Colon lamina propria dendritic cells induce a proinflammatory cytokine response in lamina propria T cells in the SCID mouse model of colitis.
Intestinal immune responses are normally regulated to maintain a state of immune balance. Dendritic cells (DC) are antigen-presenting cells, which induce immune responses against microbes and other stimuli and are key players in the regulation of tolerance in the gut. These cells influence the differentiation of cytokine responses in T cells, and in the gut, in particular, such interactions may be critical to the course of inflammatory bowel disease (IBD). Using the CD45RBhi CD4+ T cell-reconstituted severe combined immunodeficient mouse model of colitis, we investigated the ability of isolated colon DC to stimulate immune responses in syngeneic and allogeneic spleen CD4+ T cells, as well as in colon T cells isolated from the same tissue as DC in IBD mice. We found that the frequency of DC in IBD mice colons and spleens was elevated in comparison with control mice, but colon and spleen DC exhibited different phenotypic and functional properties. Colon DC stimulated significantly higher levels of interferon-gamma and interleukin-6 when cocultured with autologous colon T cells than in cocultures with syngeneic or allogeneic spleen T cells. These data suggest that in the IBD colon, DC-T cell interactions may create conditions with an abundance of proinflammatory cytokines, which favor the inflammatory state.


In vivo nitric oxide sensor using non-conducting polymer-modified carbon fiber.
Nitric oxide (NO) is emerging as a very important and ubiquitous gaseous messenger in the body. The response characteristics of NO sensors made of non-conducting polymer modified carbon fiber electrodes are investigated to determine their selectivity, sensitivity, and stability for in vivo use. A composite polymer, comprising Nafion, m-phenylenediamine, and resorcinol, showed the best selectivity and stability to amperometric NO detection. The non-conducting, self-limiting polymer film protects the electrode from interference and fouling by other biochemicals. Although the relative sensitivity to NO of the modified sensor is lower than that of the unmodified carbon fiber electrodes (less than 6%), the composite polymer electrode showed high selectivity against ascorbic acid (> 2000:1), nitrite (> 600:1), and dopamine (> 200:1). The stability of the NO sensor was maintained for at least 1 week. The NO sensitivity after in vivo experiments (n = 8) is 88.1 +/- 5.6% of initial sensitivity data obtained before in vivo experiments. Preliminary in vivo experiments done with this electrode are shown to capture elevated NO levels in brain following an ischemic injury.


Processing of one, two or four natural scenes in humans: the limits of parallelism.
The visual processing of objects in natural scenes is fast and efficient, as indexed by behavioral and ERP data [Nature 381 (1996) 520]. The results from a recent experiment suggested that such fast routines work in parallel across the visual field when subjects were presented with two natural scenes simultaneously [Nature Neurosci. 5 (2002) 629]. In the present experiment, the visual system was driven to its limits by presenting one, two or four scenes simultaneously. Behavior and ERP reveal a clear cost in processing an increasing number of scenes. However, a parallel-late selection model can still account for the results. This model is developed and discussed with reference to behavioral, single-unit and ERP data.


Highly dynamic changes of regional HBV epidemiology over two decades.
HBV epidemiology is highly heterogeneous and rapidly evolving worldwide: we studied its last two-decades dynamics in a large single center cohort. In all consecutive HBsAg-positive subjects firstly admitted (2000-2019) at the Pisa-University-Hospital Hepatology-Referral-Center, demographic, virologic and clinical variables were analyzed by admission decade (2000-2009 vs 2010-2019) and origin (Italian vs non-Italian natives). Of 2003, 1878 (93.7%) subjects were eligible: 1798(95.7%) with HBV-chronic [126(7%) HDV, 72(4%) HCV, 11(0.6%) HIV co-infected] and 80(4.3%) HBV-primary infections (93.7% Italians). Among 1589(88.4%) mono-infected, 496(31.2%) were immigrants, younger than Italians [34.0(5.1-77.1)-52.5(10.0-87.2) years], with female prevalence [204/496(41.1%)-340/1093(31.1%); p<0.001] increasing overtime (14.6-45.0%; p<0.001). Italians aged across decades [50.3(11.1-87.2)-56.2(10.0-86.7) years; p<0.001], HBeAg-positivity remained stable (12.3-14.5%) and acute hepatitis increased (4.0-8.0%; p = 0.003). CHB declined [439/721(60.9%)-320/868(36.9%); p<0.001] whereas HBeAg-negative infection increased [277/626(44.2%)-538/755(71.3%); p<0.001]. Cirrhosis declined [195/721(27.0%)-125/868(14.4%); p<0.001], except in anti-HDV-patients [93/126(73.8%); 42(45.1%) non-Italians], younger than HBV-mono-infected (47.4-57.6 years; p<0.001). Effective preventive health care policies and immigration flows account for increasing prevalence of HBeAg-negative infection across the last two decades. Antiviral therapy mitigated disease progression in aging Italian CHB but not in CHD patients, mainly young immigrants, emphasizing the unmet need of effective CHD therapies; HBeAg-positive CHB and acute hepatitis B persist in non-vaccinated Italian adults, prompting vaccination in the elderly with risky behaviors.


Early initiation of DNA synthesis in G1 phase HeLa cells following fusion with red cell ghosts loaded with S-phase cell extracts.
A modification of polyethylene glycol-mediated cell fusion procedure has been described and standardized for red blood cell mediated microinjection of proteins into cells in suspension. Using this procedure, proteins are routinely introduced into 50% of the target cells. We have applied this microinjection procedure to introduce cytoplasmic extracts obtained from S-phase HeLa cells into HeLa cells synchronized in G1. This experiment resulted in an accelerated entry of the G1 cells into S phase as measured by the incorporation of [3H]thymidine. This technique may provide a means to identify and characterize the S-phase factors responsible for the induction of DNA synthesis.


Production of live offspring from mouse germinal vesicle-stage oocytes vitrified by a modified stepwise method, SWEID.
To evaluate viability and subsequent developmental ability in mouse germinal vesicle (GV) oocytes ultrarapidly vitrified with serial stepwise exposure. Experimental animal study. University-based research laboratory. Three- to 4-week-old female (C57BL/6J x CBA) F1 mice in a laboratory environment. Vitrified and thawed GV oocytes were subjected to in vitro maturation, fertilization, and culture, some of which were transferred to recipients. Postthaw survival, maturation, cleavage, development to blastocysts, and live births. In the single-step preequilibrium, the rates of postthaw survival, maturation to metaphase II, and development to blastocysts were 97.5%, 95.8%, and 23.7%, respectively. In the serial 10-step preequilibrium developed in this study, which is named SWEID, the corresponding rates were 98.6%, 92.6%, and 42.9%, respectively, showing a statistically significantly higher rate of development to blastocysts in the SWEID group than in the single-step group. Transfer of two-cell-stage embryos derived from the GV oocytes vitrified by SWEID resulted in the production of live offspring. This is the first report that shows live birth after cryopreservation of mouse GV oocytes using an ultrarapid vitrification. Our method, SWEID, may have advantage in allowing storage of female gametes toward advances in infertility treatment and reproductive biology.


Structure and chain conformation of five water-soluble derivatives of a beta-D-glucan isolated from Ganoderma lucidum.
A linear water-insoluble (1-->3)-beta-D-glucan, coded as GL-IV-I, was isolated from the fruit body of Ganoderma lucidum by extracting with NaOH solution. Its derivatives were prepared by using sulfation, carboxymethylation, hydroxyethylation, hydroxypropylation, and methylation, respectively, and these were labeled as S-GL, CM-GL, HE-GL, HP-GL and M-GL. Five derivatives exhibited good water solubility. Their structures and chain conformations were investigated with infrared spectroscopy, elemental analysis (EA), one- and two-dimensional NMR spectroscopy, laser light scattering (LLS), and size-exclusion chromatography combined with LLS (SEC-LLS). The reactivity of the hydroxyl group of GL-IV-I was ordered as C-6>C-4>C-2 for the five derivatives. The degree of substitution (DS) of the derivatives was calculated from EA and NMR spectroscopy to be from 0.32 to 1.18. The weight-average molecular mass (M(w)) of GL-IV-I, S-GL, CM-GL, HE-GL, HP-GL, and M-GL was 13.3 x 10(4), 10.1 x 10(4), 6.3 x 10(4), 7.2 x 10(4), 5.1 x 10(4), and 14.1 x 10(4), respectively. The conformation analysis studies revealed that GL-IV-I exists as a compact coil in dimethyl sulfoxide, whereas the five derivatives are slightly expanded flexible chains in 0.9% aqueous NaCl solution.


Ibuprofen and gastrointestinal safety: a dose-duration-dependent phenomenon.
In summary, scientific evidence demonstrates that the rate of serious GI adverse events associated with the use of NSAIDs is comparatively low depending on the definition used, serious GI adverse events occur in 1% of patients each year and occurs in the use of high doses with long-term treatment in chronic conditions. At OTC doses, the incidence of GI adverse events in both adults and children receiving ibuprofen has been shown to be similar to that of paracetamol. Even at prescription doses of ibuprofen, upper GI bleeding is infrequent, and is usually associated with long-term use. Of all the NSAIDs, ibuprofen appears to have one of the best GI tolerability profiles.


[Pharmacological analysis of the participation of ethanol-oxidizing enzyme systems in ethanol metabolism at different stages of experimental alcoholism].
Using head space chromatography, the pharmacological analysis of changes in the activity of ethanol-oxidizing enzymatic systems: alcohol dehydrogenase, catalase, microsomal ethanol-oxidizing system under the effect of pyrazole and aminotriazole, has been performed on the model of experimental alcoholism in rats. It was shown that the rate of ethanol elimination from the rats' blood at all stages of experimental alcoholism was determined by alcohol dehydrogenase, while catalase and microsomal ethanol-oxidizing system activities did not play an important role.


