Protective Impacts of Moringa oleifera Leaf Extract against Methotrexate-Induced Oxidative Stress and Apoptosis on Mouse Spleen.
The current study was aimed to examine the possible ameliorative impacts of MO leaf extract (MOLE) against MTX-induced alterations on oxidative stress of mouse spleen and explore the possible molecular mechanism that controls such impacts. Adult male mice were allocated into 4 groups: control, Moringa oleifera leaf extract (MOLE), MTX, and MOLE plus MTX. Mice received MOLE orally for a week before MTX injection and continued for 12 days. Serum and spleen were sampled for biochemical and quantitative gene expressions. As compared with the MTX-injected group, MOLE effectively reduced the changes in total proteins, spleen MDA, SOD and catalase activities, and changes in serum antioxidants levels. Moreover, there is downregulation of antioxidant genes (SOD and catalase) and antiapoptotic genes (XIAP and Bcl-xl) along with upregulation in Bax and caspase-3 mRNA (apoptotic genes) in the MTX-injected group. MTX induced changes in IL-1β, IL-6, TNF-α, and IL-10 expression. MOLE restored and ameliorated the changes induced in biochemical, antioxidants, apoptosis, and apoptosis associated genes that were induced by MTX intoxication. Current findings indicated that pretreatment with MOLE to MTX-intoxicated mice showed the potential usage of MO for oxidative stress and apoptosis treatment.


Comparative efficacy of chlorpromazine and meperidine with dimenhydrinate in migraine headache.
Approximately 20% of the population suffers from migraine headache, and a significant number develop "fixed" migraines, refractory to oral medications. Of this group, many become habitual narcotic users. A previously published case series using IV chlorpromazine suggested efficacy, so a randomized, double-blind, controlled trial was conducted. The study compared IV chlorpromazine against IV meperidine with dimenhydrinate. Entry criteria were emergency department patients from 18 to 60 years of age with a clinical diagnosis of common or classic migraine headache. After informed consent was obtained, an IV line with normal saline was established, and a bolus of 5 mL/kg was administered. Patients were randomized into two groups: chlorpromazine and meperidine with dimenhydrinate. The chlorpromazine group received a bolus injection of 5 mL normal saline placebo followed by 0.4 mL/kg chlorpromazine solution (0.1 mg/kg). The chlorpromazine was repeated every 15 minutes as needed up to a total of three doses. The meperidine with dimenhydrinate group received 5 mL dimenhydrinate solution (25 mg) followed by 0.04 mL/kg meperidine (0.4 mg/kg). Again, the meperidine solution was repeated in the same dosage every 15 minutes as needed up to a total of three doses. If response was inadequate 15 minutes after the third dose, the sequence was broken, and the other medication given. Blood pressure and response were assessed at 15-minute intervals for one hour. Pain was assessed by both visual and verbal analogue scales every 15 minutes. In all, 46 patients were entered in the study (24 chlorpromazine and 22 meperidine with dimenhydrinate).(ABSTRACT TRUNCATED AT 250 WORDS)


Integrating care for non-communicable diseases into routine HIV services: key considerations for policy design in sub-Saharan Africa.
There is great interest for integrating care for non-communicable diseases (NCDs) into routine HIV services in sub-Saharan Africa (SSA) due to the steady rise of the number of people who are ageing with HIV. Suggested health system approaches for intervening on these comorbidities have mostly been normative, with little actionable guidance on implementation, and on the practical, economic and ethical considerations of favouring people living with HIV (PLHIV) versus targeting the general population. We summarize opportunities and challenges related to leveraging HIV treatment platforms to address NCDs among PLHIV. We emphasize key considerations that can guide integrated care in SSA and point to possible interventions for implementation. Integrating care offers an opportunity for effective delivery of NCD services to PLHIV, but may be viewed to unfairly ignore the larger number of NCD cases in the general population. Integration can also help maintain the substantial health and economic benefits that have been achieved by the global HIV/AIDS response. Implementing interventions for integrated care will require assessing the prevalence of common NCDs among PLHIV, which can be achieved via increased screening during routine HIV care. Successful integration will also necessitate earmarking funds for NCD interventions in national budgets. An expanded agenda for addressing HIV-NCD comorbidities in SSA may require adding selected NCDs to conditions that are routinely monitored in PLHIV. Attention should be given to mitigating potential tradeoffs in the quality of HIV services that may result from the extra responsibilities borne by HIV health workers. Integrated care will more likely be effective in the context of concurrent health system reforms that address NCDs in the general population, and with synergies with other HIV investments that have been used to strengthen health systems.


The sensitivity of phage DNA and plasmid DNA for a restriction enzyme for Staphylococcus aureus.
In Staphylococcus aureus transduction of different tetracycline and chloramphenicol plasmids with a group I/III modification was possible to group I and III strains. Group II strains, containing a restriction endonuclease, had a restriction both for the phage and the plasmids: two restriction-deficient group II strains were good acceptors for these plasmids.


A monoclonal antibody recognizes an O-acylated sialic acid in a human melanoma-associated ganglioside.
Monoclonal antibody D1.1 originally prepared against the B49 cell line derived from a rat brain tumor was shown to react with a ganglioside present in fetal rat brain. We have found that this antigen is also present in human malignant melanoma tumors as well as many melanoma cell lines. The ganglioside from human melanoma cell lines migrates between GM1 and GM2 on one-dimensional thin layer chromatography. Analysis by two-dimensional thin layer chromatography with intermediate ammonia treatment suggests that the ganglioside contains one or more base-labile O-acyl esters. Mild base hydrolysis under conditions known to remove O-acyl esters results in complete loss of antigenic reactivity. Thus, the alkali-labile moiety is a critical component of the epitope recognized by the antibody. Analysis of the sialic acids of total gangliosides from [6-3H]glucosamine-labeled melanoma cells showed that approximately 10% of these molecules are O-acylated. Similar analysis of the purified ganglioside showed that greater than 30% of the sialic acids comigrated with authentic 9-O-acetyl-N-acetylneuraminic acid. The antibody did not cross-react with normal human skin melanocytes nor with any of a large number of normal human adult and fetal tissues. The antibody also did not react with numerous other malignant cell lines studied. These findings suggest that the antigenic epitope defined by antibody D1.1 contains an O-acylated sialic acid and may arise from aberrant O-acetylation occurring in human malignant melanoma cells.


Wnt activation downregulates olfactomedin-1 in Fallopian tubal epithelial cells: a microenvironment predisposed to tubal ectopic pregnancy.
Ectopic pregnancy (EP) occurs when the embryo fails to transit to the uterus and attach to the luminal epithelium of the Fallopian tube (FT). Tubal EP is a common gynecological emergency and more than 95% of EP occurs in the ampullary region of the FT. In humans, Wnt activation and downregulation of olfactomedin-1 (Olfm-1) occur in the receptive endometrium and coincided with embryo implantation in vivo. Whether similar molecular changes happen in the FT leading to EP remains unclear. We hypothesized that activation of Wnt signaling downregulates Olfm-1 expression predisposes to EP. We investigated the spatiotemporal expression of Olfm-1 in FT from non-pregnant women and women with EP, and used a novel trophoblastic spheroid (embryo surrogate)-FT epithelial cell co-culture model (JAr and OE-E6/E7 cells) to study the role of Olfm-1 on spheroid attachment. Olfm-1 mRNA expression in the ampullary region of non-pregnant FT was higher (P<0.05) in the follicular phase than in the luteal phase. Ampullary tubal Olfm-1 expression was lower in FT from women with EP compared to normal controls at the luteal phase (histological scoring (H-SCORE)=1.3±0.2 vs 2.4±0.5; P<0.05). Treatment of OE-E6/E7 with recombinant Olfm-1 (0.2-5 μg/ml) suppressed spheroid attachment to OE-E6/E7 cells, while activation of Wnt-signaling pathway by Wnt3a or LiCl reduced endogenous Olfm-1 expression and increased spheroid attachment. Conversely, suppression of Olfm-1 expression by RNAi increased spheroid attachment to OE-E6/E7 cells. Taken together, Wnt activation suppresses Olfm-1 expression, and this may predispose a favorable microenvironment of the retained embryo in the FT, leading to EP in humans.


Functional analysis of the essential GTP-binding-protein-coding gene cgtA of Vibrio cholerae.
The cgtA gene, coding for the conserved G protein CgtA, is essential in bacteria. In contrast to a previous report, here we show by using genetic analysis that cgtA is essential in Vibrio cholerae even in a Delta relA background. Depletion of CgtA affected the growth of V. cholerae and rendered the cells highly sensitive to the replication inhibitor hydroxyurea. Overexpression of V. cholerae CgtA caused distinct elongation of Escherichia coli cells. Deletion analysis indicated that the C-terminal end of CgtA plays a critical role in its proper function.


Radionuclide bone imaging findings in recurrent calvarial infarction in sickle cell disease.
A patient with sickle cell disease developed bi-parietal calvarial infarctions, and subsequently developed bi-frontal calvarial infarctions. The findings on [99mTc]MDP bone imaging showed decreased activity in the parietal and frontal regions during the phase of acute infarction and increased activity in the parietal region during the later healing phase. Thus the findings on radionuclide bone imaging in cortical infarcts will depend upon the stage of the condition.


A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity.
Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8+ T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.


Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement.
This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility, along with the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis available through the USPSTF Web site (http://www.preventiveservices.ahrq.gov). The recommendation is also posted on the Web site of the National Guideline Clearinghouse (http://www.guideline.gov).


