Quantitative analysis of cardiac tissue including fibroblasts using three-dimensional confocal microscopy and image reconstruction: towards a basis for electrophysiological modeling.
Electrophysiological modeling of cardiac tissue is commonly based on functional and structural properties measured in experiments. Our knowledge of these properties is incomplete, in particular their remodeling in disease. Here, we introduce a methodology for quantitative tissue characterization based on fluorescent labeling, 3-D scanning confocal microscopy, image processing and reconstruction of tissue micro-structure at sub-micrometer resolution. We applied this methodology to normal rabbit ventricular tissue and tissue from hearts with myocardial infarction. Our analysis revealed that the volume fraction of fibroblasts increased from 4.83±0.42% (mean ± standard deviation) in normal tissue up to 6.51±0.38% in myocardium from infarcted hearts. The myocyte volume fraction decreased from 76.20±9.89% in normal to 73.48±8.02% adjacent to the infarct. Numerical field calculations on 3-D reconstructions of the extracellular space yielded an extracellular longitudinal conductivity of 0.264±0.082 S/m with an anisotropy ratio of 2.095±1.11 in normal tissue. Adjacent to the infarct, the longitudinal conductivity increased up to 0.400±0.051 S/m, but the anisotropy ratio decreased to 1.295±0.09. Our study indicates an increased density of gap junctions proximal to both fibroblasts and myocytes in infarcted versus normal tissue, supporting previous hypotheses of electrical coupling of fibroblasts and myocytes in infarcted hearts. We suggest that the presented methodology provides an important contribution to modeling normal and diseased tissue. Applications of the methodology include the clinical characterization of disease-associated remodeling.


Glutamate receptor subunit expression in the rhesus macaque locus coeruleus.
The locus coeruleus (LC) is a major noradrenergic brain nucleus that regulates states of arousal, optimizes task-oriented decision making, and may also play an important role in modulating the activity of the reproductive neuroendocrine axis. Rodent studies have shown that the LC is responsive to glutamate receptor agonists, and that it expresses various glutamate receptor subunits. However, glutamate receptor subunit expression has not been extensively examined in the primate LC. We previously demonstrated expression of the NR1 NMDA glutamate receptor subunit in the rhesus macaque LC and now extend this work by also examining the expression of non-NMDA (AMPA and kainate) ionotropic glutamate receptor subunits. Using in situ hybridization histochemistry and immunohistochemistry, we confirmed the presence of the obligatory NR1 subunit in the LC. In addition, we demonstrated expression of the AMPA glutamate receptor subunits GluR1, GluR2, and GluR3. More extensive receptor profiling, using rhesus monkey gene microarrays (Affymetrix GeneChip), further corroborated the histological findings and showed expression of mRNA encoding ionotropic glutamate receptor subunits NR2A, NR2D, GluR4, and GluR6, as well as the metabotropic glutamate receptor subunits mGluR1, mGluR3, mGluR4, mGluR5, and mGluR7. These data provide a foundation for future examination of how changes in glutamate receptor composition contribute to the control of primate physiology.


Examining the impact of specific types of item-writing flaws on student performance and psychometric properties of the multiple choice question.
This article was migrated. The article was marked as recommended. Background: Item-writing flaws (IWFs) are common in multiple choice questions (MCQs) despite item-writing guidelines. Previous studies have shown that IWFs impact validity as observed through student performance, item difficulty, and discrimination. Most previous studies have examined IWFs collectively and have shown that they have a diverse impact. The aim of the study was to determine if the effects of individual types of IWFs are systematic and predictable. Method: A cross-over study design was used. 100 pairs of MCQ items (with and without an IWF) were constructed to test 10 types of IWFs. Medical students were invited to participate in a mock examination. Paper A consisted of 50 flawed followed by 50 unflawed items. Paper B consisted of 50 unflawed followed by 50 flawed items. The effect of each of the IWFs on mean item scores, item difficulty and discrimination were examined. Results: The hypothesised effect of IWFs on mean item scores was confirmed in only 4 out of 10 cases. ' Longest choice is correct', 'Clues to the right answer (Eponymous terms)' and ' Implausible distractors' positively impacted, while 'Central idea in choices rather than stem' negatively impacted mean item scores. Other flaws had either the opposite or no statistically significant effect. IWFs did not impact item difficulty or discrimination. Conclusion: The effect of IWFs is neither systematic nor predictable. Unpredictability in assessment produces error and thus loss of validity. Therefore, IWFs should be avoided. Faculties should be encouraged to invest in item-writing workshops in order to improve MCQs. However, the cost of doing so should be carefully weighed against the benefits of developing programmes of assessment.


BNP level predicts bleeding event in patients with heart failure after percutaneous coronary intervention.
This study aimed to investigate the association between heart failure (HF) severity measured based on brain natriuretic peptide (BNP) levels and future bleeding events after percutaneous coronary intervention (PCI). The Academic Research Consortium for High Bleeding Risk presents a bleeding risk assessment for antithrombotic therapy in patients after PCI. HF is a risk factor for bleeding in Japanese patients. Using an electronic medical record-based database with seven tertiary hospitals in Japan, this retrospective study included 7160 patients who underwent PCI between April 2014 and March 2020 and who completed a 3-year follow-up and were divided into three groups: no HF, HF with high BNP level and HF with low BNP level. The primary outcome was bleeding events according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. The secondary outcome was major adverse cardiovascular events (MACE). Furthermore, thrombogenicity was measured using the Total Thrombus-Formation Analysis System (T-TAS) in 536 consecutive patients undergoing PCI between August 2013 and March 2017 at Kumamoto University Hospital. Multivariate Cox regression showed that HF with high BNP level was significantly associated with bleeding events, MACE and all-cause death. In the T-TAS measurement, the thrombogenicity was lower in patients with HF with high BNP levels than in those without HF and with HF with low BNP levels. HF with high BNP level is associated with future bleeding events, suggesting that bleeding risk might differ depending on HF severity.


Developments on drug delivery systems for the treatment of mycobacterial infections.
The clinical management of tuberculosis and other mycobacterial diseases with antimycobacterial chemotherapy remains a difficult task. The classical treatment protocols are long-lasting; the drugs reach mycobacteria-infected macrophages in low amounts and/or do not persist long enough to develop the desired antimycobacterial effect; and the available agents induce severe toxic effects. Nanotechnology has provided a huge improvement to pharmacology through the designing of drug delivery systems able to target phagocytic cells infected by intracellular pathogens, such as mycobacteria. Liposomes and nanoparticles of polymeric nature represent two of the most efficient drug carrier systems that after in vivo administration are endocytosed by phagocytic cells and then release the carried agents into these cells. This article reviews the relevant publications describing the effectiveness of the association of antimycobacterial agents with liposomes or nanoparticles for the treatment of mycobacterioses, particularly for Mycobacterium tuberculosis and M. avium infections. The increased therapeutic index of antimycobacterial drugs; the reduction of dosing frequency; and the improvement of solubility of hydrophobic agents, allowing the administration of higher doses, have been demonstrated in experimental infections. These advantages may lead to new therapeutic protocols that will improve patient compliance and, consequently, lead to a more successful control of mycobacterial infections. The potential therapeutic advantages resulting from the use of non-invasive administration routes for nanoparticulate systems are also discussed.


Gain control from beyond the classical receptive field in primate primary visual cortex.
Gain control is a salient feature of information processing throughout the visual system. Heeger (1991, 1992) described a mechanism that could underpin gain control in primary visual cortex (V1). According to this model, a neuron's response is normalized by dividing its output by the sum of a population of neurons, which are selective for orientations covering a broad range. Gain control in this scheme is manifested as a change in the semisaturation constant (contrast gain) of a V1 neuron. Here we examine how flanking and annular gratings of the same or orthogonal orientation to that preferred by a neuron presented beyond the receptive field modulate gain in V1 neurons in anesthetized marmosets (Callithrix jacchus). To characterize how gain was modulated by surround stimuli, the Michaelis-Menten equation was fitted to response versus contrast functions obtained under each stimulus condition. The modulation of gain by surround stimuli was modelled best as a divisive reduction in response gain. Response gain varied with the orientation of surround stimuli, but was reduced most when the orientation of a large annular grating beyond the classical receptive field matched the preferred orientation of neurons. The strength of surround suppression did not vary significantly with retinal eccentricity or laminar distribution. In the marmoset, as in macaques (Angelucci et al., 2002a,b), gain control over the sort of distances reported here (up to 10 deg) may be mediated by feedback from extrastriate areas.


Chronic intrahepatic cholestasis due to sarcoidosis.
Two West Indian patients with Kveim-biopsy proven sarcoidosis developed chronic cholestatic liver disease, clinically and biochemically similar to primary biliary cirrhosis. Liver histology revealed multiple granulomas with reduction in bile ducts and, in one patient, progression to biliary cirrhosis. Portal hypertension was present in both patients leading to severe variceal haemorrhage in one. Mitochondrial antibody was negative in both patients and when used in conjunction with the Kveim-Siltzbach skin test serves to differentiate chronic intrahepatic cholestasis secondary to sarcoidosis from primary biliary cirrhosis.


Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis.
To perform a review and metaanalysis of the studies evaluating the status of serum inflammatory markers in women with polycystic ovary syndrome (PCOS). Systematic review and metaanalysis of articles published in English before January 2010 and identified using the PubMed search engine. Academic hospital. Women with PCOS and appropriate controls. Measurement of serum concentrations of inflammatory markers by high-sensitivity techniques. Metaanalyses of the mean difference in serum C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations among patients with PCOS and appropriate controls, applying random-effects models to limit interstudy variability, and using appropriate estimates of evidence dissemination bias. Metaanalysis of the 31 articles meeting inclusion criteria showed that circulating CRP was 96% higher in women with PCOS compared to controls (95% confidence interval, 71%-122%; z = 7.32) without evidence of dissemination bias (Egger's regression intercept, 0.45; 95% confidence interval, -2.30 to 3.21). These findings persisted after excluding five studies with mismatches in body mass, frequency of obesity, or both, between women with PCOS and controls. Metaanalyses involving 10 studies of IL-6, and nine studies of TNF-α revealed no statistically significant differences between PCOS and controls. Women with PCOS exhibit an elevation in circulating CRP that is independent of obesity. This finding corroborates existing molecular evidence of the chronic low-grade inflammation that may underpin the pathogenesis of this disorder.


Association of age of ram with distribution of epididymal lesions and etiologic agent.
A 2-year study of the frequency of isolation of various organisms from mature and yearling rams with epididymitis was conducted at the US Sheep Experiment Station at Dubois, Idaho. Investigation into the distribution of lesions in the epididymis in relation to age of the ram also was studied. Serologic or bacteriologic evidence of Brucella ovis infection was demonstrated in 79.5% of the mature rams with epididymal lesions. Actinobacillus seminis and Histophilus ovis were the 2 most frequently isolated organisms from yearling rams with lesions. The tail(s) of the epididymis was the most frequent site of lesion development in the mature rams (86.4%). Yearling rams developed lesions twice as frequently in the tail(s) of the epididymis as in the head(s) of the epididymis. When lesions were localized in the head(s) of the epididymis, an etiologic agent usually was not demonstrated.


Perceived Advantages and Disadvantages of Using Pre-Exposure Prophylaxis (PrEP) among Sexually Active Black Women: An Exploratory Study.
Knowledge of pre-exposure prophylaxis (PrEP) continues to remain scarce among Black women who are disproportionally affected by HIV in the United States. A thematic analysis of open-ended questions from a sample of Black women (n=119) who completed a mix-methods, online, e-health study was conducted to examine the perceived advantages and disadvantages of using PrEP. Being a female controlled method, empowerment, option for women with risky sex partners, and serodiscordant couples were advantages described. Disadvantages of PrEP were identified as the complexity of the choice, encouragement of sex with risky partners, increased burden, promotion of unprotected sex, and newness of the drug.


Opioid overdose and naloxone education in a substance use disorder treatment program.
Opioid users in treatment are at high risk of relapse and overdose, making them an important target for efforts to reduce opioid overdose mortality. Overdose Education (OE) is one such intervention, and this study tests the effectiveness of OE in a community substance use disorder treatment program. Opioid users were recruited from a community treatment center for the study. The Opioid Overdose Knowledge Scale (OOKS) was administered before and after an educational intervention (small group lecture, slideshow, and handout based on previously published content) to assess knowledge of the risks, signs, and actions associated with opioid overdose, including use of naloxone. Additional survey questions assessed naloxone access, naloxone education, and overdose experiences at treatment and 3-month follow-up. Subjects (n = 43) were 28% female and had a mean age of 31 years. OOKS scores were compared at pre-intervention, post-intervention, and follow-up, and results were also compared with a historical non-intervention control group (n = 14). Total score on the OOKS increased significantly from pre- to post-education, and improvement was maintained at follow-up (p < .0001). OOKS subdomains of actions and naloxone use also had significant increases (p < .0001). Four subjects reported possessing naloxone in the past, and only one subject who did not already have naloxone at the time of treatment had obtained it at follow-up. Education about opioid overdose and naloxone use in a community treatment program increases overdose knowledge, providing support for the idea of making OE a routine part of substance use disorder treatment. However, the rate of follow through on accessing naloxone was low with this education-only intervention.


Radiation pressure of active dispersive chiral slabs.
We report a mechanism to obtain optical pulling or pushing forces exerted on the active dispersive chiral media. Electromagnetic wave equations for the pure chiral media using constitutive relations containing dispersive Drude models are numerically solved by means of Auxiliary Differential Equation Finite Difference Time Domain (ADE-FDTD) method. This method allows us to access the time averaged Lorentz force densities exerted on the magnetoelectric coupling chiral slabs via the derivation of bound electric and magnetic charge densities, as well as bound electric and magnetic current densities. Due to the continuously coupled cross-polarized electromagnetic waves, we find that the pressure gradient force is engendered on the active chiral slabs under a plane wave incidence. By changing the material parameters of the slabs, the total radiation pressure exerted on a single slab can be directed either along the propagation direction or in the opposite direction. This finding provides a promising avenue for detecting the chirality of materials by optical forces.


Postpackage pasteurization of ready-to-eat deli meats by submersion heating for reduction of Listeria monocytogenes.
A mixed cocktail of four strains of Listeria monocytogenes was resuspended in product purge and added to a variety of ready-to-eat (RTE) meat products, including turkey, ham, and roast beef. All products were vacuum sealed in shrink-wrap packaging bags, massaged to ensure inoculum distribution, and processed by submersion heating in a precision-controlled steam-injected water bath. Products were run in pairs at various time-temperature combinations in either duplicate or triplicate replications. On various L. monocytogenes-inoculated RTE deli meats, we were able to achieve 2- to 4-log cycle reductions when processed at 195 degrees F (90.6 degrees C), 200 degrees F (93.3 degrees C), or 205 degrees F (96.1 degrees C) when heated from 2 to 10 min. High-level inoculation with L. monocytogenes (approximately 10(7) CFU/ml) ensured that cells infiltrated the least processed surface areas, such as surface cuts, folds, grooves, and skin. D- and z-value determinations were made for the Listeria cocktail resuspended in product purge of each of the three meat categories. However, reduction of L. monocytogenes in product challenge studies showed much less reduction than was observed during the decimal reduction assays and was attributed to a combination of surface phenomena, including surface imperfections, that may shield bacteria from the heat and the migration of chilled purge to the product surface. The current data indicate that minimal heating regimens of 2 min at 195 to 205 degrees F can readily provide 2-log reductions in most RTE deli meats we processed and suggest that this process may be an effective microbial intervention against L. monocytogenes on RTE deli-style meats.


Effect of Improved Water Quality, Sanitation, Hygiene and Nutrition Interventions on Respiratory Illness in Young Children in Rural Bangladesh: A Multi-Arm Cluster-Randomized Controlled Trial.
Acute respiratory infections cause mortality in young children. We assessed the effects of water, sanitation, hygiene (WASH) and nutritional interventions on childhood ARI. Geographic clusters of pregnant women from rural Bangladesh were randomly assigned to receive 1) chlorinated drinking water and safe storage (W); 2) upgraded sanitation (S); 3) handwashing promotion (H); 4) combined water, sanitation, and handwashing (WSH); 5) nutrition intervention including lipid-based nutrient supplements; 6) combined WSH plus nutrition (WSHN); or 7) no intervention (control). Masking of participants was not possible. Acute respiratory illness was defined as caregiver-reported persistent cough, panting, wheezing, or difficulty breathing in the past 7 days among index children, those born to enrolled women. We assessed outcomes at 12 and 24 months of intervention using intention to treat. Compared with children in the control group (ARI prevalence, P: 8.9%), caregivers of index children reported significantly lower ARI in the water (P: 6.3%, prevalence ratio (PR): 0.71; 95% CI: 0.53, 0.96), sanitation (P: 6.4%, PR: 0.75, 95% CI: 0.58, 0.96), handwashing (P: 6.4%, PR: 0.68, 95% CI: 0.50, 0.93), and the combined WSH+N arms (P: 5.9%, PR: 0.67, 95% CI: 0.50, 0.90). Those in the nutrition (P: 7.4%, PR: 0.84, 95% CI: 0.63, 1.10) or the WSH arm (P: 8.9%, PR: 0.99, 95% CI: 0.76, 1.28) reported similar ARI prevalence compared with control children. Single targeted water, sanitation, and hygiene interventions reduced reported respiratory illness in young children. There was no apparent respiratory health benefit from combining WASH interventions.


[Cytologic profile of mouse thymus and spleen after gamma-irradiation].
Quantitative study of thymus and spleen cytoarchitectonics performed in mice one day after gamma irradiation revealed peculiarities of response of certain morphological zones of the organs along with common changes of the organ cellular composition (lymphocytopenia, destructive processes intensification, granulocyte reaction and decrease of mitotic activity). In thymus changes of cytoarchitectonics of cortical substance (especially in subcapsular zone) are connected with sharp intensification of cell destruction, which implicates lymphocyte loss and with complete suppression of cell mitotic activity and differentiation, with medullar substance of thymus being the most stable structure in cellular composition. Lymphoid nodules without germinal centres, cytoarchitectonics of which, despite certain changes to greater extent resembles control indexes, can be considered the most stable structure in spleen, where irradiation completely suppresses germinal centres of lymphoid nodules. Red pulp appeares to be more labile zone in the organ and its architectonics is mostly subjected to alteration in irradiation.


