The effect of unitization on associative recognition was not moderated by the unitization-congruence between original and rearranged picture pairs (UC) for picture stimuli.
It is widely accepted that associative recognition can be supported by familiarity through integrating more than two stimuli into a unit, but the role of unitization in recollection-based associative recognition remains unclear. In this study, we aimed to illustrate how the level of unitization (LOU) affected recollection-based associative recognition and to examine whether the unitization-congruence between original and rearranged picture pairs (UC) could have effect on the relationship between LOU and associative recognition. In encoding, participants were asked to learn related and unrelated picture pairs, and in retrieval, they needed to distinguish intact pairs from rearranged pairs. We also distinguished the LOU of the pairs based on its status at encoding or retrieval separately. The results showed that: (1) LOU-at-encoding could improve associative recognition through increasing recollection-based associative recognition selectively; (2) LOU-at-retrieval could improve associative recognition through increasing familiarity-based and recollection-based associative recognitions; (3) UC did not moderate the relationship between LOU and associative recognition. Hence, in future studies, researchers do not need to pay much attention to the construction of rearranged pairs to ensure that the LOU between original and rearranged picture pairs is matched. It greatly reduces the difficulty of materials selection.


Childhood-onset autosomal recessive ataxias: a cross-sectional study from Turkey.
Autosomal recessive ataxias (ARAs) are a heterogeneous group of inherited neurodegenerative disorders that affect the cerebellum, the spinocerebellar tract, and/or the sensory tracts of the spinal cord. This study is aimed at establishing molecular classification and phenotypic correlation of childhood-onset ARAs in Southeast Anatolia of Turkey. Sixty-five children (aged 0 to 18) from 40 unrelated families who were analyzed through hereditary ataxia NGS panel between the years of 2015-2018 were selected for the study. Seventeen different, clinically significant ARA-related pathogenic variants were detected in 33 of 40 families (82.5%), 12 of which were noted to be unreported variants. Among these 33 families, 24 had ATM-related (72.72%), four had SACS-related (12.12%), three had COQ8A-related (9.09%), and two had APTX-related (6.06%) pathogenic variants. The c.3576G>A (p.K1192=) was the most common homozygous pathogenic ATM variant (33.33%) that was associated with milder phenotype of ataxia telangiectasia (AT) with the onset of age of 3. Patients with SACS variants demonstrated developmental delay and progressive ataxia before the age of 3. Slowly progressive ataxia and intellectual disability were the common clinical manifestations of the patients with homozygous c.1396delG (p. E466Rfs*11) pathogenic variant in COQ8A. Homozygous APTX c.689T>G (p.V230G) pathogenic variant was identified in two patients who had chief complaint of ataxic gait onset after puberty. The most common types of ARAs in this region are AT- and Charlevoix-Saguenay-type spastic ataxia. ATM gene analysis should be performed foremost on children presenting early-onset ataxia from Southeastern Anatolia. If there is a concomitant peripheral neuron involvement, SACS gene analysis should be preferred. This valuable data will be a guide for the first step molecular diagnostic approach before requesting the NGS panel for ARA.


The historical path of evaluation as reflected in the content of Evaluation and Program Planning.
This paper examines the intellectual structure of evaluation by means of citation analysis. By using various article attributes and citation counts in Google Scholar and (Social) Science Citation Index Web of Science, we analyze all articles published in Evaluation and Program Planning from 2000 until 2012. We identify and discuss the characteristics and development of the field as reflected in the history of those citations.


3.0 vs 1.5 T MRI in the detection of focal cartilage pathology--ROC analysis in an experimental model.
To use receiver operator characteristics (ROC) analysis for assessing the diagnostic performance of three cartilage-specific MR sequences at 1.5 and 3 T in detecting cartilage lesions created in porcine knees. Eighty-four cartilage lesions were created in 27 porcine knee specimens at the patella, the medial and lateral femoral and the medial and lateral tibial cartilage. MR imaging was performed using a fat saturated spoiled gradient echo (SPGR) sequence (in plane spatial resolution/slice thickness: 0.20 x 0.39 mm2/1.5 mm) and two fat saturated proton density weighted (PDw) sequences (low spatial resolution: 0.31 x 0.47 mm2/3 mm and high spatial resolution: 0.20 x 0.26 mm2/2 mm). The images were independently analyzed by three radiologists concerning the absence or presence of lesions using a five-level confidence scale. Significances of the differences for the individual sequences were calculated based on comparisons of areas under ROC curves (A(Z)). The highest A(Z)-values for all three radiologists were consistently obtained for the SPGR (A(Z) = 0.84) and the high-resolution (hr) PDw (A(Z) = 0.79) sequences at 3T. The corresponding A(Z)-values at 1.5 T were 0.77 and 0.69; the differences between 1.5 and 3 T were statistically significant (P < 0.05). A(Z)-values for the low-resolution PDw sequence were lower: 0.59 at 3 T and 0.55 at 1.5 T and the differences between 1.5 and 3T were not significant. With optimized hr MR sequences diagnostic performance in detecting cartilage lesions was improved at 3 T. For a standard, lower spatial resolution PDw sequence no significant differences, however, were found.


Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes.
TLRs are critical for innate immunity, but excessive activation can lead to tissue damage and disease. Specialized proresolving mediators (SPMs), including resolvin D2 (RvD2), promote the active resolution of inflammation. How SPMs regulate early LPS signaling, including activation of TLR4, is unknown. We treated human THP-1 monocytic cells and primary human blood monocytes with RvD2 and LPS to evaluate modulation of TLRs. miRNA-146a overexpression and inhibition were used to dissect the mechanism of RvD2-mediated actions. We validated our studies using ELISAs for cytokines, PCR, Western blot analysis, and flow cytometry. Cells treated with 0.1% ethanol (control for RvD2) and/or PBS (control for LPS), and control microRNA mimics and inhibitors were used as controls. RvD2 reduced LPS-induced cytokines and TLR4 expression in human monocytes by up to 75%. In THP-1 cells, RvD2 reduced expression of TLR4, lymphocyte antigen 96 (MD-2), and downstream signals (MyD88, TRIF, and TAK1). These effects were partially mediated through RvD2 induction of microRNA-146a, and RvD2's actions were blocked by microRNA-146a inhibition. These new findings reveal the ability of RvD2 to reduce TLR4 expression and attenuate LPS-induced inflammation, providing a new area of SPM activity to investigate in this major area of therapeutic research.-Croasdell, A., Sime, P. J., Phipps, R. P. Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes.


Photocatalytic Pt/Ag3VO4 micromotors with inherent sensing capabilities for corroding environments.
Autonomous self-propelled micromachines based on semiconductors are at the forefront of environmental pollutants degradation research to palliate the effects of the contamination arising from the constant manufacturing of new products. Nonetheless, testing these micromotors with real-life products is almost an unexplored field, limiting the degradation of pollutants to single-component aqueous solutions or suspensions at the laboratory scale, which hinders the translation of these micromachines into useful systems. Herein, Ag3VO4 has been devised as a micromotor by an asymmetric deposition of a thin layer of Pt, giving rise to Pt/Ag3VO4 micromotors (Janus particle). Their motion capabilities have been demonstrated under UV light in fuel-free conditions. Their photocatalytic performance at laboratory scale has been confirmed for the degradation of Rhodamine B while, as a first approximation of a real-life application, the degradation of an energy drink has also been tested. During this latter exploration, the Pt/Ag3VO4 micromotors were corroded by the citric acid present in the pollutant, releasing Ag nanoparticles into the media. As a proof of concept, the position of the generated Ag nanoparticles' surface plasmon resonance absorption maximum has been demonstrated to show a dependency on the concentration of citric acid.


Theranostics and Patient-Specific Dosimetry.
Radiopharmaceutical therapy (RPT) is an invigorated form of cancer therapy that systemically delivers targeted radioactive drugs to cancer cells. Theranostics is a type of RPT that utilizes imaging, either of the RPT drug directly or a companion diagnostic, to inform whether a patient will benefit from the treatment. Given the ability to image the drug onboard theranostic treatments also lends itself readily to patient-specific dosimetry, which is a physics-based process that determines the overall absorbed dose burden to healthy organs and tissues and tumors in patients. While companion diagnostics identify who will benefit from RPT treatments, dosimetry determines how much activity these beneficiaries can receive to maximize therapeutic efficacy. Clinical data is starting to accrue suggesting tremendous benefits when dosimetry is performed for RPT patients. RPT dosimetry, which was once performed by florid and often inaccurate workflows, can now be performed more efficiently and accurately with FDA-cleared dosimetry software. Therefore, there is no better time for the field of oncology to adopt this form of personalize medicine to improve outcomes for cancer patients.


Adenomyosis in mice resulting from mechanically or thermally induced endometrial-myometrial interface disruption and its possible prevention.
Do uterine procedures potentially disrupting the endometrial-myometrial interface (EMI) induce adenomyosis? Six prospective, randomized controlled experiments were conducted involving a total of 106 female BALB/c and 12 female C57BL/6 mice. The incidence of adenomyosis was evaluated in these two strains of mouse after mechanically induced EMI disruption (EMID), or thermally induced EMID using electrocoagulation of different intensities. Finally, the incidence was evaluated in mice that had received perioperative administration of aprepitant (an NK1R inhibitor), propranolol (a beta-blocker) or vehicle. Body weight, hot plate latency and grade of myometrial infiltration were evaluated. Histology, immunohistochemistry and histochemistry analyses were also performed. Mechanical injury to the EMI caused EMID. Adenomyosis developed in the majority of mice in the EMID groups 3 months after mechanically induced EMID but did not develop in the control group (83.3% in C57BL/6 mice, P = 0.015; 100% in BALB/c mice, P = 0.0002). With thermally induced EMID, adenomyosis was found in 30% of the EMID mice 10 weeks later, but the incidence increased to 66.7% if the extent of EMID damage was increased. In mice with perioperative administration of aprepitant or propranolol, the incidence of adenomyosis was reduced from 100% to 58.3% (both P = 0.00034). This study provides the first piece of experimental evidence that EMID resulting from iatrogenic uterine procedures can substantially increase the risk of developing adenomyosis, with the risk in proportion to the severity of disruption. More intriguingly, perioperative administration of an NK1R antagonist or beta-blocker significantly reduced the risk of developing adenomyosis.


