AI-Human Hybrid Workflow Enhances Teleophthalmology for the Detection of Diabetic Retinopathy.
Detection of diabetic retinopathy (DR) outside of specialized eye care settings is an important means of access to vision-preserving health maintenance. Remote interpretation of fundus photographs acquired in a primary care or other nonophthalmic setting in a store-and-forward manner is a predominant paradigm of teleophthalmology screening programs. Artificial intelligence (AI)-based image interpretation offers an alternative means of DR detection. IDx-DR (Digital Diagnostics Inc) is a Food and Drug Administration-authorized autonomous testing device for DR. We evaluated the diagnostic performance of IDx-DR compared with human-based teleophthalmology over 2 and a half years. Additionally, we evaluated an AI-human hybrid workflow that combines AI-system evaluation with human expert-based assessment for referable cases. Prospective cohort study and retrospective analysis. Diabetic patients ≥ 18 years old without a prior DR diagnosis or DR examination in the past year presenting for routine DR screening in a primary care clinic. Macula-centered and optic nerve-centered fundus photographs were evaluated by an AI algorithm followed by consensus-based overreading by retina specialists at the Stanford Ophthalmic Reading Center. Detection of more-than-mild diabetic retinopathy (MTMDR) was compared with in-person examination by a retina specialist. Sensitivity, specificity, accuracy, positive predictive value, and gradability achieved by the AI algorithm and retina specialists. The AI algorithm had higher sensitivity (95.5% sensitivity; 95% confidence interval [CI], 86.7%-100%) but lower specificity (60.3% specificity; 95% CI, 47.7%-72.9%) for detection of MTMDR compared with remote image interpretation by retina specialists (69.5% sensitivity; 95% CI, 50.7%-88.3%; 96.9% specificity; 95% CI, 93.5%-100%). Gradability of encounters was also lower for the AI algorithm (62.5%) compared with retina specialists (93.1%). A 2-step AI-human hybrid workflow in which the AI algorithm initially rendered an assessment followed by overread by a retina specialist of MTMDR-positive encounters resulted in a sensitivity of 95.5% (95% CI, 86.7%-100%) and a specificity of 98.2% (95% CI, 94.6%-100%). Similarly, a 2-step overread by retina specialists of AI-ungradable encounters improved gradability from 63.5% to 95.6% of encounters. Implementation of an AI-human hybrid teleophthalmology workflow may both decrease reliance on human specialist effort and improve diagnostic accuracy. Proprietary or commercial disclosure may be found after the references.


Influence of dexmedetomidine and clonidine on human liver microsomal alfentanil metabolism.
Perioperative administration of the alpha 2 agonist clonidine has been shown to increase plasma alfentanil concentrations; however, the mechanism for this pharmacokinetic drug interaction is unknown. Because alfentanil undergoes extensive hepatic biotransformation, clonidine inhibition of alfentanil metabolism may alter alfentanil disposition. The first purpose of this investigation was to test the hypothesis that clonidine impairs human liver alfentanil metabolism. The new highly selective alpha 2 agonist dexmedetomidine (D-medetomidine) is a substituted imidazole and thus may inhibit hepatic drug biotransformation. The second purpose of this study, therefore, was to assess the effect of D-medetomidine and its levo (L) isomer on alfentanil biotransformation. Human liver microsomal alfentanil metabolism was assessed in vitro using a gas chromatography--mass spectrometry assay. Clonidine, at concentrations as great as 10 microM (far exceeding therapeutic levels), had no significant effect on alfentanil oxidation. In contrast, D-medetomidine and its optical isomer L-medetomidine were potent inhibitors of human liver microsomal alfentanil metabolism. The concentration producing 50% inhibition (IC50) of alfentanil (10 microM) oxidation was 0.7-1.0 and 2.8-4.0 microM for D-medetomidine and L-medetomidine, respectively. Preincubation of D-medetomidine with microsomes did not enhance the inhibition of alfentanil metabolism. These results suggest that the increased alfentanil plasma concentrations and potentiation of alfentanil anesthesia associated with clonidine do not result from clonidine inhibition of alfentanil metabolism. D-medetomidine impairment of alfentanil metabolism, however,if present at therapeutic concentrations, may influence alfentanil disposition.(ABSTRACT TRUNCATED AT 250 WORDS)


Functionalities tuned enantioselectivity of phenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC.
The mixed chloro- and methyl- functionalities can greatly modulate the enantioselectivities of phenylcarbamate cyclodextrin (CD) clicked chiral stationary phases (CSPs). A comparison study is herein reported for per(4-chloro-3-methyl)phenylcarbamate and per(2-chloro-5-methyl)phenylcarbamate β-CD clicked CSPs (i.e., CCC4M3-CSP and CCC2M5-CSP). The enantioselectivity dependence on column temperature was studied in both normal-phase and reversed-phase mode high performance liquid chromatography (HPLC). The thermodynamic study revealed that the stronger intermolecular interactions can be formed between CCC4M3-CSP and chiral solutes to drive the chiral separation. The higher enantioselectivities of CCC4M3-CSP were further demonstrated with the enantioseparation of 17 model racemates in HPLC.


Re-Prioritizing Digital Health and Health Literacy in Healthy People 2030 to Affect Health Equity.
The U.S. Healthy People 2030 health objective-setting process has taken place in an inequitable social structure with significant implications for health literacy, health equity, and population health. The draft 2030 objectives have greatly reduced the number of digital health and health literacy objectives, meaning our national agenda is poised to capture only a fraction of what will evolve in digital and health literacy between 2020 and 2030. This paper synthesizes two decades of Healthy People data on health literacy and digital health objectives, highlights the digital health and health literacy trends and disparities that persist and proposes remedies to ensure that health literacy and digital health issues receive the attention they deserve in the next decade. These remedies can inform policies, research, and interventions that touch health communication and digital health issues.


Pulmonary arteriovenous malformations.
Within the past decade, pulmonary arteriovenous malformations (PAVMs) have evolved from rare curiosities to not uncommon clinical states, with the latest estimates suggesting a prevalence of ~1 in 2,600. PAVMs provide anatomic right-to-left shunts, allowing systemic venous blood to bypass gas exchange and pulmonary capillary bed processing. Hypoxemia and enhanced ventilatory demands result, although both are usually asymptomatic. Paradoxical emboli lead to strokes and cerebral abscesses, and these commonly occur in individuals with previously undiagnosed PAVMs. PAVM hemorrhage is rare but is the main cause of maternal death in pregnancy. PAVM occlusion by embolization is the standard of care to reduce these risks. However, recent data demonstrate that currently recommended management protocols can result in levels of radiation exposure that would be classified as harmful. Recent publications also provide a better appreciation of the hematologic and cardiovascular demands required to maintain arterial oxygen content and oxygen consumption in hypoxemic patients, identify patient subgroups at higher risk of complications, and emphasize the proportion of radiologically visible PAVMs too small to treat by embolization. This review, therefore, outlines medical states that exacerbate the consequences of PAVMs. Chief among these is iron deficiency, which is commonly present due to concurrent hereditary hemorrhagic telangiectasia: iron deficiency impairs hypoxemia compensations by restricting erythropoiesis and increases the risk of ischemic strokes. Management of periodontal disease, dental interventions, pulmonary hypertension, and pregnancy also requires specific consideration in the setting of PAVMs. The review concludes by discussing to what extent previously recommended protocols may benefit from modification or revision.


Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans.
Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association. This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years. Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically significant interaction between thigh muscle area and BMI was observed, i.e., greater thigh muscle area was associated with lower risk of incident T2DM for subjects at lower levels of BMI, but this association diminished at higher BMI levels. Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.


Utility of Lymphocyte Transformation Test for Assisting Updated Roussel Uclaf Causality Assessment Method in Drug-Induced Liver Injury: A Case-Control Study.
Background: The Roussel Uclaf Causality Assessment Method (RUCAM) is a validated tool for assessing causality in cases of suspected drug-induced liver injury (DILI). However, RUCAM cannot discriminate between concomitant hepatotoxic drugs with the same temporal sequence. Objective: To analyse the utility of the lymphocyte transformation test (LTT) for assisting updated RUCAM in 45 patients and 40 controls with a clinical diagnosis of DILI. Methods: Suspected DILI cases were detected through the Prospective Pharmacovigilance Program from Laboratory Signals in Hospital (PPLSH) or by consultations. The controls completed the drug therapy with no adverse reactions during the study period. A receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value for the stimulation index (SI), corresponding to the largest sum for the specificity and sensitivity values of LTT for true DILI cases. Results: Out of 45 patients diagnosed with DILI, 42 cases were detected by the PPLSH, two cases by consultation and one case by both methods. Most DILI cases (64.4%) arose during hospitalization. According to the biochemical parameters, 24 cases (53.3%) had the hepatocellular phenotype, 14 (31.1%) had the cholestatic phenotype, and 7 cases (15.6%) had the mixed phenotype. Considering the severity criteria, 7 (15.5%) cases were classified as moderate DILI, and 4 (8.9%) were severe DILI; there were no fatal cases. A total of 149 drugs (median/case, 3; IQR, 2-5) were suspected to be involved in the DILI cases (RUCAM score ≥3). In 8 cases, only one drug was suspected, and polypharmacy (≥5 drugs) was identified in 29% of the cases. Of all DILI cases, 46 (30.9%) of the 149 suspected drugs produced positive LTT results, and the LTT was positive in 34 (75.5%) of the 45 patients. No exposed controls produced positive LTT results. The optimal cut-off of 1.95 for the SI was obtained with a sensitivity of 77% and specificity of 100% (area under the curve, 0.91; 95% asymptotic confidence interval 0.84-0.97; p < 0.001). The sensitivity of the hepatocellular phenotype was 92%. Conclusion: Our results demonstrate that LTT is an add on strengthening causality in cases of suspected idiosyncratic DILI, especially for patients with several suspected drugs and a hepatocellular phenotype.


