An Exercise and Educational and Self-management Program Delivered With a Smartphone App (CareHand) in Adults With Rheumatoid Arthritis of the Hands: Randomized Controlled Trial.
Rheumatoid arthritis (RA) is a prevalent autoimmune disease that usually involves problems of the hand or wrist. Current evidence recommends a multimodal therapy including exercise, self-management, and educational strategies. To date, the efficacy of this approach, as delivered using a smartphone app, has been scarcely investigated. This study aims to assess the short- and medium-term efficacy of a digital app (CareHand) that includes a tailored home exercise program, together with educational and self-management recommendations, compared with usual care, for people with RA of the hands. A single-blinded randomized controlled trial was conducted between March 2020 and February 2021, including 36 participants with RA of the hands (women: 22/36, 61%) from 2 community health care centers. Participants were allocated to use the CareHand app, consisting of tailored exercise programs, and self-management and monitoring tools or to a control group that received a written home exercise routine and recommendations, as per the usual protocol provided at primary care settings. Both interventions lasted for 3 months (4 times a week). The primary outcome was hand function, assessed using the Michigan Hand Outcome Questionnaire (MHQ). Secondary measures included pain and stiffness intensity (visual analog scale), grip strength (dynamometer), pinch strength (pinch gauge), and upper limb function (shortened version of the Disabilities of the Arm, Shoulder, and Hand questionnaire). All measures were collected at baseline and at a 3-month follow-up. Furthermore, the MHQ and self-reported stiffness were assessed 6 months after baseline, whereas pain intensity and scores on the shortened version of the Disabilities of the Arm, Shoulder, and Hand questionnaire were collected at the 1-, 3-, and 6-month follow-ups. In total, 30 individuals, corresponding to 58 hands (CareHand group: 26/58, 45%; control group: 32/58, 55%), were included in the analysis; 53% (19/36) of the participants received disease-modifying antirheumatic drug treatment. The ANOVA demonstrated a significant time×group effect for the total score of the MHQ (F1.62,85.67=9.163; P<.001; η2=0.15) and for several of its subscales: overall hand function, work performance, pain, and satisfaction (all P<.05), with mean differences between groups for the total score of 16.86 points (95% CI 8.70-25.03) at 3 months and 17.21 points (95% CI 4.78-29.63) at 6 months. No time×group interaction was observed for the secondary measures (all P>.05). Adults with RA of the hands who used the CareHand app reported better results in the short and medium term for overall hand function, work performance, pain, and satisfaction, compared with usual care. The findings of this study suggest that the CareHand app is a promising tool for delivering exercise therapy and self-management recommendations to this population. Results must be interpreted with caution because of the lack of efficacy of the secondary outcomes. ClinicalTrials.gov NCT04263974; https://clinicaltrials.gov/ct2/show/NCT04263974. RR2-10.1186/s13063-020-04713-4.


Identification of 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone (4-MEAP), a New "Legal High" Sold by an Internet Vendor as 4-Methyl Pentedrone.
Online vendors are offering a new legal high, 4-methylpentedrone (4-MPD). Information for potential users provided by internet vendors of 4-MPD includes incorrect structures and nonexistent CAS numbers. A sample of 4-MPD was obtained and analyzed using GC-MS, NMR, and LC-EIS. The fragmentation data from the GC-MS and LC-EIS produced an M-1 ion that suggested the molecular mass was 219 amu, rather than 205 amu as calculated for 4-methylpentedrone. The difference in molecular mass corresponded to the addition of a methyl group. Based on the mass and fragmentation pattern, two standards were synthesized, 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone and 1-(4-methylphenyl)-2-(propylamino)-1-butanone. The synthesis involved bromination of the appropriate ketone followed by the reaction with ethylamine or propylamine. Based on the NMR data and unique fragmentation patterns produced by these molecules, the sample was identified as 2-(ethylamino)-1-(4-methylphenyl)-1-pentanone, not 4-methylpentedrone.


Application of medical information system to identify dengue outbreak factors: Insights from a hyperendemic city in Malaysia.
Dengue is widespread globally, but it is more severe in hyperendemic regions where the virus, its vectors, and its human hosts naturally occur. The problem is particularly acute in cities, where outbreaks affect a large human population living in a wide array of socio-environmental conditions. Controlling outbreaks will rely largely on systematic data collection and analysis approaches to uncover nuances on a city-by-city basis due to the diversity of factors. The main objective of this study is to consolidate and analyse the dengue case dataset amassed by the e-Dengue web-based information system, developed by the Ministry of Health Malaysia, to improve our epidemiological understanding. We retrieved data from the e-Dengue system and integrated a total of 18,812 cases from 2012 to 2019 (8 years) with meteorological data, geoinformatics techniques, and socio-environmental observations to identify plausible factors that could have caused dengue outbreaks in Ipoh, a hyperendemic city in Malaysia. The rainfall trend characterised by a linearity of R2 > 0.99, termed the "wet-dry steps", may be the unifying factor for triggering dengue outbreaks, though it is still a hypothesis that needs further validation. Successful mapping of the dengue "reservoir" contact zones and spill-over diffusion revealed socio-environmental factors that may be controlled through preventive measures. Age is another factor to consider, as the platelet and white blood cell counts in the "below 5" age group are much greater than in other age groups. Our work demonstrates the novelty of the e-Dengue system, which can identify outbreak factors at high resolution when integrated with non-medical fields. Besides dengue, the techniques and insights laid out in this paper are valuable, at large, for advancing control strategies for other mosquito-borne diseases such as malaria, chikungunya, and zika in other hyperendemic cities elsewhere globally.


Comparison of the selenium level with GSH-Px activity in the liver of mice treated with 7,12 DMBA.
In this study, the relationship between selenium (Se) and glutathione peroxidase (GSHPx) levels was investigated in 7,12-dimethylbenz(a)anthracene (7,12-DMBA)-treated mouse liver. The potential mammary carcinogen 7,12-DMBA, was injected intraperitoneally (20 mg kg(-1) day(-1)) into 10-12 month old female mice. After 21 days of application the mice were sacrificed and GSHPx and Se levels of liver homogenates were measured. Se and GSHPx levels in 7,12-DMBA-treated mice were significantly lower than those of controls (p < 0.05). The control group exhibited 0.9 +/- 0.066 U mg(-1) protein and 0.86 +/- 0.058 p.p.m. levels of GSHPx and Se respectively. The 7,12-DMBA-treated group had significantly (p < 0.05) decreased GSHPx and Se levels (0.42 +/- 0.062 U mg(-1) protein and 0.69 +/- 0.034 p.p.m. respectively). The results show a direct relationship between Se and GSHPx activity and a negative correlation between antioxidant capacity and existence of a carcinogen in metabolism.


Characterization of the hepatitis C virus E2/NS1 gene product expressed in mammalian cells.
Truncated and full-length versions of the hepatitis C virus protein domain encoding a presumptive envelope glycoprotein designated E2/NS1 were stably expressed in CHO cell lines. Characterization of the processing events involved in the maturation of E2/NS1 revealed that a high-mannose form resident in the endoplasmic reticulum was the most abundant form detected intracellularly. The ionophore carboxyl cyanide m-chlorophenyl-hydrazone was used to show that the E2/NS1 glycoprotein resided in the endoplasmic reticulum. The full-length form of E2/NS1 appeared to be cell-associated and could not be detected as a secreted product. C-terminal truncated molecules could be detected in the extracellular media as fully processed glycoproteins containing terminal sialic acid additions. These truncated glycoproteins are predicted to be biologically relevant targets of the host immune response and are therefore potential subunit vaccine candidates.


A unique case of sclerosing polycystic adenosis of the sinonasal tract.
Sclerosing polycystic adenosis is an extremely uncommon, recently described, sclerosing lesion of the salivary glands that appears histologically similar to fibrocystic changes of the breast. The key histopathologic features of sclerosing polycystic adenosis include lobular proliferation of ductal and acinar elements, cystically dilated ducts exhibiting frequent apocrine and sebaceous metaplasia, eosinophilic intracytoplasmic granules within some acinar-type cells, intraductal epithelial hyperplasia, and dense fibrosis. Most described cases have occurred in the major salivary glands, particularly the parotid gland. Although most authorities consider sclerosing polycystic adenosis to be a pseudoneoplastic process, the occurrence of dysplasia and carcinoma in situ of ductal epithelium reported recurrence rates of up to 30%, and recent evidence of clonality suggests a possible neoplastic etiology. However, there have been no cases of metastasis. Herein, we report the first case of sclerosing polycystic adenosis of the sinonasal tract in a 79-year-old woman presenting with a sinonasal mass.


Determination of 6-methyladenine in DNA by high-performance liquid chromatography.
A method for the determination of 6-methyladenine (6MA) by high-performance liquid chromatography (HPLC) has been developed. DNA bases were separated by using the strong cation-exchange resin Zipax SCX. Purine bases were obtained by hydrolysis and dialysis of DNA and analysed by HPLC. 6MA in DNA from Escherichia coli was determined by the proposed method. It is suggested that the method could be applicable to analyses of 6MA from other biological sources.


Enlarged hilar and mediastinal nodes (and especially lower right hilar node enlargement) as a sign of metastasis of a renal tumour.
Hilar and mediastinal node enlargement may be a manifestation of the spread of renal tumours. However, the author believes the spread to these nodes may occur either via the upper para-aortic nodes or directly by way of lymphatic vessels from the kidneys by-passing the upper abdominal nodes. It seems that in some cases the hilar node may even be acting as a regional lymph node for the kidney. Thus an enlarged hilar node and especially a lower right hilar node may be the presenting feature of a renal tumour.


Involvement of p38 MAPK and JNK in heat stress-induced cardioprotection.
The present study investigated whether heat stress-induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2 - terminal kinase (JNK) activation during ischaemia - reperfusion in a model of isolated perfused rat heart. Wistar rats were subjected to whole-body hyperthermia at 42 degrees C for 15 min (HS), while untreated animals served as controls (CON). Twenty four hours later, CON and HS isolated hearts were perfused in a Langendorff mode and subjected to 20 min of zero-.ow global ischaemia followed by 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value (LVDP%). Activation of p38 MAPK and JNK was assessed by standard Western blotting techniques using a dual phospho-p38 MAPK and phospho-p46 JNK and p54 JNK antibodies. The levels of phospho-p38 MAPK at the end of reperfusion were not different in HS as compared to CON hearts. The levels of phospho-p46 JNK and p54 JNK were 1.4- and 1.6-fold less in HS than in CON hearts respectively, p < 0.05. LVDP% was 60.3 (s.e.m., 6.3) for HS and 42.9 (4.1) for CON, p < 0.05. In summary, heat stress pretreatment improves postischaemic recovery of function in isolated rat hearts and this is associated with suppressed JNK activation in response to ischaemia-reperfusion.


