IL-18 induces emphysema and airway and vascular remodeling via IFN-γ, IL-17A, and IL-13.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, alveolar destruction, and airway and vascular remodeling. However, the mechanisms that lead to these diverse alterations have not been defined. We hypothesized that IL-18 plays a central role in the pathogenesis of these lesions. We generated and characterized lung-specific, inducible IL-18 transgenic mice. Here we demonstrate that the expression of IL-18 in the mature murine lung induces inflammation that is associated with the accumulation of CD4(+), CD8(+), CD19(+), and NK1.1(+) cells; emphysema; mucus metaplasia; airway fibrosis; vascular remodeling; and right ventricle cardiac hypertrophy. We also demonstrate that IL-18 induces type 1, type 2, and type 17 cytokines with IFN-γ-inhibiting macrophage, lymphocyte, and eosinophil accumulation while stimulating alveolar destruction and genes associated with cell cytotoxicity and IL-13 and IL-17A inducing mucus metaplasia, airway fibrosis, and vascular remodeling. We also highlight interactions between these responses with IL-18 inducing IL-13 via an IL-17A-dependent mechanism and the type 1 and type17/type 2 responses counterregulating each another. These studies define the spectrum of inflammatory, parenchymal, airway, and vascular alterations that are induced by pulmonary IL-18; highlight the similarities between these responses and the lesions in COPD; and define the selective roles that type 1, type 2, and type 17 responses play in the generation of IL-18-induced pathologies.


The role of mean platelet volume as an inflammatory marker in children with chronic spontaneous urticaria.
Previous studies have shown that platelets are involved in the inflammatory process. Mean platelet volume (MPV) has been frequently used as an inflammatory marker in various diseases associated with inflammation. The role of MPV in children with chronic spontaneous urticaria (CU), however, has not yet been evaluated. In this study we compared MPV levels between children with and without CU. Children with CU and age-matched healthy children were enrolled in the study. Complete blood count and C-reactive protein (CRP) levels were assessed in children with CU whilst MPV levels were compared between children with and without CU. Forty children with CU (19 males; mean age: 8.0 ± 3.8 year; range: 3-15 years) and 40 healthy children (17 males; mean age: 6.9 ± 3.0 year; range: 2-14 year) were enrolled on the prospective, case-control study. MPV (fL) levels were significantly lower in children with CU when compared to healthy children (7.42 ± 0.77 and 7.89 ± 0.65, respectively; p=0.004). Both mean platelet number and median CRP levels were significantly higher in children with CU when compared to healthy children (p=0.008, p=0.014, respectively). To our knowledge, this study is the first to evaluate the role of MPV as an inflammatory marker in children with CU. A decline in MPV may be considered as an indicator of inflammation in children with CU.


The role of spinal cord MRI in the diagnosis of multiple sclerosis.
In this study we evaluated the effectiveness of high field thin slice surface coil MRI in demonstrating MS plaques in the cervical and upper thoracic spinal cord. MRI seems to be in our experience a sensitive indicator of spinal cord involvement in patients suffering from MS.


Ocean current redistributed the currently using Organoamine Pesticides in Arctic summer water.
In a comprehensive study on the presence and distribution of Currently Using Organoamine Pesticides (CUOAPs) in the Arctic Ocean, this study collected and analyzed 36 surface seawater samples during the summer of 2021. The study detected 36 CUOAPs, 17 of these compounds at levels exceeding the Method Detection Limits (MDLs). Concentrations of CUOAPs ranged from 0.11 to 2.94 ng/L, exhibiting an average of 1.83 ± 0.83 ng/L. Spatial distribution analysis revealed lower CUOAP concentrations in the central Arctic Ocean, with Cycloate constituting the most abundant component (23.66 %). The investigation identified terrestrial inputs and long-range atmospheric transport as potential sources of CUOAPs in the Arctic Ocean region. The origins of individual CUOAPs appeared to be associated with application procedures and their propensity for co-occurrence at low latitudes. The study also examined the role of ocean currents in the transport and redistribution of CUOAPs in surface seawater across different regions. While ocean currents played a significant role, the influence of sea ice cover on CUOAP distribution was minimal. An ecological risk assessment analysis underscored the need for regional attention to the presence of CUOAPs in the Arctic Ocean.


Application of dibutyltin oxide method to regioselective acylation and alkylation of tylosin at C-4''.
4''-O-Acyl-, 4''-O-alkyl- and 4''-deoxy-tylosin derivatives were synthesized using 2'-O-acetyl-3'',4''-O-(dibutyl-stannio)tylosin as a synthetic intermediate. The in vitro biological evaluation showed that the new derivatives were active against macrolide-resistant clinical isolates of bacteria and mycoplasmas, and that they were resistant to hepatic esterase.


The HIF pathway in cancer.
The transcription factor hypoxia-inducible factor-1 (HIF) is commonly activated in cancer. This has major effects on gene expression, and is important in tumor angiogenesis. Besides being activated by low oxygen, genetic events in cancer contribute to activating HIF. Most striking is that loss of function of the VHL tumour suppressor protein results in constitutive activation of the HIF pathway. An important aim is to define the contribution of HIF activation to the evolution of different cancers, and its potential as a therapeutic target.


Longitudinal functional performance among children with cochlear implants and disabilities: a prospective study using the Pediatric Evaluation of Disability Inventory.
Functional outcomes are important in children with cochlear implants (CI) and additional disabilities as studies on auditory skill and speech/language development may not identify functional benefits from implantation. This study sought to measure functional performance skills of young children with developmental disabilities post-CI. Eight children with cognitive disabilities undergoing cochlear implantation were enrolled in a prospective study of language and functional abilities; 6 with 1 year follow-up were included in the analysis. Functional performance was measured using Pediatric Evaluation of Disability Inventory (PEDI), providing standardized (mean: 50) and scaled scores (range: 0-100) of functional domains: Self-Care, Mobility and Social Function. The PEDI was administered pre-implant, 6 and 12 months post-implantation along with language testing at the same intervals. All children had cognitive disability; 5 also had motor delay. The ages at CI ranged from 13.8 to 134 months. For functional abilities, children did not make significant changes in domain-specific standard scores over 1 year. Children made progress in scaled scores by 1-year post-implant. The largest increase for all domains occurred in the first 6 months (7-11.5 point increase). For language abilities, children made a median 5.5-month increase in receptive language age (p=0.06) and 5-month increase in expressive language age (p=0.03) in the first year post-CI with no change in language quotients. Receptive language level was significantly (p<0.05) associated with increasing scores in the domains of Self-Care and Social Function. This is the first study to measure daily functional abilities in children with implants and disabilities using a standardized tool. Although our small group of complex children did not have an increase in standard scores (gap-closing trajectories), they made progress in skill development on scaled scores. Receptive language appears to play a key role in social functioning in this population. Functional assessments are informative for treatment planning and identifying specific areas to target intervention.


Complementation between mutants of CHO cells resistant to a variety of plant lectins.
Chinese hamster cell mutants resistant to the lectins PHA, WGA, RIC, LCA, and CON A were previously grouped into 8--10 distinct phenotypes on the basis of their unique patterns of lectin resistance and lectin-binding properties. All but one of these classes of lectin-resistant (LecR) mutants behave recessively in somatic cell hybrids. One ricin-resistant class (RicRII) behaves dominantly. Tests for complementation, by measuring the lectin-resistant properties of appropriate hybrids, show that seven distinct complimentation groups can be delineated among the phenotypically recessive mutants.


What do Spanish registries report about worsening events in chronic heart failure? Needs and challenges.
Worsening heart failure (HF) is associated with a high risk of death and rehospitalization. Despite that, real world evidence about the impact of worsening HF on clinical practice is scarce. A narrative review about registries addressing recent worsening HF events in Spain, with special emphasis on patients recently hospitalized for HF was performed. Worsening HF can be defined as situations where the patient's HF deteriorates to the extent that it necessitates initiation or intensification of diuretic treatment (mainly intravenous). The events can occur at the outpatient level, generally in the day hospital, in the emergency department or even hospitalization. Early identification of worsening HF events is essential to establish appropriate treatment as soon as possible. In this context, robust clinical benefits have been reported for renin-angiotensin system inhibitors, sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and vericiguat. In Spain, several registries of patients with HF have been developed, some of them including patients recently hospitalized for HF, but not with recent worsening HF events. Therefore, registries addressing recent worsening events would be desirable. Using a practical approach, this review analyzes the importance of worsening HF events, with special emphasis on Spanish data.


High throughput sample preparation in combination with gas chromatography coupled to triple quadrupole tandem mass spectrometry (GC-MS/MS): a smart procedure for (ultra)trace analysis of brominated flame retardants in fish.
In this study, gas chromatography (GC) coupled to triple quadrupole tandem mass spectrometry (MS/MS) operated in electron ionisation mode (EI) has been shown to be an effective tool for the (ultra)trace analysis of several representative brominated flame retardants (BFRs) including polybrominated diphenyl ethers (PBDEs), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB), etc. in complex food and environmental matrices. Using this type of instrumentation, improved selectivity and sensitivity of the instrumental analysis was achieved. In addition to GC-MS/MS (EI), a GC-MS method employing QqQ as a single quadrupole in negative chemical ionisation (NCI) mode was also developed, as this technique might be preferred for those compounds where EI did not provide suitable (intensive enough) mass transitions (e.g., decabromodiphenyl ethane). Following the development of the GC-MS/MS method, a substantial simplification of the sample preparation method was achieved by employing an ethyl acetate QuEChERS-based extraction followed by silica minicolumn clean-up. Using this novel approach, six samples may be prepared in approx. one hour, thus significant time savings were achieved compared to routinely used methods. In addition, the method employs the reduced amounts of organic solvent and other chemicals. Under the optimised conditions, recoveries of all target analytes using both GC-MS/MS (EI) and GC-MS (NCI) were within the range of 70-119% and repeatabilities of the analytical procedure were ≤ 16% at all three spiking levels (0.1, 1 and 5 μg kg(-1)). Regarding quantification limits (LOQs), as expected, a single quadruple operated in NCI provided significantly lower LOQs compared to EI. However, using the triple quadrupole mass analyser, comparable LOQs were achieved for both methods (0.005-1 μg kg(-1) and 0.005-0.1 μg kg(-1) for GC-MS/MS (EI) and GC-MS (NCI), respectively). Moreover, when highly selective mass transitions in GC-MS/MS (EI) were used for identification and quantification, a significant decrease of problematic interferences was observed compared to NCI where most of the compounds were quantified according to the less selective m/z 79 corresponding to a bromine atom.


