Chemical and toxicological characterisation of residues from offshore in-situ burning of spilled fuel oils.
Burn residues collected after large scale experimental in situ burns performed in the North Sea were characterised with emphasis on chemistry and acute toxicity. Low-energy water accommodated fractions (WAFs) of three marine fuels (Ultra Low Sulphur Fuel Oil (ULSFO), bunker oil (IFO180), and marine gas oil (MGO) and their field-generated residues from in situ burning (ISB). were prepared to evaluate the potential impact of ISB residue to the environment. The toxicity effects on primary consumers were assessed by testing on early life stage (nauplii) of the marine copepod Calanus finmarchicus. Toxicity studies showed that ISB decreased the acute toxicity of the WAFs compared to the initial oils. WAF of MGO had highest toxicity, and ISB residue of MGO seems to be more toxic than WAFs of fresh ULSFO and IFO180. Additive toxicity expressed as toxic unit (TU) based on the chemical composition also indicated that the toxicity of WAFs from ISB residues were lower than for the initial oils. The 2-3 ring PAHs seem to contribute most to the TU. Overall, the three offshore burns reduced the total mass of PAHs in the water accommodated fractions by >90 % compared to the released unburned oils and caused a reduction of the acute toxicity to copepod nauplii.


Electrochemical degradation of crystal violet with BDD electrodes: effect of electrochemical parameters and identification of organic by-products.
This paper explores the applicability of electrochemical oxidation on a triphenylmethane dye compound model, hexamethylpararosaniline chloride (or crystal violet, CV), using BDD anodes. The effect of the important electrochemical parameters: current density (2.5-15 m A cm(-2)), dye concentration (33-600 mg L(-1)), sodium sulphate concentration (7.1-50.0 g L(-1)) and initial pH (3-11) on the efficiency of the electrochemical process was evaluated. The results indicated that while the current density was lower than the limiting current density, no side products (hydrogen peroxide, peroxodisulphate, ozone and chlorinated oxidizing compounds) were generated and the degradation, through OH radical attack, occurred with high efficiency. Analysis of intermediates using GC-MS investigation identified several products: N-methylaniline, N,N-dimethylaniline, 4-methyl-N,N-dimethylaniline, 4-methyl-N-methylaniline, 4-dimethylaminophenol, 4-dimethylaminobenzoic acid, 4-(N,N-dimethylamino)-4'-(N',N'-dimethylamino) diphenylmethane, 4-(4-dimethylaminophenyl)-N,N-dimethylaniline, 4-(N,N-dimethylamino)-4'-(N',N'-dimethylamino) benzophenone. The presence of these aromatic structures showed that the main CV degradation pathway is related to the reaction of CV with the OH radical. Under optimal conditions, practically 100% of the initial substrate and COD were eliminated in approximately 35 min of electrolysis; indicating that the early CV by-products were completely degraded by the electrochemical system.


Urinary lipid changes during the development of chemically-induced renal papillary necrosis: a study using mefenamic acid and N-phenylanthranilic acid.
Acute renal papillary necrosis (RPN) in animals is characterized by increased renal lipid accumulation. The excretion of renal lipids into urine has been determined to evaluate their possible use as sensitive early biomarkers for the diagnosis of RPN. This study investigates injury induced by two model nephrotoxins, mefenamic acid (MFA), a non-steroidal anti-inflammatory drug (NSAID), and its analogue N-phenylanthranilic acid (NPAA). Oral NPAA was given repeatedly at doses of 100, 250 and 500 mg kg(-1) daily for 5 days, followed by a 2 day respite over the weekend, and then four further daily doses. The same dosing procedure was used with MFA, but at doses of 75, 150 and 300 mgkg(-1). The control groups were given vehicle orally using the same volume given to the test groups. Urinary phospholipids (PLs), notably sphingomyelin (SPM), phosphatidylcholine (PC) and phosphatidylethanolamine (PE), were measured and compared with other urinary parameters. Histopathological investigations were also performed to confirm the presence or absence of RPN. Following MFA treatment, PC, PI and PE were raised significantly (p < 0.001) on days 1 and 3 and for the remaining part of the experiment. After NPAA treatment, PI showed a transient elevation, and PC and PE levels were significantly increased from day 2 onwards. Both drugs caused a dose-related increase in PLs. There was no significant increase in the level of other urinary parameters. However, histopathological examination of the kidney on day 11 revealed lesions in the medulla and papilla following treatment with the two papillotoxins. These findings demonstrate the potential of urinary PLs as diagnostic non-invasive biomarkers for early renal injury associated with RPN, which may provide an important improvement in the approach to the therapeutic management of analgesic nephropathy.


Apoptosis pathway signature for prediction of treatment response and clinical outcome in childhood high risk B-Precursor acute lymphoblastic leukemia.
The most common cancer in children is acute lymphoblastic leukemia (ALL) and it had high cure rate, especially for B-precursor ALL. However, relapse due to drug resistance and overdose treatment reach the limitations in patient managements. In this study, integration of gene expression microarray data, logistic regression, analysis of microarray (SAM) method, and gene set analysis were performed to discover treatment response associated pathway-based signatures in the original cohort. Results showed that 3772 probes were significantly associated with treatment response. After pathway analysis, only apoptosis pathway had significant association with treatment response. Apoptosis pathway signature (APS) derived from 15 significantly expressed genes had 88% accuracy for treatment response prediction. The APS was further validated in two independent cohorts. Results also showed that APS was significantly associated with induction failure time (adjusted hazard ratio [HR] = 1.60, 95% confidence interval [CI] = [1.13, 2.27]) in the first cohort and significantly associated with event-free survival (adjusted HR = 1.56, 95% CI = [1.13, 2.16]) or overall survival in the second cohort (adjusted HR = 1.74, 95% CI = [1.24, 2.45]). APS not only can predict clinical outcome, but also provide molecular guidance of patient management.


Kinetics, thermodynamics, and physical characterization of corn stover (Zea mays) for solar biomass pyrolysis potential analysis.
Solar pyrolysis of agricultural waste has huge potential for sustainable production of fuel and chemical feedstock. In this paper, the kinetics, thermodynamics, and physical characterization of corn stover (CS) collected from Wyoming, USA was conducted with respect to solar pyrolysis. The kinetics and thermodynamics of the CS pyrolysis was analyzed in detail using the methods described by KAS (Kissinger-Akahira-Sunose) and FWO (Flynn-Wall-Ozawa), from which the activation energy, Gibbs energy, Arrhenius pre-exponential factor, enthalpy, and entropy were derived.14 other kinetics models based on reaction order, diffusion, nucleation, geometric contraction, power models were also examined, and models based on diffusion was found to be best suited. The CS was used for solar pyrolysis of biomass and the products were analyzed by mass spectroscopy, ICP-MS, GPC, micro-GC, and Elemental analyzer. The results show that CS is suitable for solar pyrolysis to produce chemicals and other fuels.


T4 phage gene 32 protein as a candidate organizing factor for the deoxyribonucleoside triphosphate synthetase complex.
After T4 bacteriophage infection of Escherichia coli, the enzymes of deoxyribonucleoside triphosphate biosynthesis form a multienzyme complex that we call T4 deoxyribonucleoside triphosphate (dNTP) synthetase. At least eight phage-coded enzymes and two enzymes of host origin are found in this 1.5-mDa complex. The complex may shuttle dNTPs to DNA replication sites, because replication draws from small pools, which are probably highly localized. Several specific protein-protein contacts within the complex are described in this paper. We have studied protein-protein interactions in the complex by immobilizing individual enzymes and identifying radiolabeled T4 proteins that are retained by columns of these respective affinity ligands. Elsewhere we have described interactions involving three T4 enzymes found in the complex. In this paper we describe similar analysis of five more proteins: dihydrofolate reductase, dCTPase-dUTPase, deoxyribonucleoside monophosphokinase, ribonucleotide reductase, and E. coli nucleoside diphosphokinase,. All eight proteins analyzed to date retain single-strand DNA-binding protein (gp32), the product of T4 gene 32. At least one T4 protein, thymidylate synthase, binds directly to gp32, as shown by affinity chromatographic analysis of the two purified proteins. Among its several roles, gp32 stabilizes single-strand template DNA ahead of a replicating DNA polymerase. Our data suggest a model in which dNTP synthetase complexes, probably more than one per growing DNA chain, are drawn to replication forks via their affinity for gp32 and hence are localized so as to produce dNTPs at their sites of utilization, immediately ahead of growing DNA 3' termini.


SnRK1α1 Antagonizes Cell Death Induced by Transient Overexpression of Arabidopsis thaliana ABI5 Binding Protein 2 (AFP2).
Plants are continuously exposed to environmental stressors. They have thus evolved complex signaling pathways to govern responses to a variety of stimuli. The hormone abscisic acid (ABA) has been implicated in modulating both abiotic and biotic stress responses in plants. ABI5 Binding Proteins (AFPs) are a family of negative regulators of bZIP transcription factors of the AREB/ABF family, which promote ABA responses. AFP2 interacts with Snf1-Related protein Kinase 1 (SnRK1), which belongs to a highly conserved heterotrimeric kinase complex that is activated to re-establish energy homeostasis following stress. However, the role of this interaction is currently unknown. Here, we show that transient overexpression of Arabidopsis thaliana AFP2 in Nicotiana benthamiana leaves induces cell death (CD). Using truncated AFP2 constructs, we demonstrate that CD induction by AFP2 is dependent on the EAR domain. Co-expression of the catalytic subunit SnRK1α1, but not SnRK1α2, rescues AFP2-induced CD. Overexpression of SnRK1α1 has little effect on AFP2 protein level and does not affect AFP2 subcellular localization. Our results show that a high level of AFP2 is detrimental for cell function and that SnRK1α1 antagonizes AFP2-induced CD most likely through a mechanism that does not involve AFP2 protein degradation or a change in subcellular localization.


