Digestibility of dinosaur food plants revisited and expanded: Previous data, new taxa, microbe donors, foliage maturity, and seasonality.
Although the living relatives of the Mesozoic flora were once assumed to constitute a nutritionally poor diet for dinosaur herbivores, in vitro fermentation of their foliage has shown that gymnosperms, ferns, and fern relatives can be as highly digestible as angiosperm grasses and dicots. Because nutritional information cannot be preserved in the fossil record, this laboratory approach, first published in 2008, provides a novel alternative to evaluate the digestive quality of the plants that were available to dinosaur megaherbivores such as sauropods. However, very few further studies have since been conducted to supplement and confirm the high fermentative capacity of nonangiospermous taxa. Here we show that the living relatives of the Araucariaceae and Equistaceae are consistently highly digestible, even between taxa and when influenced by environmental and biological factors, while fern taxa are inconsistent on the family level. These results reinforce previous findings about the high energetic potential of Jurassic-age plant families. Fourteen species of fern and gymnosperm foliage from five Jurassic families were collected in the spring and fall, then analyzed for their digestibility using the in vitro Hohenheim gas test. Equisetum, Araucaria, and Angiopteris were the most digestible genera in both seasons, while Agathis, Wollemia, and Marattia were the least digestible. The season in which specimens were collected was found to have to a significant effect on gas production in four out of 16 samples (P < 0.05). Furthermore, leaf maturity influences digestibility in Marattia attenuata (P < 0.05), yet not in Cyathea cooperi (P = 0.24). Finally, the species of the rumen fluid donor did not influence digestibility (P = 0.74). With the original data set supplemented by one new genus and four species, this study confirms and expands previous results about the nutritional capacity of the living relatives of the Jurassic flora.


Risk analysis of analytical validations by probabilistic modification of FMEA.
Risk analysis is a valuable addition to validation of an analytical chemistry process, enabling not only detecting technical risks, but also risks related to human failures. Failure Mode and Effect Analysis (FMEA) can be applied, using a categorical risk scoring of the occurrence, detection and severity of failure modes, and calculating the Risk Priority Number (RPN) to select failure modes for correction. We propose a probabilistic modification of FMEA, replacing the categorical scoring of occurrence and detection by their estimated relative frequency and maintaining the categorical scoring of severity. In an example, the results of traditional FMEA of a Near Infrared (NIR) analytical procedure used for the screening of suspected counterfeited tablets are re-interpretated by this probabilistic modification of FMEA. Using this probabilistic modification of FMEA, the frequency of occurrence of undetected failure mode(s) can be estimated quantitatively, for each individual failure mode, for a set of failure modes, and the full analytical procedure.


Accuracy of endoscopic ultrasonography and magnetic resonance cholangiopancreatography for the diagnosis of chronic pancreatitis: a prospective comparison study.
The diagnosis of chronic pancreatitis (CP) remains challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) have been proposed as highly accurate diagnostic modalities. Although endoscopic retrograde cholangiopancreatography (ERCP) has been previously used as a gold standard, it is associated with a small but significant risk. We aim to compare the accuracy of EUS and MRCP with the composite gold standard using ERCP, surgical pathology, and/or long-term clinical follow-up. Ninety-nine patients with clinical signs and/or symptoms suggestive of CP were prospectively enrolled. The diagnosis of CP by MRCP was established when one or more of these features were present: main duct dilation without obstruction, dilated side branches, intraductal stones, ductal irregularity, reduced T1-signal intensity, parenchymal atrophy, and reduced secretory response to secretin administration. The diagnosis of CP by EUS was made when 4 or more of the established criteria were present. Accuracy of all criteria used ("EUS only," "MRCP only," "either EUS or MRCP," and "both EUS and MRCP") was compared with the composite gold standard. Forty patients were diagnosed with CP by the composite gold standard whereas the remaining 59 patients were controls. EUS only seemed more sensitive but equally specific compared with MRCP only to diagnose CP. The combination of EUS and MRCP had a sensitivity of 98% for either EUS or MRCP and a specificity of 100% for both EUS and MRCP. EUS and MRCP are highly accurate modalities for the diagnosis of CP and are complementary when used together. If confirmed in larger series, the diagnosis of CP by both EUS and MRCP is highly predictive and ERCP is unlikely to add any useful information.