Down-regulation of fast-twitch skeletal muscle fiber with cardiac troponin-C and recombinant mutants. Structure/function studies with site-directed mutagenesis.
Structure/function relationships in troponin C are studied with vertebrate fast-twitch fibers by exchanging the skeletal troponin C with two bacterially synthesized recombinant proteins designed by site-directed mutagenesis of cardiac troponin C. One mutant (CBM1) contained an additional active site, by deleting Val-28 and converting Leu-29, Gly-30, Ala-31 and Glu-32 to Asp, Ala, Asp and Gly, respectively, in the normally inactive trigger site 1 in the N-terminus. In another mutant (CBM2A), the normally active site 2 was inactivated by conversion of Asp-65 to Ala. The fibers were found to be down-regulated with recombinant cardiac troponin C (CTnC3), as with tissue-cardiac-troponin-C. With mutants, in one case (CBM1) the regulation was unmodified despite Ca2+ coordination by all sites. In contrast, regulation was found to be completely blocked with the mutant (CBM2A) where both trigger sites were inactive. The results provide the first indication that structural specification of the entire EF-hand motif of site 1, and not just Ca2+ coordination, is needed to operate fully the Ca2+ switch in fast-twitch fibers.


Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations.
Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy.


Economic burden of torture for a refugee host country: development of a model and presentation of a country case study.
Torture is an important social and political problem worldwide that affects millions of people. Many host countries give victims of torture the status of refugee and take care of them as far as basic needs; health care, professional reinsertion, and education. Little is known about the costs of torture. However, this knowledge could serve as an additional argument for the prevention and social mobilization to fight against torture and to provide a powerful basis of advocacy for rehabilitation programs and judiciary claims. Development of a model for estimating the economic costs of torture and applying the model to a specific country. The estimation of the possible prevalence of victims of torture was based on a review of the literature. The identification of the socioeconomic factors to be considered was done by analogy with various health problems. The estimation of the loss of the productivity and of the economic burden of disease related to torture was done through the human capital approach and the component technique analysis. The model was applied to the situation in Switzerland of estimated torture victims Switzerland is confronted with. When applied to the case study, the direct costs - such as housing, food, and clothing - represent roughly 130 million Swiss francs (CHF) per year; whereas, health care costs amount to 16 million CHF per year, and the costs related to education of young people to 34 million CHF per year. Indirect costs, namely those costs related to the loss of the productivity of direct survivors of torture, have been estimated to one-third of 1 billion CHF per year. This jumps to 10,073,419,200 CHF in the loss of productivity if one would consider 30 years of loss per survivor. Our study shows that a rough estimation of the costs related to torture is possible with some prerequisites, such as access to social and economic indicators at the country level.


Construction and application of a novel library: Fourier transform infrared wavelet coefficients library.
This article aims at designing a wavelet alternative to Fourier transform infrared spectra (FTIR). In order to select the most suitable wavelet parameters to perform, several decomposition levels and 53 wavelets were tested by trial and error approach, respectively. The result indicated that discrete meyer wavelet (dmey) associated with its third decomposition level was very efficient for this purpose. On the base of it, a novel library named as Fourier transform infrared wavelet coefficients library (FTIR-WC) has been constructed. Finally, two tools such as library search and structure elucidation were developed to evaluate the capability of the new library system. The results obtained were also compared with those from FTIR library by a variety of indices. The results suggested that the new library performed better but with less volume. This work is expected to propose a novel and practical strategy in infrared spectroscopic analysis.


Sorption of ionic liquids in soil enriched with polystyrene microplastic reveals independent behavior of cations and anions.
Recently, much attention has been focused on the application of the Ionic Liquids (ILs) with herbicidal activity in agriculture. It has been suggested that through the appropriate selection of cations and anions, one can adjust the properties of ILs, particularly the hydrophobicity, solubility, bioavailability, toxicity. In practical agricultural conditions, it will be beneficial to reduce the mobility of herbicidal anions, such as the commonly applied 2,4-dichlorophenoxyacetic acid [2,4-D] in the soil. Furthermore, microplastics are becoming increasingly prevalent in the soil, potentially stimulating herbicidal sorption. Therefore, we investigated whether cations in ILs influence the mobility of anions in OECD soil supplemented with polystyrene microplastic (PS). For this purpose, we used the 2,4-D based ILs consisting of: a hydrophilic choline cation [Chol][2,4-D] and a hydrophobic choline cation with a C12chain [C12Chol][2,4-D]. Characterization of selected micropolystyrene was carried out using the BET sorption-desorption isotherm, particle size distribution and changes in soil sorption parameters such as soil sorption capacity and cation exchange capacity. Based on the batch sorption experiment, the effect of microplastic on the sorption of individual cations and anions in soil contaminated with micropolystyrene was evaluated. The results obtained indicate that the introduction of a 1-10% (w/w) PS resulted in an 18-23% increase of the soil sorption capacity. However, the sorption of both ILs' cations increased only by 3-5%. No sorption of the [2,4-D] anion was noted. This suggests that cations and anions forming ILs, behave independently of each other in the environment. The results indicate the fact that ILs upon introduction into the environment are not a new type of emerging contaminant, but rather a typical mixture of ions. It is worth noting that when analyzing the behavior of ILs in the environment, it is necessary to follow the fate of both cations and anions.


Evaluation of a pilot school health education program for asthmatic children.
A pilot program was conducted and evaluated as a part of the development of a health education program designed to meet the needs of a specified target population. By focusing on a group of children with a common chronic health problem, it was possible to measure specific variables to evaluate the effectiveness of the program. Outcome evaluation together with subjective process information resulted in modification and changes in the program prior to implementation with a larger number of children and schools. The pilot phase conducted with a small number of children was demonstrated to be a critical part of the overall program development.


18F-FDG PET/computed tomography may predict the outcome of newly diagnosed indolent non-Hodgkin lymphoma in patients managed with initial 'watch-and-wait' approach.
The aim of this study was to investigate the role of F-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) in the outcome of non-Hodgkin lymphoma (NHL) in patients managed with initial 'watch-and-wait' treatment. Sixteen patients with newly diagnosed NHL treated with initial watchful waiting were retrospectively recruited. They had a baseline F-FDG PET/CT and at least one follow-up PET/CT. The standard uptake values (SUV), metabolic tumor volume (MTV) and total lesions glycolysis (TLG) of lymphoma were measured in PET/CT. They were followed up for at least 2 years or until disease progression. The endpoint was the time to initiation of lymphoma treatment (TLT). Comparing the baseline and the follow-up PET/CT, four out of 16 patients showed spontaneous regression of lymphoma, three of the 16 patients had stable disease and the remaining nine of the 16 patients had progressive disease in the follow-up PET/CT. After a median follow-up of 32 months (range 14-90 months), 10/16 patients had progressive disease and chemotherapy was initiated. The median TLT was 21.0 months. In univariate analysis, MTV and TLG in baseline PET/CT were significant to predict TLT. Kaplan-Meier curves showed a statistical difference for TLT in the two groups of patients stratified by MTV or TLG at baseline (median TLT, 66.0 months vs. 12.0 months, P = 0.007). However, patients' age, Ann Arbor staging, International Prognostic Index and SUVmax were not significant. A proportion of patients with NHL might experience spontaneous regression of lymphoma. F-FDG PET/CT turned out as a prognostic factor for TLT in patients with NHL under watchful waiting.


Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans.
Trauma-related nightmares are highly prevalent among veterans and are associated with higher-severity insomnia and posttraumatic stress disorder. Cognitive behavioral therapy for insomnia (typically 6-8 sessions) has been shown to reduce trauma-related nightmares. Brief behavioral treatment for insomnia (BBTI, 4 sessions) has been found to be comparable to CBT-I in decreasing insomnia severity; however, the effects of BBTI on nightmares have not been investigated. The current study tested the effects of BBTI on both trauma-related nightmares and nontrauma-related bad dreams using an active control group treated using progressive muscle relaxation therapy. In addition, we tested whether baseline trauma-related nightmare frequency and baseline nontrauma-related bad dream frequency moderated changes in insomnia severity. Participants were 91 military veterans with insomnia disorder randomized to BBTI or progressive muscle relaxation therapy. Participants reported insomnia severity on the Insomnia Severity Index and reported trauma-related nightmare frequency and nontrauma-related bad dream frequency on the Pittsburgh Sleep Quality Index-PTSD Addendum. We found that BBTI significantly reduced trauma-related nightmares from baseline to posttreatment, whereas progressive muscle relaxation therapy did not. However, reductions in trauma-related nightmares were not maintained at the 6-month follow up. Neither BBTI nor progressive muscle relaxation therapy reduced nontrauma-related bad dreams from baseline to posttreatment. We also found that neither baseline trauma-related nightmare frequency nor baseline nontrauma-related bad dream frequency moderated changes in insomnia symptom severity. Findings from the current study suggest that BBTI may help reduce trauma-related nightmares. Further research is needed to better understand the potential mechanisms underlying how improved sleep may reduce trauma-related nightmares. Registry: ClinicalTrials.gov; Name: Brief Behavioral Insomnia Treatment Study (BBTI); URL: https://clinicaltrials.gov/ct2/show/NCT02571452; Identifier: NCT02571452. Ranney RM, Gloria R, Metzler TJ, Huggins J, Neylan TC, Maguen S. Brief behavioral treatment for insomnia decreases trauma-related nightmare frequency in veterans. J Clin Sleep Med. 2022:18(7):1831-1839.