EpCAM: structure and function in health and disease.
Injection of tumor cells in mice more than 30 years ago resulted in the discovery of an epithelial antigen, later defined as a cell adhesion molecule (EpCAM). Although EpCAM has since evoked significant interest as a target in cancer therapy, mechanistic insights on the functions of this glycoprotein have been emerging only very recently. This may have been caused by the multitude of functions attributed to the glycoprotein, its localization at different subcellular sites and complex posttranslational modifications. Here, we review how EpCAM modifies cell-cell contact adhesion strength and tissue plasticity, and how it regulates cell proliferation and differentiation. Major knowledge derived from human diseases will be highlighted: Mutant EpCAM that is absent from the cell surface leads to fatal intestinal abnormalities (congenital tufting enteropathy). EpCAM-mediated cell proliferation in cancer may result from signaling (i) via regulated intramembrane proteolysis and/or (ii) the localization and association with binding partners in specialized membrane microdomains. New insight in EpCAM signaling will help to develop optimized cancer therapies and open new avenues in the field of regenerative medicine.


Structural and biochemical characterization of glycoside hydrolase family 79 β-glucuronidase from Acidobacterium capsulatum.
We present the first structure of a glycoside hydrolase family 79 β-glucuronidase from Acidobacterium capsulatum, both as a product complex with β-D-glucuronic acid (GlcA) and as its trapped covalent 2-fluoroglucuronyl intermediate. This enzyme consists of a catalytic (β/α)(8)-barrel domain and a β-domain with irregular Greek key motifs that is of unknown function. The enzyme showed β-glucuronidase activity and trace levels of β-glucosidase and β-xylosidase activities. In conjunction with mutagenesis studies, these structures identify the catalytic residues as Glu(173) (acid base) and Glu(287) (nucleophile), consistent with the retaining mechanism demonstrated by (1)H NMR analysis. Glu(45), Tyr(243), Tyr(292)-Gly(294), and Tyr(334) form the catalytic pocket and provide substrate discrimination. Consistent with this, the Y292A mutation, which affects the interaction between the main chains of Gln(293) and Gly(294) and the GlcA carboxyl group, resulted in significant loss of β-glucuronidase activity while retaining the side activities at wild-type levels. Likewise, although the β-glucuronidase activity of the Y334F mutant is ~200-fold lower (k(cat)/K(m)) than that of the wild-type enzyme, the β-glucosidase activity is actually 3 times higher and the β-xylosidase activity is only 2.5-fold lower than the equivalent parameters for wild type, consistent with a role for Tyr(334) in recognition of the C6 position of GlcA. The involvement of Glu(45) in discriminating against binding of the O-methyl group at the C4 position of GlcA is revealed in the fact that the E45D mutant hydrolyzes PNP-β-GlcA approximately 300-fold slower (k(cat)/K(m)) than does the wild-type enzyme, whereas 4-O-methyl-GlcA-containing oligosaccharides are hydrolyzed only 7-fold slower.


Transcranial sonographic measurement of the third ventricle to detect hydrocephalus in children population: Correlation to computed tomography.
In neuro-intensive care, transcranial temporal ultrasound is used in adults and children to monitor brain-injured patients. It is accepted as a valuable tool for exploring brain structures. Our study aims to establish a correlation between the measurement of the third ventricle (V3) by transcranial ultrasound via temporal window and a reference method, computed tomography (CT), which could validate the method for hydrocephalus detection in the children population. This is a prospective double-blind study of 34 children under 15 years. Two consultants in intensive care performed the ultrasound while a radiologist performed the CT measurements. Of the 34 patients included, the V3 could be measured in 88% of cases. Among these 30 patients, there is a good correlation between CT and ultrasound measurements with a Spearman correlation coefficient of 0.773. This correlation is more important as the diameter of the V3 increases. We could determine a threshold of 3.65 mm in diameter to identify hydrocephalus on ultrasound with a detection sensitivity of 100%, and a specificity of 94.1%. Measuring the diameter of the V3 by trans-cranial sonography remains a simple, reproducible, non-invasive tool and has a good correlation with reference examinations such as CT.


Determination of malondialdehyde, acrolein and four other products of lipid peroxidation in edible oils by Gas-Diffusion Microextraction combined with Dispersive Liquid-Liquid Microextraction.
A new and sensitive analytical method for the simultaneous determination of secondary lipid peroxidation aldehydes has been successfully developed and validated. Malondialdehyde, acrolein, formaldehyde, acetaldehyde, propanal, and pentanal were extracted and derivatized using 2,4-dinitrophenylhydrazine (DNPH) by gas-diffusion microextraction (GDME) combined with dispersive liquid-liquid microextraction (DLLME) for gas chromatography-mass spectrometry (GC-MS) analysis. The experimental conditions have been optimized by experimental designs. The analytical method validation, in accordance to the Food and Drug Administration (FDA) guidance, provided good results in terms of linearity with r2≥0.9974, in the range from 0.15 or 0.3 µg·g-1 to 3 µg·g-1. Limits of detection and limits of quantification were 0.05 or 0.10 and 0.15 or 0.3 µg·g-1, respectively. Precision was tested as a relative standard deviation (RSD≤ 9.5%) and recoveries were between 95% and 110%. The method was applied in the characterization of aldehydes in forty-eight edible oil samples; with the highest concentration found in pomace olive oil for malondialdehyde at 6.64 µg·g-1.


Prognostic significance of modal DNA value and other factors in malignant tumours, based on 1465 cases.
The modal DNA values of 1465 tumours, together with other factors of possible prognostic importance, were related to the survival of the patients, using regression models (Kay, 1977). For most tumour sites except the testis, the distributions of modal DNA values were bimodal, with peaks at the diploid level and in the triploid-tetraploid range. For all tumour sites except the cervix uteri, patients in the low (near-diploid) range showed better survival; the reverse was true for squamous-cell carcinoma of the cervix uteri. Other variables showed the following effects: for all sites except the testis, younger patients showed a better survival; for the cervix and corpus uteri, breast and ovary, increasing clinical stage was associated with poorer survival. Where evaluated, histological grade appeared to be associated with survival rate, the less well differentiated tumours having a worse prognosis, except for the breast, where the reverse correlation was noted. For carcinoma of the bladder, females and a poorer survival rate than males.


Triple negative breast cancer: any closer to cracking the code?
Triple negative breast cancer is the most aggressive subtype of breast cancer and has traditionally lacked targeted therapies leading to worse prognosis in most patients. We will review new targeted therapies for triple negative breast cancer including immunotherapy, antibody-drug conjugates, and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors. Immunotherapy is now a backbone of PD-L1 positive metastatic triple negative breast cancer in the front-line setting as well as part of neoadjuvant therapy for high risk localized triple negative breast cancer. PARP inhibitors and a new antibody-drug conjugate are additional new therapies that can be used to improve the outcome for localized and metastatic triple negative breast cancers. None of these treatments were available before the review period for this paper.


PPARG and FTO polymorphism can modulate the outcomes of a central European diet and a Mediterranean diet in centrally obese postmenopausal women.
The aim of this study was to test the hypothesis that polymorphism of genes with the biggest effects on body mass (FTO and PPARG) can affect the results of dieting in centrally obese postmenopausal women. A total of 144 volunteers were randomized to a 16-week intervention with two hypocaloric diets: either a Mediterranean diet (MED) moderate in fat (37% total energy as fat) or the Central European diet (CED) moderate in carbohydrates (55% total energy as carbohydrates). The associations between FTO and PPARG polymorphism on the baseline body mass, body composition, blood pressure, lipid and non-lipid parameters, and their changes after the trial were analyzed. None of the examined baseline outcomes differed in the rs9939609 FTO subgroups; abdominal fat was higher in the minor (G) allele carriers of the PPARG rs1801282. After the intervention, in the CED group, the PPARG G allele carriers showed greater reductions in weight (-6.58 ± 0.61 vs -9.58 ± 0.83; P < .01), lean mass (-0.38 ± 0.29 vs -1.79 ± 0.38; P < .05) and high-density lipoprotein (HDL) cholesterol (-0.46 ± 0.77 vs -5.25 ± 1.49; P < .01) than the CC homozygotes, and the TT individuals of the rs9939609 FTO had greater reductions in diastolic blood pressure (-9.03 ± 1.78 vs. -7.58 ± 1.50; P < .05). In the MED group, greater reductions in abdominal fat were observed in the G allele carriers than in the CC homozygotes (-3.31 ± 0.26 vs. -4.23 ± 0.41; P < .05). PPARG and FTO polymorphism may affect the outcomes of the diets aimed at weight reduction in postmenopausal women.


Novel dihydroquinoline-based MABAs; clues to the identity of LAS-190792: evaluation of WO20111411802.
Bifunctional aromatic compounds are claimed to contain a β(2) agonist pharmacophore linked by a flexible lipophilic spacer incorporating a trans-4-aminocyclohexanol group to a muscarinic antagonist pharmacophore. The compounds display nanomolar affinity at both β(2) and M(3) receptors and a prolonged duration of action in animal models. This application is the first from Almirall claiming such compounds although it has recently disclosed that LAS-190792 is progressing toward clinical development.