Mass school physicals at military treatment facilities: a successful approach.
Mass physicals are commonly employed by military treatment facilities (MTFs) as a way to complete school physicals for large numbers of military dependents. Because these events are usually held a few times yearly, military staff may lack the experience necessary to conduct these events efficiently. Patient and staff satisfaction at these events can be very low if they are poorly planned and executed. At Martin Army Community Hospital (BMACH), the primary care clinics have developed an efficient and effective mass physical plan. The use of appointments for these physicals and prescreening immunization records are crucial to smooth mass physical operation. The use of color-coded signs, clear command structure, and pre-event training for staff are important tools for success. We describe our approach to mass physicals which can be adapted for use at other MTFs.


[Comparison of distribution of Ophiopogon japonicas polysaccharide in hearts of normal rats and myocardial ischemic rats].
To investigate the distribution of Ophiopogon Japonicas polysaccharide (OJP) in hearts of normal rats and myocardial ischemic rats, and obtain the further evidences for determining the mechanism of its anti-myocardial ischemia. Hearts of normal and myocardial ischemic groups were obtained at 5, 10, 30 and 60 min after once intravenous administration of OJP with the dose of 50 mg/kg. The concentration of OJP in samples was subsequently determined by HPGPC with a fluorescence detector. The distribution of OJP in hearts of myocardial ischemic rats was much more than that in normal groups at all the sampling times. Moreover, the differences were proved to be significant by SPSS software with the exception of the situation in the 30 min sampling time. The enhanced permeability and retention effect caused by ischemia can overcome the negative effect of the reduction of blood flow on the distribution of OJP from blood into myocardial ischemic zones and actually help OJP target myocardial ischemic zones where it can exert its pharmacological effect directly.


A novel validated procedure for the determination of nicotine, eight nicotine metabolites and two minor tobacco alkaloids in human plasma or urine by solid-phase extraction coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry.
A novel validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedure was developed and fully validated for the simultaneous determination of nicotine-N-beta-D-glucuronide, cotinine-N-oxide, trans-3-hydroxycotinine, norcotinine, trans-nicotine-1'-oxide, cotinine, nornicotine, nicotine, anatabine, anabasine and cotinine-N-beta-D-glucuronide in human plasma or urine. Target analytes and corresponding deuterated internal standards were extracted by solid-phase extraction and analyzed by LC-MS/MS with electrospray ionization (ESI) using multiple reaction monitoring (MRM) data acquisition. Calibration curves were linear over the selected concentration ranges for each analyte, with calculated coefficients of determination (R(2)) of greater than 0.99. The total extraction recovery (%) was concentration dependent and ranged between 52-88% in plasma and 51-118% in urine. The limits of quantification for all analytes in plasma and urine were 1.0 ng/mL and 2.5 ng/mL, respectively, with the exception of cotinine-N-beta-D-glucuronide, which was 50 ng/mL. Intra-day and inter-day imprecision were < or = 14% and < or = 17%, respectively. Matrix effect (%) was sufficiently minimized to < or = 19% for both matrices using the described sample preparation and extraction methods. The target analytes were stable in both matrices for at least 3 freeze-thaw cycles, 24 h at room temperature, 24 h in the refrigerator (4 degrees C) and 1 week in the freezer (-20 degrees C). Reconstituted plasma and urine extracts were stable for at least 72 h storage in the liquid chromatography autosampler at 4 degrees C. The plasma procedure has been successfully applied in the quantitative determination of selected analytes in samples collected from nicotine-abstinent human participants as part of a pharmacokinetic study investigating biomarkers of nicotine use in plasma following controlled low dose (7 mg) transdermal nicotine delivery. Nicotine, cotinine, trans-3-hydroxycotinine and trans-nicotine-1'-oxide were detected in the particular sample presented herein. The urine procedure has been used to facilitate the monitoring of unauthorized tobacco use by clinical study participants at the time of physical examination (before enrollment) and on the pharmacokinetic study day.


Kinematic analysis during toe-gripping strength exertion: angular changes in the ankle joint and leg muscle activities.
[Purposes] To investigate angular changes in the ankle joint and leg muscle activities during toe-gripping, and to examine the relationship between these changes and toe-gripping strength. [Subjects] Eleven healthy young women were selected. [Methods] We measured the toe-gripping strength, angular changes in the ankle joint, and leg muscle activities of all patients during toe-gripping. [Results] The mean change in the ankle angle in dorsiflexion from a neutral position was 3°, and a positive correlation was observed between this angle and toe-gripping strength (r = 0.61). Thus, toe-gripping strength increased with the angle of dorsiflexion. Regarding the leg muscle activities, activities of the tibialis anterior muscle and medial head of the gastrocnemius muscle demonstrated positive correlations with toe-gripping strength (r = 0.75 and r = 0.72, respectively). [Conclusion] These findings suggest that the ankle dorsiflexes in order to exert great toe-gripping strength, and the crural muscles contract simultaneously because of ankle fixation.


Carbon nanotubes: from nano test tube to nano-reactor.
Confinement of molecules and atoms inside carbon nanotubes provides a powerful strategy for studying structures and chemical properties of individual molecules at the nanoscale. In this issue of ACS Nano, Allen et al. explore the nanotube as a template leading to the formation of unusual supramolecular and covalent structures. The potential of carbon nanotubes as reactors for synthesis on the nano- and macroscales is discussed in light of recent studies.


Successful excision of an isolated mediastinal cystic lymphangioma with bilateral thoracoscopic surgery.
Lymphangioma is a well-known benign tumor and its cystic abnormalities of the lymph vessels are predominantly congenital. Cystic lymphangioma usually occurs in the neck, axillary region, and rarely in the mediastinum, which frequently occurs in children and young adults. A 20-year-old woman had symptoms of palpitation, cough, and dyspnea during the recent 1 month. Both chest comuted tomography and magnetic resonance imaging of the chest revealed a well-defined, 13 × 10-cm cystic lesion in the anterior mediastinum. The patient underwent bilateral video-assisted thoracoscopic excision of the cyst and lymphangioma was confirmed based on histopathologic examination. Here, we report a rare case of isolated mediastinal cystic lymphangioma that was successfully excised using a minimally invasive technique.


Acute vertebral compression fracture: differentiation of malignant and benign causes by diffusion weighted magnetic resonance imaging.
To evaluate the sensitivity, specificity and accuracy of diffusion weighted (DWI) magnetic resonance imaging (MRI) in the diagnosis and differentiation between benign (osteoporotic/infectious) and malignant vertebral compression fractures in comparison with histology findings and clinical follow up. The study was conducted at the Radiology Department, Aga Khan University Hospital (AKUH) Karachi. It was a one year cross-sectional study from 01/01/2009 to 01/01/2010. Forty patients with sixty three vertebral compression fractures were included. Diffusion-weighted sequences and apparent diffusion coefficient (ADC) images on a 1.5 T MR scanner were obtained in all patients to identify the vertebral compression fracture along with benign and malignant causes. Imaging findings were compared with histopathologic results and clinical follow-up. Diffusion-weighted MR imaging found to have, 92% sensitivity, 90% specificity and accuracy of 85% in differentiation of benign and malignant vertebral compression fracture while PPV and NPV were 78 % and 90% respectively. Diffusion weighted magnetic resonance imaging offers a safe, accurate and non invasive modality to differentiate between the benign and malignant vertebral compression fracture.


[Pancreatic resection for metastatic tumors to the pancreas].
We report 3 cases of resectable pancreatic metastasis. CASE 1: A 76-year-old woman was followed after nephrectomy for renal cell carcinoma for 13 years. CT examination demonstrated a high vascular lesion in the pancreatic body and tail. We conducted distal pancreatectomy and diagnosed with metastatic tumor from renal cell carcinoma. She died of liver metastasis 8 years after pancreatic resection. CASE 2: A 64-year-old man, who had undergone right lower lobectomy for lung cancer a year ago, was found to have a mass in the pancreatic tail. We performed distal pancreatectomy and diagnosed with metastatic tumor from lung cancer. He died of lung metastasis 12 months after pancreatic resection. CASE 3: A 62- year-old woman, who had undergone left nephrectomy for renal cell carcinoma 3 years ago, was found to have a mass in the pancreatic body. With a diagnosis of metastatic pancreatic tumor from renal cell carcinoma, distal pancreatectomy was done. She died of liver and lung metastases 15 months after pancreatic resection. Long-term survival can be achieved in patients undergoing a pancreatic standard resection including lymphadenectomy for isolated metastasis from nonpancreatic sites.


Institutional self-help therapy for alcoholism: clinical outcome.
Self-help peer-led therapy can yield improved cost effectiveness and clinical outcome in hospital-based alcoholism treatment. This was demonstrated by comparing two ambulatory alcoholism treatment programs: a control program operated solely by professional staff, and an experimental one based on peer-led self-help (SH). The SH program was staffed by only half as many primary therapists as the control. Patients in both programs were evaluated over the course of one year. By means of the Patient Status Form, a clinical assessment instrument applied monthly, SH patients were found to score significantly higher on social adjustment, although retention and drinking rates, and utilization of Alcoholics Anonymous and disulfiram were no different from controls. This study is the continuation of an initial comparison in which SH patients were found to have enhanced retention in treatment after discharge from an impatient service.


SVR-PAIRWISE method to predict MHC-II binding peptides.
Peptides binding to MHC molecules is of great importance in the process of triggering and initiating immune responses. There are two main kinds of MHC molecules, MHC class I and class II, and the prediction of MHC-II binding peptides is much more difficult due to their variable lengths, which makes it difficult to construct a preferable prediction model by using most of the existing methods. This paper presents a method, called as SVR-PAIRWISE, to combine Support Vector Regression (SVR) and pairwise alignment, to quantitatively predict the MHC-II binding peptides. The comparison results with some popular methods show its satisfying performances.