Evaluation of real-time polymerase chain reaction assays for the detection of herpes simplex virus in swab specimens.
An in-house herpes simplex virus (HSV) real-time polymerase chain reaction (PCR) hydrolysis probe assay and three commercial real-time HSV assays were evaluated for the detection of HSV from genital, oral, ocular and dermal clinical samples. Five hundred and sixty samples from patients displaying signs and symptoms of HSV infection were used to evaluate the in-house HSV assay. A representative 151 samples were processed using the artus HSV-1/2 TM PCR Kit, SmartCycler Non-typing and SmartCycler Typing ASR kits. The in-house PCR assay demonstrated an overall positivity rate of 38% (211/560), equating to a 14% increase in HSV detection compared to 24% for culture (135/560). All 76 culture-negative, in-house PCR-positive samples were confirmed using at least one HSV commercial kit. The in-house, SmartCycler Non-typing, artus and SmartCycler Typing assays showed improved sensitivity (100%, 100%, 98% and 99%, respectively) compared to culture (37%), and all real-time assays were highly specific (100%). The in-house and commercial real-time HSV PCR assays performed well and, combined with careful clinical interpretation, should improve the detection, differentiation and quantification of HSV from mucocutaneous swab samples.


Rosuvastatin attenuated contrast-induced nephropathy in diabetes patients with renal dysfunction.
The protective effect of statins against CIN is still controversial. We investigated the efficacy of pretreatment of rosuvastatin in decreasing the risk of CIN in a high-risk population of patients undergoing coronary angiography. We conducted a prospective, randomized, controlled study, involving 120 patients with diabetes and mild to moderate renal dysfunction undergoing coronary angioplasty. Patients were randomly assigned to receive rosuvastatin (n = 60, 10 mg/day) or no statins (n = 60) for at least 2 days before and 3 days after contrast media administration. Serum cystatin (SCysC), serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary N-acetyl-β-D-glucosaminidase/urinary creatinine (NAG/UCr) were also observed before and after procedure. Baseline demographic characteristics and nephropathy risk factors were similar between groups. The NGAL levels after procedure were higher than baseline (P < 0.05). Both the peak NGAL values occurred at 2 hours. In rosuvastatin group the peak NGAL values were lower compared with that in control group [(47.60 ± 18.72) μg/L vs (62.19 ± 44.68) μg/L, P = 0.014]. No differences of the peak values of SCr were found between the two groups. But the peak levels of SCysC in rosuvastatin group were significantly lower compared with that in control group [(0.96 ± 0.30) mg/L vs (1.08 ± 0.34) mg/L, P = 0.043]. There were significant statistical differences of NAG/Cr levels in the two groups. No clinical events occurred within the following 30 days in the two groups. Rosuvastatin could reduce the effect of degrading glomerular filtration function and renal tubular damage in patients with DM and mild to moderate renal dysfunction.


Onset of the lymphocytic infiltration and hyperplasia preceding the proliferation in F1 mouse lungs from the N-ethyl-N-nitrosourea exposed mothers: Prevention during the lactation period by inositol hexaphosphate.
Maternal exposure to a carcinogen is associated with increased risk of different cancers in the offspring. The foetus is highly sensitive to carcinogens and this contributes to the foetal basis of the onset of disease. The better understanding of the molecular mechanisms involved in the early stage of lung tumourigenesis in the offspring is needed for the newer preventive strategies. We evaluated the effects of N-ethyl-N-nitrosourea (ENU) given on the 17th day of gestation and antitumour agent inositol hexaphosphate (IP6) to the mothers at the early stage of lung tumourigenesis in F1 mice. There was no treatment related effects on the litter size or body weight of the F1 mice at the PND12 or 24. Analysis of PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, caspase-3, caspase-9, PARP, Akt signalling and downstream cyclin D1 along with miR-155, suggested the modulation of proliferation, inflammation and apoptosis at PND12 and 24. IP6 administration to the predisposed mothers prevented the proliferation, inflammation and enhanced apoptosis in F1 lung as showed by a reduction in PCNA, NF-κB (p50), IL-6, COX-2, pSTAT3, STAT3, miR-155 and increase in caspases, cleavage of poly (ADP-ribose) polymerase. IP6 administration also inhibited the activation of Akt and cyclin D1. Our study shows that tumourigenic changes take place in the lungs of the F1 generation from the carcinogen predisposed mothers even before the onset of tumours and the simultaneous intake of chemopreventive agent during the gestation or lactation period could prevent the lymphocytic infiltration and hyperplasia preceding the tumourigenesis.


Prevalence and risk factors of barrett's esophagus in lynch syndrome.
Lynch syndrome (LS), the most common hereditary cause of colorectal cancer, predisposes to upper gastrointestinal neoplasia. The prevalence of Barrett's esophagus (BE) is elevated in some hereditary gastrointestinal cancer syndromes but has not been systematically evaluated in LS. We assessed the prevalence of BE, BE-related dysplasia, esophageal adenocarcinoma (EAC), and factors associated with BE in LS. Asymptomatic patients with a germline pathogenic variant (PV) in the DNA mismatch repair (MMR) genes undergoing EGD for LS surveillance were identified from a hereditary colorectal cancer registry. We assessed the prevalence of BE and compared demographic, clinical, and endoscopic factors in LS patients with and without BE by logistic regression analysis. 323 patients were included. 21 patients (6.5%) were diagnosed with BE including 38% of females and 33% without gastroesophageal reflux disease (GERD). Dysplasia was diagnosed in two patients (9.5%) and EAC in one (4.8%) patient. Factors associated with BE included male gender (OR 3.00, 1.21-7.46), age at last LS EGD (OR 1.04, 1.01-1.08), presence of hiatal hernia (OR 20.09, 4.57-88.23), hiatal hernia > 3 cm (OR 11.25, 2.41-51.94), and GERD (OR 3.39, 1.32-8.67). No MMR PV was associated with BE. BE was diagnosed in 1 of 15 patients undergoing EGD surveillance for LS and nearly 10% had dysplasia including one EAC. Risk factors associated with BE in LS are similar to those established for BE in the general population. More studies are needed to evaluate if an association between BE and LS exists.


Investigation of cosolvent application to enhance POPs' mass transfer in partitioning passive sampling in sediment.
The freely dissolved concentration of persistent organic pollutants (POPs) is one of the most important parameters for risk assessment in aquatic environments, due to its proportionality to the chemical activity. Chemical activity difference represents the driving force for a spontaneous contaminant transport, such as water-aquatic biota or water-sediment. Freely dissolved concentrations in sediment pore water can be estimated from the concentrations in a partition-based passive sampler equilibrated in suspensions of contaminated sediment. Equilibration in the sediment/passive sampler system is slow, since concentrations of most POPs in the water phase, which is the main route for mass transfer, are very low. Adding methanol to sediment in suspension increases the POPs' solubility and, consequently, the permeability in the water phase. The resulting higher aqueous concentrations enhance POPs mass transfer up to three times for investigated POPs (polycyclic aromatic hydrocarbons, polychlorinated biphenyls, organochlorine pesticides) and shorten equilibrium attainment to less than 6 weeks. The addition of methanol to the aqueous phase up to a molar fraction of 0.2 changed the POPs equilibrium distribution ratio between sediment and passive sampler by less than a factor of two. As a result, the pore water concentrations of POPs, calculated from their amounts accumulated in a passive sampler, are affected by methanol addition not more than by the same factor.


Long-term efficacy of globus pallidus stimulation for the treatment of Parkinson's disease.
To determine the long-term efficacy and safety of globus pallidus internus (GPi) stimulation for Parkinson's disease (PD). We previously reported 3-month data for 5 patients who underwent GPi stimulation for PD. We now report long-term data on these 5 patients and 4 additional patients. Nine PD patients, 5 men and 4 women, with an average age of 49 years and disease duration of 10 years, underwent GPi stimulation. Six patients had staged bilateral implants and 3 patients had unilateral implants. The mean follow-up was 48.5 months. All patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and completed 2-day diaries before and after surgery. There was a 21% improvement in UPDRS Part II (activities of daily living; ADL) scores and a 37% improvement in UPDRS Part III (motor) scores when the longest follow-up in the 'stimulation-on/medication-off' state was compared to the 'medication-off' state at baseline. The UPDRS Part II (ADL) scores improved by 30% and the UPDRS Part III (motor) scores improved by 39% when the longest follow-up in the 'stimulation-on/mediation-on' state was compared to the 'medication-on' state at baseline. As measured by patient diaries, 'on' time increased from 25 to 59% and 'on with dyskinesia' decreased from 42 to 15%. Surgical- and device-related complications included transient hemiparesis in the operating room, postoperative seizures, and implantable pulse generator and lead problems. There were seven device-related events requiring additional surgical procedures. GPi stimulation continues to be effective for the long-term treatment of the disabling symptoms of PD; however, the physician and patient should be aware that device-related problems are not uncommon and additional surgery may be necessary.


Number of objectives and conclusions in dissertations and thesis.
To analyze the number of objectives and conclusions presented in dissertations and thesis defended at Federal University of São Paulo-Paulista School of Medicine (UNIFESP-EPM). It was realized a search in the master degree dissertations and doctor degree thesis defended at Federal University of São Paulo-Paulista School of Medicine in the years 2002 and 2003 that were found available in the central library of this university. From 723 master dissertations analyzed, 62 (8.57%) presented only one objective and one conclusion, 134 (18.53%) presented one objective and more than one conclusion and 527 (72.89%) had more than one objective and more than one conclusion. From 502 doctor thesis analyzed, 23 (4.58%) presented only one objective and one conclusion, 123 (24.50%) presented one objective and more than one conclusion and 376 (74.90%) had more than one objective and more than one conclusion. It wasn't found in researched literature the number of objectives and conclusions a scientific work must have. A highest number of thesis and dissertations presented more than one objective and more than one conclusion.