A Preoperative Scoring System for Adnexal Mass in Children and Adolescents to Preserve Their Future Fertility.
To develop a predictive score for ovarian malignancy to avoid unnecessary adnexectomy in cases of adnexal mass in pediatric and adolescent girls. A population-based retrospective study on girls who underwent surgery for an ovarian mass with normal levels of human chorionic gonadotrophin and alpha fetoprotein between 1996 and 2016. Rennes University Hospital, Rennes, France. Eighty-one patients who received surgery for ovarian tumor. The main outcome measure was the rate of malignant and borderline tumor. A preoperative scoring system was constructed after multivariate analysis. The rate of malignant ovarian tumor was 6/81 (7%), borderline tumor was 7/81 (9%) (ie, outcome measure: 16%), and benign tumor was 84%. In a univariate analysis, the characteristics significantly associated with malignancy were early puberty, palpable mass, size and content of the tumor, and positive epithelial tumor markers (carcinoma antigen 125, carcinoembryonic antigen, and carcinoma antigen 19-9). The predictive malignancy score was on the basis of 2 variables obtained after multivariate analysis: tumor size and cystic content. The score defined 3 groups at risk for malignancy: low risk, middle-risk, and high-risk. The sensitivity for detecting malignancy was 1.3% (95% confidence interval [CI], 0.1-18.4), 26.2% (95% CI, 11.6-49.0), and 53.1% (95% CI, 29.1-75.8), respectively. We set up a simple predictive score of malignancy on the basis of objective criteria to help decision-making on whether or not ovarian-sparing surgery is feasible in case of children and adolescents with ovarian tumors and normal human chorionic gonadotrophin and alpha fetoprotein levels while ensuring oncologic safety.


The structure of the canary's incubation patch.
The gross morphology, histology and ultrastructure of the canary's incubation patch and the ventral apterium from which it arises are described. The apterium is vascularized by pectoral, external mammary, incubation, and prepubic arteries. It is innervated by cutaneous branches of spinal nerves. It has a surface area of 6 cm2 . Its epidermis is a stratified squamous epithelium with basal, intermediate, transitional and cornified layers. Cells in the stratum germinativum contain a normal array of organelles, but are characterized by tonofilaments, desmosomes and interdigitating surfaces. Cellular organelles disappear in the stratum transitivum and are replaced by large vacuoles and keratohyalin bands. Nonmyelinated nerve fibers are abundant in the stratum germinativum. The dermis consists of (1) an avascular layer of dense collagen subjacent to the epidermis and containing many nonmyelinated nerves, and (2) an underlying layer of areolar connective tissue containing blood vessels, lamellar corpuscles and nerves. A layer of coarse elastic fibers, reinforced by collagen and smooth muscle, separates the dermis from subcutaneous tissue. In contrast to the ventral apterium, the incubation patch is featherless and visibly hypervascular and edematous. Its epidermis is both hypertrophic and hyperplastic. Large spaces separate cells in the stratum germinativum. The visible hypervascularity is due to hyperemia and increased number and size of blood vessels in the dermis. Visible edema is due to the accumulation of fluid interstitially. Although no histological differences exist among various regions of the ventral apterium, such differences are present in the incubation patch.


MicroRNA-548j functions as a metastasis promoter in human breast cancer by targeting Tensin1.
MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that participate in important biological processes. Although the functions of many miRNAs in breast cancer metastasis have been established, the role of others remains to be characterized. To identify additional miRNAs involved in metastasis, we performed a genetic screen by transducing a Lenti-miR™ virus library into MCF-7 cells. Using transwell invasion assays we identified human miR-548j as an invasion-inducing miRNA. The endogenous levels of miR-548j expression in breast cancer cell lines were shown to correlate with invasiveness. Moreover, miR-548j was shown to stimulate breast cancer cell invasion and metastasis in vitro and in vivo, but had no effect on proliferation. Next, using a series of in vitro and in vivo experiments, we found that Tensin1 served as a direct and functional target of miR-548j. Both miR-548j and Tensin1 modulated the activation of Cdc42 to regulate cell invasion and siCdc42 or the selective Cdc42 inhibitor ML141 suppressed the pathway of miR-548j-mediated cell invasion. Furthermore, a strong correlation between miR-548j, Tensin1, metastasis and survival was observed using two sets of clinical breast cancer samples. Our findings demonstrate that miR-548j functions as a metastasis-promoting miRNA to regulate breast cancer cell invasion and metastasis by targeting Tensin1 and activating Cdc42, suggesting a potential therapeutic application in breast cancer.


Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists.
Single cardiac transmembranous Ca channels have three modes of gating behaviour in the absence of drugs, expressed as current records with brief openings (mode 1), with no openings because of channel unavailability (mode 0 or null mode) and with long-lasting openings and very brief closings that appear only rarely (mode 2). The dihydropyridine Ca agonist Bay K 8644 enhances Ca channel current by promoting mode 2, while the Ca antagonists nitrendipine and nimodipine inhibit the current by favouring mode 0.


Combinatorial development of bulk metallic glasses.
The identification of multicomponent alloys out of a vast compositional space is a daunting task, especially for bulk metallic glasses composed of three or more elements. Despite an increasing theoretical understanding of glass formation, bulk metallic glasses are predominantly developed through a sequential and time-consuming trial-and-error approach. Even for binary systems, accurate quantum mechanical approaches are still many orders of magnitude away from being able to simulate the relatively slow kinetics of glass formation. Here, we present a high-throughput strategy where ∼3,000 alloy compositions are fabricated simultaneously and characterized for thermoplastic formability through parallel blow forming. Using this approach, we identified the composition with the highest thermoplastic formability in the glass-forming system Mg-Cu-Y. The method provides a versatile toolbox for unveiling complex correlations of material properties and glass formation, and should facilitate a drastic increase in the discovery rate of metallic glasses.


N-acetyl-beta-glucosaminidase (NAG) and alpha-glycosidase released by PAF in isolated perfused rat kidney.
The action of PAF is involved in various biological activities, including alterations at the renal level. Previous experiments of ours have shown that PAF is capable of inducing histamine release at this level, and causing histological damage in the isolated perfused rat kidney. On the basis of these observations, the same experimental model was used to evaluate the release of enzymes such as NAG and alpha-glycosidase, which are precocious markers of renal damage. Results show that both NAG and alpha-glycosidase increase after PAF administration.


General and controllable synthesis strategy of metal oxide/TiO2 hierarchical heterostructures with improved lithium-ion battery performance.
We demonstrate a simple, efficient, yet versatile strategy for the synthesis of novel hierarchical heterostructures composed of TiO(2) nanofiber stem and various metal oxides (MOs) secondary nanostructures, including Co(3)O(4), Fe(2)O(3), Fe(3)O(4), and CuO, by advantageously combining the versatility of the electrospinning technique and hydrothermal growth method, for which the controllable formation process and possible formation mechanism are also investigated. Moreover, as a proof-of-concept demonstration of the functional properties of these hierarchical heterostructures, the Co(3)O(4)/TiO(2) hierarchical heterostructures are investigated as the lithium-ion batteries (LIBs) anode materials for the first time, which not only delivers a high reversible capacity of 632.5 mAh g(-1) and 95.3% capacity retention over 480 cycles, but also shows excellent rate capability with respect to the pristine TiO(2) nanofibers. The synergetic effect between Co(3)O(4) and TiO(2) as well as the unique feature of hierarchical heterostructures are probably responsible for the enhanced electrochemical performance.


Expression and diagnostic value of circulating miRNA-190 and miRNA-197 in patients with pulmonary thromboembolism.
Diagnosing pulmonary thromboembolism (PTE) remains challenging due to the lack of specific clinical symptoms and biomarkers. Circulating microRNAs (miRNAs) have proved to be potential biomarkers for numerous cardiovascular diseases. The aims of this study were to quantitatively analyze the expression of plasma miRNA-190 and miRNA-197 in patients with PTE and to evaluate the diagnostic value for PTE. Thirty patients diagnosed with PTE by computed tomographic pulmonary angiography at the emergency department were enrolled in this study, and plasma was collected immediately. For comparison, myocardial infarction (MI, n = 45) and healthy participants (NC, n = 45) were recruited as the control groups. Quantitative reverse transcription PCR (qRT-PCR) was conducted to reveal the relative expression levels of miRNA-190 and miRNA-197 in each group. The plasma concentrations of D-dimer were measured by immunoturbidimetric assay. The diagnostic value was evaluated by analyzing the area under the receiver operating characteristic curve (AUC). The relative expression levels of miRNA-190 and miRNA-197 in the PTE group were both significantly higher than in the MI group (t = 3.602 t = 4.791, P < .05, respectively) and the healthy control group (t = 5.814, t = 5.886, P < .05, respectively). As diagnostic indicator, the sensitivity and specificity of miRNA-190 were 75.56% and 80%, respectively, with an AUC of 0.7844 (95%CI: 0.6858-0.8831, P < .001). The sensitivity and specificity of miRNA-197 were 73.33% and 86.67%, respectively, with an AUC value of 0.7931 (95%CI: 0.6870-0.8991, P < .001). Combining miRNA-190 and miRNA-197 with D-dimer levels significantly increased the diagnostic power, improving the AUC to 0.9536 (95% CI: 0.9083-0.9989, P < .001). The relative expression levels of miRNA-190 and miRNA-197 in PTE patients were significantly higher than in the MI and healthy control groups, indicating that (a) both may be involved in the pathophysiological process of PTE and (b) both may serve as potential noninvasive diagnostic markers for PTE. The combination of miRNA-190, miRNA-197, and D-dimer levels showed better sensitivity and specificity, which is more conducive to the diagnosis of PTE.