Comparative Study of Essential Oils from Different Organs of Syzygium cumini (Pamposia) Based on GC/MS Chemical Profiling and In Vitro Antiaging Activity.
Syzygium cumini L. is an evergreen tree belonging to family Myrtaceae, employed for different traditional uses like diabetes, inflammation, and fever. The current study aimed to compare the chemical compositions of the essential oils (EOs) isolated from different organs of Syzygium cumini (leaves (Scl), fruits (Scf), seeds (Scs), and bark (Scb)) using a GC/MS analysis. Also, a chemometric analysis was applied to explore the main similarities and differences among different organs using a Principal Component Analysis (PCA) and a hierarchal cluster analysis (HCA). Furthermore, in vitro antiaging activities were investigated via anti-collagenase, anti-elastase, and anti-hyaluronidase assays. The GC-MS analysis revealed 82 compounds representing 92.13%, 99.42%, 100%, and 92.97% in Scl, Scf, Scs, and Scb, respectively. The predominant components were α-pinene, β-pinene, (E)-β-caryophyllene, α-caryophyllene, caryophyllene oxide, and α-humulene epoxide II with variable percentages. All EOs were positioned on positive PC1, except for Scs, which was positioned on the negative side in a separate quadrant. The HCA dendrogram displayed the closeness of Scl and Scb, which was not clearly recognized in the PCA score plot. Moreover, the Scs oils were totally discriminated from other parts. The Scl and Scs oils showed superior anti-collagenase, anti-elastase, and anti-hyaluronidase activities. Thus, S. cumini oils should be considered for cosmetic preparations to retard skin aging manifestations.


[Effect of melittin on ion currents in heart cell membranes].
It has been shown on auricle fibres of the frog that neurotoxin from bee poison melittin suppresses the ionic currents entering the cell through calcium and sodium channels of the membrane, increases the background potassium current, suppresses phasic and tonic contraction of the fibres. Toxin modifies the kinetics of calcium channels, but does not affect activation and desensitization of beta adrenoreceptors. Effects of melittin are not decreased when adding the inhibitor of phospholipase A2 indomethacin. The results show that melittin directly affects the protein components of the membrane-ionic channels, probably binding with them.


Effects of dietary nitrate on respiratory physiology at high altitude - Results from the Xtreme Alps study.
Nitric oxide (NO) production plays a central role in conferring tolerance to hypoxia. Tibetan highlanders, successful high-altitude dwellers for millennia, have higher circulating nitrate and exhaled NO (ENO) levels than native lowlanders. Since nitrate itself can reduce the oxygen cost of exercise in normoxia it may confer additional benefits at high altitude. Xtreme Alps was a double-blinded randomised placebo-controlled trial to investigate how dietary nitrate supplementation affects physiological responses to hypoxia in 28 healthy adult volunteers resident at 4559 m for 1 week; 14 receiving a beetroot-based high-nitrate supplement and 14 receiving a low-nitrate 'placebo' of matching appearance/taste. ENO, vital signs and acute mountain sickness (AMS) severity were recorded at sea level (SL) and daily at altitude. Moreover, standard spirometric values were recorded, and saliva and exhaled breath condensate (EBC) collected. There was no significant difference in resting cardiorespiratory variables, peripheral oxygen saturation or AMS score with nitrate supplementation at SL or altitude. Median ENO levels increased from 1.5/3.0 mPa at SL, to 3.5/7.4 mPa after 5 days at altitude (D5) in the low and high-nitrate groups, respectively (p = 0.02). EBC nitrite also rose significantly with dietary nitrate (p = 0.004), 1.7-5.1 μM at SL and 1.6-6.3 μM at D5, and this rise appeared to be associated with increased levels of ENO. However, no significant changes occurred to levels of EBC nitrate or nitrosation products (RXNO). Median salivary nitrite/nitrate concentrations increased from 56.5/786 μM to 333/5,194 μM with nitrate supplementation at SL, and changed to 85.6/641 μM and 341/4,553 μM on D5. Salivary RXNO rose markedly with treatment at SL from 0.55 μM to 5.70 μM. At D5 placebo salivary RXNO had increased to 1.90 μM whilst treatment RXNO decreased to 3.26 μM. There was no association with changes in any observation variables or AMS score. In conclusion, dietary nitrate supplementation is well tolerated at altitude and significantly increases pulmonary NO availability and both salivary and EBC NO metabolite concentrations. Surprisingly, this is not associated with changes in hemodynamics, oxygen saturation or AMS development.


The role of implantable pacemakers in the therapy of tachycardias.
Antitachycardia electrical stimulation involves significant problems of sensing the cardiac rhythm and determining whether a tachycardia exists. The simple algorithms developed for bradycardia pacing are inadequate for tachycardia pacing. Electrogram signal analysis and cardiac activation analysis with at least two leads will be required to make a device diagnosis of a tachycardia. Termination of a tachycardia reliably and consistently is difficult and has only been accomplished uniformly by defibrillation. Further development of devices which are multimodal in termination capability is necessary. A registry for tachycardias and for tachycardia management is required to provide concentrated and analyzable data from a modality as yet infrequently used.


Carbon monoxide-releasing molecule CORM-3 suppresses vascular endothelial cell SOD-1/SOD-2 activity while up-regulating the cell surface levels of SOD-3 in a heparin-dependent manner.
The role of CO in the modulation of antioxidant enzyme function has not been investigated, yet. In this study we assessed the effects and potential mechanisms of the ruthenium-based water-soluble CO-releasing molecule CORM-3 in the modulation of superoxide dismutase (SOD) activity/binding in vascular endothelial cells (HUVECs). To this end, HUVECs were treated with CORM-3 (100 μM) and assessed for total SOD activity in cell lysates (cell-associated SOD activity) and cell culture supernatants (soluble SOD). In parallel, release/binding of extracellular SOD (SOD-3) in the absence or presence of heparin (1-10 IU/ml), a key factor regulating SOD-3 cell-surface binding, was investigated. In addition, the effects of CORM-3 on the modulation of purified SOD-1 and SOD-2 activity in a cell-free system were also assessed. The results obtained indicate that CORM-3 effectively suppresses the activity of both purified SOD-1 and SOD-2. These findings were accompanied by CORM-3-dependent attenuation of total cell-associated SOD activity (without affecting SOD-1/SOD-2 protein expression) and a subsequent increase in ROS production (DHR123 oxidation) in HUVECs. In parallel, a concomitant increase in soluble-SOD activity (due to increased SOD-3 release from the cell surface) was observed in the cell culture supernatants. However, in the presence of heparin, total cell-associated SOD activity was significantly increased by CORM-3, because of increased binding of SOD-3 to HUVECs. Taken together these findings indicate for the first time that CORM-3 modulates both the activity of intracellular SOD (i.e., SOD-1 and SOD-2) and the binding of extracellular SOD (SOD-3) to the cell surface.


Failure of heavy chain glycosylation of IgG in some patients with common, variable agammaglobulinemia.
Four patients with common, variable agammaglobulinemia were preveiously reported to have normal numbers of circulating B lymphocytes which synthesized normal amounts of IgG in tissue culture but failed to secrete the newly synthesized IgG. The B lymphocytes of these patients fail to incorporate [3H]mannose and/or [3H]glucosamine into newly synthesized IgG, whereas such incorporation appears to occur just before IgG secretion in cultures of normal B lymphocytes.


Preoperative Bladder Capacity Predicts Social Continence following Bladder Neck Reconstruction in Children Born with Exstrophy-Epispadias Complex.
The aim of the study is to review the continence and volitional voiding rate in a single center cohort of exstrophy-epispadias patients following Young-Dees-Leadbetter bladder neck reconstruction and to explore factors which predict continence. Children who underwent Young-Dees-Leadbetter bladder neck reconstruction as a final stage of repair in a large single low-volume center in a small-population country between 1997 and 2019 were included. Demographic and clinical details were extracted from the patients' charts. The primary end point was continence and volitional voiding. Patients were categorized as incontinent, socially continent (daytime dry intervals > 3 hours, wet nights) and fully continent (daytime dry intervals > 3 hours, dry nights). The study cohort included 27 patients whose median age at reconstruction was 5 years, and median follow-up was 7.8 years (interquartile range [IQR] 6-11.2). The cohort included 24 classic exstrophy patients (89%, 17 males and 7 females) and 3 isolated complete epispadias patients (11%, 1 male and 2 females). Nine (33%) patients achieved full continence and social continence was achieved by nine (33%) patients, for an overall social continence rate of 67%. Preoperative bladder capacity of 110 mL or more was associated with achieving social continence (odds ratio = 6.4, p = 0.047). The overall volitional voiding rate was 67%. Young-Dees-Leadbetter bladder neck reconstruction yielded rates of 33% for full continence and 67% for social continence and volitional voiding. These rates are comparable to those of large high-volume centers. A preoperative capacity of 110 mL or more was the sole predictor of social continence.


Tobacco 21 Laws and Youth Tobacco Use: The Role of Policy Attributes.
Objectives. To estimate Tobacco-21 policies' relationships to 18- to 20 year-old youth cigarette, cigar, and electronic nicotine delivery system (ENDS) use, and to test for effect modification by policy attributes. Methods. In fall 2022, we used Tobacco 21 Population Coverage Database data to calculate the percentage of state residents covered by state or local Tobacco 21 (T21) laws monthly through June 2020. Matching T21 coverage to Population Assessment of Tobacco and Health and Behavioral Risk Factor Surveillance System data, we used 2-way fixed effect analyses to assess the relationship between T21 laws and 18- to 20-year-old youth cigarette, cigar, and ENDS use, and tested for differences by policy attributes: possession, use, or purchase (PUP) penalties, retailer noncompliance penalties, and compliance check requirements. Results. Increased T21 exposure yielded significant reductions in cigarette and cigar use, as well as in ENDS use, when accounting for policy attributes. These effects were dampened in T21 laws with PUP penalties relative to those without. Conclusions. Tobacco-21 laws yield reductions in 18- to 20-year-old youth cigarette, cigar, and ENDS use, with dampened effects when policies include PUP penalties. Public Health Implications. State policymakers should consider implementing T21 laws without PUP penalties to reduce underage nicotine and tobacco use. (Am J Public Health. 2024;114(1):90-97. https://doi.org/10.2105/AJPH.2023.307447).