Lipid Profile and Subsequent Cardiovascular Disease among Young Adults Aged < 50 Years.
Epidemiological evidence on the relationship between lipid profile and cardiovascular disease (CVD) events in young adults remains insufficient. Thus, we sought to explore the association of lipid profile with subsequent CVD among young adults. Medical records of 1,451,997 young adults (20 to 49 years old) without prior history of CVD and not taking lipid lowering medications were extracted from the Japan Medical Data Center, a nationwide epidemiological database. We conducted multivariable Cox regression analyses to identify the association between lipid profile and the subsequent risk of CVD and used multiple imputation for missing data on body mass index, waist circumference, hypertension, diabetes mellitus, and cigarette smoking in our database. The mean age was 39.0 ± 7.4 years, and 58.5% were men. After a mean follow-up of 1,148 ± 893 days, myocardial infarction, angina pectoris, stroke, and heart failure developed in 1,638 (0.1%), 15,887 (1.1%), 5,593 (0.4%), and 14,351 (1.0%) subjects, respectively. Multivariable Cox regression analyses including covariates after multiple imputation for missing values demonstrated that LDL-C ≥ 140 mg/dL, HDL-C < 40 mg/dL, and triglycerides ≥ 150 mg/dL were independently associated with the incidence of myocardial infarction, angina pectoris, and heart failure. However, they were not associated with the incidence of stroke. Multivariable Cox regression analyses including the number of abnormal lipid profiles and covariates showed that the incidence of myocardial infarction, angina, and heart failure increased stepwise with the number of abnormal lipid profiles. However, the number of abnormal lipid profiles was not associated with the subsequent risk of stroke. In conclusion, the comprehensive analysis of a nationwide epidemiological database demonstrated a close relationship between lipid profile and subsequent CVD, suggesting the importance of maintaining an optimal lipid profile for the primary prevention of CVD in young generations.


Sea level rise and climate change acting as interactive stressors on development and dynamics of tropical peatlands in coastal Sumatra and South Borneo since the Last Glacial Maximum.
Southeast Asian peatlands, along with their various important ecosystem services, are mainly distributed in the coastal areas of Sumatra and Borneo. These ecosystems are threatened by coastal development, global warming and sea level rise (SLR). Despite receiving growing attention for their biodiversity and as massive carbon stores, there is still a lack of knowledge on how they initiated and evolved over time, and how they responded to past environmental change, that is, precipitation, sea level and early anthropogenic activities. To improve our understanding thereof, we conducted multi-proxy paleoecological studies in the Kampar Peninsula and Katingan peatlands in the coastal area of Riau and Central Kalimantan, Indonesia. The results indicate that the initiation timing and environment of both peatlands are very distinct, suggesting that peat could form under various vegetation as soon as there is sufficient moisture to limit organic matter decomposition. The past dynamics of both peatlands were mainly attributable to natural drivers, while anthropogenic activities were hardly relevant. Changes in precipitation and sea level led to shifts in peat swamp forest vegetation, peat accumulation rates and fire regimes at both sites. We infer that the simultaneous occurrence of El Niño-Southern Oscillation (ENSO) events and SLR resulted in synergistic effects which led to the occurrence of severe fires in a pristine coastal peatland ecosystem; however, it did not interrupt peat accretion. In the future, SLR, combined with the projected increase in frequency and intensity of ENSO, can potentially amplify the negative effects of anthropogenic peatland fires. This prospectively stimulates massive carbon release, thus could, in turn, contribute to worsening the global climate crisis especially once an as yet unknown threshold is crossed and peat accretion is halted, that is, peatlands lose their carbon sink function. Given the current rapid SLR, coastal peatland managements should start develop fire risk reduction or mitigation strategies.