Specific modulation of the Hoffmann reflex cutaneous facilitation during a reaction-time task.
The Hoffmann (H) reflex and its facilitation produced by electrical stimulation of the sural area were examined before a ballistic extension of the right foot. Modulations of the cutaneous facilitation of the H reflex (CFH) were used to assess the control exerted over the transmission of low threshold cutaneous afferents. The time-course of H and CFH changes were investigated at the end of the foreperiod and during the premotor period, i.e. between the response signal and the onset of the electromyogram (EMG) of the soleus muscle. Four stimulation conditions were set up depending on whether the H reflex was elicited on the contracting or non-contracting limb, and whether cutaneous stimulation was ipsilateral or contralateral to the reflex. During the 100 ms preceding the response signal, the inhibition of the H reflex was more marked in the contracting limb than in the non-contracting limb. At the end of the foreperiod, the CFHs had a symmetric time course: the CFHs evoked by conditioning stimulation of the contracting limb were facilitated just before the response signal, while those produced by conditioning stimulation to the non-contracting limb were depressed. It is suggested that these variations are related to postural adjustments taking place before the movement is performed. As previously reported, the H reflex of the contracting limb exhibited a marked increase in amplitude over the 50 ms preceding the EMG. Reflex facilitations showed specific variations according to the ankle stimulated and the soleus muscle tested. The CFHs produced by stimulation of the non-contracting limb regained, at the end of the premotor period, a value close to their reference level recorded in trials without movement. The CFHs, produced by conditioning stimulation of the contracting limb were modulated differently according to whether the tested soleus muscle was contracting or not: when the CFH was tested on the contracting muscle, it was found to be depressed throughout the premotor period; this contrasted significantly with the isolated depression recorded on the non-contracting muscle. Therefore, only the cutaneous afferents from the mobilized limb, modulating the H reflex of the same limb, were subject to a specific inhibition during the premotor period. Throughout the preparatory and premotor periods, negative correlations were observed between H and CFH amplitude, except just before the EMG onset in the condition where the H reflex was delivered to the contracting muscle and the cutaneous stimulation to the ankle of the non-contracting limb: in this case, CFH amplitude increase paralleled that of the reflex amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)


Administration of Orexin-A into the Rat Thalamic Paraventricular Nucleus Enhances the Naloxone Induced Morphine Withdrawal.
Orexin neuropeptides are implicated in physical dependence on opioids and expression of withdrawal symptoms in drug abuse. The paraventricular nucleus of the midline thalamus (PVT) has a high expression of orexin receptors. The current research studied the effect of orexin-A in the PVT area on the development of behavioral indices produced by morphine withdrawal in rats. Male Wistar rats weighing 250-300 gr were utilised. To produce drug dependence, morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) was injected at an interval of 24 hrs for 7 days. To assess the involvement of the orexin in withdrawal syndrome, we injected orexin-A (100 μM, 200 nl) into the PVT for 7 days before each morphine injection. On the day after the last injection of morphine, naloxone (2.5 mg/kg, i.p.) was injected to elicit the morphine withdrawal symptoms which were observed and checked for 25 min. The results of the current research showed that the orexin-A in PVT enhances the severity of behavioral symptoms prompted by the injection of naloxone in drug-dependent rats. These observations imply that targeting the orexin receptors in PVT might exhibit a new therapeutic strategy for the future treatment of dependence.


Memory impairment in schizophrenic patients with tardive dyskinesia.
Memory functioning was contrasted in 40 schizophrenic patients with and without tardive dyskinesia (TD). Visual and verbal memory tests were used to investigate specific types of impairments. The presence of TD was ascertained using the Abnormal Involuntary Movement Scale (AIMS). TD patients scored significantly lower than non-TD patients on two measures of visual learning, though no differences were found for verbal learning or immediate recall. These results are consistent with previous reports that schizophrenic patients with TD demonstrate impaired cognitive functioning. They also raise the possibility that the neurochemical and structural changes underlying TD may produce specific deficits in memory for visual materials. In addition, a significant relationship was found between total score on the Brief Psychiatric Rating Scale (BPRS) and performance on all of the test measures included in the cognitive test battery. This demonstrates the importance of attending to the overall level of schizophrenic symptomatology when evaluating results from experimental learning tasks.


Do cellulose binding domains increase substrate accessibility?
This article provides an overview of various theories proposed during the past five decades to describe the enzymatic hydrolysis of cellulose highlighting the major shifts that these theories have undergone. It also describes the effect of the cellulose-binding domain (CBD) of an exoglucanase/xylanase from bacterium Cellulomonas fimi on the enzymatic hydrolysis of Avicel. Pretreatment of Avicel with CBDCex at 4 and 37 degrees C as well as simultaneous addition of CBDCex to the hydrolytic enzyme (Celluclast, Novo, Nordisk) reduced the initial rate of hydrolysis owing to irreversible binding of CBD proteins to the substrate's binding sites. Nonetheless, near complete hydrolysis was achieved even in the presence of CBDCex. Protease treatment of both pure and CBDCex-treated Avicel reduced the substrates' hydrolyzability, perhaps owing to proteolysis of the hydrolyzing enzyme (Celluclast) by the residual Proteinase K remaining in the substrate. Better protocols for complete removal of CBD proteins from the substrate need to be developed to investigate the effect of CBD adsorption on cellulose digestibility.


Clinical and imaging features of Kaposiform hemangioendothelioma in infants.
Kaposiform hemangioendothelioma (KHE) is a locally aggressive tumor of vascular origin. This study investigated the clinical and imaging features of KHE to provide a reference for its early diagnosis. The clinical and imaging findings of 27 clinically confirmed KHE cases (including 21 with focal lesions and 6 with diffuse lesions) between January 2016 and December 2021 were retrospectively analyzed. The mean age of the 27 patients was 105 ± 80.27 days. Twenty-two (81.5%) of these patients had Kasabach-Merritt phenomenon. Most KHEs were located in the trunk and/or extremities (22/27). Ultrasonography showed heterogeneous echogenicity and/or striated hypoechoic bands with abundant or patchy blood flow within the tumor. On plain computed tomography (CT), they appeared as heterogeneous lesions isodense with the muscles, with a CT value of 29.58 ± 11.53 HU. In the arterial phase, the KHEs showed striated or lamellar heterogeneous enhancement, with a CT value of 153.91 ± 52.11 HU after enhancement. All KHEs showed uneven and high signal intensity on T2-weighted imaging, mixed high and low signal intensity on fat-saturated images, and no significant diffusion restriction on diffusion-weighted imaging. KHEs can occur in various locations and present as highly infiltrative and heterogeneous masses that can invade the skin, adjacent muscles, and bones. A vascularized mass with purpuric skin changes, with uneven and high T2WI signal is highly suggestive of the diagnosis of KHE.


[Splenic rupture revealing metastasis of a yolk sac tumor].
We report a rare entity in adults with an exceptional secondary complication. This is a case of a splenic localization of a yolk sac tumor responsible for a splenic rupture in a 52-year-old man.


Altered invariant natural killer T cell subsets and its functions in patients with oral squamous cell carcinoma.
Invariant natural killer T (iNKT) cells are glycolipid-reactive T lymphocytes that share receptors and function with natural killer (NK) cells and reportedly play a pivotal role in various immune responses. However, iNKT cells are not well characterized in patients with oral squamous cell carcinoma (OSCC). We investigated the populations and functions of circulating iNKT (CD3(+) 6B11(+) ) cells from thirty-eight patients with OSCC and twenty-eight healthy donors by flow cytometry. Circulating iNKT cells were significantly lower (P < 0.01) in patients as compared to those in healthy controls. Further, iNKT subsets revealed a marked decrease in CD4(-) CD8(-) (double negative, DN) subset with concomitant increase in CD8(+) subset in patients as compared to healthy controls (P = 0.03 and P < 0.01, respectively), whereas CD4(+) subset was similarly distributed in both groups. The functional analysis demonstrated that residual iNKT cells from patients had impaired proliferative response to α-galactosylceramide (α-GalCer)-pulsed dendritic cells (DCs) and Th2-like cytokine profile. However, in vitro activation with α-GalCer-pulsed DCs restores IFN-γ expression and enhances antitumour activity to human cancer cells lines (SCC-4, KB and MCF7). It appears that the selectively enriched iNKT subsets and modulation of their function by specific ligand/agonist may be useful for cellular therapy in patients with OSCC. Further, reduced levels of iNKT cells and its DN subset may be used as potential prognostic factors for patients with OSCC.


Assessment of medication errors that involved drug allergies at a university hospital.
To determine the reporting accuracy of true patient-related allergies to drugs in a large teaching institution (908 licensed beds), and to identify factors contributing to medication errors that involved drug allergies. Of particular interest was the accuracy of allergy information in the medical record and the occurrence of medication errors that involved penicillin antibiotics. From a sample population of 340 patients, 50 adult patients admitted to our university-affiliated hospital who met criteria and had an allergy to selected drugs that was documented in the hospitalwide computer system were randomly selected and interviewed to determine the timing, nature, and extent of the reaction. Furthermore, data were collected from identified Medication Error Reports when an agent was prescribed for a patient with a reported allergy to that agent or class. Prospective data collection was conducted from November 2000-February 2001. Using the information obtained by the patient interview and chart documentation, we assessed the reported allergy. In addition, contributing factors for medication errors that involved drug allergies were identified. Of the sample population, 133 patients (39%) reported allergies to at least one drug. Allergies to beta-lactams, sulfonamides, and opioid narcotics were reported in 12.6% (43 patients), 9.1% (31), and 14.4% (49) of the sample population, respectively. Most agents involved in medication errors were beta-lactam antibiotics, with an overwhelming number of these errors due to piperacillin-tazobactam (51.4%, 36 errors). Other drugs involved were ampicillin (10%, 7 errors), other beta-lactams (24.3%, 17 errors), opioid narcotics (10%, 7 errors), and sulfonamides (4.3%, 3 errors). Most contributing factors were classified as "MD [prescribing physician] not aware of allergy." These results suggest a need for ensuring that prescribers review each patient's allergy profile before order entry.