Trends in child mortality: a prospective, population-based cohort study in a rural population in south-west Uganda.
Although there has been substantial global progress in decreasing child mortality over the past two decades, progress in sub-Saharan Africa has largely lagged behind. The temporal trends in child mortality and associated risk factors were investigated in a cohort of children in rural Uganda. Information on children's vital status, delivery, breastfeeding, vaccination history, maternal vital and HIV status, and children's HIV status for 1993-2007 was retrieved from the Medical Research Council/Uganda Virus Research Institute's (MRC/UVRI) Annual Population Census and Survey in Uganda. Regression models were employed to assess the association of these factors with child mortality. From 1993 to 2007, the death rate (/1000 person-years) in children <13 years of age decreased significantly from 16 to six. Apart from neonates, age-specific death rates fell in all age-groups. A reduction since 1999 in the risk of child mortality was associated with vaccination, birth in a health facility, exclusive breastfeeding for 6 months, 2-3 years since the previous sibling's birth, maternal vital status, and negative mother and child HIV serostatus. Although HIV seropositive children had a 26-fold increased risk of death before 13 years of age, HIV prevalence in children was about 1% and so had a small overall impact on child mortality. These findings are consistent with those of repeated national cross-sectional surveys. Meeting the Millennium Development Goals for child survival in sub-Saharan Africa depends on faster progress in implementing measures to improve birth-spacing, safe delivery in health facilities, infant feeding practices and vaccination coverage.


Exosomes Facilitate Transmission of Enterovirus A71 From Human Intestinal Epithelial Cells.
Enterovirus A71 (EV-A71) has been noted for its tendency to lead to neurological manifestations in young children and infants. Although the alimentary tract has been identified as the primary replication site of this virus, how EV-A71 replicates in the gut and is transmitted to other organs remains unclear. By using differentiated C2BBe1 cells as a model, we observed that intestinal epithelial cells (IECs) were permissive to EV-A71 infection, and viral particles were released in a nonlytic manner. The coexistence of active caspase 3 and EV-A71 protein was observed in the infected undifferentiated C2BBe1 and RD cells but not in the infected differentiated C2BBe1 cells. Furthermore, EV-A71 infection caused differentiated C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the ability to establish active infection. Inhibition of the exosome pathway decreased EV-A71 replication and release in IECs and increased the survival rates of infected animals. Our findings showed that EV-A71 is able to be actively replicated in enterocytes, and that the exosome pathway is involved in the nonlytic release of viral particles, which may be useful for developing antiviral strategies.


[Molecular organization of glutamate-sensitive, chemoexcitatory membranes of nerve cells. Physico-chemical characteristics of the glutamate-binding synaptic membrane proteins of the rat cerebral cortex].
Some physico-chemical properties of glutamate-binding proteins solubilized from rat cerebral cortex synaptic membranes and purified by affinity chromatography were studied. Purified proteins were shown to be homogenous during SDS polyacrylamide gel electrophoresis (Mr 14000). The Scatchard plots for L-[3H]glutamate binding to the purified membrane proteins revealed the presence of one type of binding sites with Kd 800-1000 nM and Bmax 180-200 pmol/mg of protein. Ultracentrifugation of the glutamate-binding membrane protein in sucrose linear gradient demonstrated that the position of the protein peak depends on protein concentration, i.e. after dilution of the sample the protein peak is shifted from 28 000-30 000 to 12 000-15 000. The values of sedimentation coefficients decrease correspondingly to 2.1S. Presumably, these processes are due to dissociation of receptor macromolecules. The glutamate receptor is a glycoprotein-lipid complex made up of several low molecular weight subunits.


Effects of overnight military training and acute battle stress on the cognitive performance of soldiers in simulated urban combat.
Understanding the effect of stress, fatigue, and sleep deprivation on the ability to maintain an alert and attentive state in an ecologically valid setting is of importance as lapsing attention can, in many safety-critical professions, have devastating consequences. Here we studied the effect of close-quarters battle (CQ battle) exercise combined with overnight military training with sleep deprivation on cognitive performance, namely sustained attention and response inhibition. In addition, the effect of the CQ battle and overnight training on cardiac activity [heart rate and root mean square of the successive differences (RMSSD)] during the cognitive testing and the relationship between cardiac activity and cognitive performance were examined. Cognitive performance was measured with the psychomotor vigilance task (PVT) and the sustained attention to response task (SART). Altogether 45 conscripts participated in the study. The conscripts were divided into control (CON) and experimental (EXP) groups. The CON completed the training day after a night of sleep and the EXP after the overnight military training with no sleep. Results showed that the effect of the overnight training on cognitive performance and the between-group difference in heart rate (HR) and heart rate variability (HRV) depended on the cognitive test. Surprisingly, the cognitive performance was not largely affected by the CQ battle. However, as expected, the CQ battle resulted in a significant decrease in RMSSD and an increase in HR measured during the cognitive testing. Similarly, the HR parameters were related to cognitive performance, but the relationship was found only with the PVT. In conclusion, fatigue due to the overnight training impaired the ability to maintain sufficient alertness level. However, this impairment in arousal upregulation was counteracted by the arousing nature of the SART. Hence, the conscripts' cognitive performance was mainly preserved when performing a stimulating task, despite the fatigue from the sleep loss of the preceding night and physical activity.


Catalytic M Center of Copper Monooxygenases Probed by Rational Design. Effects of Selenomethionine and Histidine Substitution on Structure and Reactivity.
The M centers of the mononuclear monooxygenases peptidylglycine monooxygenase (PHM) and dopamine β-monooxygenase bind and activate dioxygen en route to substrate hydroxylation. Recently, we reported the rational design of a protein-based model in which the CusF metallochaperone was repurposed via a His to Met mutation to act as a structural and spectroscopic biomimic. The PHM M site exhibits a number of unusual attributes, including a His2Met ligand set, a fluxional Cu(I)-S(Met) bond, tight binding of exogenous ligands CO and N3-, and complete coupling of oxygen reduction to substrate hydroxylation even at extremely low turnover rates. In particular, mutation of the Met ligand to His completely eliminates the catalytic activity despite the propensity of CuI-His3 centers to bind and activate dioxygen in other metalloenzyme systems. Here, we further develop the CusF-based model to explore methionine variants in which Met is replaced by selenomethionine (SeM) and histidine. We examine the effects on coordinate structure and exogenous ligand binding via X-ray absorption spectroscopy and electron paramagnetic resonance and probe the consequences of mutations on redox chemistry via studies of the reduction by ascorbate and oxidation via molecular oxygen. The M-site model is three-coordinate in the Cu(I) state and binds CO to form a four-coordinate carbonyl. In the oxidized forms, the coordination changes to tetragonal five-coordinate with a long axial Met ligand that like the enzymes is undetectable at either the Cu or Se K edges. The EXAFS data at the Se K edge of the SeM variant provide unique information about the nature of the Cu-methionine bond that is likewise weak and fluxional. Kinetic studies document the sluggish reactivity of the Cu(I) complexes with molecular oxygen and rapid rates of reduction of the Cu(II) complexes by ascorbate, indicating a remarkable stability of the Cu(I) state in all three derivatives. The results show little difference between the Met ligand and its SeM and His congeners and suggest that the Met contributes to catalysis in ways that are more complex than simple perturbation of the redox chemistry. Overall, the results stimulate a critical re-examination of the canonical reaction mechanisms of the mononuclear copper monooxygenases.


[Opening of the Geneva University Hospital Prostate Cancer Center].
In 2014, Geneva University Hospital has opened the first certified prostate cancer Center of western Switzerland. It incorporates 29 entities implicated in the diagnosis and treatment of this disease, thereby assuring that all available ressources are made available to patients, regardless of the division to which they were initially referred. The main strength of the Center lies in the synergy generated by its multidisciplinary tumor board. Furthermore, regular conferences, staff meetings, propectively held registers and the yearly re-certification audit support its constant quality improvement.


Differential translational regulation of IRE-containing mRNAs in Drosophila melanogaster by endogenous IRP and a constitutive human IRP1 mutant.
Insects, like vertebrates, express iron regulatory proteins (IRPs) that may regulate proteins in cellular iron storage and energy metabolism. Two mRNAs, an unspliced form of ferritin H mRNA and succinate dehydrogenase subunit b (SDHb) mRNA, are known to comprise an iron responsive element (IRE) in their 5'-untranslated region making them susceptible to translational repression by IRPs at low iron levels. We have investigated the effect of wild-type human IRP1 (hIRP1) and the constitutively active mutant hIRP1-S437 in transgenic Drosophila melanogaster. Endogenous Drosophila IRE-binding activity was readily detected in gel retardation assays. However, translational repression assessed by polysome gradients was only visible for unspliced IRE-containing ferritin H mRNA, but not for SDHb mRNA. Upon expression of exogenous hIRP1-S437 both mRNAs were strongly repressed. This correlated with a diminished survival rate of adult flies with hIRP1 and complete lethality with hIRP1-S437. We conclude that constitutive IRP1 expression is deleterious to fly survival, probably due to the essential function of SDHb or proteins encoded by yet unidentified target mRNAs.