Reconstruction of oropharyngeal defects utilizing a free radial forearm flap.
The authors report their experience with free radial forearm flaps for oropharyngeal reconstruction. Fifteen patients who submitted to intraoral reconstruction with this flap were followed for periods ranging from 3 to 36 months, with a mean of 14 months. Ages ranged from 15 to 58 years with a mean of 41. The defects were secondary to tumor ablation (11 patients), complications of conventional treatment for congenital deformities (3 patients) and trauma resulting from a gunshot wound to the upper lip and palate (1 patient). Total necrosis of 1 flap occurred and 1 patient required reoperation on the first postoperative day for revision of the anastomoses. Our results enable us to recommend the radial forearm flap as the flap of choice for reconstruction of extensive oropharyngeal defects.


The use of leeches to monitor aquatic PCB contamination at Mid-Canada Radar Line site 050: four years post-remediation.
The Mid-Canada Radar Line (MCRL) was built by the Canadian government during the 1950s and closed in the 1960s. MCRL Site 050 located in close proximity to Fort Albany First Nation was a source of polychlorinated biphenyls (PCBs); thus, this site was remediated in 2001. There has been concern in Fort Albany that the Albany River by MCRL Site 050 is still contaminated. We examined whether the aquatic environment surrounding MCRL Site 050 has returned to background levels four years post-remediation using leeches (Haemopis spp.) as bioindicators. Leech data for 2005 indicates that PCB levels remain higher near Site 050 than at the control site upstream; however, there has been a decrease in difference between Site 050 and the control site for leech body burden between years. Thus, the removal of the terrestrial source of PCB contamination at Site 050 appears to have removed the main source of aquatic PCBs.


Mummified fruits of Canarium from the upper Pleistocene of South China.
Canarium L. contains approximately 78 species distributed in low to middle altitudes of the Paleotropics and northern Australia. Canarium fruit fossils are known mainly from Paleogene to Neogene of North America, Africa, and Eurasia. Here, we described a new species Canarium maomingense sp. nov. from the upper Pleistocene of the Maoming Basin, Guangdong, South China. Similarly to extant Canarium species, each of three locules of C. maomingense possesses two ovules, but only one or two of six ovules develop into a seed, indicating that the ovules undeveloped into seeds in Canarium species have existed at least since the late Pleistocene. The natural habitats of extant relatives and associated fossil plants suggest subtropical evergreen broad-leaved and mixed forests in the late Pleistocene of this region. Some special damage traces are observed on pyrene surfaces, indicating possible plant interactions with animals and fungi.


Usefulness of Morphology-Voltage-P-wave duration (MVP) score as a predictor of atrial fibrillation recurrence after pulmonary vein isolation.
Atrial fibrillation (AF) is known to be the most common arrhythmia, and the successful rate of long-term ablation can vary comparatively. Therefore, a clinical scoring system to predict rhythm outcome remains a critical unmet need. The electrocardiographic (ECG) risk score which is named Morphology-Voltage-P-wave duration (MVP) score was reported to be useful for predicting new-onset AF. The goal of the current study was to investigate whether the MVP score was a useful scheme in the prediction of rhythm outcome following pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF). We retrospectively analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in the medical records of 207 consecutive patients with PAF undergoing PVI in General Hospital of Ningxia medical University from 2010 to 2018. Two hundred and seven patients (71 females, median age 58.7 years) with symptomatic PAF underwent PVI. From the cohort, 32.3% (67) had a recurrence of AF within 1 year of the PVI. The area of the MVP score under the curve in the receiver operating characteristics (ROC) analysis was 0.789 (95% CI 0.730-0.840, p < .001). A score cut-off value of >3 showed the best predictive ability for AF recurrence within 1 year after PVI, with sensitivity (53.03%) and specificity (89.87%). The results of our study suggest that the easy-to-measure ECG MVP score can be used to predict recurrence of PAF after PVI.


Muscle-invasive bladder cancer following radiotherapy for prostate adenocarcinoma.
We present a case of muscle-invasive bladder cancer arising in a man who had previously been diagnosed with prostate cancer. His prostate cancer diagnosis and subsequent treatment with external beam radiation therapy occurred over 20 years prior to being diagnosed with bladder cancer. Biopsies of the bladder mass revealed a high-grade urothelial carcinoma with prostatic invasion and MRI showed significant concern for invasion into the pelvic floor. Metastatic lesions on his right rib and left clavicle were discovered on bone scan.


Expression of the mouse Fc receptor B2 in bovine cells rescues the infectivity of conditionally neutralized bovine viral diarrhea virus.
We examined the infectivity of bovine viral diarrhea virus (BVDV) particles opsonized with monoclonal antibodies on bovine cells expressing the murine Fcgamma receptor B2 (FcgammaRB2). Incubation of BVDV with each of five monoclonal antibodies (Mabs) to the envelope glycoprotein E2 led to efficient virus-neutralization, as evidenced by the failure to infect standard bovine testicle cells. In contrast, inoculation of four of these Mab-virus complexes onto transfectant bovine testicle cells expressing FcgammaRB2 resulted in a significant rescue of virus infectivity. Mab-virus complexes were 13.1, 7.37, 5.56 and 4.49 times more infectious for FcgammaR-expressing cells than for cells lacking FcgammaR. Because Mab-opsonized BVDV virion complexes uninfectious for standard cells may initiate productive infection in cells expressing the FcgammaR, the virion-Mab interaction should be described as a conditional neutralization. Interestingly, the infectivity of BVDV complexed with a specific virus neutralizing Mab (10f9) could not be rescued in FcgammaRB2-expressing cells. We postulate that attachment of antibody-virus complexes to FcR may only result in productive infection if the binding of antibody to virions does not interfere with post-attachment entry functions. Conditionally neutralized virions may play a role in the pathogenesis of any of the multiple diseases resulting from BVDV infections in cattle.


Prenatal greenspace exposure and cord blood cortisol levels: A cross-sectional study in a middle-income country.
Exposure to greenspace has been associated with reduced stress; however, the available evidence on such an association for the fetus is still very scarce. We, for the first time, investigated the association between maternal greenspace exposure and the level of cortisol, a stress hormone, in the cord blood. Our study was based on a cohort of 150 pregnant women in Sabzevar, Iran (2018). We comprehensively assessed greenspace exposure for each participant through (i) residential surrounding greenspace (using two satellite-derived vegetation indices), (ii) residential proximity to green spaces, (iii) maternal visual access to greenspace, (iv) use of public and private green spaces, (v) having a private garden, and (vi) the number of plant pots at home. Linear regression models were developed to assess the association of each indicator of greenspace exposure with cord blood cortisol levels, controlled for the relevant covariates. We observed that a higher residential surrounding greenspace (100 m buffer), having a window with greenspace view, window greenspace coverage of more than 50%, frequently looking at greenspace through window, residential proximity to large green spaces, and more time spent in green spaces were associated with lower cortisol levels in the cord blood. The findings for residential surrounding greenspace at 300 m and 500 m buffers, residential proximity to any green space regardless of its size, having a private garden, and number of plant pots at home were not conclusive. While about one-third of the association between residential surrounding greenspace (100 m buffer) could be mediated through reduction in exposure to air pollution, we did not observe any strong evidence for such a mediatory role for the visual access to greenspace. The findings stratified for parental education and housing type showed mixed patterns. Our findings suggest that more greenspace exposure might reduce cortisol level in the cord blood.


Detection of three wound-induced proteins in papaya latex.
The effects of routine mechanical wounding for latex collection from unripe fruits of the tropical Carica papaya tree were investigated. For that purpose, the protein composition of three different latexes was analyzed. The first one, commercially available, was provided in the form of a spray-dried powder, the second one was harvested from fully grown but unripe papaya fruits that are regularly tapped for latex production and the last one, was obtained from similar fruits wounded for the first time. Repeated mechanical wounding was found to profoundly affect the protein content of the latex inducing, among others, activation of papain. Regularly tapped latexes also accumulated several low molecular weight proteins not yet identified, as well as three proteins identified as a trypsin inhibitor, a class-II chitinase and a glutaminyl cyclase on the basis of their enzymatic or inhibitory activities and chromatographic elution profiles. This latter was found here, for the first time, to be a wound-induced protein. The roles of these proteins in the plant defense mechanism are discussed.


The impact of extreme summer temperatures in the United Kingdom on infant sleep: Implications for learning and development.
The U.S. Global Change Research Program reports that the frequency and intensity of extreme heat are increasing globally. Studies of the impact of climate change on child health often exclude sleep, despite its importance for healthy growth and development. To address this gap in the literature, we studied the impact of unusually high temperatures in the summer of 2022 on infants' sleep. Sleep was assessed objectively using Nanit camera monitors in infants' homes. Generally, sleep was not impacted when temperatures stayed below 88° but was negatively impacted when temperatures reached over 100°. Compared to non-heatwave nights, infants had less total sleep, less efficient sleep, took longer to fall asleep, had more fragmented sleep, and parents' visits were more frequent during the night. Following peaks in temperature, sleep metrics rebounded to better than average compared to non-peak nights, suggesting that infants compensated for disrupted sleep by sleeping more and with fewer interruptions once the temperature dropped below 85°. Increased instances of disrupted sleep in infancy have important implications for psychological health and development. Climate disruptions such as heat waves that create occasional or ongoing sleep disruptions can leave infants vulnerable and unprepared for learning.


Consequences of mixed pollinations in Campsis radicans.
I examined the effects of pollen loads containing pollen from one, three and five donors on fruit production and fruit quality in Campsis radicans. Number of pollen donors had no significant effect on % fruit production, seed number, seed weight or seed germination. In singledonor pollinations the identity of the donor did have a strong effect on the above parameters. Furthermore, the best single donor sired fruits with more seeds and heavier seeds than any mixture containing this donor. This pattern indicates interference of pollens or preemption of some ovules by the inferior pollen. In Campsis, therefore, the number of pollen donors contributing to a pollen load is less important than the identity of these donors in determining fruit production and fruit quality. Seeds from fruits resulting from mixed pollination were slightly more variable than seeds from fruits resulting from single-donor pollinations.