Distribution, abundance and diversity of the extremely halophilic bacterium Salinibacter ruber.
Since its discovery in 1998, representatives of the extremely halophilic bacterium Salinibacter ruber have been found in many hypersaline environments across the world, including coastal and solar salterns and solar lakes. Here, we review the available information about the distribution, abundance and diversity of this member of the Bacteroidetes.


Association of secondary prevention medication use after myocardial infarction with mortality in hemodialysis patients.
Mortality after myocardial infarction (MI) among patients undergoing dialysis is high. However, studies investigating the use of secondary prevention medications after MI and clinical outcomes in dialysis patients are lacking. This study aimed to examine the association of the number of guideline-recommended medications (antiplatelets, β-blockers, statins and renin-angiotensin-aldosterone system inhibitors) with all-cause mortality after MI in hemodialysis (HD) patients. We conducted a nationwide cohort study of incident HD patients who were admitted for MI between 1 January 2010 and 31 December 2014 and were followed up until 31 December 2015, using Taiwan's national health insurance research database. Of 1471 patients (mean age 68 years, 41.9% women) included in the analysis, 281 (19.1%) were treated with one cardioprotective medication, 406 (27.6%) with two, 490 (33.3%) with three and 294 (20%) with four. During a median follow-up of 1.0 years, 458 (31.1%) patients died. In a multivariable Cox model, each additional use of guideline-recommended therapies was associated with a significant 12% reduction in the risk of mortality {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.80-0.97]}. Similar results were obtained in the analysis with the inverse probability of treatment weighting [HR 0.84 (95% CI 0.77-0.92)] and in the propensity score-matched subcohort [HR 0.87 (95% CI 0.77-0.98)]. The decreased mortality risk was consistently observed across all subgroups. The use of more evidence-based medications for secondary prevention after MI was associated with a lower risk of all-cause mortality in HD patients.


Theoretical Insights into the Solubility Polarity Switch of Metal-Organic Nanoclusters for Nanoscale Patterning.
Metal-organic nanoclusters(MOCs) are being increasingly used as prospective photoresist candidates for advanced nanoscale lithography technologies. However, insight into the irradiation-induced solubility switching process remains unclear. Hereby, the theoretical study employing density functional theory (DFT) calculations of the alkene-containing zirconium oxide MOC photoresists is reported, which is rationally synthesized accordingly, to disclose the mechanism of the nanoscale patterning driven by the switch of solubility from the acid-catalyzed or electron-triggered ligand dissociation. By evaluating the dependence of MOCs' imaging process on photoacid, lithographies of photoresists with and without photoacid generators after exposure to ultraviolet (UV), electron beam, and soft X-ray, it is revealed that photoacid is essential in UV lithography, but it demonstrates little effect on exposure dose in high-energy lithography. Furthermore, theoretical studies using DFT simulations to investigate the plausible photoacid-catalyzed, electron-triggered dissociation, and accompanying radical reaction are performed, and a mechanism is demonstrated that the nanoscale patterning of this type of MOCs is driven by the solubility switch resulting from dissociation-induced strong electrostatic interaction and low-energy barrier radical polymerization with other species. This study can give insights into the chemical mechanisms of patterning, and guide the rational design of photoresists to realize high resolution and high sensitivity.


Thrombotic Microangiopathy in Interferon-beta-Treated Multiple Sclerosis Patient.
A 43-year-old man who was treated with interferon-beta for multiple sclerosis was presented with hypertension, headache, nausea/vomiting, blurred vision, and renal dysfunction. The treatment with drugs and dialysis relieved the symptoms. Despite plasmapheresis is known to cause improvement in renal function, no such improvement was seen in patient.


A further step in the evolution of rabbit hemorrhagic disease virus: the appearance of the first consistent antigenic variant.
Rabbit hemorrhagic disease virus (RHDV) is a noncultivable calicivirus that infects rabbits (Oryctolagus cuniculus) and causes epidemics of an acute fatal hepatitis. In 1997 we identified two RHDV isolates from geographically distant Italian regions, which differed antigenically from the reference strain RHDV.Bs89. In fact, they were not reactive with mAb 1H8, that is able to protect rabbits from RHD and showed a low reactivity with the rabbit convalescent serum raised against RHDV.Bs89. Experimental infection of rabbits with either RHDV isolates confirmed their high pathogenicity and their peculiar antigenic profile; nevertheless, rabbits vaccinated with the current vaccine were protected against challenge infection with these isolates. Sequence comparison definitely demonstrated that the two isolates originated from the same RHDV variant and that the similarity of their structural protein (VP60) sequences with the RHDV.Bs89 is equal to 93%. This variant was named RHDVa since shows consistent genetic and antigenic differences from the wild-type RHDV. In particular, 44% of amino acid substitutions in RHDVa VP60 were located between amino acids 344 and 370, where the similarity with RHDV.Bs89 drops to 70%, suggesting that this region probably contains the epitope recognized by mAb 1H8. In addition, this paper presents preliminary data concerning the amino acids of VP60 involved in the hemagglutination site of the virus.


Pituitary and adrenal response to ovine corticotropin-releasing hormone in women with polycystic ovarian syndrome.
It has been hypothesized that there is an adrenal abnormality in the polycystic ovary syndrome (PCO). This study was undertaken to examine this hypothesis in a more physiological way, by enhancing the ACTH secretion in response to ovine corticotropin releasing hormone (oCRH) injection so that adrenal androgen and glucocorticoid responsiveness to endogenous stimulation could be examined. Plasma ACTH and the ACTH and cortisol (F) response to oCRH were normal. The plasma T and dehydroepiandrosterone (DHEA) responses were also normal. The androstenedione (A) response, however, was exaggerated. This study supports the hypothesis that the adrenal gland in patients with PCO produces increased amounts of androstenedione in response to ACTH stimulation.


Enhancing fitness, enjoyment, and physical self-efficacy in primary school children: a DEDIPAC naturalistic study.
Physical activity (PA) (e.g., sport, physical education) promotes the psychophysical development of children, enhances health and wellbeing, offers opportunities for enjoyable experiences, and increases self-efficacy. In the DEDIPAC framework, we conducted a naturalistic, cross-sectional study to evaluate the effects of a school-based, long-term intervention on fitness (i.e., cardiovascular endurance, muscular strength, flexibility, speed, and finger dexterity), body mass index (BMI), PA levels, sedentary levels, enjoyment, and physical self-efficacy in primary school children. A group of Italian children (41 boys and 39 girls, aged 10-11 years) involved in the project-named "Più Sport @ Scuola" (PS@S)-was compared with a group of children (41 boys and 39 girls) of the same age not involved in the project. After a four-year long attendance to the PS@S project, participants reported higher scores of cardiovascular endurance, muscular strength, enjoyment, and physical self-efficacy compared to children not involved in the project. Correlation analysis results showed that muscular strength scores correlated positively with BMI, PA levels, and enjoyment. Flexibility of the upper body was positively related to physical self-efficacy, and negatively related to speed and BMI. Findings suggest that the PS@S project enhanced fitness level, enjoyment, and physical self-efficacy of children.


Revealing the impact of China's clean air policies on synergetic control of CO2 and air pollutant emissions: Evidence from Chinese cities.
China is presently confronted with the intricate challenge of simultaneously mitigating air pollution and decelerating the pace of climate change. An integrated perspective to investigate the synergetic control of CO2 and air pollutant emissions is in an urgent need. Using data for 284 Chinese cities from 2009 to 2017, we introduced an indicator called coupling and coordination degree of CO2 and air pollutant emissions control (CCD) and found an upward and spatial agglomeration trend of CCD distribution during the research period. Then, this study posed a specific focus on the impact of China's Air Pollution Prevention and Control Action Plan (APPCAP). The DID model revealed that implementation of the APPCAP resulted in a 4.0% increase in CCD for cities with special emission limits, attributed to industrial structural adjustments and the promotion of technology innovation. Furthermore, we also identified positive spillover effects of the APPCAP on neighboring control group cities situated within 350 km of the treatment group cities, providing an explanation for the spatial agglomeration trend observed in CCD distribution. These findings hold significant implications for the synergetic control in China and underscored the potential benefits of industrial structural adjustments and technology innovation in mitigating environmental pollution.


A multi-perspective approach to developing the Saudi Health Informatics Competency Framework.
Determining the key sets of competencies necessary for a Health Informatics (HI) professional to practice effectively either solo or as a member of a multidisciplinary team has been challenging for the regulator and registration body responsible for the healthcare workforce in Saudi Arabia, which is the Saudi Commission for Health Specialties (SCFHS). The aim of this study was to develop a HI competency framework to guide SCFHS to introduce a HI certification program that meets local healthcare needs and is aligned with the national digital health transformation strategy. A two-phase mixed methods approach was used in this study. For phase 1, a scoping review was conducted to identify HI competencies that have been published in the relevant literature. Out of a total 116 articles found relevant, 20 were included for further analysis. For phase 2, Saudi HI stakeholders (N = 24) that included HI professionals, administrators, academics, and healthcare professionals were identified and participated in an online survey, and asked to rank the importance of HI competencies distinguished in phase 1. To further validate and contextualize the competency framework, multiple focus groups and expert panel meetings were undertaken with the key stakeholders. For phase 1, about 1315 competencies were initially extracted from the included studies. After iterative reviews and refinements of codes and themes, 6 preliminary domains, 23 sub-domains and 152 competencies were identified. In phase 2, a total of 24 experts participated in the online surveys and ranked 58 out of 152 competencies as 'very important/required', each received 75 % or more of votes. The remaining competencies (N = 94) were included in a list for a further discussion in the focus groups. A Total of fourteen HI experts accepted and joined in the focus groups. The multiphase approach resulted in a competency framework that included 92 competencies, that were grouped into 6 domains and 22 subdomains. The six key domains are: Core Principles; Information and Communication Technology (ICT); Health Sciences; Health Data Analytics; Education and Research; Leadership and Management. The study developed the Saudi Health Informatics Competency Framework (SHICF) that is based on an iterative, evidence-based approach, with validation from key stakeholders. Future work should continue the validation, review, and development of the framework with continued collaboration from relevant stakeholders representing both the healthcare and educational communities. We anticipate that this work will be expanded and adopted by relative professional and scientific bodies in the Gulf Cooperation Council (GCC) region.


