Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia.
While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital. A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression. A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31-40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection. The prevalence of smear positive extra pulmonary tuberculosis infection in Gondar is high. Screening of lymph node and other body fluid specimens for extra pulmonary tuberculosis could help for treatment, control and prevention of the disease.


Extracorporeal life support as bridge to recovery in yew poisoning: case reports and literature review.
This short communication aims to review the treatment of cardiogenic shock in patients with yew poisoning based on two case reports from our institution, focusing on the use of extracorporeal life support (ECLS). We report two cases of Taxus baccata poisoning treated with ECLS at our institution and review the literature based on a search in PubMed and Google Scholar on the topic of yew poisoning and ECLS. All cases were combined for analysis of demographics, ECLS therapy, and outcome. Case 1: A 35-year-old woman developed polymorphic ventricular tachycardia followed by cardiovascular arrest 5 h after orally ingesting a handful of yew needles. Successful resuscitation required ECLS for 72 h due to ongoing cardiac arrhythmias and cardiogenic shock. The patient left the hospital without neurological sequelae after 10 days. Case 2: A 30-year-old woman developed refractory cardiac arrhythmias and circulatory arrest. Resuscitation included ECLS for 71 h. T. baccata needles found by gastroscopy confirmed the diagnosis. The patient had no neurologic deficits and was transferred to psychiatry after 11 days. Nine case reports were found and analysed along with our two cases. Five out of the 11 (45%) patients were female. Median (range) age was 28 (19-46) years. T. baccata needles were ingested with a suicidal intention in all patients. Median (range) duration of ECLS was 70 h (24-120 h). Eight (73%) patients had full neurological recovery. Yew poisoning is a differential diagnosis in young psychiatric patients presenting with polymorphic ventricular tachycardia and cardiogenic shock. A characteristic cardiac contraction pattern in echocardiography may present a diagnostic clue. The early use of ECLS is a valuable bridge to recovery in most of these patients.


Aortitis with antiphospholipid antibodies: CT and MR findings.
Two cases of aortitis associated with the presence of antiphospholipid antibodies (APAs) are reported. Only CT and MR imaging were able to show these unusual form of aortitis preferentially affecting the outer aortic tunics. We conclude that aortitis could be a new manifestation of primary antiphospholipid syndrome (APS) and the initial pathological process before the development of aortic thrombosis, reported as a classical complication of APS.


Visual outcomes and treatment adherence of patients with macular pathology using a mobile hyperacuity home-monitoring app: a matched-pair analysis.
We compared patients with neovascular age-related macular degeneration (nvAMD), diabetic macular oedema (DMO) and other macular pathologies testing their vision with the hyperacuity home-monitoring app Alleye to patients not performing home-monitoring regarding clinical outcomes and clinical management. Matched-pair analysis. Retina Referral Centre, Switzerland. For each eye using Alleye, we matched 2-4 controls not using home-monitoring based on age, gender, number of previous intravitreal injections (IVI), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study letters), central macular thickness (CRT) and time point of enrolment, using the Mahalanobis distance matching algorithm. We included 514 eyes (288 patients); 107 eyes with nvAMD using home monitoring and 218 controls not using home monitoring, 25 eyes with DMO (n=52 controls) and 40 eyes with miscellaneous conditions (n=72 controls). 173 eyes (33.7%) received no IVI during follow-up. Improvement of ≥5 letters, number of injection visits and treatment retention after correcting for differences in baseline characteristics with multivariate analyses. The mean follow-up duration was 809 days (range 147-1353) and the mean number of IVI/year among treated eyes was 6.7 (SD 3.1). Mean age at baseline was 70.4 years (SD 10.9), BCVA was 77.6 letters (SD 11.6) and CRT was 263.6 µm (SD 86.7) and was similar between patients using and not using home monitoring. In multivariate analyses, patients using home monitoring had a higher chance to improve visual acuity by ≥5 letters (OR 1.67 (95% CI 1.01 to 2.76; p=0.044)) than controls. Treated eyes using home monitoring had less injection visits/year (-0.99 (95% CI -1.59 to -0.40; p=0.001)) and a longer treatment retention +69.2 days (95% CI 2.4 to 136.0; p=0.042). These effects were similar across retinal pathologies. This data suggest that patients capable of performing mobile hyperacuity home monitoring benefit in terms of visual acuity and discontinue treatment less often than patients not using home monitoring.


Lipo-PGE1, a new lipid-encapsulated preparation of prostaglandin E1: placebo-and prostaglandin E1-controlled multicenter trials in patients with diabetic neuropathy and leg ulcers.
Several clinical trials have shown that prostaglandin E1 (PGE1) is effective in treating peripheral occlusive vascular disease, but not definitely for diabetic neuropathy. We developed a new preparation of PGE1 incorporated in lipid microspheres (lipo-PGE1) that was designed to accumulate at vascular lesions. The effect of lipo-PGE1 (10 micrograms/day) was compared with placebo and the normal dose of a free PGE1 preparation (PGE1-CD, 40 micrograms/day) in two studies (double-blind and well-controlled) which enrolled 364 diabetic patients with neuropathy and/or leg ulcers. The drugs were given intravenously (bolus or drip infusion) for 4 weeks. Clinical improvement was noted in 61.6% of the lipo-PGE1 group and 30.0% of the placebo group in Trial 1 (p < 0.01), while the figures were 58.3% in the lipo-PGE1 group and 37.1% in the PGE1-CD group in Trial 2 (p < 0.01). Leg ulcers became smaller in the lipo-PGE1 groups in both trials (p < 0.01). In Trial 2, motor conduction velocity improved in the lipo-PGE1 group (p = 0.016). Side effects occurred in few patients receiving lipo-PGE1 or placebo, but more patients developed local side effects in the PGE1-CD group (p < 0.01). Thus, bolus intravenous injection of lipo-PGE1 improved diabetic neuropathy and leg ulcers with minimal side effects.


Method for screening water physicochemical parameters to calculate water quality index based on these parameters' correlation with water microbiota.
Water quality index (WQI) plays a crucial role in guiding water resource management. However, WQI calculation methods are not uniform, especially the selection of water parameters and the weighting given to each water parameter (Pi). To optimize WQI calculation, 132 water samples from seven rivers and from Chaohu Lake (33 sampling sites in Chaohu Lake Basin) in four seasons were collected, and the water parameters and microbiota composition were analyzed using high-throughput sequencing of 16 S rDNA. The correlation coefficient R2 between water parameters and microbiota composition using redundancy analysis with the Monte Carlo method were calculated, and the water parameters that significantly correlated with the microbiota composition were selected to calculate WQImin. The results showed that TP, COD, DO, and Chl a correlated significantly with water microbiota composition. WQIb calculated by substituting R2 for Pi was more consistent with the similarity between the microbiota compositions. WQIminb calculated using TP, COD, and DO was consistent with WQIb. The results of WQIb and WQIminb were more consistent than those of WQI and WQImin. These results imply that using R2 instead of Pi could help obtain a more stable WQIb that could better reflect the biological characteristics of the Chaohu Lake Basin.


Group I p21-activated kinases facilitate Tax-mediated transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats.
Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and tropical spastic paraparesis. HTLV-1 encodes transactivator protein Tax that interacts with various cellular factors to modulate transcription and other biological functions. Additional cellular mediators of Tax-mediated transcriptional activation of HTLV-1 long terminal repeats (LTR) remain to be identified and characterized. In this study, we investigated the regulatory role of group I p21-activated kinases (Paks) in Tax-induced LTR activation. Both wild-type and kinase-dead mutants of Pak3 were capable of potentiating the activity of Tax to activate LTR transcription. The effect of Paks on the LTR was attributed to the N-terminal regulatory domain and required the action of CREB, CREB-regulating transcriptional coactivators (CRTCs) and p300/CREB-binding protein. Paks physically associated with Tax and CRTCs. Paks were recruited to the LTR in the presence of Tax. siRNAs against either Pak1 or Pak3 prevented the interaction of Tax with CRTC1 and the recruitment of Tax to the LTR. These siRNAs also inhibited LTR-dependent transcription in HTLV-1-transformed MT4 cells and in cells transfected with an infectious clone of HTLV-1. Group I Paks augment Tax-mediated transcriptional activation of HTLV-1 LTR in a kinase-independent manner.


Sulphydryl groups and iodo-[3H]acetic acid labeling in proteolipids from Torpedo electroplax.
Several fractions of proteolipids from Torpedo electroplax were separated by DEAE-cellulose chromatography in organic solvents, and the sulphydryl groups were determined by a spectrophotometric method. On the same fractions the covalent labeling with iodo-[3H]acetic acid to sulphydryl groups was studied. In total proteolipids there were 30.3 nmol/mg protein of sulphydryl groups of which 20.6 nmoles were in the form of disulfide bonds and 10.9 nmol as free--SH groups. The highest content of sulphydryl groups (36.7 nmol/mg protein) was found in fraction II; while fraction I, that binds the cholinergic ligands, has a lower content (23.7 nmol/mg protein). The 42 Kdaltons polypeptide, which is the major band in Fraction II, has the strongest labeling with iodo-[3H]acetic acid, while the 39 Kdaltons cholinergic polypeptide shows a lower labeling. The importance of proteolipids as channel-forming macromolecules is discussed in connection with the possible significance of the 42 Kdaltons polypeptide.