[Effect of impulse-sensory training on various electrophysiological indicators in the human body].
The author reviews the effect of pulse-sensory training (PST) on some electrophysiological parameters of human body. Discusses the research data and an assumption about the effect of the PST on metabolic processes in the tissues. Describes some mechanisms of space and time organization of the biopotentials recorded from the biologically active points occurring on the head surface and in other parts of the body. Stresses the necessity of taking the ECG from these points.


Sleeve lobectomy for carcinoma of the lung.
Sleeve lobectomy for non-oat cell carcinoma involving a major bronchus preserves functioning lung tissue and, in carefully selected patients, provides long-term survival comparable to pneumonectomy. Seventy patients underwent sleeve lobectomy between 1967 and 1978. Twenty-seven patients were considered compromised (Group I) because they had severe respiratory impairment which contraindicated pneumonectomy. Forty-three patients were considered uncompromised (Group 2) and underwent elective sleeve lobectomy. Seventy patients with a similar non-oat cell carcinoma involving the proximal bronchi underwent pneumonectomy (Group 3) during this period. Perioperative complications occurred more frequently in Group 1 (59%) than in Group 2 (21%) or Group 3 (23%). Both periopeative mortality rate and the incidence of bronchial disruption (bronchovascular and bronchopleural fistulas) were higher in Group I (19% and 22%) than in Group 2 (9% and 5%) or Group 3 (3% and 7%). Survival depended primarily on the surgeon's ability to perform a complete resection of the tumor. An incomplete resection resulted when tumor was found in the highest lymph node or in the last bronchial resection margin when paraffin sections were reviewed. The 5 year survival rate was 18% for compromised patients (Group 1) who underwent complete resection, and there were no survivors among patients undergoing incomplete resections. Uncompromised patients ( Group 2) had a 5 year survival rate of36% with complete and 12% with incomplete resections. Pneumonectomy patients (Group 3) had a 64% 5 year survival rate with a complete resection and 16% with an incomplete resection. The stage of the disease at the time of operation had a profound effect on the survivail. There was no difference inthe 5 and 8 year survival rates between uncompromised patients undergoing sleeve resection ( Group 2) and patients undergoing peneumonectomy (Group 3) for comparable stage of their disease. A careful pre- and postoperative functional assessment revealed that pulmonary performance was improved in 44% of Group 1, 63% of Group 2, and only 14% of Group 3 patients. Patients wiht impaired pulmonary reserve underwent sleeve lobectomy with an adequate disease-free interval when complete tumor excision was possible. Uncompromised patients whose extensive disease required incomplete resection had palliation by sleeve lobectomy equivalent to that by pneumonectomy. When complete t-mor resection was possible, patients with uncompromised pulmonary reserve had a perioperative complication rate and long-term survival equivalent to that of pneumonectomy while preserving pulmonary parenchyma, which permitted an improvement in postoperative pulmonary performance.


Prevalence and characteristics of opioid use in the US adult population.
This report describes the prevalence of opioid use in the US adult population, overall and in subgroups, the characteristics of opioid use, and concomitant medication use among opioid users. Data were obtained from the Slone Survey, a population-based random-digit dialing survey. One household member was randomly selected to answer a series of questions regarding all medications taken during the previous week. There were 19,150 subjects aged > or = 18 interviewed from 1998 to 2006. Opioids were used 'regularly' ( > or = 5 days per week for > or = 4 weeks) by 2.0%; an additional 2.9% used opioids less frequently. Regular opioid use increased with age, decreased with education level, and was more common in females and in non-Hispanic whites. The prevalence of regular opioid use increased over time and was highest in the South Central region. Nearly one-fifth of regular users had been taking opioids for > or = 5 years. Concomitant use of > or = 10 non-opioid medications was reported by 21% of regular opioid users compared to 4.5% of subjects who did not use opioids. Regular opioid users were more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally-representative telephone survey, we estimate that over 4.3 million US adults are taking opioids regularly in any given week. Information on the prevalence and characteristics of use is important as opioids are one of the most widely prescribed classes of drugs in the US.


Attenuation of age-related increase of protein carbonylation in the liver of mice by melatonin and curcumin.
Protein carbonyls are formed as a consequence of the oxidative modification of proteins by reactive oxygen species and are commonly used as a marker of protein oxidation in cells and tissues. Melatonin has free radical scavenging ability besides its classical role as a hormonal signaling agent. Curcumin, a phytochemical, has a wide variety of biological actions including anti-inflammatory and antioxidative. In the present study, the effects of melatonin and curcumin on age-related carbonyl content of liver in mice were investigated. Young (1 month) and aged (18 month) were administered with melatonin (10 mg/kg body weight) and curcumin (90 mg/kg body weight) in dimethyl sulfoxide intraperitoneally. Livers were excised from each experimental group and processed. The level of protein carbonylation was assessed spectrophotometrically and further confirmed by Western blotting analysis. Protein carbonyls of liver have been found to be significantly higher in 18-month-old mice as compared to 1-month-old mice. The carbonyl content in 1- and 18-month-old mice decreases significantly upon administrations of melatonin and curcumin. This study thus suggests that the formation of protein carbonyls in the liver of the aging mice can be prevented by the antioxidative effects of melatonin and curcumin, which may provide health benefits in aging animals.


Contemporary quality of life issues affecting gynecologic cancer survivors.
Regardless of cancer origin or age of onset, the disease and its treatment can produce short- and long-term sequelae (ie, sexual dysfunction, infertility, or lymphedema) that adversely affect quality of life (QOL). This article outlines the primary contemporary issues or concerns that may affect QOL and offers strategies to offset or mitigate QOL disruption. These contemporary issues are identified within the domains of sexual functioning, reproductive issues, lymphedema, and the contribution of health-related QOL in influential gynecologic cancer clinical trials.


The Secreted Larval Acidic Proteins (SLAPs) of Onchocerca spp. are encoded by orthologues of the alt gene family of Brugia malayi and have host protective potential.
Onchocerca volvulus is a tissue-dwelling, vector-borne nematode parasite of humans and the causative agent of onchocerciasis, or 'River Blindness'. Resistance to infection is associated with immune responses to the infective, third-stage (L3) larvae. The antigens of greatest interest for their vaccine potential are surface and secreted molecules. We have previously identified a family of Secreted Larval Acidic Proteins (SLAPs) from the L3 larvae of O. volvulus by biosynthetic labelling. Here, we provide further characterisation of these molecules following cloning and expression of the corresponding cDNAs. Using protein sequencing, we show that SLAPs are members of the alt gene family, first described in the lymphatic filarial parasite, Brugia malayi. Ov-ALT-1 and Ov-ALT-2 correspond with 20 and 18kDa SLAPs. Both proteins are highly acidic and related by sequence, differing chiefly in an 8-amino acid deletion from Ov-ALT-2. By immunochemistry, we confirm that Ov-ALTs are highly stage-specific, being expressed exclusively in late L2 and L3 larvae during growth in the vector. They are synthesised and stored in the glandular oesophagus. Secretion is triggered by the resumption of development in the definitive host and occurs via the pseudocoelom and cuticle. Serological responses in humans to recombinant Ov-ALT-1 indicate that the level of IgG production may be governed by the force of transmission but does not overtly reflect infection status. Immunisation of mice with recombinant Ov-ALT-1 resulted in a modest level of protection against challenge with O. volvulus L3 larvae (P = 0.036). We conclude that Ov-ALT genes, like those of other filariae, are of interest from the standpoint of parasite transmission and infectivity. They may also offer promise as components of a future sub-unit vaccine should the means to enhance protection be achieved.


Moderate alcohol consumption and lower levels of inflammatory markers in US men and women.
Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (p-trend<0.001 men; 0.03 women) and sTNF-R2 (p-trend=0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1-2 drinks/day had 26% lower CRP (-0.66 mg/L, p=0.13), and 36% lower IL-6 (-1.12 pg/ml, p=0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1-2 drinks/drinking day had significantly lower sTNF-R1 (-9% in men, -6% in women) and sTNF-R2 (-7% in men, -6% in women) levels as well as lower CRP (-10% in men, -32% in women) and IL-6 (-45% in men, -27% in women) levels. Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms.


A new model for evaluation of thrombosis and ischaemia/reperfusion injury.
The purpose of the present study was to describe infarct size and platelet accumulation when reperfusion injury was combined with a thrombogenic lesion in the coronary artery. The left anterior descending artery was damaged in 11 pigs and subsequently occluded proximal to the lesion for 50 min, followed by 4 h of reperfusion. The infarct size/area at risk was 40 (35 63)%. Infarct size correlated with troponin-T-3 h (p=0.85, p<0.002), but not with creatine kinase-3 h. Platelet aggregation decreased by 34% (p<0.01) at 15 min of reperfusion, but returned to baseline. Platelet accumulation in the left ventricle was significantly higher in the area at risk (194 (157-206)%) compared to the right ventricle (137 (120-142)%); p<0.05). A decreased platelet reactivity and increased accumulation of platelets in the area at risk indicates that activated platelets become entrapped in the myocardium. Troponin-T was a better marker of myocardial damage than creatine kinase in this in vivo model with pigs.


Effect of cochlear implantation on middle ear function: A three-month prospective study.
To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. Prospective cohort study. Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. 4. Laryngoscope, 128:1207-1212, 2018.