Ocean migration and recaptures of tagged, triploid, mixed-sex and all-female Atlantic salmon (Salmo salar L.) released from rivers in Ireland.
Fiftyfour thousand diploid and triploid Atlantic salmon were tagged with coded-wire micro-tags and released to the sea as smolts from two freshwater sites in Ireland in 1996 and 1997. Over 36,000 were mixed-sex groups in which the triploids (MS3N) were treated batches and the diploids (MS2N) were untreated batches of a single group of fertilized eggs at each site and year class. Over 17,000 were all-females, the triploids (AF3N) being treated batches and the diploids (AF2N) untreated batches of a single group of fertilized eggs at each site and year class. Adult tagged fish were subsequently recovered in the coastal fishery and in freshwater traps and angling fisheries in the rivers of release during 1997, 1998 and 1999. Recoveries from migration ranged from 0.08 to 9.79%. Diploid recoveries were within the normal ranges for salmon ranched from these sites, being between 0.64 and 1.82% at one site and between 3.85 and 9.79% at the other. Triploid recoveries, which occurred in the coastal fishery and in freshwater, ranged from 0.08 to 0.40% at the first site and from 0.98 to 2.05% at the other. Overall, triploid recoveries were between 12 and 24% of their diploid siblings within each release group. There were two peaks of recapture in the coastal fishery, the first in mid-June and the second in mid to late July. All-female diploids appeared to enter the fishery in advance of mixed-sex diploids. Triploids were the latest to arrive. There was no evidence of increased straying in triploids relative to diploids and the mean lengths, weights and condition factors were not significantly different between the ploidy groups. Triploidisation therefore reduced the home water harvest of treated salmon to less than 25% but did not completely eliminate triploid recaptures. The way in which triploidisation may influence the return of salmon from the oceanic feeding grounds is discussed.


Differences between children and adults with otitis media with effusion treated with CO(2) laser myringotomy.
The safety and advantages of CO(2) laser myringotomy for otitis media with effusion (OME) are well described. The goal of such treatment is to avoid unnecessary ventilation tube insertion. Comparisons between different age groups treated with this modality are lacking, and prognostic factors for treatment outcomes are not available. We conducted a retrospective cohort study that included 130 children (160 ears) and 96 adults (108 ears) with OME persisting after conservative antibiotic treatment. In eligible patients, we performed laser myringotomy in the affected ear. Follow-up was scheduled every week for 1 month and then every month for 6 months. Results for 233 ears were available for analysis; 24 ears were excluded (19 due to cancer, four due to a cleft palate, and one due to Down syndrome) and 10 patients (11 ears) were lost during follow-up. A logistic regression model was used for analysis, with success of therapy as the binary outcome. Adult patients had more unilateral lesions (p < 0.001) and serous fluid effusions (p < 0.001) than did the pediatric patients. However, there was no significant difference in the cure rate (children: 58.1%; adults: 64.7%) and positive culture rate (children: 15.1%; adults: 14.3%) between patient groups. Three factors were found to be associated with a poor prognosis: multiple occurrences in children (p < 0.001), mucoid effusion (p = 0.04), and a history of ventilation tube use in adults (p < 0.001). No other variables predicted treatment outcome. Our findings suggest that CO(2) laser myringotomy is a useful treatment modality for OME in children and adults, except for children with multiple occurrences and in adults with mucoid effusions and a history of ventilation tube use.


The difficult--and often delayed--diagnosis of CTCL.
High-throughput sequencing of T cell receptors to define and quantify T cell populations emerges as a diagnostic tool with the remarkable ability to discriminate between CTCL and benign inflammatory conditions (Kirsch et al., this issue).


Time-dependent recruitment of GAF, ISGF3 and IRF1 complexes shapes IFNα and IFNγ-activated transcriptional responses and explains mechanistic and functional overlap.
To understand in detail the transcriptional and functional overlap of IFN-I- and IFN-II-activated responses, we used an integrative RNAseq-ChIPseq approach in Huh7.5 cells and characterized the genome-wide role of pSTAT1, pSTAT2, IRF9 and IRF1 in time-dependent ISG expression. For the first time, our results provide detailed insight in the timely steps of IFNα- and IFNγ-induced transcription, in which pSTAT1- and pSTAT2-containing ISGF3 and GAF-like complexes and IRF1 are recruited to individual or combined ISRE and GAS composite sites in a phosphorylation- and time-dependent manner. Interestingly, composite genes displayed a more heterogeneous expression pattern, as compared to GAS (early) and ISRE genes (late), with the time- and phosphorylation-dependent recruitment of GAF, ISGF3 and IRF1 after IFNα stimulation and GAF and IRF1 after IFNγ. Moreover, functional composite genes shared features of GAS and ISRE genes through transcription factor co-binding to closely located sites, and were able to sustain IFN responsiveness in STAT1-, STAT2-, IRF9-, IRF1- and IRF9/IRF1-mutant Huh7.5 cells compared to Wt cells. Thus, the ISRE + GAS composite site acted as a molecular switch, depending on the timely available components and transcription factor complexes. Consequently, STAT1, STAT2 and IRF9 were identified as functional composite genes that are part of a positive feedback loop controlling long-term IFNα and IFNγ responses. More important, in the absence of any one of the components, the positive feedback regulation of the ISGF3 and GAF components appeared to be preserved. Together, these findings provide further insight in the existence of a novel ISRE + GAS composite-dependent intracellular amplifier circuit prolonging ISG expression and controlling cellular responsiveness to different types of IFNs and subsequent antiviral activity. It also offers an explanation for the existing molecular and functional overlap between IFN-I- and IFN-II-activated ISG expression.


PATIKAmad: putting microarray data into pathway context.
High-throughput experiments, most significantly DNA microarrays, provide us with system-scale profiles. Connecting these data with existing biological networks poses a formidable challenge to uncover facts about a cell's proteome. Studies and tools with this purpose are limited to networks with simple structure, such as protein-protein interaction graphs, or do not go much beyond than simply displaying values on the network. We have built a microarray data analysis tool, named PATIKAmad, which can be used to associate microarray data with the pathway models in mechanistic detail, and provides facilities for visualization, clustering, querying, and navigation of biological graphs related with loaded microarray experiments. PATIKAmad is freely available to noncommercial users as a new module of PATIKAweb at http://web.patika.org.


Efficacy of Carbon Nanodots and Manganese Ferrite (MnFe2O4) Nanoparticles in Stimulating Growth and Antioxidant Activity in Drought-Stressed Maize Inbred Lines.
Despite being the third most-consumed crop, maize (Zea mays L.) is highly vulnerable to drought stress. The predominant secondary metabolite in plants is phenolic acids, which scavenge reactive oxygen species to minimize oxidative stress under drought stress. Herein, the effect of carbon nanodots (CND) and manganese ferrite (MnFe2O4) nanoparticles (NP) on the drought stress tolerance of maize has been studied. The experimental results revealed that the highest leaf blade length (54.0 cm) and width (3.9 cm), root length (45.2 cm), stem diameter (11.1 mm), root fresh weight (7.0 g), leaf relative water content (84.8%) and chlorogenic (8.7 µg/mL), caffeic (3.0 µg/mL) and syringic acid (1.0 µg/mL) contents were demonstrated by CND-treated (10 mg L-1) inbred lines (GP5, HW19, HCW2, 17YS6032, HCW3, HCW4, HW7, HCW2, and 16S8068-9, respectively). However, the highest shoot length (71.5 cm), leaf moisture content (83.9%), shoot fresh weight (12.5 g), chlorophyll content (47.3), and DPPH free radical scavenging activity (34.1%) were observed in MnFe2O4 NP-treated (300 mg L-1) HF12, HW15, 11BS8016-7, HW15, HW12, and KW7 lines, respectively. The results indicate that CND and MnFe2O4 NP can mitigate drought stress effects on different accessions of the given population, as corroborated by improvements in growth and physio-biochemical traits among several inbred lines of maize.


An investigation of the general, reproductive and postnatal developmental toxicity of Betapol, a human milk fat equivalent.
Betapol consists of triglyceride fatty acids commonly found in vegetable and animal fats. A similarity to human milk fat indicated a potential use in infant formulae as well as for food use in general. To test the potential for substantial equivalence with a related food grade oil, palm oil, Betapol was fed to rats at 15% content in the diet using an augmented two-generation study, in order to obtain information on general (6 months), reproductive and postnatal developmental toxicity in a single study rather than separate studies. For comparison there were two control groups, namely a comparative control fed a diet containing 15% of food grade oil and a negative, or laboratory standard control fed a commercial rodent breeding diet (LAD), containing 2.3-4.7% fat. It was reasoned that if Betapol fed groups showed differences from the comparative control in the direction of the negative control these would reflect differences in the nutritional value of the high fat diets. Presence of a toxicant might be indicated by differences from the comparative control group opposite to the negative control group. The group fed 15% Betapol showed occasional, statistically significant differences from the comparative control group but the direction of difference was towards the negative control group and did not indicate the presence of an unexpected toxicant.


#PlasticsTwitter: The Use of Twitter Data as a Tool for Evaluating Public Interest in Cosmetic Surgery Procedures.
Plastic surgeons are increasingly turning to social media to market their services. The newly released Twitter Academic Research Product Track (TARPT) database provides free, customizable analysis of keywords that are included in tweets on the Twitter platform. The TARPT tool may provide valuable insight into public interest in cosmetic surgery procedures. The aim of this study was to determine TARPT's utility in tracking and predicting public interest in cosmetic surgery procedures and to examine temporal trends in tweets related to cosmetic facial and body procedures. The TARPT tool was used to calculate the total number of tweets containing keywords related to 10 facial cosmetic procedures and 7 cosmetic body procedures from 2010 to 2020. Annual volumes for respective procedures were obtained from annual statistics reports of The Aesthetic Society from 2010 to 2020. Tweet volumes and procedure volumes were compared by univariate linear regression, taking P < 0.05 as the cutoff for significance. Variations in tweet volume were observed. Univariate linear regression analysis demonstrated statistically significant positive correlations between tweet volumes and procedure volumes for 7 search terms: "eyelid lift," "facelift," "lip injections," "mastopexy," "butt lift," "butt implants," and "liposuction." Many procedure-related keywords were not significant, demonstrating the importance of careful selection of Twitter search terms. The TARPT database represents a promising novel source of information for plastic surgeons, with the potential to inform marketing and advertising decisions for emerging trends in plastic surgery interest before these patterns become apparent in surgical or clinical volumes.