Simultaneous and quantitative monitoring of co-cultured Pseudomonas aeruginosa and Staphylococcus aureus with antibiotics on a diffusometric platform.
Successful treatments against bacterial infections depend on antimicrobial susceptibility testing (AST). However, conventional AST requires more than 24 h to obtain an outcome, thereby contributing to high patient mortality. An antibiotic therapy based on experiences is therefore necessary for saving lives and escalating the emergence of multidrug-resistant pathogens. Accordingly, a fast and effective drug screen is necessary for the appropriate administration of antibiotics. The mixed pathogenic nature of infectious diseases emphasizes the need to develop an assay system for polymicrobial infections. On this basis, we present a novel technique for simultaneous and quantitative monitoring of co-cultured microorganisms by coupling optical diffusometry with bead-based immunoassays. This simple integration simultaneously achieves a rapid AST analysis for two pathogens. Triple color particles were simultaneously recorded and subsequently analyzed by functionalizing different fluorescent color particles with dissimilar pathogen-specific antibodies. Results suggested that the effect of the antibiotic, gentamicin, on co-cultured Pseudomonas aeruginosa and Staphylococcus aureus was effectively distinguished by the proposed technique. This study revealed a multiplexed and time-saving (within 2 h) platform with a small sample volume (~0.5 μL) and a low initial bacterial count (50 CFU per droplet, ~105 CFU/mL) for continuously monitoring the growth of co-cultured microorganisms. This technique provides insights into timely therapies against polymicrobial diseases in the near future.


Prevalence and determinants of Campylobacter infection among under five children with acute watery diarrhea in Mwanza, North Tanzania.
Campylobacteriosis, a zoonotic bacterial disease observed world-wide, is becoming the most commonly recognized cause of bacterial gastroenteritis in humans. This study was done to determine the prevalence and determinants of Campylobacter infection among under-fives with acute watery diarrhea in Mwanza City, Tanzania. This cross-sectional hospital-based study was conducted at Bugando Medical Centre (BMC) and Sekou Toure Hospital in Mwanza City. All inpatients and outpatients under-fives who met the inclusion criteria from October 2012 to April 2013 were enrolled in the study. Demographic and clinical data were obtained using standardized data collection tools. Stool samples were collected for gram staining and culture for Campylobacter spp. on Preston selective agar media. In addition, blood slides for malaria and HIV tests were done to all patients. A total of 300 children were enrolled with a median age of 12 [interquartile range, 8-19] months. Of these, 169 (56.5%) were from BMC and 131 (43.7%) from Sekou-Toure hospital. One hundred and seventy (56.7%) of the participating children were male. Of 300 under-fives with acute watery diarrhea, 29 patients (9.7%) were found to have Campylobacter infection. A significant higher number of children with Campylobacter infection were found in Sekou Toure hospital compared to BMC [16.0% (21/29) versus 4.7% (8/29), p = 0.002)]. Age above 2 years was independently found to predict campylobacter infection (OR: 2.9, 95% CI 1.1-7.7, p = 0.0037). Of 30 patients with a positive blood slide for Plasmodium falciparum, 20.0% were also positive for Campylobacter infection (OR: 3.9, 95% CI 1.2-10.1, p = 0.021). Campylobacter infection shows a comparatively low prevalence in under-fives with acute watery diarrhea in Mwanza city and is independently associated with positive slides for malaria and an age above 2 years. Further studies are needed to type the most prevalent Campylobacter species and to determine their antibiotic susceptibility pattern.


Epidemiological study of provision of cholecystectomy in England from 2000 to 2009: retrospective analysis of Hospital Episode Statistics.
The aim of this study was to report the trends in provision of cholecystectomy in the National Health System in England over the 9 year period from 2000 to 2009 and to determine the major risk factors associated with subsequent poor outcome. The Hospital Episode Statistics database was interrogated to identify all cholecystectomy procedures for biliary stone disease in adult patients (>16 years). Multivariate regression analyses were used to identify independent predictors of in-patient death, 1 year death, conversion to open, major bile duct injury (BDI) requiring operative repair, and length of stay. A total of 418,214 cholecystectomy procedures for biliary stone disease were identified. Laparoscopic surgery was used in 348,311 (83.3%) cases and increased by 14.6% over the study period. The in-patient mortality rate (0.2%), 1 year mortality rate (1%), proportion of cases converted to open (5.0%), major BDI rate (0.4%), and mean length of stay (3 days) all decreased over the study period. 52,242 (12.5%) cases were carried out during an emergency admission and uptake has remained stable over the decade. Emergency surgery was more likely to be performed at high-volume centres (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.35-1.44) and specialist units (OR 1.32, 95% CI 1.30-1.35). High-volume centres were more likely to complete emergency cases laparoscopically (OR 1.11, 95% CI 1.05-1.18). Multivariate regression analysis demonstrated that patient- (male gender, increasing age, and comorbidity) and disease-specific (inflammatory pathology and emergency admission) factors rather than hospital institutional characteristics (annual cholecystectomy volume and presence of specialist surgical units) were associated with poorer outcomes. The provision of laparoscopic cholecystectomy in England has increased. This has been associated with improvements in outcomes such as mortality and length of stay. However, emergency cholecystectomy uptake remains sub-optimal and is more likely to be performed at high-volume or specialist hospitals without adverse outcomes. Further research into the routine provision of emergency cholecystectomy in England is needed in order to optimize patient outcomes.


Filarioid nematodes in cattle, sheep and horses in Finland.
In autumn 2006, Finnish meat inspection data revealed lesions in tendons, muscles and ligaments of bovine hind legs leading to partial condemnation of carcasses. In gross pathological examination at Finnish Food Safety Authority Evira, Oulu (now Fish and Wildlife Health) Research Unit, Onchocerca sp. (Filarioidea; Onchocercidae) nematodes were detected in lesions. Due to this, a pilot study was made in order to find out what filarioid nematodes do occur in cattle, horses and sheep in Finland. Ventral skin biopsies from 209 dairy cattle and 42 horses, as well as blood samples from 209 cattle, 146 horses and 193 sheep, were collected from different parts of Finland and examined for microfilariae. Visceral organs and other tissues from 33 cattle with parasitic lesions were studied histopathologically. Onchocerca sp. microfilariae (mf), 240 mum long, range 225-260 mum, 5.4 mum thick, were found in 37% of the skin biopsies of cattle. All blood samples from cattle, horses and sheep and skin biopsies from horses were negative for mf. Ventral skin microfilaria prevalence in cattle was higher in southern Finland than in the North (p = 0.001). Animal age and sampling time was not associated with mf prevalence. The infection was evenly distributed among young and older animals. Macroscopic lesions on tissues included greenish-grey discolouration and often oedema. In most of the lesions, small pale nodules were seen on the fasciae. Histopathologic examination of the samples revealed mild to intense infiltration with eosinophilic granulocytes and multifocal nodular lymphoplasmacytic aggregations were seen. In some samples, there were granulomatotic lesions with central necrotic tissue and cell detritus, surrounded by eosinophilic granulocytes, lympho-, plasma- and histiocytes and some multinucleated giant cells. Around living nematodes no or only weak inflammatory changes were observed. Onchocerca sp. infection in cattle was found to be common in Finland, but the amount of pathological changes leading to condemnation of infected parts is low compared to the mf prevalence. Pronounced pathological changes are distinct but rare and mild changes are difficult to distinguish. No other filarioid nematodes were observed from the animals and it appears that horses and sheep may be free from filarioid nematodes in Finland.


A novel role of CDX1 in embryonic epicardial development.
The molecular mechanism that regulates epicardial development has yet to be understood. In this study, we explored the function of CDX1, a Caudal-related family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in the migration and the differentiation of epicardium-derived progenitors into vascular smooth muscle cells. We detected a transient expression of CDX1 in murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline-inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In addition, a low-dose CDX1 induction led to enhanced migration and differentiation of epicardium-derived cells into α-SMA+ vascular smooth muscles. In contrast, either continued high-level induction of CDX1 or CDX1 deficiency attenuated the ability of epicardium-derived cells to migrate and to mature into smooth muscles induced by TGF-β1. Further RNA-seq analyses showed that CDX1 induction altered the transcript levels of genes involved in neuronal development, angiogenesis, and cell adhesions required for EMT. Our data have revealed a previously undefined role of CDX1 during epicardial development, and suggest that transient expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of EPDCs and contribution to coronary vascular endothelium or smooth muscle cells.


[Peptidergic and serotoninergic regulation of the pancreas].
The paper contain the literature and own experimental data on peptid/serotoninergic regulation of pancreatic activity. Peptid- and serotoninergic mechanisms of regulation of pancreas activity are described. The experimental data on serotonin influence on pancreatic duct motility under pancreatitis are given.


Focal Thickness Reduction of the Ganglion Cell-Inner Plexiform Layer Best Discriminates Prior Optic Neuritis in Patients With Multiple Sclerosis.
The goal was to visualize topographic thickness maps of the intraretinal layers and evaluate their discrimination abilities and relationships with clinical manifestations in patients with multiple sclerosis (MS) and a history of optic neuritis (ON). Thirty patients with relapsing-remitting MS (34 eyes with a history of ON [MSON] and 26 non-ON fellow eyes [MSFE]) were recruited together with 63 age- and sex-matched controls (HC). Ultrahigh resolution optical coherence tomography was used to image the macula and the volumetric data set was segmented to yield six intraretinal layers. Topographic thickness maps were aligned and averaged for the visualization. The thickness maps were partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) and related to Sloan low-contrast letter acuity (LCLA), Expanded Disability Status Scale (EDSS), and disease duration. Focal thickness reduction occurred in the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL), with the most profound reduction occurring in MSON eyes (P < 0.05). A horseshoe-like thickness reduction pattern (U Zone) in the GCIPL appeared in MSON. The thickness of the U Zone had better discrimination power than the ETDRS partitions (area under the curve = 0.97) and differentiated 96% of MSON from HC. The thickness of the U Zone was positively correlated to 2.5% LCLA (r = 0.38, P < 0.05) and 1.25% LCLA (r = 0.57, P < 0.05). The horseshoe-like thickness reduction of the GCIPL appeared to be an ON-specific focal thickness alteration with the highest discrimination power of prior ON.