NBQX inhibits AMPA-induced locomotion after injection into the nucleus accumbens.
The role of glutamate receptors in locomotor activity was investigated by examining the ability of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX), a non-NMDA antagonist, to inhibit the stimulation of locomotion produced by the activation of various excitatory amino acid receptors in the nucleus accumbens. NBQX inhibited the stimulation of locomotor activity produced by intra-accumbens alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) at doses which had no effect on the locomotion produced by kainate or NMDA. Furthermore, this dose of NBQX had no effect on locomotion when injected alone into this brain region. These data suggest that AMPA receptors in the nucleus accumbens may play a very different role in the control of locomotion than NMDA receptors.


Catechin potentiates the antifungal effect of miconazole in Candida glabrata.
The rising number of invasive fungal infections caused by drug-resistant Candida strains is one of the greatest challenges for the development of novel antifungal strategies. The scarcity of available antifungals has drawn attention to the potential of natural products as antifungals and in combinational therapies. One of these is catechins-polyphenolic compounds-flavanols, found in a variety of plants. In this work, we evaluated the changes in the susceptibility of Candida glabrata strain characterized at the laboratory level and clinical isolates using the combination of catechin and antifungal azoles. Catechin alone had no antifungal activity within the concentration range tested. Its use in combination with miconazole resulted in complete inhibition of growth in the sensitive C. glabrata isolate and a significant growth reduction in the azole resistant C. glabrata clinical isolate. Simultaneous use of catechin and miconazole leads to increased intracellular ROS generation. The enhanced susceptibility of C. glabrata clinical isolates to miconazole by catechin was accompanied with the intracellular accumulation of ROS and changes in the plasma membrane permeability, as measured using fluorescence anisotropy, affecting the function of plasma membrane proteins.


Different modes of action of substance P in the motor control of the feline stomach and pylorus.
In an experimental in vivo model to study gastropyloric motility in the cat a contraction of the stomach and the pyloric sphincter was regularly obtained in animals subjected to electrical vagal nerve stimulation or local intraarterial (i.a.) injection of substance P (SP). Much more infrequently contractile motor responses were recorded at splanchnic nerve stimulation. The contractile effects of SP were sensitive to atropine or local infusion of a SP analogue, (D-Pro2,D-Trp7,9)-SP, indicating that SP activated a final common cholinergic neuron in both stomach and pylorus. However, there seemed to be separate transmission mechanisms in these two regions based on the results of the physiological studies. The vagally induced pyloric contraction was noncholinergic, nonadrenergic, but sensitive to ganglionic blockade (hexamethonium) or the SP analogue, indicating involvement of SP in a peptidergic pathway to the sphincter. The infrequent splanchnically induced pyloric contraction was sensitive to atropine, the SP analogue or ganglionic blockade (hexamethonium) in favour of SP acting on a final cholinergic neuron in this system. On the other hand the gastric contraction, obtained at either extrinsic nerve stimulations or local i.a. injection of SP, was sensitive to atropine or the SP analogue but hexamethonium resistant. These findings suggest antidromic activation of SP-containing axon collaterals of the extrinsic nerves terminating on cholinergic neurons of the gastric wall. When afferent C-fibres of the vagal nerve were selectively activated by local heating, pyloric contraction and gastric relaxation were obtained via vago-vagal reflexes. After cervical vagotomy heating of the distal end of the vagal nerve elicited a gastric contraction, previously demonstrated to be atropine sensitive and hexamethonium resistant, but no pyloric motor response. This suggests that the antidromic activation mechanism was present only in the stomach, not in the pylorus.


Drosophila grim induces apoptosis in mammalian cells.
Genetic studies have shown that grim is a central genetic switch of programmed cell death in Drosophila; however, homologous genes have not been described in other species, nor has its mechanism of action been defined. We show here that grim expression induces apoptosis in mouse fibroblasts. Cell death induced by grim in mammalian cells involves membrane blebbing, cytoplasmic loss and nuclear DNA fragmentation. Grim-induced apoptosis is blocked by both natural and synthetic caspase inhibitors. We found that grim itself shows caspase-dependent proteolytic processing of its C-terminus in vitro. Grim-induced death is antagonized by bcl-2 in a dose-dependent manner, and neither Fas signalling nor p53 are required for grim pro-apoptotic activity. Grim protein localizes both in the cytosol and in the mitochondria of mouse fibroblasts, the latter location becoming predominant as apoptosis progresses. These results show that Drosophila grim induces death in mammalian cells by specifically acting on mitochondrial apoptotic pathways executed by endogenous caspases. These findings advance our knowledge of the mechanism by which grim induces apoptosis and show the conservation through evolution of this crucial programmed cell death pathway.


Electron correlation effects and density analysis of the first-order hyperpolarizability of neutral guanine tautomers.
Dipole moments (μ), charge distributions, and static electronic first-order hyperpolarizabilities (β(μ)) of the two lowest-energy keto tautomers of guanine (7H and 9H) were determined in the gas phase using Hartree-Fock, Møller-Plesset perturbation theory (MP2 and MP4), and DFT (PBE1PBE, B97-1, B3LYP, CAM-B3LYP) methods with Dunning's correlation-consistent aug-cc-pVDZ and d-aug-cc-pVDZ basis sets. The most stable isomer 7H exhibits a μ value smaller than that of the 9H form by a factor of ca. 3.5. The β μ value of the 9H tautomer is strongly dependent on the computational method employed, as it dramatically influences the β(μ) (9H)/β(μ) (7H) ratio, which at the highest correlated MP4/aug-cc-pVDZ level is predicted to be ca. 5. The Coulomb-attenuating hybrid exchange-correlation CAM-B3LYP method is superior to the conventional PBE1PBE, B3LYP, and B97-1 functionals in predicting the β(μ) values. Differences between the largest diagonal hyperpolarizability components were clarified through hyperpolarizability density analyses. Dipole moment and first-order hyperpolarizability are molecular properties that are potentially useful for distinguishing the 7H from the 9H tautomer.


Structure-Based Discovery of Potent Staphylococcus aureus Thymidylate Kinase Inhibitors by Virtual Screening.
Multidrug-resistant bacteria are rapidly increasing worldwide, increasing antibiotic resistance. The exploitation, misuse, overuse, and decrease of the therapeutic potential of currently available antibiotics have resulted in the development of resistance against bacteria. As the most common bacterial pathogen in humans, Staphylococcus aureus can cause many adverse health effects. In fighting multidrug-resistant Staphylococcus aureus, scientists have identified an extremely relevant target - SaTMPK. SaTMPK is essential for DNA synthesis, which, in turn, is necessary for the replication and cell division of bacteria. To perform multi-stage screening using the ZINC database, followed by molecular docking, ADMET profiling, molecular dynamics simulations, and energy calculations. Based on the similar pharmacophoric characteristics of existing SaTMPK crystal structures, a model of interaction-based pharmacophores was developed. We then performed molecular docking studies on the positive hits obtained from the pharmacophore screening. Compounds that exhibited good molecular interactions within the SaTMPK binding sites were further evaluated using in-silico ADMET profiling. In a multi-stage screening campaign, three compounds were shortlisted that exhibited physicochemical characteristics suitable for human administration. The findings from this study should contribute to in vitro and in vivo studies for clinical applications.


Stromal vascular fraction therapy for knee osteoarthritis: a systematic review.
Regenerative cell therapies, such as adipose-derived stromal vascular fraction (SVF), have been postulated as potential treatments for knee osteoarthritis (KOA). To assess the efficacy and safety of SVF treatment against placebo and other standard therapies for treating KOA in adult patients. A systematic review. We searched the following databases: MEDLINE via PubMed, Epistemonikos, PEDro, DynaMed, TripDatabase, Elsevier via Clinicalkey and Cochrane Controlled Trials Register. We included prospective interventional studies where treatment with SVF in adults with KOA was compared against placebo or other standard therapies, and results were objectively measured with at least one widely recognised osteoarthritis scale. Among 266 studies published until May 2021, nine met our inclusion criteria. A total of 239 patients (274 knees) were included in our study. The follow-up ranged from 6 to 24 months. Six studies had a control group (only one being placebo). All studies showed that SVF improved pain and functionality measured, in most cases, with the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index. In addition, five studies reported an improvement in anatomical structures, as detected in MR images. However, the number of cells contained in SVF varied substantially between different studies, which could induce a comparison bias. Although based on a small number of dissimilar studies, SVF was considered a safe treatment for KOA and could be promising in terms of pain, functionality and anatomical structure improvement. However, SVF products need to be standardised, the number of cells homogenised and the use of concomitant treatments reduced to establish proper comparisons. PROSPERO registration number: CRD42021284187.


Enhanced soluble protein expression using two new fusion tags.
Production of soluble recombinant proteins is vital for structure-function analysis and therapeutic applications. Unfortunately, when expressed in a heterologous host, such as Escherichia coli, most proteins are expressed as insoluble aggregates. Two new fusion partners have been identified to address these solubility problems. One of the tags was derived from a bacteriophage T7 protein kinase and the other one from a small E. coli chaperone, Skp. We have expressed a panel of insoluble human proteins including Hif1alpha, IL13, and folliculin as fusion proteins using these tags. Most of these fusion proteins were able to be expressed in a soluble form and could be purified by virtue of a Strep-tag II installed at the amino-terminal end of the fusion partners. In addition, we show that some of these proteins remained soluble after removal of the fusion tags by a site-specific protease. The results with these tags compare favorably to results with the most commonly used solubility tags described in the literature. Therefore, these two new fusion tags have the potential to express soluble proteins when fused with many recalcitrant proteins.


Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients.
This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.


Effects of a team-based assessment and intervention on patient safety culture in general practice: an open randomised controlled trial.
The measurement of safety culture in healthcare is generally regarded as a first step towards improvement. Based on a self-assessment of safety culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare teams to improve safety culture in their organisations. In this study we assessed the effects of FraTrix on safety culture in general practice. We conducted an open randomised controlled trial in 60 general practices. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practices. At baseline and after 12 months, scores were allocated for safety culture as expressed in practice structure and processes (indicators), in safety climate and in patient safety incident reporting. The primary outcome was the indicator error management. During the team sessions, practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it. After 12 months, no significant differences were found between intervention and control groups in terms of error management (competing probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety culture indicators and safety climate scales. Intervention practices showed better reporting of patient safety incidents, reflected in a higher number of incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than control practices. Applied as a team-based instrument to assess safety culture, FraTrix did not lead to measurable improvements in error management. Comparable studies with more positive results had less robust study designs. In future research, validated combined methods to measure safety culture will be required. In addition, more attention should be paid to evaluation of process parameters. Implemented actions and incident reporting may be more appropriate target endpoints. German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145.


Pan-mediastinal neoplasm diagnosis via nationwide federated learning: a multicentre cohort study.
Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.


Anesthesia for cesarean section in pregnancies complicated by placenta previa.
To evaluate the factors affecting the choice of anesthetic technique for cesarean section in women with placenta previa. In this retrospective study, the records of the Labor Ward Theatre of the University of Benin Teaching Hospital, Benin City, Nigeria were examined from January 2000 to December 2004 to identify all the women who had cesarean section for placenta previa. The patients' socio-demographic characteristics, type of placenta previa, anesthetic technique, estimated blood loss, maternal and fetal outcomes were recorded. One hundred and twenty-six patients had cesarean section for placenta previa, however, only 81 patients (64.3%) were available for analysis. General anesthesia was administered to 52/81 patients (64.2%), and 29/81 patients (35.8%) received spinal anesthesia. A history of antepartum bleeding was recorded in 61.7% (n =50). Of the 31 patients without antepartum hemorrhage (APH), 15/31 had general anesthesia, and 16/31 had spinal anesthesia. The patients who had APH, 37/50 had general anesthesia, and 13/50 had spinal anesthesia. There was an increased chance of using general anesthesia if APH were present (p=0.03, odds ratio = 3.1, 95% confidence interval = 1.2-7.8). Spinal anesthesia may be useful in patients with placenta previa. The presence of APH may encourage the use of general anesthesia for cesarean delivery.


Identification of a New Set of Polypeptidic Sex Pheromones from Cuttlefish (Sepia officinalis).
The common English Channel cuttlefish (Sepia officinalis) reproduces every year on very localized coastal spawning areas after a west-east horizontal migration of several tens of kilometers (80-200 km). The massive arrival of spawners on the coasts of west Cotentin and the Bay of Seine is suspected to be driven by the action of sex pheromones expressed and secreted by the genitals of sexually mature females. The present study aims to verify the existence of polypeptide pheromones, of a higher molecular weight than those described above. Their size could confer them a wider range of action than that of the previously identified peptide pheromones. The implementation of an experimental strategy combining transcriptomics and proteomics with functional tests and an in silico study led to the identification of a cocktail of pheromones with molecular weights ranging between 22 and 26 kDa. Proteomic analyses combined to functional tests revealed partial pheromone release in the environment, and their accumulation in the outer capsule of the egg, suggesting the eggs as pheromone diffusers, also able to induce stimulation by contact when the eggs are handled by females.


Technical report: xMAPr - High-dynamic-range (HDR) quantification of antigen-specific antibody binding.
Here, we demonstrate a high-dynamic-range quantification of antibody binding to single antigens in a multiplexed suspension bead array format. Using a dilution-based approach and the newly developed data analysis tool the quantitative dynamic range is increased by three orders of magnitude in the selected samples. The strong increase in dynamic range results in a more robust data basis for downstream analyses.


Hierarchical Plasmonic Nanorods and Upconversion Core-Satellite Nanoassemblies for Multimodal Imaging-Guided Combination Phototherapy.
DNA-driven hierarchical core-satellite nanostructures with plasmonic gold nanorod dimers and upconversion nanoparticles are fabricated. Once the core-satellite structure is activated, combined photothermal therapy and photodynamic therapy are carried out under the guidance of upconversion luminesce, T1 -weighted magnetic resonance, photoacoustics, and computed tomography imaging of tumors in vivo, which exhibit the multifunctional biological applications of the DNA-based self-assemblies.


Quantitative atomic resolution elemental mapping via absolute-scale energy dispersive X-ray spectroscopy.
Quantitative agreement on an absolute scale is demonstrated between experiment and simulation for two-dimensional, atomic-resolution elemental mapping via energy dispersive X-ray spectroscopy. This requires all experimental parameters to be carefully characterized. The agreement is good, but some discrepancies remain. The most likely contributing factors are identified and discussed. Previous predictions that increasing the probe forming aperture helps to suppress the channelling enhancement in the average signal are confirmed experimentally. It is emphasized that simple column-by-column analysis requires a choice of sample thickness that compromises between being thick enough to yield a good signal-to-noise ratio while being thin enough that the overwhelming majority of the EDX signal derives from the column on which the probe is placed, despite strong electron scattering effects.


Quantitative ultrastructural analysis of coronary atherosclerotic involvement in two macaque species.
Ultrastructural analyses were employed to observe and to compare in detail lesions of the coronary artery of cynomolgus and rhesus monkeys. Animals were fed individually with the same atherogenic ration under identical conditions for 4, 8, and 12 months, and controls of each species were fed with a low fat, cholesterol-free ration. Transmission electron microscopic studies of coronary arteries from these animals led to the following conclusions: (1) Synthetic smooth muscle cells (SMC) without lipid and macrophages without lipid appeared more frequently in the cynomolgus lesions than in the rhesus lesions. Furthermore, phenotypic expression of synthetic SMCs in the cynomolgus was more active with greater diversity, while the rhesus showed less phenotypic modulation. Macrophages without lipid appeared frequently in the cynomolgus media. (2) Increased percentages of both synthetic SMCs with lipid and macrophages with lipid were demonstrated in the cynomolgus lesions as compared to those in the rhesus. This indicates that foam cells, including SMC- and macrophage-derived foam cells, are more prevalent in cynomolgus than in rhesus. They are considered to play an important role in atherogenesis. (3) Medial disruption, synthetic SMCs, and macrophages containing lipid appeared more often in cynomolgus media than in rhesus media. (4) There were greater percentages of both synthetic SMCs and macrophages in the intima of the myocardial side of coronary arteries in both species. (5) Approximately 42% of all foam cells in the cynomolgus lesions were derived from SMCs. There were fewer macrophages in rhesus lesions. (6) The difference in expression between the two macaque species reflects different responses of macrophages to medial smooth muscle cell (SMC) components. The configuration of the artery wall could be one of the important indicators of these different expressions.


Socioeconomic (SES) differences in language are evident in female infants at 7months of age.
Language skills, strongly linked to academic success, are known to differ by socioeconomic status (SES), with lower SES individuals performing less well than higher SES. To examine the effect of SES on infant language at 7months of age and the relationship between maternal vocabulary skills and infant language function. To determine if the relationships between SES and infant language are mediated by maternal vocabulary skills. Longitudinal follow-up of healthy term female African American infants born to mothers in two SES groups: Low SES (income-to-needs≤1, no education beyond high school) and Higher SES (Income-to-Needs >1, at least a high school diploma). 54 infants tested at 7months of age; 54 mothers tested at infant age 7months. Preschool Language Scale-5 (PLS-5), Vocabulary and Matrix Reasoning subtests of the Wechsler Adult Intelligence Scale-IV. Low SES infants (n=29) performed less well than Higher SES (n=25) on PLS-5 Total Language, Auditory Comprehension, and Expressive Communication (p≤0.012). Maternal Vocabulary subtest scores were lower in Low SES than Higher SES (p=0.002), but not related to infant PLS Language scores (p≥0.17). Maternal vocabulary did not mediate the relationship between SES and infant language skills at age 7months. In this single sex and race cohort of healthy, term, female infants, lower SES exerted negative effects on infant language by 7months of age. While maternal vocabulary scores showed no relation with infant language skills at 7months, continued study of the relations between SES, infant outcomes and maternal characteristics is needed to determine how low SES conditions impact early language. These findings underscore the importance of early interventions, as well as policies designed to improve socioeconomic conditions for infants and families.


Contribution of voluntary fortified foods to micronutrient intake in The Netherlands.
In the Netherlands, voluntary fortification of foods with micronutrients is allowed under strict regulations. This study investigates the impact of voluntary food fortification practices in the Netherlands on the frequency and type of fortified food consumption and on the micronutrient intakes of the Dutch population. Data of the Dutch National Food Consumption Survey (2012-2016; N = 4314; 1-79 year) and the Dutch Food Composition Database (NEVO version 2016) was used. To determine if voluntary fortified foods could be classified as healthy foods, criteria of the Dutch Wheel of Five were used. Habitual intakes of users and non-users of voluntary food fortification were calculated using Statistical Program to Assess Dietary Exposure (SPADE) and compared. Within the Dutch population, 75% could be classified as user of voluntary fortified foods. Consumed voluntary fortified foods were mostly within food groups 'Fats and Oils', 'Non-alcoholic Beverages' and 'Dairy products and Substitutes' and fell mostly outside the Wheel of Five. Voluntary foods contributed between 9 and 78% to total micronutrient intake of users. Users had up to 64% higher habitual micronutrient intakes, compared to non-users. These higher intakes resulted into lower risks on inadequate intakes, and did not contribute to increased risks of excessive intakes. Although voluntary fortified foods increased micronutrient intakes, most of these foods cannot be classified as healthy foods. Future studies should study the association between higher micronutrient intakes and (potential) excessive intakes of e.g. saturated fat and sugar to better understand the role of voluntary fortified foods in a healthy food pattern.


Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis.
BACKGROUNDHepatic encephalopathy (HE) is associated with poor outcomes. A prior randomized, pilot trial demonstrated safety after oral capsular fecal microbial transplant (FMT) in HE, with favorable changes in microbial composition and cognition. However, microbial functional changes are unclear. The aim of this study was to determine the effect of FMT on the gut-brain axis compared with placebo, using microbial function based on bile acids (BAs), inflammation (serum IL-6, LPS-binding protein [LBP]), and their association with EncephalApp.METHODSTwenty cirrhotic patients were randomized 1:1 into groups that received 1-time FMT capsules from a donor enriched in Lachnospiraceae and Ruminococcaceae or placebo capsules, with 5-month follow-up for safety outcomes. Stool microbiota and BA; serum IL-6, BA, and LBP; and EncephalApp were analyzed at baseline and 4 weeks after FMT/placebo. Correlation networks among microbiota, BAs, EncephalApp, IL-6, and LBP were performed before/after FMT.RESULTSFMT-assigned participants had 1 HE recurrence and 2 unrelated infections. Six placebo-assigned participants developed negative outcomes. FMT, but not placebo, was associated with reduced serum IL-6 and LBP and improved EncephalApp. FMT-assigned participants demonstrated higher deconjugation and secondary BA formation in feces and serum compared with baseline. No change was seen in placebo. Correlation networks showed greater complexity after FMT compared with baseline. Beneficial taxa, such as Ruminococcaceae, Verrucomicrobiaceae, and Lachnospiraceae, were correlated with cognitive improvement and decrease in inflammation after FMT. Fecal/serum secondary/primary ratios and PiCRUST secondary BA pathways did not increase in participants who developed poor outcomes.CONCLUSIONGut microbial function in cirrhosis is beneficially affected by capsular FMT, with improved inflammation and cognition. Lower secondary BAs in FMT recipients could select for participants who develop negative outcomes.TRIAL REGISTRATIONClinicaltrials.gov NCT03152188.FUNDINGNational Center for Advancing Translational Sciences NIH grant R21TR002024, VA Merit Review grant 2I0CX001076, the United Kingdom National Institute for Health Research Biomedical Facility at Imperial College London, the British Heart Foundation, Wellcome Trust, and King's College London.


Effect of coffee consumption on dyslipidemia: A meta-analysis of randomized controlled trials.
Dyslipidemia is a common metabolic disease worldwide and also an important predisposing factor for cardiovascular diseases (CVDs). Coffee is loved by people all over the world; however, the association between coffee consumption and blood lipids has yielded inconsistent results. So we carried this meta-analysis to explore the effects of coffee consumption on blood lipids. Medline, PubMed, Web of science, Embase, and Cochrane Library databases were systematically searched until April 2020. Combined weighted mean differences (WMD) with their 95% confidence interval (CI) were calculated using random-effects models, and between-study heterogeneity was assessed by Cochran's Q test and I2 statistics. Subgroup analysis and meta-regression analysis were also conducted to explore the potential heterogeneity. A total of 12 RCT studies involving the association between coffee consumption and blood lipid levels were included in the meta-analysis. The pooled results showed that coffee consumption significantly increased total cholesterol (TC) (WMD: 0.21 mmol/L, 95% CI: 0.04; 0.39, P = 0.017), triglyceride (TG) (WMD: 0.12 mmol/L, 95% CI: 0.03; 0.20, P = 0.006) and low-density lipoprotein (LDL-C) (WMD: 0.14 mmol/L, 95% CI: 0.05; 0.24, P = 0.003) while had no significant effect on high-density lipoprotein (HDL-C) (WMD: -0.01 mmol/L, 95% CI: -0.06; 0.04, P = 0.707). Dose-response analysis results revealed significant positive nonlinear associations between coffee consumption and the increase in TC, LDL-C, and TG levels. Evidence from this meta-analysis suggested that coffee consumption may be associated with an elevated risk for dyslipidemia and CVDs. So a reasonable habit of coffee consumption (<3 cups/d) is essential for the prevention of dyslipidemia.


Diarrhea, red diapers, and child abuse: clinical alertness needed for recognition; clinical skill needed for success in management.
Three children were chronically given phenolphthalein in the form of laxatives by emotionally disturbed mothers. All children had repeated hospitalizations and extensive diagnostic testing because of recurrent intractable unexplained diarrhea. One child died. Pink-red urine and stool were passed at some time during their illnesses. The presence of phenolphthalein was tested for by application of dilute acid of dilute alkali to the diapers causing respectively disappearance of deepening of the pink-red color. Cases went undiagnosed for prolonged intervals because mothers seemed exemplary. Evidence of their psychiatric illnesses was found once the possibility was considered. Phenolphthalein poisoning should be tested for in any case of intractable diarrhea when objective evidence of intestinal mucosal damage cannot be found. The condition represents a heretofore unrecognized variant of child abuse of battering.


Lack of CYP1A1 expression is involved in unresponsiveness of the human hepatoma cell line SK-HEP-1 to dioxin.
The aryl hydrocarbon receptor (AhR) mediates a wide variety of toxic effects due to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The human hepatoma cell line SK-HEP-1 expresses AhR and ARNT. However, TCDD failed to induce CYP1A1 and XRE-dependent reporter genes in these cells. Although CYP1A1 was not induced by TCDD exposure, both CYP1B1 and AhR repressor (AhRR) were constitutively expressed. The AhR antagonist alpha-naphthoflavone altered the basal level of XRE-dependent reporter gene expression dose-dependently. As our results suggested the activation of AhR signals by putative endogenous ligands, we established SK-HEP-1-derived cell lines that stably expressed CYP1A1. The inducibility of XRE-dependent reporter genes and CYP1B1 by TCDD was restored in these cells. Our findings demonstrated the presence of endogenous ligands in SK-HEP-1 cells due to the absence of the metabolizing enzyme CYP1A1, but not CYP1B1, which allowed the constitutive expression of AhR target genes.


Gene expression regulation in the plant growth promoting Bacillus atrophaeus UCMB-5137 stimulated by maize root exudates.
Despite successful use of Plant Growth Promoting Rhizobacteria (PGPR) in agriculture, little is known about specific mechanisms of gene regulation facilitating the effective communication between bacteria and plants during plant colonization. Active PGPR strain Bacillus atrophaeus UCMB-5137 was studied in this research. RNA sequencing profiles were generated in experiments where root exudate stimulations were used to mimic interactions between bacteria and plants. It was found that the gene regulation in B. atrophaeus UCMB-5137 in response to the root exudate stimuli differed from the reported gene regulation at similar conditions in B. amyloliquefaciens FZB42, which was considered as a paradigm PGPR. This difference was explained by hypersensitivity of UCMB-5137 to the root exudate stimuli impelling it to a sessile root colonization behavior through the CcpA-CodY-AbrB regulation. It was found that the transcriptional factor DegU also could play an important role in gene regulations during plant colonization. A significant stress caused by the root exudates on in vitro cultivated B. atrophaeus UCMB-5137 was noticed and discussed. Multiple cases of conflicted gene regulations showed scantiness of our knowledge on the regulatory network in Bacillus. Some of these conflicted regulations could be explained by interference of non-coding RNA (ncRNA). Search through differential expressed intergenic regions revealed 49 putative loci of ncRNA regulated by the root exudate stimuli. Possible target mRNA were predicted and a general regulatory network of B. atrophaeus UCMB-5137 genome was designed.


Assessment and Management of Postoperative Pain Associated with Sleep Apnea Surgery.
A literature review was conducted regarding the assessment and treatment of postoperative pain following surgery for obstructive sleep apnea (OSA). Given the risks of opioid use by patients with OSA, special attention to opioid risk reduction and avoidance is warranted in this population. The results of this review demonstrate the existence of a body of evidence that supports the use of nonopioid analgesics and nonpharmacologic approaches pain management. Strategies for managing postoperative pain should emphasize the use of local anesthetic infiltration, nonsteroidal antiinflammatory drugs, acetaminophen, topical analgesics, surgical wound cooling, and when necessary, safer opioid medications, such as tramadol and intranasal butorphanol.


Determinants of severity of menopausal symptoms among Saudi women in Riyadh city.
To determine the relationship between sociodemographic, reproductive and lifestyle factors and the severity of menopausal symptoms among Saudi women attending a university hospital in Riyadh city. A cross-sectional survey was carried out during 2010 in Riyadh city. Women aged > 40 years attending or accompanying their relatives in outpatient clinics in King Khalid University Hospital were invited to participate in the study. The English version of the Menopause Rating Scale (MRS) was used to assess the severity of menopausal symptoms after translation and validation on a sample of 30 women. A total of 490 women were included. Severe urogenital symptoms were more common among housewives compared to working women (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.12-4.68) and women living in apartments or small houses compared to women living in villas (OR 1.70, 95% CI 1.90-2.64). Nulliparous women had more severe somatic symptoms compared to those who had been pregnant (OR 2.83, 95% CI 1.10-7.69). Women who exercised regularly were less likely to experience severe somatic and urogenital symptoms (OR 0.57, 95% CI 0.37-0.86; OR 0.65, 95% CI 0.44-0.98, respectively). Obese women experienced more severe psychosomatic symptoms compared to those of normal body mass index (OR 2.01, 95% CI 0.96-4.93). Women who are housewives, living in apartments, not exercising regularly and obese are more likely to suffer from severe symptoms of menopause.


