepressants and contribute to the adaptive plasticity induced in the brain by these drugs. We review results from various clinical and basic research studies. Studies demonstrate that chronic antidepressant treatment increases the rate of neurogenesis in the adult hippocampus. Studies also show that antidepressants up-regulate the cyclic adenosine monophosphate (cAMP) and the neurotrophin signaling pathways involved in plasticity and survival. In vitro and in vivo data provide direct evidence that the transcription factor, cAMP response element-binding protein (CREB) and the neurotrophin, brain derived-neurotrophic factor (BDNF) are key mediators of the therapeutic response to antidepressants. These results suggest that depression maybe associated with a disruption of mechanisms that govern cell survival and neural plasticity in the brain. Antidepressants could mediate their effects by increasing neurogenesis and modulating the signaling pathways involved in plasticity and survival.


Toric trans-scleral plugs IOL to correct aphakia with significant corneal astigmatism.
To describe the use of toric trans-plugs IOL to correct aphakia with significant corneal astigmatism. Case report and literature review. A 62-year-old man with an history of aphakia in his left eye after a traumatic cataract extraction and significant corneal astigmatism was referred to our clinic. Surgery plan was cataract remnants removal and secondary IOL implantation of toric sutureless trans-scleral plugs fixated IOL (FIL SSF, Soleko, Italy). The postoperative course was uneventful. At 12 months, the IOL was well-centered and the optic alignment remained stable with minimal total astigmatism. The e uncorrected distance visual acuity (UDVA) was 20/25 Snellen while correct distance visual acuity (CDVA) was 20/20 with a manifest refraction of -0.25-50 40° D; the patient was satisfied by the visual outcome. This novel toric trans-scleral plug fixated lens provides valuable outcomes also for astigmatic correction for a comprehensive correction of the aphakia in patients with poor zonular support and high expectations for postoperative visual quality.


Characterization of highly oriented organoclay/ poly(methyl methacrylate) moulded nanocomposites.
In the present paper, the effects of nanoparticles' content and orientation were studied on the structure, phase morphology and thermo-mechanical properties of highly oriented montmorillonite/ poly(methyl methacrylate) moulded nanocomposites. The nanocomposites were compounded using a co-rotating high-shear twin-screw extruder. Square plates were prepared by a two-stage compression-moulding process from the previously extruded materials, with the test specimens being directly machined in both parallel and perpendicular directions with respect to the plate's surface. Wide-angle X-ray diffraction (WAXD) revealed a highly-ordered structure of silicate platelets parallel to the plate's surface. Observations by transmission electron microscopy (TEM) supported this analysis, demonstrating the high anisotropy degree of the nanocomposites. Dynamic mechanical thermal analysis (DMTA) showed that the perpendicular specimens were stiffer than the parallel ones, with the presence of the oriented nanoparticles decreasing PMMA's mobility during the glass transition, although no significant differences were registered in the T(g) temperatures with increasing the amount of clay content or with orientation. Remarkable improvements regarding the fracture energy were observed for the perpendicular specimens, with the 20 wt% oMMT nanocomposite showing a fracture energy almost 10 times that of pure PMMA.


Individual predisposition to Staphylococcus aureus colonization in pigs on the basis of quantification, carriage dynamics, and serological profiles.
Previous research on Staphylococcus aureus in pigs focused on livestock-associated methicillin-resistant S. aureus (MRSA) and had a qualitative cross-sectional design. This study aimed to elucidate the frequency, load, and stability of S. aureus nasal carriage in pigs over time and investigated possible associations between carriage and immune response. Nasal swabs were collected three times weekly from 480 tagged adult pigs in 20 Danish production farms. S. aureus and MRSA were quantified on selective media by the most-probable-number method. The levels of IgG against 10 S. aureus antigens in serum were quantified in selected pigs by a Luminex assay. All the farms were positive for S. aureus and 15 for MRSA, leading to overall prevalences of persistent and intermittent carriers and noncarriers of 24, 52, and 23%, respectively. Carriage frequency and nasal loads were significantly higher on MRSA-positive farms. Logistic-regression modeling revealed the presence of individual pigs characterized by high nasal loads (>10,000 CFU per swab) and stable carriage regardless of farm- and pen-associated factors. On the other hand, the humoral response was strongly influenced by these environmental factors. The existence of a minority of shedders contributing to maintenance of S. aureus within farms opens up new perspectives on the control of MRSA in pig farming.