Expression of mucin carbohydrate antigens (T, Tn and sialyl Tn) and MUC-1 gene product in intraductal papillary-mucinous neoplasm of the pancreas.
Aberrant or incomplete glycosylation of mucins results in expression of T, Tn, and sialyl-Tn (STn) antigens in various malignant neoplasms. MUC-1 gene product (a mucin core protein of mammary type) is known to alter or overexpress in several malignant tumors. However, expression of these mucin-related antigens has rarely been examined in intraductal papillary-mucinous neoplasm (IPN) of the pancreas. The authors examined immunohistochemically the expression of these antigens and MUC-1 gene product in nine IPN. In normal pancreas (n = 5), pancreatic ducts did not express T, Tn, or STn antigens, but expressed MUC-1 gene product. Among the nine IPNs, two (22%) expressed T antigen, nine (100%) expressed Tn antigen, and seven (78%) expressed STn antigen. MUC-1 gene product was expressed in nine (100%) IPNs. In invasive ductal adenocarcinoma of the pancreas (n = 6), all cases showed strong expression of Tn and STn antigens and the MUC-1 gene product, but expressed no T antigen. The expression of these antigens and MUC-1 gene product was focal in IPN, whereas it was diffuse in invasive ductal adenocarcinoma of the pancreas. These data suggest that aberrant or incomplete glycosylation occurs in epithelial mucins of IPN, that IPN is a borderline or low grade malignant neoplasm in terms of mucin-related antigen expression, and that mucin core protein (MUC-1 gene product) does not alter during pancreatic ductal carcinogenesis.


Rapid protein identification using N-terminal "sequence tag" and amino acid analysis.
Proteins can be identified by amino acid analysis and database matching, but it is often desirable to increase the confidence in identity through the use of other techniques. Here we describe a rapid protein identification method that uses Edman degradation to create a 3 or 4 amino acid N-terminal "sequence tag," following which proteins are subjected to amino acid analysis protein identification procedures. Edman degradation methods have been modified to take only 23 min per cycle, and rapid amino acid analysis techniques are used. The Edman degradation and amino acid analysis is done on a single PVDF membrane-bound protein sample. A computer database matching program is also presented which uses both amino acid composition and "sequence tag" data for protein identification. This method represents the most inexpensive, accurate, and rapid means of protein identification, which is ideal for the screening of proteomes separated by 2-D gel electrophoresis. The creation of N-terminal Edman degradation "sequence-tags" prior to peptide mass fingerprinting of samples should also be useful.


[Sonography of muscles].
Sonography constitutes a method of choice in the evaluation of muscular structures. Traumatic lesions represent the majority of muscular injuries. A good anatomical knowledge of the weakness sites, as well as knowledge of traumatic signs and symptoms is essential in order to deliver a precise report to the referring physician. Sonography may suggest other causes of muscle lesions, tumoral or dystrophic, before confirmation by MRI.


Cardiopulmonary effects of raised intra-abdominal pressure before and after intravascular volume expansion.
The cardiopulmonary effects of acutely elevated intra-abdominal pressure (IAP) were studied in a porcine model to help define more clearly IAP effects in patients with trauma. IAP was increased in six anesthetized swine by intra-abdominal instillation of isotonic ethylene glycol up to an IAP of 25 mm Hg above baseline. Systemic and pulmonary hemodynamic parameters were measured, as well as the effects on bladder pressure, pleural pressure, and pulmonary function. At IAP of 25 mm Hg above baseline, intravascular volume expansion with saline was administered to return the cardiac index (CI) to baseline. Raising IAP correlated with measured bladder pressures (r = 0.9, p = 0.001). At IAP of 25 mm Hg, CI was significantly decreased (p < 0.05, analysis of variance (ANOVA); 3.6 +/- 0.3 vs. 2.2 +/- 0.3 L/min/m2); whereas wedge, pulmonary arterial, and pleural pressures were all elevated (p < 0.05, ANOVA). However, transarterial wedge pressure (wedge--pleural pressure) declined nonsignificantly with increasing IAP. Raised IAP caused impaired pulmonary function with a decreased (p < 0.05, ANOVA) PaO2 and increased (p < 0.05, ANOVA) PaCO2. Despite the elevated wedge pressure, fluid resuscitation returned CI to baseline. These data clarify the hemodynamic changes associated with raised IAP and indicate that care must be taken in interpreting hemodynamic measurements to determine intravascular fluid status in patients with elevated IAP.


Nitridoborates of the lanthanides: synthesis, structure principles, and properties of a new class of compounds.
Investigations of the nitridoborates of lanthanides (Ln) have progressed significantly during the last few years. New compounds have been synthesized and characterized and are presented here together with some of their properties. Currently two distinct methods serve for the preparation of nitridoborate compounds; either hexagonal boron nitride undergoes a fragmentation through the reaction with LnN, or dinitridoborate ions are converted into other nitridoborate ions. Lanthanide nitridoborates contain molecular anions such as [BN]n-, [BN2]3-, [B2N4]8-, [B3N6]9-, and [BN3]6- which may occur in combinations with other nitridoborates or with additional nitride ions. In crystal structures of lanthanide nitridoborates these anions are arranged in layers and are surrounded by metal atoms in a characteristic fashion. Terminal N atoms are capped by metal atoms forming a square-pyramid, and B atoms prefer a trigonal-prismatic environment of metal atoms. Nitridoborates form saltlike as well as metal-rich compounds and have the potential to show a lot of what are considered to be important solid-state properties, thus they have a good chance to establish their position within the group of relevant materials.


Sex-Dependent Motor Deficit and Increased Anxiety-Like States in Mice Lacking Autism-Associated Gene Slit3.
Altered neuronal connectivity has been implicated in the pathophysiology of Autism Spectrum Disorder (ASD). SLIT/ROBO signaling plays an important role in developmental processes of neuronal connectivity, including axon guidance, neuronal migration, and axonal and dendritic branching. Genetic evidence supports that SLIT3, one of the genes encoding SLITs, is associated with ASD. Yet the causal link between SLIT3 mutation and autism symptoms has not been examined. Here we assessed ASD-associated behaviors in Slit3 knockout (KO) mice. Our data showed that Slit3-KO mice exhibited reduced marble burying behaviors but normal social behaviors. In addition, Slit3-KO mice displayed hypolocomotion in the open field test and impaired motor coordination in the rotarod test. Anxiety-like behaviors were mainly observed in female KO mice assessed by three types of behavioral tests, namely, the open field test, elevated plus maze test, and light/dark box test. No differences were observed between KO and wildtype mice in recognition memory in the novel object recognition test or depression-like behavior in the tail suspension test. Taken together, loss of Slit3 may result in disrupted neural circuits related to motor function and increased anxiety-like states, which are co-occurring symptoms in ASD.


Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.
We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.


A micro-computed tomography evaluation of long-oval canal preparation using reciprocating or rotary systems.
To evaluate, using micro-computed tomography, the preparation of long-oval root canals using a single reciprocating system versus a multiple-file rotary system. Distal canals of thirty mandibular molars were selected and randomly assigned to one of two instrument groups (n = 15): Reciproc 40 (VDW, Munich, Germany) or BioRaCe system (FKG Dentaire, La Chaux-de-Fonds, Switzerland). The teeth were scanned before and after preparation of the canal by a SkyScan 1172 micro-computed tomography scanner at 11-μm resolution. Morphometric variations were measured by volume increases and by the remaining untreated canal surface area in the entire canal and as well as in each third of the canal. Data were compared using the Mann-Whitney test. The Reciproc system left significantly more areas untouched (P < 0.001) in the cervical and middle thirds (18.14% and 21.82%) as compared to BioRaCe (8.14% and 11.35%). The Reciproc system had the greatest increase in volume of both the entire canal and the apical third (P < 0.5). Neither technique was able to completely prepare the outline of long-oval canals. The Reciproc system removed more tooth structure. The BioRaCe left fewer untouched dentine walls in the more coronal thirds of the canal, whilst Reciproc left fewer in the apical third.


B cell ligand discrimination through a spreading and contraction response.
B cells recognize foreign antigens by virtue of cell surface immunoglobulin receptors and are most effectively activated by membrane-bound ligands. Here, we show that in the early stages of this process, B cells exhibit a two-phase response in which they first spread over the antigen-bearing membrane and then contract, thereby collecting bound antigen into a central aggregate. The extent of this response, which is both signaling- and actin-dependent, determines the quantity of antigen accumulated and hence the degree of B cell activation. Brownian dynamic simulations reproduce essential features of the antigen collection process and suggest a possible basis for affinity discrimination. We propose that dynamic spreading is an important step of the immune response.


[Cochlear implants for the patients with cochlear nerve defects].
By watching the effects of cochlear implants in the children with cochlear nerve defects, to evaluate the relationship and efficiency of HRCT AND MRI in diagnostic for cochlear nerve defects. The imaging dates and the post-operative effects of the 10 cochlear nerve defect patients were retrospectively analyzed. Three patients with bilateral IAC stenosis by HRCT and cochlear nerve defects by MRI but no other abnormal. Seven other patients showed normal IAC by HRCT including 1 showed type IP- I plus vestibular semi circular canal dysplasia. These 7 patients MRI showed 3 bilateral cochlear nerve absent and 4 bilateral cochlear nerve dysplasia. Ten cases of children after 12-32 month follow-up, 3 patients began speaking simple language, whose MAIS scale, CAP and SIR scores improved. One case just began speaking but pronunciation vague. Four cases had reactions to sounds, and can say monosyllabic words. Two cases without effects (1 CI abolished). Compared with other patients with normal cochlear nerve, the effects of the 10 cases were disappointed. The effects of cochlear implant for the patients with cochlear nerve defects were poor. The preoperative MRI as sessment including oblique sagittal view for cochlear nerve is necessary. The preoperative communication with the parents telling ineffective result possibility is important.