A pharmacological comparison of 3-methoxy-4,5-methylenedioxyamphetamine and LSD in the dog.
3-Methoxy-4,5-methylenedioxyamphetamine (MMDA), which has been reported to have hallucinogenic actions in man, was compared to LSD in single dose, antagonist interaction, cross-tolerance and appetite suppression studie in the dog. In single doses, MMDA partially resembled LSD: both facilitated the flexor reflex and produced tachypnea, hyperthermia, and analgesia; however, MMDA had greater activity than LSD in producing mydriasis. Only LSD consistently elicited the stepping reflex and produced tachycardia. In both the interaction studies and cross-tolerance studies in LSD-tolerant dogs the effects of MMDA were generally not like those of LSD, except for its spinal cord facilitatory effect. Cyproheptadine antagonized most of the effects of LSD but only the facilitatory effect of MMDA on the flexor reflex. On the other hand, phenoxybenzamine antagonized the mydriasis, analgesia, and hyperthermia caused by MMDA but not LSD. Cross-tolerance to MMDA developed only to its effects on the flexor and skin twitch reflexes. In intact dogs, the anorexigenic potency of MMDA was 16 times less than that of d-amphetamine. It is concluded that MMDA has primarily amphetamine-like activity with some LSD-like actions.


Circulating miRNAs in Breast Cancer Diagnosis and Prognosis.
Great improvement has been made in the diagnosis and therapy of breast cancer patients. However, the identification of biomarkers for early diagnosis, prognosis, therapy assessment and monitoring, including drug resistance and the early detection of micro-metastases, is still lacking. Recently, circulating microRNAs (miRNAs), circulating freely in the blood stream or entrapped in extracellular vesicles (EVs), have been shown to have a potential diagnostic, prognostic or predictive power. In this review, recent findings are summarized, both at a preclinical and clinical level, related to miRNA applicability in the context of breast cancer. Different aspects, including clinical and technical challenges, are discussed, describing the potentialities of miRNA use in breast cancer. Even though more methodological standardized studies conducted in larger and selected patient cohorts are needed to support the effective clinical utility of miRNA as biomarkers, they could represent novel and accessible tools to be transferred into clinical practice.


Liver transplantation at a university hospital, faculty of the medicine of Ribeirão Preto, University of São Paulo: results for the first 60 recipients.
The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.


Group and phase velocity coupling of colliding pulses in a nanostructure.
It is generally accepted that, in a laser cavity, the group delay--responsible for the round trip time--and the phase delay both have a linear dependence on the cavity length. We show that nanostructures, such as quantum wells, can create a coupling between phase and group velocities, resulting in a periodic dependence of the repetition rate on the laser cavity length.


Securing sustainable price levels of innovative anticancer drugs: How to move forward?
Novel cancer treatments come with high price tags that compromise access to treatment and the sustainability of healthcare systems. Innovative policies are needed to reach a system that balances innovation and reasonable prices. However, structured approaches to explore, test, and compare innovative proposals are lacking. We surveyed experts to evaluate seven promising proposals to reduce drug prices: Transparency, Combined European purchasing, Public drug development, Public clinical trials, Two-part-pricing, Orphan drug reform, and De-linkage. Experts were asked to rank proposals, identify main risk and success factors, and to reflect on missing proposals. The survey was distributed via the networks of the European Cancer League and the Organisation of European Cancer Institutes. Respondents (n = 41) originated from 19 European countries and included stakeholders in health economics, law, medicine, drug discovery, and healthcare policy.Transparency (M = 2; SD = 2 1) and Combined purchasing (M = 3; SD = 1 9) were ranked as the most promising proposals, Two-part pricing (M = 5; SD = 2 3) and De-linkage (M = 6; SD = 2 4) were considered as the most controversial. Main risk categories were a negative impact on R&D (n = 47), technical feasibility (n = 38), and reduced access to medicines (n = 33). Main success categories were international collaboration (n = 34) and agreement of pricing mechanisms (n = 25). Experts considered value assessment and strengthening of the competitive market as additional proposals for further analysis. We recommend expanding on these results to further specify actionable policies that can be tested. Pilots should consider uncertainties and conducted with a focus on international collaboration, preferably in cooperation with the pharmaceutical industry.


Plasmid profile analysis of Salmonella ser. Typhimurium phage untypable strains encountered in diverse geographic regions of India.
Plasmid profile analysis and antibiotic resistance pattern determination were carried out for 117 phage untypable S. Typhimurium strains. Majority of the strains (82%) were resistant to all the seven antibiotics tested, R-pattern being ApCmKmSmSuTcTp, rest (12%) showed heterogenous R-patterns. Plasmid DNA analysis revealed phage untypable strains to harbour large (58.8-114.3 MDal), intermediate size (36 MDal, 42 MDal) and small (1.8-5.2 MDal) plasmids with varying molecular weights. All the phage untypable strains could be subgrouped by plasmid profile analysis into 23 plasmid patterns. Plasmid profile analysis could discriminate large number of phage untypable strains on the basis of their plasmid pattern.


UBQLN2 mutations are not a frequent cause of amyotrophic lateral sclerosis in Ireland.
Mutations in UBQLN2 have been shown to be a cause of dominant X-linked amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary across ALS populations. We screened UBQLN2 for mutations in a final cohort of 150 Irish ALS patients. Individuals who were from families with male-to-male transmission or who carried pathogenic hexanucleotide repeat expansions in C9orf72 were excluded. Apart from common synonymous variation, no sequence variants in UBQLN2 were observed. Mutations in UBQLN2 are therefore not a frequent cause of ALS in the Irish population.


The association between the obesogenic environment and 6-month and 24-month weight change in a rural weight loss intervention trial in the United States.
The unique obesogenic environment may influence the ability to effectively maintain weight loss in rural areas. The aim of this study was to examine the contextual relationship of neighborhood disadvantage, distance to supermarkets and supercenters, and fast food, dollar store, and exercise facility environments on weight loss following a weight-loss intervention in the United States. This analysis (n = 1177) linked weight loss outcomes from a rural, primary care-based randomized controlled trial to contextual data collected from residential addresses. Outcomes include 6-month and 24-month percent weight loss. These outcomes were compared across contextual variables, including tract level disadvantage, food accessibility, and food/exercise availability. Covariates were included in ordinary least squares (OLS) multivariable regression models for 6-month and 24-month weight loss measures, across three weight loss interventions. Contextual variables were not significantly related to percent weight loss overall across treatment arms. Participants living in a 5-mile buffer to dollar stores experienced approximately a 2% (p < 0.05) lower weight loss, but only in the least effective counseling arm (individual clinic visits), while controlling for both individual and contextual factors. Our results suggest that specific contextual variables in rural populations may play an important role in moderating weight loss outcomes especially under the conditions of less effective interventions.


Epidermal Growth Factor Receptor, Excision-Repair Cross-Complementation Group 1 Protein, and Thymidylate Synthase Expression in Penile Cancer.
To describe the expression of tissue epidermal growth factor receptor (EGFR), excision-repair cross-complementation group 1 protein (ERCC1), and thymidylate synthase (TS) in patients with penile cancer and explore their association with stage and outcome. A total of 52 patients with penile squamous cell cancer who were treated at the University of Southern California from 1995 to 2010 were identified. Paraffin-embedded tissue underwent mRNA quantitation and immunohistochemistry for expression of EGFR, ERCC1, and TS. KRAS mutations were evaluated using polymerase chain reaction-based sequencing. EGFR overexpression was common by mRNA (median, 5.09; range, 1.92-104.5) and immunohistochemistry. EGFR expression > 7 was associated with advanced stage and poor differentiation (P = .01 and .034 respectively) but not with survival in multivariate analysis. ERCC1 mRNA expression was a median of 0.65 (range, 0.21-1.87). TS expression was a median of 1.88 (range, 0.54-6.47). ERCC1 and TS expression were not associated with grade, stage, or survival. There were no KRAS mutations identified. A total of 17 men received chemotherapy; 8 (47%) had an objective response, including 1 with a pathologic complete response. There was a trend for lower expression of EGFR corresponding to a higher likelihood of response (response rate [RR]) to chemotherapy: 67% RR in EGFR mRNA < 7 versus 33% RR in EGFR > 7 (P = .31). High expression of EGFR mRNA in squamous cell carcinoma of the penis is associated with advanced stage and poor differentiation, but not survival. In our small heterogeneous subset, molecular marker expression did not show a correlation with the likelihood of chemotherapy response. A prospective evaluation of the role of the EGFR pathway and its regulatory environment in penile cancer is warranted. Given the rarity of this cancer, collaborative prospective cohort evaluations and trials need to be encouraged.


Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis.
Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.