MALDI-TOF as a tool for microbiological monitoring in areas considered aseptic.
To maintain asepsis in production environments, contamination must be constantly controlled. To this end, microbiological monitoring is constantly used with the objective of evaluating the incidence of microorganisms prevalent in the sampling of air, surface, and people, in the area of an environment considered aseptic, isolated, and identified using the rapid and automated phenotypic microbiological methodology, highlighting the MALDI-TOF mass spectrometry analysis technique (MS), being identified at the level of genus and/or species. For that purpose, microbiological control of environmental monitoring of environments considered aseptic in a pharmaceutical industry was conducted for 12 months. The isolated microorganisms were identified using the mass spectrometry identification method (MALDI-TOF). In area classification A, the most prevalent microorganisms were bacteria in the sampling person. The microbial population was composed of bacteria of the genus Micrococcus sp. and Staphylococcus sp. Based on the results, it is possible to observe that in an environment where the process requires human operations, possible microbial contamination is inevitable and requires the identification of microorganisms at least at the level of species and/or genus. The microorganisms identified and found in the sampling of the aseptic environment must be evaluated with frequency to ensure that the productive environment guarantees the quality of the product produced.


Use of veterinary services by Latino dog and cat owners with various degrees of English-language proficiency.
To characterize patterns of dog and cat ownership and veterinary service use among Latino dog and cat owners with various degrees of English-language proficiency. DESIGN :Cross-sectional telephone survey. Data from 393 Latino pet owners. Telephone surveys were conducted with Latino dog and cat owners from a random sample of US households to determine the number of dogs and cats owned, factors associated with veterinary service use, and satisfaction with veterinary care. 393 of 1,026 (38.3%) respondents were pet owners. Two hundred fifty-nine of 330 (78.5%) dog owners and 70 of 115 (60.9%) cat owners reported taking their pet to the veterinarian in the past 12 months, most commonly for vaccination or examination or because of illness. Respondents were most satisfied with veterinary care provided, least satisfied with cost, and moderately satisfied with quality of communication. English-language proficiency was not significantly associated with whether owners sought veterinary care. A large proportion of respondents who wanted to receive pet health information in Spanish described themselves as speaking English well or very well. Although having limited proficiency in English was not associated with Latino pet owners seeking veterinary care, opportunities exist for veterinary personnel to improve communications with these clients. Personnel can assess their clients' language needs by asking each about the language in which they would prefer to receive their pet's health information.


Laminin gamma 1 chain peptide, C-16 (KAFDITYVRLKF), promotes migration, MMP-9 secretion, and pulmonary metastasis of B16-F10 mouse melanoma cells.
Laminin-1, a heterotrimer of alpha 1, beta 1, and gamma 1 chains specific to basement membrane, promotes cell adhesion and migration, proteinase secretion and metastases of tumour cells. Several active sites on the alpha 1 chain have been found to promote B16-F10 melanoma lung colonisation and here we have determined whether additional tumour promoting sites exist on the beta 1 and gamma 1 chains. Recently, we have identified novel cell adhesive peptides derived from laminin beta 1 and gamma 1 chains by systematic screening of synthetic peptides. Nine beta 1 peptides and seven gamma 1 peptides active for cell adhesion were tested for their effects on experimental pulmonary metastases of B16-F10 mouse melanoma cells in vivo. The most active adhesive peptide derived from the gamma 1 chain globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases of B16-F10 cells, whereas no other peptides showed enhancement. C-16 also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro. Furthermore, C-16 significantly induced the production of MMP-9 from B16-F10 cells. These results suggest that this specific laminin gamma 1 chain peptide has a metastasis-promoting activity and might be a new molecular target of anti-cancer treatment.


Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice.
Tau protein serves a pro-inflammatory function in neuroinflammation. However, the role of tau in other inflammatory disorders such as rheumatoid arthritis (RA) is less explored. This study is to investigate the role of endogenous tau and the potential mechanisms in the pathogenesis of inflammatory arthritis. We established collagen-induced arthritis (CIA) model in wild-type and Tau-/- mice to compare the clinical score and arthritis incidence. Micro-CT analysis was used to evaluate bone erosion of ankle joints. Histological analysis was performed to assess inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Serum levels of pro-inflammatory cytokines were measured by ELISA. The expression levels of macrophage markers were determined by immunohistochemistry staining and quantitative real-time PCR. Tau expression was upregulated in joints under inflammatory condition. Tau deletion in mice exhibited milder inflammation and protected against the progression of CIA, evidenced by reduced serum levels of pro-inflammatory cytokines and attenuated bone loss, inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Furthermore, tau deficiency led to the inhibition of classically activated type 1 (M1) macrophage polarization in the synovium. Tau is a previously unrecognized critical regulator in the pathogenesis of RA and may provide a potential therapeutic target for autoimmune and inflammatory joint diseases.


Evaluation of Seeplex® STD6 ACE Detection kit for the diagnosis of six bacterial sexually transmitted infections.
Traditionally, the diagnosis of bacterial sexually transmitted infection (STI) has been dependent on the isolation of the causative pathogens by culturing endocervical or urethral swab specimens on selective media. While such procedures typically provide excellent diagnostic accuracy, they are often time-consuming and expensive. A multiplex polymerase chain reaction (PCR) assay, based on a semi-automated detection system, was evaluated for the detection of six STI causative organisms. The Seeplex(®) STD6 ACE (auto-capillary electrophoresis) Detection assay employed six pairs of dual priming oligonucleotide (DPO™) primers specifically targeted to unique genes of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis. A total of 739 specimens (304 cervical swabs and 435 urine samples) collected for 4 months were tested, and results were compared to those obtained with a combined monoplex PCR. The concordance between the multiplex PCR and monoplex PCR assay was 100% for both sensitivity and specificity. We also tested for the presence of two pathogenic bacteria (C. trachomatis and N. gonorrhoeae) and compared the results obtained with the multiplex PCR and BD ProbeTec duplex strand displacement amplification (SDA). The results of the multiplex PCR and duplex SDA were 99.7% concordant for C. trachomatis and 100% concordant for N. gonorrhoeae. The multiplex PCR assay using the Seeplex(®) STD6 ACE Detection kit proved to be a novel cost-effective and fast diagnostic tool with high sensitivity and specificity for the simultaneous detection of six STI pathogens.


[Should locomotor disorders of upper extremities under exposure to local vibration be considered as a pathogenetic sign of vibration disease?].
To understand role of local vibration in development of locomotory disorders in hands of vibration disease patients, the authors studied relationship between these disorders with major syndromes in vibration disease. Findings are that the main etiologic factor leading to locomotory changes at work with local vibration is a degree of static efforts in this type of work.


Atrophic gastritis and vitamin C status in two towns with different stomach cancer death-rates.
A survey was conducted of 513 men aged 65 74 years living in two British towns with high and low stomach cancer death-rates. The prevalence of severe atrophic gastritis (defined as a serum pepsinogen I less than 20 micrograms l-1) was significantly higher in the high-risk than in the low-risk town (14.5% and 7.7% respectively); it also tended to be higher in the manual workers, who are known to have a greater risk of stomach cancer than non-manual workers. The manual workers in the high-risk town were particularly likely to have had a partial gastrectomy. Plasma ascorbate concentration and fruit intake were lower in the high-risk area and lower social classes, suggesting a poorer vitamin C status. There was, however, no direct relationship between ascorbate concentration and the presence of severe atrophic gastritis. These findings are consistent with the hypothesis that risk of stomach cancer is determined in two stages--a long-term effect, producing atrophic gastritis; and a short-term effect in which vitamin C is protective.


Reverse remodeling after percutaneous transluminal septal myocardial ablation in severe but asymptomatic LVOT obstruction (RASTA) study: Rationale and design of transcatheter septal reduction in asymptomatic patients with severe hypertrophic obstructive cardiomyopathy.
The aim of this study is to evaluate the impact of percutaneous transluminal septal myocardial ablation (PTSMA) on remodeling in asymptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular outflow tract (LVOT) obstruction. Symptoms justify invasive treatment in HOCM patients with LVOT obstruction. Adverse structural and functional changes (remodeling) in the heart occur preceding heart failure and sudden cardiac death. Early invasive treatment in asymptomatic patients may reverse adverse remodeling to the same extent as in symptomatic patients. Reverse remodeling after PTSMA in severe but asymptomatic LVOT obstruction (RASTA) study is a prospective single-blind randomized trial (ClinicalTrials.gov number: NCT04230551). Ten asymptomatic HOCM patients with an exertional LVOT gradient ≥50 mmHg (or >30 mmHg in rest) are randomized 1:1 to PTSMA versus conservative therapy, in the absence of mitral valve disease or other indications for cardiac surgery. Five symptomatic (reference group) will undergo PTSMA according to the current guidelines. Remodeling is assessed using extensive cardiac imaging with transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance at baseline and during follow-up at 1, 12, and 24 months. Extracellular volume fraction, global, and regional strain analysis, geometry, pressure gradients and changes in four-dimensional velocity mapping are primary parameters to study (reversal of) adverse remodeling. The RASTA study gives insight in cardiac remodeling that may occur in asymptomatic patients after PTSMA. It will provide arguments whether to pursue (or not) a larger trial with clinical endpoints in asymptomatic HOCM patients with severe LVOT obstruction.


Testosterone: more than having the guts to win the Tour de France.
Sex bias in susceptibility to autoimmune diseases is evident but poorly characterized. Yurkovetskiy et al. (2013) report that host testosterone mediates changes in the microbiome to confer protection to adult male NOD mice from type 1 diabetes.


Isolation and characterization of nonhistone proteins associated with DNase-II hypersensitive sites of Sarcoma-180 chromatin.
Limited digestion (2 min) of Sarcoma-180 nuclei by DNase-II released two nonhistone proteins from the hypersensitive sites of chromatin. The apparent molecular weights of these two proteins were 34 and 21 kDa. These proteins showed a moderate but specific inhibition in in vitro cell free transcription assay with native chromatin as template as opposed to no effect on native DNA transcription.