Acute cholangitis following mRNA COVID-19 vaccine booster in a patient receiving an anti-amyloid antibody for Alzheimer's disease: A case report.
A 77-year-old woman had 2 weeks of fever and flu-like symptoms starting several hours after receiving an mRNA booster for SARS-CoV-2 and the influenza vaccine, in separate shots. Laboratory tests showed cholangitis. Medical history included APOE-ε4 carrier genotype, mild Alzheimer's disease, participation in a clinical trial of aducanumab, and resolving polymyalgia rheumatica. The patient recovered with at-home supportive care. She had aducanumab-associated amyloid-related imaging abnormalities-edema (ARIA-E) both before and after the acute cholangitis. Two months following the vaccinations polymyalgia rheumatica recurred. This case raises questions about interactions among immune-mediated disease, complications of anti-amyloid monoclonal antibodies, and adverse events following SARS-CoV-2 mRNA vaccination.


Direct Hydrogenation of Aluminum via Stabilization with Triethylenediamine: A Mechanochemical Approach to Synthesize the Triethylenediamine ⋅ AlH3 Adduct.
Two approaches for the synthesis of the triethylenediamine (TEDA) ⋅ AlH3 adduct have been discovered. Both, the mechanochemical procedure and the wet chemical method lead to crystalline products. Starting from metallic Al powder and TEDA, ball milling under a pressure of 100 bar H2 facilitates a direct hydrogenation of aluminum with conversions up to 90 %. Structure determination from X-ray powder diffraction data revealed an 1-D-coordination polymer of the type [TEDA-AlH3 ]n . Furthermore, solid-state NMR techniques have been applied to analyze composition and structure of the products. Due to the polymeric arrangement, an enhanced stability of the material occurred which was investigated by thermal analysis showing a decomposition located above 200 °C. Overall, the stabilization of AlH3 by TEDA holds promise for hydrogen storage applications.


Hypoxia and etanidazole alter radiation-induced apoptosis in HL60 cells but not in MOLT-4 cells.
To examine how hypoxia influences ionizing irradiation-induced apoptosis in cultured mammalian cells and how a hypoxic cell radiosensitizer sensitizes apoptosis under hypoxic conditions. Two cell lines derived from human lymphocytes, HL60 and MOLT-4, were exposed to 15 Gy X-rays under aerobic and hypoxic conditions. Etanidazole was used as a hypoxic cell radiosensitizer. The apoptotic morphological changes of nuclei and the induction of ladder-like DNA fragmentation were assessed by fluorescence microscopy and agarose gel electrophoresis, respectively. In HL60 cells, apototic cell death and the activation of caspases 8, 9 and 3 were less induced under the hypoxic conditions than under the aerobic ones. Treatment of hypoxic cells with etanidazole enhanced X-ray-induced apoptosis and caspase activation. However, in MOLT-4 cells, neither hypoxia nor etanidazole influenced X-ray-induced apoptosis and caspase activation. In both cell lines, the frequency of X-ray-induced DNA double-strand breaks (DSB) under hypoxia was significantly smaller than that in aerobic conditions. Treatment of hypoxic cells with etanidazole enhanced them. These results suggested that X-ray-induced apoptosis in HL60 cells was initiated by DNA DSB and the treatment of hypoxic cells with etanidazole sensitized them through the enhancement of DSB induction, whereas X-ray-induced apoptosis in MOLT-4 cells occurred through damage other than to DNA.


[Reproducibility and validity of radiographic measurements for the calculation of proximal femur morphometric indices predictive of hip fractures].
Cross-sectional-retrospective study with 120 anteroposterior pelvic radiographs. Eight measurements were taken by three raters in two times to calculate the morphological-cortical (MCI), cortico-metaphyseal (CMI), and cortico-diaphysaire (CDI) indices. Intra/interobserver reproducibility was evaluated with the Bland-Altman method, and hip fracture occurrence was predicted by comparing cut-off points between raters maximizing sensitivity/specificity. The proportion of measurements outside ± 2 SD was similar for diameters/corticals (~5%), but exceeded 1 mm in some corticals, representing 10-20% of distances < 1 cm. Cut-off points fluctuated between 2.45 and 2.53 for MCI (3% difference), between 0.37 and 0.41 for CMI (12% difference), and between 0.23 and 0.33 for CDI (44% difference).


Non-negligible factors in studying the ApoM-S1P axis using EA.hy926 cells.
The apolipoprotein M (ApoM)-sphingosine-1-phosphate (S1P) axis was recently identified, and research into its function has received increasing attention. However, there are some factors which might influence the results of studies into the function of the ApoM-S1P axis using the EA.hy926 cells. This study investigated related factors, including coagulation factor VIII (FVIII), ApoM, S1P receptor subtypes (S1PRs), C-myc-tagged, and His-tagged proteins in EA.hy926 cells, as well as the effects of ApoM overexpression on S1PRs. The expression of FVIII, ApoM, S1PRs, C-myc, and His-tagged proteins in EA.hy926 cells was investigated through cellular immunofluorescence. EA.hy926 cells were infected with lentiviruses carrying (OE group) or lacking (NC group) the ApoM gene sequence. A stable cell line expressing ApoM was obtained, and the expression of ApoM mRNA was detected through single tube duplex fluorescence reverse transcription quantitative polymerase chain reaction (RT-qPCR). S1PRs expression was detected by RT-qPCR and Western blotting. The results showed that EA.hy926 cells expressed FVIII, ApoM, C-myc-tagged, and His-tagged proteins. Moreover, they highly expressed S1PR1, slightly expressed S1PR3, weakly expressed S1PR2, and did not express S1PR4 and S1PR5. ApoM overexpression significantly increased S1PR1 mRNA and protein expression but did not affect the expression of S1PR3. EA.hy926 cells expressed FVIII, suggesting the cell line possesses endothelial cell characteristics and could be used for in vitro studies of the ApoM-S1P axis. EA.hy926 cell line is suitable for investigation of the ApoM-S1P axis in vitro. However, Since EA.hy926 cells expressed endogenous ApoM, C-myc and His tagged proteins, the exogenous recombinant ApoM should not be labeled with C-myc and His tags for distinguishing from endogenous ApoM. In addition, overexpression of ApoM should be considered to significantly increase the expression of S1PR1 when studying the APOM-S1P axis.


Changes in hypophyseal luteinizing hormone (LH) content during fetal and early postnatal life, and capacity of fetal and early postnatal pituitaries to synthesize and release LH in vitro.
The developmental pattern of hypophyseal luteinizing hormone (LH) during fetal and early postnatal life, and the capacity of fetal and early postnatal pituitaries to synthesize, release and store LH in the absence of any hypothalamic influence were investigated. Pituitary radioimmunoassayable LH was detectable by fetal day 12; its level remained low up to fetal day 17 and thereafter continued to increase up to postnatal day 2 with sharp rises occurring between day 17 and 18 of gestation and after birth. Cultured fetal and early postnatal pituitary primordia were able to synthesize, to release and store the hormone, however, the pattern of these cellular functions varied according to the animal age when explantation was performed. Data derived from cultured pituitaries showed a gradual rise in the daily hormone content of the medium between fetal day 13 to 17. From fetal day 19 onwards, however, the daily discharge of LH decreased. These findings suggest that the fetal and early postnatal pituitary has the capacity to synthesize and release LH, furthermore after a period of independent differentiation hypothalamic signals appear to be required for pituitary hormone release.


The interrelationship of nutritional risk factors, indicators of nutritional risk, and severity of disability among home-delivered meal participants.
This study examines the direct and indirect relationships between individual components of nutritional risk and increased severity of disability among a large and diverse sample of homebound older adults. Using routinely collected nutrition and function data, structural equation modeling of recursive and nonrecursive models examined the interrelationships of nutritional risk factors, indicators of nutritional risk, and disability severity among 1,010 home-delivered meals program participants in Wake County, NC. The equally good fit for both the recursive and nonrecursive structural models revealed that specific nutritional risk factors were directly and indirectly associated with indicators of nutritional risk and increased severity of disability. The nonrecursive model also revealed significant reciprocal associations of increased disability with unintended weight change and medication use. The findings from this study acknowledge aspects of the complex direct and indirect relationships between nutrition and function among homebound older persons. This knowledge will help service providers with the development of effective elderly nutrition programs with nutritional and functional status outcomes.


Treatment planning for replacing missing teeth in UK general dental practice: current trends.
The aim of this study was to examine the confidence, barriers and attitudes towards the replacement of missing teeth by general dental practitioners (GDPs). The perceived impact of the recently introduced National Health Service (NHS) contract on the provision of prosthodontic treatments was also considered. Pre-piloted postal questionnaires were mailed to 500 GDPs in Wales. Open- and closed-ended questions were utilised to establish confidence, adequacy of training and attitudes towards treatments for replacing missing teeth. Two hundred and seventeen completed questionnaires were received (response rate = 43.4%). Many respondents described themselves as 'confident' or 'very confident' in the provision of removable partial dentures (RPDs) (acrylic = 100%, metal based = 99.5%), cantilever resin-bonded bridges (94.4%) and conventional bridgework (98.6%). GDPs were 'not confident' providing fixed-fixed resin-bonded bridges (21.1%) or implants (81.4%). Financial barriers were identified to the provision of prosthodontic treatments, including comments such as "the new [National Health Service] contract does limit the treatments available". Privately funded patients were more likely to be offered a fixed bridge or implant replacement of a missing upper first molar, whereas non-privately funded patients were more likely to be offered no treatment (P < 0.01). Most respondents reported confidence at providing more routine forms of prosthodontic care such as RPDs and bridges. It appears that funding arrangements may have an impact on treatments offered to replace missing teeth, particularly under the current NHS contract.


Tuning the Reactivities of the Heteronuclear [Aln V3-n O7-n ]+ (n=1, 2) Cluster Oxides towards Methane by Varying the Composition of the Metal Centers.
The thermal gas-phase reactions of [Al2 VO5 ]+ and [AlV2 O6 ]+ with methane have been explored by using Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry complemented by high-level quantum chemical calculations. Both cluster ions chemisorbed methane as the major reaction channels at room temperature. [Al2 VO5 ]+ could break only one C-H bond to liberate CH3 , whereas [AlV2 O6 ]+ exhibited higher oxidizing ability such that it brings about the selective generation of formaldehyde. Mechanistic aspects are revealed and the crucial roles of the metal centers are discussed.