Electrochemical Synthesis of Mesoporous CoPt Nanowires for Methanol Oxidation.
A new electrochemical method to synthesize mesoporous nanowires of alloys has been developed. Electrochemical deposition in ionic liquid-in-water (IL/W) microemulsion has been successful to grow mesoporous CoPt nanowires in the interior of polycarbonate membranes. The viscosity of the medium was high, but it did not avoid the entrance of the microemulsion in the interior of the membrane's channels. The structure of the IL/W microemulsions, with droplets of ionic liquid (4 nm average diameter) dispersed in CoPt aqueous solution, defined the structure of the nanowires, with pores of a few nanometers, because CoPt alloy deposited only from the aqueous component of the microemulsion. The electrodeposition in IL/W microemulsion allows obtaining mesoporous structures in which the small pores must correspond to the size of the droplets of the electrolytic aqueous component of the microemulsion. The IL main phase is like a template for the confined electrodeposition. The comparison of the electrocatalytic behaviours towards methanol oxidation of mesoporous and compact CoPt nanowires of the same composition, demonstrated the porosity of the material. For the same material mass, the CoPt mesoporous nanowires present a surface area 16 times greater than compact ones, and comparable to that observed for commercial carbon-supported platinum nanoparticles.


Cushing's syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: an in vivo and in vitro study.
Cortisol secretion in adrenal Cushing's syndrome can be regulated by aberrant hormone receptors, such as gastric inhibitory polypeptide, V1 vasopressin, catecholamines, LH/human chorionic gonadotropin, and serotonin receptors. We report the case of a patient with Cushing's syndrome due to bilateral adrenal macronodular hyperplasia. Extensive in vivo testing for the presence of aberrant receptors revealed a 5-fold increase of plasma cortisol after the administration of cisapride, an agonist of the serotonin 4 (5-HT(4)) receptor. Primary cell cultures were established from adrenocortical specimens obtained at surgery, and in vitro studies also showed that cisapride determined an increase [133.7 +/- 5.5% (mean +/- SE) of baseline, considered 100%) of cortisol secretion from cultured cells. The presence of 5-HT(4) receptor transcript, and in particular of isoforms c, g, and n, was confirmed by RT-PCR, and the determination of the mRNA levels by real-time RT-PCR revealed a higher expression than in normal adrenal glands. To our knowledge, this is one of the first reports of Cushing's syndrome in which cortisol secretion is regulated mainly by the 5-HT(4) receptor, among known aberrant receptors. In addition, it is noteworthy that hypocortisolism ensued after the removal of the most enlarged adrenal gland, but the in vivo response to cisapride persisted.


[Changes in the content of total sugars present in potato tubers depending on the agrotechnical treatments].
The aim of this paper was determination of the effect of the soil tillage systems (traditional and simplified) and weed control methods for herbicides (Plateen 41,5 WG, Plateen 41,5 WG + Fusilade Forte 150 EC, Plateen 41,5 WG + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC, Barox 460 SL, Barox 460 SL + Fusilade Forte 150 EC, Barox 460 SL + Fusilade Forte 150 EC + adjuvant Atpolan 80 EC) on the content of total sugars in the edible potato tubers cv. Wiking. The statistical analysis revealed a significant effect of the soil tillage and weather conditions over the experimental years on the content total sugars. The simplified used in the tillage soil increased the content sugars, as compared with the traditional tillage. During hot and dry vegetation weather the potato tubers accumulated the least total sugars. It was stated that the content of total sugars decreased after preliminary processing (after peeling) as compared to level of sugars non-peeled potato tubers.


Remote Gating of Schottky Barrier for Transistors and Their Vertical Integration.
This paper introduces a strategy to modulate a Schottky barrier formed at a graphene-semiconductor heterojunction. The modulation is performed by controlling the work function of graphene from a gate that is placed laterally away from the graphene-semiconductor junction, which we refer to as the remote gating of a Schottky barrier. The remote gating relies on the sensitive work function of graphene, whose local variation induced by locally applied field effect affects the change in the work function of the entire material. Using Kelvin probe force microscopy analysis, we directly visualize how this local variation in the work function propagates through graphene. These properties of graphene are exploited to assemble remote-gated vertical Schottky barrier transistors (v-SBTs) in an unconventional device architecture. Furthermore, a vertical complementary circuit is fabricated by simply stacking two remote-gated v-SBTs (pentacene layer as the p-channel and indium gallium zinc oxide layer as the n-channel) vertically. We consider that the remote gating of graphene and the associated device architecture presented herein facilitate the extendibility of graphene-based v-SBTs in the vertical assembly of logic circuits.


Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells.
Diabetic nephropathy (DN) is a common complication of diabetes. Tamsulosin is a selective α1-AR antagonist. α1-AR is expressed widely in kidney tissues and has displayed its various physiological functions. However, whether Tamsulosin has affects DN is unknown. To our knowledge, this is the first time it has been examined whether Tamsulosin possesses a beneficial effect in high glucose-challenged glomerular endothelial cells (GECs). Firstly, we found that Tamsulosin reduced high glucose-induced expressions of TNF-α, IL-6, and IL-8. Secondly, Tamsulosin alleviated high glucose-induced expressions of MMP-2 and MMP-9. Thirdly, Tamsulosin inhibited the expressions of VCAM-1 and ICAM-1. Importantly, our results indicate that Tamsulosin inhibited high glucose-induced expressions of fibrosis factors such as Col-1 and TGF-β1. Additionally, we found that Tamsulosin ameliorated oxidative stress via reducing the generation of ROS and preventing the activation of p38. Mechanistically, we found that Tamsulosin attenuated high glucose-induced activation of NF-κB. Based on these findings, we conclude that Tamsulosin could attenuate high glucose-induced injury in GECs through alleviating oxidative stress and inflammatory response.


Insulin resistance and beta-cell dysfunction in aging: the importance of dietary carbohydrate.
Aging is associated with a progressive decrease in glucose tolerance. This decrease is associated with insulin resistance and beta-cell dysfunction. This study was performed to evaluate the possible role of dietary factors in the glucose intolerance of aging. Two groups of men were studied: one young (Y; n = 8; age range, 18-36 yr) and one elderly (E; n = 10; age range, 65-82 yr). Frequently sampled iv glucose tolerance tests were performed in random order: 1) during ad libitum home dietary conditions; 2) after a 3- to 5-day regimen of very high (85%) carbohydrate intake; and 3) after a 3- to 5-day regimen of low (30%) carbohydrate intake (Y only). From the frequently sampled iv glucose tolerance test data, we calculated the glucose disappearance rate (Kg) and metabolic parameters according to the minimal model method, including the insulin sensitivity index (S1) and the first and second phase beta-cell responsivity to glucose (phi 1 and phi 2). The elderly men, while eating an ad libitum diet, were less tolerant to glucose than the young [mean Kg: E = 1.5 +/- 0.2% (+/- SE) min-1; Y = 2.3 +/- 0.3% min-1; P less than 0.025], had relative insulin resistance (mean Si: Y = 6.1 +/- 1.1; E = 2.4 +/- 0.7 min-1 10(-4)/(microU/mL) [0.85 +/- 0.15 vs. 0.33 +/- 0.10 min-1 10(-4)/(pmol/L)]; P less than 0.01), and lesser second phase beta-cell responsiveness to glucose (mean phi 2: Y = 18.5 +/- 3.6; E = 8.7 +/- 2.7 (microU/mL).min-2/(mg/dL) [2390 +/- 465 vs. 1120 +/- 349 (pmol/L).min-2/(mmol/L)]; P less than 0.05). A maximum improvement in Kg and S1 occurred at 41% carbohydrate feeding in the young men, whereas in the elderly men there was a significant increase in both of these parameters while eating the very high (85%) carbohydrate diet. Thus, the difference in glucose tolerance between groups was corrected by the very high carbohydrate diet (mean Kg: Y = 2.2 +/- 0.2%; E = 2.0 +/- 0.3%/min; P greater than 0.05), as was the age-related difference in insulin sensitivity (mean S1: Y = 5.6 +/- 1.2; E = 4.4 +/- 1.3 min-1 10(-4)/(microU/mL) [0.78 +/- 0.17 vs. 0.61 +/- 0.18 min-1 10(-4)/(pmol/L)]; P greater than 0.5).(ABSTRACT TRUNCATED AT 400 WORDS)


Relationship between first-twitch depression and train-of-four ratio during sugammadex reversal of rocuronium-induced neuromuscular blockade.
The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex. The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB. The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine. If you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB.