Comparison of iPACK and periarticular block with adductor block alone after total knee arthroplasty: a randomized clinical trial.
The infiltration between the popliteal artery and the capsule of the posterior knee (iPACK) has been described to provide analgesia without loss of muscle strength and is effective in functional recovery. This study compared iPACK + ACB (adductor canal block) with PAI (periarticular infiltration) + ACB and ACB alone in terms of postoperative analgesia and functional improvement. This double-blinded randomized controlled trial included 105 patients undergoing unilateral total knee arthroplasty. Patients received ACB, iPACK + ACB, and PAI + ACB along with spinal anesthesia. The primary outcome was the area under the curve (AUC) numeric rating scale (NRS) at 48 h. Secondary outcomes were cumulative postoperative analgesic consumption within 48 h, timed up-and-go test, range of motion, length of hospital stay, patient satisfaction, and adverse events. The 48-h AUC movement NRS score in the iPACK + ACB group was significantly lower than in the PAI + ACB and ACB groups (p < 0.05). At the postoperative 48th h, the opioid consumption of the iPACK + ACB group was lower than those of the ACB and PAI + ACB groups (p < 0.001). The patients in the iPACK + ACB group had significantly shorter discharge and mobilization days than the ACB and PAI + ACB groups (p < 0.001). The adding of an iPACK block to the ACB improves postoperative analgesia and reduces opioid consumption. In addition, this approach improves functional performance and reduces hospital stay.


A novel phosphorylation site involved in dissociating RAF kinase from the scaffolding protein 14-3-3 and disrupting RAF dimerization.
Rapidly accelerated fibrosarcoma (ARAF, BRAF, CRAF) kinase is central to the MAPK pathway (RAS-RAF-MEK-ERK). Inactive RAF kinase is believed to be monomeric, autoinhibited, and cytosolic, while activated RAF is recruited to the membrane via RAS-GTP, leading to the relief of autoinhibition, phosphorylation of key regulatory sites, and dimerization of RAF protomers. Although it is well known that active and inactive BRAF have differential phosphorylation sites that play a crucial role in regulating BRAF, key details are still missing. In this study, we report the characterization of a novel phosphorylation site, BRAFS732 (equivalent in CRAFS624), located in proximity to the C-terminus binding motif for the 14-3-3 scaffolding protein. At the C terminus, 14-3-3 binds to BRAFpS729 (CRAFpS621) and enhances RAF dimerization. We conducted mutational analysis of BRAFS732A/E and CRAFS624A/E and revealed that the phosphomimetic S→E mutant decreases 14-3-3 association and RAF dimerization. In normal cell signaling, dimerized RAF phosphorylates MEK1/2, which is observed in the phospho-deficient S→A mutant. Our results suggest that phosphorylation and dephosphorylation of this site fine-tune the association of 14-3-3 and RAF dimerization, ultimately impacting MEK phosphorylation. We further characterized the BRAF homodimer and BRAF:CRAF heterodimer and identified a correlation between phosphorylation of this site with drug sensitivity. Our work reveals a novel negative regulatory role for phosphorylation of BRAFS732 and CRAFS624 in decreasing 14-3-3 association, dimerization, and MEK phosphorylation. These findings provide insight into the regulation of the MAPK pathway and may have implications for cancers driven by mutations in the pathway.


Surgical treatment of the incontinent female patient with myelomeningocele.
Surgical therapy was required for 42 incontinent female patients with myelomeningocele who had urodynamically documented high pressure bladders. Conservative treatment consisting of cholinolytic and alpha-adrenergic agents, and intermittent self-catheterization had failed. The surgical approach consisted of perivesical denervation (for hyperreflexia), Burch bladder neck suspension, enlargement cystoplasty and ureteral reimplantation when required. Among 33 patients (79 per cent) there was no incontinence on intermittent self-catheterization and 6 (14 per cent) had improvement with rare urgency or stress incontinence. In 3 patients (7 per cent) sphincteric incompetence required a transvaginal sling procedure.


Corpus luteum--conceptus--follicle relationships during the fertile cycle in rhesus monkeys: pregnancy maintenance despite early luteal removal.
To determine how early in pregnancy cyclic follicle growth is interrupted, 6 pregnant monkeys were luteectomized (CLX) on day 29 or 30 of the cycle (approximately 1 week after implantation) to abbreviate the fertile cycle to approximately the length of nonfertile cycles. Unexpectedly, 3 of 6 monkeys remained pregnant despite early removal of luteal support. In the remainder, which aborted, the next ovulation was delayed beyond the interval typically observed after CLX in nonfertile cycles. Two of 4 other monkeys ovariectomized on day 29 also maintained their pregnancies. Our findings demonstrate that: 1) in 5 of 10 monkeys, the conceptus could survive without luteal support within a week after luteal rescue, and 2) secretion(s) of the conceptus also contribute to an arrest of cyclic follicle growth early in pregnancy.


Cellular and field potential properties of epileptogenic hippocampal slices.
Epileptogenic activity was induced in hippocampal slices by addition of penicillin (2.0mM) to the bathing medium. Field potential epileptiform events were recorded and single cell bursts studied with intracellular electrodes. Epileptogenic activity was seen in areas CA1 and CA3 of the slice, with bursts in CA3 always leading CA1 bursts; a cut between CA1 and CA3 abolished spontaneous bursting in CA1 but not in CA3. Increased (Mg2+) and decreased (Ca2+) abolished epileptiform discharge, thus demonstrating its dependence on synaptic activity; burst occurrence was also sensitive to (K+). Measurements of single cell resting potentials, resistance, and time constant in CA1 cells revealed no difference between cells in normal medium and cells made epileptogenic by penicillin. Depolarization shifts in CA1 neurons during epileptogenesis did not behave like 'giant EPSPs' but rather were complexes to which depolarizing spike after-potentials, fast prepotentials, and underlying slow depolarizing events all contributed.


Differentiation of usual vertebral compression fractures using CT histogram analysis as quantitative biomarkers: A proof-of-principle study.
To investigate the utility of CT histogram analysis (CTHA) for discrimination of traumatic, osteoporotic and malignant fractures in patients with vertebral compression fractures (VCFs). To evaluate the feasibility and accuracy of CTHA in differentiating non-malignant (traumatic and osteoporotic) from malignant VCFs. Totally, 235 patients with VCFs were enrolled in the current experimental study. There were 132 patients with traumatic VCFs, 51 with osteoporotic VCFs and 52 with malignant VCFs, with MRI and histology as the standard references. All the patients underwent unenhanced CT scans. Nineteen histogram-based parameters were derived using Omni-Kinetics software (Omni-Kinetics, GE Healthcare). The reproducibility of those parameters was evaluated using two independent delineations conducted by two observers. These histogram parameters were compared among the three different VCFs using Kruskal-Wallis H test. Traumatic VCFs and osteoporotic VCFs were combined as non-malignant VCFs and compared with malignant VCFs using Mann-Whitney U test Multivariable logistic regression analysis was performed on the significantly different features and built a diagnosis model. Receiver operating characteristic (ROC) curve was carried out to observe the difference of diagnostic performance between the single positive parameter and the combination of parameters. All the 19 parameters presented excellent reproducibility, with intraclass correlation coefficient values from 0.789 to 0.997. At quantitative evaluation, the best predictive histogram parameters in discrimination of the three different types of VCFs were relative min intensity (p = 0.022), relative entropy (p = 0.043), and relative frequency size (p < 0.001). Relative frequency size (p < 0.001) and relative quantile5 (p = 0.012) resulted in statistically significant difference between non-malignant and malignant VCFs. The area under ROC curve indicated that relative frequency size combined with relative quantile5 (0.754; 95 % confidence intervals: 0.661∼0.829; p < 0.001) was of best performance in differentiating malignant from non-malignant VCFs. Our results are encouraging and suggest that histogram parameters derived from unenhanced CT could be reliable quantitative biomarkers for diff ;erential diagnosis of usual VCFs.


Identification in turkey gizzard of an acidic protein related to the C-terminal portion of smooth muscle myosin light chain kinase.
The isolation of an acidic protein, pI 4.5, that is abundant in turkey gizzard is described. Its apparent molecular weight measured by electrophoretic procedures is 24,000. This protein is phosphorylated by the catalytic subunit of the cAMP-dependent protein kinase and one phosphorylation site is indicated. From sequence determinations of tryptic peptides it is concluded that this protein is closely related to the C-terminal part of smooth muscle myosin light chain kinase. The initiation site for the protein is to the C-terminal side of the calmodulin-binding site. From the sequence data an estimated molecular weight is 18,000. This protein is expressed independently, as indicated by a blocked N terminus, and is probably the translation product of the 2.7-kilobase RNA detected previously in chicken gizzard (Guerriero, V., Jr., Russo, M. A., Olson, N. J., Putkey, J. A., and Means, A. R. (1986) Biochemistry 25, 8372-8381). Because of its putative origin as the C-terminal end of smooth muscle myosin light chain kinase, it is termed "telokin" (from a combination of kinase and the Greek telos, "end").


SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease.
Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients with recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit-β (SUCLA2), causing global protein hyper-succinylation. Using mass spectrometry, we quantify nearly 1,000 protein succinylation sites on 366 proteins from patient-derived fibroblasts and myotubes. Interestingly, hyper-succinylated proteins are distributed across cellular compartments, and many are known targets of the (NAD+)-dependent desuccinylase SIRT5. To test the contribution of hyper-succinylation to disease progression, we develop a zebrafish model of the SCL deficiency and find that SIRT5 gain-of-function reduces global protein succinylation and improves survival. Thus, increased succinyl-CoA levels contribute to the pathology of SCL deficiency through post-translational modifications.


Cost effectiveness and budgetary impact of the Boston University approach to Psychiatric Rehabilitation for societal participation in people with severe mental illness: a randomised controlled trial protocol.
People with Severe Mental Illness (SMI) frequently experience problems with regard to societal participation (i.e. work, education and daily activities outside the home), and require professional support in this area. The Boston University approach to Psychiatric Rehabilitation (BPR) is a comprehensive methodology that can offer this type of support. To date, several Randomised Controlled Trials (RCT's) investigating the effectiveness of BPR have yielded positive outcomes with regard to societal participation. However, information about the cost-effectiveness and budgetary impact of the methodology, which may be important for broader dissemination of the approach, is lacking. BPR may be more cost effective than Care As Usual (CAU) because an increase in participation and independence may reduce the costs to society. Therefore, the aim of this study is to investigate, from a societal perspective, the cost-effectiveness of BPR for people with SMI who wish to increase their societal participation. In addition, the budget impact of implementing BPR in the Dutch healthcare setting will be assessed by means of a budget impact analysis (BIA) after completion of the trial. In a multisite RCT, 225 adults (18-64 years of age) with SMI will be randomly allocated to the experimental (BPR) or the control condition (CAU). Additionally, a pilot study will be conducted with a group of 25 patients with severe and enduring eating disorders. All participants will be offered support aimed at personal rehabilitation goals, and will be monitored over a period of a year. Outcomes will be measured at baseline, and at 6 and 12 months after enrolment. Based on trial results, further analyses will be performed to assess cost-effectiveness and the budgetary impact of implementation scenarios. The trial results will provide insight into the cost-effectiveness of BPR in supporting people with SMI who would like to increase their level of societal participation. These results can be used to make decisions about further implementation of the method. Also, assessing budgetary impact will facilitate policymaking. The large sample size, geographic coverage and heterogeneity of the study group will ensure reliable generalisation of the study results. Current Controlled Trials: ISRCTN88987322. Registered 13 May 2014.