Hemodynamic properties of a new quinidine analog, cupreidine (6'-hydroxycinchonine).
Cupreidine 96'-hydroxycinchonine) is a recently synthesized analog of quinidine (6'-methoxycinchonine). Previous studies in mice have shown that quinidine and cupreidine have equivalent antiarrhythmic potencies, whereas the acute toxicity of cupreidine is about 50% less than that of quinidine. Many of the serious adverse effects of quinidine are due to undesirable cardiovascular properties. We have, therefore, compared the effects of the two drugs on blood pressure, heart rate, and peripheral vasodilation in rats, and on myocardial contractility in isolated rabbit hearts at a series of comparable doses. Quinidine produces a more marked bradycardia and depression of blood pressure than does cupreidine. The vasodilation produced by intraarterial administration of quinidine was significantly greater than cupreidine. Furthermore, quinidine elicited a greater negative inotropic effect. Cupreidine exhibited a much more favorable hemodynamic profile than quinidine with regard to the properties that were examined. These results, coupled with the fact that cupreidine has significant antiarrhythmic activity and a lower acute toxicity profile, suggest that this drug may be useful in the therapy of cardiac arrhythmias.


Ecological suitability modeling for anthrax in the Kruger National Park, South Africa.
The spores of the soil-borne bacterium, Bacillus anthracis, which causes anthrax are highly resistant to adverse environmental conditions. Under ideal conditions, anthrax spores can survive for many years in the soil. Anthrax is known to be endemic in the northern part of Kruger National Park (KNP) in South Africa (SA), with occasional epidemics spreading southward. The aim of this study was to identify and map areas that are ecologically suitable for the harboring of B. anthracis spores within the KNP. Anthrax surveillance data and selected environmental variables were used as inputs to the maximum entropy (Maxent) species distribution modeling method. Anthrax positive carcasses from 1988-2011 in KNP (n = 597) and a total of 40 environmental variables were used to predict and evaluate their relative contribution to suitability for anthrax occurrence in KNP. The environmental variables that contributed the most to the occurrence of anthrax were soil type, normalized difference vegetation index (NDVI) and precipitation. Apart from the endemic Pafuri region, several other areas within KNP were classified as ecologically suitable. The outputs of this study could guide future surveillance efforts to focus on predicted suitable areas for anthrax, since the KNP currently uses passive surveillance to detect anthrax outbreaks.


[Impact of salvianolic acid-B on TGF-beta1-induced HK-2 epithelial-mesenchymal transition].
To investigate the effect of salvianolic-acid B (SA-B) on epithelia-mesenchymal transition in human renal proximal tubular cells (HK2), induced by transforming growth factor beta1 (TGF-beta1). Epithelia-mesenchymal transition (EMT) was induced with TGF-beta1 in HK2 cultured in vitro. Different concentrations (2, 5, 10, 20 microg x L(-1)) and stimulant periods (12, 24, 48 h) were tried to find the perfect condition for EMT. At the same time bone morphogenetic protein-7 (BMP-7, positive control) and the SA-B intervention were given to observe their effect on EMT. Western blot and immunofluorescent microscopy were used to analyze the expression of E-cadherin and alpha-smooth muscle actin (alpha-SMA) in HK2. BMP-7 significantly inhibited the down-regulation of E-cadherin and the up-regulation of alpha-SMA induced by TGF-beta1 (P < 0.05), and SA-B significantly inhibited the up-regulation of alpha-SMA expression induced by TGF-beta1 (P < 0.05), but not the down-regulation of E-cadherin induced by TGF-beta1. SA-B and BMP-7 can inhibit TGF-beta1-induced EMT in HK2. Their common role is to inhibit the up-regulation of alpha-SMA, and the effect of SA-B on the regulation of E-cadherin needs further study to be confirmed.


Microbial thermogenesis is dependent on ATP concentrations and the protein kinases ArcB, GlnL, and YccC.
Organisms necessarily release heat energy in their pursuit of survival. This process is known as cellular thermogenesis and is implicated in many processes from cancer metabolism to spontaneous farm fires. However, the molecular basis for this fundamental phenomenon is yet to be elucidated. Here, we show that the major players involved in the cellular thermogenesis of Escherichia coli are the protein kinases ArcB, GlnL, and YccC. We also reveal the substrate-level control of adenosine triphosphate (ATP)-driven autophosphorylation that governs cellular thermogenesis. Specifically, through live cell microcalorimetry, we find these regulatory proteins, when knocked out in a model E. coli strain, dysregulate cellular thermogenesis. This dysregulation can be seen in an average 25% or greater increase in heat output by these cells. We also discover that both heat output and intracellular ATP levels are maximal during the late log phase of growth. Additionally, we show that microbial thermogenesis can be engineered through overexpressing glnL. Our results demonstrate a correlation between ATP concentrations in the cell and a cell's ability to generate excess heat. We expect this work to be the foundation for engineering thermogenically tuned organisms for a variety of applications.


Effects of (-)-epigallocatechin gallate on RPE cell migration and adhesion.
In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and age-related macular degeneration (AMD), retinal pigment epithelial (RPE) cells can initiate proliferation and migration and secrete extracellular matrix (ECM) proteins. (-)-Epigallocatechin gallate (EGCG)-a natural anti-oxidant flavonoid that is abundant in green tea-has been shown to suppress the migration and adhesion of many cell types, but its effects on RPE cell migration and adhesion were unknown. Several studies have shown that platelet-derived growth factor (PDGF) enhances proliferation and migration effects on RPE cells in PVR, and that fibronectin is a major ECM component of PVR tissue. Therefore, we investigated the inhibitory effects of EGCG on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion by fibronectin. The migration of RPE cells was detected by an electric cell-substrate impedance sensing (ECIS) migration assay and a Transwell migration assay. Cells were loaded with 2',7'-bis-(carboxyethyl)-5(6')-carboxyfluorescein acetoxymethyl ester (BCECF/AM), and their adhesion to fibronectin was examined. The interactions of EGCG with PDGF-BB were analyzed by a dot binding assay. Cytoskeletal reorganization was examined by immunofluorescence microscopy. The PDGF-BB-induced signaling pathways were detected by western blotting. In the present study, we find that EGCG can inhibit PDGF-BB-induced human RPE cell migration and, in a dose-dependent manner, RPE cell adhesion to fibronectin. Our analysis demonstrates that EGCG does not directly bind to PDGF-BB and the inhibition of EGCG against fibronectin-induced cytoskeletal reorganization is observed. Furthermore, EGCG is shown to suppress PDGF-BB-induced PDGF-beta receptors, downstream PI3K/Akt, and MAPK phosphorylation. Our results provide the first evidence that EGCG is an effective inhibitor of RPE cell migration and adhesion to fibronectin and, therefore, may prevent epiretinal membrane formation.


[Problematic online gaming. A review of the literature].
In parallel with the increasing popularity of online games, researchers have reported an increasing number of problematic users. For this reason there is a growing amount of literature analyzing the effects of online games. The present review described the evolution of online games as well as their types and specific characteristics of these types. This review examines (i) the question of definition, (ii) symptoms of problematic use, (iii) the measurement instruments (iv) prevalence data, (v) issues of etiology, (vi) the results of comorbidity, and (vii) the main trends and results in the area of prevention and treatment.


Increased diversity of Malassezia species on the skin of Parkinson's disease patients.
Parkinson's disease (PD) is characterized by motor disorders and the composition of Lewy bodies (LBs) in the substantia nigra. Due to the lack of a definitive biomarker, the current treatments do not modify the progression of PD. Recently, researchers revealed lipid dysregulation and some potential volatile biomarkers of PD related to a unique odor from PD patients by metabolomics of sebum, which is supposed to cause a potential change for skin microflora. In this study, we identified the 4 Malassezia species in PD patients and compared them with healthy controls. We collected 95 sebum samples (47 PDs and 48 Controls) by cotton swabs and extracted the DNA. The identification of Malassezia species was performed by Nested PCR. Specific primers for each species were used to amplify corresponding yeasts in each sample. M. restricta and M. globosa are the most common species for both groups. The prevalence of M. slooffiae and M. sympodialis were significantly higher in the PD group compared with controls (63.8% vs. 29.1 and 74.5% vs. 54.2% respectively), the binary logistic regression model further indicated that M. slooffiae (OR = 9.358, p < 0.001) was associated with PD. Moreover, the diversity of Malassezia species was significantly greater (3.5 vs. 2.9 species per individual, p = 0.002) in the PD group. Based on our results, we preliminarily observed a change in Malassezia species incidence and diversity on the skin of PD patients, which could be associated with lipid dysregulation; meanwhile, it might also be a noninvasive biomarker for PD.


Antimicrobial resistance including Extended Spectrum Beta Lactamases (ESBL) among E. coli isolated from kenyan children at hospital discharge.
Children who have been discharged from hospital in sub-Saharan Africa remain at substantial risk of mortality in the post-discharge period. Antimicrobial resistance (AMR) may be an important factor. We sought to determine the prevalence and risk factors associated with AMR in commensal Escherichia coli (E. coli) from Kenyan children at the time of discharge. Fecal samples were collected from 406 children aged 1-59 months in western Kenya at the time of discharge from hospital and cultured for E. coli. Susceptibility to ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol was determined by disc diffusion according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Poisson regression was used to determine associations between participant characteristics and the presence of extended-spectrum beta-lactamases (ESBL) producing E. coli. Non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of ESBL (44%) was high. Receipt of antibiotics during the hospitalization was associated with the presence of ESBL (aPR = 2.23; 95% CI: 1.29-3.83) as was being hospitalized within the prior year (aPR = 1.32 [1.07-1.69]). Open defecation (aPR = 2.02; 95% CI: 1.39-2.94), having a toilet shared with other households (aPR = 1.49; 95% CI: 1.17-1.89), and being female (aPR = 1.42; 95% CI: 1.15-1.76) were associated with carriage of ESBL E. coli. AMR is common among isolates of E. coli from children at hospital discharge in Kenya, including nearly half having detectable ESBL.