Respiratory-associated rhythmic firing of midbrain neurones in cats: relation to level of respiratory drive.
1. We recorded phrenic nerve activities and single unit firing of mesencephalic neurones in unanaesthetized supracollicularly decerebrated, paralysed and ventilated cats, in which vagi and carotid sinus nerves had been ablated. We made these measurements first at low levels of respiratory drive associated with normal PCO2 levels, then with increased respiratory drive and levels of phrenic activity produced by hypercapnia or by carotid sinus nerve stimulation. 2. We found that at least a quarter of the neurones in the central tegmental field of the mesencephalon, which were irregularly tonic or silent at low respiratory drives, developed a rhythmic increase of firing associated with each respiration. There appeared to be a threshold at about 50% of maximum respiratory activity, below which the respiratory-associated rhythm did not occur. Above this level, neuronal firing increased in graded fashion with increasing magnitude of respiratory activity. The latency from onset of phrenic activity to onset of increased neuronal firing was quite long (1.0 s) at drives just above the threshold but shortened to as little as 0.3 s as drive increased towards its maximum. 3. Cutting the spinal cord at C1-C2 had no effect on the ability of increased respiratory activity to generate a respiratory-associated rhythm in mesencephalic neurones. 4. Short-lasting anaesthesia with the agent Saffan caused mesencephalic neurones to lose the respiratory-associated rhythm with little change in phrenic activity and no change in respiratory cycle timing. 5. We also found a mesencephalic response to ventilator-induced chest expansion. The latency of the response from onset of expansion, indexed by fall of airway PCO2, to onset of neurone firing was shorter (0.2 s) than that found with the respiratory-associated rhythm. In seventeen neurones we found both the respiratory-associated rhythm and the independent ventilator-associated rhythm. 6. We interpret our findings to show that the respiratory-associated rhythmic firing of midbrain neurones is not primarily involved in generation or modulation of the motor function of the respiratory oscillator. We believe, instead, that these neurones are part of a sensory pathway conveying information about the magnitude of central neural respiratory drive, as well as spinally transmitted information from receptors in the chest wall, to thalamus and cortex. We suggest that the sensation ultimately generated may be that of 'air hunger' or dyspnoea.


Effects of physical stress on peroxide scavengers in normal and sickle cell trait erythrocytes.
Sickle cell trait subjects are potentially at risk with microvascular complications frequently associated with high altitude and extreme exertion. Studies conducted in our laboratory suggest that exposure of sickle cell trait subjects to treadmill exercise resulted in an increase not only in the susceptibility of red blood cells to oxidation but also in the density of RBC membrane. The trend of increased susceptibility of red cells to oxidation as a consequence of exercise was associated with relatively excessive production of H2O2, inefficient breakdown of H2O2 by GSH-Px- and catalase-catalyzed reactions, and inability/failure to show a transitory increase in the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-generating enzymes.


Human Gut Microbiota and Mental Health: Advancements and Challenges in Microbe-Based Therapeutic Interventions.
Gut microbes play prime role in human health and have shown to exert their influence on various physiological responses including neurological functions. Growing evidences in recent years have indicated a key role of gut microbiota in contributing to mental health. The connection between gut and brain is modulated by microbes via neural, neuroendocrinal and metabolic pathways that are mediated through various neurotransmitters and their precursors, hormones, cytokines and bioactive metabolites. Impaired functioning of this connection can lead to manifestation of mental disorders. Around 1 billion of the world population is reported to suffer from emotional, psychological and neurological imbalances, substance use disorders and cognitive, psychosocial and intellectual disabilities. Thus, it becomes imperative to understand the role of gut microbes in mental disorders. Since variations occur in the conditions associated with different mental disorders and some of them have overlapping symptoms, it becomes important to have a holistic understanding of gut dysbiosis in these disorders. In this review, we consolidate the recent data on alterations in the gut microbes and its consequences in various neurological, psychological and neurodegenerative disorders. Further, considering these evidences, several studies have been undertaken to specifically target the gut microbiota through different therapeutic interventions including administration of live microbes (psychobiotics) to treat mental health disorders and/or their symptoms. We review these studies and propose that an integrative and personalized approach, where combinations of microbe-based therapeutic interventions to modulate gut microbes and in-use psychological treatment practices can be integrated and based on patient's gut microbiome can be potentially adopted for effective treatment of the mental disorders.


Methylammonium antimony sulfide.
Bis(methylammonium) octaantimony(III) dodecasulfide persulfide, (CH3NH3)2[Sb8S12(S2)], contains pairs of [Sb4S7]2- chains joined through an unusual persulfide bond to create infinite double [Sb8S14]2- chains. The double chains are interlocked by longer Sb...S interactions to form sheets approximately parallel to the (101) crystallographic plane. Methylammonium cations, formed by decomposition of 2-methylpropane-1,2-diamine during the synthesis, are located in large (Sb8S10) hetero-ring apertures created within the double chains.


The 5-hydroxytryptamine receptor 1F stimulates mitochondrial biogenesis and angiogenesis in endothelial cells.
A hallmark of acute kidney injury (AKI) is vascular rarefication and mitochondrial dysfunction. Promoting vascular recovery following AKI could facilitate kidney repair as the vasculature is responsible for oxygen and nutrient delivery to extravascular tissues. Little is known about mitochondrial biogenesis (MB) in endothelial cells, and the role of 5-HT1F receptor signaling in MB has only been studied in epithelial cells. Our laboratory has shown that stimulating MB through the 5-HT1F receptor promotes recovery from AKI and that 5-HT1F receptor knockout mice have decreased MB and poor renal recovery. We hypothesized that the 5-HT1F receptor plays a role in vascular homeostasis and mediates MB in renal endothelial cells. 5-HT1F receptor knockout mice had decreased renal vascular content, as evidenced by decreased CD31+ endothelial cells and αSMA+ vessels. Human glomerular endothelial cells (HEC) and mouse glomerular endothelial cells (MEC) expressed the 5-HT1F receptor. Treatment of HEC and MEC with 5-HT1F receptor agonists LY344864 or lasmiditan (0-500 nM) induced MB as evidenced by maximal mitochondrial respiration, a marker of MB. HEC and MEC treated with lasmiditan or LY344864 also had increased nuclear- and mitochondrial-encoded proteins (PGC1α, COX-1, and VDAC), and mitochondrial number, confirming MB. Treatment of HEC with LY344864 or lasmiditan enhanced endothelial branching morphogenesis and migration, indicating a role for 5-HT1F receptor stimulation in angiogenic pathways. We propose that stimulation of 5-HT1F receptor is involved in MB in endothelial cells and that treatment with 5-HT1F receptor agonists could restore stimulate repair and recovery following kidney injury.


Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis.
(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico "A. Gemelli" University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants (p = 0.003). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC (p = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic.


Percutaneous Nephrolithotomy in the 80 Years of Age and Older Population.
To evaluate feasibility of percutaneous nephrolithotomy (PCNL) for complex nephrolithiasis in patients 80 years of age and older compared to younger individuals. From an institutional IRB-approved database, 1,647 patients were identified who underwent PCNL from 1999 to 2019. Patients were stratified by age: group 1 (20-59), group 2 (60-79), and group 3 (>80). Statistics were performed using chi-square and ANOVA to compare outcomes. Of the 1,647 patients, median age was 46, 66, and 83, respectively (P <0.0001). Three patients within group 3 were 90 or older. Females made up 54%, 46%, 56% of patients (P = 0.02). Average stone size with SD was 2.6 ± 2.2, 2.5 ± 2.3, 2.2± 1.9 cm for each group (P = 0.06). Mean preoperative hemoglobin (Hgb) was significantly lower in the 80+ group (13.8, 13.4, 13.1 g/dL, P <.0001). Change in Hgb was not significantly different. There were more Clavien II-IV complications (10.4, 14.4, 28.8%; P = 0.02) and transfusions (2.3, 4.7, 10.2%; P <0.001) in the elderly. The most common complications in the 80+ group were bleeding related (10.1%). No difference in readmission rates or ICU admissions was noted. PCNL is feasible in the extremely elderly; however with a higher rate of complications and longer hospitalizations. No long-term sequelae or deaths in the 80 and older cohort were seen. This study allows us to appropriately counsel older patients on a realistic postoperative course and supports use of PCNL as the best means of long-term survival.


Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease.
Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end-stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non-albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever-evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre-disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time-course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high-throughput metabolomic techniques will be discussed.


Evaluating impact of medium variation on dose calculated through planning system in a low cost in-house phantom.
Purpose: In radiotherapy, accuracy in dose estimation of dose calculation methods is critical. The influence of deformity on radiation dose calculations derived by planning system is evaluated in present study. The goal of study was to create a low-cost inhomogeneous phantom for measuring absorbed dose using an Ionisation chamber and Gafchromic film, which was validated using treatment planning system (TPS) dose outcome.Methods:and Materials: The central axis dose calculations were computed using Pencil Beam Convolution algorithm (PBC), Collapsed Cone Convolution (CCC) and Monte Carlo (MC) algorithm in the Monaco treatment planning system using an In-house phantom (20 × 20 × 20cm3) made up of acrylic sheet containing water and inhomogeneous material wooden powder equivalent to lung. Phantom was scanned in Computed Tomography (CT) scanner and image set was sent to the planning workstation. The depth dose evaluations were performed using ionization chamber and Gafchromic film with same beam settings and monitor units in every setup. Following that, the calculated doses obtained from TPS and measured depth doses were compared.Results: The results was reported for photon energies 6MV, 10MV, 15MV, 6FFF and 10FFF at varying field sizes of 4 × 4 cm2, 5 × 5 cm2, 10 × 10 cm2, and 15 × 15 cm2. MC maximum dose variation predicted was 2.06% in 15MV of measured chamber dose and -2.06% of measured gafchromic film dose in 6MVFFF. CCC maximum dose variation predicted was 2.68% of measured chamber dose in 6MV and 3.31% of measured gafchromic film dose in 6MV whereas PB maximum dose variation predicted was -5.94% in 15MV of measured chamber dose and -11.6% of measured gafchromic film dose in 6MVFFF.Conclusion: Low-cost in-house phantoms can be utilised to assess point and planar doses during patient-specific quality assurance in centres that don't have accessibility to phantoms due to the high cost of commercially available tools.