Concomitant weekly cisplatin and thoracic radiotherapy for Pancoast tumors of the lung: pilot experience of the San Antonio Cancer Institute.
Pancoast (superior sulcus tumors) comprise a subset of non-small-cell lung cancers that have a unique clinical presentation by virtue of the locoregional pattern of disease progression. We herein report a brief report on our group's pilot experience in managing these challenging lung neoplasms with an aggressive concomitant modality approach. These results and those of the recent Southwest Oncology-lead Intergroup prospective phase 2 trial (SWOG-9416/INT-0160) support the use of concomitant chemoradiation followed by an attempt at surgical resection.


Human antibody-dependent cellular cytotoxicity mediated by interferon gamma-activated neutrophils is impaired by vasoactive intestinal peptide.
The aim of the present study was to evaluate the effect of vasoactive intestinal peptide (VIP) on the expression and activity of receptors for the Fc portion of IgG (Fc gamma R) in human neutrophils. Cells were assayed under basal conditions and following in vitro stimulation with interferon gamma (IFN gamma). Antibody dependent-cellular cytotoxicity (ADCC) was chosen as a means of evaluating Fc gamma R activity. The results indicated that incubation with VIP (10(-6) M) during 18 h slightly diminished cytotoxicity of non stimulated neutrophils. In contrast, VIP exerted a marked inhibitory effect on neutrophils activated with IFN gamma. Similar results were obtained with forskolin, another agent that increases intracellular cAMP. Finally, using monoclonal antibodies and flow cytometry analysis, we found decreased membrane expression of Fc gamma R after VIP incubation. Taken together, these results show that VIP is able to act on human neutrophils, partially blocking IFN gamma-activation of Fc gamma R mediated functions. Modulation of neutrophil cytotoxic response by VIP may have an important role in limiting tissue injury during inflammation.


Role of CYP3A4 and CYP2C19 in the stereoselective metabolism of lansoprazole by human liver microsomes.
The aim of this investigation was to clarify the stereoselective properties in lansoprazole metabolism by monitoring the metabolic consumption for each enantiomer and the formation of the main metabolites, lansoprazole sulfone and 5-hydroxylansoprazole, in the presence of human liver microsomal enzymes. Human liver microsomes or recombinant cytochrome P450 (CYP) enzymes were incubated with either (+/- )-, (+)-, or (-)-lansoprazole in the presence of reduced nicotinamide adenine dinucleotide phosphate. The metabolic consumption of lansoprazole enantiomers was estimated from the amounts of enantiomers consumed by microsomal enzymes after incubation at 37 degrees C for 60 min. Metabolites of lansoprazole, lansoprazole sulfone, and 5-hydroxylansoprazole were determined after incubation at 37 degrees C for 20 min, and kinetic parameters [Michaelis constant (Km) and maximum velocity (Vmax)] were obtained using Eadie-Hofstee plots. (-)-Lansoprazole was metabolized more preferentially than (+)-lansoprazole in human liver microsomes. Stereoselective sulfoxidation and hydroxylation [(+) > (-)] were observed in human liver microsomes. Strikingly, in sulfoxidation, a significantly higher intrinsic clearance (Vmax,l/Km,l) of (-)-lansoprazole (0.023 +/- 0.001 ml/min/mg) than (+)-lansoprazole (0.006 +/- 0.000 ml/min/mg) was observed. Consequently, sulfoxidation is likely to play an important role in the stereoselective metabolism of lansoprazole enantiomers. P450-isoform specificity for each enantiomer was evident. CYP3A4, which mainly catalyzed sulfoxidation, was more active toward (-)-lansoprazole in either a chiral or racemic drug as a substrate. CYP2C19, which catalyzed hydroxylation, preferentially metabolized (+)-lansoprazole. The consumption of (+)-lansoprazole was markedly inhibited by (-)-lansoprazole, indicating a metabolic enantiomer/enantiomer interaction. However, this alteration of recombinant CYP2C19 specificity for (+)-lansoprazole did not appear in metabolism in human liver microsomes. Stereoselective metabolism was observed in human liver microsomes, and this stereoselectivity was mainly based on CYP3A4 specificity for preferable metabolism of (-)-lansoprazole.


Measuring Asian nurses' organizational commitment: a critical analysis of the psychometric properties of two organizational commitment instruments.
To analyze and compare the psychometric properties and cultural attributes of the Organizational Commitment Questionnaire and the Organizational Commitment Scale to determine their appropriateness for measuring commitment of Asian nurses, the biggest portion of international nurses. The Organizational Commitment Questionnaire was cross-culturally cross-validated when compared with the Organizational Commitment Scale. Both instruments were not tested on Asian nurses. More studies are needed to validate the cultural properties of the Organizational Commitment Scale. Healthcare administrators can use culturally validated instruments, which concern cultural context, including languages and cultural values, to understand Asian nurses' organizational commitment and further lower turnover behavior among them.


Three-dimensional volumetric analysis of condylar head and glenoid cavity after mandibular advancement.
The aim of this study was to assess condylar resorption, spatial change in glenoid cavity, and its risk factors after mandibular advancement by three-dimensional volumetric analysis. Subjects consisted of 30 condyles of 15 patients diagnosed with mandibular retrognathism who underwent Le Fort I and bilateral sagittal split ramus osteotomy advancement. CBCT images were taken before surgery (T0), immediately after surgery (T1), and postoperatively at 6 months (T2) and 1 year (T3). Condylar resorption was observed in 21 condyles. The posterior was the most affected region, while the anterior was the least affected. The volume of the glenoid cavity was significantly increased after surgery regardless of the presence or absence of resorption. However, the cavity recovered close to its original volume over time. At 1 year after surgery, the volume was not significantly different from the preoperative volume. Counterclockwise rotation of the proximal segment was found to be a risk factor affecting resorption based on correlation analysis. Mandibular advancement appeared to generate excessive mechanical stress on the posterior condyle, and might be responsible for the resorption. Counterclockwise rotation might have added stress to the region. Articular spatial change was transient and did not appear to be related to condyle resorption.


Etiology of Obesity Over the Life Span: Ecologic and Genetic Highlights from New Zealand Cohorts.
The origins of the New Zealand population are highly diverse. New Zealand Māori are the indigenous peoples with a population of approximately half a million (~12 %), with the remainder comprising predominantly European/Caucasian (~50 %), Pacific Island Polynesian (~28 %) and Asian (~10 %) peoples. With a prevalence of overweight and obesity of 65 % for adults >15 years of age, of which 28 % have a BMI > 30 kg/m(2), New Zealand has been ranked third highest in a global OECD obesity review, behind only the US and Mexico. Levels of childhood obesity are also significant, with 31 % of New Zealand's children either overweight or obese. Few gender differences exist, but there are significant differences between ethnicities (Asian > European Caucasian > Māori > Pacific) with disproportionate representation by those poorer and with less formal education. A high 62 % of Pacifika are obese and virtually the entire adult population has a BMI >25 kg/m(2). Public health measures to limit progressive increases in weight are unsuccessful, and clearly should be priority for government focused on disease prevention.


Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.
A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.


Approaches used to enhance transition and retention for newly qualified nurses (NQNS): A rapid evidence assessment.
To undertake a rapid evidence assessment of approaches used to enhance nurse transition and retention for newly qualified nurses and to evaluate the strength of the evidence for specific approaches to nurse transition and retention. A rapid evidence assessment was undertaken. Electronic databases were searched, and the full texts of relevant papers were retrieved. Studies were appraised using relevant Critical Appraisal Skills Programme and Mixed Methods Assessment Tools and a single descriptor of quality: high; medium; or low was assigned to each output. Given the disparity in methods, the lack of randomised trials, results could not be combined; therefore, a descriptive approach was used to synthesise and present the data. The search was undertaken using: specific database searching; and secondary searching of relevant websites. Electronic databases (CINAHL complete, Academic search premier, Open Grey, ERIC* (Education), Web of Science-Social Science Citation Index and PubMed) were searched during February 2018. Orientation and creating supportive environments were frequently reported as being effective in enhancing transition across a range of studies. A range of methods: quasi-experimental, survey and qualitative were used. Generally, the quality of most studies was poor. Despite decades of research into the experiences of newly qualified nurses and development of schemes and frameworks to support them during this period, there is little substantive or robust evidence in terms of impact on retention. Further research into the longer-term retention of newly qualified nurses is recommended. Longitudinal studies would be beneficial in assessing the efficacy of approaches to enhancing retention.


Pesticide pollution associations with riverine invertebrate communities in England.
Globally freshwater biodiversity has experienced major decline and chemical pollutants are believed to have played a significant role in this decline, but this has not been well quantified for most riverine invertebrate populations. Here we applied a biogeographically independent trait-based bioindicator, SPEARpesticides across sites across five regions (Northern, Midlands and Western, Anglian, Southeast, and Southwest) in England to investigate for associations specifically between pesticide use/pollution and riverine invertebrate communities over a 55-year period (1965-2019). Both spatially and temporally post-1990, the Anglian and Thames regions consistently showed the lowest SPEARpesticides scores, illustrating the presence of fewer pesticide sensitive species. The Anglian region had the highest pesticide use compared to all other regions from 1990 to 2018 and there were negative relationships between the level of pesticide/insecticide use and the regional SPEARpesticides score. Biochemical Oxygen Demand and ammonia, as measures of general water quality, were also negatively correlated with the SPEARpesticides scores across the regions, but these factors were not the driver for the lower SPEARpesticides scores seen in the Anglian region. Based on SPEARpesticides scores, riverine invertebrate communities in England have been most impacted in the Anglian region and we evidence chronic insecticide exposure is likely a significant factor in shaping the status of those invertebrate communities.