Hepatic mitochondrial efficiency in lines of mice differing in feed intake.
Selection was practiced for high (MH) and low (ML) heat loss using direct calorimetry to create lines of mice differing in feed intake per unit average BW (FI/BW). A total of 25 generations of selection was practiced during maintenance of an unselected control (MC). As a percentage of MC, mice of MH and ML lines differed in heat loss and FI/BW by 56 and 34%, respectively, when selection ceased. The purpose of this study was to determine hepatic mitochondrial efficiency in mice at maintenance across the genetic lines. After measurement of feed intakeand BW over a 2-wk period, mice were euthanized, and their livers were extracted. Livers were homogenized and mitochondria were isolated in buffer for measurement of oxygen consumption and, hence, mitochondrial activity using a Clark-type oxygen electrode. Mitochondria of ML mice expressed greater (P < 0.03) respiratory control ratio by 22% than that for MH mice, revealing greater degree of uncoupling during electron transport in MH mice. Difference in FI/BW (P < 0.001) was large with MH mice consuming 34% more than ML mice. The respiratory control ratio differed between mice of MH and ML lines as expected; however, regression analysis revealed that it explained essentially no variation in feed intake per BW.


Pulmonary Rehabilitation of a Case With Worsening Dyspnea Due to Acute Exacerbation of Interstitial Pneumonia After Video-Assisted Thoracic Surgery.
We report a case of acute exacerbation of interstitial pneumonia after video-assisted thoracic surgery. The case was a 69-year-old man with left upper lobe lung cancer. Acute exacerbation was suspected on postoperative day 6 due to worsening dyspnea and frosted shadows on computed tomography. High-dose corticosteroids and low-to-moderate-dose corticosteroids were administered. Step-by-step rehabilitation with oxygen administration commenced as soon as possible, and the patient was able to be discharged. However, dyspnea, knee extension strength, and exercise capacity were significantly worse than before surgery. Eighteen months later, pulmonary function and knee extension strength showed improvements, but exercise capacity was unchanged from the time of discharge. Continued follow-up will be necessary.


[Pharmaco-economics of anti-influenza vaccinations].
The types of pharmacoeconomic analysis performed in the assessment of influenza vaccination, including cost-benefit and cost-effectiveness analysis are presented in this study. The studies concerned working adults or high-risk elderly people who were selected from Medline and Embase databases. The primary difference between the two types of vaccination programmes is related to the major type of benefits: direct benefits related to averted hospitalizations for elderly versus indirect benefits of averted production losses for healthy working people. In the group of persons aged over 65 years the disease costs are influenced mainly by complications and hospitalizations. Vaccination is most cost-effective in influenza prophylaxis as compared with other strategies (chemoprophylaxis and treatment using neuraminidase or ion channel inhibitors) and may be recommended from the pharmacoeconomic point of view.


War and disaster in Sri Lanka: Depression, family adjustment and health among women heading households.
The civil war, lasting from 1983 to 2009, and the tsunami that struck Southeastern Asia in 2004 were major stressors that changed the demographic landscape of the northern province of Sri Lanka. The composition of families changed dramatically, with an increase in female-headed households, largely due to casualties. The conservation of resources (COR) model was applied in this study to examine relationships between risk and resiliency factors among women heading households, including women widowed by war or disaster. This study represents an investigation of the association between predictive risk and resiliency factors (i.e. war damage and loss, social support, economic status, religious participation and discrimination) and outcomes representing well-being (depressive symptoms, family adjustment and a rating of physical health). Data from 514 women heading households living in the Kilinochchi district of Sri Lanka were collected through face-to-face interviews in 2013, and associations among the data were estimated using path analysis. Results suggest that resiliency factors that are representative of greater resources generally predicted lower levels of distress and vice versa. Further study informing intervention development with women heading households in Sri Lanka is warranted to better understand which individual, family and community resources are most important to mobilize for sustainable recovery efforts to be successful in the decades following war and natural disaster.


Novel biomimetic thermosensitive β-tricalcium phosphate/chitosan-based hydrogels for bone tissue engineering.
Among the less invasive surgical procedures for tissue engineering application, injectable in situ gelling systems have gained great attention. In this contest, this article is aimed to realize thermosensitive chitosan-based hydrogels, crosslinked with β-glycerophosphate and reinforced via physical interactions with β-tricalcium phosphate. The kinetics of sol-gel transition and the composite hydrogel properties were investigated by rheological analysis. The hydrogels were also characterized by Fourier transform infrared study, X-ray diffraction, scanning electron microscopy, transmission electron microscopy analysis, and thermal and biological studies. The hydrogels exhibit a gel-phase transition at body temperature, and a three-dimensional network with typical rheological properties of a strong gel. The presence of the inorganic phase, made up of nanocrystals, provides a structure with chemico-physical composition that mimics natural bone tissue, favoring cellular activity. These findings suggest the potential of the materials as promising candidates for hard tissue regeneration.


Congress Boosts NIH, NCI Funding.
Appropriations for the 2022 fiscal year increase NIH funding by 4.7% and raise NCI funding by 5.3%. The budget also includes $1 billion to launch the Advanced Research Projects Agency for Health, which will foster potentially groundbreaking research that could improve patient care.


Two new species of Xanthagaricus and some notes on Heinemannomyces from Asia.
Xanthagaricus flavosquamosus and X. necopinatus, two new species of Agaricaceae, are described and illustrated from Asia. Macroscopically, both species are closely related to each other, but there are obvious micromorphological and molecular differences between them. Morphological and phylogenetic data showed that the two new species are distinct from other known species of the genus Xanthagaricus. Xanthagaricus flavosquamosus from China is characterized by its small, yellow basidiomata, short clavate cheilocystidia, epithelial pileipellis, and verrucose basidiospores measuring 5-5.5 × 3-3.5 μm. Xanthagaricus necopinatus from Bangladesh is characterized by having small, yellow basidiomata, a fugacious annulus, clavate to narrowly clavate cheilocystidia, epithelial pileipellis, and rugulose-rough basidiospores measuring 4-5 × 2.7-3.2 μm. In addition to the new species, a Heinemannomyces collection from China is reported. Morphological data and molecular phylogenetic analyses fully support the Chinese collection being Heinemannomyces splendidissimus, a species of Agaricaceae, originally described from Southeast Asia. Detailed descriptions, color photos and illustrations of the three species are presented. A key to the genus Xanthagaricus occurring in Bangladesh and China is provided.


The Impact of Sex-Specific Survival on the Incidence of Dementia in Parkinson's Disease.
The aim of our study is to analyze sex-specific patterns of Parkinson's disease dementia (PDD) incidence. We are investigating the extent to which sex differences in survival after initial Parkinson's disease (PD) diagnosis influence differences in PDD risk among PD patients. We used a random sample of German longitudinal health claims data of persons ages 50+ (2004-2019; n = 250,000) and identified new PD cases ages 65+ who were followed-up for a PDD diagnosis or death between 2006 and 2017. We performed Cox and competing-risk regression models, with death as competing event, to calculate PDD hazard ratios (HR) adjusted for age at PD onset, PD severity as measured by the modified Hoehn and Yahr (HY) scale, comorbidities, and medications. Of 2195 new PD cases, 602 people died before PDD and 750 people developed PDD by the end of 2017. The adjusted risk of PDD differs by sex, with men having a higher PDD risk than women. When accounting for death, men and women do not differ in their PDD risk (HR = 1.02, P = 0.770). Sex-specific analyses showed significant age and severity effects in women (age: HR = 1.05, P < 0.001; HY 3-5 vs. 0-2.5: HR = 1.46, P = 0.011), but not in men. Older age at first PD diagnosis and higher disease severity increase PDD risk, but this association is attenuated for PD men when controlling for death. This implies that the most frail PD men die rapidly before receiving a dementia diagnosis, whereas women with PD survive at higher rates, regardless of their age at onset and disease severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Value of an expanded range of lesions on contrast-enhanced ultrasound for the diagnosis of hypervascular breast masses.
Breast cancer lesions show an expanded range on contrast-enhanced ultrasound (CEUS). Here, we quantitatively analyze this index to explore its effective cutoff value for distinguishing benign and malignant lesions and the corresponding diagnostic performance and investigate its role in prognostic assessment of malignant lesions. Consecutive patients who underwent CEUS for breast lesions during the period from September 2017 to June 2019 were included. Original CEUS images were selected, displayed in dual-frame mode, and measured when enhancement of the lesion reached its peak. The longitudinal diameter, transverse diameter, and area of the lesion on the two-dimensional images and the corresponding postenhancement images were measured to calculate six indicators: longitudinal diameter increment, transverse diameter increment, area increment, percent increase in longitudinal diameter, percent increase in transverse diameter, and percent increase in area increment. With postoperative pathology as the gold standard, the cutoff values for distinguishing benign and malignant lesions and the correlations of these indicators with pathological subtypes and pathological grades were evaluated. Malignant lesions showed a more significantly expanded range after enhancement compared to benign lesions, especially in terms of area increase. When the cutoff value of the area increment was set at 0.47 cm2 for distinguishing between benign and malignant lesions, the area under the curve (AUC) was 0.945, and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90.1%, 91.5%, 90.9%, 87.2%, and 93.5%, respectively. The pathologically measured maximum diameter of malignant masses correlated with the percent increase in transverse diameter, area increment, and percent increase in area increment. The longitudinal diameter increment in the luminal A group was significantly smaller than that in the human epidermal growth factor receptor 2 (HER2)+ group. The percent increase in transverse diameter was helpful for predicting the pathological grade of malignant masses. When the cutoff value of the percent increase in transverse diameter was set at 10.84% for pathological grading, the AUC was 0.623, and the sensitivity was 90.8%. Indicators related to the expanded lesion range on CEUS are helpful in differential diagnosis of benign and malignant lesions and in prognostic assessment of pathological grades.


Heterogeneous dissipation and size dependencies of dissipative processes in nanoscale interactions.
Here, processes through which the energy stored in an atomic force microscope cantilever dissipates in the tip-sample interaction are first decoupled qualitatively. A formalism is then presented and shown to allow quantification of fundamental aspects of nanoscale dissipation such as deformation, viscosity, and surface energy hysteresis. Accurate quantification of energy dissipation requires precise calibration of the conversion of the oscillation amplitude from volts to nanometers. In this respect, an experimental methodology is presented that allows such calibration with errors of 3% or less. It is shown how simultaneous decoupling and quantification of dissipative processes and in situ tip radius quantification provide the required information to analyze dependencies of dissipative mechanisms on the relative size of the interacting bodies, that is, tip and surface. When there is chemical affinity, atom-atom dissipative interactions approach the energies of chemical bonds. Such atom-atom interactions are found to be independent of cantilever properties and tip geometry thus implying that they are intensive properties of the system; these interactions prevail in the form of surface energy hysteresis. Viscoelastic dissipation on the other hand is shown to depend on the size of the probe and operational parameters.