Intensive Bimanual Intervention for Children Who Have Undergone Hemispherectomy: A Pilot Study.
To conduct a pilot study to assess the feasibility and effectiveness of an intensive bimanual intervention on upper limb function in children who have undergone hemispherectomy. Thirteen children received 90 hours of intensive bimanual training (Hand-Arm Bimanual Intensive Therapy, HABIT). The Jebsen-Taylor Test of Hand Function (JTTHF), Box and Block Test (BBT), Assisting Hand Assessment (AHA), ABILHAND-Kids, and Canadian Occupational Performance Measure (COPM) were assessed by a masked clinician twice before, immediately, and 6 months after treatment. Significant improvements over time were found in the JTTHF, AHA, ABILHAND-Kids, and COPM. Completion of HABIT was feasible for children with hemispherectomy. Improvement of bimanual function and functional goals can be related to the nature of the activities prioritized in HABIT training.


Clostridium pasteurianum W5 synthesizes two NifH-related polypeptides under nitrogen-fixing conditions.
Previous studies identified five nifH-like genes (nifH2 through nifH6) in Clostridium pasteurianum (strain W5), where the nifH1 gene encodes the nitrogenase iron protein. Transcripts of these nifH genes, with the exception of nifH3, were detected in molybdenum-sufficient nitrogen-fixing cells. However, the size of the transcripts, the level of transcription and the presence of polypeptides encoded by the nifH-like genes were not reported. The nifH2 and nifH6 genes were extremely similar, as they seemed to differ by only two bases in a span of 2481 bp, one in the coding region and another in the upstream region. Re-examination of the DNA sequences revealed that the coding region of nifH2 and nifH6 was identical, whereas the difference in the upstream region was confirmed. Results from the authors' ongoing study of the nif genes of single-colony isolates of C. pasteurianum suggest that the nifH6 designation should be eliminated. Here the size of mRNA from nifH2 and the detection of the NifH2 polypeptide in nitrogen-fixing cells of C. pasteurianum are reported. Northern blot analysis of periodically collected nitrogen-fixing cells showed that the nifH1 and nifH2 mRNAs were present throughout growth. Addition of ammonium acetate repressed the transcription of both these genes similarly. Using an antiserum raised against NifH of Azotobacter vinelandii, two NifH-related bands were detected by Western blot analysis after electrophoretic separation of proteins in extracts of nitrogen-fixing C. pasteurianum cells. After separation of proteins by preparative SDS-PAGE, the NifH polypeptides were characterized by MALDI-TOF-MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry) and by ES-MS/MS (electrospray tandem mass spectrometry) analyses. The results confirmed the presence of NifH2, in addition to NifH1, in nitrogen-fixing C. pasteurianum cells.


Dried fluid spots for HIV type-1 viral load and resistance genotyping: a systematic review.
Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and practical alternative specimen source to liquid plasma for HIV type-1 (HIV-1) viral load determination and drug resistance genotyping in the context of the rapidly expanding access to antiretroviral therapy (ART) for HIV-1-infected individuals in low- and middle-income countries. This report reviews the current evidence for their utility. We systematically searched the English language literature published before 2009 on Medline, the websites of the World Health Organization and US Centers for Disease Control and Prevention, abstracts presented at relevant international conferences and references from relevant articles. Data indicate that HIV-1 viral load determination and resistance genotyping from DBS and DPS is feasible, yielding comparable test performances, even after storage. Limitations include reduced analytical sensitivity resulting from small analyte volumes (approximately 3.5 log(10) copies/ml at 50 microl sample volume), nucleic acid degradation under extreme environmental conditions, impaired efficiency of nucleic acid extraction, potential interference of archived proviral DNA in genotypes obtained from DBS and the excision of spots from the filters in high-volume testing. This technology offers the advantages of a stable specimen matrix, ease of sample collection and shipment. The current sensitivity in drug resistance testing is appropriate for public health surveillance among pretreatment populations. However, consistently improved analytical sensitivity is needed for their routine application in the therapeutic monitoring of individuals receiving ART, particularly at the onset of treatment failure.