Role of macrophage lipids in regulating tumoricidal activity. II. Internal genetic and external physiologic regulatory factors controlling macrophage tumor cytotoxicity also control characteristic lipid changes associated with tumoricidal cells.
Peritoneal macrophages (M phi) from C3H/HeN mice became cytotoxic for 1023 tumor cells after incubation with lymphokine (LK) for 8-12 hr and lost tumoricidal activity by 22 hr in the continued presence of LK; bacterial endotoxin (LPS) was ineffective in inducing tumoricidal activity. M phi from C3H/HeJ mice were not activated for tumor cytotoxicity after treatment with LK or LPS. C3H/HeN M phi acquisition of tumoricidal activity was accompanied by unique changes in M phi lipid composition: cellular content of cholesterol (CHOL) and polyunsaturated fatty acids (UFA) increased two- to threefold when the cells showed maximal tumoricidal activity and returned to control levels when the M phi lost tumoricidal activity. LPS treatment of C3H/HeN M phi and LK or LPS treatment of C3H/HeJ M phi did not cause characteristic M phi lipid alterations. To determine at what stage during M phi activation the correlative CHOL and UFA compositional changes were occurring, C3H/HeN M phi were primed with LPS or low concentrations of LK and triggered with LPS or Lk; M phi lipid and fatty acid composition was monitored at each stage. LK was shown to be able to prime and trigger whereas LPS could only trigger LK-primed M phi for tumor cytotoxicity. In all cases, the increase in M phi CHOL and UFA content occurred at the triggering step for tumor cytotoxicity rather than at the priming step. These data suggest that there is a correlation between the effects of endogenous and exogenous factors that control expression of M phi tumoricidal activity and their effects on M phi CHOL and UFA content; the establishment of these changes in M phi lipid composition occurs at a time when the cells are triggered for tumor cytotoxicity.


Patient perspectives on use of electronic health records for research recruitment.
EHR phenotyping offers the ability to rapidly assemble a precisely defined cohort of patients prescreened for eligibility to participate in health-related research. Even so, stakeholders in the process must still contend with the practical and ethical challenges associated with research recruitment. Patient perspectives on these matters are particularly important given that the success of research recruitment depends on patients' willingness to participate. We conducted 15 focus groups (n = 110 participants) in four counties in diverse regions of the southeastern US: Appalachia, the Mississippi Delta, and the Piedmont area of North Carolina. Based on a hypothetical study of a behavioral intervention for type 2 diabetes, we asked about the acceptability and appropriateness of direct investigator versus physician-mediated contact with patients for research recruitment, and whether patients should be asked to opt in or opt out of further contact in response to recruitment letters. For initial contact, nearly all participants said it would be acceptable for researchers to contact patients directly and three-fourths said that it would be acceptable for researchers to contact patients through their physicians. When we asked which would be most appropriate, a substantial majority chose direct contact. Themes that arose in the discussion included trust and transparency, decision-making power, the effect on research, and the effect on patient care. For response expectations, the vast majority of participants said both opt-in and opt-out would be acceptable-typically finding neither especially problematic and noting that both afford patients the opportunity to make their own decisions. External validity relies heavily on researchers' success enrolling eligible patients and failure to reach accrual targets is a costly and common barrier to advancing scientific knowledge. Our results suggest that patients recognize multiple advantages and disadvantages of different research recruitment strategies and place value on the implications not just for themselves, but also for researchers and healthcare providers. Our findings, including rich qualitative detail, contribute to the body of empirical and ethical literature on improving research recruitment and suggest specific ways forward as well as important areas for future research.


Methodological reviews of economic evaluations in health care: what do they target?
An increasing number of published studies of economic evaluations of health technologies have been reviewed and summarized with different purposes, among them to facilitate decision-making processes. These reviews have covered different aspects of economic evaluations, using a variety of methodological approaches. The aim of this study is to analyze the methodological characteristics of the reviews of economic evaluations in health care, published during the period 1990-2010, to identify their main features and the potential missing elements. This may help to develop a common procedure for elaborating these kinds of reviews. We performed systematic searches in electronic databases (Scopus, Medline and PubMed) of methodological reviews published in English, period 1990-2010. We selected the articles whose main purpose was to review and assess the methodology applied in the economic evaluation studies. We classified the data according to the study objectives, period of the review, number of reviewed studies, methodological and non-methodological items assessed, medical specialty, type of disease and technology, databases used for the review and their main conclusions. We performed a descriptive statistical analysis and checked how generalizability issues were considered in the reviews. We identified 76 methodological reviews, 42 published in the period 1990-2001 and 34 during 2002-2010. The items assessed most frequently (by 70% of the reviews) were perspective, type of economic study, uncertainty and discounting. The reviews also described the type of intervention and disease, funding sources, country in which the evaluation took place, type of journal and author's characteristics. Regarding the intertemporal comparison, higher frequencies were found in the second period for two key methodological items: the source of effectiveness data and the models used in the studies. However, the generalizability issues that apparently are creating a growing interest in the economic evaluation literature did not receive as much attention in the reviews of the second period. The remaining items showed similar frequencies in both periods. Increasingly more reviews of economic evaluation studies aim to analyze the application of methodological principles, and offer summaries of papers classified by either diseases or health technologies. These reviews are useful for finding literature trends, aims of studies and possible deficiencies in the implementation of methods of specific health interventions. As no significant methodological improvement was clearly detected in the two periods analyzed, it would be convenient to pay more attention to the methodological aspects of the reviews.


Tongue necrosis secondary to mucormycosis in a diabetic patient: A first case report in Malaysia.
Mucormycosis is a rare fungal infection and high mortality that commonly affects patients with the weakened immune system. We present an unusual case of tongue necrosis probably due to the healthcare-associated mucormycosis (HCM) in a diabetic patient. Although cannot be proved with certainty, we surmise that intubation as a risk factor in our case. The diagnosis was confirmed by histopathological examination (HPE) of the necrotic tissue specimen. The patient was responded well to lipid complex amphotericin B (250mg) regime after surgery. Subsequent follow up revealed that no signs of recurrence. Early, recognition, diagnosis, prompt treatment and awareness among clinician are representing the most effective way of managing the disease.


The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model.
During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.


Effect of physical activity and vitamin D compared with vitamin D alone on muscle strength, back flexibility and aerobic activity in patients with chronic kidney disease: A comparative study from Pakistan.
To compare the differences in musculoskeletal health with vitamin D alone in comparison with vitamin D with physical activity (PA) among chronic kidney disease (CKD) patients. An open labeled, randomized, controlled trial was conducted at two tertiary care centers in Pakistan. Patients with CKD stage 2-4 and vitamin D deficiency (<20 ng/mL) were recruited in the trial. Both the arms were given oral vitamin D (cholecalciferol) drops (4000 IU) once daily for three months. One arm received only vitamin D (VD arm), while the second arm received vitamin D along with PA (VDPA arm). Of the 1,235 CKD stage 2-4 subjects contacted, forty-six subjects were enrolled. Eighteen were assigned to VD arm and twenty-eight were assigned to VDPA arm. Between groups comparison shows that bicep strength increases from 15 to 17 kg. Likewise, back flexibility and aerobic fitness also increased among those who receive vitamin D and physical activity, however these differences were not statistically significant (p>0.05). Sensitivity analysis within group comparison shows rise of bicep strength from 13.8 kg to 15.2 kg in the VD alone arm (p=0.05); however, in the VDPA arm, there is a greater difference of 14.3 kg to 17.2 kg (p<0.001). Targeted PA among CKD patients has potential to improve bicep strength and back flexibility. However, as the sample size was small, further studies would be required to suggest whether a PA should be included as part of the treatment regimen.


Effects of some antibiotics on human erythrocyte glutathione reductase: an in vitro study.
Inhibitory effects of some antibiotics on purified human erythrocyte glutathione reductase were investigated. Human erythrocyte glutathione reductase was purified 2800-fold (29% yield) at 4 degrees C using 2', 5'-ADP Sepharose 4B affinity gel and Sephadex G-200 gel filtration chromatography. SDS polyacrylamide gel electrophoresis showed a single band for the enzyme. Imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol, seftriaxon, vancomycin, cefuroxime and ornidazole exhibited inhibitory effects but clindamycin, lincomycin, amoxicillin, amikacin exhibited activatory effects on the enzyme in vitro. The IC(50) values of imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol, seftriaxon, vancomycin, cefuroxime and ornidazole were 0.030, 0.146, 0.59, 2.476, 2.36, 2.88, 4.83, 15.43 and 19.632 mM, respectively, and the K(i) constants were 0.06 +/- 0.01, 0.275 +/- 0.10, 0.85 +/- 0.05, 3.59 +/- 0.51, 3.85 +/- 0.40, 3.71 +/- 0.60, 15.11 +/- 2.50, 23.50 +/- 2.94 and 28.49 +/- 6.50 mM, respectively. While imipenem, rifamycin, sulfanylacetamide, ceftazidime, chloramphenicol and seftriaxon cefuroxime and ornidazole showed competitive inhibition, vankomycine displayed noncompetitive inhibition.


Single intratumoral injection of long-acting benzyl ester of D-penicillamine inhibits the growth of melanoma tumor in mice.
Using a murine model of melanoma we tested the effect of D-penicillamine administered in repetitive, daily injections, or as a single large dose injected either in saline or in a biodegradable polymer. We also studied the effect of a single intratumoral injection of benzyl-ester-D-penicillamine on the growth of the tumor. Daily injections of the drug or its administration in a polymer or benzyl-ester of D-penicillamine were all significantly inhibitory. The inhibitory effect manifested 4-5 days after injection. The inhibition lasted 8-10 days. There was no evidence of local or systemic toxicity and no changes in body weight. Several possible mechanisms for the inhibitory effect are presented.


Complete Genome Sequence of Multidrug-Resistant Strain Nocardia wallacei FMUON74, Isolated from a Sputum Culture.
Nocardia wallacei is one of the members of the N. transvalensis complex which possess a highly unique susceptibility pattern. Here, we describe the closed complete genome sequence of the multidrug-resistant strain N. wallacei FMUON74, which was obtained using a hybrid approach combining Nanopore long-read sequencing and Illumina and DNBseq short-read sequencing.