Integrated proteomic analysis of major isoaspartyl-containing proteins in the urine of wild type and protein L-isoaspartate O-methyltransferase-deficient mice.
The formation of isoaspartyl residues (isoAsp or isoD) via either aspartyl isomerization or asparaginyl deamidation alters protein structure and potentially biological function. This is a spontaneous and nonenzymatic process, ubiquitous both in vivo and in nonbiological systems, such as in protein pharmaceuticals. In almost all organisms, protein L-isoaspartate O-methyltransferase (PIMT, EC126.96.36.199) recognizes and initiates the conversion of isoAsp back to aspartic acid. Additionally, alternative proteolytic and excretion pathways to metabolize isoaspartyl-containing proteins have been proposed but not fully explored, largely due to the analytical challenges for detecting isoAsp. We report here the relative quantitation and site profiling of isoAsp in urinary proteins from wild type and PIMT-deficient mice, representing products from excretion pathways. First, using a biochemical approach, we found that the total isoaspartyl level of proteins in urine of PIMT-deficient male mice was elevated. Subsequently, the major isoaspartyl protein species in urine from these mice were identified as major urinary proteins (MUPs) by shotgun proteomics. To enhance the sensitivity of isoAsp detection, a targeted proteomic approach using electron transfer dissociation-selected reaction monitoring (ETD-SRM) was developed to investigate isoAsp sites in MUPs. A total of 38 putative isoAsp modification sites in MUPs were investigated, with five derived from the deamidation of asparagine that were confirmed to contribute to the elevated isoAsp levels. Our findings lend experimental evidence for the hypothesized excretion pathway for isoAsp proteins. Additionally, the developed method opens up the possibility to explore processing mechanisms of isoaspartyl proteins at the molecular level, such as the fate of protein pharmaceuticals in circulation.


A pulse-burst laser system for a high-repetition-rate Thomson scattering diagnostic.
A "pulse-burst" laser system is being constructed for addition to the Thomson scattering diagnostic on the Madison Symmetric Torus (MST) reversed-field pinch. This laser is designed to produce a burst of up to 200 approximately 1 J Q-switched pulses at repetition frequencies 5-250 kHz. This laser system will operate at 1064 nm and is a master oscillator, power amplifier. The master oscillator is a compact diode-pumped Nd:YVO(4) laser, intermediate amplifier stages are flashlamp-pumped Nd:YAG, and final stages will be flashlamp-pumped Nd:glass (silicate). Variable pulse width drive (0.3-20 ms) of the flashlamps is accomplished by insulated-gate bipolar transistor switching of large electrolytic capacitor banks. The burst train of laser pulses will enable the study of electron temperature (T(e)) and electron density (n(e)) dynamics in a single MST shot, and with ensembling, will enable correlation of T(e) and n(e) fluctuations with other fluctuating quantities.


Security screening system based on terahertz-wave spectroscopic gas detection.
Tunable terahertz (THz)-wave absorption spectroscopy is a promising technique to detect trace gases suspended in ambient air owing to their strong absorption fingerprints in the THz-wave spectral region. Here, we present a THz-wave spectroscopic gas detection platform based on a frequency-tunable injection-seeded THz-wave parametric generator and compact multipass gas absorption cells. Using a 1.8-m-path-length multipass cell, we detected gas-phase methanol (CH3OH) down to a trace concentration of 0.2 ppm at the 1.48-THz transparent atmospheric window. We also developed a transportable walk-through screening prototype using a 6-m-path-length multipass cell to identify suspicious subjects. Our results demonstrate the potential of the proposed system for security screening applications.


The Global Gag Rule: The death trap for comprehensive sexual and reproductive healthcare and way to overcome the US gag rule.
The United States of America (USA) is one of the largest bilateral donors in the field of global health assistance. There are beneficiaries in 70 countries around the world. In 2015, the USA released US$638 million for the improvement of global health status by promoting family planning services. Unfortunately, in 2017, Trump administration reinstated Mexico City Policy/Global Gag Rule (GGR). This policy prevents non-US nongovernmental organizations (NGOs) from receiving US health financial assistance if they have any relationship with abortion-related services. This restriction pushed millions of lives into great danger due to the lack of comprehensive family planning services, especially lack of abortion-related services. This article has attempted to let the readers know about the impacts of GGR around the world and how global leaders are trying to overcome the harmful effects of this rule. Finally, it proposes some solutions to the impacts of the extension of Mexico City Policy.


Histologic evaluation of intrahepatic micrometastases in patients treated with or without neoadjuvant chemotherapy for colorectal carcinoma liver metastasis.
In the present retrospective study, we tested the hypothesis that neoadjuvant chemotherapy (NAC) as a treatment for patients with colorectal carcinoma liver metastases (CRLM) may reduce intrahepatic micrometastases. The incidence and distribution of intrahepatic micrometastases were determined in specimens resected from 63 patients who underwent hepatectomy for CRLM (21 treated with NAC and 42 without). In addition, the therapeutic efficacy of NAC was evaluated histologically. Intrahepatic micrometastases were defined as microscopic lesions spatially separated from the gross tumor. The distance from these lesions to the border of the hepatic tumor was measured on histological specimens and the density of intrahepatic micrometastases (number of lesions/mm(2)) was determined in regions close to (<1 cm) the gross hepatic tumor. Of the 21 patients treated with NAC, 13 were identified as having a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; thus, the overall response rate was 62%. Histologic evaluation of the therapeutic efficacy of NAC was significantly associated with tumor response to NAC according to the RECIST guidelines (p=0.048). In all, 260 intrahepatic micrometastases were detected in 39 patients (62%). Intrahepatic micrometastases were less frequently detected in NAC-treated patients than in untreated patients (5/21 [24%] vs. 34/42 [81%], respectively; p<0.001). There were no significant differences in the distance and density of intrahepatic micrometastases between the two groups (p=0.313 and p=0.526, respectively). In conclusion, NAC reduces the incidence of intrahepatic micrometastases in patients with CRLM, but NAC has no significant effect on their distribution when intrahepatic micrometastases are present.


Chemo- and immunotherapy of an adenovirus-induced transplantable sarcoma in hamsters.
The subcutaneous transplantable adenovirus sarcoma (TAVS) in hamsters was created in 1972 at the Oncological Research Institute and maintained by serial subcutaneous transplantation. It showed the highest sensitivity against some alkylating drugs and antimetabolites--cyclophosphamide, sarcolysine, methotrexate and 6-mercaptopurine. In some degree, TAVS is able to differentiate antitumor drugs of one group by the intensity of their antitumor activity. Among the drugs, cyclophosphamide was the most active and 6-mercaptopurine and 5-fluorouracil the least active. Antitumor drugs of plant origin, antibiotics and methyl-CCNU had a weak activity on subcutaneous TAVS. Intramuscular TAVS showed a similar sensitivity, with some differences for olivomycin, bruneomycin and vinblastine. Intracerebral TAVS was sensitive against antitumor agents penetrating through the hemato-encephalic barrier and which were active against its subcutaneous and intramuscular form. BCG vaccine and levamisole applied separately did not show any activity on the growth of TAVS. Combined immunochemotherapy with cyclophosphamide plus BCG gave a better enhancement of the antitumor effect of the cytostatic than that of the combination of methotrexate plus BCG and cyclophosphamide plus levamisole. These results showed that TAVS in hamsters may be used as a suitable experimental model for pharmacological studies of antitumor agents and combined immunochemotherapy.


Anti-hepatocarcinoma activity of TT-1, an analog of melittin, combined with interferon-α via promoting the interaction of NKG2D and MICA.
Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality. Immunotherapy has emerged in clinical treatment, owing to the limitation and severe side effects of chemotherapy. In the immune system, natural killer (NK) cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex (MHC) molecule issues. Hence, treatment which could stimulate NK cells is of great interest. Here, we investigated the efficacy of the combined therapy of TT-1 (a mutant of melittin) and interferon-α (IFN-α) on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo, as well as the mechanism involved. The combination therapy significantly inhibited the growth of HepG-2/Huh7 cells in vivo, but this effect was impaired after depleting NK cells. TT-1 not only up-regulated MHC class I-related chain molecules A (MICA) expression, but also prevented the secretion of soluble MICA (sMICA). Both the mRNA and protein of a disintegrin and metallopeptidase 10 (ADAM 10) in HepG-2/Huh7 cells were decreased after TT-1 treatment. The combined therapy of TT-1 and IFN-α could suppress the growth of HepG-2/Huh7 xenografted tumor effectively via promoting the interaction of NK group 2, member D (NKG2D) and MICA, indicating that TT-1+IFN-α would be a potential approach in treating liver cancer.


Synthesis and biological evaluation of some novel Schiff's bases from 1,2,4-triazole.
We have synthesized a number of novel Schiff's bases from 4-amino-3-(D-glucoheptonic-hexitol-1-yl)-1H-1,2,4-triazole-5-thione. By attaching D-glucoheptonic-hexitol-1-yl residues to 1,2,4-triazole at the 3-position, the solubility of the title compounds has been improved greatly. All the products have been characterized by elemental analysis, IR, 1H-NMR, 13C-NMR and MS. The plant-growth regulating effects of the title compounds were examined. From the biological activity results, we found that most compounds showed weak to moderate activities.


Do cultivar, geographical location and crop season influence phenolic profile of walnut leaves?
Walnut leaves from nine different cultivars (Arco, Franquette, Hartley, Lara, Marbot, Mayette, Meylannaise, Parisienne and Rego) were studied for their phenolic compounds. Samples were harvested along three consecutive years, at two different geographical locations, in order to evaluate if significant differences in the phenolics composition can be related with genetic, climatic or geographical factors. Nine compounds (3-caffeoylquinic, 3-p-coumaroylquinic and 4-p-coumaroylquinic acids, quercetin 3- galactoside, quercetin 3-arabinoside, quercetin 3-xyloside, quercetin 3-rhamnoside, a quercetin 3-pentoside derivative and a kaempferol 3-pentoside derivative) were quantified using an HPLC-DAD methodology. The qualitative profiles were identical for all samples, but differences were observed in terms of individual compounds' contents. Multivariate statistical analysis was carried out, showing that significant differences exist among production years, which can be related to climatic reasons.