A scintigraphic study of oral, pharyngeal, and esophageal transit in patients with stroke.
Although stroke affects mainly the oral and pharyngeal phases of swallowing, it may also impair esophageal contractions. Our hypothesis is that stroke may affect esophageal transit. The oral, pharyngeal, and esophageal transit was studied by the scintigraphic method in 26 patients (age range=26-83 years), eight of whom had mild dysphagia but all were able to feed orally and who had suffered an acute first-ever ischemic stroke 10-56 days (median = 43 days) before transit evaluation. The control group included 15 healthy volunteers (age range=27-86 years). All subjects swallowed a 5-ml liquid bolus and a 5-ml paste bolus labeled with technetium-99m phytate while sitting in front of the collimator of a gamma camara. The oral, pharyngeal, and proximal, middle, and distal esophageal transit was measured for 20 s. Three patients did not swallow the bolus during the scintigraphic evaluation. There was no difference between patients and controls with respect to oral and pharyngeal transit or clearance of liquid. For paste, the pharyngeal transit time was shorter for patients (0.48+/-0.17 s) than for controls (0.61+/-0.18 s, p=0.027). Also for the paste bolus, the residue in the mouth was greater in patients (18.4+/-13.6%) than in controls (10.2+/-4.9%, p=0.031). The liquid transit duration in the distal esophagus was shorter in patients with stroke (1.74+/-0.84 s) than in controls (2.68+/-1.65 s, p=0.028). There was no difference between patients and controls in esophageal residue. In conclusion, patients with stroke and able to feed orally may have alterations in the esophageal transit of a liquid bolus.


Evidence for the existence of an agent in the serum of the cyclic hematopoietic dog which influences hemoglobin synthesis.
Serum samples collected through the cycle of a cyclic hematopoietic (CH) dog under reduced atmospheric conditions, were assayed for their ability to affect hemoglobin synthesis by normal canine bone marrow. Varying levels of hemoglobin synthesis in the presence of different serum samples suggest an agent cycles in the serum of CH dogs which influences hemoglobin synthesis.


Standardized amino acid digestibility and protein quality in extruded canine diets containing hydrolyzed protein using a precision-fed rooster assay.
Protein hydrolysate has become a choice of alternative protein source in canine diets as it showed greater digestibility, lower allergenic responses, and various functional properties when compared with intact proteins. The objective of the study was to determine the effect of hydrolyzed protein inclusion on amino acid digestibility and protein quality in extruded canine diets when compared with a traditional protein source for adult dogs. Five treatment diets were formulated to have similar compositions except for the main protein source. The control diet was formulated with chicken meal (CM) as the primary protein source. Test hydrolyzed proteins, chicken liver and heart hydrolysate (CLH) and chicken hydrolysate (CH) were used to partially or completely substitute CM. The diets were: CONd: CM (30%) diet; 5%CLHd: 5% CLH with 25% CM diet; CLHd: CLH (30%) diet; 5%CHd: 5% CH with 25% CM diet; CHd: CH (30%) diet. A precision-fed rooster assay was used to determine standardized amino acid digestibility for the ingredients and diets. In addition, Digestible Indispensable Amino Acid Score (DIAAS)-like values were calculated for the protein ingredients. All protein ingredients had higher than 80% of digestibility for all indispensable amino acids with no difference among sources (P > 0.05). From the DIAAS-like values referencing AAFCO nutrient profile for adult dogs, CLH and CH did not have any limiting amino acid; on the other hand, CM has a lower DIAAS-like value (93.3%) than CLH and CH (P < 0.05) with tryptophan being the first-limiting amino acid. The DIAAS-like values were often lower when the amino acid combinations methionine + cysteine and phenylalanine + tyrosine were included in the calculation. When referencing NRC recommended allowances and minimal requirements, methionine was the first-limiting amino acid for all protein sources. Amino acid digestibility was mostly above 80% and comparable among the treatment diets. Regarding the digestible indispensable amino acid concentrations in the diets, all of them met the AAFCO nutrient profile for adult dogs at maintenance. In conclusion, both protein hydrolysates were highly digestible, high-quality protein sources, and a full substitution from CM to protein hydrolysate could result in greater protein quality, according to the DIAAS-like values of the ingredients, when compared with CM in extruded canine diets.


Double suicide gene therapy using a replication defective herpes simplex virus vector reveals reciprocal interference in a malignant glioma model.
Herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli cytosine deaminase (CD) are non-mammalian enzymes capable of converting innocuous prodrugs into cytotoxic metabolites. Both enzymes have been utilized independently, as well as together in 'suicide' gene therapy protocols to eliminate tumor cells in vitro and in vivo. We have used a set of replication defective HSV vectors expressing either or both enzymes to compare the efficacies of single and double suicide gene therapies in the 9L gliosarcoma model in vitro and in vivo. In cell culture experiments at high and low multiplicities of infection, combined expression of the two genes by vector TOCD/TK along with exposure to the matching prodrugs (ganciclovir and 5-fluorocytosine) showed increased cytotoxicity compared with exposure to either prodrug alone. However, the two gene combination was inferior to single gene treatments, suggesting that HSVtk and CD are mutually counteractive in the prodrug-dependent killing of glioma cells. In animal experiments, survival was not significantly prolonged by administration of both prodrugs to TOCD/TK-treated animals, while each single gene/prodrug pair resulted in increased survival. These results indicate that single suicide gene systems employing HSVtk or CD may be preferable over combinations of the two.


Tritiated thymidine autoradiographic study on the origin and renewal of argentaffin cells in the pyloric gland of hamsters.
The origin and renewal of the argentaffin cells in the pyloric glands of hamsters were studied by flash, cumulative and pulse labelling autoradiography with 3H-thymidine. The argentaffin cells were identified by the Diazo Method using Fast Red B Salt. By flash labelling autoradiography, it was shown that the argentaffin cells located from the middle to the lower level of the pyloric mucosa were not labelled with 3H-thymidine, indicating that this cell type has no proliferative activity. On the 10th and the 20th day of cumulative labelling, 31% and 63% of the argentaffin cells in the gland were found to be labelled, respectively. The labelled argentaffin cells were concentrated in the upper part of the gland (around the region of the isthmus), and no label was found over nuclei of the cells at the lowermost level of the gland. These labelled cells were shown to undergo a downward migration in the days following pulse labelling. They were replaced by unlabelled (and weakly or very weakly labelled) cells which arose at the region of the isthmus. The argentaffin cells in the pyloric gland are thought to arise from epithelial precursor cells at the region of the isthmus. The labelled argentaffin cells in the gland were found to decrease in number almost exponentially after pulse labelling. This indicates that the life span of argentaffin cells is not fixed, but their renewal conforms to the "random loss system". The half time of turnover of this cell population was 15 days on average.


Pain perception expressed by postoperative analgetica need in patients with nephropathia interstitialis chronica e phenacetin.
The consumption of narcotic analgesics was investigated after uncomplicated renoallotransplantation of 21 patients with nephropathia interstitialis chronica e phenacetin and in a control group (N = 21) with renal insufficiency of another origin. We find significantly greater consumption in the former group. The possibility of a previously existing increased pain sensibility in these patients as a disposing factor is discussed.


Visual field defects after vigabatrin treatment during infancy: retrospective population-based study.
To investigate the prevalence of vigabatrin-attributed visual field defect (VAVFD) in infantile spasms and the utility of optical coherence tomography (OCT) in detecting vigabatrin-related damage. We examined visual fields by Goldmann or Octopus perimetry and the thickness of peripapillary retinal nerve fiber layer (RNFL) with spectral-domain OCT at school age or adolescence. Out of 88 patients (38 females, mean age at study 15y, SD 4y 3mo, range 6y 4mo-23y 3mo [n=65] or deceased [n=21] or moved abroad [n=2]) exposed to vigabatrin in infancy, 28 were able to perform formal visual field testing. Two had visual field defect from structural causes. We found mild VAVFD in four patients and severe VAVFD in one patient. Median vigabatrin treatment duration for those with normal visual field was 11 months compared to 19 months for those with VAVFD (p=0.04). OCT showed concomitant attenuated RNFL in three children with VAVFD, and was normal in one. The temporal half of the peripapillary RNFL was significantly thinner in the VAVFD group compared to the normal visual field group. The overall prevalence of VAVFD is lower after exposure in infancy compared to 52% which has been reported after exposure in adulthood. The risk increases with longer treatment duration. Further studies should identify infants particularly susceptible to VAVFD and clarify the role of OCT.