[Erratum to: Histopathological findings following SARS-CoV-2 infection with and without treatment-Report of three autopsies].
[This corrects the article DOI: 10.1007/s00194-020-00408-x.].


Adaptation and validation of the Van Rie tuberculosis stigma scale in Vietnam.
Tuberculosis (TB) stigma contributes to diagnostic delay, disease concealment, and reduced wellbeing for affected individuals. Despite the availability of several TB stigma scales, most high-TB burden countries do not have a culturally validated version available. This study evaluated the Van Rie TB stigma scale (VTSS) among people with TB in Vietnam. This study consisted of two phases. In phase 1, the VTSS was culturally and linguistically adapted to the Vietnamese context. In phase 2, people with TB were invited to complete a survey containing the VTSS, a depression scale, and a quality of life scale. The data analysis included confirmatory factor analysis (CFA), exploratory factor analysis (EFA), construct validity, and floor or ceiling effects. In phase 1, items were reworded from the third person to the first person. The TB/HIV co-infection items (items 7 and 11) were the least relevant for people with TB (62% and 73% relevance, respectively). In phase 2, the CFA demonstrated adequate goodness-of-fit indices (GFI = 0.88, CFI = 0.96, RMSEA = 0.058); however several of the item factor loadings were low. The EFA demonstrated good internal consistency (α = 0.85) and revealed one dominant factor. Construct validity was low. The VTSS demonstrated good psychometric properties in Vietnam. Depending on the purpose of the scale, the HIV co-infection items and item 10 could be considered for removal.


On the wavelet-based compressibility of continuous-time sampled ECG signal for e-health applications.
This paper presents a compression study of electrocardiogram (ECG) signals for e-Health cardiac online diagnostic systems. The study uses 75 real electrocardiogram records sampled with continuous-time level-crossing (LC) analog-to-digital converter (ADC). This signal-dependent LC-ADC compresses signals compared to conventional ADC but further compression is needed especially for long-time monitoring applications. The orthogonal matching pursuit algorithm is simulated to evaluate ECG compression with 54 orthogonal and biorthogonal wavelets. For LC-ADC amplitude output compression, Biorthogonal3.1 (bior3.1) wavelet achieves optimal performances in terms of compression ratio (CR) while ensuring 2-% percentage root-mean-square difference (PRD). The PRD must be limited to this value to ensure a very good quality signals after decompression. For circuit implementation purposes, bior3.1 wavelet is proposed as a multiplier-free decomposition step and a noncomplex global and hard thresholding process is achieved. The average CR is 63% and PRD varies between 0.1 and 2.1% leading to a very good diagnostic quality.


Treatment of wastewater containing azo dye reactive brilliant red X-3B using sequential ozonation and upflow biological aerated filter process.
In this work, the treatment of wastewater containing azo dye reactive brilliant red X-3B using sequential ozonation and upflow biological aerated filter process has been studied. Decolorization was almost complete after 120min with an ozone concentration of 34.08mg/L, the biological oxygen demand for 5 days (BOD5)/chemical oxygen demand (COD) ratio increased from 0.102 to 0.406, which was more effective for the subsequent upflow biological aerated filter (UBAF) to reduce COD concentration. Under the conditions of gas/liquid=3, hydraulic load=4.8m3/m3.d, T=20-25 degrees C, the mass ratio of ozone to dye=4.5, pH 11, the COD and color of the effluent were less than 40mg/L and 20 Pt-Co units, respectively, and the average decolorization and COD removal efficiency were 97% and 90%, respectively. The experimental results showed that the combination of ozone oxidation and upflow biological aerated filter was a promising technique to treat wastewater containing azo dye.


Does HIV status influence the anatomy of anal fistulas?
Although anorectal disease is common in human immunodeficiency virus-positive patients, little is known about the type and anatomic distribution of anal fistulas in this patient group. The aim of this study was to compare anatomic characteristics of anal fistulas in human immunodeficiency virus-positive patients with those in human immunodeficiency virus-negative patients by use of a retrospective chart review. The charts of 146 male patients younger than 50 years with an anal fistula were reviewed. Incomplete fistulas referred to those tracts arising from an internal opening into either a blind sinus or an undrained abscess cavity. There were 60 human immunodeficiency virus-positive patients and 86 human immunodeficiency virus-negative patients. Mean age of the human immunodeficiency virus-positive patient group was 37 years vs. 40 years for the human immunodeficiency virus-negative patient group. Thirty-one human immunodeficiency virus-positive patients (52 percent) were classified as having AIDS, and the remaining 29 patients (48 percent) were asymptomatic. Mean T helper cell count in the human immunodeficiency virus-positive patient group was 277 cells per microliter. Fistulous tracts were intersphincteric (n = 56), transsphincteric (n = 41), suprasphincteric (n = 2), and incomplete (n = 47). Incomplete fistulas were identified in 33 (55 percent) human immunodeficiency virus-positive patients vs. 14 (16 percent) human immunodeficiency virus-negative patients (P < 0.001). Of the 47 incomplete fistulas, 37 (79 percent) were found in association with an abscess cavity. All ten patients with an incomplete fistula into a blind sinus were human immunodeficiency virus-positive. The incidence of an incomplete fistula without an abscess was significantly higher in the human immunodeficiency virus-positive patient group (17 percent) compared with the human immunodeficiency virus-negative patient group (0 percent; P < 0.001). Anal fistulas in HIV-positive patients arise from the dentate line in similar locations to human immunodeficiency virus negative patients. However, human immunodeficiency virus-positive patients were more likely to have incomplete anal fistulas than human immunodeficiency virus-negative patients. Furthermore, human immunodeficiency virus-positive patients are predisposed to incomplete fistulas leading into a blind sinus.


Editorial Commentary: Biologic Stimulation Using Marrow Venting for Meniscus Repair is Cost Effective and Recommended.
Current literature offers little guidance on the most cost-effective approach to intraoperative biologic stimulation in the setting of arthroscopic meniscus repair. Combining data from robust systematic reviews into a Markov Decision Making Model reveal the ideal strategy: Strong consideration should be given to biologic stimulation for all meniscal repairs, and the most cost effective technique is marrow stimulation.


Characterizing multivariate decoding models based on correlated EEG spectral features.
Multivariate decoding methods are popular techniques for analysis of neurophysiological data. The present study explored potential interpretative problems with these techniques when predictors are correlated. Data from sensorimotor rhythm-based cursor control experiments was analyzed offline with linear univariate and multivariate models. Features were derived from autoregressive (AR) spectral analysis of varying model order which produced predictors that varied in their degree of correlation (i.e., multicollinearity). The use of multivariate regression models resulted in much better prediction of target position as compared to univariate regression models. However, with lower order AR features interpretation of the spectral patterns of the weights was difficult. This is likely to be due to the high degree of multicollinearity present with lower order AR features. Care should be exercised when interpreting the pattern of weights of multivariate models with correlated predictors. Comparison with univariate statistics is advisable. While multivariate decoding algorithms are very useful for prediction their utility for interpretation may be limited when predictors are correlated.


Experimental Analysis of Imprinted Mouse X-Chromosome Inactivation.
X-chromosome inactivation is a dosage compensation mechanism that equalizes X-linked gene expression between male and female mammals through the transcriptional silencing of most genes on one of the two X-chromosomes in females. With a few key exceptions, once the X-chromosome is inactivated replicated copies of that X-chromosome are maintained as inactive in all descendant cells. X-inactivation is therefore a paradigm of epigenetic inheritance. Imprinted X-inactivation is a specialized form of X-inactivation that results in the silencing of the paternally derived X-chromosome. Due to its parent-of-origin-specific pattern of inactivation, imprinted X-inactivation is a model of mitotic as well as meiotic, i.e., transgenerational, epigenetic inheritance. All cells of the early mouse embryo undergo imprinted X-inactivation, a pattern that is subsequently maintained in extraembryonic cell types in vivo and in vitro. Here, we describe both high- and low-throughput approaches to interrogate imprinted X-inactivation in the mouse embryo as well in cultured extraembryonic stem cells.


M2 polarization of monocytes in ankylosing spondylitis and relationship with inflammation and structural damage.
The aim of this study was to evaluate the polarization of peripheral blood monocytes in the patients with ankylosing spondylitis (AS) and to determine the correlations between monocyte polarization and inflammation and structural damage. A total of 120 AS patients, 50 rheumatoid arthritis (RA) patients and 100 healthy controls were enrolled in the study. M1 (CD68+CD192+) and M2 (CX3CR1+CD163+) monocytes were characterized by flow cytometry. Demographic, clinical, radiographic and laboratory data were collected and analyzed. A large increase in M2 (CX3CR1+CD163+) monocytes was observed in AS, and M2/M1 ratio was 7.18 ± 6.12, 2.54 ± 3.14 and 35.61 ± 20.04 in control, RA and AS, respectively. The M2/M1 ratio correlated with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) (r = 0.565; p < 0.001), ESR (r = -0.321; p < 0.001, CRP (r = -0.265; p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (r = -0.201; p = 0.028). Anti-TNF-α therapy induced a significant reduction in the percentage of M1 monocyte, ESR, CRP and BASDAI in AS patients. The present results demonstrated that M2 type polarized monocytes are predominant in the peripheral blood in AS and the M2/M1 ratio is correlated with structural damage (mSASSS), inflammatory biomarkers (ESR and CRP) and BASDAI.