A new multiprogrammable isotopic powered cardiac pacemaker.
A new multiprogrammable, isotopic-powered cardiac pacemaker was implanted in six patients as a custom device. Five were initial implants and one was a replacement. The patients were studied for up to two years. In five of the six cases it was found advantageous to change one of the programmable parameters. Multiprogrammability is obviously as important in an isotopic pulse generator as in a lithium unit, if not more so, because of the unit's greater longevity. Further studies are continuing in an FDA approved clinical trial.


Assessing the conservation and enhancement value of revegetated strips on arthropod assemblages in a pasture landscape.
Examining population dynamics of arthropod communities in habitats neighboring arable lands is essential to understanding how agroecosystems can be engineered to enhance ecosystem services and contribute to sustainable intensification. Arthropods comprise the bulk of faunal biomass on farms, are taxonomically diverse, and are the main drivers of many ecosystem functions. This study aimed to compare arthropod assemblages in revegetated strips of native plants and exotic pastures, and examine taxa of beneficial arthropods in revegetated strips and adjacent pasture in early spring (September 2009) and mid-summer (December 2009-January 2010) on two farms in southeastern Gippsland, Victoria, Australia. Arthropod community assemblages were distinctly different between revegetated strips and adjacent pasture with the exception of functional groups in early spring. Several taxa of beneficial arthropods including Carabidae (ground beetles) and Syrphidae (hoverflies) were of similar abundance in the two habitats. Only Formicidae (ants) were of higher abundances in revegetated strips compared to adjacent pasture in both seasons. Five of the 10 ant genera present, seven spider families and Dolichopodidae flies (long-legged flies) were found exclusively in revegetated strips. Apidae (bees) and Tachinidae (tachinid flies) had higher abundances in revegetated strips compared to 80 m into the adjacent pasture in mid-summer. Lycosidae (wolf spiders) were more abundant along the edge of revegetated strips and 20 m into adjacent pasture compared to the center (core) of revegetated strips and 80 m into pasture. These results illustrate that beneficial arthropods use revegetated strips as refugia and that revegetated strips clearly enhanced biological conservation of arthropods in pasturelands. Relevance of findings to enhanced biological control is also discussed.


When is an invasive palliative intervention in an acute internal medical patient worth it? A structured palliative approach.
A 67-year-old patient with coronary artery disease (CAD), diabetes, and chronic obstructive pulmonary disease (COPD) was scheduled for coronary artery bypass graft (CABG) surgery after a recent myocardial infarction despite a high perioperative risk of death. While waiting, acute renal failure developed, and the patient was admitted to the intensive care unit (ICU). After the patient and his wife were informed that CABG surgery was no longer possible, he declined further intensive care treatment and subsequently died peacefully.We show that a structured palliative approach which has been proposed for cancer patients may also be feasible in palliative situations concerning nononcologic patients.


Preliminary study of whole-body diffusion-weighted imaging in detecting pulmonary metastatic lesions from clear cell renal cell carcinoma: comparison with CT.
Whole-body diffusion-weighted imaging (DWI) has been widely used in detecting malignant metastases, including pulmonary metastases. To evaluate the possible utility of whole-body DWI in detecting pulmonary metastases of patients with clear cell renal cell carcinoma (ccRCC) and compare the exact differences between MR and CT in detecting pulmonary lesions. Whole-body DWI and chest CT examinations were performed on nine consecutive patients (8 men and 1 woman) with histologically confirmed ccRCC and possible metastatic lesions before chemotherapy. CT and MR demonstrated pulmonary metastases in seven patients and no metastatic lesions in two patients. The numbers of pulmonary metastases detected on CT, DWI-only, T1WI-only and DWI in combination with T1WI were 83, 35, 34 and 39, respectively. Metastases with a diameter above 1.0 cm could all be detected by DWI and a diameter above 0.7 cm could all be detected by DWI in combination with T1WI. Significant differences were obtained both for correlationship between diameter and detection rates of DWI and T1WI by using Spearman rank correlation analysis. Although MR cannot be considered a replacement for CT in pulmonary metastases from ccRCC, whole-body DWI, with the combination of T1 dual echo, might be helpful for the evaluation of tumor response to chemotherapy in the follow-up of patients when the diameter of the pulmonary metastases is over 1.0 cm.


The AIDS autopsy spleen: a comparison of the pre-anti-retroviral and highly active anti-retroviral therapy eras.
Pathologic findings attributed to human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) are described in the spleen in studies that encompassed the years preceding highly active anti-retroviral therapy (HAART). Major findings included white-pulp depletion, hemosiderin deposition, spindle cell proliferations, and perivascular hyalinization. Infectious and malignant infiltrates were commonly noted and characterized. The histopathology of AIDS autopsy spleens since the introduction of protease inhibitors has not been studied. Histologic sections from 168 cases of AIDS spleens examined at autopsy over a 19-year period (1982-2000) were evaluated for significant pathologic findings. Multiple morphologic parameters were recorded, including a graded estimation of white-pulp depletion. Significantly less white-pulp depletion was observed in the 39 HAART-era spleens (1995-2000) compared with the 129 spleens from the 1982-1994 patient group (P =.001). The rates of splenic involvement by atypical mycobacteria and cytomegalovirus were similar to those in the past, although the overall clinical rates of these opportunistic infections were found to be decreased. The annual numbers of AIDS autopsies have decreased, reflecting a nationwide trend of lower autopsy rates. Increased survival with HIV infection and AIDS is now apparent. Protease inhibitors, in conjunction with other contemporary therapies, may have contributed to the preservation of white pulp observed in the HAART patient group.


Associations between food insecurity and other social risk factors among U.S. adults.
Food insecurity (FI) often co-exists with other social risk factors, which makes addressing it particularly challenging. The degree of association between FI and other social risk factors across different levels of income and before and during the COVID-19 pandemic is currently unknown, impeding the ability to design effective interventions for addressing these co-existing social risk factors. To determine the association between FI and other social risk factors overall and across different levels of income-poverty ratios and before (2019) and during (2020-2021) the pandemic. We used nationally representative data from the 2019-2021 National Health Interview Survey for our cross-sectional analysis. Social risk factors available in NHIS included difficulties paying for medical bills, difficulties paying for medications, receiving income assistance, receiving rental assistance, and "not working last week". 93,047 adults (≥18 years old). Individuals with other social risk factors (except receiving income assistance) were more likely to report FI, even after adjusting for income and education inequalities. While poverty leads to a higher prevalence of FI, associations between FI and other social risk factors were stronger among people with higher incomes, which may be related to their ineligibility for social safety net programs. Associations were similar before and during the pandemic, perhaps due to the extensive provision of social safety net programs during the pandemic. Future research should explore how access to a variety of social safety net programs may impact the association between social risk factors. With the expiration of most pandemic-related social supports, further research and monitoring are also needed to examine FI in the context of increasing food and housing costs. Our findings may also have implications for the expansion of income-based program eligibility criteria and screening for social risk factors across all patients and not only low-income people.


Effect of EDTA and Fe-EDTA complex concentration on TCF Kraft mill effluent degradability. Batch and continuous treatments.
The effect of ethylenediaminetetracetic acid (EDTA) and Fe-EDTA complex on synthetic totally chlorine-free (TCF) effluent degradability in batch and continuously operating reactors was evaluated. Under batch treatment, the addition of EDTA and Fe-EDTA complex was studied in the range of 80 to 320 mg l(-1). Under continuously operated reactors, the Fe-EDTA complex concentration varied from 20 to 80 mg l(-1), and the hydraulic retention time (HRT) varied from 48 to 24 h. Sludge oxygen uptake rate (OUR) and chemical oxygen demand (COD) removal decreased when EDTA concentration increased in the influent under batch treatment; however, this inhibitory effect was reduced by the addition of Fe-EDTA complex. Without the addition of EDTA, COD removal decreased from 71% to 8%. The most efficient EDTA removal treatment (almost 10%) was the treatment of 80 mg l(-1) Fe-EDTA. Under continuously operated reactors, COD removal was greater than 57% in the synthetic TCF effluent with a Fe-EDTA concentration that varied from 20 to 80 mg l(-1); however, EDTA removal was lower than 25% in all cases. Synthetic TCF effluent with a Fe -EDTA concentration higher than 80 mg l(-1) could not be treated by the activated sludge treatment due to EDTA's inhibitory effect on the sludge.


Hypothesis: a role for EBV-induced molecular mimicry in Parkinson's disease.
Current concepts regarding the pathogenesis of Parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. The identity of the responsible environmental trigger has remained elusive. There is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis. A novel hypothesis of Parkinson's pathogenesis, articulated by Braak and colleagues, implicates a pathogen acting in the olfactory mucosa and gastrointestinal tract as the inciting agent. In this point-of-view article, we hypothesize that α-synuclein aggregation in Parkinson's disease is an Epstein-Barr virus (EBV)-induced autoimmune phenomenon. Specifically, we have shown evidence for molecular mimicry between the C-terminal region of α-synuclein and a repeat region in the latent membrane protein 1 encoded by EBV. We hypothesize that, in genetically-susceptible individuals, anti-EBV latent membrane protein antibodies targeting the critical repeat region cross react with the homologous epitope on α-synuclein and induce its oligomerization. Consistent with the Braak's proposed pattern of spread, we contend that axon terminals in the lamina propria of the gut are among the initial targets, with subsequent spread of pathology to the CNS. While at this time, we can only provide evidence from the literature and preliminary findings from our own laboratory, we hope that our hypothesis will stimulate the development of tractable experimental systems that can be exploited to test it. Further support for an EBV-induced immune pathogenesis for Parkinson's disease could have profound therapeutic implications.