[Express-method of a valuation of fat products authention wth using computes program].
The present investigation was devoted on the processing of program for express analysis of fat products detecting in the Access. The program can to establish nature of milk fat and to give detailed characteristic of combined fat products, including information about technology, used under production of combined fat products and their preferable field of application.


Effect of cosolvents on nano-confined water: a molecular dynamics study.
We present results from atomistic molecular dynamics simulations to characterize the effects of cosolvents, such as urea and guanidinium (Gdm) salts, on the water confined in hydrophobic carbon nanotubes. We observed complete drying of the nanotube interiors of diameter ranging from 8 to 17 Å in urea. In contrast, the water population within nanotube cores smaller than 12 Å remains unaffected in GdmCl solution, whereas larger nanotube interiors become partially dehydrated with prevailing presence of stable Gdm(+)-Gdm(+) dimers. The molecular arrangement and the lifetime inside the nanotube were found to be characteristics of a particular cosolvent. In both urea and GdmCl solutions, preferential cosolvent intrusion resulting in nanotube dehydration is driven by the stronger dispersion interaction of cosolvent than water with the nanotube. The partial drying of the hydrophobic core is attributed to guanidinium's better hydration and weaker self-association propensity compared to urea, as well as to its moderate ion-pairing with strongly hydrated chloride ions. The Gdm(+) induced dehydration varies with the charge density of counter-ions, as the presence of high charge-density sulfate ions impedes penetration of guanidinium, and consequent dehydration of the nanotube. These findings provide important insights into the effect of cosolvents on the nano-confined water in a hydrophobic environment.


The tooth-worm: historical aspects of a popular medical belief.
The concept of a tooth-worm, which according to popular belief, caused caries and periodontitis, has existed in diverse cultures and across the ages. During the Enlightenment, however, the theory of the tooth-worm was assigned by medical doctors almost exclusively to superstition. Even so, the idea that toothache was caused by gnawing worms held on even into this century. There were many different ideas with regard to the appearance of tooth-worms. In England, for instance, it was thought that the tooth-worm looked like an eel. In Northern Germany, people supposed the tooth-worm to be red, blue, and gray and in many cases the worm was compared to a maggot. The gnawing worm was held responsible for many evils and, in particular, was blamed for toothache provoked by caries. The question is discussed of how the belief in the existence of the tooth-worm in former times can be explained. In popular medicine, numerous therapies were applied in order to eradicate the tooth-worm. In addition to the fumigations with henbane seeds, which allowed the "tooth-worm" to develop in the form of burst seeds, there were also magical formulas and oaths.


Determination of hazardous VOCs and nicotine released from mainstream smoke by the combination of the SPME and GC-MS methods.
In this study, the contents of nicotine and volatile organic compounds (VOCs) in mainstream smoke (MSS) were analyzed using samples of four cigarette types consisting of two common brands (R and E) with full (F) and light (L) flavor, coded with R-F, R-L, E-F, and E-L. These cigarettes were also analyzed after removing the filter portions with the assignment of a new sample code of (N) as the third letter (e.g., R-L-N). A total of 44 VOCs (including nicotine) were quantified by the combination of the SPME and GC-MS methods. Out of the 44 VOCs, 10 were identified as hazardous air pollutants listed by the U.S. EPA, while their concentrations exceeded the reference exposure limits set by various agencies. A clear distinction was apparent in the concentration levels of VOCs between different brands or between full and light flavors. Nicotine concentrations varied greatly between different cigarettes types of the R brand, whereas such changes were insignificant in the counterpart E brand. This thus suggests that light-flavor cigarettes do not necessarily guarantee low doses of carcinogens (and tar) than regular cigarettes, as their differences can be balanced by the inhaling behavior of the smoker.


Cannabis use is associated with a lower risk of diabetes in chronic hepatitis C-infected patients (ANRS CO22 Hepather cohort).
Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients' clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.


Reductions in home-range size and social interactions among dehorned black rhinoceroses (Diceros bicornis).
Poaching for horns and tusks is driving declines of megaherbivores worldwide, including the critically endangered African black rhinoceros (Diceros bicornis). By proactively dehorning entire rhinoceros populations, conservationists aim to deter poaching and prevent species loss. However, such conservation interventions may have hidden and underestimated effects on animals' behavior and ecology. Here, we combine >15 y of black rhino-monitoring data across 10 South African game reserves, comprising >24,000 sightings of 368 individuals, to determine the consequences of dehorning for black rhino space use and social interactions. While preventative dehorning at these reserves coincided with a nationwide decrease in black rhino mortality from poaching and did not infer increased natural mortality, dehorned black rhinos decreased their home range area by, on average, 11.7 km2 (45.5%) and were 37% less likely to engage in social encounters. We conclude that dehorning black rhinos as an antipoaching measure alters their behavioral ecology, although the potential population-level effects of these changes remain to be determined.


Genitourinary infections after a routine pelvic exam.
To determine if genitourinary problems are more common in women in the first 1 to 2 months after a routine pelvic examination. This was a historical cohort study in 2 family medicine teaching clinics at an urban university. Participants included all women who received a Papanicolaou smear during calendar year 2006. Subjects included all participants for weeks 1 to 7 after their Papanicolaou smear. Controls were all participants in weeks 8 to 52 after their Papanicolaou smear. The independent variable was time after Papanicolaou smear, and dependent variables included frequency of visits for urinary complaints, diagnosed urinary tract infections (UTIs), vaginal complaints, diagnosed vaginitis, and sexually transmitted diseases. Relative frequencies compared using 2-tailed t tests. UTIs and urinary complaints were significantly more frequent during the first 7 weeks after a Papanicolaou smear compared with weeks 8 to 14, 8 to 48, and 8 to 52. The overall rate of UTIs was 7.33 per 100 person-years; the attributable risk during the first 7 weeks was 0.82 per 100 person-years, or 11% of observed UTIs. Combined Candidal and bacterial vaginitis was marginally more frequent during the first 7 weeks compared with weeks 8 to 48 and 8 to 52 only. The incidence of sexually transmitted diseases combined was 1.13 per 100 person-years, distributed evenly over the study period unrelated to time. The risk of UTI is increased in the 7 weeks after a Papanicolaou smear.


[Prevention of complications after surgery in patients with upper limbs' lymphedema].
The results of surgical treatment of patients with the fourth stage of the upper limbs' lymphedema was studied. Of all 170 patients with lymphedema, 16 (9.4%) had the fourth stage of the disease. The debulking procedures were performed in 15 patients (8 had standart operations, 7 - simultaneous rwo-stage operations). Beeing a preliminary stage of the radical surgical excision of lymphoedematously changed tissues, the liposuction allows a more precisional hemostasis for the accurate vessel visualization. It led to the 4,4 times decrease of the postoperative morbidity rate and shortened the time of the operation.


Vitamin D Status and Prevalent Early Age-Related Macular Degeneration in African Americans and Caucasians: The Atherosclerosis Risk in Communities (ARIC) Study.
Vitamin D status has been hypothesized to protect against development of early age-related macular degeneration (AMD) via its anti-inflammatory properties and its possible beneficial influence on blood pressure control. We investigated the association between vitamin D status and prevalent early AMD in a community-based cohort. This was a cross-sectional study. This was a secondary data analysis of already existing data from the Atherosclerosis Risk in Communities Study (ARIC) cohort collected from 1990 to 1995. There were 9,734 (7,779 Caucasians, 1,955 African American) ARIC participants (aged 46 to 70 at visit 2 [1990-1992]) with 25(OH)D data available at visit 2, AMD assessment at visit 3 (1993-1995), and complete covariate data. Vitamin D status was assessed with serum 25-hydroxyvitamin D (25(OH)D) concentrations from bloods drawn at visit 2. Prevalent, early AMD (n=511) was assessed at visit 3 (1993-95) with nonmydriatic retinal photographs of one randomly chosen eye. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD by categories of 25(OH)D in nmol/L (deficient <30, inadequate 30-<50, and two categories of adequate status: 50-<75 and ≥75). Linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, and smoking status. We further adjusted for hypertension status to examine if vitamin D status influenced early AMD via its effects on blood pressure. Exploratory analyses of effect modification by age, sex, race and high risk genotypes [Y402H complement factor H (CFH) rs1061170 and the A69S age-related maculopathy susceptibility 2 (ARMS2) rs10490924 polymorphisms] were conducted. The prevalence of early AMD was 5%, and 5% of participants were vitamin D deficient. The adjusted OR (95% CIs) for early AMD among those with adequate (≥75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59-1.50), p-trend=0.86. Further adjustment for hypertension status did not influence results (OR [95% CI]=0.95 [0.59-1.52], p-trend=0.84). Results did not vary significantly by age, race, sex, early AMD subtype (soft drusen or retinal pigment epithelium depigmentation), or ARMS2 genotype. Results did not vary significantly by CFH genotype in African Americans. The p for multiplicative interaction between 25(OH)D and CFH genotype was 0.06 in Caucasians, but OR [95% CIs] for AMD by vitamin D status were similar in each CFH genotype and not statistically significant. Vitamin D status was not associated with early AMD in this cohort sample.