Side effects of pharmacotherapy on bone with long-acting gonadorelin agonist triptorelin for paraphilia.
There have been limited research studies concerning the use of libido inhibitors for the treatment of patients with a paraphilia. Observational studies suggest that agents that lower testosterone are an effective treatment for paraphilia. We report a case of hormonal treatment of paraphilia that was associated with side effects. A 35-year-old man with a paraphilia was treated with long-acting gonadorelin. The desired result was reduced preoccupation with sexuality, but there were various side effects including a serious amount of bone loss. We believe that more attention should be given to the adverse effects of long-term treatment with triptorelin. In our view the drug regime needs to be revised.


Mechanical Comparison of High-Strength Tape Suture Versus High-Strength Round Suture.
To compare knot and loop characteristics of commonly used high-strength tapes and high-strength round sutures. Twenty tied 30-mm loops were prepared for using suture-knot combinations of 4 common arthroscopic knots or a hand-tied surgeon's knot and 7 sutures. Two tapes (BroadBand, SutureTape) and three no. 2 sutures (MaxBraid, FiberWire, DynaCord) were compared. Two additional larger tape sutures (FiberTape, PermaTape) not commonly tied arthroscopically were included in the hand-tied group. Each suture-knot combination was evaluated for loop integrity (single load to a specified elongation), knot security (plastic loop deformation with cyclic testing), loop security, and knot volume. Data were compared using analysis of variance followed by Tukey-Kramer post hoc tests. BroadBand and SutureTape demonstrated superior loop integrity compared to most no. 2 suture-knot combinations. FiberTape (430.48 ± 89.00 N) and PermaTape (545.16 ± 95.09 N) required significantly greater force to undergo 3 mm of displacement than all other hand-tied sutures (P < .001). All suture-knot configurations demonstrated significant plastic deformation (cyclic elongation) over 1000 cycles (P < 0.001). DynaCord displayed the best loop security except when paired with the Duncan loop. Overall, BroadBand and SutureTape had lower knot volumes compared to all other sutures. This study exhibits the ability of narrow tape sutures to provide reliable tissue apposition and fixation in multiple suture-knot configurations, while decreasing the potential adverse effects accompanying knot prominence. Generally, BroadBand and SutureTape demonstrated an ideal balance of mechanical characteristics to achieve the optimal suture-knot construct among those tested. Dynacord displayed superior loop security and performed best among round sutures. PermaTape and FiberTape showed greater loop integrity, albeit to the detriment of loop security and knot volume. When securing a rotator cuff repair construct with a knot, one should have a basic understanding of the mechanical properties of the suture and knot being used to provide the best possible repair. This study will provide information about the mechanical characteristics of commonly used high-strength tape suture knots and loops to help determine what knot type may provide the best overall construct.


Primary diffuse meningeal melanomatosis - a rare form of meningeal melanoma: case report.
Meningeal melanomatosis is a rare type of central nervous system neoplasm (with incidence ranging between 3 and 5%) that develops in the course of malignant melanoma. In a small percentage of cases, meningeal melanomatosis may develop without a primary focus. It affects the leptomeninx. The clinical activity of the disease is uncharacteristic, with a number of neurological symptoms developing over weeks or months. A 45-year-old male patient presented with consciousness disturbance, cognitive dysfunctions, seizures and progressive paresis. None of the examinations performed, including cerebrospinal fluid examination, neuroimaging and biopsy of the leptomeninges, permitted us to establish a diagnosis during the patient's hospital stay. The diagnosis of meningeal melanomatosis was established after an autopsy had been carried out. In the absence of unequivocal test results, it is also worth taking into account the primary changes in the leptomeninx, including those caused by melanoma.


Arteriovenous malformation simulating encephalocele: CT findings.
Congenital arteriovenous malformation (AVM) of the scalp is a rare lesion, which usually is easily diagnosed. A case of a newborn infant with a midline occipital soft tissue mass that clinically simulated an encephalocele is reported. Postcontrast CT was useful in ruling out encephalocele and suggesting the diagnosis of AVM.


Single-photon cardiac imaging in patients with cardiac implantable electrical devices.
Nuclear imaging techniques like single-photon emission computed tomography (SPECT) and radionuclide angiography have wide applications in patients receiving a cardiac implantable electrical device (CIED), who cannot usually undergo cardiac magnetic resonance. Our aim was to provide an update of single-photon imaging clinical applications, with a specific focus on CIED recipients. SPECT imaging is commonly used in CIED patients to assess myocardial perfusion, but it can also be used to evaluate myocardial viability, which is an important predictor of LV function improvement by cardiac resynchronization therapy (CRT). Radionuclide angiography has shown higher temporal resolution and reproducibility than SPECT in the evaluation of cardiac function and dyssynchrony. Left ventricular dyssynchrony as assessed by radionuclide angiography with phase analysis may be reliably used for CRT patient selection and evaluation of CRT response. SPECT imaging with meta-iodo-benzyl-guanidine allows for cardiac sympathetic innervation examination, which may be used for prognostic stratification of heart failure patients and prediction of ventricular tachyarrhythmias. Finally, promising results in CIED infection diagnosis have been shown by SPECT with radiolabeled autologous white blood cells.


Visual hemispace differences reflect hemisphere asymmetries.
The relationship between the representation of the extracorporeal visual hemispace and the contralateral hemisphere has been investigated by presenting visual stimuli foveally either in the right or in the left hemispace. In a lexical decision task (Exp. 1) and a face-familiarity decision task (Exp. 2) lateral asymmetries very similar to those obtained using the divided visual field technique have been found. These results suggest that under particular circumstances the hemispace representation in the contralateral hemisphere overrides the retinal representation. Finally, it was found that in a lexical decision task performance with stimuli in the right hemispace was very similar to that with stimuli in a central position. The physiological and adaptive meaning of this phenomenon is discussed.


Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma.
BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.


Decreased endothelial size and connexin expression in rat caudal arteries during hypertension.
Hypertension is accompanied by endothelial dysfunction. The present study has investigated endothelial cell morphology and connexin expression in the caudal artery of the rat during the development of hypertension. A significant increase in systolic blood pressure was detected from 9 weeks of age in spontaneously hypertensive male rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats, reaching a maximum by 11-12 weeks of age. Immunohistochemistry was used to quantify cell size and expression of connexins (Cxs) 37, 40 and 43 in the endothelium of prehypertensive (3-week-old) and hypertensive (12-week-old) rats. At 12 weeks, the size of endothelial cells and the expression of all three Cxs per endothelial cell were significantly less in SHR than WKY rats. At 3 weeks, there was no significant difference in cell size nor in the expression of Cxs 37 or 43; however, expression of Cx40 was significantly lower in SHR than in WKY rats. Between 3 and 12 weeks in WKY rats, there was no change in endothelial cell size, nor in the expression of Cxs 37, 40 and 43. In SHR, both cell size and Cx expression per endothelial cell were significantly decreased during the same developmental period, with a significant decrease in the density of Cx40 plaques. The development of hypertension in the SHR is accompanied by significant decreases in endothelial cell size and expression of Cx40, which may contribute to the endothelial dysfunction present in hypertension.


Atomistic Simulations of Electroporation of Model Cell Membranes.
Electroporation is a phenomenon that modifies the fundamental function of the cell since it perturbs transiently or permanently the integrity of its membrane. Today, this technique is applied in fields ranging from biology and biotechnology to medicine, e.g., for drug and gene delivery into cells, tumor therapy, etc., in which it made it to preclinical and clinical treatments. Experimentally, due to the complexity and heterogeneity of cell membranes, it is difficult to provide a description of the electroporation phenomenon in terms of atomically resolved structural and dynamical processes, a prerequisite to optimize its use. Atomistic modeling in general and molecular dynamics (MD) simulations in particular have proven to be an effective approach for providing such a level of detail. This chapter provides the reader with a comprehensive account of recent advances in using such a technique to complement conventional experimental approaches in characterizing several aspects of cell membranes electroporation.


Inhibition of mitochondrial fusion via SIRT1/PDK2/PARL axis breaks mitochondrial metabolic plasticity and sensitizes cancer cells to glucose restriction therapy.
Mitochondria dynamically change their morphology via fusion and fission, a process called mitochondrial dynamics. Dysregulated mitochondrial dynamics respond rapidly to metabolic cues, and are linked to the initiation and progression of diverse human cancers. Metabolic adaptations significantly contribute to tumor development and escape from tissue homeostatic defenses. In this work, we identified oroxylin A (OA), a dual GLUT1/mitochondrial fusion inhibitor, which restricted glucose catabolism of hepatocellular carcinoma cells and simultaneously inhibited mitochondrial fusion by disturbing SIRT1/PDK2/PARL axis. Based the dual action of OA in metabolic regulation and mitochondrial dynamics, further results revealed that mitochondrial functional status and spare respiratory capacity (SRC) of cancer cells had a close correlation with mitochondrial metabolic plasticity, and played important roles in the susceptibility to cancer therapy aiming at glucose restriction. Cancer cells with healthy mitochondria and high SRC exhibit greater metabolic flexibility and higher resistance to GLUT1 inhibitors. This phenomenon is attributed to the fact that high SRC cells fuse mitochondria in response to glucose restriction, enhancing tolerance to energy deficiency, but undergo less mitochondrial oxidative stress compared to low SRC cells. Thus, inhibiting mitochondrial fusion breaks mitochondrial metabolic plasticity and increases cancer cell susceptibility to glucose restriction therapy. Collectively, these finding indicate that combining a GLUT1 inhibitor with a mitochondrial fusion inhibitor can work synergistically in cancer therapy and, more broadly, suggest that the incorporations of mitochondrial dynamics and metabolic regulation may become the targetable vulnerabilities bypassing the genotypic heterogeneity of multiple malignancies.