Respiratory syncytial virus-associated hospitalisation in children aged ≤5 years: a scoping review of literature from 2009 to 2021.
Following the easing of COVID-19 restrictions in many countries, a surge in respiratory syncytial virus (RSV) hospitalisations was reported, surpassing yearly trends pre-pandemic. The changes to RSV epidemiology may have unforeseen effects on healthcare systems and populations globally, adding to the burden generated during the pandemic and placing increased demand on resources. Here we aim to identify recent global trends of RSV hospitalisation amongst children aged ≤5 years, to help inform policy makers in the planning of preventative interventions. We conducted a scoping review of published literature between January 2009 and May 2021. Using keywords "Hospital admissions, Respiratory syncytial virus, RSV, Bronchiolitis, Children" we located studies using Medline, EMCARE, CINAHL and HMIC. Studies were eligible if they reported on trends/data for RSV hospitalisation amongst children aged ≤5 years. The articles were reviewed by two independent reviewers. We assessed 3310 abstracts, reviewed 70 studies and included 56 studies in the final review. Findings were categorised into themes. The review highlighted that, although RSV incidence has been steadily increasing since 2009, the number of reported RSV hospitalisations decreased during lockdown. The highest numbers of hospitalisations were reported in children <1 year of age, particularly 0-2-month-old infants. Globally, RSV hospitalisations tend to peak in the winter months; however, since COVID-19 restrictions have eased, countries are reporting incidence peaks at different times, in contrast to the trends of previous years. With greater physical interactions due to the relaxation of COVID-19 restriction measures, RSV-related hospitalisations can be seen to increase amongst children aged ≤5 years, possibly surpassing the numbers reported in previous RSV seasons.


Sensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma.
To determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. Hundred and twenty cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1∧ E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, six (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx.


Activation of ALDH2 attenuates high glucose induced rat cardiomyocyte fibrosis and necroptosis.
Necroptosis is one of a regulated programmed death mode, fibrosis is closely related with cell death. It has been reported that inhibition of necroptosis can play the protective role in cardiac ischemia and reperfusion injury, stroke and other diseases, but the mechanisms of aldehyde dehydrogenases 2 (ALDH2) against high glucose induced neonatal rat ventricular primary cardiomyocytes fibrosis and necroptosis had not been elucidated clearly. This study was to observe the effect of ALDH2 on high glucose (HG) induced myocardial fibrosis and necroptosis in primary rat cardiomyocytes model. In contrast to normal glucose group, in HG group, with the decreases of ALDH2 activity, mRNA and protein levels, the cardiomyocytes viability was decreased, reactive oxygen species (ROS), the inflammation factors - tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) levels, collagen I (col I) and col III mRNA expressions and tissue inhibitors of matrix metalloproteinase 4 (TIMP4) protein expression were increased, while matrix metalloproteinase 14 (MMP14) protein level, the ratio of MMP14/TIMP4 were decreased, and the necroptosis key factors - the receptor interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) at mRNA and protein expressions were increased, the inflammasome core proteins - NLRP3 and ASC protein expressions were also increased, the apoptosis rate and necrosis rate were also increased. When the cardiomyocytes were treated with Alda-1 (the ALDH2 agonist) in HG intervention, the cell viability, ALDH2 activity, mRNA and protein levels, MMP14 protein level, the ratio of MMP14/TIMP4 were higher, ROS and TNF-α, IL-6, IL-1β levels, RIP1, RIP3, MLKL, NLRP3 and ASC expressions, col I and col III, TIMP4 expressions, the apoptosis rate and necrosis rate were lower than in HG group. Daidzin, the antagonist of ALDH2 abolished the role of Alda-1. In summary, ALDH2 maybe is a key regulator in high glucose induced cardiomyocytes injury. Activation of ALDH2 prevented the happening of fibrosis, apoptosis and necroptosis in high glucose induced primary cardiomyocytes injury model, the protective effects were related to the inhibiting of oxidative stress and inflammation, changing of MMP14 and TIMP4, then inhibiting the happening of fibrosis, apoptosis and necroptosis. These findings advance our understanding of the intensive mechanisms of ALDH2's cardioprotection, and provide the targeted basis for clinical diabetes treatment.


Direct quantification of ligand-induced lipid and protein microdomains with distinctive signaling properties.
Lipid rafts are ordered lipid domains that are enriched in saturated lipids, such as the ganglioside GM1. While lipid rafts are believed to exist in cells and to serve as signaling platforms through their enrichment in signaling components, they have not been directly observed in the plasma membrane without treatments that artificially cluster GM1 into large lattices. Here, we report that microscopic GM1-enriched domains can form, in the plasma membrane of live mammalian cells expressing the EphA2 receptor tyrosine kinase in response to its ligand ephrinA1-Fc. The GM1-enriched microdomains form concomitantly with EphA2-enriched microdomains. To gain insight into how plasma membrane heterogeneity controls signaling, we quantify the degree of EphA2 segregation and study initial EphA2 signaling steps in both EphA2-enriched and EphA2-depleted domains. By measuring dissociation constants, we demonstrate that the propensity of EphA2 to oligomerize is similar in EphA2-enriched and -depleted domains. However, surprisingly, EphA2 interacts preferentially with its downstream effector SRC in EphA2-depleted domains. The ability to induce microscopic GM1-enriched domains in live cells using a ligand for a transmembrane receptor will give us unprecedented opportunities to study the biophysical chemistry of lipid rafts.


Neighborhood Socioeconomic Disadvantage, Healthcare Access, and Outcomes of Hospitalizations for Common Pulmonary Conditions: A National Study of Medicare Beneficiaries.
Rationale: Understanding how systemic forces and environmental exposures impact patient outcomes is critical to advancing health equity and improving population health for patients with pulmonary disease. This relationship has not yet been assessed at the population level nationally. Objectives: To determine whether neighborhood socioeconomic deprivation is independently associated with 30-day mortality and readmission for hospitalized patients with pulmonary conditions, after controlling for demographics, access to healthcare resources, and characteristics of admitting healthcare facilities. Methods: This was a retrospective, population-level cohort study of 100% of United States nationwide Medicare inpatient and outpatient claims from 2016-2019. Patients were admitted for one of four pulmonary conditions (pulmonary infections, chronic lower respiratory disease, pulmonary embolism, and pleural and interstitial lung diseases), defined by diagnosis-related group. The primary exposure was neighborhood socioeconomic deprivation, measured by the area deprivation index. The main outcomes were 30-day mortality and 30-day unplanned readmission, defined by Centers for Medicare and Medicaid Services methodologies. Generalized estimating equations were used to estimate logistic regression models for the primary outcomes, addressing clustering by hospital. A sequential adjustment strategy was first adjusted for age, legal sex, Medicare-Medicaid dual eligibility, and comorbidity burden, then adjusted for metrics of access to healthcare resources, and finally adjusted for characteristics of the admitting healthcare facility. Results: After full adjustment, patients from low socioeconomic status neighborhoods had greater 30-day mortality after admission for pulmonary embolism (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.13-1.40), respiratory infections (OR, 1.20; 95% CI, 1.16-1.25), chronic lower respiratory disease (OR, 1.31; 95% CI, 1.22-1.41), and interstitial lung disease (OR, 1.15; 95% CI, 1.04-1.27) when compared to patients from the highest SES neighborhoods. Low neighborhood socioeconomic status was also associated with 30-day readmission for all groups except the interstitial lung disease group. Conclusions: Neighborhood socioeconomic deprivation may be a key factor driving poor health outcomes for patients with pulmonary diseases.


Self-Preferred Route of Delivery of Thai Obstetricians and Gynecologists.
The attitude of Obstetricians and Gynecologists (OB-GYNs) towards performing cesarean delivery on maternal request (CDMR) together with their preferred route of delivery for themselves or their wives is considered as important responsible factors of increasing cesarean delivery. To assess the attitudes of Thai Obstetricians and Gynecologists with regard to their self-preferred route of delivery, willingness to perform cesarean delivery on maternal request, and associated factors. From July 1, 2013 to September 30, 2013, a cross-sectional study was carried out of 1,950 members of The Royal Thai College of Obstetricians and Gynaecologists who were randomized before being sent mailed questionnaires. The questionnaires requested details of the OB-GYNs' demographic data and asked about their self-preferred route of delivery for themselves or their wives (in the case of male doctors) and their willingness to perform cesarean delivery on maternal request (CDMR). The questionnaires were returned via mail. Three hundred and seventy OB-GYNs (18.9%) completed and returned the questionnaires via mail. In a scenario of uncomplicated singleton cephalic presentation pregnancy at term, vaginal delivery was chosen as the most preferred route of delivery (68.9%). The significant associated factors for preferred cesarean delivery were male, age < 40 years, experience in practice as OB-GYN < 10 years and prior cesarean delivery. Many (53.2%) were willing to perform cesarean delivery on maternal request. Most Thai Obstetricians and Gynecologists (68.9%) preferred vaginal delivery for themselves or their wives, but many (53.2%) were willing to perform cesarean delivery on maternal request.


Overall pharmacokinetics during prolonged treatment of healthy volunteers with digoxin and beta-methyldigoxin.
Five healthy volunteers received digoxin 0.4 mg or beta-methyldigoxin 0.4 mg i.v., daily for 14 days, in a randomized cross-over arrangement. By monitoring minimal plasma concentrations during multiple dosing, it was found that the steady state pharmacokinetics of digoxin and beta-methyldigoxin could be estimated even better by a one-compartment than by a two-compartment model. The following mean parameters were calculated: the half life of digoxin of 1.54 +/- 0.31 days was significantly shorter than the half life of 2.29 +/- 0.34 days for beta-methyldigoxin. The distribution volume of 807 +/- 187 liters for digoxin was not significantly larger than the 735 +/- 227 liters for beta-methyldigoxin. Renal digoxin clearance of 191 +/- 25 ml/min was significantly higher than both the renal clearance of beta-methyldigoxin of 111 +/- 23 ml/min and also the creatinine clearance, which indicates tubular secretion of digoxin. There was a 2.8-fold accumulation of beta-methyldigoxin injected once a day, which was significantly higher than the 1.80-fold accumulation of digoxin.