Murine T cell responses to melittin and its analogs.
The 26-residue peptide melittin from bee venom elicits high IgG1 and IgE responses in selected strains of mice. The antibody responses were shown previously to be specific mainly for the region of residue 20-26. The T cell epitope of melittin in H-2d-restricted mice is now found to be primarily in residue 11-19, corresponding to an alpha-helical amphiphilic segment of the molecule. Melittin-specific T cell lines have varying responses to different structural analogs of the melittin T cell epitope, and the results indicate that the antigenicity of T cell epitope peptides depend more on their primary structure than on their secondary structure. Melittin-specific T cell clones are found to be CD4+ and secrete IL-4, and are restricted to presentation on I-Ad or I-Ed. The I-Ad- or I-Ed-restricted clones differ in their responses to different analogs of melittin.


Neonatal ovarian torsion: report of three cases and review of the literature.
Ovarian cysts are common incidental findings in term infants and, if unusually large, may result in dystocia, torsion, or rupture. Torsion and infarction of a normal ovary tend to occur in older childhood. During a 4-month period, 3 cases of neonatal ovarian torsion were observed after antenatal ultrasonography had detected fetal pelvico-abdominal cystic lesions. The three infants were explored between 4 and 16 days of age. Ovarian torsion was right-sided in all 3, and 1 ovary had been autoamputated. The resected specimens were nontense, thin-walled cysts, filled with hemorrhagic fluid, that measured between 4.5 and 8 cm in diameter. Microscopically, focal calcification and widespread necrosis precluded recognition of underlying histologic landmarks. Neonatal ovarian cysts or cystic ovaries greater than 4 cm in diameter should be excised, even if asymptomatic, because they are prone to, or have undergone, torsion.


Associated factors and consequences of late preterm births: results from the 2004 Pelotas birth cohort.
Although neonatal and infant mortality rates have fallen in recent decades in Brazil, the prevalence of preterm deliveries has increased in certain regions, especially in the number of late preterm births. This study was planned to investigate: (1) maternal antenatal characteristics associated with late preterm births and (2) the consequences of late preterm birth on infant health in the neonatal period and until age 3 months. A population-based birth cohort was enrolled in Pelotas, Southern Brazil, in 2004. Mothers were interviewed and the gestational age of newborns was estimated through last menstrual period, ultrasound and Dubowitz's method. Preterm births between 34 and 36 completed weeks of gestational age were classified as late preterm births. Only singleton live births from mothers living in the urban area of Pelotas were investigated. Three months after birth, mothers were interviewed at home regarding breast feeding, morbidity and hospital admissions. All deaths occurring in the first year of life were recorded. A total of 447 newborns (10.8%) were late preterms. Associations were observed with maternal age <20 years (prevalence ratio [PR] 1.3 [95% CI 1.1, 1.6]), absence of antenatal care (PR 2.4 [1.4, 4.2]) or less than seven prenatal care visits, arterial hypertension (PR 1.3 [1.0, 1.5]), and preterm labour (PR 1.6 [1.3, 1.9]). Compared with term births, late preterm births showed increased risk of depression at birth (Relative risk [RR] 1.7 [1.3, 2.2]), perinatal morbidity (RR 2.8 [2.3, 3.5]), and absence of breast feeding in the first hours after birth (PR 0.9 [0.8, 0.9]). RRs for neonatal and infant mortality were, respectively, 5.1 [1.7, 14.9] and 2.1 [1.0, 4.6] times higher than that observed among term newborns. In conclusion, in our setting, the prevention of all preterm births must be a priority, regardless of whether early or late.


Reasons and circumstances for the late notification of Acute Flaccid Paralysis (AFP) cases in health facilities in Luanda.
As the polio eradication effort enters the end game stage, surveillance for Acute Flaccid Paralysis in children becomes a pivotal tool. Thus given the gaps in AFP surveillance as identified in the cases of late notification, this study was designed to explore the reasons and circumstances responsible for late notification of AFP and collection of inadequate stools (more than 14 days of onset of paralysis until collection of the 2nd stool specimen) of AFP cases in health facilities equipped to manage AFP cases. Eleven AFP cases with inadequate stools were reported from January 2 to July 8, 2012 - Epidemiological Weeks 1-27. The families of these cases were interviewed with an in-depth interview guide. The staff of the seven health units, where they later reported, was also enlisted for the study which used in-depth interview guide in eliciting information from them. Ignorance and wrong perception of the etiology of the cases as well as dissatisfaction with the health units as the major reasons for late reporting of AFP cases. The first port of call is usually alternative health care system such as traditional healers and spiritualists because the people hold the belief that the problem is spiritually induced. The few, who make it to health units, are faced with ill equipped rural health workers who wait for the arrival of more qualified staff, who may take days to do so. An understanding of the health seeking behavior of the population is germane to effective AFP surveillance. There is thus a need to tailor AFP surveillance to the health seeking behavior of the populations and expand it to community structures.


Micropenis with testicular regression, low LH levels, and poor androgen and HCG responses: a distinct syndrome?
We report three boys, including two brothers, with micropenis and poor phallic growth in response to both exogenous human chorionic gonadotropin (HCG) and testosterone therapy in the newborn period. They exhibited low neonatal testosterone levels that failed to respond to HCG stimulation. These boys displayed a unique gonadotropin profile with reduced luteinizing hormone levels and elevated follicle-stimulating hormone levels. They had small, cryptorchid testes with subsequent testicular regression and atrophy. Moreover, all three boys have developed microcephaly and mild learning delays. We review the hormonal profiles and phenotypes of known causes of micropenis, and compare them to the features of our three patients. Although individuals with similar features may have been described in past series of males with micropenis, the data presented previously were insufficient for classification; thus, we propose that our patients may represent a distinct, not previously recognized, syndrome with either X-linked recessive inheritance or autosomal recessive inheritance with male sex limitation.


Clinical implications of frailty in peritoneal dialysis patients - A prospective observational study.
Frailty is an age-related condition that predicts adverse outcomes. The study was aimed to investigate the clinical implications of frailty evolution in patients undergoing peritoneal dialysis (PD). In this prospective study, all new-onset (<6 months) and prevalent (≧6 months) PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≧13/80 (FI80 > 0.16) or ≧3/5 (frailty phenotype) was designated to define frailty. 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged <55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization). Poisson regression showed frailty was associated with increased utilizations of outpatient and ER services; however multivariate Cox models identified only diabetes, gout and low body mass index (<19 kg/m2), but not frailty, predicted overall death and hospitalizations. Frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout) and undernutrition appeared to be more robust in the prediction of adverse outcomes.


Universal childhood and adolescent obesity prevention programs: review and critical analysis.
Authors reviewed randomly controlled studies of universal prevention of childhood obesity, identifying 29 studies that met review criteria. Review suggested that outcomes are generally modest across all age groups and there were few replications of any program; thus, at this time no universal prevention program for childhood obesity meets criteria for a well-established intervention of the American Psychological Association. A wide variety of intervention targets have been investigated (knowledge and attitudes, family involvement, physical activity, television watching, water consumption, vegetable consumption, breast feeding, etc.) in a wide number of countries. Effects seem to be stronger for girls than for boys, for unknown reasons. Many studies fail to achieve sufficient statistical power and/or a sophisticated measurement strategy, neglecting key variables such as cost, treatment fidelity, longer-term follow up data, and process variables. Questions as to the theories of change associated with the interventions are also raised and suggestions for future research in this area are provided.


Charge Detection Mass Spectrometry with Almost Perfect Charge Accuracy.
Charge detection mass spectrometry (CDMS) is a single-particle technique where the masses of individual ions are determined from simultaneous measurement of each ion's mass-to-charge ratio (m/z) and charge. CDMS has many desirable features: it has no upper mass limit, no mass discrimination, and it can analyze complex mixtures. However, the charge is measured directly, and the poor accuracy of the charge measurement has severely limited the mass resolution achievable with CDMS. Since the charge is quantized, it needs to be measured with sufficient accuracy to assign each ion to its correct charge state. This goal has now been largely achieved. By reducing the pressure to extend the trapping time and by implementing a novel analysis method that improves the signal-to-noise ratio and compensates for imperfections in the charge measurement, the uncertainty has been reduced to less than 0.20 e rmsd (root-mean-square deviation). With this unprecedented precision peaks due to different charge states are resolved in the charge spectrum. Further improvement can be achieved by quantizing the charge (rounding the measured charge to the nearest integer) and culling ions with measured charges midway between the integral values. After ions with charges more than one standard deviation from the mean are culled, the fraction of ions assigned to the wrong charge state is estimated to be 6.4 × 10(-5) (i.e., less than 1 in 15 000). Since almost all remaining ions are assigned to their correct charge state, the uncertainty in the mass is now almost entirely limited by the uncertainty in the m/z measurement.


Testing graceful degradation in a patient with aphasia.
We report an investigation of phonological priming of a picture naming task in an anomic aphasic, PB, using caffeine as a pharmacological manipulation. We compare her results to controls on a similar paradigm testing the hypothesis that qualitative results in controls would carry over to the damaged brain demonstrating a "graceful degradation" in performance. When primed with words phonologically related to a target, PB made more word retrieval failures on caffeine as a function of related primes (controls make fewer) and fewer word retrieval failures as a function of unrelated primes (controls make more). The results thus supported the rejection of the hypothesis and we conclude that the use of the pharmacological manipulation provides a sensitive test for the graceful degradation of function.


Long-term survival in a dog with primary hepatic neuroendocrine tumor treated with toceranib phosphate.
Primary hepatic neuroendocrine tumors (PHNETs) are rare in dogs, and limited information exists about the treatment of these tumors. A 12-year-old castrated male French bulldog was presented to our clinic with gastrointestinal signs. Diagnostic tests revealed increased hepatic enzyme levels, a mass in the hepatic quadrate lobe, multiple intrahepatic nodules, and enlarged hepatic hilar lymph nodes. The liver mass was diagnosed cytologically as a malignant epithelial tumor suspected to be of neuroendocrine origin. The dog was treated with single-agent toceranib phosphate (TOC) and survived 25.1 months after the initial presentation. On necropsy, a liver mass was found and was subsequently diagnosed as a PHNET on histopathology. To the best of our knowledge, this is the first report of long-term survival in a dog with PHNET treated with TOC.