Biophysical control of the growth of Agrobacterium tumefaciens using extremely low frequency electromagnetic waves at resonance frequency.
Isolated Agrobacterium tumefaciens was exposed to different extremely low frequencies of square amplitude modulated waves (QAMW) from two generators to determine the resonance frequency that causes growth inhibition. The carrier was 10 MHz sine wave with amplitude ±10 Vpp which was modulated by a second wave generator with a modulation depth of ± 2Vpp and constant field strength of 200 V/m at 28 °C. The exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min inhibited the bacterial growth by 49.2%. In addition, the tested antibiotics became more effective against A. tumefaciens after the exposure. Furthermore, results of DNA, dielectric relaxation and TEM showed highly significant molecular and morphological changes due to the exposure to 1.0 Hz QAMW for 90 min. An in-vivo study has been carried out on healthy tomato plants to test the pathogenicity of A. tumefaciens before and after the exposure to QAMW at the inhibiting frequency. Symptoms of crown gall and all pathological symptoms were more aggressive in tomato plants treated with non-exposed bacteria, comparing with those treated with exposed bacteria. We concluded that, the exposure of A. tumefaciens to 1.0 Hz QAMW for 90 min modified its cellular activity and DNA structure, which inhibited the growth and affected the microbe pathogenicity.


Differential visualization of dopamine D2 and D3 receptor sites in rat brain. A comparative study using in situ hybridization histochemistry and ligand binding autoradiography.
At least five members of the dopamine receptor family have been characterized at the gene level. D2, D3 and D4 dopamine receptors are related pharmacologically. In order to visualize the differential expression of D1, D2 and D3 receptors in rat brain we have combined in situ hybridization histochemistry with receptor autoradiography. Regions enriched with D3 messenger RNA (mRNA) included the islands of Calleja (ioC) and nucleus accumbens. Very low or undetectable levels were present in the caudate-putamen. In contrast, no D2 transcripts were observed in the islands of Calleja, but there were high levels in the nucleus accumbens, caudate-putamen (CP) and pyramidal layer of the olfactory tubercle. A comparison of the binding pattern of six dopamine receptor radioligands hitherto regarded as D2 receptor-selective showed that the islands of Calleja were intensely labelled by [125I]iodosulpride, [3H]CV 205 502 and [3H]SDZ 205 501, while the binding of [3H]spiperone, [3H]raclopride and [3H]YM 09151-2 was much lower or undetectable. Pharmacological analysis of the binding of D2/D3 ligands to the islands of Calleja and caudate-putamen suggests that binding sites in these two regions are of different pharmacology, consistent with the presence of D3 sites in the islands of Calleja and the predominance of D2 sites in the caudate. These results demonstrate the expression of D3 binding sites in the rat brain and provide a procedure to differentiate D2 and D3 receptor populations in binding studies.


Encapsulation of Hemin in Metal-Organic Frameworks for Catalyzing the Chemiluminescence Reaction of the H2O2-Luminol System and Detecting Glucose in the Neutral Condition.
Novel metal-organic frameworks (MOFs) based solid catalysts have been synthesized by encapsulating Hemin into the HKUST-1 MOF materials. These have been first applied in the chemiluminescence field with outstanding performance. The functionalized MOFs not only maintain an excellent catalytic activity inheriting from Hemin but also can be cyclically utilized as solid mimic peroxidases in the neutral condition. The synthesized Hemin@HKUST-1 composites have been used to develop practical sensors for H2O2 and glucose with wide response ranges and low detection limits. It was envisioned that catalyst-functionalized MOFs for chemiluminescence sensing would have promising applications in green, selective, and sensitive detection of target analytes in the future.


Screening for Congenital Heart Disease in Infants with Down Syndrome: Is Universal Echocardiography Necessary?
Current guidelines recommend that all neonates with Down syndrome (DS) be screened for congenital heart disease (CHD) with an echocardiogram. We sought to determine the effectiveness of a more accessible and less expensive screening strategy consisting of physical examination, electrocardiogram (ECG), and chest X-ray. The Intermountain Healthcare Enterprise Data Warehouse was used to identify infants with a positive karyotype for DS who were born between January 1, 2000, and June 30, 2012. Infants with the results of an echocardiogram, physical examination, ECG, and chest X-ray documented at age ≤6 months were included. Infants with an abnormality on physical examination, ECG, or chest X-ray were considered to have a positive screen. Echocardiography was the gold standard for calculating sensitivity, specificity, positive and negative predictive values for major CHD, defined as any heart defect that would typically require intervention during early childhood. Of 408 eligible infants, 240 (59 %) had major CHD, of whom 228 (95 %) had a positive screen. Screening missed eight infants with moderate/large patent ductus arteriosus and four infants with a moderate/large atrial septal defect. In 11 of these infants, the defect resolved spontaneously by age ≤4 months. One infant had a moderate atrial septal defect persisting at 2-year follow-up. Sensitivity and specificity of the screening for detecting CHD were 95 % (CI 92-98 %) and 41 % (CI 32-47 %); positive and negative predictive values were 69 % (CI 63-73 %) and 85 % (CI 75-92 %). Screening with physical examination, ECG, and chest X-ray is an effective method of identifying which infants with DS should have an echocardiogram. This method would have resulted in 69 (17 %) fewer echocardiograms without missing infants with major CHD.


Antifungal treatment in pediatric patients.
Invasive fungal infections have increased in frequency and severity over the past two decades as a result of an increasing number of immunocompromised patients. This new age of opportunistic fungal infections extends to pediatric patients. The last decade has seen the development of several new antifungal agents for the treatment of these infections. However, there is a paucity of data on the treatment of invasive fungal infections in children. This review provides a brief overview of the current state of antifungal therapy for children, discussing the important antifungal classes and the differences in mechanisms of action and resistance, pharmacology, and efficacy and safety data in pediatric patients outside the neonatal period.


Nitrogen cycling in an extreme hyperarid environment inferred from δ(15)N analyses of plants, soils and herbivore diet.
Climate controls on the nitrogen cycle are suggested by the negative correlation between precipitation and δ(15)N values across different ecosystems. For arid ecosystems this is unclear, as water limitation among other factors can confound this relationship. We measured herbivore feces, foliar and soil δ(15)N and δ(13)C values and chemically characterized soils (pH and elemental composition) along an elevational/climatic gradient in the Atacama Desert, northern Chile. Although very positive δ(15)N values span the entire gradient, soil δ(15)N values show a positive correlation with aridity as expected. In contrast, foliar δ(15)N values and herbivore feces show a hump-shaped relationship with elevation, suggesting that plants are using a different N source, possibly of biotic origin. Thus at the extreme limits of plant life, biotic interactions may be just as important as abiotic processes, such as climate in explaining ecosystem δ(15)N values.


Collagenolytic cathepsins of rabbit spleen: a kinetic analysis of collagen degradation and inhibition by chicken cystatin.
We have investigated the steady state kinetics of the degradation of native fibrillar collagen at pH 3.4 by four collagenolytic cathepsins of rabbit spleen. For each enzyme, the dependence of initial velocity on collagen concentration was well described by the Michaelis-Menten mechanism. Km, expressed as the concentration of triple-helical chains, and kcat values were determined for cathepsins B, L, N and S. The ratio of Kcat to Km suggest that cathepsins L and N are far more effective at collagen solubilization than either cathepsins S or B. Ki values were determined for the inhibition of collagenolytic activity at pH 3.4 using cystatin, a naturally-occurring cysteine proteinase inhibitor. All four cysteine proteinases were inhibited by cystatin in this assay system, although it was found to be a tighter binding inhibitor of cathepsin L, than for cathepsins N and S (approximately 5-fold less), or cathepsin B (approximately 500-fold less).


Assessing group change under conditions of anonymity and overlapping samples.
A commonly used research design in the social sciences involves the matching of observations over 2 time periods (i.e., Time 1 --> Time 2) to assess group change. Because coupled observations are usually correlated, a paired- or dependent-samples t test is generally recommended in such applications to determine if there has been a statistically significant change in mean scores across time. Consequently, it is typically believed that unless information for matching respondents' observations is available, researchers have no choice but to treat the observations as if they were independent. To demonstrate alternative statistical approaches for employing the paired samples ttest when information for matching respondents' observations is unavailable and to illustrate the applicability of these alternatives to longitudinal designs in which respondents at Time 1 are partially replaced by new respondents at Time 2. Theoretical arguments and examples are employed to achieve the specified objectives. Performing an independent-samples ttest when a paired-samples t test is more appropriate will lead to a loss of statistical power and, thus, increase the likelihood of a Type II statistical error. The statistical approaches that are demonstrated allow researchers to account for pair wise dependency across observations and, therefore, to obtain a fairer test of group change in means.


A procedure for chronic recording of diaphragmatic electromyographic activity.
A simple procedure for recording of diaphragmatic electromyographic activity in awake, freely behaving animals is described. This procedure produces highly stable recording of muscle activity for very long periods. Because of its ease of use, the procedure has become the technique of choice for acute recording in our laboratories as well. The present procedure can also be adapted for chronic recording of electromyographic activities from nonrespiratory muscles. This option thus offers a variety of applications to those involved in investigations into the central neuromotor control of movement, pattern generation and autonomic functions.


Resolution of Macular Edema secondary to rituximab after intravitreal dexamethasone: A case report and a review of the literature.
to report a case of bilateral macular edema (ME) secondary to Rituximab infusions in a woman affected by IgG4-Related Disease and to review of prior cases of ME related to Rituximab. ME completely resolved after Intravitreal Dexamethasone Implant (IDI). ME is a rare complication after Rituximab infusions and very few cases are reported in the literature. Usually, ME occurs a few weeks after systemic administration and is probably related to a local release of cytokines. It resolves with oral, subtenon or intravitreal steroids. Our case is the first showing that IDI is a safe and effective treatment in ME secondary to Rituximab. Rituximab is not required to be discontinued if treatment for ME is started.