An overview of phosphodiesterase 9 inhibitors: Insights from skeletal structure, pharmacophores, and therapeutic potential.
Cyclic nucleotide phosphodiesterase 9 (PDE9), a specifically hydrolytic enzyme with the highest affinity for cyclic guanosine monophosphate (cGMP) among the phosphodiesterases family, plays a critical role in many biological processes. Consequently, the development of PDE9 inhibitors has received increasing attention in recent years, with several compounds undergoing clinical trials for the treatment of central nervous system (CNS) diseases such as Alzheimer's disease, schizophrenia, and psychotic disorders, as well as heart failure and sickle cell disease. This review analyzes the recent primary literatures and patents published from 2004 to 2023, focusing on the structure, pharmacophores, selectivity, and therapeutic potential of PDE9 inhibitors. It hoped to provide a comprehensive overview of the field's current state to inform the development of novel PDE9 inhibitors.


Shape of the isolated ex-vivo human crystalline lens.
To develop an age-dependent mathematical model of the isolated ex-vivo human crystalline lens shape to serve as basis for use in computational modeling. Profiles of whole isolated human lenses (n=27) aged 6 to 82, were measured from shadow-photogrammetric images. Two methods were used to analyze the lenses. In the two curves method (TCM) the anterior and posterior surfaces of the lens were fit to 10th-order even polynomials and in the one curve method (OCM) the contour of one half-meridional section of the lens was fit to 10th-order polynomials. The age-dependence of the polynomial coefficients was assessed. The analysis was used to produce an age-dependent polynomial model of the whole lens shape. The root mean squared errors for the fits ranged from 11 to 70 microm for the OCM, 9 to 27 microm for the posterior surface of the TCM and 8 to 134 microm for the anterior surface of the TCM. The coefficients of the OCM did not display a significant trend with age. The 2nd-, 6th- and 10th-order coefficients of the anterior surface of the TCM decreased with age while the 8th-order coefficient increased. For the posterior surface of the TCM, the 8th-order coefficient significantly decreased with age and the 10th-order coefficient increased. The age-dependent equations of both the models provide a reliable model from age 20 to 60. The OCM model can be used for lenses older than 60 as well. The shape of the whole human crystalline lens can be accurately modeled with 10th-order polynomial functions. These models can serve to improve computational modeling, such as finite element (FE) modeling of crystalline lenses.


The use of intralesional steroids in the treatment of chalazion.
Intralesional injection of triamcinolone acetonide 5 mg/mL suspension was used in the treatment of 110 cases of chalazion; 92.3% of the cases resolved completely with one to three injections, irrespective of the duration and consistency of the chalazion. Recurrence and yellow deposits were seen at the site of injection in a minority of patients.


Patchwork organization of the yeast plasma membrane into numerous coexisting domains.
The plasma membrane is made up of lipids and proteins, and serves as an active interface between the cell and its environment. Many plasma-membrane proteins are laterally segregated in the plane of the membrane, but the underlying mechanisms remain controversial. Here we investigate the distribution and dynamics of a representative set of plasma-membrane-associated proteins in yeast cells. These proteins were distributed non-homogeneously in patterns ranging from distinct patches to nearly continuous networks, and these patterns were in turn strongly influenced by the lipid composition of the plasma membrane. Most proteins segregated into distinct domains. However, proteins with similar or identical transmembrane sequences (TMSs) showed a marked tendency to co-localize. Indeed we could predictably relocate proteins by swapping their TMSs. Finally, we found that the domain association of plasma-membrane proteins has an impact on their function. Our results are consistent with self-organization of biological membranes into a patchwork of coexisting domains.


Atypical complications encountered with epicardial electrophysiological procedures.
With the increasing use, complexity, anatomical approaches, and tools related to epicardial procedures, complications previously not seen during endovascular ablation are now well recognized with epicardial ablation. Whether newer approaches and the regional anatomy of the pericardial space contribute to unexpected complications after epicardial access (EpiAcc) is presently unknown. To characterize underreported, or novel, complications associated with percutaneous EpiAcc as part of an electrophysiology procedure. We retrospectively reviewed percutaneous EpiAcc as part of an ablation procedure from January 1, 2004, to December 31, 2011. Of 116 attempts in 107 patients, 8 atypical ablation complications (no procedural deaths) were noted; complications included delayed pericarditis (2 weeks), chronic refractory pericarditis, requirement for snaring of broken intrapericardial wire, pleural perforation, phrenic nerve injury despite protective strategies, hemoperitoneum, and abdominal-pericardial fistula. Vigilance both during and after EpiAcc is needed to recognize these complications, some of which may be life-threatening.


The Analysis of Yeast Mitochondrial Translation.
The mitochondrial genome encodes only a handful of proteins, but methods to track their synthesis are highly limited. Saccharomyces cerevisiae is a model organism that offers possibilities to expand the classical systems to analyze mitochondrial translation. In this chapter, we present two approaches of monitoring mitochondrial protein synthesis. Labeling of mitochondrially translated products with radioactive amino acids can be performed either in intact cells or in isolated mitochondria. However, these classical methods have disadvantages that can affect cell physiology and hence are not suitable for all types of research questions. Some of these limitations can be overcome by the use of reporter genes that are inserted into yeast genetic screens mitochondrial DNA via biolistic transformation. These reporter genes can be used for yeast genetic screen and to monitor regulation and efficiency of mitochondrial translation with a variety of methods.


Ten year follow up of models 1260 and 2400 Starr-Edwards isolated aortic valve replacement.
In our experience the structural durability of the S-E models 1260 and 2400 aortic prostheses is excellent, with no episodes of mechanical valve failure recorded over a 10 year period. Long term performance characteristics compare favourably with other published series and other prostheses, with a specifically low incidence of thromboembolism recorded. Such data will provide a useful comparison against newer prostheses in the search for the ideal cardiac valve substitute.


Variable chlorophyll a fluorescence from P-700 enriched photosystem I particles dependent on the redox state of the reaction centre.
1. Photosystem I particles enriched in P-700 prepared by Triton X-100 treatment of chloroplasts show a light-induced increase in fluorescence yield of more than 100% in the presence of dithionite but not in its absence. 2. Steady state light maintains the P-700, of these particles, in the oxidised state when ascorbate is present but in the presence of dithionite only a transient oxidation occurs. 3 EPR data show that, in these particles, the primary electron acceptor (X) is maintained in the reduced state by light at room temperature only when the dithionite is also present. In contrast, the secondary electron acceptors are reduced in the dark by dithionite. 4. Fluorescence emission and excitation spectra and fluorescence lifetime measurements for the constant and variable fluorescence indicate a heterogeneity of the chlorophyll in these particles. 5. It is concluded that the variable fluorescence comes from those chlorophylls which can transfer their energy to the reaction centre and that the states PX and P+X are more effective quenchers of chlorophyll fluorescence than PX-, where P is P-700.


Cytotoxicity of ochratoxin A and citrinin in different cell typesin vitro.
Cytotoxic effects resulting from the two mycotoxins ochratoxin A (OTA) and citrinin were evaluatedin vitro using cell cultures of different origin. Cytotoxicity was estimated by the neutral red (NR) uptake assay which allows to determine the viability of cells by detecting dye uptake into the cells and its storage in the lysosomes. The assay was performed with primary cell cultures derived from isolated porcine urinary bladder epithelial cells (PUBEC), which are competent in metabolism of xenobiotics, and with V79 hamster fibroblasts, a well established and frequently used cell line. In both systems, OTA was more cytotoxic compared to citrinin. When both mycotoxins were applied simultaneously no additive or synergistic effects were detected. Obviously, the primary cell culture system which represents a target tissue of the mycotoxins was more susceptible to the toxins, expressed in lower IC50-values. These results indicate that origin of a cell system and its competence in metabolism of xenobiotics have to be considered inin vitro investigations particularly when different systems were used.


Prospective study of concentric and eccentric leg muscle torques, flexibility, physical conditioning, and variation of injury rates during one season of amateur ice hockey.
Twenty-three male ice hockey players in a third division amateur ice hockey team were prospectively studied during the 1987-1988 season. O2 uptake, muscle flexibility, and isokinetic concentric and eccentric leg muscle strength were measured before and after the season. All injuries were recorded by one and the same physician attending all the games: 68 injuries occurred altogether but only six of these led to absence from training or matches. O2 uptake and muscle flexibility were unchanged during the season, but a significant drop of both concentric and eccentric quadriceps and hamstring torques occurred in spite of the fact that the team played two games and trained twice per week during the entire season. No correlation between the fall in muscle strength and the injury rate was found. Although many injuries occur in ice hockey, the majority are minor ones that do not lead to absence from playing.


The influence of provider sex on neurologists' annual incomes.
We sought to determine the influence of provider sex on neurologists' annual incomes after controlling for work effort, provider characteristics, and practice characteristics. We used survey responses collected throughout the 1990s from 216 actively practicing neurologists and linear regression modeling to determine the independent influence of provider sex on neurologists' annual incomes. White female neurologists reported seeing 11% fewer visits and working 6% fewer annual hours than their white male counterparts. White female neurologists had practiced medicine for fewer years than white males (p = 0.01). In addition, females were less likely to be employees, as opposed to having an ownership interest in the practice, and were more likely to be board certified, though not statistically significantly so. After adjustment for work effort, provider characteristics, and practice characteristics, white female neurologists' mean annual income was 165,321 dollars, or 47,854 dollars (22%) lower than that for white males (95% CI: 82,710 dollars lower to 12,997 dollars lower, p = 0.007). During the 1990s, female sex was associated with lower annual incomes among neurologists. Just as policymakers are exploring sex differences in access to and outcomes health care, they should further explore these findings to ensure that income differences among physicians who provide that care are not unjustly driven by provider sex.