Early postnatal demoralisation among primiparous women in the community: measurement, prevalence and associated factors.
Demoralisation is a psychological state occurring in stressful life situations where a person feels unable to respond effectively to their circumstances, characterised by feelings of distress, subjective incompetence, helplessness and hopelessness. The period after the birth of a first baby is a time of great changes and disruptions to many aspects of the mother's physical, psychological and social functioning. This can lead to feelings of distress, a sense of incompetence and helplessness. This study aimed to examine: (1) the psychometric properties of the Demoralisation Scale in a community setting; (2) the prevalence of demoralisation symptoms among primiparous women in the community; and (3) factors that are uniquely associated with demoralisation in the early postnatal period. Primiparous women attending community maternal health centres (n = 400) were recruited and administered the study's questionnaires through a telephone interview. The Demoralisation Scale was found to be a reliable and valid tool among women in the community who had recently given birth. Higher levels of demoralisation were independently associated with lower confidence on going home from the hospital after birth, lower rating of mother's self-rated global health, more than 3 h of infant crying and fussing in the last 24 h, and a controlling partner, after symptoms of depression and anxiety, and vulnerable personality characteristics were controlled for. The relevance of demoralisation to postnatal health practitioners in the community is in helping them to better understand women's experiences and to intervene in a way that is more meaningful and less stigmatising to women.


The long-term function of the knee in patients with fibular hemimelia and anterior cruciate ligament deficiency.
Most patients (95%) with fibular hemimelia have an absent anterior cruciate ligament (ACL). The purpose of this study was to assess the long-term outcome of such patients with respect to pain and knee function. We performed a retrospective review of patients with fibular hemimelia and associated ACL deficiency previously treated at our institution. Of a possible 66 patients, 23 were sent the Musculoskeletal Outcomes Data Evaluation and Management System (MODEMS) questionnaire and Lysholm knee score to complete. In all, 11 patients completed the MODEMS and nine completed the Lysholm score questionnaire. Their mean age was 37 years (27 to 57) at review. Five patients had undergone an ipsilateral Symes amputation. There was no significant difference in any subsections of the Short-Form 36 scores of our patients compared with age-matched controls. The mean Lysholm knee score was 90.2 (82 to 100). A slight limp was reported in six patients. No patients had episodes of locking of the knee or required a supportive device for walking. Four had occasional instability with sporting activities. These results suggest that patients with fibular hemimelia and ACL deficiency can live active lives with a similar health status to age-matched controls.


SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites.
Human single-stranded DNA-binding protein 1 (hSSB1) is required for the efficient recruitment of the MRN complex to DNA double-strand breaks and is essential for the maintenance of genome integrity. However, the mechanism by which hSSB1 recruits NBS1 remains elusive. Here, we determined that hSSB1 undergoes SUMOylation at both K79 and K94 under normal conditions and that this modification is dramatically enhanced in response to DNA damage. SUMOylation of hSSB1, which is specifically fine-tuned by PIAS2α, and SENP2, not only stabilizes the protein but also enhances the recruitment of NBS1 to DNA damage sites. Cells with defective hSSB1 SUMOylation are sensitive to ionizing radiation, and global inhibition of SUMOylation by either knocking out UBC9 or adding SUMOylation inhibitors significantly enhances the sensitivity of cancer cells to etoposide. Our findings reveal that SUMOylation, as a novel posttranslational modification of hSSB1, is critical for the functions of this protein, indicating that the use of SUMOylation inhibitors (e.g., 2-D08 and ML-792) may be a new strategy that would benefit cancer patients being treated with chemo- or radiotherapy.


FDG-PET/CT imaging during the Covid-19 emergency: a southern Italian perspective.
To assess the impact of the Covid-19 pandemic on FDG-PET/CT work volume and to evaluate the occurrence of abnormal imaging findings suspicious or potentially diagnostic for interstitial pneumonia by Covid-19 infection in south Italy. We retrospectively reviewed the number and the findings of FDG-PET/CT studies acquired between February and April 2020 during the Covid-19 pandemic at the University of Napoli Federico II. The number and the findings of FDG-PET/CT studies acquired in the corresponding period of 2019 were also assessed for direct comparison. The number of FDG-PET/CT studies performed during the pandemic (n = 299) and in the corresponding period of 2019 (n = 335) were comparable. The percentage of abnormal FDG-PET/CT findings, suspicious for interstitial pneumonia by Covid-19 infection, was significantly higher during the pandemic (9%) compared with that found in the corresponding period of 2019 (4%) (χ2 5.45, P = 0.02). No significant differences were observed in the distribution of Covid-19 reporting and data system (CO-RADS) classification and in the maximum standardized uptake value between the pandemic (2.6 ± 2.2) and the corresponding period of 2019 (3.2 ± 1.4). Of note, patients with abnormal imaging findings during the pandemic time had clinical data and/or laboratory tests negative for Covid-19 infection. Despite the restrictive medical measures for the emergency, the number of FDG-PET/CT studies was unchanged during the pandemic compared with the previous year. Our findings also indicate that Covid-19 infection was contained in our series of patients from southern Italy.


Comparison of procedures to determine protein content of developing bean seeds (Phaseolus vulgaris).
Micro-Kjeldahl, Lowry and Bradford procedures were compared for determining the protein content of Phaseolus vulgaris seeds during their development. Micro-Kjeldahl and biuret techniques were also compared with mature seeds of a normal and a genetically-improved bean cultivar. The protein contents of casein and soy protein isolate were as well estimated by these four methods. For many samples of both bean and food protein products large disagreements were found between micro-Kjeldahl and the other three procedures.


[Juvenile dermatomyositis].
Juvenile dermatomyositis (JDM) is a chronic multisystem inflammatory disease that primarily involves skin and muscles. The clinical picture is mainly characterized by the typical cutaneous rash and by skeletal muscle weakness. Nevertheless the vasculitic process may extend in some cases to other organs such as lung, joints or gastrointestinal system. Calcinosis represents a relatively frequent complication of JDM and occurs in most cases during the late stage of the disease. Usually serum levels of muscle enzymes are elevated and electromyography shows signs of myositis. Muscle biopsy is generally performed only in doubtful cases. JDM should be differentiated from the muscle involvement of other diffuse inflammatory connective tissue diseases and from non inflammatory myopathies. The treatment is mainly based on steroids, whose dosage and regimen depend on disease severity. Steroid therapy has greatly improved the prognosis of JDM.


The relationship between long-term blood pressure variability and cortical thickness in older adults.
High blood pressure variability (BPV) is a risk factor for cognitive decline and dementia, but its association with cortical thickness is not well understood. Here we use a topographical approach, to assess links between long-term BPV and cortical thickness in 478 (54% men at baseline) community dwelling older adults (70-88 years) from the ASPirin in Reducing Events in the Elderly NEURO sub-study. BPV was measured as average real variability, based on annual visits across three years. Higher diastolic BPV was significantly associated with reduced cortical thickness in multiple areas, including temporal (banks of the superior temporal sulcus), parietal (supramarginal gyrus, post-central gyrus), and posterior frontal areas (pre-central gyrus, caudal middle frontal gyrus), while controlling for mean BP. Higher diastolic BPV was associated with faster progression of cortical thinning across the three years. Diastolic BPV is an important predictor of cortical thickness, and trajectory of cortical thickness, independent of mean blood pressure. This finding suggests an important biological link in the relationship between BPV and cognitive decline in older age.


Trans-kingdom conjugation in vitro by using toluenized cells.
To establish in vitro trans-kingdom conjugation, we developed a novel direct cell PCR by using toluenized cells which permeate enzymes, primers and substrates. The cells was shown to be successful recipients in conjugation.


Cancer-associated fibroblasts promote malignancy of gastric cancer cells via Nodal signalling.
The roles of cancer-associated fibroblasts (CAFs) in progression of gastric cancer (GC) are far from well illustration. Here, we show that CAFs can trigger the proliferation and decrease the doxorubicin (Dox) sensitivity of GC cells via secretion of Nodal, one embryonic morphogen that can promote malignancy of various cancers. The neutralization antibody of Nodal can attenuate CAFs-induced cell proliferation. Further, CAFs can activate the Smad2/3 signal, which further increase the phosphorylation and nuclear localization of Akt, in GC cells. While anti-Nodal can abolish the CAFs-induced activation of Smad2/3/Akt signals. Further, both inhibitors of Smad2/3 and Akt can attenuate CAFs-induced proliferation of GC cells. All these data suggest that CAFs can increase the malignancy of GC cells via Nodal-induced activation of Smad2/3/Akt signals. It indicates that CAFs/Nodal signals might be a potential new target of clinical interventions for GC patients. SIGNIFICANCE OF THE STUDY: The roles about CAFs in progression of GC are not well illustrated. Our present study reveals that CAFs can increase the proliferation and decrease the Dox sensitivity of GC cells via secretion of Nodal. The secreted Nodal further activated Samd2/3/Akt signals to trigger the GC progression. It suggests that targeted inhibition CAFs/Nodal might be a potential approach for GC therapy.


Cell free expression put on the spot: advances in repeatable protein arraying from DNA (DAPA).
We have previously described the 'DNA array to protein array' (DAPA) method for microarraying of proteins expressed by cell-free systems in situ on the array surface. In this technique, a DNA array on one slide acts as the template for generating a protein array on a second slide, mediated by a cell free lysate between the two juxtaposed slides. Here we explore the feature of the repeatability of the technology, in which the same DNA array is reused several times, and use the method to generate a microarray of 116 diverse proteins. The capabilities of DAPA technology in comparison with other protein array methods are discussed.