Endosomal Traffic Jams Represent a Pathogenic Hub and Therapeutic Target in Alzheimer's Disease.
While clues have existed that endosomal trafficking is associated with Alzheimer's disease (AD), whether it plays a central role in the disease and if so how has remained unknown. Here we rely on recent genetic and cellular findings to construct a model proposing that traffic jams in the early endosome can act as an upstream pathogenic hub in AD. We also rely on an independent series of findings to suggest how the traffic jams can act as a unified mediator of downstream pathophysiology. The model predicts, therefore, that interventions designed to unjam the endosome carry high therapeutic promise.


Biomarkers in Duchenne Muscular Dystrophy.
This review highlights the key studies investigating various types of biomarkers in Duchenne muscular dystrophy (DMD). Several proteomic and metabolomic studies have been undertaken in both human DMD patients and animal models of DMD that have identified potential biomarkers in DMD. Although there have been a number of proteomic and metabolomic studies that have identified various potential biomarkers in DMD, more definitive studies still need to be undertaken in DMD patients to firmly correlate these biomarkers with diagnosis, disease progression, and monitoring the effects of novel treatment strategies being developed.


Enhancing effect of taurine on CYP7A1 mRNA expression in Hep G2 cells.
Taurine has been reported to enhance cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in animal models. However, no in vitro studies of this effect have been reported. The Hep G2 human hepatoma cell line has been recognized as a good model for studying the regulation of human CYP7A1. This work characterizes the effects of taurine on CYP7A1 mRNA levels of Hep G2 cells in a dose- and time-dependent manner. In the dose-dependent experiment, Hep G2 cells were treated with 0, 2, 10 or 20 mM taurine in the presence or absence of cholesterol 0.2 mM for 48 h. In the time-dependent experiment, Hep G2 cells were treated with 0 or 20 mM taurine for 4, 24 and 48 h with and without cholesterol 0.2 mM. Our data revealed that taurine showed time- and dose-response effects on CYP7A1 mRNA levels in Hep G2 cells. However, glycine - a structural analogue of taurine - did not have an effect on CYP7A1 gene expression. These results show that, in agreement to previous studies on animal models, taurine induces the mRNA levels of CYP7A1 in Hep G2 cells, which could enhance cholesterol conversion into bile acids. Also, Hep G2 cell line may be an appropriate model to study the effects of taurine on human cholesterol metabolism.


Development and refinement of the mobile anger reduction intervention for veterans with posttraumatic stress disorder.
Problematic anger is commonly reported among veterans with posttraumatic stress disorder (PTSD) and is associated with numerous psychosocial impairments. There is a clear need to develop innovative and effective anger interventions. One of the cognitive mechanisms associated with anger is the hostile interpretation bias, which is the tendency to interpret ambiguous interpersonal situations as hostile. The current study presents a successive cohort design methodology to develop and refine a mobile treatment application, entitled Mobile Anger Reduction Intervention (MARI), which uses interpretation bias modification techniques to modify hostile interpretation bias. Two cohorts (total N = 13) of veterans with PTSD and problematic anger used the MARI application for 4 weeks. After each cohort, qualitative and quantitative data were used to modify the MARI application. The intervention is described, as well as the qualitative and quantitative findings and subsequent changes made to the mobile application based on participant feedback. Treatment adherence was high (90% of participants completed all sessions). Participants reported that they found the treatment helpful and easy to use and experienced improvements in hostile interpretation bias and problematic anger. This study demonstrates the utility of a successive cohort treatment design for the development of mobile interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Deep learning study of tyrosine reveals that roaming can lead to photodamage.
Amino acids are among the building blocks of life, forming peptides and proteins, and have been carefully 'selected' to prevent harmful reactions caused by light. To prevent photodamage, molecules relax from electronic excited states to the ground state faster than the harmful reactions can occur; however, such photochemistry is not fully understood, in part because theoretical simulations of such systems are extremely expensive-with only smaller chromophores accessible. Here, we study the excited-state dynamics of tyrosine using a method based on deep neural networks that leverages the physics underlying quantum chemical data and combines different levels of theory. We reveal unconventional and dynamically controlled 'roaming' dynamics in excited tyrosine that are beyond chemical intuition and compete with other ultrafast deactivation mechanisms. Our findings suggest that the roaming atoms are radicals that can lead to photodamage, offering a new perspective on the photostability and photodamage of biological systems.


Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications.
To evaluate the relationship between global oxygen delivery (DO(2)I), microvascular flow and tissue oxygenation in patients who did and did not develop complications following major abdominal surgery. Prospective observational study. Post-operative critical care unit. Twenty-five patients receiving standard peri-operative care following major abdominal surgery. Data were collected before, and for 8 h after surgery. DO(2)I was measured by lithium dilution and arterial waveform analysis. Cutaneous PtO(2) was measured at two sites on the abdominal wall using a Clark electrode. The sublingual microcirculation was visualised using sidestream darkfield imaging. Cutaneous red cell flux was measured using laser Doppler flowmetry. Fourteen patients (56%) developed complications with two deaths. Small vessel (<20 microm) microvascular flow index in those patients who developed complications was lower before (P < 0.05) and after surgery (P < 0.0001) compared to patients who did not develop complications. Both the proportion and density of perfused small vessels were also lower in patients who developed complications after surgery (P < 0.01) but not before surgery. DO(2)I was low in all patients but did not differ between patients who did and did not develop complications. Similarly, there were no associated differences in cutaneous red cell flux or PtO(2). In a group of patients with low DO(2)I following major abdominal surgery, microvascular flow abnormalities were more frequent in patients who developed complications. However, there were no differences in DO(2)I, cutaneous PtO(2) or red cell flux between the two groups. Impaired microvascular flow may be associated with the development of post-operative complications.


Filamentous fungi in artisanal cheeses: A problem to be avoided or a market opportunity?
The microbial diversity of artisanal cheeses has been ever more extensively explored over recent years. Many new studies have been particularly focused on the detection and identification of fungi associated with cheese rinds. This is not surprising given that the composition and abundance of fungi on the cheese surface can significantly contribute to desirable sensory qualities, while also contributing to defects, particularly during ripening, and risks associated with the production of mycotoxins. Here we critically review the impact of fungi on the quality of artisanal cheeses, as well as the risks associated with the presence of particular species or strains with specific phenotypes. Ultimately, we address the question; should fungi be predominantly considered villains when it comes to artisanal cheese safety or could their presence be better exploited by producers in order to generate innovative products with greater added value? Such discussions will be increasingly important from the perspective of the future commercialization and regulation of artisanal cheeses that frequently contain a high abundance of moulds.


Overview of Quantitative Methodologies to Understand Antimicrobial Resistance via Minimum Inhibitory Concentration.
The development of antimicrobial resistance (AMR) represents a significant threat to humans and food animals. The use of antimicrobials in human and veterinary medicine may select for resistant bacteria, resulting in increased levels of AMR in these populations. As the threat presented by AMR increases, it becomes critically important to find methods for effectively interpreting minimum inhibitory concentration (MIC) tests. Currently, a wide array of techniques for analyzing these data can be found in the literature, but few guidelines for choosing among them exist. Here, we examine several quantitative techniques for analyzing the results of MIC tests and discuss and summarize various ways to model MIC data. The goal of this review is to propose important considerations for appropriate model selection given the purpose and context of the study. Approaches reviewed include mixture models, logistic regression, cumulative logistic regression, and accelerated failure time-frailty models. Important considerations in model selection include the objective of the study (e.g., modeling MIC creep vs. clinical resistance), degree of censoring in the data (e.g., heavily left/right censored vs. primarily interval censored), and consistency of testing parameters (e.g., same range of concentrations tested for a given antibiotic).


Overexpression of cutaneous mitochondrial superoxide dismutase in recent-onset type 2 diabetes.
Oxidative stress and microvascular damage have been implicated in the pathogenesis of diabetic neuropathy, with manganese superoxide dismutase 2 (SOD2) responsible for superoxide detoxification in mitochondria. We hypothesised that patients with recently diagnosed type 2 diabetes would show an altered cutaneous expression of SOD2 and endothelial cell area. In this cross-sectional study, we assessed skin biopsies using immunohistochemistry, peripheral nerve function and heart rate variability in 69 participants of the German Diabetes Study with recently diagnosed type 2 diabetes and 51 control individuals. Subepidermal SOD2 area in the distal leg was increased by ~60% in the diabetic group vs the controls (0.24 ± 0.02% vs 0.15 ± 0.02%; p = 0.0005) and was correlated with an increasing duration of diabetes (r = 0.271; p = 0.024) and with the low frequency/high frequency ratio (β = 0.381; p = 0.002) as an indicator of sympathovagal balance. The area of the subepidermal endothelial cells (measured by CD31 staining) did not differ between the groups. Cutaneous antioxidative defence is enhanced in relation to the duration of diabetes and is linked to a cardiac sympathovagal imbalance towards a sympathetic predominance in individuals with recently diagnosed type 2 diabetes without evidence of endothelial cell damage. Whether cutaneous SOD2 levels can predict the development of diabetic neuropathy remains to be determined in prospective studies.


Vaginal distension induces milk ejection-related burst of oxytocin neurones interacting with suckling stimuli in lactating rats.
Milk ejection-related bursts of action potentials recurred at fairly regular intervals during suckling in oxytocin cells of anesthetized lactating rats. Additional milk ejection-related bursts were frequently induced in response to vaginal distension. The latency for the induced response was 2.9 +/- 0.2 s and the size of the induced bursts was similar to that of spontaneous ones. When animals were not suckled, the burst was in no case induced by the stimulus. The findings indicate that the two afferent stimuli arising from the mammary gland and vagina can interact with each other in generating milk ejection-related bursts of oxytocin cells.