A sensitive and quantitative microassay for the detection of mycoplasma contamination: inhibition of IL-2 dependent cell line proliferation.
A simple, rapid and sensitive microassay for mycoplasma detection in cell culture is reported. The assay is based on the fact that culture supernatants from contaminated cells inhibit [3H]thymidine incorporation by an IL-2 dependent mouse cytotoxic T cell line (CTLL). The mechanism of inhibition is related to the production by several mycoplasma strains of a pyrimidine-specific nucleoside phosphorylase which can degrade the radiolabelled thymidine used for the measurement of DNA synthesis. These strains were the commonest contaminants in cultures of 24 cell lines from 5 different sources. To establish the sensitivity of the test to detect mycoplasmas we have also used the inhibition assay to monitor the clearance of mycoplasma from 2 contaminated cell lines.


Reconstructing topography and extent of injury to the superior mesenteric artery plexus in right colectomy with extended D3 mesenterectomy: a composite multimodal 3-dimensional analysis.
Superior mesenteric artery plexus (SMAP) injury is reported to cause postoperative intractable diarrhea after pancreatic/colonic surgery with extended lymphadenectomy. This study aims to describe the SMAP microanatomy and extent of injury after right colectomy with extended D3 mesenterectomy for cancer. Three groups (I) anatomical dissection, (II) postmortem histology, and (III) surgical specimen histology were included. Nerve count and area were compared between groups II and III and paravascular sheath thickness between groups I and II. 3D models were generated through 3D histology, nanoCT scanning, and finally through 3D printing. A total of 21 specimens were included as follows: Group (I): 5 (3 females, 80-93 years), the SMAP is a complex mesh surrounding the superior mesenteric artery (SMA), branching out, following peripheral arteries and intertwining between them, (II): 7 (5 females, 71-86 years), nerve count: 53 ± 12.42 (38-68), and area: 1.84 ± 0.50 mm2 (1.16-2.29), and (III): 9 (5 females, 55-69 years), nerve count: 31.6 ± 6.74 (range 23-43), and area: 0.889 ± 0.45 mm2 (range 0.479-1.668). SMAP transection injury is 59% of nerve count and 48% of nerve area at middle colic artery origin level. The median values of paravascular sheath thickness decreased caudally from 2.05 to 1.04 mm (anatomical dissection) and from 2.65 to 1.17 mm (postmortem histology). 3D histology models present nerve fibers exclusively within the paravascular sheath, and lymph nodes were observed only outside. NanoCT-derived models reveal oblique nerve fiber trajectories with inclinations between 35° and 55°. Two 3D-printed models of the SMAP were also achieved in a 1:2 scale. SMAP surrounds the SMA and branches within the paravascular sheath, while bowel lymph nodes and vessels lie outside. Extent of SMAP injury on histological slides (transection only) was 48% nerve area and 59% nerve count. The 35°-55° inclination range of SMAP nerves possibly imply an even larger injury when plexus excision is performed (lymphadenectomy). Reasons for later improvement of bowel function in these patients can lie in the interarterial nerve fibers between SMA branches.


Gallbladder carcinoma and epithelial dysplasia: Appropriate sampling for histopathology.
Gallbladder carcinoma (GC) is an uncommon malignancy with an overall 5-year survival of <5%. Due to overlap of clinical presentation with the more common cholecystitis, an estimated 50-65% of all GCs are found incidentally. Epithelial dysplasia is identified in ~50% of specimens with invasive carcinoma. Recent expert panel guidelines have recommended histologic examination of the entire gallbladder in cases where initial sampling reveals dysplasia. 89 cases of GC, 34 high grade dysplasia (HGD), and 60 low grade dysplasia (LGD) were identified in cholecystectomy specimens assessed at our institution over the last 15 years. Pre-operative imaging (either ultrasound or CT) only identified 52% of mass lesions in GC cases. Among gallbladder specimens with epithelial dysplasia only at initial sampling, additional sectioning was performed in 59% of HGD and 55% of LGD. Additional sectioning of gallbladder specimens with HGD had a higher yield (10%) for identifying invasive carcinoma than those with LGD (0 of 28). The diagnostic yield of additional sectioning is significantly higher in the setting of high grade as compared to low grade dysplasia, suggesting that sampling at the discretion of the pathologist may be sufficient for the latter.


Normalizing and scaling of data to derive human response corridors from impact tests.
It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed.


Improving the differential diagnosis between myelodysplastic syndromes and reactive peripheral cytopenias by multiparametric flow cytometry: the role of B-cell precursors.
Immunophenotyping is a valuable ancillary technique for the differential diagnosis between myelodysplastic syndromes (MDS) with low bone marrow (BM) blast counts and a normal karyotype, and reactive peripheral (PB) cytopenias. Our aim was to search for the most important variables for this purpose. We also analyzed the age variation of BM B-cell precursors (BCP) and its differences in reactive and clonal cytopenias. Immunophenotypic analyzes were performed in BM of 54 patients with MDS (76% with BM blasts <5%) and 35 cases of reactive cytopenias. Healthy allogeneic BM transplantation donors (n = 41) were used as controls. We used a four-color panel of antibodies analyzing 9 granulocytic, 8 monocytic and 6 CD34(+) cell features. Asynchronous shift to the left in maturing granulocytes and increase in CD16(+) monocytes were also found in reactive PB cytopenias, but the most important aberrancies in MDS were seen in myeloid CD34(+) cells. Decrease in BCP, that is a hallmark of MDS, could also be found in reactive cytopenias, especially in patients >55 years. % BM BCP could be calculated by the formula: (-7.97 × log age) + (4.24 × log % CD34 (+) cells) - (0.22 x nr. alterations CD34 (+) cells) + 0.577. Corrected R(2) = 0.467. Analysis of myelomonocytic precursors and CD34(+) cells was satisfactory for the differential diagnosis between reactive PB cytopenias and MDS. The most specific alterations were found in CD34(+) cells. Comparison of the values obtained with those of normal age-matched controls is recommended. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1975931809154663.


Predicting peptides that bind to MHC molecules using supervised learning of hidden Markov models.
The binding of a major histocompatibility complex (MHC) molecule to a peptide originating in an antigen is essential to recognizing antigens in immune systems, and it has proved to be important to use computers to predict the peptides that will bind to an MHC molecule. The purpose of this paper is twofold: First, we propose to apply supervised learning of hidden Markov models (HMMs) to this problem, which can surpass existing methods for the problem of predicting MHC-binding peptides. Second, we generate peptides that have high probabilities to bind to a certain MHC molecule, based on our proposed method using peptides binding to MHC molecules as a set of training data. From our experiments, in a type of cross-validation test, the discrimination accuracy of our supervised learning method is usually approximately 2-15% better than those of other methods, including backpropagation neural networks, which have been regarded as the most effective approach to this problem. Furthermore, using an HMM trained for HLA-A2, we present new peptide sequences that are provided with high binding probabilities by the HMM and that are thus expected to bind to HLA-A2 proteins. Peptide sequences not shown in this paper but with rather high binding probabilities can be obtained from the author.


Healthy families study: design of a childhood obesity prevention trial for Hispanic families.
The childhood obesity epidemic disproportionately affects Hispanics. This paper reports on the design of the ongoing Healthy Families Study, a randomized controlled trial testing the efficacy of a community-based, behavioral family intervention to prevent excessive weight gain in Hispanic children using a community-based participatory research approach. The study will enroll 272 Hispanic families with children ages 5-7 residing in greater Nashville, Tennessee, United States. Families are randomized to the active weight gain prevention intervention or an alternative intervention focused on oral health. Lay community health promoters implement the interventions primarily in Spanish in a community center. The active intervention was adapted from the We Can! parent program to be culturally-targeted for Hispanic families and for younger children. This 12-month intervention promotes healthy eating behaviors, increased physical activity, and decreased sedentary behavior, with an emphasis on parental modeling and experiential learning for children. Families attend eight bi-monthly group sessions during four months then receive information and/or support by phone or mail each month for eight months. The primary outcome is change in children's body mass index. Secondary outcomes are changes in children's waist circumference, dietary behaviors, preferences for fruits and vegetables, physical activity, and screen time. Enrollment and data collection are in progress. This study will contribute valuable evidence on efficacy of a childhood obesity prevention intervention targeting Hispanic families with implications for reducing disparities.


Carotid intima-media thickness predicts the development of cardiovascular events in patients with rheumatoid arthritis.
To establish whether carotid intima-media wall thickness (IMT) may be a good predictor for the development of cardiovascular (CV) events in patients with rheumatoid arthritis (RA). A series of 47 RA patients who at the time of recruitment did not have traditional CV risk factors or CV disease were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. Then, a prospective assessment of the CV outcome was performed over a 5-year period. Logistic regression models and receiver operating characteristic curves were performed to evaluate the ability of different variables to predict CV events. Carotid IMT was greater in RA patients who over the extended follow-up experienced CV events (1.01 +/- 0.16 mm) compared with the remaining RA patients who did not have CV complications (0.74 +/- 0.12 mm) (P < 0.001). Also, carotid IMT categorized in quartiles was strongly associated with CV events. In this regard, none of the patients with carotid IMT less than 0.77 mm had CV events. However, 6 of the 10 patients with carotid IMT greater than 0.91 mm experienced CV events (P value for the trend <0.001). Carotid IMT yielded a high predictive power for the development of CV events over the 5-year follow-up period. The area under the receiver operating characteristic curve was 0.93 for a model that only included carotid IMT and 0.90 for carotid plaque. The results from the present study support the use of carotid ultrasonography as a predictor of CV events in RA.