Identification of genomic functional hotspots with copy number alteration in liver cancer.
Copy number alterations (CNAs) can be observed in most of cancer patients. Several oncogenes and tumor suppressor genes with CNAs have been identified in different kinds of tumor. However, the systematic survey of CNA-affected functions is still lack. By employing systems biology approaches, instead of examining individual genes, we directly identified the functional hotspots on human genome. A total of 838 hotspots on human genome with 540 enriched Gene Ontology functions were identified. Seventy-six aCGH array data of hepatocellular carcinoma (HCC) tumors were employed in this study. A total of 150 regions which putatively affected by CNAs and the encoded functions were identified. Our results indicate that two immune related hotspots had copy number alterations in most of patients. In addition, our data implied that these immune-related regions might be involved in HCC oncogenesis. Also, we identified 39 hotspots of which copy number status were associated with patient survival. Our data implied that copy number alterations of the regions may contribute in the dysregulation of the encoded functions. These results further demonstrated that our method enables researchers to survey biological functions of CNAs and to construct regulation hypothesis at pathway and functional levels.


Study on anion electrochemical recognition based on a novel ferrocenyl compound with multiple binding sites.
A novel ferrocenyl anion receptor N, N, N, N-(dimethyl, ethyl, ferrocenecarboxylic amidodimethylene) ammonium fluoborate 2 with multiple binding sites was synthesized. Its anion recognition behaviors were investigated by CV, 1H NMR and UV-vis spectrum. It was found that the combination of two interactions enforced the anion binding ability and the binding selectivity of 2 to phosphate anion. The effects of scan rate on the CV curves of 2 with phosphate were also investigated. In different scan rate, the CV curves kept stable which indicated the strong binding between 2 and phosphate. According to relationships of peak potential, peak currents and scan rate of 2 binding with phosphate, the kinetic parameters of electrode process such as diffusion coefficient Dapp, surface transfer coefficient alphan alpha, and standard rate constant k0 were calculated.


Rotavirus vaccine series completion and adherence to vaccination schedules among infants in managed care in the United States.
Two rotavirus vaccines are currently approved in the United States: 3-dose RotaTeq (RV5; Merck & Co., Inc., Whitehouse Station, NJ, USA) is administered at ages 2, 4, and 6 months; and 2-dose Rotarix (RV1; GlaxoSmithKline, Research Triangle Park, NC, USA) is administered at ages 2 and 4 months. Our objective was to compare rotavirus vaccine series completion and dosing schedule compliance between cohorts of infants who received these vaccines. Infants aged less than 1 year who initiated a rotavirus vaccine series between 01 January 2009 and 30 June 2009 were identified in US health insurance claims data. Cohorts were formed based on vaccine brand use. Series completion and compliance with the FDA-approved and ACIP-recommended harmonized schedules were analyzed descriptively and a log binomial model was used to estimate the difference in series completion by vaccine brand while adjusting for demographic variables. Among infants in the RV1 and RV5 cohorts (N=55,584), 84.3% completed a full series. A greater proportion of the RV1 cohort than the RV5 cohort completed their series (91.0% vs. 83.4%; P<0.001; multivariate-adjusted relative risk 1.07; 95% CI 1.06-1.08). In the RV1 and RV5 cohorts, respectively, 75.0% and 59.5% of infants were fully compliant with the FDA-approved administration schedule for their vaccine (P<0.001); 83.3% and 76.4% of infants were fully compliant with the harmonized schedule (P<0.001). The proportion of infants that completed the series was greater and compliance with respective FDA-approved and harmonized dosing schedules was higher among infants vaccinated with RV1 than among infants who received RV5.


Chiral Phonon Diode Effect in Chiral Crystals.
The diode effect means that carriers can only flow in one direction but not the other. While diode effects for electron charge, spin, or photon have been widely discussed, it remains a question whether a chiral phonon diode can be realized, which utilizes the chiral degree of freedom of lattice vibrations. In this work, we reveal an intrinsic connection between the chiralities of a crystal structure and its phonon excitations, which naturally leads to the chiral phonon diode effect in chiral crystals. At a certain frequency, phonons with a definite chirality can propagate only in one direction but not the opposite. We demonstrate the idea in concrete materials including bulk Te and α-quartz (SiO2). Our work discovers the fundamental physics of chirality coupling between different levels of a system, and the predicted effect will provide a new route to control phonon transport and design information devices.


A Polyhydroxyalkanoates-Based Carrier Platform of Bioactive Substances for Therapeutic Applications.
Bioactive substances (BAS), such as small molecule drugs, proteins, RNA, cells, etc., play a vital role in many therapeutic applications, especially in tissue repair and regeneration. However, the therapeutic effect is still a challenge due to the uncontrollable release and instable physico-chemical properties of bioactive components. To address this, many biodegradable carrier systems of micro-nano structures have been rapidly developed based on different biocompatible polymers including polyhydroxyalkanoates (PHA), the microbial synthesized polyesters, to provide load protection and controlled-release of BAS. We herein highlight the developments of PHA-based carrier systems in recent therapeutic studies, and give an overview of its prospective applications in various disease treatments. Specifically, the biosynthesis and material properties of diverse PHA polymers, designs and fabrication of micro- and nano-structure PHA particles, as well as therapeutic studies based on PHA particles, are summarized to give a comprehensive landscape of PHA-based BAS carriers and applications thereof. Moreover, recent efforts focusing on novel-type BAS nano-carriers, the functionalized self-assembled PHA granules in vivo, was discussed in this review, proposing the underlying innovations of designs and fabrications of PHA-based BAS carriers powered by synthetic biology. This review outlines a promising and applicable BAS carrier platform of novelty based on PHA particles for different medical uses.


Evaluation of the SafeHeal Colovac+ Anastomosis Protection Device: A Preclinical Study.
BackgroundThe protective ostomy is the current standard of care to protect a low colorectal anastomosis from leakage, but exposes patients to complications requiring an alternative strategy. The Colovac+ is a vacuum-based intraluminal bypass device designed to shield the anastomosis from fecal content, preventing the clinical outcomes of anastomotic leakage. The objective of this study was to evaluate the preliminary efficacy, safety, and technical feasibility of the Colovac+ in a porcine model. Methods: Twelve pigs received a colorectal anastomosis with Colovac+ implantation. The device was left in situ for 10 days and then retrieved endoscopically. Six pigs were to be sacrificed immediately after device retrieval and the other 6 were to be sacrificed on day 38. Clinical, endoscopic, and histopathological examinations were performed to evaluate the following endpoints: prevention of contact between the anastomosis and fecal content, device migration, feasibility of the implantation and retrieval procedure, collateral damage to the colonic wall, colon healing after device retrieval, and systemic toxicity related to the device. Results: Eleven pigs completed the study. One pig died prematurely due to a surgical complication unrelated to the device (bladder damage with uroperitoneum). There was no evidence of contact between the anastomosis and fecal content, none of the pigs developed symptomatic anastomotic leakage, there were no significant device migrations, and there was no evidence of systemic toxicity. Colovac+ implantation was easily performed in all cases except 1 (due to an inappropriate lubricant). Colovac+ retrieval was achieved successfully in all cases. Postretrieval examinations on day 10 revealed ulcerations at the anchoring site in 4 cases indicating mechanical damage caused by the stent. However, in the recovery group, no ulcerations were observed on day 38, and the colonic wall had properly healed in all animals. Conclusions: The Colovac+ is a technically feasible, safe, and efficient device for the protection of a colorectal anastomosis in a porcine model. The device holds promise for clinical use and warrants further research.


Effectiveness of Mediterranean Diet's Adherence in children with Inflammatory Bowel Diseases.
Nutritional support is very important in the treatment of Paediatric Inflammatory Bowel Disease (IBD). The role of the Mediterranean Diet (MD) has been understudied in children with IBD. The aims of this study were to assess the dietary intakes of IBD children in comparison with healthy controls (HCs), their adherence to MD; and the relationship between inflammation and dietary behaviors. Paediatric IBD patients in clinical remission and HCs were enrolled. The nutritional status and adherence to the Mediterranean Diet was evaluated through a 3-day food diary and the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). The analysis of food diaries showed a significantly higher kilocalorie intake in IBD patients compared to HCs (p = 0.012), an increase in carbohydrates (p = 0.015) and in protein intake (p = 0.024). Both IBD and HCs have an intermediate adherence to MD. The comparison between Crohn's disease (CD) and Ulcerative colitis (UC) patients showed significant difference in protein intake in CD patients (p = 0.047), as well as for vitamin D (p = 0.044) and iron intake (p = 0.023). Interestingly; in IBD patients we found a significant association between adherence to MD and a low level of fecal calprotectin (p = 0.027). Children with IBD in remission have a sub-optimal food intake compared to HCs. MD seems to correlate to decreased intestinal inflammation.


Awareness of Preconception Care and Its Related Factors Among Women of Childbearing Age with Type 1 Diabetes in the South of Saudi Arabia: A Cross-Sectional Survey Study.
Pregnancies in women with type 1 diabetes mellitus (T1DM) are associated with an increased risk of poor outcomes for mothers and their infants. To assess the awareness of preconception care among women with T1DM and their self-management status in the southern region of Saudi Arabia. This study is a cross-sectional study that was done on 187 women participated of childbearing age with T1DM who were seen in diabetic centers between June 2019 and September 2020. Pre-pregnancy care and disease management were assessed via a questionnaire. The prevalence of preconception awareness of diabetes management was 66.9%. Several factors significantly influenced the level of awareness, including education level (P= 0.001) and HbA1c (P= 0.014). In multivariate analysis, the lower educational level turns out to be a significant risk factor for low awareness (OR = 3.71, 95% CI [1.65, 8.31], P= 0.001). Additionally, compared to controlled DM, uncontrolled diabetes had a twofold increased risk of low awareness (OR = 2.03, 95% CI [1.08, 3.81], P= 0.027). The awareness level was significantly correlated with a high educational level and better glycemic control. Meanwhile, it was not significantly correlated with diabetes duration.