Virtual karyotyping of pluripotent stem cells on the basis of their global gene expression profiles.
The genomic instability of stem cells in culture, caused by their routine in vitro propagation or by their genetic manipulation, is deleterious both for their clinical application and for their use in basic research. Frequent evaluation of the genomic integrity of stem cells is thus required, and it is usually performed using cytogenetic or DNA-based methods at variable sensitivities, resolutions and costs. Here we present a detailed protocol for determining the genomic integrity of pluripotent stem cells (PSCs) using their global gene expression profiles. This expression-based karyotyping (e-karyotyping) protocol uses gene expression microarray data (either originally generated or derived from the literature) and describes how to organize it properly, subject it to two complementary bioinformatic analyses and conservatively interpret the results in order to generate an accurate estimation of the chromosomal aberrations in the autosomal genome of examined stem cell lines. The experimental steps of e-karyotyping can be carried out in ∼20-30 h.


The structure of the receptor-binding domain of the bacteriophage T4 short tail fibre reveals a knitted trimeric metal-binding fold.
Adsorption of T4 bacteriophage to the Escherichia coli host cell is mediated by six long and six short tail fibres. After at least three long tail fibres have bound, short tail fibres extend and bind irreversibly to the core region of the host cell lipo-polysaccharide (LPS), serving as inextensible stays during penetration of the cell envelope by the tail tube. The short tail fibres consist of a parallel, in-register, trimer of gene product 12 (gp12).X-ray crystallography at 1.5A resolution of a protease-stable fragment of gp12 generated in the presence of zinc chloride reveals the structure of the C-terminal receptor-binding domain. It has a novel "knitted" fold, consisting of three extensively intertwined monomers. It reveals a metal-binding site, containing a zinc ion coordinated by six histidine residues in an octahedral conformation. We also suggest an LPS-binding region.


A phantom and in vivo simulation of coronary flow to calculate fractional flow reserve using a mesh-free model.
Moving particle semi-implicit (MPS) method is a mesh-free method to perform computational fluid dynamics (CFD). The purpose of this study was to calculate the simulated fractional flow reserve (sFFR) using a coronary stenosis model, and to validate the MPS-derived sFFR against invasive FFR using clinical coronary CT data. Coronary flow simulation included 21 stenosis models with stenosis ranging 30-70%. Patient coronary analysis was performed in 76 consecutive patients (100 vessels) who underwent coronary CT angiography and subsequent invasive FFR between November 2016 and March 2020. Accuracy of sFFR and CT angiography for diagnosis of invasive FFR ≤ 0.80 was compared. Quantitative morphological stenosis data of CT angiography were also obtained. Area stenosis showed a good correlation to sFFR (R2 = 0.996, p < 0.001) in coronary stenosis models. In the patient study, the mean FFR value was 0.82 ± 0.10, and 37 out of 100 vessels showed FFR ≤ 0.80. FFR and sFFR values showed a good correlation (R2 = 0.59, p < 0.001) with a slight underestimation of sFFR as compared with FFR (mean difference - 0.015 ± 0.096, p = 0.12). The sensitivity, specificity, positive predictive value, and negative predictive value of sFFR to predict FFR ≤ 0.80 was 86%, 89%, 82%, 92%, respectively. The accuracy to predict FFR ≤ 0.80 using sFFR was greater than using diameter stenosis and minimum lumen area (88% vs. 74%, p = 0.008). CFD using the MPS method showed feasible results validated against invasive FFR. The accuracy to predict significant stenosis was higher than morphological stenosis.


HPV 16 DNA in autopsy material of a metastatic cervical carcinoma.
Human papillomavirus (HPV) DNA has been regularly detected in primary cervical carcinomas and in some metastatic lesions. Using Southern blot hybridization on autopsy material we found HPV 16 DNA in a primary cervical carcinoma and in multiple metastases therefrom.


The susceptibility pattern and distribution of blaOXA-23 genes of clinical isolate Acinetobacter baumannii in a tertiary hospital, Indonesia.
Acinetobacter baumannii, a pathogen of concern in hospitals worldwide, has diverse antimicrobial resistance mechanisms leading to limiting the antibiotic options and carbapenemase enzyme production is one of the common mechanisms in carbapenem resistance. The epidemiology and resistance pattern of clinical isolates are critical in developing a prevention and treatment strategy. The aim of this was to determine the prevalence and resistance pattern of carbapenem non-susceptible strains (CNS) A. baumannii at Arifin Achmad General Hospital, Pekanbaru, Indonesia. Data were retrieved from the culture and susceptibility test results from various clinical specimens from January 2015 to December 2019. A susceptibility test was conducted using Vitek 2 Compact following the manufacturer's protocol. To explore the genetic profile of CNS A. baumannii, we amplified the blaOXA-23 and blaOXA-51 genes, carbapenemase producing genes, using a duplex polymerase chain reaction (PCR) among 24 isolates Chi-squared was used to assess the factors associated with the presence of CNS A. baumannii. Between 2015-2019, 1.263 A. baumannii isolates were tested and the prevalence of CNS A. baumannii was 50%. The trend decreased from 53% in 2016 to 45% in 2019. The proportion of CNS A. baumannii was higher among samples from patients treated in the Intensive Care Unit (ICU) compared to non-ICU (p < 0.001). The CNS A. baumannii was also more frequently detected from sputum than from non-sputum samples (p = 0.009). CNS A. baumannii were highly resistant to almost all antibiotics and the highest susceptibility was to amikacin, tigecycline, and trimethoprim/sulfamethoxazole with 64%, 53%, and 43%, respectively. The blaOXA-23 gene was detected in 92% of tested CNS A. baumannii isolates. The prevalence of CNS A. baumannii is high at Arifin Achmad Hospital Riau, Indonesia. This is also supported by the high prevalence of the blaOXA-23 gene among tested isolates. Based on the antibiotic susceptibility pattern there are limited antibiotic choices for CNS A. baummannii urging the strengthening of antimicrobial stewardship programs in the country.


Depression and Service Use Among Caregivers Dually Involved in the Child Welfare and Mental Health Systems.
The purpose of this study was to investigate the prevalence of depression, use of mental health services, and correlates of service use among caregivers who are dually involved in the child welfare and child mental health systems. This study analyzed baseline data from 129 caregivers who reported child welfare system involvement and were participating in a Multiple Family Group service delivery model to reduce childhood disruptive behavior disorders. Seventy-eight (60.5%) of caregivers met or exceed the clinical-cut off for depression; of them 50 (64.1%) reported utilizing mental health services for their emotional health. Race, employment status, and CES-D score were significantly associated with lifetime mental heath services use. Depression rates exceeded those found among caregiver involved in either the child welfare or child mental health systems. Rates of service use were higher than found in existing research. As expected, racial differences and depression were associated with service use; contrary to expectations, full time employment was not associated with service use. Discrepancies between this study and existing research are discussed, as are practice, policy, and research implications.


Breast radiologic complete response is associated with favorable survival outcomes after neoadjuvant chemotherapy in breast cancer.
The aim of this study was to examine the accuracy of radiologic complete response (rCR) in predicting pathologic complete response (pCR), and determine whether rCR is a predictor of favorable survival outcomes. We retrospectively reviewed breast cancer patients treated with neoadjuvant chemotherapy (NAC) followed by surgery from September 2007 to June 2016. Breast lesions and axillary nodes were measured by MRI and categorized into either disappeared (breast rCR) or residual disease (breast non-rCR) and either normalized (axillary rCR) or abnormal findings (axillary non-rCR) in the axillary nodes. Correlation between rCR and pCR were compared using Cohen's Kappa statistics, and the recurrence-free survival (RFS) and overall survival (OS) rates were calculated by the Kaplan-Meier method. Out of the 1017 eligible patients, 287 (28.2%) achieved breast pCR, 165 (16.2%) achieved breast rCR, 529 (52.0%) had axillary pCR, and 274 (26.9%) achieved axillary rCR. The correlation between a breast rCR and pCR showed a Cohen's Kappa value of 0.459, and between axillary rCR and pCR, the value was 0.384. During a median follow-up time of 48.0 months, the 5-year RFS rates were 90.6% for breast rCR, and 69.2% for breast non-rCR. The 5-year RFS rates were 82.3% for axillary rCR, and 68.8% for axillary non-rCR. Patients without breast rCR had a 2.4-fold significant increase in the risk of recurrence (p = 0.004) compared to patients with breast rCR. Although rCR correlated with pCR by only moderate to fair degrees, breast rCR was a strong predictor for a favorable RFS outcome.


Factors associated with symptomatic improvement and recovery from major depression in primary care patients.
This article describes a post-hoc analysis of clinical and psychosocial factors and beliefs about health associated with treatment outcome in a sample of depressed primary care patients (N=181) randomly assigned to a standardized treatment or physician's usual care (UC). Different factors were found to predict clinical outcomes for treatment modality [UC vs. interpersonal psychotherapy (IPT) or nortriptyline (NT)] and the type of outcome evaluated (i.e., depressive symptoms at 8 months or symptomatic and functional recovery at 8 months). Factors associated with treatment-specific outcomes are also described. Consistent with prior studies, lower depressive symptom severity at 8 months was associated with higher baseline functioning, minimal medical co-morbidity, race, and standardized pharmacologic or psychotherapeutic treatment. Additionally, an interaction between treatment modality and health locus of control indicated that individuals perceiving more self-control of their health and who received a standardized treatment experienced greater depressive symptom reduction at 8 months. Factors associated with symptomatic and functional recovery from the depressive episode were also examined. Patients who received a standardized treatment (IPT or NT) perceived greater control of their health and lacked a lifetime generalized anxiety disorder or panic disorder were more likely to recover by month 8 than those who received usual care. While clinical severity and treatment adequacy play an important role in both symptomatic improvement and full recovery from a depressive episode, other key factors such as health beliefs and non-depressive psychopathology also influence recovery.