Antimicrobial study of the resinous exudate and of diterpenoids isolated from Eupatorium salvia (Asteraceae).
The antimicrobial properties of the resinous exudate from twigs and leaves of Eupatorium salvia were tested against five gram-negative and five gram-positive bacteria. Comparison of the antimicrobial activities of 7-hydroxy-8(17)-labden-15-oic acid (salvic acid) and of its acetate, both compounds isolated from the plant, with that of the crude extract suggested that the latter ester derivative was the major active component in the exudate. These results validate the vernacular medicinal use of Eupatorium salvia as an antiseptic agent.


Is metabolic dysregulation associated with antidepressant response in depressed women in climacteric treated with individualized homeopathic medicines or fluoxetine? The HOMDEP-MENOP Study.
Climacteric is associated with both depression and metabolic dysregulation. Scarce evidence suggests that metabolic dysregulation may predict poor response to conventional antidepressants. Response to depression treatment has not been studied in homeopathic medicine. The aim of this study was to investigate the prevalence of metabolic disorders in depressed climacteric women treated with homeopathic medicines, fluoxetine or placebo, and if these alterations have any association with response to depression treatment. One hundred and thirty-three Mexican women (40-65 years) with depression, enrolled in the HOMDEP-MENOP study, a randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a 6 week follow-up, underwent a complete medical history and clinical examination. Metabolic parameters were assessed at baseline. Association between baseline metabolic parameters and response to depression treatment was analyzed with bivariate analysis in the three groups. Odds ratios (OR) with their 95% confidence interval (95% CI) were calculated. Metabolic parameters were considered for inclusion in the logistic regression model if they had a statistically significant relationship with response rate on bivariate analysis at p<0.05 or if they were clinically relevant. Overall combined prevalence (obesity and overweight) was 86.5%; 52.3% had hypertriglyceridemia; 44.7% hypercholesterolemia; 46.7% insulin resistance; and 16% subclinical hypothyroidism. There was no statistically significant association between dyslipidemia, overweight, or insulin resistance and non-response in the homeopathy group [OR (95% CI) 1.57 (0.46-5.32), p=0.467; 0.37 (0.003-1.11), p=0.059; 0.67 (0.16-2.7), p=0.579, respectively]. Metabolic dysregulation was not significantly associated with response to depression treatment in depressed climacteric women treated with individualized homeopathic treatment (IHT), fluoxetine or placebo. Due to the high prevalence of metabolic disorders and its relationship with depression in the climacteric, further investigation should be focused on whether individualized prescriptions based on classical homeopathy for depressed climacteric women have an effect on metabolic parameters, and/or if treating the metabolic disorders at the same time could lead to higher response rates. ClinicalTrials.gov Identifier: NCT01635218 URL: http://clinicaltrials.gov/ct2/show/NCT01635218?term=depression+homeopathy&rank=1.


Use of spineless cactus (Opuntia ficus indica f. inermis) for dairy goats and growing kids: impacts on milk production, kid's growth, and meat quality.
The objective of this study was to determine the effect of spineless cactus incorporation in food of dairy goats and growing kids on milk production and composition and on kid's growth and meat characteristics. Two experiments were conducted on Tunisian local goats. In the first, 30 females were divided into two groups; goats of Control group were reared on grazing pasture receiving indoor 0.5 kg of hay and 0.4 kg of concentrate. Goats for the second group (Cac-FL) were kept in feedlot and fed cactus ad libitum more 0.5 kg of hay and 0.4 kg of concentrate. In the second experiment, 14 kids were divided into 2 groups receiving 600 g of hay. The Control group received ad libitum a concentrate containing 130 g crude protein (CP) per kg of dry matter. The second group received cactus ad-libitum plus the half concentrate quantity of control one with 260 g CP/kg DM (Cactus). The daily milk production averaged 485 ml for Control group and 407 ml for Cac-FL one. The milk fat content was significantly higher for Control than Cac-FL group. In the second experiment, animals in Control and Cactus groups had similar growth rate. Carcass fat was significantly lower in Cactus than in the Control group. Cactus in the diet was associated with more C18:2 and conjugated linoleic acid as well as a higher proportion of PUFA than Control ones.


The treatment of orbital rhabdomyosarcoma with irradiation and chemotherapy.
Fifty-eight patients with orbital rhabdomyosarcoma were treated with irradiation alone (25) or irradiation and chemotherapy (33) with follow-ups of 6 months to 14 years (mean 5.2 yr). At present, 74% are alive and 26% have died. Local control of the tumor was accomplished in 91% of cases. When local sinuses were invaded the survival rate was 55%. Chemotherapy appears to be of greatest value when disease is limited to the orbit. Irradiation or irradiation and chemotherapy should now be the treatment of choice for orbital rhabdomyosarcoma.


Gastroprotective effects of Corchorus olitorius leaf extract against ethanol-induced gastric mucosal hemorrhagic lesions in rats.
Corchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats. The rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations. Compared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole. Our study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats.


Association between renal function and co-infection with Clonorchis sinensis and Helicobacter pylori: a cross-sectional study.
Studies have shown that liver fluke infections may be associated with kidney injury and that Helicobacter pylori (Hp) may be involved in the pathogenesis of kidney diseases. However, no studies have reported the relationship between co-infection with Clonorchis sinensis (Cs) and Hp and renal function. The aim of this study was to examine the relationship between co-infection with Cs and Hp and estimated glomerular filtration rate (eGFR) in a general population, and gender-related differences were also investigated. In the cross-sectional study, 4122 subjects from the Health Examination Center of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine from January 2017 to December 2018 were enrolled. All participants underwent stool examination for the diagnosis of Cs infection and 13C-urea breath test (UBT) for the diagnosis of Hp infection. Participants were categorized into four groups: (1) co-infection with Cs and Hp group comprising 207 cases (Hp(+) + Cs(+) group), (2) Cs infection group comprising 1392 cases (Hp(-) + Cs(+)group), (3) Hp infection group comprising 275 cases (Hp(+) + Cs(-) group), and (4) non-infection group comprising 2248 cases (Hp(-) + Cs(-) group). Multiple linear regression analysis was performed to evaluate the relationship between co-infection with Cs and Hp and eGFR. Hp infection without Cs infection was present in 6.67% (275/4122) of subjects, while Cs infection without Hp infection was present in 33.77% (1392/4122) of subjects. Co-infection with Hp and Cs were present in 5.02% (207/4122) of subjects. Median age of the participants was 43 years (IQR 35-51). Most of the participants were male (2955/4122, 71.69%). Median eGFR was 96.61 ml/min/1.73 m2 (IQR 85.05-106.24). Co-infection with Cs and Hp was negatively associated with eGFR after full adjusting (β = - 1.89, 95% CI: - 3.33 to - 0.45, p = 0.01). The relationship remained significant in females (β = - 9.37, 95% CI: - 11.60 to - 7.1, p < 0.001), but not in males. Our findings suggest that co-infection with Cs and Hp may be associated with reduced renal function in females, but not in males.


Synchronous rectal and esophageal cancer associated with prurigo chronica multiformis: report of a case.
The skin lesions that appear in association with internal malignancies are called dermadromes or paraneoplastic cutaneous disorders. These skin changes characteristically develop with progression of the internal malignancy. A 75-year-old Japanese man who had been diagnosed as having prurigo chronica multiformis, a form of dermadrome, 5 years previously was referred to our hospital for further investigation. On admission, numerous itchy red papules were present on the right side of the abdomen and the inner aspect of both thighs. Intensive screening for internal malignancies revealed advanced rectal cancer and early esophageal cancer. After surgical resection, the skin lesions improved without any treatment. To the best of our knowledge, this is the first case of synchronous double cancers associated with prurigo chronica multiformis.


Mimicry of snail host antigens by miracidia and primary sporocysts of Schistosoma mansoni.
Polyvalent antisera generated in rabbits to soluble haemolymph components from Schistosoma mansoni-susceptible (PR albino 'M line') and S. mansoni-resistant (10-R2) stocks of the snail Biomphalaria glabrata were employed as membrane probes to determine if antigens related to snail haemolymph were produced by the early larval stages of S. mansoni (PR-1 strain). Using immunofluorescence and immunoelectron microscopical methods we have demonstrated that antibodies to susceptible (anti-Suscept) and resistant (anti-Resist) snail haemolymph (Hg-depleted fraction) crossreact with miracidial epidermal and ciliary membranes as well as the surface membranes of intercellular ridges. Primary sporocysts, both transformed in vitro and maintained in culture for various time intervals in the absence of snail-derived factors, retain haemolymph-like antigens on their surface tegument although at reduced levels in comparison to miracidial stages. Furthermore prolonged cultivation of sporocysts (48 h) has little effect on the density of crossreacting tegumental antigens suggesting that as sporocysts mature these antigenic components are continually being expressed at the surface membrane. Since miracidia and sporocysts were derived in media devoid of snail host materials, shared antigens on larval surfaces are believed to be of parasite origin and constitute true molecular mimicry as defined by Damian (1979). The occurrence of crossreacting antibodies in both anti-Suscept and anti-Resist antisera further suggests that mimicked haemolymph-like antigens include at least some which are common to both snail stocks.