Isoprenylation modification is required for HIPP1-mediated powdery mildew resistance in wheat.
Powdery mildew (Pm), caused by Blumeria graminis f.sp. tritici (Bgt), is one of the most important wheat diseases. Heavy-metal-associated isoprenylated plant protein (HIPP1) has been proved playing important roles in response to biotic and a biotic stress. In present study, we proved HIPP1-V from Haynalidia villosa is a positive regulator in Pm resistance. HIPP1-V was rapidly induced by Bgt. Transiently or stably heterologous overexpressing HIPP1-V in wheat suppressed the haustorium formation and enhanced Pm resistance. HIPP1-V isoprenylation was critical for plasma membrane (PM) localization, interaction with E3-ligase CMPG1-V and function in Pm resistance. Bgt infection recruited the isoprenylated HIPP1-V and CMPG1s on PM; blocking the HIPP1 isoprenylation reduced such recruitment and compromised the resistance of OE-CMPG1-V and OE-HIPP1-V. Overexpressing HIPP1-VC148G could not enhance Pm resistance. These indicated the Pm resistance was dependent on HIPP1-V's isoprenylation. DGEs related to the ROS and SA pathways were remarkably enriched in OE-HIPP1-V, revealing their involvement in Pm resistance. Our results provide evidence on the important role of protein isoprenylation in plant defense.


Routine antepartum human immunodeficiency virus infection screening in an inner-city population.
Human immunodeficiency virus (HIV) infection occurs disproportionately among inner-city minority women of reproductive age. Once pregnant, these women have a high risk of delivering infants with perinatally acquired infection. Identification and counseling of HIV-infected parturients may be an effective means of preventing perinatal HIV infection. Few data are available on the seroprevalence of HIV infection in the inner-city population or on the clinical and demographic determinants of risk. To better characterize HIV infection in inner-city parturients in Atlanta, we conducted routine antepartum screening for HIV antibody in 3472 women. Ten (2.8 per 1000) were seropositive on enzyme-linked immunosorbent assay (ELISA) and Western blot testing. Four women were seropositive on repeat ELISA but negative on Western blot. Four infected women had had heterosexual contact with a person at risk for HIV, three were intravenous drug users, one had possibly become infected via blood transfusion, and two had no apparent risk factors. Seven of the seropositive women had no self-identified risk factors and would not have been identified if screening had been performed using current Centers for Disease Control criteria. Ten percent of the women screened had self-identified risk factors for HIV infection and were seronegative. Ninety-six percent of women consented to HIV testing. These data suggest that inner-city parturients in Atlanta are at risk for HIV infection and that routine antepartum HIV screening can be performed provided the appropriate multidisciplinary team is in place for counseling and follow-up.


[Surgical treatment of carcinoma of the oesophagus (author's transl)].
Cervical oesolphagogastrostomy (Kirschner's operation) was performed on 16 patients with carcinoma of the oesophagus. There were five hospital deaths (two due to myocardial infarction). The average hospital stay of the survivals was 22 days. This operation is preferred to colon interpolation because it requires only one anastomosis, which is extrathoracic.


Idiopathic condylar resorption: A systematic review of etiology and management.
The aim of this study was to evaluate the level of evidence in the literature on etiology and management of idiopathic condylar resorption (ICR) of the mandible. A systematic search of articles published from 1982 to 2019 was conducted via PubMed, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. English language reports of human studies that addressed the etiology or management of ICR were included. Case reports, opinion or perspective articles, and nonhuman or non-English language articles were excluded. The quality of the included studies was assessed by using the Oxford Center for Evidence-Based Medicine criteria. The search yielded 230 studies, and 40 met the criteria for inclusion. The etiology of ICR was the focus of 33 studies; the remaining 8 assessed its management. The total number of patients in the included studies was 1399. The level of evidence assessing the etiology of ICR averaged 3.16 (range 2b-to 3b). Proposed etiologies and contributing factors included female gender, 17β-estradiol levels, condylar anatomy, and history of orthognathic surgery. The level of evidence of studies assessing the management of ICR was 3.7 (range 2b-4). Treatment strategies included disk repositioning, autologous condylar reconstruction (costochondral graft), and alloplastic total joint reconstruction. Average follow-up was 46.8 ± 38.2 months. The proposed etiology and management of ICR, as reported in the literature, vary considerably. Condylectomy with autogenous or alloplastic reconstruction appears to be the most stable management strategy. The levels of evidence regarding the etiology and management of ICR are low.


Bilinguals Show Proportionally Greater Benefit From Visual Speech Cues and Sentence Context in Their Second Compared to Their First Language.
Speech perception in noise is challenging, but evidence suggests that it may be facilitated by visual speech cues (e.g., lip movements) and supportive sentence context in native speakers. Comparatively few studies have investigated speech perception in noise in bilinguals, and little is known about the impact of visual speech cues and supportive sentence context in a first language compared to a second language within the same individual. The current study addresses this gap by directly investigating the extent to which bilinguals benefit from visual speech cues and supportive sentence context under similarly noisy conditions in their first and second language. Thirty young adult English-French/French-English bilinguals were recruited from the undergraduate psychology program at Concordia University and from the Montreal community. They completed a speech perception in noise task during which they were presented with video-recorded sentences and instructed to repeat the last word of each sentence out loud. Sentences were presented in three different modalities: visual-only, auditory-only, and audiovisual. Additionally, sentences had one of two levels of context: moderate (e.g., "In the woods, the hiker saw a bear.") and low (e.g., "I had not thought about that bear."). Each participant completed this task in both their first and second language; crucially, the level of background noise was calibrated individually for each participant and was the same throughout the first language and second language (L2) portions of the experimental task. Overall, speech perception in noise was more accurate in bilinguals' first language compared to the second. However, participants benefited from visual speech cues and supportive sentence context to a proportionally greater extent in their second language compared to their first. At the individual level, performance during the speech perception in noise task was related to aspects of bilinguals' experience in their second language (i.e., age of acquisition, relative balance between the first and the second language). Bilinguals benefit from visual speech cues and sentence context in their second language during speech in noise and do so to a greater extent than in their first language given the same level of background noise. Together, this indicates that L2 speech perception can be conceptualized within an inverse effectiveness hypothesis framework with a complex interplay of sensory factors (i.e., the quality of the auditory speech signal and visual speech cues) and linguistic factors (i.e., presence or absence of supportive context and L2 experience of the listener).


Enzyme-assisted extraction of lipids directly from the culture of the oleaginous yeast Rhodosporidium toruloides.
Lipids produced by oleaginous microorganisms are a potential feedstock for biodiesel production and chemical synthesis. Yet, the costs of microbial lipids remain high, partially because the lipid recovery process is tedious and costly. In the present study, enzyme-assisted extraction of lipids from the culture of the yeast Rhodosporidium toruloides was carried out. With a heat pre-treatment with microwave, enzymatic treatment with the recombinant β-1,3-glucomannanase, plMAN5C, and extraction with ethyl acetate, 96.6% of the total lipids were extracted from R. toruloides cells at room temperature and atmospheric pressure directly from the culture without dewatering. Therefore, this process could significantly reduce energy consumption and costs for lipids extraction from the yeast.


Ultrastructural demonstration of dehydrogenases in rat cerebral cortex.
Techniques for the ultrastructural demonstration of dehydrogenases in cerebral cortex are described. The best fixation for good fine structural preservation and retention of LDH and NADH-diphorase was obtained by perfusion with a misture of formaldehyde and glutaraldehyde and for SDH by perfusion with formaldehyde. Comparison of incubation conditions showed that consistent results were obtained using enzyme markers NBT and DS-NBT for LDH and NADH-diaphorase: DS-NBT was more satisfactory than NBT and BSPT for SDH. Penetration of incubation media was improved by Triton X-100: DMSO and ultrasonic treatment were less effective. The techniques enabled the first electron cytochemical demonstration of dehydrogenases in different elements of prefixed cerebral cortex. Ultrastructural sites of enzyme activities were localized within cristae and inter-membrane spaces of mitochondria in nerve cell cytoplasm and its processes, oligodendrocytes and astrocytes. Authenticity of the ultrastructural sites was confirmed by four different control experiments.


Men's migration and women's mortality in rural Mozambique.
Labor migration is widespread and growing across the world. As migration grows, the economic outcomes of migration increasingly diversify, and so do its consequences for the well-being and health of both migrants and non-migrating household members. A considerable body of scholarship has examined the effects of migration on the physical and mental health of 'left-behind' household members. The impact of migration on mortality, particularly of non-migrating marital partners, is less well understood. Addressing this gap, we use data from a longitudinal survey of married women conducted over twelve years in rural Mozambique to examine the association between men's labor out-migration and their non-migrating wives' mortality. The analyses detect no significant differences when comparing non-migrants' wives to migrants' wives in the aggregate but point to instructive variation among migrants' wives according to the economic success of migration, as measured by the effects of migration on the household's material well-being. Specifically, women married to less successful migrants had higher mortality risks over the project span than women married to more successful migrants, regardless of other individual and household-level factors. Importantly for this setting with high HIV prevalence, the advantage of wives of more successful migrants is significant for HIV/AIDS-unrelated deaths but not for HIV/AIDS-related deaths. We situate these findings within the cross-national scholarship on migration and health.