Free radical-mediated degradation of proteins: the protective and deleterious effects of membranes.
Lipid membranes have been shown to scavenge free radicals generated by various means. However, under oxidative conditions, unsaturated lipids within membranes can produce damaging free radicals. We have determined the relative importance of these two conflicting properties of lipid membranes with the use of liposomal membrane studies. (1) Liposome membranes can protect extra-liposomal albumin from free radicals derived from sources other than peroxidizing lipid. When albumin or copper (an essential component of the free radical generating systems used) were encapsulated, protein damage was further reduced. (2) Using sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE) we demonstrate that the exposure of albumin to peroxidizing liposome membranes results in both cross-linking and degradation. Our results indicate that protein damage is substantially less than in the case of other biologically relevant free radical generating systems. We discuss our findings with respect to membrane function and the in vivo exposure of cells to free radicals.


Quantitation of dexamethasone in biological fluids using high-performance liquid chromatography.
A sensitive and specific method for the quantitation of dexamethasone in plasma and urine is described. The specificity of the method is obtained using adsoprtion chromatography on a high-performance liquid chromatograph. The dexamethasone is detected with a variable-wavelength UV detector. An internal standard technique is used for quantitation of dexamethasone with a minimum sensitivity of 15 ng. Preliminary results of the application of the method to pharmacokinetic studies of dexamethasone in humans are reported.


Statistical topics in the laboratory sciences.
This chapter concerns statistical concepts and procedures that are applicable to diagnostic testing performed in the clinical laboratory. Three important laboratory issues are addressed: the estimation of analytical imprecision, the design of an effective laboratory quality control strategy, and the establishment of population reference ranges. These three topics were selected because each demonstrates a valuable statistical principle. Estimation of analytical imprecision highlights the important role of study design. Evaluating laboratory quality control strategies emphasizes the importance of choosing appropriate statistical models. The estimation of population reference ranges demonstrates that there can be many different approaches to developing good statistical estimators.


Intravitreal Ranibizumab Alone or in Combination with Calcium Dobesilate for the Treatment of Diabetic Macular Edema in Nonproliferative Diabetic Retinopathy Patients: 12-Month Outcomes of a Retrospective Study.
This study investigates the efficacy of CaD combined with intravitreal ranibizumab for the treatment of diabetic macular edema (DME) in patients with nonproliferative DR. This retrospective, observational, case-control study enrolled consecutive patients newly diagnosed with DME. The patients were treated with 3-monthly loading dose injections of intravitreal ranibizumab (IVR) followed by pro re nata injections (3 + PRN), with or without daily oral CaD. The patients were treated and followed up for 12 months. We reviewed their medical records to determine the optical coherence tomography (OCT) findings, number of injections, best-corrected visual acuity (BCVA), and central macular thickness (CMT) at 3, 6, and 12 months after the first injection. We reviewed 102 eyes of 102 patients; 54 patients received IVR combined with oral CaD (IVR + CaD group) and 48 received only IVR (IVR group). In both groups, BCVA was higher, and CMT was lower, at 3, 6, and 12 months after the injection compared to those at the baseline (p < 0.05 for all), while there were no significant differences in BCVA improvement or CMT reduction between the two groups (p > 0.05). The mean number of IVR injections was significantly lower in the IVR + CaD group than the IVR group (5.4 ± 1.1 vs. 6.7 ± 1.6 injections, p < 0.05) during 1 year of treatment. No adverse events were noted in either group. Compared to IVR alone, the addition of oral CaD to IVR in DME patients was safe and effective for improving visual function and restoring the retinal anatomy and was associated with the need for fewer injections.


Lymphocyte antigens of sheep: identification and characterization using a panel of monoclonal antibodies.
A panel of monoclonal antibodies has been developed and used to identify and characterize the lymphocyte antigens of sheep. These studies have shown that sheep lymphocyte antigens display similar, if not identical, tissue distributions to their analogues in other species. Some of the major sheep antigens, including CD5, CD4, CD8, SBU-T19, Pgp-1, LCA and the MHC antigens, are described in detail.


Immunohistochemical localization of S-100 protein, glial fibrillary acidic protein, and neuron-specific enolase in the pars distalis of quail, rat, and human hypophyses.
In the present study, we have localized immunohistochemically S-100 protein, glial fibrillary acidic (GFA) protein, and neuron-specific enolase (NSE) by the unlabelled antibody peroxidase-antiperoxidase technique. Special attention was paid to the influence of fixation and of pretreatment of sections with proteolytic enzymes. It appeared that the final immunostaining of a given antigen largely depends on the fixative and on the species used. Moreover, pepsin pretreatment proved to be necessary to unmask S-100 protein in quail and GFA protein in rat. S-100 protein (rat, human) and GFA protein (human) immunoreactivities were detected in the folliculo-stellate (FS) cells. In quail, S-100 protein was also found in cells, which were not arranged around a follicular lumen and, in rat, the endothelial cells were immunostained for GFA protein. Clusters of granular cells were weakly immunostained for NSE in all species. An exclusive relationship between FS cells and S-100 protein could not be ascertained from this study.


Oxidative burst, jasmonic acid biosynthesis, and taxol production induced by low-energy ultrasound in Taxus chinensis cell suspension cultures.
This work aims to detect the two signal events in the elicitation of plant defense responses and secondary metabolism in plant cell cultures by low-energy ultrasound (US), transient production of reactive oxygen species (ROS) or the oxidative burst and jasmonic acid (JA) biosynthesis, and examine their influence on secondary metabolism. Experiments were carried out in Taxus chinensis cell suspension culture which produces the anticancer diterpenoid Taxol (paclitaxel). The culture was exposed to low-frequency US for a short period of time (2 min). At sufficiently high US power levels the US exposure significantly enhanced the Taxol production and slightly depressed cell growth and viability. The US exposure induced transient production of O(2)*- and H(2)O(2) and an increase in the intracellular JA level as well as the activities of enzymes for JA synthesis, lipoxygenase (LOX), and allene oxide synthase (AOS). Inhibition of the ROS production by putative ROS scavengers or the JA accumulation by LOX inhibitors effectively suppressed the US-stimulated Taxol production. Inhibition of the ROS production also suppressed the US-induced JA accumulation. These results suggest that oxidative burst is an upstream event to JA accumulation, and both ROS from the oxidative burst and JA from the LOX pathway are key signal elements in the elicitation of Taxol production of T. chinensis cells by low-energy US.


Complex phase mixing of phosphatidylcholine and phosphatidylserine in multilamellar membrane vesicles.
The phase mixing in dipalmitoyl phosphatidylcholine and bovine brain phosphatidylserine mixtures suspended in aqueous salt solutions was studied by differential scanning calorimetry, freeze-fracture electron microscopy and X-ray and electron diffraction. The pure dipalmitoyl phosphatidylcholine has two well-defined solidus phases P beta' and L beta' and a liquidus phase L alpha while the pure phosphatidylserine has a broad transition from L beta to L alpha. The mixture exhibits some dipalmitoyl phosphatidylcholine characteristics up to 30% phosphatidylserine when pure P beta' phase no longer exists. Phase mixing is observed at all compositions. An addition of 3% phosphatidylserine is found to be sufficient to destroy the sharp L beta'--P beta' transition observed in pure dipalmitoyl phosphatidylcholine. The transition between L beta' and P beta' in these mixtures is displaced to lower temperatures and becomes gradual as depicted by all three techniques, but freeze-fracture gives more definite information of the continuous transition. The most striking observation on the morphology of the mixed membranes (3--30% phosphatidylserine in dipalmitoyl phosphatidylcholine) is the presence of banded patterns (P beta') at temperatures well below the main transition peak as detected by differential scanning calorimetry.


Topographic specificity of aberrant cerebellorubral projections following neonatal hemicerebellectomy in the rat.
Anterograde transport of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) was used to examine the topographic specificity of ascending cerebellar efferent projections in adult rats which were hemicerebellectomized at birth. The results were compared to similar cerebellar projections in unlesioned adults. HRP-WGA placement in the nucleus interpositus of control rats resulted in a dense projection of labeled fibers which decussated in the midbrain, caudal to the red nucleus. In the red nucleus, dense terminal labeling was confined to the magnocellular region, while retrogradely labeled rubrocerebellar neurons were present throughout both parvo- and magnocellular areas. Similar HRP-WGA placements in the nucleus lateralis gave rise to fewer labeled fibers which terminated in the parvocellular red nucleus. In addition to the cerebellorubral projection, other areas of terminal labeling included the mid-brain reticular formation, nucleus parafascicularis prerubralis, zona incerta, fields of Forel and ventral thalamus. In neonatally lesioned adults, aberrant cerebellorubral and cerebellothalamic projections were observed deflecting ipsilaterally at the decussation of the normal contralateral projection. Topographic specificity of the aberrant ipsilateral cerebellorubral projection mirrored that of the normal contralateral fibers. In addition, an ipsilateral projection from the cerebellum could be followed rostral to the red nucleus, to terminate in the ipsilateral ventral thalamus. Lesioned animals also demonstrated marked cell loss in the red nucleus contralateral to the hemicerebellectomy.