[Simultaneous detection of Vibrio Cholerae O1 and O139 by real-time quantitative PCR].
Targeting the specific O-antigen gene cluster, a Taq-Man real-time fluorescence PCR assay was developed to detect 01 and O139 Vibrio cholera concurrently and avoid frequently occurred false positives. Two pairs of specific primers and two Taq-Man fluorescent probes respectively targeting rfbM gene of Vibrio cholerae O1 and wbfR of 0139 were designed. After optimization of conditions, the specialty and sensitivity of the detection method were evaluated and ten simulated food samples and 128 clinical samples were tested. The detection limits of Vibrio cholerae O1 and O139 were 92 CFU/ml and 116 CFU/ml, which were almost the same with the usual PCR method. The developed real-time fluorescence PCR protocol detected only Vibrio cholerae O1 and O139 and it was not affected by many normal food pathogens such as Staphylococcus aureus and Salmonella, especially Vibrio cholerae O141 which contained TCP genes and Vibrio mimicus which contained ZOT gene. The clinical detect results of the developed assay and routine culture method were exactly the same. The developed detection assay could quantitatively detect Vibrio cholerae O1 and O139 concurrently in only 3 hours, and could avoid false positive, and thus was an efficacious method for detecting Vibrio cholerae O1 and O139 and could be used in a wide area such as entry-exit inspection and quarantine, food safety detection and clinical diagnose.


Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19.
Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19. Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.


[Rhythmic inotropic phenomena in ventricular extrasystoles].
Mechanic activity of the heart was examined in 310 patients of different age groups with ventricular premature heart beat. Tetrapolar impedance rheocardiography was used to study postextrasystolic potentiation and mechanic restitution. It is shown that mechanic restitution is a sensitive indicator of heart failure. The time of complete restitution progressively increases with developing heart failure. With progression of heart failure, postextrasystolic potentiation increases. The authors describe potentiation and mechanic restitution in children. Emphasis is laid on the necessity of an analysis of postextrasystolic potentiation and mechanic restitution of heart contractility only with regard to concrete correlations between durations of the pre-extrasystolic and postextrasystolic intervals. Provided the method of determining postextrasystolic potentiation and mechanic restitution is adhered to, these indicators can be used in comprehensive assessment of heart failure.


How Sensitive is the Amide I Vibration of the Polypeptide Backbone to Electric Fields?
Site-selective isotopic labeling of amide carbonyls offers a nonperturbative means to introduce a localized infrared probe into proteins. Although this strategy has been widely used to investigate various biological questions, the dependence of the underlying amide I vibrational frequency on electric fields (or Stark tuning rate) has not been fully determined, which prevents it from being used in a quantitative manner in certain applications. Herein, through the use of experiments and molecular dynamics simulations, the Stark tuning rate of the amide I vibration of an isotopically labeled backbone carbonyl in a transmembrane α-helix is determined to be approximately 1.4 cm(-1) /(MV/cm). This result provides a quantitative basis for using this vibrational model to assess local electric fields in proteins, among other applications. For instance, by using this value, we are able to show that the backbone region of a dipeptide has a surprisingly low dielectric constant.


Identification of compound heterozygous variants in the noncoding RNU4ATAC gene in a Chinese family with two successive foetuses with severe microcephaly.
Whole-exome sequencing (WES) over the last few years has been increasingly employed for clinical diagnosis. However, one caveat with its use is that it inevitably fails to detect disease-causative variants that occur within noncoding RNA genes. Our experience in identifying pathogenic variants in the noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had been affected by severe microcephaly, is a case in point. These foetuses exhibited remarkably similar phenotypes in terms of their microcephaly and brain abnormalities; however, the paucity of other characteristic phenotypic features had made a precise diagnosis impossible. Given that no external causative factors had been reported/identified during the pregnancies, we sought a genetic cause for the phenotype in the proband, the second affected foetus. A search for chromosomal abnormalities and pathogenic copy number variants proved negative. WES was also negative. These initial failures prompted us to consider the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive disease characterised by dwarfism, severe microcephaly and neurological abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the identification of compound heterozygous variants, one being the most frequently reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A variant. Four distinct lines of evidence (allele frequency in normal populations, evolutionary conservation of the affected nucleotide, occurrence within a known mutational hotspot for MOPD1-causative variants and predicted effect on RNA secondary structure) allowed us to conclude that 29T>A is a new causative variant for MOPD1. Our findings highlight the limitations of WES in failing to detect variants within noncoding RNA genes and provide support for a role for whole-genome sequencing as a first-tier genetic test in paediatric medicine. Additionally, the identification of a novel RNU4ATAC variant within the mutational hotspot for MOPD1-causative variants further strengthens the critical role of the 5' stem-loop structure of U4atac in health and disease. Finally, this analysis enabled us to provide prenatal diagnosis and genetic counselling for the mother's third pregnancy, the first report of its kind in the context of inherited RNU4ATAC variants.