Lung surfactant dysfunction in tuberculosis: effect of mycobacterial tubercular lipids on dipalmitoylphosphatidylcholine surface activity.
In pulmonary tuberculosis, Mycobacterium tuberculosis bacteria reside in the alveoli and are in close proximity with the alveolar surfactant. Mycolic acid in its free form and as cord factor, constitute the major lipids of the mycobacterial cell wall. They can detach from the bacteria easily and are known to be moderately surface active. We hypothesize that these surface-active mycobacterial cell wall lipids could interact with the pulmonary surfactant and result in lung surfactant dysfunction. In this study, the major phospholipid of the lung surfactant, dipalmitoylphosphatidylcholine (DPPC) and binary mixtures of DPPC:phosphatidylglycerol (PG) in 9:1 and 7:3 ratios were modelled as lung surfactant monolayers and the inhibitory potential of mycolic acid and cord factor on the surface activity of DPPC and DPPC:PG mixtures was evaluated using Langmuir monolayers. The mycobacterial lipids caused common profile changes in all the isotherms: increase in minimum surface tension, compressibility and percentage area change required for change in surface tension from 30 to 10 mN/m. Higher minimum surface tension values were achieved in the presence of mycolic acid (18.2+/-0.7 mN/m) and cord factor (13.28+/-1.2 mN/m) as compared to 0 mN/m, achieved by pure DPPC film. Similarly higher values of compressibility (0.375+/-0.005 m/mN for mycolic acid:DPPC and 0.197+/-0.003 m/mN for cord factor:DPPC monolayers) were obtained in presence of mycolic acid and cord factor. Thus, mycolic acid and cord factor were said to be inhibitory towards lung surfactant phospholipids. Higher surface tension and compressibility values in presence of tubercular lipids are suggestive of an unstable and fluid surfactant film, which will fail to achieve low surface tensions and can contribute to alveolar collapse in patients suffering from pulmonary tuberculosis. In conclusion a biophysical inhibition of lung surfactant may play a role in the pathogenesis of tuberculosis and may serve as a target for the development of new drug loaded surfactants for this condition.


Afferent innervation of extraocular muscles in the rat studied by retrograde and anterograde horseradish peroxidase transport.
After injection of horseradish peroxidase (HRP) into extraocular muscles of rat perikarya were labeled mainly along the medial edge of the ophthalmic subdivision of the trigeminal ganglion but not in the mesencephalic nucleus of the trigeminal nerve. Injections of HRP into the trigeminal ganglion labeled simple as well as branching and meandering free fiber endings in extraocular muscles. No evidence for muscle spindles was found, but the meandering endings may be considered as candidates for stretch receptors.


Epidemiology of Limb Amputations and Prosthetic Use During COVID-19 Pandemic in the Netherlands.
To evaluate the trends in the incidence of major limb amputations and the prevalence of Dutch prosthetic users at the national level in The Netherlands between 2012 and 2021 (during the COVID-19 pandemic). Local hospitals in The Netherlands reported a doubling of major lower limb amputations during COVID-19, information about a change in the incidence of major upper limb amputations was not reported. We could not confirm this remarkable increase in major lower limb amputations in our institution, nor did we observe a change in the incidence of major upper limb amputations. We hypothesize that the COVID-19 pandemic had no effect on the number of major limb amputations. Observational retrospective study analyzing national open-access databases of health insurance claims. The Dutch national opensource database www.opendisdata.nl was used to retrieve the incidence of limb amputations in the period 2012-2021, stratified by the level of amputation and the cause of amputation. The results were verified using the www.gipdatabank.nl databank. This period included 4 intervals of nationwide COVID-19 lockdowns. 60,848 patients who underwent limb amputations at the upper or lower extremity in the Netherlands from 2012 to 2021 (N=60,848) were included in this study. Not applicable. Upper- and lower-limb amputation and prosthetic use. Data were retrieved for a total of 60,848 patients in the Netherlands, who underwent 68,180 amputations of the upper and lower extremities at any level from 2012 to 2021, including 22,095 major amputations of the lower extremities. The ongoing trend of stable numbers of major lower-limb amputations from 2012 to 2019 continued in 2020 and 2021. The verification of these data at the level of prosthetic users confirmed that the annual trends were unchanged. The reported increased numbers of major lower-limb amputations during the COVID-19 pandemic in the Netherlands could not be confirmed using nationwide epidemiologic data.


Psychometric properties of Korean Infant Sensory Profile 2.
This study aimed to evaluate test-retest reliability and convergent validity of the Korean Infant Sensory Profile 2 (K-ISP2) and explore whether the sensory processing of infants differs according to age, gender, and culture. Participants were 140 Korean caregivers of infants aged 0-6 months. They completed the K-ISP2 and the Korean version of 'What My Baby Is Like' (K-WBL), a scale for measuring infant temperament, for convergent validity. The K-ISP2 was re-administrated for test-retest reliability with a mean interval of 16 days. The K-ISP2 showed good test-retest reliability (ICC = .84) and significant but weak convergent validity with the K-WBL (amenability/persistence, r = -.28, p < .001; adaptability, r = -.30, p < .001; reactivity, r = .24, p = .004; activity, r = .20, p = .02). There were no significant age and gender differences in the K-ISP2 total score. The K-ISP2 total score was similar to that of the Infant Sensory Profile 2 (ISP2). This study provides reliability and validity evidence of the K-ISP2. Normative data of K-ISP2 total score can be established regardless of age or gender. The ISP2 has showed similar psychometric properties for populations of both Korea and the United States.KEY MESSAGESSensory processing is a fundamental component for adaptive responses to environment and begins to develop before birth.The Korean Infant Sensory Profile 2 (K-ISP2) can be used to assess sensory processing patterns of Korean infants, with evidence of reliability and validity.Total scores of the K-ISP2 can be interpreted with one normative data set regardless of age and gender.


Housing as a determinant of health equity: A conceptual model.
Housing is a major pathway through which health disparities emerge and are sustained over time. However, no existing unified conceptual model has comprehensively elucidated the relationship between housing and health equity with attention to the full range of harmful exposures, their cumulative burden and their historical production. We synthesized literature from a diverse array of disciplines to explore the varied aspects of the relationship between housing and health and developed an original conceptual model highlighting these complexities. This holistic conceptual model of the impact of housing on health disparities illustrates how structural inequalities shape unequal distribution of access to health-promoting housing factors, which span four pillars: 1) cost (housing affordability); 2) conditions (housing quality); 3) consistency (residential stability); and 4) context (neighborhood opportunity). We further demonstrate that these four pillars can lead to cumulative burden by interacting with one another and with other structurally-rooted inequalities to produce and reify health disparities. We conclude by offering a comprehensive vision for healthy housing that situates housing's impact on health through a historical and social justice lens, which can help to better design policies and interventions that use housing to promote health equity.


Action of fenfluramine, phenylpropanolamine, phentermine and diethylpropion on acoustic startle in rats.
Four commonly used anorectics which are amphetamine analogues were tested for their action on responsiveness in an acoustic startle test when rats were given daily IP injections adequate to produce a change in body weight. Drugs were given for 22 days. None of these drugs increased startle responsiveness as does the amphetamine parent compound. Instead, fenfluramine and phenylpropanolamine decreased startle responsiveness and phentermine and diethylpropion produced no change. There was no relationship between drug action and body weight. Partial tolerance was found for the fenfluramine action on startle and complete tolerance was found for its action on body weight gain. The fenfluramine action is compatible with the extensive literature on humans and animals indicating sedative properties.


[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].
The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process.


Solid and papillary neoplasms of the pancreas.
Solid and papillary neoplasms of the pancreas are rare, low-grade malignant tumors histologically distinct from usual ductal adenocarcinomas and islet cell tumors and amendable to cure by surgical excision. Because these lesions have been incorrectly diagnosed in the past as adenocarcinomas or cystadenocarcinomas, they may have contributed to reports with confusing survival statistics following resections for malignant neoplasms of the pancreas. In young women with large, relatively asymptomatic tumors of the pancreas, solid and papillary neoplasms should be high on the list of the differential diagnoses.


The use of mid-level providers in dermatology: a liability risk?
The use of mid-level providers, nurse practitioners, and physician assistants is growing in the practice of dermatology, fueled by a perceived shortage of dermatologists and the promise of practice enhancement. Exactly how the physician extender is used in the dermatology practice can either increase or decrease the risk of malpractice liability and ultimately may be a factor in whether the dermatologist prevails in a malpractice case. Although dermatologists can delegate care to physician extenders, they cannot delegate the liability risk. It is up to the dermatologist to embrace those principles and practices that enhance patient care, decrease medical errors, and improve physician/practice patient relationships to ultimately decrease the risk of malpractice liability.


Revisiting agency and medical health technology: actor network theory and breast cancer survivors' perspectives on an adherence tool.
Optimal treatment adherence is critical in the management of breast cancer patients/survivors taking hormonal therapy. However, lack of adherence is common. Many technologies have been developed to encourage medication intake, such as reminders on phones or digital pills, with varying degrees of success. To explore the role of technology in medical adherence requires a framework that considers all complexities of technology, from software to the end user's beliefs. Actor Network Theory (ANT) defines technology based on its technical, social, and abstract components. We conducted three focus groups, which we analyzed using a thematic analysis to determine topics in breast cancer survivors' discussions of these technologies. We also conducted a deductive content analysis using ANT concepts as codes. In discussing the use of technology to improve medical adherence, participants had an empowering view of technology (48.8%) a neutral one (41.5%) or a disempowering view (9.8%). When it comes to their medication adherence, breast cancer survivors taking hormonal therapy perceived technology as something on which they could assert agency while their own agency dictated their adherence behaviors. In line with a non-technologically deterministic view of medical technologies, this finding shows that technology can be both constraining and enabling, depending on the specific context of human use. This networked understanding of technology in terms of social dynamics has relevant implications in designing interventions that use technology to improve adherence.


Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat.
Dose-response curves for the elevation of homovanillic acid levels in corpus striatum and olfactory tubercle of rats were determined by mass fragmentography after treatment with antipsychotic drugs. The older of potency in both regions was: haloperidol greater than chlorpromazine greater than thioridazine and clozapine. The relative elevation of the content of homovanillic acid was significantly greater in the striatum than in the olfactory tubercle for all drugs except thioridazine. The antipsychotic effect of the drugs tested may be related to the interference with dopaminergic mechanisms in striatal and/or limbic areas.