Correction: Excitation of vibrational soft modes in disordered systems using active oscillation.
Correction for 'Excitation of vibrational soft modes in disordered systems using active oscillation' by Elsen Tjhung et al., Soft Matter, 2016, DOI: .


The social network of children with special healthcare needs in the (in)visibility of nursing care.
This study aimed to identify the (in)visibility of nursing care and discuss ways of (dis)articulating this care with family care in the social network of children with special healthcare needs. A qualitative research was performed with health professionals at a pediatric hospital, four units of the Family Medical Program (FMP), and children's relatives living in Niterói (RJ). The field work was put in practice after IRB approval (HESFA/EEAN), consisting of five semi-structured interviews and two group dynamics. Critical Discourse Analysis indicated that nursing care is visible in the child's social network through the nurse's educational and care activities and home visits by the nurisng aide of the FMP. Due to errors in the national health system's referral and counter-referral, mothers articulate the network and not the health service; thus, the reorganization of the system in the State would foster social networks that are less wearing for their families.


Immersion Experiences for Biomedical Engineering Undergraduates: Comparing Strategies and Local Partnerships at Two Institutions.
Immersion experiences for undergraduate students in biomedical engineering are key contributors to their ability to identify medical needs. Despite this, as few as 25% of surveyed programs report providing such opportunities. Since 2010 when the National Institute of Health began its R25 grant mechanism to support curricular development toward team-based design, several institutions have established programs for immersion experiences, which provide precedent for their implementation. Published results from such immersion experiences highlight successes in structure and changes in student perspectives after these experiences. As more institutions expand their biomedical engineering curriculum with new immersion-focused programs, it is important to learn from these precedents while also considering opportunities to improve. For newly funded groups that are developing and implementing programs, they may find improved success by strategic use of unique partnerships. However, these partnerships may not be immediately evident to program organizers. Our objective is to discuss two institutions that recently established programs for immersion experience. In the comparison of our two immersion programs, we found five overlapping core features that include: immersion partner collaboration, team-based immersion experiences, needs-finding emphasis, team-based engineering design experiences, and immersion assessment and evaluation. Both programs developed collaborative partnerships with nearby medical schools. Additionally, one program partnered with a community resource (i.e., Human Development Institute). Despite nuanced program differences, we found that students at both programs self-reported increased knowledge or confidence in aspects of the design process (e.g., identifying and refining user needs, concept generation). Our results also highlight student gains unique to their programs - UK students self-reported gains on disability topics and IUPUI students self-reported gains on socioeconomic awareness. In summary, immersion partner collaboration, or partnership, surfaced as a core feature for both programs, and students in both immersion programs endorsed enhanced knowledge or confidence in engineering design.


Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography.
We aimed to investigate the prevalence of undiagnosed abnormal glucose regulation (AGR, including diabetes and prediabetes) in patients undergoing coronary angiography (CAG) by using both glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to screen, and to compare the performance of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and HbA1c for screening for AGR. Eligible patients were adults without known diabetes who were admitted for CAG. Patients' glucose regulation status was defined by conducting HbA1c and OGTT 2-4 weeks after hospital discharge. The performance of FPG, 2hPG, and HbA1c for detecting AGR was evaluated using receiver operating characteristic (ROC) analysis. A total of 689 subjects were included. According to OGTT, the prevalence rates of diabetes and prediabetes were 19.9% and 41.7%, respectively. The corresponding values were 28.0% and 60.4%, respectively, when HbA1c was adopted as a diagnostic criterion in addition to OGTT. For detecting diabetes, the area under the ROC curve (AUC) was higher for HbA1c than for FPG (0.87 vs. 0.80, p=0.005), but was not significantly different from that for 2hPG (0.87 vs. 0.88, p=0.58). For detecting AGR, the AUC was higher for HbA1c than for either FPG (0.94 vs. 0.74, p<0.001) or 2hPG (0.94 vs. 0.83, p<0.001). Using HbA1c and OGTT to screen, we reported an extremely high prevalence of previously undiagnosed AGR (28.0% diabetes and 60.4% prediabetes) in patients admitted for CAG. HbA1c may be adopted as an alternative to OGTT for screening for AGR in patients undergoing CAG.


Primary health care providers knowledge of dementia and cognitive assessment tools for elderly populations in Southeast Nigeria: A pilot survey.
Primary health care remains the widely available first point of medical care in Nigeria and in other low- and middle-income countries. Recognizing the rising prevalence of dementia in these settings, primary healthcare providers should be trained on cognitive assessment. However, little is known about the current Nigerian primary healthcare providers' knowledge of dementia, cognitive assessment tools, and use in elderly populations. The aim of this study was to evaluate primary healthcare providers' knowledge of dementia and cognitive assessment tools in Southeast Nigeria in preparation for the introduction of digital tablet-based assessment tool. This is a cross-sectional mixed method descriptive pilot survey carried out in a comprehensive healthcare center affiliated with Nnamdi Azikiwe University Teaching Hospital. Fifty healthcare workers participated. Convenience sampling was employed involving all consenting primary healthcare providers in comprehensive healthcare center-Nnamdi Azikiwe University Teaching Hospital. A structured questionnaire was distributed for generation of both qualitative and quantitative data. The mean age of the 50 primary healthcare providers was 36.6 years, with females constituting 80%. Mean practice duration was 10.8 years. Their response on the mean age at which patients may need a cognitive assessment was reported as 52.8 years. Primary healthcare providers reported that dementia is associated with memory loss and can be genetically inherited. None of the respondents were familiar with Montreal cognitive assessment, or any form of tablet-based cognitive assessment tool. Most (86%) knew about the mini mental state examination. Primary healthcare providers are deficient in knowledge of dementia Alzheimer's or cognitive assessment tools, and so they do not routinely carryout cognitive screening in elderly patients during clinic visits. It is important to train all cadres of primary healthcare staff on the use and benefit of cognitive assessment using culturally validated user-friendly tool to improve quality of care for the elderly population.


Gastrointestinal involvement by mantle cell lymphoma observed by endoscopy: A case report.
Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin B-cell lymphoma, accounting for 6% of all non-Hodgkin lymphoma. The typical appearance of intestinal MCL is multiple lymphomatous polyposis, whereas presentation as protruding lesions is uncommon. We herein report the case of a 64-year-old male patient who was admitted to our hospital with epigastric pains. On endoscopy, submucosal neoplasma were identified in the gastric antrum, the duodenal bulb, and the rectum. On endoscopic ultrasonography (EUS) (OLYMPUS EUS EU-ME2, Miniprobe sonography), the lesions were homogeneously hypoechoic and originated from the submucous layer or muscularis mucosa. Pathological examination of biopsied specimens from the lesions of the rectum revealed diffuse lymphomatous proliferation and dense infiltration by monomorphic and small cleaved cells with irregularly shaped nuclei. On immunohistochemistry, the cells were positive for cyclin D1, CD20, CD21, SOX-11, and Bcl-2, but negative for CD3 and CD10; these findings were compatible with a diagnosis of MCL. The EUS characteristics initially led to the suspicion of digestive neuroendocrine tumors, since MCL presenting as submucosal tumors on EUS is rarely reported. We herein present this case to suggest clinician to include MCL in the differential diagnosis of submucosal intestinal lesions, as early diagnosis and timely treatment may improve patient prognosis.


Pulmonary vein isolation for atrial fibrillation in patients with symptomatic sinus bradycardia or pauses.
Sick sinus syndrome is commonly associated with tachyarrhythmias and bradyarrhythmias that often are symptomatic. The aim of this study was to assess the effect of pulmonary vein isolation in patients with sick sinus syndrome and atrial fibrillation (AF). Three hundred fourteen consecutive patients who underwent pulmonary vein isolation between December 2000 and January 2002 were included in the study. Thirty-one patients had sick sinus syndrome, which was defined as a preprocedural history of symptomatic sinus bradycardia or pauses. Endpoints included AF recurrence, change in the frequency of sinus pauses, and symptoms of presyncope or syncope, as well as mean heart rate and percentage of atrial pacing in patients with pacemakers implanted prior to the pulmonary vein isolation. Patients had AF for an average of 6 +/- 3 years. Patients were 58 +/-8 years old and had ejection fractions of 55 +/- 4%. Sixty-one percent had implanted pacemakers. AF recurred within 6 months in 4 patients. Two had a successful second pulmonary vein isolation procedure. There were no recurrences of presyncopal events (P < 0.05) or documented sinus pauses (P < 0.05) after successful pulmonary vein isolation in the patients without permanent pacemakers. Patients with pacemakers had a 13-fold reduction in the percentage of atrial pacing (P < 0.05). Both groups showed a significant increase in average heart rates at 6-month follow-up. Cure of AF by pulmonary vein isolation helped resolve the clinical manifestations of sick sinus syndrome, suggesting that the occurrence of AF and/or the associated treatment could be partially responsible for sick sinus syndrome.


Vitamin D and microRNAs in bone.
MicroRNAs (miRNAs) are short noncoding RNAs that orchestrate complex posttranscriptional regulatory networks essential to the regulation of gene expression. Through complementarity with messenger RNA (mRNA) sequences, miRNAs act primarily to silence gene expression through either degradation or inhibited translation of target transcripts. In this way, miRNAs can act to fine-tune the transcriptional regulation of gene expression, but they may also play distinct roles in the proliferation, differentiation, and function of specific cell types. miRNA regulatory networks may be particularly important for signaling molecules such as vitamin D that exert pleiotropic effects on tissues throughout the body. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) functions as a steroid hormone that, when bound to its nuclear vitamin D receptor, is able to regulate target gene expression. However, recent studies have also implicated 1,25(OH)2D in epigenetic regulation of genes most notably as a modulator of miRNA function. The current review details our understanding of vitamin D and miRNAs with specific emphasis on the implications of this interaction for biological responses to vitamin D in one of its classical target tissues, i.e., bone.