Quantifying the mechanical properties of the endothelial glycocalyx with atomic force microscopy.
Our understanding of the interaction of leukocytes and the vessel wall during leukocyte capture is limited by an incomplete understanding of the mechanical properties of the endothelial surface layer. It is known that adhesion molecules on leukocytes are distributed non-uniformly relative to surface topography (3), that topography limits adhesive bond formation with other surfaces (9), and that physiological contact forces (≈ 5.0 - 10.0 pN per microvillus) can compress the microvilli to as little as a third of their resting length, increasing the accessibility of molecules to the opposing surface (3, 7). We consider the endothelium as a two-layered structure, the relatively rigid cell body, plus the glycocalyx, a soft protective sugar coating on the luminal surface (6). It has been shown that the glycocalyx can act as a barrier to reduce adhesion of leukocytes to the endothelial surface (4). In this report we begin to address the deformability of endothelial surfaces to understand how the endothelial mechanical stiffness might affect bond formation. Endothelial cells grown in static culture do not express a robust glycocalyx, but cells grown under physiological flow conditions begin to approximate the glycocalyx observed in vivo (2). The modulus of the endothelial cell body has been measured using atomic force microscopy (AFM) to be approximately 5 to 20 kPa (5). The thickness and structure of the glycocalyx have been studied using electron microscopy (8), and the modulus of the glycocalyx has been approximated using indirect methods, but to our knowledge, there have been no published reports of a direct measurement of the glycocalyx modulus in living cells. In this study, we present indentation experiments made with a novel AFM probe on cells that have been cultured in conditions to maximize their glycocalyx expression to make direct measurements of the modulus and thickness of the endothelial glycocalyx.


Aortic Artery and Cardiac Valve Calcification are Associated with Mortality in Chinese Hemodialysis Patients: A 3.5 Years Follow-up.
This study was to investigate the relationship among aortic artery calcification (AAC), cardiac valve calcification (CVC), and mortality in maintenance hemodialysis (MHD) patients. All MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up for 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay. Totally, 110 MHD patients were involved in this study. Of which, 64 (58.2%) patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 (3.0-225.5) months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 (22.7%) patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause mortality (hazard ratio [HR]: 3.149, P = 0.025) in addition to lower albumin level and lower 25-hydroxy Vitamin D (25(OH)D) level. The presence of CVC was a significant factor associated with cardiovascular mortality (HR: 3.800, P = 0.029) in addition to lower albumin level and lower 25(OH)D level. Lateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.


Expression of the p24 silencing suppressor of Grapevine leafroll-associated virus 2 from Potato virus X or Barley stripe mosaic virus vector elicits hypersensitive responses in Nicotiana benthamiana.
The 24-kDa protein (p24) encoded by Grapevine leafroll-associated virus 2 (GLRaV-2) is an RNA-silencing suppressor (RSS), but its effect on active viral infection is unclear. Using a Potato virus X (PVX)-based expression system, we demonstrated that p24 elicits lethal systemic necrosis in Nicotiana benthamiana, sharing typical characteristics of the hypersensitive response (HR), and that NbRAR1 (a cytoplasmic Zn2+-binding protein) is involved in the PVX-p24-mediated systemic necrosis. Moreover, expression of p24 from Barley stripe mosaic virus (BSMV) vector triggered local necrosis in infiltrated patches of N. benthamiana, likely inhibiting viral systemic spread. By deletion analysis, we demonstrated that amino acids (aa) 1 to 180, which are located in the region (aa 1-188) previously shown to be necessary for p24's RSS activity, is sufficient for p24 to elicit systemic necrosis in the context of PVX infection. Using substitution mutants, we revealed that silencing-suppression-defective mutants R2A and W54A induce only a mild necrotic response; two mutants without self-interaction ability previously shown to lose or retain weak suppression function also displayed decreased pathogenicity: W149A without RSS activity elicited a mild necrotic response, whereas V162H/L169H/L170H which retains weak RSS activity was able to induce systemic necrosis, but with a 1- to 2-day delay. Taken together, p24 plays an important role in GLRaV-2 pathogenesis, triggering HR-like necrosis in N. benthamiana plants when expressed from PVX or BSMV vector; both the silencing suppression and self-interaction are crucial for p24's pathogenicity activity, and the region of p24 for determining systemic necrosis is mapped to aa 1-180.