Oxidation of hydroxyurea with oxovanadium(V) ions in acidic aqueous solution.
Hydroxyurea (HU) effectively reduces vanadium(V) into vanadium(IV) species (hereafter V(V) and V(IV) species, respectively) in acidic aqueous solution via the formation of a transient complex followed by an electron transfer process that includes the formation and subsequent fading out of a free radical, U* (U* identical with H(2)N-C(=O)N(H)O*). The electron paramagnetic resonance (EPR) spectra of U* in H(2)O/D(2)O solutions suggest that the unpaired electron is located predominantly on the hydroxamate hydroxyl-oxygen atom. Visible and V(IV)-EPR spectroscopic data reveal HU as a two-electron donor, whereas formation of U*, which reduces a second V(V), indicates that electron transfer occurs in two successive one-electron steps. At the molarity ratio [V(V)]/[HU]=2, the studied reaction can be formulated as: 2 V(V)+HU-->2 V(IV)+0.98 CO(2)+0.44 N(2)O+1.1 NH(3)+0.1 NH(2)OH. Lack of evidence for the formation of NO is suggested to be a consequence of the slow oxidation of HNO due to the too low reduction potential of the V(V)/V(IV) couple under the experimental conditions used. The nuclear magnetic resonance ((51)V-NMR) spectral data indicate protonation of (H(2)O)(4)V(V)O(2)(+), and the protonation equilibrium constant was determined to be K=0.7 M(-1). Spectrophotometric titration data for the V(V)-HU system reveal formation of (H(2)O)(2)V(V)O(OH)U(+) and (H(2)O)(3)V(V)OU(2+). Their stability constants were calculated as K(110)=5 M(-1) and K(111)=22 M(-2), where the subscript digits refer to (H(2)O)(4)V(V)O(2)(+), HU and H(+), respectively.


Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.
Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. Pubmed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval). Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.


Construction of 1,2,4-Triazole Derivatives via Cyclocondensation of Alkylidene Dihydropyridines and Aryldiazonium Salts.
Alkylidene dihydropyridines (anhydrobases) prepared via dearomatization of N-acylated 4-(aminomethyl)pyridines participate in [3 + 2] cyclocondensation reactions with aryldiazonium cations to afford substituted 1,2,4-triazolium salts or neutral 1,2,4-triazoles in high isolated yield. The reaction proceeds in the presence of a variety of N-acyl groups and aryl-susbtituted diazonium salts and offers a general route to pyridyl-substituted 1,2,4-triazoles.


[Comparative quantitative-cytochemical and ultrastructura-morphometric studies for the characterization of the rat heart in experimental myocardial infarct].
Some oxidative enzymes of undamaged sites of the left ventricle were examined with the aid of ultrastructural morphometric and quantified cytochemical methods 1, 2, 7 and 14 days after the ligature of the descending branch of the left coronary artery. A comparison of the ultrastrastructural morphometric data with the densitometric data showed that increases in the activities of some oxidative enzymes are accompanied by enlargements of the mitochondria.


CopyMean: A new method to predict monotone missing values in longitudinal studies.
Longitudinal studies are those in which the same variable is repeatedly measured at different times. More likely than others, these studies suffer from missing values. Because the missing values may impact the statistical analyses, it is important that they be dealt with properly. In this paper, we present "CopyMean", a new method to impute (predict) monotone missing values. We compared its efficiency to sixteen imputation methods dedicated to the treatment of missing values in longitudinal data. All these methods were tested on four datasets, real or artificial, presenting markedly different caracteristics. The analysis showed that CopyMean was more efficient in almost all situations.


Social isolation and well-being.
We examined 10 common indicators of social isolation and assessed which, if any, are related to subjective well-being among elderly individuals. The quantitative measures (no daily contact and minimal weekly contact), no children, having no children plus being unmarried, and having no children plus living alone, were unrelated to either global happiness or life satisfaction. The combined indicators of living alone and being unmarried as well as single indicators of having no companions or having no confidants were related at the bivariate level to both measures of well-being. When controlling for demographic, economic, and health factors, having no confidants and no companions were significantly and independently related to subjective well-being. These findings suggest that practitioners who seek information on living arrangements or marital status as proxy measures of lower psychological well-being are utilizing the wrong predictors.


Method for multilevel threshold of binarization in a hybrid joint Fourier-transform correlator.
A hybrid system is proposed that performs joint transform correlation with a multireference by use of a self-generated threshold function.


Carotid artery corrected flow time and respiratory variations of peak blood flow velocity for prediction of hypotension after induction of general anesthesia in elderly patients.
Postinduction hypotension is closely related to postoperative complications. Elderly patients with compromised cardiovascular compensatory reserve are more susceptible to hypotension after induction of general anesthesia. This study investigated whether the carotid artery corrected flow time (FTc) and respiratory variation of peak blood flow velocity in the common carotid artery (ΔVpeak) could predict postinduction hypotension in elderly patients. This prospective observational study included elderly patients aged 65 to 75 who were scheduled for elective surgery under general anesthesia with ASA physical status class of I-II, without cardiovascular disease, hypertension, diabetes, or obesity. Anesthesia was induced by midazolam, sufentanil, and etomidate and was maintained by sevoflurane. The carotid artery FTc and ΔVpeak were measured by ultrasound before induction of anesthesia. Hemodynamic data were recorded before induction and then during the first 10 min after induction. Ninety-nine patients were included in the final analysis, of whom 63 developed postinduction hypotension. The area under the receiver operating characteristic curves was 0.87 (0.78 to 0.93) for carotid artery FTc and 0.67 (0.56 to 0.76) for ΔVpeak, respectively. The optimal cutoff value for predicting postinduction hypotension was 379.1 ms for carotid artery FTc, with sensitivity and specificity of 72.2 and 93.7%, respectively. The best cutoff value was 7.5% for ΔVpeak, with sensitivity and specificity of 55.6 and 75.0%, respectively. The carotid artery FTc is a reliable predictor of postinduction hypotension in elderly patients with ASA status of I or II, without cardiovascular disease, hypertension, diabetes, or obesity. Elderly patients with a carotid artery FTc less than 379.1 ms before anesthesia have a higher risk of postinduction hypotension. Clinical Trial Registry on August 2nd, 2020 ( www.chictr.org.cn ; ChiCTR2000035190).


The interplay between effector binding and allostery in an engineered protein switch.
The protein design rules for engineering allosteric regulation are not well understood. A fundamental understanding of the determinants of ligand binding in an allosteric context could facilitate the design and construction of versatile protein switches and biosensors. Here, we conducted extensive in vitro and in vivo characterization of the effects of 285 unique point mutations at 15 residues in the maltose-binding pocket of the maltose-activated β-lactamase MBP317-347. MBP317-347 is an allosteric enzyme formed by the insertion of TEM-1 β-lactamase into the E. coli maltose binding protein (MBP). We find that the maltose-dependent resistance to ampicillin conferred to the cells by the MBP317-347 switch gene (the switch phenotype) is very robust to mutations, with most mutations slightly improving the switch phenotype. We identified 15 mutations that improved switch performance from twofold to 22-fold, primarily by decreasing the catalytic activity in the absence of maltose, perhaps by disrupting interactions that cause a small fraction of MBP in solution to exist in a partially closed state in the absence of maltose. Other notable mutations include K15D and K15H that increased maltose affinity 30-fold and Y155K and Y155R that compromised switching by diminishing the ability of maltose to increase catalytic activity. The data also provided insights into normal MBP physiology, as select mutations at D14, W62, and F156 retained high maltose affinity but abolished the switch's ability to substitute for MBP in the transport of maltose into the cell. The results reveal the complex relationship between ligand binding and allostery in this engineered switch.


Compressed gastric image generation based on soft-label dataset distillation for medical data sharing.
Sharing of medical data is required to enable the cross-agency flow of healthcare information and construct high-accuracy computer-aided diagnosis systems. However, the large sizes of medical datasets, the massive amount of memory of saved deep convolutional neural network (DCNN) models, and patients' privacy protection are problems that can lead to inefficient medical data sharing. Therefore, this study proposes a novel soft-label dataset distillation method for medical data sharing. The proposed method distills valid information of medical image data and generates several compressed images with different data distributions for anonymous medical data sharing. Furthermore, our method can extract essential weights of DCNN models to reduce the memory required to save trained models for efficient medical data sharing. The proposed method can compress tens of thousands of images into several soft-label images and reduce the size of a trained model to a few hundredths of its original size. The compressed images obtained after distillation have been visually anonymized; therefore, they do not contain the private information of the patients. Furthermore, we can realize high-detection performance with a small number of compressed images. The experimental results show that the proposed method can improve the efficiency and security of medical data sharing.


Changes in preneoplastic response to aflatoxin B1 in rats fed green beans, beets or squash.
Weanling male Fischer rats were fed diets containing 25% freeze-dried green beans, beets or squash either with or without 1 ppm aflatoxin B1 for 8 wk. Plasma alpha-foetoprotein concentrations were determined weekly from wk 4 to 7. During wk 8 the animals were killed and hepatic sections were stained for gamma-glutamyl transpeptidase. All three vegetable diets, as compared to the basal semi-purified diet, enhanced both aflatoxin-B1-induced elevation of plasma alpha-foetoprotein and aflatoxin-B1-induced emergence of hepatic cell foci of gamma-glutamyl transpeptidase. The data suggest that these vegetables contain natural factors that enhance aflatoxin B1 carcinogenicity.