Association of Childhood and Midlife Neighborhood Socioeconomic Position With Cognitive Decline.
Early-life socioeconomic adversity may be associated with poor cognitive health over the life course. To examine the association of childhood and midlife neighborhood socioeconomic position (nSEP) with cognitive decline. This cohort study included 5711 men and women enrolled in the community-based Atherosclerosis Risk in Communities (ARIC) Study with repeated cognitive data measured over a median 27.0 years (IQR, 26.0-27.9 years) (1990-2019). Statistical analysis was performed from December 2022 through March 2023. Residence addresses for ARIC Study cohort participants were obtained at midlife (1990-1993) and as recalled addresses at 10 years of age (childhood). A composite nSEP z score was created as a sum of z scores for US Census-based measures of median household income; median value of owner-occupied housing units; percentage of households receiving interest, dividend, or net rental income; percentage of adults with a high school degree; percentage of adults with a college degree; and percentage of adults in professional, managerial, or executive occupations. Childhood nSEP and midlife nSEP were modeled as continuous measures and discretized into tertiles. A factor score for global cognition was derived from a battery of cognitive tests administered at 5 in-person visits from baseline to 2019. The rate of cognitive decline from 50 to 90 years of age was calculated by fitting mixed-effects linear regression models with age as the time scale and adjusted for race, sex, birth decade, educational level, and presence of the apolipoprotein E ε4 allele. Among 5711 ARIC Study participants (mean [SD] baseline age, 55.1 [4.7] years; 3372 women [59.0%]; and 1313 Black participants [23.0%]), the median rate of cognitive decline was -0.33 SDs (IQR, -0.49 to -0.20 SDs) per decade. In adjusted analyses, each 1-SD-higher childhood nSEP score was associated with a slower (β, -9.2%; 95% CI, -12.1% to -6.4%) rate of cognitive decline relative to the sample median. A comparable association was observed when comparing the highest tertile with the lowest tertile of childhood nSEP (β, -17.7%; 95% CI, -24.1% to -11.3%). Midlife nSEP was not associated with the rate of cognitive decline. In this cohort study of contextual factors associated with cognitive decline, childhood nSEP was inversely associated with trajectories of cognitive function throughout adulthood.


The Effect of Ambient Light Conditions on Quantitative Pupillometry.
Automated devices collecting quantitative measurements of pupil size and reactivity are increasingly used for critically ill patients with neurological disease. However, there are limited data on the effect of ambient light conditions on pupil metrics in these patients. To address this issue, we tested the range of pupil reactivity in healthy volunteers and critically ill patients in both bright and dark conditions. We measured quantitative pupil size and reactivity in seven healthy volunteers and seven critically ill patients with the Neuroptics-200 pupillometer in both bright and dark ambient lighting conditions. Bright conditions were created by overhead LED lighting in a room with ample natural light. Dark conditions consisted of a windowless room with no overhead light source. The primary outcome was the Neurological Pupil Index (NPi), a composite metric ranging from 0 to 5 in which > 3 is considered normal. Secondary outcomes included resting and constricted pupil size, change in pupil size, constriction velocity, dilation velocity, and latency. Results were analyzed with multi-level linear regression to account for both inter- and intra-subject variability. Fourteen subjects underwent ten pupil readings each in bright and dark conditions, yielding 280 total measurements. In healthy subjects, median NPi in bright and dark conditions was 4.2 and 4.3, respectively. In critically ill subjects, median NPi was 2.85 and 3.3, respectively. Multi-level linear regression demonstrated significant differences in pupil size, pupil size change, constriction velocity, and dilation velocity in various light levels in healthy patients, but not NPi. In the critically ill, NPi and pupil size change were significantly affected. Ambient light levels impact pupil parameters in both healthy and critically ill subjects. Changes in NPi under different light conditions are small and more consistent in healthy subjects, but significantly differ in the critically ill. Practitioners should standardize lighting conditions to maximize measurement reliability.


"Pyruvate recycling" and its influence on the estimation of the pentose pathway in intact liver and Morris hepatoma 5123TC cells.
The phenomenon of "pyruvate recycling" is demonstrated in perfused rat liver, rabbit liver in situ and in Morris Hepatoma 5123TC cells and quantitatively measured using [2-14C]pyruvate and the method of Friedmann et al. (1971). Various metabolites, viz. lactate, DHAP, glucose, glucose 6-P and fructose 6-P were isolated and degraded following the metabolism of [2-14C]pyruvate and [2-14C]glycerol in order to assess the 14C-distributions imparted by "pyruvate recycling" reactions. The labelling of DHAP, lactate, glucose and glucose 6-P showed 14C randomizations consistent with the operation and the quantitative extent of "pyruvate recycling". These findings support the proposal that the actions of "pyruvate recycling" may account for the failure to find significant levels of 14C isotope at C-1 of glucose 6-P following the metabolism of [4,5,6-14C]- or [6-14C]glucose by L-type pentose pathway metabolism in aerobic intact tissues. "Pyruvate recycling" diminishes the measured value of the L-type pentose cycle in intact tissues and qualifies one of the mechanistic predictions of the L-type pentose pathway which was unravelled by tracing its reactions with labelled ribose 5-P and liver enzymes (Horecker et al., 1954; Williams et al., 1978a,b) in vitro. The demonstration of an association of L-type pentose pathway reactions with "pyruvate recycling" by way of the common reactions of their triose-P intermediates qualifies the superficial acceptance of the predictions of the L-type pathway in vitro for the distribution of isotopic labels by aerobic tissues in vivo.


A single institution experience with concurrent capecitabine and radiation therapy in weak and/or elderly patients with urothelial cancer.
To describe a single institution experience in delivering concurrent capecitabine and radiation in elderly patients with urothelial cancer. The records of patients with urothelial carcinoma treated with capecitabine and radiation at Wayne State University were reviewed. Capecitabine was administered at a median dose of 1600 mg/m2/day (range, 1200-1800 mg/m2). Concurrent radiation therapy (RT) of 40-45 Gy was delivered to a small pelvic field with a four-field technique, with additional boost to tumor area (total, 54-68.4 Gy). Fourteen patients who were not candidates for cystectomy or cisplatin-based therapy were treated with capecitabine and concurrent radiation therapy. Median age was 80 years (range, 46-88 years). Five patients had a performance status of 3. Nine patients had localized disease, and 5 patients had advanced disease. The most common overall toxicities were fatigue (43%), diarrhea (Grade 2, 14% and Grade 3, 29%), and dehydration (43%), with no Grade 4 or 5 toxicities. Of 14 patients, 3 (20%) required hospitalization for management of toxicities. Seven patients required dose modification, and the therapy was relatively well tolerated. Clinical complete response was seen in 11 of 13 evaluable patients (77%). At a median follow-up of 10.5 months, only 3 of 11 responders had relapsed. Concurrent capecitabine and radiation therapy is well-tolerated and demonstrates promising efficacy in urothelial carcinoma, thus offering a tolerable therapeutic option in elderly patients or those with impaired performance status.


[Culture of chondrocytes seeded onto chitin scaffoldings coating with different materials: experimental study].
To find the possibility of chitin used as scaffolds in tissue engineering. Chondrocytes were cultured when they were seeded onto chitin meshcoated with polylactic acid (PLA) lecithin (LEC) and poly-l-lysine (PLYS). With light microscope and scanning electron microscope, the scaffolds in hydrophilia and absorptivity to chondrocytes and the function of the cells were observed. LEC can change the hydrophilia of scaffolds. PLYS can strengthen the absorptivity of the scaffolds. and promote the matrices production of chondrocytes. The chitin coated with LEC and PLYS can be used as scaffolds in tissue engineering.


Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats.
Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n=7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P<0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P<0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P>0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.


Oxidation and formation of oxidation products of β-carotene at boiling temperature.
β-Carotene is one of the most important lipid component extensively used in food industries as source of pro-vitamin A and colorant. During processing and storage β-carotene is oxidized and degraded to various oxidation compounds. Some of these compounds are also the key aroma compounds in certain flowers, vegetables and fruits. The methods for analysis and determination of these oxidized products formed during food boiling or preparation are key to the understanding the chemistry of these compounds. This paper presents a novel analytical method incorporating high performance liquid chromatography with diode array and mass spectrometric detection for the characterization of oxidation, isomerization and oxidation products of β-carotene in toluene at boiling temperature. HPLC and APCI-MS was optimized using oxidized sample and flow injection analysis of the standard β-carotene respectively. β-Carotene was oxidized in the Rancimat at 110°C for 30, 60 and 90 min. The oxidized samples were than analyzed by HPLC system at 450 nm and 350 nm as well as scanning and single ion monitoring mass spectrometry. A total of ten oxidation products and three Z-isomers were reported. Extensive isomerization was observed during treatment at the control accelerated conditions. The oxidation products include five apo-carotenals, three diepoxides, one mono-epoxide and one short chain species. Results show that the method was reproducible, accurate and reliable for the separation and identification of oxidation products of β-carotene.


Discovery of novel potential selective HDAC8 inhibitors by combine ligand-based, structure-based virtual screening and in-vitro biological evaluation.
Neuroblastoma is the most common extracranial solid tumor found in children and survival rate is extremely meager. HDAC8, a class I zinc-dependent enzyme, is a potential drug target for treatment of neuroblastoma and T cell lymphoma. Most of the HDAC8 inhibitors discovered till date contains a hydroxamic acid group which acts as a zinc binding group. The high binding affinity to the zinc and other ions results in adverse effects. Also, the non-selective inhibition of HDACs cause a variety of side effects. The objective of this is to identify structurally diverse, non-hydroxamate, novel, potential and selective HDAC8 inhibitors. A number of five featured pharmacophore hypotheses were generated using 32 known selective HDAC8 inhibitors. The hypotheses ADDRR.4 were selected for building 3D QSAR model. This model has an excellent correlation coefficient and good predictive ability, which was employed for virtual screening of Phase database containing 4.3 × 106 molecules. The resultant hits with fitness score >1.0 were optimized using in-silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) and XP glide docking studies. On the basis of pharmacophore matching, interacting amino acid residues, XP glide score, more affinity towards HDAC8 and less affinity towards other HDACs, and ADME results five hits- SD-01, SD-02, SD-03, SD-04 and SD-05 with new structural scaffolds, non-hydroxamate were selected for in vitro activity study. SD-01 and SD-02 were found to be active in the nanomolar (nM) range. SD-01 had considerably good selectivity for HDAC8 over HDAC6 and SD-02 had marginal selectivity for HDAC6 over HDAC8. The compounds SD-01 and SD-02 were found to inhibit HDAC8 at concentrations (IC50) 9.0 nM and 2.7 nM, respectively.


Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites.
Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26-month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred. The major toxicity observed was delayed cerebral oedema. We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose. A comparison of an enzyme immunoassay and gas liquid chromatographic methodologies for measuring valproic acid in this setting is also presented. It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity.


Peptide amphiphile nanostructure-heparin interactions and their relationship to bioactivity.
Heparin-protein interactions are important in many physiological processes including angiogenesis, the growth of new blood vessels from existing ones. We have previously developed a highly angiogenic self-assembling gel, wherein the self-assembly process is triggered by the interactions between heparin and peptide amphiphiles (PAs) with a consensus heparin binding sequence. In this report, this consensus sequence was scrambled and incorporated into a new peptide amphiphile in order to study its importance in heparin interaction and bioactivity. Heparin was able to trigger gel formation of the scrambled peptide amphiphile (SPA). Furthermore, the affinity of the scrambled molecule for heparin was unchanged as shown by isothermal titration calorimetry and high Förster resonance emission transfer efficiency. However, both the mobile fraction and the dissociation rate constant of heparin, using fluorescence recovery after photobleaching, were markedly higher in its interaction with the scrambled molecule implying a weaker association. Importantly, the scrambled peptide amphiphile-heparin gel had significantly less angiogenic bioactivity as shown by decreased tubule formation of sandwiched endothelial cells. Hence, we believe that the presence of the consensus sequence stabilizes the interaction with heparin and is important for the bioactivity of these new materials.


Phototherapy for Vitiligo.
Vitiligo is a common disorder with a severe impact on quality of life. The authors review recent advances in phototherapy for vitiligo focusing on narrowband ultraviolet B including mechanisms, treatment recommendations, and combination therapies. Phototherapy is the first-line treatment of choice for vitiligo with narrowband UVB preferred for widespread vitiligo and excimer used for localized lesions. However, unfamiliarity with prescribing phototherapy may be limiting clinicians from using it to its full potential. This article provides clinicians with the critical information needed to safely and effectively provide phototherapy for their patients with vitiligo.


Failure to interact with Brd4 alters the ability of HPV16 E2 to regulate host genome expression and cellular movement.
The E2 protein of the carcinogen human papillomavirus 16 (HPV16) regulates replication and transcription of the viral genome in association with viral and cellular proteins. Our previous work demonstrated that E2 can regulate transcription from the host genome. E2 can activate transcription from adjacent promoters when located upstream using E2 DNA binding sequences and this activation is dependent upon the cellular protein Brd4; this report demonstrates that a Brd4 binding E2 mutant alters host genome expression differently from wild type E2. Of particular note is that highly down regulated genes are mostly not affected by failure to interact with Brd4 suggesting that the E2-Brd4 interaction is more responsible for the transcriptional activation of host genes rather than repression. Therefore failure to interact efficiently with Brd4, or altered levels of Brd4, would alter the ability of E2 to regulate the host genome and could contribute to determining the outcome of infection.


Posterior tibial tendoscopy: Description of an accessory proximal portal and assessment of tendon vascularization lesion according to portal.
Posterior tibial tendoscopy was codified in 1997 by Van Dijck, who described a portal between 1.5 and 2cm proximally and distally to the tip of the medial malleolus. However, this approach does not allow proximal exploration of the posterior tibial tendon (PTT). We here describe an accessory portal 7cm proximal to the medial malleolus, enabling complete PTT exploration. Posterior tibial tendoscopy was performed on 12 cadaver specimens, mapping PTT exploration and vascularization. The accessory portal enabled the whole PTT to be explored, from the myotendinous junction to the entry into the retromalleolar groove. PTT observation quality was improved compared to using a submalleolar portal. Dissection confirmed systematic presence of a vincula on the posterior side of the tendon, connected to the flexor digitorum longus (FDL) tendon, containing collateral vessels of the posterior tibial artery. None of these elements were damaged by the tendoscopy as long and the scope and motorized instruments were not rotated on the posterior side of the supramalleolar part of the PTT. This accessory entry portal provides complete PTT exploration without the risk of neurovascular bundle lesion.


Microfluidics-Based Nanobiosensors for Healthcare Monitoring.
Efficient healthcare management demands prompt decision-making based on fast diagnostics tools, astute data analysis, and informatics analysis. The rapid detection of analytes at the point of care is ensured using microfluidics in synergy with nanotechnology and biotechnology. The nanobiosensors use nanotechnology for testing, rapid disease diagnosis, monitoring, and management. In essence, nanobiosensors detect biomolecules through bioreceptors by modulating the physicochemical signals generating an optical and electrical signal as an outcome of the binding of a biomolecule with the help of a transducer. The nanobiosensors are sensitive and selective and play a significant role in the early identification of diseases. This article reviews the detection method used with the microfluidics platform for nanobiosensors and illustrates the benefits of combining microfluidics and nanobiosensing techniques by various examples. The fundamental aspects, and their application are discussed to illustrate the advancement in the development of microfluidics-based nanobiosensors and the current trends of these nano-sized sensors for point-of-care diagnosis of various diseases and their function in healthcare monitoring.


Isolation and preliminary characterization of rat liver cells resistant to 7-ketocholesterol.
Two clones of the rat liver cell line, GAI, were selected and propagated in 4 microgram/ml of the cholesterol analogue, 7-ketocholesterol. One of the variants was also found to be resistant to another toxic analogue, 25-hydroxycholesterol. 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 220.127.116.11) activity was elevated in both variant clones, but was not increased substantially upon incubation of the cells in lipid-depleted medium. The reductase activity was increased 3-fold in the wild type cells under the same conditions. Incubation of the cells in lipid-depleted medium resulted in a 3-fold increase in the rate of sterol synthesis from [14C]acetate in all three types. In the presence of 2 microgram/ml 7-ketocholesterol, the reductase activity in all three cell lines decreased at an equal rate, but activity of the enzyme was still measurable after 48 h in the presence of the analogue. Sterol synthesis was reduced almost to zero in the wild type cells under these conditions, while the variant cells retained 12--15% of their capacity for sterol synthesis. These results are interpreted to indicate that 7-ketocholesterol, besides affecting sterol synthesis at the level to 3-hydroxy-3-methylglutaryl coenzyme A reductase, must also affect sterol synthesis at another step further along the synthetic pathway.


Safety, reliability and limitations of the given patency capsule in patients at risk of capsule retention: a 3-year technical review.
The patency capsule may prevent capsule retention in high-risk patients. However data on its use in routine clinical practice is limited. Patients referred to our institution between Feb-04 and Jan-07 were reviewed. The following data was collected: presenting symptoms; medical/surgical history; medication; radiology; patency/video capsule result; subsequent investigations; clinical outcomes. 373 patients were referred. In 315 (84%) 'low-risk' patients (no patency capsule): delayed transit occurred in three, with no cases of capsule retention. In 58 (16%) 'high risk' patients (patency capsule): asymptomatic retention occurred in eight, all with pathology despite normal prior barium studies in six; in four cases patency location was incorrectly assessed radiologically, leading to video capsule retention and surgery in one. Most patients can safely undergo capsule endoscopy without a patency capsule. The patency capsule appears safe and is indicative of pathology when retained. Assessment of patency capsule location post ingestion can be difficult, and if barium radiology is equivocal a limited abdominal computed tomography (CT) scan is suggested.


The toxicokinetics of cadmium in carp under normoxic and hypoxic conditions.
Temporal depletion of oxygen, i.e. hypoxic events, frequently occurs in natural waters. It has been suggested that accumulation of micro-pollutants increases in aquatic animals as a result of an increased ventilation rate during such occasions. The observed increased toxicity under hypoxia of micro-pollutants may support this hypothesis, but for heavy metals the available uptake studies are contradictory. The present study tests whether accumulation of cadmium in common carp, Cyprinus carpio (L.) is increased under hypoxia and if the toxicokinetics are altered. A cadmium toxicity study was performed in which the cadmium uptake rates were determined using the radiotracer 109Cd under hypoxia and normoxia. The cadmium toxicokinetics were studied with radiotracer experiments at 100% air saturation, 50%, and 25% saturation from 6.5 nmol/L Cd at 25 degrees C. We could confirm the higher sensitivity of carp to cadmium under hypoxia. Hypoxic conditions did not influence the uptake rates or the accumulation dynamics. Therefore, the increased sensitivity of carp for Cd under hypoxia cannot be explained by a higher Cd body burden, initiated by a higher uptake rate or lower elimination rate under hypoxia. Additional, possible indirect effects, such as internal anoxia due to gill damage, could play a role in Cd toxicity under hypoxia.


Factors affecting survival in patients with oral cancer: an Australian perspective.
Little is known regarding disease-specific cumulative survival and factors affecting survival in Australian populations with oral squamous cell carcinoma. Kaplan Meier and Cox proportional hazards models were used to determine survival factors in 116 consecutive patients treated surgically at a single institution. Overall 5-year disease-specific survival rate was 83.3%. Five-year disease-specific survival probability was 88.7%, 83.8%, 83.3% and 76.5% for stage I, II, III and IV, respectively. Univariate analysis revealed that local and regional recurrence, distant metastases, N stage, margin status, radiotherapy, perivascular spread and extra-capsular spread (ECS) significantly influenced survival. Significant multivariate factors included local and regional recurrence, positive margins, and ECS. Better survival rates were found than in previous, older Australian reports. Close observation for early recurrence and aggressive management of patients with recurrence, positive margins and ECS, is advised.