Evidence for pattern generator control of the effects of spindle afferent input during rhythmical jaw movements.
The following recordings were made during spontaneous rhythmic jaw movements in the anesthetized guinea pig: jaw movement in the vertical plane, electromyograms from the digastric muscle (a jaw opener), and intracellular recordings from motoneurons and spindle afferent fibers of the jaw-closer muscles. The rapid jaw-opening phase of these rhythmic movements is characterized by a marked increase in activity in the spindle afferent fibers of the jaw-closer muscles and a coincident pronounced hyperpolarization of the membranes of the jaw-closer motoneurons. It is proposed that the excitatory spindle afferent input evoked by passive stretch of the jaw-closer muscles resulting from a centrally programmed contraction of the jaw-opener muscles impinges upon closer motoneurons that have been hyperpolarized as part of te central program. The hyperpolarization inhibits the motoneurons and nullifies the effect of the spindle afferent input thereby assuring relaxation of the closer muscles and an unimpeded rapid jaw-opening movement.


Association between renin-angiotensin system gene polymorphism and recurrent wheezing in Chinese children: a 4-year follow-up study.
This study aimed to clarify the association between angiotensin-converting enzyme (ACE) gene polymorphisms and infant wheezing, and to determine whether an association may contribute to early prediction of persistent wheezing and asthma. The study cohort comprised 149 patients with asthma, 169 patients with wheezing but no clinical diagnosis of asthma and 165 healthy control subjects. The insertion/deletion (I/D) polymorphism of the ACE gene was determined by polymerase chain reaction. Total serum immunoglobulin E was determined for the wheezy group and a 4-year follow-up study was carried out to observe wheezing relapse. Significant differences were found between patients and controls in allele frequency and genotype distribution. The DD genotype was more frequent in patients in the wheezing and asthma groups than in the control subjects. Patients with the DD genotype had a higher frequency of relapse than patients expressing the ID or II genotypes. It is concluded that the DD genotype of ACE is a risk factor for recurrent wheezing in early childhood.


Recurrent thrombosis of prosthetic mitral valve in idiopathic hypereosinophilic syndrome.
A 41-year old man, with idiopathic hypereosinophilic syndrome, had severe mitral regurgitation. He had two subsequent mechanical mitral valve thromboses in the setting of rising eosinophilia. A Carpentier-Edwards bioprosthesis was used for the third valve replacement. Some features of myeloproliferative disease, including chromosome 10 abnormality, were identified. A normal eosinophil count and disappearance of the chromosomal abnormality were obtained with interferon, hydroxyurea and prednisone therapy. At 30 months postoperatively, the patient had a normal lifestyle.


[Carpal tunnel syndrome. Comparative studies of pre- and postoperative magnetic resonance and electromyography].
A comparative wrist study was conducted in a total of 36 subjects: 20 normal volunteers and 16 patients with diagnosed carpal tunnel syndrome. 1.5 Tesla MR was used with a cylindrical extremity coll. The authors reviewed the anatomy of the wrist in the normal subjects. The accuracy of MR diagnostic criteria for carpal tunnel syndrome was assessed in comparison with EMG results and surgical findings. The authors conclude that MRI has proved to be reliable and useful in the diagnostic work up of carpal tunnel syndrome. Its main indication would be in cases of negative or doubtful EMG.


Suppression of ventricular output by noise in the atrial channel in a dual chamber pacemaker.
In a pacemaker dependent, 60-year-old man with complete heart block, programming high (5.0 V and 1.0 ms) atrial output and 5.0 volt and 0.5 ms ventricular output while in the DDD mode of a pulse generator, resulted in loss of ventricular channel output with resulting asystole, while the simultaneous, pulse generator produced ECG interpretation channel falsely indicated continuing ventricular channel output. Ventricular pacing was promptly restored by programming to the emergency VVI mode. At later operation the atrial lead was determined to be defective, with a low impedance, while the ventricular lead was intact (lead impedance telemetry was not available). The manufacturer has acknowledged a pulse generator design anomaly that may occur in the setting of a low atrial impedance and issued a Health Safety Alert.


Validation of the Radimer/Cornell measures of hunger and food insecurity.
Hunger and food insecurity have been identified as core indicators of an individual's nutritional state that should be assessed in nutrition surveillance activities. Such an assessment requires a valid measure of these phenomena. This paper describes further work on the construction of measures of hunger and food insecurity based on the Radimer/Cornell items and provides an assessment of their validity. A random sample survey of 193 households with women and children living at home was conducted in 1993 in a rural county in New York State. A questionnaire containing the Radimer/Cornell hunger and food insecurity items, information about demographic characteristics, frequency of fruit and vegetable consumption, and household food supplies was administered to subjects. Measures were constructed that identified households experiencing household- and individual-level food insecurity and households with hungry children. The construct and criterion-related validity of the measures was assessed. In relation to criterion-related validity, as food insecurity worsened, there was a significant and progressive increase in the percentage of subjects participating in food programs and having low income, education and employment and a significant decline in average household food availability and fruit and vegetable consumption. These results support the validity of the Radimer/Cornell measures and illustrate their ability to differentiate among groups of households experiencing increasingly severe food insecurity and hunger.


Uterine torsion in a full-term pregnant cat.
A 5-year-old intact female Maine Coon cat presented with a 2 day history of lethargy, anorexia and anaemia. The cat had bred 60 days previously and jumped from a height 3 days earlier, which was followed by a worsening of its condition. Ultrasonography revealed that two fetuses had died and one remained alive. Urgent surgical intervention was deemed necessary, and the cat underwent a blood transfusion and laparotomy. The right uterine horn was dark red in appearance and had rotated 360° in the clockwise direction at its base. Subsequently, an ovariohysterectomy and caesarean section were performed, and the fetus in the left uterine horn initially survived. Although the cat appeared to recover from anaemia and physical injury, the kitten died on postoperative day 1. In cases involving only one twisted uterine horn, the fetuses located in the contralateral horn could potentially survive; however, many such fetuses do not survive, and only a few reports have described fetal survival in a pregnant cat with uterine torsion. In the present case, early surgical intervention and blood transfusion allowed us to save the cat. Our findings demonstrate the life-saving abilities of initial support treatment and early surgical intervention for both the pregnant cat and fetuses in cases of acute abdomen caused by uterine torsion.


Temporal variation in pelagic food chain length in response to environmental change.
Climate variability alters nitrogen cycling, primary productivity, and dissolved oxygen concentration in marine ecosystems. We examined the role of this variability (as measured by six variables) on food chain length (FCL) in the California Current (CC) by reconstructing a time series of amino acid-specific δ15N values derived from common dolphins, an apex pelagic predator, and using two FCL proxies. Strong declines in FCL were observed after the 1997-1999 El Niño Southern Oscillation (ENSO) event. Bayesian models revealed longer FCLs under intermediate conditions for surface temperature, chlorophyll concentration, multivariate ENSO index, and total plankton volume but not for hypoxic depth and nitrate concentration. Our results challenge the prevalent paradigm that suggested long-term stability in the food web structure in the CC and, instead, reveal that pelagic food webs respond strongly to disturbances associated with ENSO events, local oceanography, and ongoing changes in climate.


Immunological monitoring of melanoma patients on BCG immunotherapy. I. Enzyme-linked immunosorbent assay of human sera after BCG-treatment.
Purified lipopolysaccharide (LPS), isolated from BCG and purified protein derivative of tuberculin (PPD) were used as antigens in an enzyme-linked immunosorbent assay (ELISA) of sera from patients with malignant melanoma undergoing immunotherapy with BCG. It was found that LPS and ELISA are useful tools in the monitoring of humoral immune response against BCG.


How Radiologists Can Benefit From Direct Communication With Patients.
Effective communication is foundational to Radiology. Historically, radiologists have been considered "doctors' doctors," communicating primarily with referring physicians and other radiologists. Aside from interventional radiology and breast imaging, direct communication between radiologists and patients has typically been limited. In recent years, major radiology professional societies have launched initiatives aimed toward increasing direct radiologist and patient communication. These include the American College of Radiology's Imaging 3.0 and Radiological Society of North America's Radiology Cares initiatives. Prior work has highlighted potential patient benefits of increased communication by demonstrating patient preferences for speaking with imaging experts about the results of their imaging studies and introducing strategies to harness existing information technology resources to achieve this goal. In this review, we explore the unique benefits that radiologists can derive from communicating with patients in regular and meaningful ways.


A mathematical algorithm of the facial symmetry plane: Application to mandibular deformity 3D facial data.
The three-dimensional (3D) symmetry reference plane (SRP) is the premise and basis of 3D facial symmetry analysis. Currently, most methods for extracting the SRP are based on anatomical landmarks measured manually using a digital 3D facial model. However, as different clinicians have varying definitions of landmarks, establishing common methods suitable for different types of facial asymmetry remains challenging. The present study aimed to investigate and evaluate a novel mathematical algorithm based on power function weighted Procrustes analysis (PWPA) to determine 3D facial SRPs for patients with mandibular deviation. From 30 patients with mandibular deviation, 3D facial SRPs were determined using both our PWPA algorithms (two functions) and the traditional PA algorithm (experimental groups). A reference plane, defined by experts, was considered the 'truth plane'. The 'position error' index of mirrored landmarks was created to quantitatively evaluate the difference among the PWPA SRPs and the truth plane, including overall differences and regional differences of the face (upper, middle and lower). The 'angle error' values between the SRPs and the truth plane in the experimental groups were also evaluated in this study. Statistics and measurement analyses were used to comprehensively evaluate the clinical suitability of the PWPA algorithms to construct the SRP. The average angle error values between the PWPA SRPs of the two functions and the truth plane were 1.21 ± 0.65° and 1.18 ± 0.62°, which were smaller than those between the PA SRP and the truth plane. The position error values of mirrored landmarks constructed using the PWPA algorithms for the whole face and for each facial partition were lower than those constructed using the PA algorithm. In conclusion, for patients with mandibular deviation, this novel mathematical algorithm provided a more suitable SRP for their 3D facial model, which achieved a result approaching the true effect of experts.