Nitric oxide production by bone cells is fluid shear stress rate dependent.
Shear stress due to mechanical loading-induced flow of interstitial fluid through the lacuno-canalicular network is a likely signal for bone cell adaptive responses. Moreover, the rate (determined by frequency and magnitude) of mechanical loading determines the amount of bone formation. Whether the bone cells' response to fluid shear stress is rate dependent is unknown. Here we investigated whether bone cell activation by fluid shear stress is rate dependent. MC3T3-E1 osteoblastic cells were subjected for 15 min to fluid shear stress of varying frequencies and amplitudes, resulting in peak fluid shear stress rates ranging from 0 to 39.6 Pa-Hz. Nitric oxide production, a parameter for bone cell activation, was found to be linearly dependent on the fluid shear stress rate; the slope was steepest at 5 min (0.11 Pa-Hz(-1)) and decreased to 0.03 Pa-Hz(-1) at 15 min. We conclude that the fluid shear stress rate is an important parameter for bone cell activation.


Lifestyle Variables Such as Daily Internet Use, as Promising Protective Factors against Cognitive Impairment in Patients with Subjective Memory Complaints. Preliminary Results.
Subjective memory complaints (SMCs) may be important markers in the prediction of cognitive deterioration. The aim of this study was to find associations between individual lifestyle factors, which may contribute to cognitive impairment (CI) in people with SMCs and to conduct a literature review on the relationship between internet use and CI in subjects over 50 years old, as a related factor. This was a case-controlled study that included 497 subjects aged over 50 years with SMCs who were recruited from 19 community pharmacies. Three screening tests were used to detect possible CIs, and individuals with at least one test result compatible with a CI were referred to primary care for evaluation. Having self-referred SMC increased the odds of obtaining scores compatible with CI and this factor was significantly related to having feelings of depression (OR = 2.24, 95% CI [1.34, 3.90]), taking anxiolytics or antidepressants (OR = 1.93, 95% CI [1.23, 3.05]), and being female (OR = 1.83, 95% CI [1.15, 2.88]). Thirty percent of our sample obtained scores compatible with CI. Age over 70 years increased the odds of obtaining scores compatible with CI. A high-level education, reading, and daily internet use were factors associated with a reduced risk of positive scores compatible with CI (37-91%, 7-18%, and 67-86%, respectively), while one extra hour television per day increased the risk by 8-30%. Among others, modifiable lifestyle factors such as reading, and daily internet usage may slow down cognitive decline in patients over 50 with SMCs. Four longitudinal studies and one quasi-experimental study found internet use to be beneficial against CI in patients over 50 years of age.


Aflatoxin and Ochratoxin - a contamination of dried figs (Ficus carina L) from the 1988 crop.
The study examines the occurrence of aflatoxin and ochratoxin A in the !988 dried figs crop. Mycotoxin content, moisture, and aw (water activity) were analyzed in a total of 103 fig samples collected from various orchards and different stages of fig processing. Aflatoxins (B1, B2, G1, and G2) were present in 29% of the samples examined at 0.5-63.0, 0.5-37.7, 0.5-78.3, and 0.5-12.5μ/kg, respectively. Ochratoxin A was detected in only 3% of the samples at 5.2-8.3 μ/kg. The moisture (and aw) values of the fruits were found suitable for mycotoxin formation in firm ripened and shrivelled figs.


Preparation and lithium storage of core-shell honeycomb-like Co3O4@C microspheres.
Core-shell honeycomb-like Co3O4@C microspheres were synthesized via a facile solvothermal method and subsequent annealing treatment under an argon atmosphere. Owing to the core-shell honeycomb-like structure, a long cycling life was achieved (a high reversible specific capacity of 318.9 mA h g-1 was maintained at 5C after 1000 cycles). Benefiting from the coated carbon layers, excellent rate capability was realized (a reversible specific capacity as high as 332.6 mA h g-1 was still retained at 10C). The design of core-shell honeycomb-like microspheres provides a new idea for the development of anode materials for high-performance lithium-ion batteries.


Effect of caloric restriction and AMPK activation on hepatic nuclear receptor, biotransformation enzyme, and transporter expression in lean and obese mice.
Fatty liver alters liver transporter expression. Caloric restriction (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1 deacetylase activity in liver. This study evaluated whether CR and CR mimetics reversed obesity-induced transporter expression in liver and hepatocytes. mRNA and protein expression was determined in adult lean (lean) and leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase activators, and gene expression was determined. CR decreased Oatp1a1, Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased Abcc2 mRNA OB livers, whereas protein expression increased in both genotypes. CR increased Abcc3 protein expression increased in OB livers. CR did not alter Abcc1, 4 and 5 mRNA expression in lean mice but decreased expression in livers of OB mice. CR increased Abcc4 protein in lean, but not OB mice. CR restriction reversed the expression of some, but not all transporters in livers of OB mice. Overall, these data indicate a potential for CR to restore some hepatic transporter changes in OB mice, but suggest a functional leptin axis is needed for reversal of expression for some transporters.


Inflammatory Pseudotumor of the Mesentery.
Teaching point: An inflammatory pseudotumor can occur almost everywhere in the body and has nonspecific imaging findings.


Magnetic resonance imaging is safe in patients with left bundle branch pacing.
The use of left bundle branch pacing (LBBP) has dramatically increased since it was first described in 2016, but to date there are no published data on the safety of performing magnetic resonance imaging (MRI) in these patients. Patients with LBBP who underwent MRI between January 2016 and October 2022 were retrospectively studied in our clinical center, which has a special program for imaging patients with cardiac devices. All patients underwent close cardiac monitoring throughout the MRI scans. Occurrence of arrhythmias or other adverse effects during MRI were assessed. LBBP lead parameters immediately pre- and post-MRI and at an outpatient follow-up were compared. Fifteen patients with LBBP underwent a total of 19 MRI sessions during the study period. Lead parameters did not significantly change after the MRI or on follow-up, which took place at a median of 91 days after the MRI. No patient developed arrhythmias during the MRI sessions, and no adverse effects such as lead dislodgement were reported. Although larger studies are necessary to verify our findings, MRI in patients with LBBP appears safe based on this initial case series.


OXA-48-like carbapenemases producing Enterobacteriaceae in different niches.
The emergence of carbapenem-resistant enterobacterial species poses a serious threat to public health worldwide. OXA-48-type carbapenem-hydrolyzing class D β-lactamases are widely distributed among Enterobacteriaceae, with significant geographical differences. To date, 11 OXA-48-like variants have been identified, with classical OXA-48 being the most widespread. These enzymes show high-level hydrolytic activity against penicillins and low-level hydrolysis towards carbapenems. Since the first description of the OXA-48 carbapenemase in Turkey, bacterial strains producing the enzyme have been extensively reported in nosocomial and community outbreaks in many parts of the word, particularly in the Mediterranean area and European countries. The rapid spread of Enterobacteriaceae producing OXA-48-like enzymes in different ecosystems has become a serious issue recently. The number of reservoirs for such organisms is increasing, not only in hospitals, but also in the community, among animals (e.g., livestock, companion animals, and wildlife) and in the environment. This review aims to summarize the main characteristics of the OXA-48-type carbapenemases, covering genetic and enzymatic traits, their epidemiology, clonality and associated genes, correlation with extended-spectrum β-lactamases (ESBLs) or plasmidic AmpC (pAmpC) in different bacterial species worldwide.


Free-radical chain oxidation of rat red blood cells by molecular oxygen and its inhibition by alpha-tocopherol.
The oxidation of rat red blood cells (RBC) by molecular oxygen was performed in an aqueous suspension with an azo compound as a free-radical initiator. The RBC were oxidized at a constant rate by a free-radical chain mechanism, resulting in hemolysis. The extent of hemolysis was proportional to the concentration of free radical. alpha-Tocopherol in RBC membranes suppressed the oxidation and hemolysis to produce an induction period. Tocopherol was constantly consumed during the induction period, and hemolysis developed when tocopherol concentrations fell below a critically low level. Among the membrane lipids, phosphatidylethanolamine, phosphatidylserine, and arachidonic acids were predominantly oxidized in the absence of tocopherol. In the presence of tocopherol, however, such lipid changes were suppressed during a 120-min incubation even when hemolysis started. Membrane proteins as well as lipids were oxidized. The formation of proteins with high molecular weight and concomitant decrease of the low-molecular-weight proteins were observed on gel electrophoresis with the onset of hemolysis. This study clearly showed the damage of RBC membranes caused by oxygen radical attack from outside of the membranes, and suggested that membrane tocopherol even below a critically low level could suppress lipid oxidation but that it could not prevent protein oxidation and hemolysis.


Inpatient fall prevention from the patient's perspective: A qualitative study.
The aim of this study was to describe the patient's perspective of fall prevention in an acute care setting to aid in the design of patient centered strategies. Falls are one of the most common adverse events in hospitals and can lead to preventable patient harm, increased length of stay, and increased healthcare costs. There is a need to understand fall risk and prevention from the patients' perspectives; however, research in this area is limited. To understand the patient perspective, semi-structured interviews were conducted with twelve patients at an academic healthcare center. Qualitative analysis revealed three major themes: (1) how I see myself, (2) how I see the interventions; and (3) how I see us. The theme "How I see myself" describes patients' beliefs of their own fall risk and includes the sub-themes of awareness, acceptance/rejection, implications, emotions, and personal plan. Interventions, such as fall alarms, are illustrated in the theme "How I see the interventions" and includes the subthemes what I see and hear and usefulness of equipment. Finally, "How I see us" describes barriers to participating in the fall prevention plan. Most fall prevention programs favor clinician-led plan development and implementation. Patient fall assessments needs to shift from being clinician-centric to patient-centric. Nurses must develop relationships with patients to facilitate understanding of their needs. Developing these truly patient-centered programs may reduce the over-reliance on bed alarms and allow for implementation of strategies aimed to mitigate modifiable risk factors leading to falls.