[Results and problems set by the introduction of Zonitidae snails in some biotopes of Lymnaea trancatula Müller in Indre and Haute-Vienne, France (author's transl)].
Systematic placing of Zonitidea snails: Zonitoides nitidus and Oxychilus draparnaudi alone or in groups, in different series of habitats of Lymnaea truncatula in Haute-Vienne, France (1974-1976) shows: --the elimination of Lymnaea truncatula is entire after two years in temporary habitats covered with grass just mowed at the beginning of summer drying. The presence of stones, which make shelters, increases numbers of surviving snails. --predators-placing without previous grass-mowing is effective only on banks of rivers.


Direct C-1 hydroxylation of vitamin D compounds: convenient preparation of 1alpha-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3, and 1alpha-hydroxyvitamin D2.
An efficient procedure for the direct C-1 hydroxylation of vitamin D compounds has been developed. The method involves conversion of vitamin D3 tosylates to 3,5-cyclovitamin D derivatives, allylic oxidation with selenium dioxide, and acid-catalyzed solvolysis to the 1 alpha-hydroxyvitamin D analogs. When applied to vitamin D3,25-hydroxyvitamin D3, and vitamin D2, this sequence give the corresponding 1alpha-hydroxylated derivatives in 10-15% yield.


Correlations of nonlinear sorption of organic solutes with soil/sediment physicochemical properties.
The estimation of solute sorptive behaviors is essential when direct sorption data are unavailable and will provide a convenient way to assess the fate and the biological activity of organic solutes in soil/sediment environments. In this study, the sorption of 2,4-dichlorophenol (2,4-DCP) on 19 soil/sediment samples and the sorption of 13 organic solutes on one sediment were investigated. All sorption isotherms are nonlinear and can be described satisfactorily by a simple dual-mode model (DMM): q(e)=KpCe+Q0 . bCe/(1+bCe), where Kp (mlg(-1)) is the partition coefficient; Ce (microgml(-1)) is the equilibrium concentration; Q0 (microgg(-1)) is the maximum adsorption capacity; Q0 . b (mlg(-1)) is the Langmuir-type isotherm slope in the low concentration (Henry's law) range and b (mlmicrog(-1)) is a constant related to the affinity of the surface for the solute. Based on these nonlinear sorption isotherms and similar other nonlinear isotherms, it is observed that, for both polar 2,4-DCP and nonpolar phenanthrene, Kp, Q0 and Q0 . b are linearly correlated with soil/sediment organic carbon content (f(oc) in the range of 0.118-53.7%). The results indicate that the nonlinear sorption of organic solutes results primarily from interactions with soil/sediment organic matter. The K*oc K*oc=Kp/f(oc)), Qoc (Qoc=Q0/f(oc)), Loc (Loc=Q0 . b/f(oc)) and b for a given organic solute with different soils/sediments are largely invariant. Furthermore, logK*oc, logb and logLoc for various organic solutes are correlated significantly with the solute logKow or logSw (logKow in the range of 0.9 to 5.13 and logSw in the range of -6.176 to -0.070). A fundamental empirical equation was then established to calculate approximately the nonlinear sorption from soil/sediment f(oc) and solute Sw for a given solute equilibrium concentration.


Methionine-Based pH and Oxidation Dual-Responsive Block Copolymer: Synthesis and Fabrication of Protein Nanogels.
In this paper, we synthesized a block copolymer containing pendent thioether functionalities by reversible addition-fragmentation chain transfer polymerization of a tert-butyloxycarbonyl (Boc)-l-methionine-(2-methacryloylethyl)ester (Boc-METMA) monomer using a poly(ethylene glycol) (PEG)-based chain transfer agent. The deprotection of Boc groups resulted in an oxidation and pH dual-responsive cationic block copolymer PEG-b-P(METMA). The block copolymer PEG-b-P(METMA) possessing protonable amine groups was water-soluble at pH < 6.0 and self-assembled to form spherical micelles at pH > 6.0. In the presence of H2O2, the micelles first became highly swollen with time and completely disassembled at last, demonstrating the H2O2-responsive feature because of the oxidation of hydrophobic thioether to hydrophilic sulfoxide. The anticancer drug curcumin (Cur) was entrapped in the polymeric micelles and the Cur-loaded micelles displayed a H2O2-triggered release profile as well as a pH-dependent release behavior, making PEG-b-P(METMA) micelles promising nanocarriers for reactive oxygen species-responsive drug delivery. Taking advantage of the protonated amine groups, the cationic polyelectrolyte PEG-b-P(METMA) formed polyion complex micelles with glucose oxidase (GOx) through electrostatic interactions at pH 5.8. By cross-linking the cores of PIC micelles with glutaraldehyde, the PIC micelles were fixed to generate stable GOx nanogels under physiological conditions. The GOx nanogels were glucose-responsive and exhibited glucose-dependent H2O2-generation activity in vitro and improved storage and thermal stability of GOx. Cur can be encapsulated in the GOx nanogels, and the Cur-loaded GOx nanogels demonstrate the glucose-responsive release profile. The GOx nanogels displayed high cytotoxicity to 4T1 cells and were effectively internalized by the cells. Therefore, these GOx nanogels have potential applications in the areas of cancer starvation and oxidation therapy.


MERGE: A Multi-graph Attentive Representation learning framework integrating Group information from similar patients.
It is an important research task in the field of medical big data to predict patient's future health status according to the historical temporal Electronic Health Records (EHRs). Most of the existing deep learning-based medical prediction methods only focus on the patient's individual information. However, due to the sparseness and low quality of EHR data, individual clinical records of single patient often cannot provide complete health information, which severely limits the accuracy of the prediction models. In this paper, we propose a Multi-graph attEntive Representation learning framework integrating Group information from similar patiEnts(MERGE) for medical prediction. In this framework, while capturing the individual patient's temporal characteristics through the individual representation learning module, the group representation leaning module is used to learn group representations of similar patients from different aspects as a supplement, thereby effectively improving the accuracy of patients' representation. We evaluate our method on the MIMIC-III dataset for the task of in-hospital mortality prediction and Xiangya dataset for cardiovascular diseases (CVDs) prediction. The experimental results show that MERGE outperforms the state-of-the-art methods.


HTLV-1-associated myelopathy/tropical spastic paraplegia with sporadic late-onset nemaline myopathy: a case report.
Sporadic late onset nemaline myopathy (SLONM) is a muscle disorder characterized by the presence of nemaline rods in muscle fibers. SLONM has no known genetic cause but has been associated with monoclonal gammopathy of undetermined significance and with human immunodeficiency virus (HIV) infection. Human T-cell leukemia virus-1 (HTLV-1) is a known causative agent of adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraplegia (HAM/TSP), a chronic inflammatory neurological disease. HTLV-1 has been reported to be implicated in inflammatory myopathies, as well as in HIV infection.; however, there have been no reports of an association between HTLV-1 infection and SLONM to date. A 70-year-old Japanese woman presented with gait disturbance, lumbar kyphosis, and respiratory dysfunction. The diagnosis of HAM/TSP with SLONM was made based on characteristic clinical symptoms of HAM/TSP, such as spasticity in the lower extremities, and cerebrospinal fluid test results; and of SLONM, such as generalized head drooping, respiratory failure, and muscle biopsy results. Steroid treatment was initiated and improvement in her stooped posture was observed after 3 days of treatment. This is the first case report of SLONM combined with HTLV-1 infection. Further studies are needed to elucidate the relationship between retroviruses and muscle diseases.


The case for emulating insect brains using anatomical "wiring diagrams" equipped with biophysical models of neuronal activity.
Developing whole-brain emulation (WBE) technology would provide immense benefits across neuroscience, biomedicine, artificial intelligence, and robotics. At this time, constructing a simulated human brain lacks feasibility due to limited experimental data and limited computational resources. However, I suggest that progress toward this goal might be accelerated by working toward an intermediate objective, namely insect brain emulation (IBE). More specifically, this would entail creating biologically realistic simulations of entire insect nervous systems along with more approximate simulations of non-neuronal insect physiology to make "virtual insects." I argue that this could be realistically achievable within the next 20 years. I propose that developing emulations of insect brains will galvanize the global community of scientists, businesspeople, and policymakers toward pursuing the loftier goal of emulating the human brain. By demonstrating that WBE is possible via IBE, simulating mammalian brains and eventually the human brain may no longer be viewed as too radically ambitious to deserve substantial funding and resources. Furthermore, IBE will facilitate dramatic advances in cognitive neuroscience, artificial intelligence, and robotics through studies performed using virtual insects.


The PM2.5 concentration reduction improves survival rate of lung cancer in Beijing.
Long-term exposure to ambient fine particulate matter (PM2.5) has been linked to increases in the incidence of lung cancer. However, more evidence is needed to conclude its effects on lung cancer survival. The study aimed to explore the relationship between long-term PM2.5 exposure and lung cancer survival and evaluated the benefits of clean air actions in Beijing. A whole-population cohort study was conducted on lung cancer patients diagnosed between 2001 and 2017. An atmospheric chemical transport model was used to estimate exposure under a counterfactual scenario without the policy and then quantified the effect of the policy. Cox regression models were used with the seasonality-adjusted PM2.5 as the main effect. A 10 μg/m3 increase in PM2.5 was estimated to be with a 6.5 % (95 % CI: 4.8 %, 8.2 %) increase in the mortality rates. The association was heterogeneous and modified by individual-level characteristics. The clean air actions were estimated to have prevented 3548 (95 % CI: 3280, 3825) premature deaths and to have prolonged survival time by 4.29 months (95 % CI: 0.01, 25.11). Our findings suggest that PM2.5 exposure lowers the survival rate for lung cancer. The clean air actions implemented in Beijing can protect lung cancer patients by increasing their survival time. Long-term exposure to PM2.5 can lower lung patients' survival rates whereas the clean air actions in Beijing have prolonged these patients' survival time by reducing PM2.5 level.