THE INFLUENCE OF HIP STRENGTH ON KNEE KINEMATICS DURING A SINGLE-LEGGED MEDIAL DROP LANDING AMONG COMPETITIVE COLLEGIATE BASKETBALL PLAYERS.
A smaller knee flexion angle and larger knee valgus angle during weight-bearing activities have been identified as risk factors for non-contact anterior cruciate ligament (ACL) injuries. To prevent such injuries, attention has been focused on the role of hip strength in knee motion control. However, gender differences in the relationship between hip strength and knee kinematics during weight-bearing activities in the frontal plane have not been evaluated. The purpose of this study was to determine the influence of hip strength on knee kinematics in both genders during a single-legged landing task in the frontal plane. The hypotheses were that 1) subjects with a greater hip strength would demonstrate larger knee flexion and smaller knee valgus and internal rotation angles and 2) no gender differences would exist during the single-legged landing task. Forty-three Japanese collegiate basketball players (20 males, 23 females) participated in this study. Three-dimensional motion analysis was used to evaluate knee kinematics during a single-legged medial drop landing (SML). A hand-held dynamometer was used to assess hip extensor (HEXT), abductor (HAB), and external rotator (in two positions: seated position [SHER] and prone [PHER]) isometric strength. Spearman rank correlation coefficients (ρ) were determined for correlations between hip strength and knee kinematics at initial contact (IC) and peak (PK) during SML (p < 0.05). Negative correlations were observed between the knee valgus angle at IC and HEXT (ρ = -0.48, p = 0.02), HAB (ρ = -0.46, p = 0.03) and PHER (ρ = -0.44, p = 0.04) strength in females. In addition, a significant positive correlation was observed between the knee flexion angle at PK and HEXT strength (ρ = 0.61, p = 0.004) in males. Significant correlations between hip strength and knee kinematics during SML were observed in both genders. Hip strength may, therefore, play an important role in knee motion control during sports activities, suggesting that increased hip strength may help to prevent non-contact ACL injuries in athletes of both genders. Moreover, gender-specific programs may be needed to control abnormal knee motion, as the influence of hip strength on knee kinematics may differ based on gender. 3.


[Use of imipenem-cilastatin in neonatal septicemias caused by gram-negative bacilli multiresistant to beta-lactam antibiotics].
Seven neonates with septicemia due to Gram negative bacteria resistant to beta-lactam received imipenem-cilastatin therapy. Bacteria isolated were Enterobacter cloacae [3], Enterobacter aerogenes [1], Klebsiella pneumoniae [1], Serratia marcescens [1], Pseudomonas fluorescens [1]. The MICs of imipenem were lower 1 microgram/ml. In 3 children septicemia occurred during previous antimicrobial chemotherapy. 3 IV 60 mg/kg doses of imipenem with amikacin (15 mg kg/d) were administered every day. For five children blood cultures were negative after 48 hours of treatment. E. aerogenes septicemia required pefloxacin because blood cultures remained positive (d5) despite an increased dosage (90 mg/kg/d). All children were cured and imipenem-cilastatin was not responsible for any complication. Those results demonstrate the efficacy of imipenem in the treatment of septicemia in newborns due to multiresistant Gram negative bacteria.


Effect of decreasing pressure on soliton self-compression in higher-order modes of a gas-filled capillary.
We numerically investigate soliton self-compression in the higher-order modes of a gas-filled capillary with decreasing pressure. We demonstrate four times enhancement in the compression with the decreasing pressure compared to the equivalent constant pressure case in the HE12 mode, reaching sub-cycle duration of 1.85 fs at its output. Moreover, the negative pressure gradient effectively suppresses the intermodal coupling in the later stage of the compressor, which helps to maintain high output mode purity. These findings are of direct benefit for applications that require ultrashort light pulses in unconventional spatial beam profiles, including in nonlinear frequency conversion, microscopy, micromachining, and particle manipulation.


Effect of monoclonal antibodies to Epstein-Barr virus envelope glycoproteins on Epstein-Barr virus neutralization and binding to target cell receptors. A comparative analysis.
Viral envelope glycoproteins are important in antiviral immunity; however, their precise role in both generating virus-neutralizing antibodies as well as in viral binding to target cell receptors remains largely unexplored. We studied nine monoclonal antibodies (MoAbs) to Epstein-Barr virus (EBV) envelope glycoproteins in order to define the role(s) of their respective epitopes in both EBV neutralization and binding to cellular receptors. Only four MoAbs neutralized EBV infectivity, one requiring complement, and only 1 of these 4 did inhibit EBV binding to target cell receptors. Our results suggest that (1) the epitopes recognized by a majority of these MoAbs play no role in viral neutralization and (2) that the majority of epitopes recognized by the neutralizing antibodies play no role in EBV binding to target cell receptors. This and previous studies would also suggest that only one epitope is involved in EBV binding to its receptor or that, until now, we were able to identify only one EBV-neutralizing MoAb (i.e., 72A1) which is specific for the receptor-binding viral epitope. It is probable that the epitope recognized by 72A1 MoAb is the only glycoprotein domain with a dual role, i.e., in EBV neutralization and binding to target cell receptors.


Electron bunch trapping and compression by an intense focused pulse laser.
A focused short-pulse laser of TEM (1,0)+TEM (0,1) mode has two intensity peaks in the radial direction, so that the transverse ponderomotive force may trap electrons between the two peaks. At the same time the longitudinal ponderomotive force may accelerate electrons at the head of the laser pulse, when the laser is focused. When the electrons move to the laser tail, the laser may diverge and the electron deceleration becomes relatively weak. Our numerical analyses demonstrate that electrons are trapped well by the laser potential well, and that at the same time the acceleration by the longitudinal ponderomotive force induces the electron bunch compression. This trapping and compression mechanism is unique: the electron bunch can be compressed to the scale of the laser pulse length.


Value of Ultrasonography in Detection of Diaphragmatic Injuries Following Thoracoabdominal Penetrating Trauma; a Diagnostic Accuracy Study.
Diagnosis of diaphragmatic rupture following thoracoabdominal penetrating trauma is very challenging in asymptomatic patients with stable vital signs. This study aimed to evaluate the diagnostic accuracy of focused assessment with sonography for trauma (FAST) in this regard. This cross-sectional study was performed on patients referring to emergency department due to left thoracoabdominal stab wound during 2 years. All patients initially underwent ultrasonography and the screening performance characteristics of FAST in detection of diaphragmatic injuries were calculated, considering the findings of diagnostic laparoscopy as the gold standard test. Twenty-four patients with the mean age of 33 ± 10.64 years (16-61 years) were studied (100% male). The mean chest wall laceration size was 2.7 ± 2.7 cm (1-10 cm) and the most frequent location of wounds was posterior chest wall (42%) and in the 6th and 7th intercostal space (50%). Diaphragmatic rupture was seen in 4 (16.7%) patients based on diagnostic laparoscopy. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratio of FAST in detection of diaphragmatic raptures were 50% (95% CI: 9.18 - 90.8), 100% (95% CI: 79.9 - 100.0), 100% (95% CI: 19.8 - 100.0), 9.1% (95% CI: 1.5 - 30.6), Infinity, and 0.1 (95% CI: 0.02 - 0.37), respectively. The overall accuracy of FAST in this regard was 75.0% (95% CI: 42.3 - 100.0). In patients with penetrating trauma to the left thoracoabdominal region, FAST cannot be the definitive alternative to diagnostic laparoscopy to detect diaphragm rupture.


Uterine position and presentation of minipig-fetuses and their order and presentation at birth.
Uterine position and presentation of fetuses in 17 minipigs during pregnancy were compared with their order and presentation at birth. Fetuses from 1 or both uterine horns were marked between day 80 and day 105 of gestation by 1 or more transuterine injections of either a 2.5% solution of dianil blue (3 animals) or a radiopaque substance (14 animals). Roentgenograms of the newborn pigs, which were ear-notched immediately after birth, enabled making individual identification. Pigs seemed to be delivered randomly from the 2 uterine horns. They either followed a neighbor from the same horn (n = 42) or followed a pig from the contralateral horn (n = 52). Only in 3 dams did 1 uterine horn become empty before delivery from the other horn started. In 4 dams, 1 pig passed its neighbor from the same horn, thereby being born earlier than expected. Moreover, passing of pigs could have occurred and gone undetected in those dams from which the pigs of only 1 horn were marked. This passing might have taken place within the uterine body. From 18 of 95 pigs (19%) , the presentation at birth differed from the one observed at laparotomy.


Morphological effects of myasthenia gravis patient sera on human muscle cells.
Myasthenia gravis (MG) is caused primarily by autoantibodies against the nicotinic acetylcholine receptor (AChR), but autoantibodies to other muscle proteins may be present. Many of these proteins have structural or signalling functions, the disruption of which may affect muscle cell morphology or viability. In order to investigate the role of such autoantibodies in MG, we examined the effect of MG patient sera, of different autoantibody composition and obtained at different stages of disease severity, on primary human muscle cells. Sera from MG patients induced changes in cell morphology from typical elongated cells to an irregular phenotype, caused the formation of inclusion bodies and intracellular vesicles, and led to a disordered arrangement of actin microfilaments. Sera from the most severely affected patients also induced cell death, which did not occur via classic apoptosis. The effects were not complement-mediated and were dose- and time-dependent. As the effects observed in the cell culture system correlated with disease severity, a greater understanding of the individual factors responsible for these effects may improve our understanding of MG pathogenesis and be of value in the assessment of disease in individual patients.


Subjective memory impairment, objective cognitive functioning and social activity in French older people: findings from the Three Cities study.
To investigate the association between subjective memory impairment (SMI) and objective cognitive impairment in later life, and to ascertain whether this is modified by level of social activity, education or living alone. Data were analyzed from three French community surveys carried out in Bordeaux, Dijon and Montpellier. Representative samples of 9294 residents aged 65 years and over were included in the study. SMI was ascertained and investigated in relation to performance on the Benton Visual Retention Test (BVRT), the Isaac Set Test (IST) and Trail Making Test B (TMT). Adjustments were made for age, sex, education, depressive symptoms (Centre for Epidemiological Depression scale), site where study was carried out and living alone. Stratified analyses investigated modification by high or low social activity, education or living arrangement. SMI was reported by 21.9% of the sample, and was significantly associated with lower scores on BVRT and TMT after adjustment for age, sex, education, depressive symptoms, site and living alone. These associations were not significantly modified by social activity, education or living alone. Worse subjective memory was associated independently with worse performance on two tests of cognitive function; however, in these cohorts, no evidence was found for modification of associations by social activity/support or education.