Profile and outcome of cardiovascular admissions at the University of Uyo Teaching Hospital, Uyo--a five year review.
The incidence of cardiovascular diseases (CVD) in developing countries has been on the increase in the last few decades. Demographic changes and adoption of negative life style associated with urbanization have been incriminated. This study is to ascertain the burden of cardiovascular disease in Uyo, a town which has been undergoing rapid urbanization in the last decade. A five-year retrospective analysis of cardiovascular admissions into the Medical Wards of the University of Uyo Teaching Hospital between September 1996 and September 2001 was carried out. Medical records of patients were used. The Epi Info 2002 software was used to analyse data. Five hundred and fifty eight (19.8%) of the 2875 medical admissions were patients with cardiovascular diseases. Their mean age was 52 +/- 12.7 years and mean duration of hospital stay was 9 +/- 7 days. Hypertension accounted for 311 (55.7%) of the cases, of these 107 (34.4%) presented with cerebrovascular accident (CVA). 44.3% presented in Heart failure and causes included Hypertension (14.9%), Cardiomyopathies particularly the dilated type (15.1%), Rheumatic heart disease (6.6%) and Anaemia (7.7%). 69 (12.4%) cardiovascular deaths were recorded, of these 34 (6.1%) were in patients with Cerebrovascular accident. Most deaths occurred within seven (7) days of admission. Duration of stay significantly influenced outcome (p = 0.000). Cardiovascular diseases constitute a significant health problem in our community. Intensive cardiovascular health education and promotion of healthy life style are advocated. Tertiary health care facilities should be equipped to cope with cardiovascular care in view of the looming epidemic of cardiovascular disease even in developing countries.


Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.
Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg-/- mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease.


Work-related potential traumatic events and job burnout among operating room nurses: Independent effect, cumulative risk, and latent class approaches.
The objective of this study is to explore and compare the strength of associations between work-related potential traumatic events and burnout among operating room nurses based on three different approaches. The study followed a multisite cross-sectional design. A stratified sampling method was conducted. Cities in the Shandong Province were divided into four groups, and two tertiary hospitals were randomly selected from all tertiary hospitals in cities of each group. A total of 361 eligible operating room nurses provided valid questionnaires between June and November 2019. Work-related potential traumatic events questionnaire and the Chinese version of the Maslach Burnout Inventory were conducted. Associations between individual, cumulative potential traumatic events, as well as latent class analysis-derived patterns of potential traumatic experiences with burnout were examined using logistic regression analysis. Specific traumatic events (e.g., patients' sudden death, bullying and ostracism from colleagues) were independently associated with an increased risk of burnout. Work-related potential traumatic events had a cumulative effect on burnout, whereby operating room nurses exposed to cumulative potential traumatic events carried a higher risk for burnout than others. The "multiple work-related potential traumatic events" pattern derived by latent class analysis was related to an increased risk of high depersonalization. Operating room nurses who reported specific or multiple work-related potential traumatic events were at high risk for burnout. It is of great significance to provide qualified and timely counselling or support. This study is the first to focus on work-related potential traumatic events among operating room nurses and examine their relationship with burnout based on three perspectives. The findings could help identify those operating room nurses who are at high risk of burnout in clinical practice. Hospital managers should develop targeted interventions to prevent or mitigate the harmful impact of potential traumatic events on occupational health.


Acid Phosphatase Development during Ripening of Avocado.
The activity and subcellular distribution of acid phosphatase were assayed during ethylene-induced ripening of whole fruit or thick slices of avocado (Persea americana Mill. var. Fuerte and Hass). The activity increased up to 30-fold during ripening in both the supernatant fraction and the Triton X-100 extract of the precipitate of a 30,000g centrifugation of tissue homogenates from whole fruit or slices ripening in moist air. Enzyme activity in the residual precipitate after Triton extraction remained constant. The development of acid phosphatase in thick slices ripened in moist air was similar to that in intact fruit, except that enzyme development and ripening were accelerated about 24 hours in the slices. The increase in enzyme activity that occurs in slices ripening in moist air was inhibited when tissue sections were infiltrated with solutions, by aspiration for 2 minutes or by soaking for 2 hours, anytime 22 hours or more after addition of ethylene. This inhibition was independent of the presence or absence of cycloheximide or sucrose (0.3-0.5m). However, the large decline in enzyme activity in the presence of cycloheximide, as compared with the controls, indicated that synthesis of acid phosphatase was occurring at all stages of ripening.


Factors Associated With COVID-19 Vaccine Receipt by Health Care Personnel at a Major Academic Hospital During the First Months of Vaccine Availability.
Several COVID-19 vaccines have been authorized in the US, yet preliminary evidence suggests high levels of vaccine hesitancy and wide racial, ethnic, and socioeconomic disparities in uptake. To assess COVID-19 vaccine acceptance among health care personnel (HCP) during the first 4 months of availability in a large academic hospital, compare acceptance with previously measured vaccine hesitancy, and describe racial, ethnic, and socioeconomic disparities in vaccine uptake. This cross-sectional study included 12 610 HCP who were offered COVID-19 vaccination at a major academic hospital in Philadelphia between December 16, 2020, and April 16, 2021. For each HCP, data were collected on occupational category, age, sex, race and ethnicity (Asian or Pacific Islander, Black or African American [Black], Hispanic, White, and multiracial), and social vulnerability index (SVI) at the zip code of residence. Vaccine uptake by HCP at the employee vaccination clinic. The study population included 4173 men (34.8%) and 7814 women (65.2%) (623 without data). A total of 1480 were Asian or Pacific Islander (12.4%); 2563 (21.6%), Black; 452 (3.8%), Hispanic; 7086 (59.6%), White; and 192 (1.6%), multiracial; 717 had no data for race and ethnicity. The mean (SD) age was 40.9 (12.4) years, and 9573 (76.0%) received at least 1 vaccine dose during the first 4 months of vaccine availability. Adjusted for age, sex, job position, and SVI, Black (relative risk [RR], 0.69; 95% CI, 0.66-0.72) and multiracial (RR, 0.80; 95% CI, 0.73-0.89) HCP were less likely to receive vaccine compared with White HCP. When stratified by job position, Black nurses (n = 189; 62.8%), Black HCP with some patient contact (n = 466; 49.9%), and Black HCP with no patient contact (n = 636; 56.3%) all had lower vaccine uptake compared with their White and Asian or Pacific Islander counterparts. Similarly, multiracial HCP with some (n = 26; 52.0%) or no (n = 48; 58.5%) patient contact had lower vaccine uptake. In contrast, Black physicians were just as likely to receive the vaccine as physicians of other racial and ethnic groups. In this cross-sectional study, more than two-thirds of HCP at a large academic hospital in Philadelphia received a COVID-19 vaccine within 4 months of vaccine availability. Although racial, ethnic, and socioeconomic disparities were seen in vaccine uptake, no such disparities were found among physicians. Better understanding of factors driving these disparities may help improve uptake.


Skeletal muscle function in patients with hemophilia A and unilateral hemarthrosis of the knee.
Acute hemarthrosis is a frequent complication of hemophilia A. To test the hypothesis that recurrent hemarthrosis has an adverse effect on neuromuscular function, ten patients with hemophilia A and history of unilateral hemarthrosis of the knee were studied. The uninvolved (U) side was used as the control. The time since diagnosis, factor level, and the number of bleeding episodes in the involved (I) knee averaged 11.6 +/- 6.6 years, 7.7 +/- 5.1%, and 7.0 +/- 7.4, respectively. Neuromuscular function was evaluated on a Cybex 340 isokinetic dynamometer. Knee extensor strength measured at 60 degrees/sec was significantly (p less than .05) lower in the I side (mean = 58Nm) than in the U side (mean = 85Nm). Similarly, lower (p less than .05) total work (I = 479J, U = 656J) and average power output (I = 59W, U = 83W) values were obtained. Adjusting for thigh circumference did not eliminate any of these differences. Testing the extensors at faster angular velocities (180 degrees/sec and 240 degrees/sec) and the flexor muscle groups at the three speeds revealed no differences between I and U. X-rays showed minimal changes. These data show that patients with hemophilia A and history of unilateral hemarthrosis of the knee have neuromuscular dysfunction in the I extremity that precedes the appearance of radiologic evidence of joint pathology. It is suggested that strength training should be started early in the rehabilitation of hemophiliacs.


A correlative study of the freezing patterns in rat myocardium using scanning and transmission electron microscopes.
Rat myocardial tissue, both fresh and chemically fixed, was quench frozen in melting Freon 22 at rates that resulted in in the formation of large ice-crystals. The material was studied with both scanning and transmission electron microscopy. Particular attention was paid to the characteristic freezing patterns within the myofibrils and mitochondria, and to features exposed by such freezing that might otherwise remain obscured. The freezing patterns found in tissue subjected to different processes were compared with the ultrastructure of unfrozen, chemically fixed counterparts. Ice-crystal cavities in the contractile material varied considerably along the length of a given myofiber in which the freezing front had progressed in parallel with the long axis of the myofibers. It is suggested that the intercalated disc functioned as a barrier to the freezing process. Ice generally compressed and distorted the contractile material beyond recognition, although the positions of the Z-bands remained evident and in register. Most single-fixed mitochondria were devoid of visible ice-crystal cavities, and the cristae generally remained intact. On the other hand, ice-crystal cavities were commonly seen between cristae of double-fixed mitochondria. No signs of perforations were seen in lipid bilayer membranes. Numerous strand-like connections between mitochondria as well as between mitochondria and the myofibrillar surface, which were believed to be sarcotubules, were made visible by the slow freezing process. Other strands, transverse to the myofibrils, connecting adjacent Z-bands and joining Z-bands to the sarcolemma, were interpreted as cytoskeletal elements. These strands, together with what apparently were SR tubules, exhibited high resistance to the stresses associated with the formation of ice-crystals.