A Phenomenological Study on Substance Use and Misuse Among Nursing Students.
There is a critical need to identify and understand the current trends in substance use as well as effective approaches to manage and deter nursing students from misusing drugs. This qualitative study explored the lived experiences, attitudes, and perceptions of prelicen-sure nursing students about substance use and misuse and the management of substance use disorders among nursing students during nursing school. Using a phenomenological research design, 14 semistructured in-depth interviews were conducted. Findings from the data analysis revealed the following six themes: mental health-related issues, stressors, fears and reservations, stigma, seeking help, and awareness. The findings from this study corroborate and build on prior research illustrating nursing students encounter complex challenges that can contribute to drug-seeking behaviors during their prelicensure nursing program. Nurse educators must address these factors and their students' potential decisions to misuse drugs. [J Nurs Educ. 2021;60(11):607-613.].


Species-specific transcriptional reprogramming during adventitious root initiation.
Adventitious roots or shoot-borne roots transdifferentiate from cells close to vascular tissues after cell reprogramming, which is associated with increased transcriptional activity. Recently, Garg et al. provided a genome-wide landscape of transcriptional signatures during the early stages of adventitious root initiation in rice and showed that conserved transcription factors acquire species-specific function.


Design of polymeric carriers for cancer-specific gene targeting: utilization of abnormal protein kinase Calpha activation in cancer cells.
We succeeded in cancer cell specific gene expression by using a polyplex responsive to protein kinase Calpha, which is activated in various types of cancer cells.


Imaging the urologic patient: the utility of intravenous pyelogram in the CT scan era.
An opportunity exists to evaluate the quality of care in patients undergoing intravenous pyelogram (IVP) imaging and to define the role of IVP in the computed tomography scan era. Medical records were reviewed for patient demographics, inpatient versus outpatient setting, indication for IVP, physician/specialty who ordered IVP, and the need for subsequent imaging within a 30-day period in patients who underwent IVP from October 2007 to December 2011. Chi-square test was used to compare the number of additional radiologic examinations ordered within 30 days of the initial IVP across the different specialties ordering IVPs. Six hundred and eighty patients underwent IVP imaging during the study period. The primary reason to order an IVP was the evaluation of urolithiasis/flank pain (50%), followed by urologic evaluation after surgery (23%). Three hundred and twenty-five patients (48%) subsequently had an additional 547 radiologic studies within 30 days of the IVP to further evaluate their condition. Of the 325 patients undergoing additional imaging studies, 36% had differing or additional diagnostic information noted that could change medical decision-making. Inferior imaging of the urologic patient by IVP leads to the acquisition of additional imaging studies to render a diagnosis. IVP has a limited clinical role, and thus, its use should be strictly limited to highly select cases.


Predicting merchant future performance using privacy-safe network-based features.
Small and Medium-sized Enterprises play a significant role in most economies by contributing to job creation and economic growth. A majority of such merchants rely on business financing, and thus, financial institutions and investors need to assess their performance before making decisions on business loans. However, current methods of predicting merchants' future performance involve their private internal information, such as revenue and customer base, which cannot be shared without potentially exposing critical information. To address this problem, we first propose a novel approach to predicting merchants' future performance using credit card transaction data. Specifically, we construct a merchant network, regarding customers as bridges between merchants, and extract features from the constructed network structure for prediction purposes. Our study results demonstrate that the performance of machine learning models with features extracted from our proposed network is comparable to those with conventional revenue- and customer-based features, while maintaining higher privacy levels when shared with third-party organizations. Our approach offers a practical solution to privacy concerns over data and information required for merchants' performance prediction, enabling safe data-sharing among financial institutions and investors, helping them make more informed decisions on allocating their financial resources while ensuring that merchants' sensitive information is kept confidential.


Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells.
The cellular mass of sn-1,2-diacylglycerols, which are intracellular second messengers which activate protein kinase C, were quantitatively determined with an enzymatic assay. The method employed to harvest cultured human skin fibroblasts or human epidermal A431 cells prior to extraction of lipid into chloroform/methanol affected diacylglycerol (DAG) levels. Scraping or trypsinization significantly increased DAG levels. A method was devised to allow reliable and reproducible DAG measurements from adherent cells. The addition of methanol prior to scraping was shown to stop cellular metabolism and to permit accurate quantitation. Importantly, this solvent was compatible with cultures grown on plastic. Using this method, growth conditions which could affect DAG levels were investigated. Changes in the osmolality of the culture medium did not affect the DAG levels of A431 cells; exposure of A431 cells to acidic pH or elevated temperature lowered DAG levels. In contrast to fibroblasts, the total DAG levels of A431 cells continued to increase during serum deprivation. The highest DAG levels, normalized to phospholipids, were observed during the exponential growth phase. This ratio dropped when the cultures reached confluency. These experiments also demonstrated that A431 cells possess higher DAG levels than do normal fibroblasts. The function of DAG in cellular regulation is discussed.


[Aseptic non-union of humeral shaft fractures treated by plating and bone grafting. Report of 20 cases].
Although aseptic non-union of humeral shaft fractures is generally considered to be an exceptional complication, rates in the literature have varied from 1 to 10%. The aim of this retrospective study was to study the results of treatment by plating and bone grafting for aseptic non-union of humeral shaft fractures. The retrospective study gathered 20 patients, the mean age was 41 years. The most common fracture site was the middle third. For the follow-up evaluation, we used the Steward and Hundley score. According to this score, we noted: 13 very good results, five good results and two poor results. Management of non-union of the humerus should be optimal at immediate surgery. The best treatment of non-union of the humerus is its prevention by correct management of the initial fracture.


Synthesis of Cd-free water-soluble ZnSe(1-x)Te(x) nanocrystals with high luminescence in the blue region.
Cd-free core-shell nanocrystals (ZnSe(1-x)Te(x)/ZnS, 0<or=x<or=0.5) emitting in the pure blue region were prepared using an aqueous colloidal method followed by post-preparative ultraviolet irradiation. The photoluminescence (PL) efficiency and peak wavelength were maximized (40%, 448 nm) through a heat treatment of the nanocrystals during irradiation in a Zn(2+)-containing thiol solution. Because of the small lattice mismatch between ZnSe(1-x)Te(x) and ZnS, post-preparative irradiation at high temperature resulted in the formation of a thick ZnS shell (ca. 1.6 nm) around the core (ca. 2.2 nm in diameter) without deterioration of PL efficiency. Surface substitution of Te by S and size-selective precipitation of nanocrystals before ultraviolet irradiation resulted in intense PL. Quantum mechanical calculations show that the wave function of the electron of the exciton in the Te-containing core extends well into the ZnS shell. The calculations also reveal that a thick shell can confine the electrons inside the particles and thereby improve the PL efficiency and stability against the pH of the solution. Nanocrystals that had been post-preparatively irradiated showed good stability in solution and in a glass matrix even after months of storage in air.


Alien hand syndrome, a rare presentation of corpus callosum and cingulate infarction.
Alien hand syndrome (AHS) is a rare apraxia syndrome, characterized by involuntary and uncontrollable movements of one upper limb, often accompanied by intermanual conflict. Damage to the corpus callosum, acute infarction and neurodegenerative disease may result in AHS. Based on the presentation and impairment region, AHS has three variants: frontal, callosal and posterior. Each type may have a different clinical presentation. A total of 157 patients admitted to hospital with corpus callosum infarction between 2012 and 2022 were included for this study, of whom a number of 5 presented with AHS. 4 of them had significant symptoms of intermanual conflict and 1 had strong grip symptoms in the affected upper limb. Moreover, new infarcts involving the corpus callosum and cingulate gyrus were found on MRI in all five patients. We simultaneously performed a retrospective study on all reported AHS cases caused by infarction of the corpus callosum. Case reports and literature reviews were conducted in order to provide clinicians with a better understanding of AHS, its etiology, clinical presentation, diagnosis, and treatment.


Familial hemiplegic migraine presenting as recurrent encephalopathy in a Native Indian family.
Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, which can result from mutations in the CACNA1A (FHM1) and ATP1A2 (FHM2) genes. Typically, FHM presents with an aura of hemiplegia accompanied by a moderate-to-severe headache. FHM can be associated with other neurological findings including coma and seizures. We describe the clinical and genetic features of a two-generation, seven-member Native Indian family with recurrent encephalopathy and FHM. Two of the three affected family members presented initially with encephalopathy, the third family member presented with classic episodes of migraine and hemiparesis. The CACNA1A gene locus was excluded in this family by haplotype analysis and no mutations were identified in the coding region of the ATP1A2 gene by direct sequencing. This emphasizes the genetic and clinical heterogeneity in familial hemiplagic migraine FHM and highlights the need to consider the diagnosis of FHM in cases of recurrent encephalopathy.