Hospitalizations for pulmonary embolism in Brazil (2008-2019): an ecological and time series study.
To assess the temporal trends of hospitalizations for pulmonary embolism (PE) in Brazil, its regions, and states between 2008 and 2019. An ecological and time series study was conducted. Data were obtained from the Hospital Information System (SIH) of the Brazilian Ministry of Health. The inflection point regression model was applied for temporal trend analyses. Trends were classified as increasing, decreasing, or stationary according to the slope of the regression line. The Annual Percent Charge (APC) and the Average Annual Percent Change (AAPC) were calculated considering a confidence interval of 95% and p-value <0.05. Furthermore, spatial distribution maps of epidemiological indicators related to PE in Brazil were elaborated. There was an increasing trend in the hospitalization rate for PE in Brazil, ranging from 2.57 in 2008 to 4.44/100,000 in 2019 (AAPC=5.6%; p<0.001). Total and average hospitalizations costs also showed increasing trend in the country (AAPC=9.2% and 3.0%, respectively). Still, there was a decrease in the in-hospital mortality rate (from 21.21% to 17.11%; AAPC=-1.9%; p<0.001). Similar trends were observed in most regions. The average hospitalization time in Brazil showed a stationary trend. The hospitalization rate has also increased in 18 states (66.67%). Seven states showed a decrease in the mortality rate (25.93%), except for Roraima, which showed an increasing trend. Hospitalizations for PE represent a serious public health problem in Brazil and the temporal patterns observed herein demonstrate an increasing trend in all regions and states of the country.


Liver Transplantation in Hepatitis B/Hepatitis D (Delta) Virus Coinfected Recipients.
Hepatitis D is caused by the hepatitis D virus (HDV); it is the most severe form of viral hepatitis in humans, running an accelerated course to cirrhosis. There is no efficacious therapy, and liver transplantation provides the only therapeutic option for terminal HDV disease. However, HDV infection is prevalent in poor countries of the world with no access to liver transplant programs; liver grafting has been performed in high-income countries, where the prevalence of the infection has much diminished as a secondary effect of hepatitis B virus vaccination, and the demand for liver transplantation outlives in aging cirrhotics who acquired hepatitis D decades ago. This review describes the evolution of liver transplantation for HDV disease from its inception in 1987 to the present time, with an outlook to its future. It reports the progress in the prophylaxis of HDV reinfections to the success of the current standard of indefinite combination of hepatitis B virus antivirals with immunoglobulins against the hepatitis B surface antigen; however, the unique biology of the virus provides a rationale to reducing costs by limiting the administration of the immunoglobulins against the hepatitis B surface antigen.


Efficient Photoacoustic Image Synthesis with Deep Learning.
Photoacoustic imaging potentially allows for the real-time visualization of functional human tissue parameters such as oxygenation but is subject to a challenging underlying quantification problem. While in silico studies have revealed the great potential of deep learning (DL) methodology in solving this problem, the inherent lack of an efficient gold standard method for model training and validation remains a grand challenge. This work investigates whether DL can be leveraged to accurately and efficiently simulate photon propagation in biological tissue, enabling photoacoustic image synthesis. Our approach is based on estimating the initial pressure distribution of the photoacoustic waves from the underlying optical properties using a back-propagatable neural network trained on synthetic data. In proof-of-concept studies, we validated the performance of two complementary neural network architectures, namely a conventional U-Net-like model and a Fourier Neural Operator (FNO) network. Our in silico validation on multispectral human forearm images shows that DL methods can speed up image generation by a factor of 100 when compared to Monte Carlo simulations with 5×108 photons. While the FNO is slightly more accurate than the U-Net, when compared to Monte Carlo simulations performed with a reduced number of photons (5×106), both neural network architectures achieve equivalent accuracy. In contrast to Monte Carlo simulations, the proposed DL models can be used as inherently differentiable surrogate models in the photoacoustic image synthesis pipeline, allowing for back-propagation of the synthesis error and gradient-based optimization over the entire pipeline. Due to their efficiency, they have the potential to enable large-scale training data generation that can expedite the clinical application of photoacoustic imaging.


Data Mining and Statistical Approaches in Debris-Flow Susceptibility Modelling Using Airborne LiDAR Data.
Cameron Highland is a popular tourist hub in the mountainous area of Peninsular Malaysia. Most communities in this area suffer frequent incidence of debris flow, especially during monsoon seasons. Despite the loss of lives and properties recorded annually from debris flow, most studies in the region concentrate on landslides and flood susceptibilities. In this study, debris-flow susceptibility prediction was carried out using two data mining techniques; Multivariate Adaptive Regression Splines (MARS) and Support Vector Regression (SVR) models. The existing inventory of debris-flow events (640 points) were selected for training 70% (448) and validation 30% (192). Twelve conditioning factors namely; elevation, plan-curvature, slope angle, total curvature, slope aspect, Stream Transport Index (STI), profile curvature, roughness index, Stream Catchment Area (SCA), Stream Power Index (SPI), Topographic Wetness Index (TWI) and Topographic Position Index (TPI) were selected from Light Detection and Ranging (LiDAR)-derived Digital Elevation Model (DEM) data. Multi-collinearity was checked using Information Factor, Cramer's V, and Gini Index to identify the relative importance of conditioning factors. The susceptibility models were produced and categorized into five classes; not-susceptible, low, moderate, high and very-high classes. Models performances were evaluated using success and prediction rates where the area under the curve (AUC) showed a higher performance of MARS (93% and 83%) over SVR (76% and 72%). The result of this study will be important in contingency hazards and risks management plans to reduce the loss of lives and properties in the area.


Interactions of hydroxycarbamide (hydroxyurea) with iron and copper: implications on toxicity and therapeutic strategies.
Presented at the 19th International Conference on Chelation, London, UK, 13-16 November 2009 Preliminary spectrophotometric and potentiometric studies have shown that hydroxycarbamide or hydroxyurea (HU) can interact with copper(II) [Cu(II)], iron(II) [Fe(II)] and Fe(III) ions and form complexes, for example, a ratio of 1 HU:1 metal at pH 5. The affinity for Cu (log β1 = 3.1) and Fe (log β1 = 5) by HU is much lower than that of the Fe and Cu chelating drug deferiprone (L1), which is used for the treatment of iron overload. It is anticipated that under certain conditions of high concentrations of these metal ions such as in transfusional iron overload, the therapeutic, pharmacological and toxicological properties of HU could be affected. It is also suggested that excess chelatable and labile forms of Fe or Cu ions, such as non transferrin-bound iron (NTBI) or intracellular low molecular weight labile iron, are among the main factors that may cause variations in the therapeutic response to HU in cancer, sickle cell anemia, thalassemia intermedia and other groups of patients. Further studies are needed to clarify the interaction mechanisms of HU with metal ions in vitro, in vivo and in clinical conditions.


Laparoscopic tension-free repair of large paraesophageal hiatal hernias with a composite A-shaped mesh: two-year follow-up.
Surgical repair of large hiatal hernias is associated with a high recurrence rate when the repair is made by simple cruroplasty. The use of a mesh goes from a reinforcement of a simple cruroplasty to a tension-free repair. We discuss the evolution of this approach and evaluate the outcomes of 27 patients with type II (n = 9), type III (n = 16), and type IV (n = 2) hiatal hernias treated laparoscopically. Between November 1999 and October 2003, 27 patients (18 women and 9 men) received laparoscopic repair of large hiatal hernias by means of an A-shaped polypropylene-polytetrafluoroethylene mesh. A total or a partial fundoplication was associated in all cases. The mean age was 60.1 years (range, 36-76 years). The patients presented with symptoms of 2 months to 10 years in duration. Preoperative assessment included an upper gastrointestinal endoscopy, esophageal manometry, 24 hour pH monitoring, and barium swallow. Concomitant esophagitis was found in 16 patients and impaired esophageal peristalsis in 2 patients. Four patients had concomitant gallbladder disease treated at the same time. No conversions occurred in our series. There was no perioperative mortality, and morbidity was low. Follow-up averaged 27 months (range, 6-46 months). There has been 1 recurrence (3.7%), prolonged dysphagia in 4 cases, and no mesh erosion. Early results confirm the feasibility of the tension-free repair of large hiatal hernias and the effectiveness of the composite A-shaped mesh. Long-term follow-up for all patients is necessary to determine the real incidence of recurrence.


Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass.
Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with sham-operated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham- and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGB- versus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.


Healing at the interface between recipient sites and autologous block bone grafts affixed by either position or lag screw methods: a histomorphometric study in rabbits.
To compare the sequential healing at the interface gap occurring between autologous bone grafts and recipient sites using two types of fixation techniques. Twenty-four adult male New Zealand white rabbits were used. Two bone grafts were collected from the calvaria and secured to the lateral aspect of the angle of mandible in each animal. Cortical perforations at the recipient sites were performed. However, no modifications were applied to the graft for its adaptation to the recipient site. Two types of fixation techniques by position or lag screws were applied. This was done by preparing osteotomy holes smaller or larger than the screw diameter, respectively. The animals were sacrificed after 3, 7, 20, and 40 days. After 3 days, the distance between the graft and the recipient site was similar between the two different fixations. Due to the anatomical shapes of the recipient sites and grafts, the distance between the two parts was lower in the central region (<0.1 mm) compared to the external regions of the graft (0.5-0.6 mm). The first evidence of small amounts of new (woven) bone was seen after 7 days, forming from the parent bone. The percentage increased after 20 and 40 days. After 40 days, the grafts were well incorporated within the recipient sites in both groups without any statistically significant difference. The present study did not show superiority of one method over another. A fixation to a recipient site with perforations may be sufficient for incorporating an autologous bone graft even if its adaptation is not perfect and irrespectively of the fixation method. Distances of approximately half millimeter were bridged with newly formed bone.