Adherence to a modified nordic diet and the risk of cardiovascular events in a non-nordic population: a prospective cohort study.
Even though studies have demonstrated that the Nordic diet is beneficial for cardiovascular disease (CVD) risk factors, it is unknown if this diet is associated with actual CVD cases. So, the aim of this study was to investigate the association between a modified Nordic diet and the risk of CVD in non-Nordic adults. In this cohort study, 2918 people who participated in the third phase of the Tehran Lipid and Glucose Study (TLGS) were examined. All participants had no CVD at the beginning of the study, which was monitored until 2018. The Nordic score was calculated using a validated food frequency questionnaire (FFQ). Patients' medical records were examined for cardiovascular events such as coronary heart disease (CHD), stroke, and mortality from CVD. The Cox proportional hazards model was used to assess the relationship between the Nordic score and the risk of CVD. During a median follow-up of 10.6 years, 203 subjects experienced cardiovascular events. The third and fourth quartiles of the Nordic score were associated with a 35% (HR: 0.65; 95% CI: 0.45, 0.95) and 60% (HR: 0.40; 95% CI: 0.27 to 0.65) reduced risk of CVD compared to the lowest quartile. Subgroup analyses revealed that a high Nordic score was inversely associated with a lower risk of CVD in adults older than 45 years of age, both sexes, and all BMI categories. Each 1-score increase in cereal consumption was associated with a 24% (HR: 0.76; 95% CI: 0.67 to 0.87) lower risk of CVD; low-fat milk with a 23% (HR: 0.77; 95% CI: 0.68 to 0.87); and fish with a 22% (HR: 0.78; 95% CI: 0.69 to 0.89) lower risk of CVD. We found that high Nordic score adherence may prevent cardiovascular events in non-Nordic populations. Cereals, fish, and low-fat milk were the primary components of the Nordic diet that indicated an inverse relationship with CVD.


Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies.
A dose-escalation trial was carried out to determine the efficacy and safety of using an IgG2a anti-CD3 monoclonal antibody to treat acute graft-v-host disease (GVHD) in marrow transplant recipients. Two patients received the antibody as the initial treatment of GVHD, and 22 patients received the antibody after failure of initial treatment with corticosteroids, cyclosporine, antithymocyte globulin (ATG), or combined ATG and cyclosporine. Antibody was administered at four dose levels, beginning at approximately 0.015 mg/kg/d and increasing by threefold increments. The initial doses of antibody were nearly always associated with fever and chills, and treatment had to be discontinued in one patient because of intolerable side effects. Improvement in skin disease could be reliably achieved at a dose of 0.15 mg/kg/d, but threefold higher doses appeared to be necessary for improvement in the liver or gut. In no case was there complete resolution of all manifestations of disease, and all patients surviving after antibody treatment required additional immunosuppressive treatment. Four patients developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorders within seven to 18 days after starting antibody therapy. The overall risk of this complication in patients not given anti-CD3 monoclonal antibody is less than 1%. Anti-CD3 antibody represents an effective immunosuppressive agent for treatment of acute GVHD, but this treatment is associated with a substantial risk of EBV-associated lymphoproliferative disorders.


"Pollination" of a fungus by a fly.
The mechanism resulting in fertilization of Epichloë typhina, a heterothallic ascomycete that is an endophytic pathogen of grasses, has now been discovered. Conidia of one mating type are produced in stromata and are then transferred by insects to individuals of the opposite mating type. One insect, Phorbia phrenione, is a particularly important vector of conidia. Once conidia of the opposite mating type have been transferred to a stroma, the life cycle continues with the formation of perithecia.


Outbreak of Salmonella serotype Kottbus infections associated with eating alfalfa sprouts--Arizona, California, Colorado, and New Mexico, February-April 2001.
On March 12, 2001, the California Department of Health Services (CDHS) identified a cluster of Salmonella Kottbus isolates with indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. During February 1-May 1, CDHS identified 23 patients with S. Kottbus infections in several California counties and an additional patient from Arizona. This report summarizes the results of the investigation of this outbreak, which identified cases in four states and implicated alfalfa sprouts produced at a single facility.


Object perception in 5-month-old infants of clinically depressed and nondepressed mothers.
Five-month-old infants of clinically depressed and nondepressed mothers were familiarized to a wholly novel object and afterward tested for their discrimination of the same object presented in the familiar and in a novel perspective. Infants in both groups were adequately familiarized, but infants of clinically depressed mothers failed to discriminate between novel and familiar views of the object, whereas infants of nondepressed mothers successfully discriminated. The difference in discrimination between infants of depressed and nondepressed mothers is discussed in light of infants' differential object processing and maternal sociodemographics, mind-mindedness, depression, stress, and interaction styles that may moderate opportunities for infants to learn about their world or influence the development of their perceptuocognitive capacities.


Mycobiota associated with strawberry fruits, their mycotoxin potential and pectinase activity.
Forty-three species and variety belonging to 15 genera were collected from 30 strawberry fruit samples on Glucose-Czapek's agar medium. Among them, Aspergillus flavus, Aspergillus niger and Penicillium citrinum were the most frequent species recovered from 53.3%, 70.0% and 50.0% of the samples, respectively. According to the ITS rDNA sequence, we confirmed the morphological identification result. Moreover, aflatoxin biosynthesis gene omt-A was detected in A. flavus, while Aopks gene was found in A. niger. Interestingly, we could not detect any aflatoxin or ochratoxin biosynthesis genes in the P. citrinum strain. The concentration of detected aflatoxin was 3.5 ppb produced by A. flavus, while A. niger gave 4.1 ppb as ochratoxin. A. flavus was the most pectinase producer among the selected strains, and the highest amount was obtained at 30°C after 6 days of incubation with initial medium pH 8.


Laparoscopy in patients over 60 years old: a prospective, randomized evaluation of laparoscopic versus open adnexectomy.
To compare objective and subjective parameters of surgical stress following laparoscopic and open adnexectomy in patients older than 60 years old. Twenty patients with a benign ovarian tumour were prospectively randomized to undergo adnexectomy by a laparoscopic or an open surgical procedure. Measurements included C-reactive protein; interleukin-6 before, during, and after surgery; intensity and duration of postoperative pain; and complications and recovery period. Statistical analysis consisted of analysis of variance and a Mann-Whitney U test. The levels of the interleukin-6 and C-reactive protein differed significantly between the 2 operative procedures (P = .013) in favor of the laparoscopic approach. The laparoscopic approach was associated with a reduction in operative morbidity, postoperative pain, analgesic requirement, and recovery period. Minimally invasive surgery is of particular benefit to elderly patients if there is a plan in place for appropriate staging and treatment by laparotomy for malignancy. It should be the first choice and may help to reduce postoperative complications.


Methods of experimental study of thermal convection in cavity subject to rotation and vibration.
Vibrations of a non-isothermal fluid result in the generation of an averaged flows - "thermal vibrational convection". The effect of vibrations changes qualitatively, and their effectiveness increases significantly under conditions of rotation. This makes vibrations an important tool for controlling the dynamics of non-isothermal systems and the intensification of heat and mass transfer in rotating cavities, which could be useful for optimization of various technological processes. The article describes methods used to study convection in rotating cylinders subject to vibrations. The cases of an annulus with boundaries at different temperatures and a cylinder filled with a heat-generating fluid are discussed. Experimental complex allows one to study thermal convection under the action of various factors, such as rotation, vibrations, librations, orientation of the axis of rotation, inertial waves, and others. •The vibrations of a non-isothermal fluid in a rotating cavity is an effective tool for intensification of heat transport due to the generation of intensive averaged flows•The developed experimental technique and setup provide the investigation of thermal vibrational convection in rotating cavities of various geometries in a wide range of governing dimensionless parameters.


Successful Percutaneous Coronary Intervention With Two-Stent Technique for Unprotected True Left Main Bifurcation Lesion Via Left Snuffbox Approach.
There are few data regarding complex PCIs, such as interventions for unprotected left main coronary artery and two-stent technique for the bifurcation lesion via snuffbox approach. This case illustrates the potential feasibility of complex PCI and benefits of hemostasis via snuffbox approach.


Myosin head configuration in relaxed insect flight muscle: x-ray modeled resting cross-bridges in a pre-powerstroke state are poised for actin binding.
Low-angle x-ray diffraction patterns from relaxed insect flight muscle recorded on the BioCAT beamline at the Argonne APS have been modeled to 6.5 nm resolution (R-factor 9.7%, 65 reflections) using the known myosin head atomic coordinates, a hinge between the motor (catalytic) domain and the light chain-binding (neck) region (lever arm), together with a simulated annealing procedure. The best head conformation angles around the hinge gave a head shape that was close to that typical of relaxed M*ADP*Pi heads, a head shape never before demonstrated in intact muscle. The best packing constrained the eight heads per crown within a compact crown shelf projecting at approximately 90 degrees to the filament axis. The two heads of each myosin molecule assume nonequivalent positions, one head projecting outward while the other curves round the thick filament surface to nose against the proximal neck of the projecting head of the neighboring molecule. The projecting heads immediately suggest a possible cross-bridge cycle. The relaxed projecting head, oriented almost as needed for actin attachment, will attach, then release Pi followed by ADP, as the lever arm with a purely axial change in tilt drives approximately 10 nm of actin filament sliding on the way to the nucleotide-free limit of its working stroke. The overall arrangement appears well designed to support precision cycling for the myogenic oscillatory mode of contraction with its enhanced stretch-activation response used in flight by insects equipped with asynchronous fibrillar flight muscles.