A new asset for pathogen informatics--the Enteropathogen Resource Integration Center (ERIC), an NIAID Bioinformatics Resource Center for Biodefense and Emerging/Re-emerging Infectious Disease.
ERIC (Enteropathogen Resource Information Center) is one of the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers for Biodefense and Emerging/Re-emerging Infectious Disease. ERIC serves as a comprehensive information resource for five related pathogens: Yersinia enterocolitica, Yersinia pestis, diarrheagenic E. coli, Shigella spp., and Salmonella spp. ERIC integrates genomics, proteomics, biochemical and microbiological information to facilitate the interpretation and understanding of ERIC pathogens and select related non-pathogens for the advancement of diagnostics, therapeutics, and vaccines. ERIC (www.ericbrc.org) is evolving to provide state-of-the-art analysis tools and data types, such as genome sequencing, comparative genomics, genome polymorphisms, gene expression, proteomics, and pathways as well as expertly curated community genome annotation. Genome sequence and genome annotation data and a variety of analysis and tools for eight strains of Yersinia enterocolitica and Yersinia pestis pathogens (Yersinia pestis biovars Mediaevalis KIM, Mediaevalis 91001, Orientalis CO92, Orientalis IP275, Antiqua Angola, Antiqua Antiqua, Antiqua Nepal516, and Yersinia enterocolitica 8081) and two strains of Yersinia pseudotuberculosis (Yersinia pseudotuberculosis IP32953 and IP31758) are currently available through the ERIC portal. ERIC seeks to maintain a strong collaboration with the scientific community so that we can continue to identify and incorporate the latest research data, tools, and training to best meet the current and future needs of the enteropathogen research community. All tools and data developed under this NIAID contract will be freely available. Please contact firstname.lastname@example.com for more information.


Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro.
Prevention of the spread of epidemic keratoconjunctivitis (EKC) at eye care facilities (doctors' offices, clinics, hospitals) has been a major public health goal for ophthalmology for more than 50 years. The authors explored a potentially contributing attribute of the adenovirus serotypes that cause EKC. Specifically, they investigated the capacity of different clinical and laboratory ocular serotypes (AD8, 19, and 5) to survive for extended periods of time in a desiccated state. Twenty microliters containing 2000 plaque-forming units of different ATCC laboratory adenoviral ocular serotypes (AD8, 19, and 5) and clinical isolates (AD8 Cray, AD19 Kowalski, and AD5 McEwen) were inoculated onto 7-mm plastic disks and 6-mm aluminum foil disks and were allowed to completely desiccate. At weekly intervals up to 7 weeks, eight desiccated virus-inoculated plastic or metal disks per serotype were added to tissue culture medium, and the amount of recoverable virus was determined by plaque assay on A549 cells. Ocular adenoviral serotypes AD8, 19, and 5 could be recovered up to 49 days from plastic, and 35 to 49 days from metal. Sufficient virus concentrations (> 100 plaque-forming units/disk) to be clinically infectious were recovered up to 28 days. Differences in recovery among serotypes (AD19 > AD5, AD8) were demonstrated, but laboratory and clinical isolates of the same serotype were usually comparable. Ocular isolates of adenovirus that cause EKC are much harder than previously suspected, and the capacity to survive in a desiccated state may possibly play some role in office-based mini-epidemics of EKC.


Is Erythrocytosis More Common After Simultaneous Pancreas Kidney Transplantation? A Single-Center Experience.
Post-transplant erythrocytosis (PTE) is reported in 8% to 22% of kidney transplant recipients. Few studies have evaluated the prevalence of PTE in simultaneous kidney-pancreas transplantation (SPKT). This study aimed to evaluate the prevalence of PTE in a cohort of SPKT and same-donor single kidney transplant patients and find predictive factors for erythrocytosis development. A single-center retrospective cohort study was performed with 65 SPKT recipients and 65 same-donor single kidney transplant patients. Post-transplant erythrocytosis was defined as a hematocrit persistently >51% without a known cause of erythrocytosis. The PTE prevalence was 23.1% and was more frequent in SPKT patients than in single donor patients (38.5% vs 7.7%; P < .001). The mean time for PTE development was 11.2 ± 13.3 months. In the multivariate model, SPKT was the only predictor for PTE development. De novo hypertension was more frequent in the PTE group (P = .002), but there was no difference in stroke and pancreatic or kidney thrombosis occurrence. Post-transplant erythrocytosis is more common after SPKT than after single kidney transplantation. De novo hypertension was more frequent in the erythrocytosis group, but allograft thrombosis rates.


A practical guide to the management of menopausal symptoms in breast cancer patients.
Breast cancer is the most frequently diagnosed cancer in Canadian women. As a result of increased screening and improved treatment, more women are becoming long-term breast cancer survivors. However, due to either their treatment or prolonged survival, many of these women now have to face the consequences of premature menopause and prolonged estrogen deprivation. Hormone replacement therapy/estrogen replacement therapy (HRT/ERT) has, in the past, been recommended to healthy women at menopause not only for relief of short-term menopausal changes, particularly hot flashes, but also for its benefits on bone density, fracture reduction, and genitourinary symptoms. Recent studies have demonstrated that not only is HRT associated with an increased risk of developing breast cancer, but it also has been shown to increase the risk of recurrence in those with a breast cancer history. Until the safety of HRT/ERT in breast cancer patients can be more fully clarified, it would be wise to develop alternative strategies for the management of menopausal symptoms in these patients. This paper will discuss nonestrogen-based therapies for hot flashes, osteoporosis, and genitourinary symptoms, with emphasis on efficacy and safety in breast cancer survivors.


Metabolic changes induced by urethane-anesthesia in rats.
1. Fasting hyperglycemia was observed in urethane-anesthetized rats. No significant changes had been observed in fed animals. The effect is dose-dependent, being ineffective doses lesser than 1.4 g/kg of body weight. 2. Urethane originates a rise in glycemia during the first 10 min of anesthesia followed by control values at 30 min, and a latter hyperglycemic phase for more than 60 min that remain at 2 hr. 3. The negative correlationship between plasma glucose, lactate and amino acid levels suggest that gluconeogenesis may be the main responsibility of the observed hyperglycemia during the first phase, but it is possible that during the second phase a decrease in the consumption of glucose may take place as a consequence of the competitive effects of ketone bodies increased during the first 30 min of anesthesia. 4. We postulate that the mechanism of the hyperglycemic response to urethane is a sympathetic response with release of catecholamines both in the liver and in the adrenal gland which enhances gluconeogenesis and lipolysis.


Pharmacological or genetic inhibition of LDHA reverses tumor progression of pediatric osteosarcoma.
Reprogrammed energy metabolism is an emerging hallmark of cancer. Lactate dehydrogenase A (LDHA), a key enzyme involved in anaerobic glycolysis, is frequently deregulated in human malignancies. However, limited knowledge is known about its roles in the progression of osteosarcoma (OS). In this study, we found that LDHA is commonly upregulated in four OS cell lines compared with the normal osteoblast cells (hFOB1.19). Treatment with FX11, a specific inhibitor of LDHA, significantly reduced LDHA activity, and inhibited cell proliferation and invasive potential in a dose dependent manner. Genetic silencing of LDHA resulted in a decreased lactate level in the culture medium, reduced cell viability and decreased cell invasion ability. Meanwhile, silencing of LDHA also compromised tumorigenesis in vivo. Furthermore, knockdown of LDHA remarkably reduced extracellular acidification rate (ECAR) as well as glucose consumption. In the presence of 2-DG, a glycolysis inhibitor, LDHA-mediated cell proliferation and invasion were completely blocked, indicating the oncogenic activities of LDHA may dependent on Warburg effect. Finally, pharmacological inhibition of c-Myc or HIF1α significantly attenuated LDHA expression. Taken together, upregulated LDHA facilitates tumor progression of OS and might be a potential target for OS treatment.


Results of long-term follow-up of patients with completely resected non-small cell lung cancer.
In patients with completely resected non-small cell lung cancer, recurrence-free survival, postrecurrence survival, and metachronous primary lung cancer have not been well studied at the same time. A total of 315 patients with non-small cell lung cancer who underwent complete resection between 2001 and 2005 were examined. Patients were routinely assessed with computed tomography of the chest and physical checkups every 4 months for the first 2 years and every 6 months from the third to the fifth year. After that, they were examined annually. The overall 5-year survival was 70%. Of all 315 patients, 107 had recurrent disease. The median recurrence-free survival was 15.7 months. Multivariate analysis showed that pathologic stage and pleural invasion were associated with decreased recurrence-free survival. The median postrecurrence survival was 18.7 months. Multivariate analysis indicated that male sex, pleural invasion, extrathoracic recurrence, and supportive care for recurrence were associated with decreased postrecurrence survival. The cumulative rate of metachronous primary lung cancer at 5 years was 3.7%, and it developed even 8 years after the initial operation. Only pleural invasion of the original lung cancer was related to both recurrence-free survival and postrecurrence survival. Moreover, postrecurrence survival was related to both site and treatment of the initial recurrence. The incidence of metachronous primary lung cancer was stable over time after the initial operation.


Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.
Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales.


Diminishing striatal activation across adolescent development during reward anticipation in offspring of schizophrenia patients.
Schizophrenia is a severe psychiatric disorder associated with impaired fronto-striatal functioning. Similar deficits are observed in unaffected siblings of patients, indicating that these deficits are linked to a familial risk for the disorder. Fronto-striatal deficits may arise during adolescence and precede clinical manifestation of the disorder. However, the development of the fronto-striatal network in adolescents at increased familial risk for schizophrenia is still poorly understood. In this cross-sectional study, we investigate the impact of familial risk on fronto-striatal functioning across age related to reward anticipation and receipt in 25 adolescent offspring of schizophrenia patients (SZ offspring) and 36 age-matched healthy controls (range 10-19years). Subjects performed a reward task while being scanned with functional MRI. Overall response times and the amount of money won did not differ between the groups. Striatal activation during reward anticipation decreased across age in the SZ offspring, while it did not in the healthy controls. Activation in the orbitofrontal cortex during reward receipt did not differ between the groups. These results, taken together with data from adult schizophrenia patients and their siblings, indicate that the diminishing striatal activation across adolescence may signify a familial vulnerability for schizophrenia.


Primary tuberculosis of the eustachian tube causing otitis media with effusion.
Eustachian tube (ET) dysfunction may cause pathological changes in the middle ear, including recurrent acute otitis media and otitis media with effusion (OME). Mechanical obstruction of the ET may be caused by primary tumor-like lesions arising from ET or secondary ET infiltration due to nasopharyngeal and parapharyngeal space tumor. Tuberculosis is known to affect almost every organ in the body, and it should be a concern of each and every medical practitioner. However, tuberculosis of the ET has not been reported in the literature previously. This article reports primary tuberculosis arising in the ET that presented as aural fullness and hearing disturbance in a patient with OME.


[Ethical support units: benefits and limits of externalised ethics in times of crisis].
This health crisis has revealed the difficulties, but also the creativity of the caregiving teams. In this context, assisting health professionals through the creation of an ethical support unit is valuable. However, the implementation of such a unit requires reflection with the definition of the resulting limits. Two questions are raised: is it really possible to externalise ethical reflection? Is there such a thing as ethics of crisis?