Increased risk of death from COVID-19 in multiple sclerosis: a pooled analysis of observational studies.
To estimate whether the risk of death from COVID-19 in patients with multiple sclerosis (MS) exceeds that of the general population. We conducted a pooled analysis of cohort studies on COVID-19 in patients with MS published until July 31, 2021. We calculated the pooled crude death rate (CDR) and estimated the indirectly-adjusted age-standardized lethality ratio (SLR) to assess the risk of death from COVID-19 in patients with MS as compared to general population. Out of 520 articles, 18 fulfilled criteria for pooled analysis, with a total of 5634 patients (28.6% males, mean age 41.8 years). Of them, 111 died, yielding a CDR of 1.97% (95% confidence intervals [CIs] 1.61-2.33). The estimated SLR was 1.24 (95% CIs 1.01-1.48) after indirect age-standardization using case-fatality rates obtained from the detailed surveillance data available at the World Health Organization (WHO) website. A leave-one-out sensitivity analysis and the analysis of temporal trends of SLR from March 2020 to July 2021 provided consistent findings. Our pooled analysis suggests a 24%-increased risk of death from COVID-19 in patients with MS. These findings must be interpreted with caution, mainly because of the difficulties in COVID-19 case detection (especially in the first pandemic wave) and heterogeneity of the analyzed cohorts. Confirmation in larger population-based studies is warranted.


Validation of an immunohistochemistry assay to detect turkey coronavirus: a rapid and simple screening tool for limited resource settings.
The objective of the present study was to develop and apply the direct immunohistochemistry (D-IHC) assay to search for turkey coronavirus (TCoV) antigens in formalin-fixed embedded-paraffin tissues by the use of biotin-labeled polyclonal antibody. Twenty-eight-day-old embryonated turkey eggs (n = 50) were inoculated with TCoV-purified virus, and 3 d after inoculation, sections from ileum, ileum-cecal junction, and ceca were harvested, fixed in neutral formalin, and embedded in paraffin blocks and used as positive control. In addition, a total of 100 field samples from ileum, ileum-cecal junction, and ceca, collected from 30 to 45-d-old turkeys poults experiencing an outbreak of acute enteritis, were used to search for TCoV by the same D-IHC. All results were compared with those obtained by conventional RT-PCR and indirect fluorescent antibody assay (IFA) for all tested samples. Turkey coronavirus was detected in experimentally infected embryo tissues and also in field samples in 100% of ileum-cecal junction and ceca by the 3 detection procedures. With IFA as a reference assay, sensitivity and specificity of D-IHC were 98 and 58%, whereas sensitivity and specificity of reverse transcription-PCR were 96 and 66%, calculated from the total of tested samples from experimental infection. Each of the examined procedures was highly specific (D-IHC, 93%; RT-PCR, 90%), sensitive (D-IHC, 85%; RT-PCR, 86%), and agreement of both D-IHC and RT-PCR was 99 and 100%, respectively, compared with IFA results obtained from all the field samples. These findings demonstrated the utility of D-IHC for direct detection of TCoV from field samples and considering the sensitivity and specificity found here, can be used as an alternative technique.


Unveiling the antibacterial and antioxidant potential of Hedera helix leaf extracts: recent findings.
Hedera helix L., a member of the Araliaceae family, is a commonly known decorative plant with recognized medicinal activities. In this study, the ethanolic extract from H. helix leaves was investigated for its total polyphenolic and flavonoid contents, as well as its antioxidant and antibacterial properties. The aim was to evaluate its potential for controlling certain infections by screening its antibacterial activity against selected pathogenic bacteria. The total phenolic and flavonoid contents of the extract were determined using colorimetric methods. The antioxidant activity was assessed through two assay methods: the 1, 1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity and the reducing power ferric reducing/antioxidant power (FRAP). The antibacterial activity against different pathogenic bacteria, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa, was evaluated using the well diffusion method. The total phenolic and flavonoid contents of the H. helix extract were found to be 134.3 ± 4.9 mg gallic acid/g and 42.4 ± 3.6 mg catechin/g, respectively. The extract exhibited antioxidant activity, with a reducing power represented by an FRAP value of 9.5 ± 0.9 mmol Fe+2/g DW and a percentage inhibition of DPPH of 64.7 ± 3.8 at 80 µg/mL. The extract demonstrated antibacterial activity, inhibiting the growth of K. pneumoniae and S. aureus with zone of inhibition values of 18.5 and 23.2 mm, respectively, using 25 mg/well. However, E. coli and P. aeruginosa exhibited resistance to the extract. The findings of this study highlight the antibacterial and antioxidant properties of the ethanolic extract from H. helix leaves. The extract exhibited significant phenolic and flavonoid contents, as well as antioxidant activity. It also demonstrated antibacterial activity against selected pathogenic bacteria, suggesting its potential for controlling certain infections. Further research is warranted to identify the active compounds responsible for these activities and to explore their mechanisms of action.


Associations between negative affect and binge/purge behaviors in women with anorexia nervosa: Considering the role of negative urgency.
Evidence implicates negative affect in the occurrence of binge/purge behaviors, although the extent to which theoretically relevant individual difference variables may impact this association remains unclear. Negative urgency, the dispositional tendency to engage in rash action when experiencing negative affect, is a unique facet of impulsivity that may play a key role. Moreover, it was hypothesized that women with anorexia nervosa (AN) who are higher on measures of negative urgency, relative to those lower on negative urgency, would exhibit: 1) greater binge eating and purging frequencies on high negative affect days, and 2) a greater change in negative affect prior to and following binge eating and purging episodes. Women with AN (n=82) completed a self-report measure of negative urgency and a 2-week ecological momentary assessment protocol in which they recorded binge eating, purging, and negative affect ratings. Women with higher levels of negative urgency exhibited a greater frequency of binge eating and purging; however, in comparison to women low on negative urgency, they: 1) were more likely to binge eat on days corresponding with low-to-moderate negative affect (similar rates of binge eating were observed on high negative affect days), and 2) displayed substantially elevated levels of negative affect across time, and thus, smaller degrees of change in negative affect prior to and following binge eating and purging episodes. Negative urgency underlies individual differences in the daily experience of negative affect. Women with AN who are high on negative urgency may have an increased propensity for binge eating and purging via a relatively persistent and heightened state of negative emotions.


Facilitators and barriers in implementing the Minimum Initial Services Package (MISP) for reproductive health in Nepal post-earthquake.
Following the Nepal earthquake in April 2015, UNFPA estimated that 1.4 million women of reproductive age were affected, with approximately 93,000 pregnant and 28,000 at risk of sexual violence. A set of priority reproductive health (RH) actions, the Minimum Initial Services Package (MISP), was initiated by government, international and local actors. The purpose of this study was to identify the facilitators and barriers affecting the implementation of priority RH services in two districts. In September 2015, a mixed methods study design was used in Kathmandu and Sindhupalchowk districts to assess the implementation of the priority RH services five months post-earthquake. Data collection activities included 32 focus group discussions with male and female participants aged 18-49; 26 key informant interviews with RH, gender-based violence (GBV), and human immunodeficiency virus (HIV) experts; and 17 health facility assessments. The implementation of priority RH services was achieved in both districts. In Kathmandu implementation of emergency RH services started within days of the earthquake. Facilitating factors for successful implementation included disaster preparedness; leadership and commitment among national, international, and district level actors; resource mobilization; strong national level coordination; existing reproductive and child health services and community outreach programs; and supply chain management. Barriers included inadequate MISP training for RH coordinators and managers; weak communication between national and district level stakeholders; inadequate staffing; under-resourced and fewer facilities in rural areas; limited attention given to local GBV and HIV organizations; low availability of clinical management of rape services; and low awareness of GBV services and benefits of timely care. Ensuring RH is included in emergency preparedness and immediate response efforts and is continued through the transition to comprehensive care is critical for national governments and humanitarian response agencies. The MISP for RH remains a critical component of response efforts, and the humanitarian community should consider these learnings in future emergency response.


Streptomyces malaysiensis sp. nov., a new streptomycete species with rugose, ornamented spores.
The taxonomic position of a streptomycete strain isolated from Malaysian soil was established using a polyphasic approach. The organism, designated strain ATB-11T, was found to have chemical and morphological properties consistent with its classification in the genus Streptomyces. An almost complete 16S rRNA gene (rDNA) sequence determined for the test strain was compared with those of previously studied streptomycetes by using two treeing algorithms. The 16S rDNA sequence data not only supported classification of the strain in the genus Streptomyces but also showed that it formed a distinct phyletic line. At maturity, the aerial hyphae of strain ATB-11T differentiated into tight, spiral chains of rugose, cylindrical spores. The organism was readily distinguished from representatives of validly described Streptomyces species with rugose spores by using a combination of phenotypic features. It is proposed, therefore, that strain ATB-11T be classified in the genus Streptomyces as Streptomyces malaysiensis sp. nov.


Three-dimensional reconstruction and fractal geometric analysis of serrated adenoma.
Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 +/- 0.08 for SA, 1.23 +/- 0.07 for TA, and 1.28 +/- 0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.


Antimicrobial Activity and Action Approach of the Olive Oil Polyphenol Extract Against Listeria monocytogenes.
Olive oil polyphenol extract (OOPE) has been reported to have antibacterial activity; however, its effect on Listeria monocytogenes is less studied so far. This study, thus, aimed to reveal its antimicrobial activity and action approach against L. monocytogenes via evaluating the minimum inhibitory concentration (MIC) as well as the changes of intracellular adenosine 5'-triphosphate (ATP) concentration, cell membrane potential, bacterial protein, DNA, and cell morphology. The results showed that OOPE could inhibit the growth of L. monocytogenes with a measured MIC of 1.25 mg/ml. L. monocytogenes cells treated by OOPE showed significant reduction in intracellular ATP concentrations, bacterial protein, or DNA (p < 0.05), in comparison with those without any treatment. In addition, OOPE was observed to depolarize strain cells and alter cell morphology, resulting in damaged cell membrane and, thereby, leakage of cell fluid. These findings demonstrated that OOPE had inhibition on L. monocytogenes via its action on cells, suggesting its potential as a natural preservative.