Carbon footprint: current methods of estimation.
Increasing greenhouse gaseous concentration in the atmosphere is perturbing the environment to cause grievous global warming and associated consequences. Following the rule that only measurable is manageable, mensuration of greenhouse gas intensiveness of different products, bodies, and processes is going on worldwide, expressed as their carbon footprints. The methodologies for carbon footprint calculations are still evolving and it is emerging as an important tool for greenhouse gas management. The concept of carbon footprinting has permeated and is being commercialized in all the areas of life and economy, but there is little coherence in definitions and calculations of carbon footprints among the studies. There are disagreements in the selection of gases, and the order of emissions to be covered in footprint calculations. Standards of greenhouse gas accounting are the common resources used in footprint calculations, although there is no mandatory provision of footprint verification. Carbon footprinting is intended to be a tool to guide the relevant emission cuts and verifications, its standardization at international level are therefore necessary. Present review describes the prevailing carbon footprinting methods and raises the related issues.


What are candidate biobehavioral mechanisms underlying the association between secondhand smoke exposure and mental health?
There is a consistent positive and significant association between secondhand smoke exposure and mental health outcomes in the literature. There are potential genetic and behavioral confounders (e.g., psychological stress, maternal depression, and family functioning) were discussed, as well as potential causal neurobiological pathways (e.g., dopamine system). Further neurobiological research to establish causal pathways is needed as well as the integration of positive observational findings into clinical and public health prevention practices.


Effects in the upper face of far east Asians after Oriental blepharoplasty: a scientific perspective on why Oriental blepharoplasty is essential.
Oriental blepharoplasty is the most frequently performed aesthetic surgery among far east Asians (i.e., Korean, Chinese, Japanese, and Taiwanese). Numerous studies on oriental blepharoplasty have been published, but only a few, if any, have reported on the measurable effects of such surgeries on the upper face. To scientifically evaluate the changes in the upper face of young Korean adults after oriental blepharoplasty, a periocular morphometry study was conducted. A retrospective image analysis was used to identify the changes in the upper face after oriental blepharoplasty. Preoperative and postoperative digital facial images of 612 patients (598 women and 14 men) who underwent oriental blepharoplasty were examined. The height of the palpebral fissure (HPF), the distance between the highest point of the palpebral fissure of the upper eyelid and the eyebrow (DEE), and the distance between the eyebrow and the hairline (DEH) were measured to analyze the effects of oriental blepharoplasty in the upper face. After oriental blepharoplasty, the HPF and DEH increased in length by 11.8 and 4.9 %, respectively, and the DEE decreased in length by 14.0 %. Patients who originally did not possess double eyelids showed greater changes than those who originally did possess such eyelids. Such changes were characterized by a significant inverse correlation between the DEE and DEH. In addition, when postoperative changes were measured before and after 6 months, the palpebral fissure and forehead showed an even greater increase. Oriental blepharoplasty can induce substantial changes in the proportions of the upper face. It can not only increase the size of the eyes, but also induce changes in eyebrow position resulting in a more refreshed appearance.


High adhesion ability of anammox granular microbes directly revealed by QCM-D technique.
Anammox bacteria are widely found to grow in bioaggregates form, but the reason for their high aggregation ability remains elusive. In this study, four kinds of sludge, i.e., anammox granules, anaerobic granules, aerobic granules, and partial nitrification flocs, were studied and compared to investigate their differences in adherence properties. We directly explored the adherence properties of sludge samples before and after extracellular polymeric substances (EPS) extraction, using quartz-crystal microbalance technique with dissipation monitoring technique. Results showed that EPS indeed stimulated the adherence properties of all sludge samples. The most striking feature here is that anammox consortia had the highest adhesion rate and mass, and formed the most compact layer on the gold-coated sensor surfaces both before and after EPS extraction among the four sludge samples, indicating their inherent high adhesion ability. The composition and spectral characteristics of EPS samples were also investigated, and it reveals that the relatively high extracellular proteins/polysaccharides ratio of anammox granules (3.2 ± 0.4) rather than total EPS concentration had contributed to their high adhesion ability. The findings are helpful for understanding the adherence properties of anammox bacteria, and will serve as a guide for further researches to exploring the aggregation process of anammox bacteria.


Isolated dislocation of the proximal tibiofibular joint in a long jumper.
Acute traumatic proximal tibiofibular joint dislocation is an exceedingly rare injury. This is a case report in a rare horizontal type joint variant, following a long jump injury. The diagnostic approach when this injury is suspected is described.


Amyloidosis presenting as a mass in the neck.
A 54-year-old white male presented with a large suprahyoid midline mass. On thorough history and physical examination, he had features which characterize amyloidosis, including congestive heart failure and carpal tunnel syndrome. The classification, clinical findings, and associated syndromes are reviewed. A striking feature of the amyloid deposit is its rapid growth. Amyloidosis should now be considered in a differential diagnosis of a neck mass.


Case report: multiple and atypical amoebic cerebral abscesses resistant to treatment.
The parasite Entamoeba histolytica is the causal agent of amoebiasis, a worldwide emerging disease. Amebic brain abscess is a form of invasive amebiasis that is both rare and frequently lethal. This condition always begins with the infection of the colon by E. histolytica trophozoites, which subsequently travel through the bloodstream to extraintestinal tissues. We report a case of a 71-year-old female who reported an altered state of consciousness, disorientation, sleepiness and memory loss. She had no history of hepatic or intestinal amoebiasis. A preliminary diagnosis of colloidal vesicular phase neurocysticercosis was made based on nuclear magnetic resonance imaging (NMRI). A postsurgery immunofluorescence study was positive for the 140 kDa fibronectin receptor of E. histolytica, although a serum analysis by ELISA was negative for IgG antibodies against this parasite. A specific E. histolytica 128 bp rRNA gene was identified by PCR in biopsy tissue. The final diagnosis was cerebral amoebiasis. The patient underwent neurosurgery to eliminate amoebic abscesses and was then given a regimen of metronidazole, ceftriaxone and dexamethasone for 4 weeks after the neurosurgery. However, a rapid decline in her condition led to death. The present case of an individual with a rare form of cerebral amoebiasis highlights the importance of performing immunofluorescence, NMRI and PCR if a patient has brain abscess and a poorly defined diagnosis. Moreover, the administration of corticosteroids to such patients can often lead to a rapid decline in their condition.


Nurses' experiences regarding shift patterns in isolation wards during the COVID-19 pandemic in China: A qualitative study.
To explore nurses' experiences regarding shift patterns while providing front-line care for COVID-19 patients in isolation wards of hospitals in Shanghai and Wuhan during the novel coronavirus pandemic. Our findings will help to optimise shift work scheduling, use the existing nursing workforce more efficiently and improve nursing quality. Nurses are one of the main professionals fighting against COVID-19. Providing care for COVID-19 patients is challenging. In isolation wards, the workload has increased, and the workflow and shift patterns are completely different from the usual. More importantly, there is a shortage of nurses. Therefore, it is essential and urgent to arrange nurses' shifts correctly and use the existing workforce resources efficiently. A qualitative descriptive study of 14 nurses in Chinese hospitals was conducted. Semi-structured interviews were used based on the phenomenological research method; data were analysed using Colaizzi's method of data analysis. This study aligns with the COREQ checklist. Four themes were extracted: assess the competency of nurses to assign nursing work scientifically and reasonably, reorganise nursing workflow to optimise shift patterns, communicate between managers and front-line nurses to humanise shift patterns, and nurses' various feelings and views on shift patterns. It is necessary to arrange shift patterns scientifically and allocate workforce rationally to optimise nursing workforce allocation, reduce nurses' workload, improve nursing quality and promote physical and mental health among nurses during the COVID-19 pandemic. This study emphasised nurses' experiences on shift patterns in isolation wards, providing useful information to manage shift patterns. Nursing managers should arrange shifts scientifically, allocate nursing workforce rationally, formulate emergency plans and establish emergency response rosters during the COVID-19 pandemic.


A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.
Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1 and RefSeq2 launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref. 3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.


Acute peroneal compartment syndrome in a well conditioned athlete: report of a case.
A case report of acute peroneal compartment syndrome occurring in a 25-year-old male softball player is presented, in which neuropraxia of the common peroneal nerve occurred within 8 hr after onset and in which complete recovery occurred after fasciotomy was done 13 hr after onset of symptoms. A plea is made for early diagnosis and complete fasciotomy carried out as a surgical emergency. This must be accomplished if results previously reported, indicating permanent disability in 80%, are to be improved.


Hypocortisolism in survivors of severe acute respiratory syndrome (SARS).
Following the severe acute respiratory syndrome (SARS) outbreak, many survivors were observed to suffer from psychosomatic symptoms reminiscent of various endocrine disorders. Hence, we sought to determine the existence of any chronic endocrine sequelae in SARS survivors. Sixty-one survivors of SARS prospectively recruited were analysed for hormonal derangements 3 months following recovery. Patients with pre-existing endocrine disorders were excluded. Any endocrine abnormalities diagnosed were investigated and treated where indicated up to a year. Serial evaluation facilitated characterization of trends and prognostication of any endocrinological aberrations. Twenty-four (39.3%) patients had evidence of hypocortisolism. The hypothalamic-pituitary-adrenal (HPA) axis dysfunction of the majority resolved within a year. Two (3.3%) of the hypocortisolic cohort had transient subclinical thyrotoxicosis. Four (6.7%) were biochemically hypothyroid, being comprised of three with central hypothyroidism and one with primary hypothyroidism. Two of the three with central hypothyroidism had concomitant central hypocortisolism. Eight had subnormal DHEAS levels. These preliminary findings highlight a possible aetiologic role of SARS-associated coronavirus in causing a reversible hypophysitis or direct hypothalamic effect, with the HPA axis affected more frequently than the HPT axis.


Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy.
The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans or bovine spongiform encephalopathy (BSE) in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc) in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods. We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10(-8) nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle. We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.