Examining out-of-pocket expenditure on health care in Nouna, Burkina Faso: implications for health policy.
To examine household out-of-pocket expenditure on health care, particularly malaria treatment, in rural Burkina Faso. Comprehensive analysis of out-of-pocket expenditure on health care through a descriptive analysis and a second, multivariate analysis using the Tobit model with emphasis on malaria, based on 800 urban and rural households in Nouna health district. Households will spend less on malaria, either in or outside the health facility, if given the choice to do so, because they feel confident to self-treat malaria. Seeking health care from a qualified health worker incurs more out-of-pocket expenditure than self-treatment and traditional healers, and if necessary, households sell off assets to offset the expenditure. More than 80% of household out-of-pocket expenditure is allocated to drugs. This has policy implications for malaria control and the Roll Back Malaria Initiative. Communities need to be educated on the risks of malaria complications and the potential risk of inappropriate diagnosis and treatment. Drug or health services pricing policy needs to create an incentive to use the health services. In the fight against malaria, building alliances between households, traditional healers and health workers is essential.


Input-output properties of motor unit responses in muscles stretched by imposed displacements of the monkey wrist.
Reflex responses are "servo-like" where the output is graded with the input or are "triggered" where the output is independent of input once an input threshold is exceeded. Imposed displacements of monkey or human upper limb joints result in prolonged EMG output in the muscles stretched by the displacements. The longer-latency portions of the prolonged output have been variously reported to be servo-like or to be triggered in nature. In monkeys and humans, angular wrist displacements imposed by step loads result in three peaks (M1, M2 and M3) in the gross EMG recorded from the stretched muscles. Each gross EMG peak largely results from the firing of a separately-responding subpopulation of single motor units (SMUs). We studied the responses of SMUs to loads that were presented to the monkeys in a random order as to magnitude, duration and onset time. Average response histograms were constructed for the SMU responses for individual step load magnitudes. Averages were also constructed for the simultaneously-recorded gross EMG responses for each step load magnitude. The input parameters used were the initial velocity of displacement or the magnitude of step load, while the output was taken as the probability of firing/millisecond/presentation above baseline for the SMUs or the area under the response peaks above baseline for gross EMG. The results establish: 1) That it is not possible to unambiguously determine the input-output properties of the responses to imposed displacements utilizing the analysis of gress EMG activity due to the response characteristics of the various subpopulations of motor units contributing to the gross response. 2) That the SMU activity during all of the peak intervals is monotonically graded with increases in magnitude of the step load or the initial velocity of displacement. Hence, the long-latency portions of the EMG responses are servo-like in nature and are not preprogrammed or triggered responses. 3) That the gain (output/input) of the gross EMG responses almost entirely reflects the variation in the number of motoneurons recruited by changes in magnitude of the step loads rather than variation in the firing rates of motoneurons during the reflex responses.


Precise evaluation of bilateral pulmonary artery banding for initial palliation in high-risk hypoplastic left heart syndrome.
In patients with high-risk hypoplastic left heart syndrome (HLHS), the Norwood operation (NW) in the neonatal period still results in high mortality compared with other cardiac surgery. Bilateral pulmonary artery banding (bPAB), a very effective initial procedure for HLHS, for which the specific evaluation is as yet unsatisfactory, was performed, and we report our findings in the present study. We have performed bPAB since 2006. A total of 17 patients with HLHS or a variant underwent bPAB before the NW. Echocardiography was performed between bPAB and the NW, and the flow acceleration just after bPAB and before NW was evaluated. Before the NW, a catheter examination was also performed. bPAB was performed at 6.6 ± 0.6 days of age, and the NW at 130 ± 88 days. The patients' mean body weight (BW) was 2.5 ± 0.4 kg at bPAB and 4.0 ± 1.1 kg at the NW. The length of the tape for bPAB was 9.9 ± 0.6 mm in the right pulmonary artery (RPA) and 9.4 ± 0.6 mm in the left (LPA) because the RPA was usually wider than the LPA. The tape width was 2 mm in all cases. The catheter examination was performed at 95 ± 85 days after bPAB. The arterial oxygen saturation (SaO₂) was 71% ± 8.6%. Multivariate regression analysis revealed that SaO₂ was estimated well using 4 factors: the banding size of the RPA, BW at bPAB, BW at NW, and BW in the period between bPAB and catheter examination (R² = 0.79). Echocardiography just after bPAB showed that the blood flow at the bPAB had accelerated to 3.0 ± 0.8 m/s in the RPA and 3.3 ± 0.8 m/s in the LPA (P = .004). The estimated pressure gradient was 39.2 ± 17.6 mm Hg in the RPA and 46.1 ± 23.0 mm Hg in the LPA (P = .006). The blood flow at bPAB was accelerated to 3.7 ± 0.7 m/s in the RPA and 4.0 ± 0.6 m/s in the LPA before NW (P = .013). The estimated pressure gradient was 62.6 ± 27.6 mm Hg in the RPA and 56.1 ± 19.6 mm Hg in the LPA before NW (P = .014). The catheter examination revealed mean wedge pressures of 18.0 ± 7.2 mm Hg for the RPA and 16.2 ± 4.3 mm Hg for the LPA. The operative mortality rate was 0%. One patient required a repeat operation to adjust the bPAB, and prolonged pleural effusion was observed in 1 case. The postoperative SaO₂ after bPAB correlated closely with the banding size and BW at bPAB, NW and during the period after bPAB. Because the mean PA pressure before NW was low enough for single ventricular circulation, the bPAB in this study was an effective option for high-risk patients undergoing HLHS or a variant. We believe the bPAB sizes used were suitable and were determined as follows: BW plus 7 mm for the LPA and BW plus 7.5 mm for the RPA.


The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study.
Venous thromboembolism (VTE) is one of the major causes of morbidity and mortality in bariatric patients. The use of low-molecular-weight heparin (LMWH), as enoxaparin, is considered one of the mainstays thromboprophylaxis regimens in postoperative bariatric patients. Despite the universal agreement on the importance of thromboprophylaxis in these patients, there are inadequate strong recommendations for its dosing and duration. The aim of our study is to explore the current practice on using enoxaparin in bariatric patients, as well as to assess both the efficacy and safety of varying dosing regimens. This is a retrospective cohort study of morbidly obese patients who underwent bariatric procedure at a tertiary care hospital between 2016 and 2019. All adult patients who met the eligibility criteria for bariatric surgery and received enoxaparin with a minimum follow-up period of one month were included in our study. Participants with a history of coagulopathy, renal or hepatic insufficiency were excluded from the study. Data collected include patient demographics, VTE risk factors, and co-morbidities. The outcome of treatment failure was defined as the composite of either VTE or major bleeding. A total of 1,169 patients who underwent bariatric surgery were included in the study. The mean age was 35.54 years, with mean body mass index (BMI) of 45.78 kg/m2. The mean duration of enoxaparin use was 9 days, and the majority of patients (78%) received a prophylaxis dose of 40 mg subcutaneously (SC) once daily. The overall rate of VTE at 90 days was 1.4% while only 0.1% of patients developed major bleeding. There was no statistically significant difference in patients' age, gender, BMI, or various enoxaparin dosing regimens between patients who developed VTE or bleeding versus patients who did not develop. Patient's weight was the only statistically significant risk factor that directly correlated to higher risk of complications (P = 0.006). In the multivariable logistic regression model, higher BMI was significantly associated with treatment failure, either VTE or major bleeding [OR 1.05 (95% CI 1.0-1.09); P = 0.038]. The rate of VTE or major bleeding did not differ in patients who received various enoxaparin regimens. Patients undergoing bariatric surgery may benefit from enoxaparin thromboprophylaxis dose of 40 mg SC daily for a total duration of 14 days, with higher doses may be needed for extremely obese patients. We recommend standardizing the current practice of VTE prophylaxis post bariatric surgery and unifying the optimal dose and duration.


Effect of maternal smoking on breast milk interleukin-1alpha, beta-endorphin, and leptin concentrations and leptin concentrations.
Tobacco smoke is immunotoxic, but the effect of smoking on the immunologic function of the mammary gland of mothers who smoke cigarettes ("smoker mothers") has not been studied. Our objective was to test, in smoker mothers, the colostral and transitional milk concentrations of interleukin-(IL)1alpha. The immunomodulators beta-endorphin and leptin were also tested. Pregnant women who self-identified as smokers (greater than or equal to 5 cigarettes per day through pregnancy) or nonsmokers were recruited for study participation. The study population included 42 smoker and 40 nonsmoker nursing mothers, with otherwise uncomplicated gestation, delivery, and puerperium, who were breast-feeding ad libitum their healthy neonates. Colostrum was obtained on the third postpartum day at 0900 hr and transitional milk on the 10th postpartum day at 0900 hr. IL-1alpha concentrations were significantly reduced in the colostrum of smoker mothers compared with nonsmoker mothers (p < 0.01). Colostral beta-endorphin and leptin concentrations were comparable. No significant differences were found between smoker and nonsmoker lactating mothers in transitional milk concentrations of IL-1alpha, beta-endorphin, and leptin. Moreover, beta-endorphin and leptin concentrations were significantly reduced in transitional milk samples compared with colostrum of both smoker and nonsmoker mothers (p < 0.05); also, IL-1alpha transitional milk concentrations were reduced compared with colostrum, but without any significance. This analysis shows that maternal smoking alters the colostral milk levels of the proinflammatory cytokine IL-1alpha. The altered postnatal provision of alternative source of the proinflammatory cytokine IL-1alpha adds understanding to how breast-feeding could be nonprotective against infections among the neonates nursed by smoker mothers.


Correlation between clinical response and urinary interleukin levels using different doses and intravesical administration schedules of interferon-alpha-2b combined with epirubicin: a pilot study.
A total of 62 patients at high risk for recurrence of superficial bladder cancer were selected for a study designed to compare the prophylactic efficacy of different doses and schedules of sequential intravesical instillations of epirubicin and interferon-alpha-2b and to evaluate which sequence could enhance the release of cytokines in the urine. Our investigations showed a significant increase in urinary concentrations of interleukins in patients who received the sequential intravesical administration of epirubicin and interferon-alpha-2b. Higher urinary concentrations of interleukins and a lower recurrence rate were detected in patients who received interferon-alpha-2b 24h after epirubicin instillation.