Cutaneous leishmaniasis: knowledge, attitude and practices of the inhabitants of the Kani forest tribal settlements of Tiruvananthapuram district, Kerala, India.
Cutaneous leishmaniasis (CL) is reported among Kani tribes in forest settlements of Tiruvananthapuram district, Kerala, India. Epidemiological investigations are ongoing and 27 histopathologically confirmed cases of CL have been reported from five settlements indicating transmission of disease within settlements. One of the priorities for control/prevention of CL is to create awareness among the community and ensure optimal utilization of interventions. First step in this direction would be to carry out a situation analysis on prevailing knowledge, attitude and practice (KAP) of inhabitants. A study among 103 respondents from 10 Kani tribal settlements showed that though 39.8% of respondents recognized pictures of CL shown to them, but did not have any lay perceptions. There was absolutely no awareness on vector, transmission, risk factors and control measures. The role of sandflies in CL causation was not known to the residents and this prevented them from using any personal protection and adhering to control measures which in turn pose risk of spread of infection within settlements and to newer areas. CL has emerged as a challenging infection in this area and an urgent need for designing appropriate preventive measures and health education strategies is addressed in this article.


The role of macrophages in the regulation of high endothelial venule expression within the peripheral lymph nodes of mice exposed to ultraviolet radiation.
A number of direct and indirect immunologic consequences follow the exposure of the skin to ultraviolet radiation (UVR). One of the remote effects of UVR is the increased accumulation of lymphocytes within peripheral lymph nodes that drain irradiated skin sites. The present study was designed to evaluate the mechanisms responsible for this increased lymphocyte accumulation. Primary lymphocyte localization into draining regional lymph nodes was found to be markedly increased (up to 81%) by UVR exposure of the skin. The changes in lymphocyte localization correlated closely with increases in the number and density of lymphocyte-receptive endothelial structures (high endothelial venules, or HEV) within these regional lymph nodes. Because macrophages or their products are believed to maintain resting HEV expression and function, we assessed the role of these cells in the expansion of HEV due to UVR exposure. Our studies demonstrated that a peripheral injection of antigen-activated macrophages caused an increase in HEV expression within lymph nodes draining the injection site. Conversely, treatment of mice with silica or carrageenan to depress macrophage function produced both histologic and functional hyporesponsiveness of the microvascular endothelium to UVR-stimulated HEV expansion. These changes in endothelial cell responsiveness correlated with the absolute number of MAC-1+ cells present within the regional nodes of UVR-exposed mice. Our studies have demonstrated a striking similarity between lymph node microvascular changes in response to cutaneous UVR- and antigen-exposure. We therefore suggest that macrophage-mediated signals may initiate a general mechanism that increases lymphocyte recirculation through the regional lymph nodes in response to both antigenic and inflammatory challenge.


Species- and genome-wide dissection of the shoot ionome in Brassica napus and its relationship to seedling development.
Knowing the genetic basis of the plant ionome is essential for understanding the control of nutrient transport and accumulation. The aim of this research was to (i) study mineral nutrient concentrations in a large and diverse set of Brassica napus, (ii) describe the relationships between the shoot ionome and seedling development, and (iii) identify genetic regions associated with variation of the shoot ionome. The plant material under study was a germplasm set consisting of 509 inbred lines that was genotyped by a 6K single nucleotide polymorphism (SNP) array and phenotyped by analyzing the concentrations of eleven mineral nutrients in the shoots of 30 days old seedlings. Among mineral concentrations, positive correlations were found, whereas mineral concentrations were mainly negatively correlated with seedling development traits from earlier studies. In a genome-wide association mapping approach, altogether 29 significantly associated loci were identified across seven traits after correcting for multiple testing. The associations included a locus with effects on the concentrations of Cu, Mn, and Zn on chromosome C3, and a genetic region with multiple associations for Na concentration on chromosome A9. This region was situated within an association hotspot close to SOS1, a key gene for Na tolerance in plants.


A novel hyperthermophilic methylglyoxal synthase: molecular dynamic analysis on the regional fluctuations.
Two putative methylglyoxal synthases, which catalyze the conversion of dihydroxyacetone phosphate to methylglyoxal, from Oceanithermus profundus DSM 14,977 and Clostridium difficile 630 have been characterized for activity and thermal stability. The enzyme from O. profundus was found to be hyperthermophilic, with the optimum activity at 80 °C and the residual activity up to 59% after incubation of 15 min at 95 °C, whereas the enzyme from C. difficile was mesophilic with the optimum activity at 40 °C and the residual activity less than 50% after the incubation at 55 °C or higher temperatures for 15 min. The structural analysis of the enzymes with molecular dynamics simulation indicated that the hyperthermophilic methylglyoxal synthase has a rigid protein structure with a lower overall root-mean-square-deviation value compared with the mesophilic or thermophilic counterparts. In addition, the simulation results identified distinct regions with high fluctuations throughout those of the mesophilic or thermophilic counterparts via root-mean-square-fluctuation analysis. Specific molecular interactions focusing on the hydrogen bonds and salt bridges in the distinct regions were analyzed in terms of interatomic distances and positions of the individual residues with respect to the secondary structures of the enzyme. Key interactions including specific salt bridges and hydrogen bonds between a rigid beta-sheet core and surrounding alpha helices were found to contribute to the stabilisation of the hyperthermophilic enzyme by reducing the regional fluctuations in the protein structure. The structural information and analysis approach in this study can be further exploited for the engineering and industrial application of the enzyme.


Associating drug sensitivity with differentiation status identifies effective combinations for acute myeloid leukemia.
Using ex vivo drug screening of primary patient specimens, we identified the combination of the p38 MAPK inhibitor doramapimod (DORA) with the BCL2 inhibitor venetoclax (VEN) as demonstrating broad, enhanced efficacy compared with each single agent across 335 acute myeloid leukemia (AML) patient samples while sparing primary stromal cells. Single-agent DORA and VEN sensitivity was associated with distinct, nonoverlapping tumor cell differentiation states. In particular, increased monocytes, M4/M5 French-American-British classification, and CD14+ immunophenotype tracked with sensitivity to DORA and resistance to VEN but were mitigated with the combination. Increased expression of MAPK14 and BCL2, the respective primary targets of DORA and VEN, were observed in monocytic and undifferentiated leukemias, respectively. Enrichment for DORA and VEN sensitivities was observed in AML with monocyte-like and progenitor-like transcriptomic signatures, respectively, and these associations diminished with the combination. The mechanism underlying the combination's enhanced efficacy may result from inhibition of p38 MAPK-mediated phosphorylation of BCL2, which in turn enhances sensitivity to VEN. These findings suggest exploiting complementary drug sensitivity profiles with respect to leukemic differentiation state, such as dual targeting of p38 MAPK and BCL2, offers opportunity for broad, enhanced efficacy across the clinically challenging heterogeneous landscape of AML.


Effects of gonadal sex steroids on sexual behavior in the big brown bat, Eptesicus fuscus, upon arousal from hibernation.
Vespertilionid bats are thought to have a dissociated pattern of reproduction; mating occurs in autumn as well as during periodic arousals from hibernation when testes are regressed and ovaries are "in stasis." Sex steroid levels in both sexes are basal at this time. This pattern would indicate that sex steroids per se may not be activating sexual behavior. Gonadectomy of male and female big brown bats, Eptesicus fuscus, months before the mating season, did not significantly affect the probability of expressing sexual behavior in either sex when staged behavior tests were conducted. Ovariectomized females, in fact, mated significantly more and exhibited proceptive behavior. Males mated at the same frequency whether they were intact, orchidectomized, or given testosterone implants. These results argue that gonadal sex steroids are not the direct activators of sexual behavior in this species. However, when males were allowed to mate freely within a large flight cage, orchidectomized males were not seen to mate, while intact males mated at the same frequency as in the staged trials. Females are apparently either differentiating between the two groups of males or there is male-male competition for mates within a system that has multiple matings with different individuals in both sexes.


InAs/GaAs quantum-dot superluminescent diodes monolithically grown on a Ge substrate.
We report the first InAs/GaAs quantum-dot (QD) superluminescent diode (SLD) monolithically grown on a Ge substrate by molecular beam epitaxy. The QD SLD exhibits a 3 dB emission bandwidth of ~60 nm centered at 1252 nm with output power of 27 mW at room temperature. The 3 dB bandwidth is very stable over the temperature range from 20 °C to 100 °C, which highlights the potential for integration with high performance ICs.


Role of manidipine in the management of patients with hypertension.
Manidipine is a third-generation dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. In clinical studies, manidipine has been shown to significantly lower office and 24-h blood pressure compared with placebo in patients with essential hypertension. The resulting reduction in blood pressure is maintained over 24 h, with preservation of the circadian blood pressure pattern; its blood pressure-lowering capacity appears to be similar to that of other calcium antagonists. In elderly patients with mild-to-moderate essential hypertension, manidipine is able to significantly decrease blood pressure compared with placebo for up to 3 years of treatment. The drug also significantly lowers blood pressure in patients with hypertension and concomitant Type 2 diabetes mellitus or renal impairment, and is devoid of adverse metabolic effects. It is well-tolerated with few untoward adverse effects related to vasodilation. In particular, manidipine appears to have less potential for pedal edema than other calcium channel blockers.