LOCALIZATION OF CAROTENOID PIGMENT IN THE CYTOPLASMIC MEMBRANE OF XANTHOMONAS JUGLANDIS.
Stephens, William L. (University of California, Davis), and Mortimer P. Starr. Localization of carotenoid pigment in the cytoplasmic membrane of Xanthomonas juglandis. J. Bacteriol. 86:1070-1074. 1963.-The kinetics of release of carotenoid pigment from cells of Xanthomonas juglandis, disrupted by sonic or ballistic treatment, showed the pigment to be localized in the cell envelope. Cells subjected to ballistic disintegration released carotenoid at a rate identical to that of a membrane component (reduced nicotinamide adenine dinucleotide oxidase) and at a slightly higher rate than a wall component (hexosamine). Thus, the membrane portion of the cell envelope is the most probable locus of the unique carotenoid pigment of X. juglandis.


Smart Nanoformulation Based on Stimuli-Responsive Nanogels and Curcumin: Promising Therapy against Colon Cancer.
Curcumin (CUR) has gained much attention for its widely reported anticancer effect; however, its clinical use is restricted due to its low water solubility and, consequently, its poor bioavailability. Here, we report on the use of a nanoformulation of CUR with cationic nanogels for colon cancer therapy. Cationic stimuli-sensitive nanogels were prepared using a scale-up polymerization methodology based on surfactant-free emulsion polymerization of N,N'-diethylaminoethyl methacrylate (DEAEM) and poly(ethyleneglycol) methacrylate (PEGMA). The obtained nanogels showed a homogeneous size distribution (from 51 to 162 nm, polydispersity index (PDI) < 0.138) and exhibited a spherical form and core-shell morphology as confirmed by dynamic light scattering and electron microscopy, respectively. Nanogels were responsive to and degradable by variations of pH, temperature, or the redox environment, depending on the cross-linker used in the synthesis. Nanogels cross-linked with bis(acryloyl)cystamine incubated in a buffer (pH 7.4) containing 3 mM glutathione degraded in 60 min, while nanogels cross-linked with a divinylacetal cross-linker degraded in 10 min (pH ≤ 6). Nanoformulations of nanogels with CUR were stable as tested up to 30 days at physiological conditions. In vitro studies of the human colon cancer cell line (HCT-116) showed a synergistic effect of CUR and the degradable nanogels. Further, in vivo acute cytotoxicity tests of empty nanogels in mice demonstrate their potential as CUR nanocarriers for colon-anticancer therapies.


A fast isocratic liquid chromatography method for the quantification of xanthophylls and their stereoisomers.
A fast isocratic liquid chromatography method was developed for the simultaneous quantification of eight xanthophylls (13-Z-lutein, 13'-Z-lutein, 13-Z-zeaxanthin, all-E-lutein, all-E-zeaxanthin, all-E-canthaxanthin, all-E-β-apo-8'-carotenoic acid ethyl ester and all-E-β-apo-8'-carotenal) within 12 min, compared to 90 min by the conventional high-performance liquid chromatography method. The separation was achieved on a YMC C30 reversed-phase column (100 mm x 2.0 mm; 3 μm) operated at 20°C using a methanol/tert-butyl methyl ether/water solvent system at a flow rate of 0.8 mL/min. The method was successfully applied to quantify lutein and zeaxanthin stereoisomers in egg yolk, raw and cooked spinach, and a dietary supplement. The method can be used for the rapid analysis of xanthophyll isomers in different food products and for quality control purposes.


Syringe fading as treatment for feeding refusal.
The efficacy of nonremoval of the cup or spoon as treatment for feeding refusal is dependent on prevention of escape from presentations. In the current investigation, 1 child with feeding refusal escaped presentations during nonremoval of the cup and spoon by clenching his teeth. Therefore, we used a syringe to deposit liquids and solids, increased the volume of liquids and solids in the syringe, and conducted syringe-to-cup and syringe-to-spoon fading.