Serpinc1 Acts as a Tumor Suppressor in Hepatocellular Carcinoma Through Inducing Apoptosis and Blocking Macrophage Polarization in an Ubiquitin-Proteasome Manner.
Serpinc1 is a serine protease inhibitor in the coagulation cascade, but its role in tumor biology remains obscure. Here, we report an unexpected role of serpinc1 in suppression of hepatocellular carcinoma (HCC). In HCC patients, the mRNA and protein expression of serpinc1 is upregulated, which is negatively correlated with tumor grade, and has a better prognosis than patients with low serpinc1. In addition, patients with high expression of serpinc1 generally have a better tumor immune microenvironment, accompanied by changes in multiple immune cells and mediators. In particular, tumor-promoting M2 macrophages are negatively correlated with serpinc1 expression and the prognosis of HCC patients. In vitro experiments further show that overexpression of serpinc1 inhibits the growth of HCC cells (HepG2 and SMMC7721) by inducing apoptosis. Accordingly, cell co-culture experiments reveal the direct role of serpinc1-overexpressed HCC cells in inhibiting the formation of M2 macrophages. Subsequent unbiased quantitative proteomic and ubiquitinome analyses identify that multiple poly-ubiquitination of proteins involved in signal pathways (such as autophagy, apoptosis, lactate metabolism, and VEGF signaling) are regulated by serpinc1. Overall, these findings establish a serpinc1-dependent ubiquitin-proteasome system to control apoptosis and antitumor immunity.


Mechanism and nature of the different viscosity sensitivities of hemicyanine dyes with various heterocycles.
A series of hemicyanine derivatives are excellent fluorescent viscosity sensors in live cells and in imaging of living tissues due to their low quantum yields in solution but large fluorescence enhancements in viscous environments. Herein, three carbazole-based hemicyanine dyes with different heterocycles are studied. They have different background quantum yields, and hence different sensitivities to viscosity detection, large Stokes shifts, and high sensitivity. Better understanding of the structure-property relationships for viscosity sensitivity could benefit the design of improved dyes. Computational studies on these dyes reveal the mechanism of viscosity sensitivity of fluorescent molecular rotors and the nature of the difference in viscosity sensitivity of the three dyes. The results show that the greatly raised HOMO and greatly lowered LUMO in the S1 state compared with the S0 state are responsible for the large Stokes shift of the three dyes. The heterocyclic moieties have the primary influence on the LUMO levels of the three hemicyanine dyes. Rotation about the C-C bond adjacent to the carbazole moiety of the three dyes drives the molecule toward a small energy gap between the ground state and the first excited state, which causes mainly nonradiative deactivation. The oscillator strengths in the lowest singlet excited state drop rapidly with increasing rotation between 0 and 95°, which leads to a dark state for these dyes when fully twisted at 95°. We draw a mechanistic picture at the molecular level to illustrate how these dyes work as viscosity-sensitive fluorescent probes. The activation barriers and energy gaps of C-C bond rotation strongly depend on the choice of heterocycle, which plays a major role in reducing fluorescence quantum yield in the free state and provides high sensitivity to viscosity detection in viscous environments for the carbazole-based hemicyanine dyes.


Biopathological Significance of PIWI-piRNA Pathway Deregulation in Invasive Breast Carcinomas.
The PIWI proteins emerging in the development of human cancers, edify PIWI-piRNA ribonucleoproteic complexes acting as pivotal regulators of genome integrity, differentiation and homeostasis. The aim of this study is to analyze the four PIWILs gene expression in invasive breast carcinomas (IBCs): at RNA level using quantitative RT-PCR (n = 526) and protein level using immunohistochemistry (n = 150). In normal breast tissue, PIWILs 2 and 4 were solely expressed, whereas an abnormal emergence of PIWIL1 and 3 was observed in respectively 30% and 6% of IBCs. Conversely, PIWIL2 was underexpressed in 48.3% and PIWIL4 downregulated in 43.3% of IBCs. Significant positive associations were observed between PIWIL4 underexpression, HR+ status and HR+ ERBB2+ molecular subtype and PIWIL2 underexpression, PR- status, ERBB2- status and molecular subtype. Similar patterns of PIWIL deregulation were observed in a multitumoral panel, suggesting a generic mechanism in most cancers. PIWIL2-4 underexpression was mainly regulated at epigenetic or post-transcriptional levels. PIWIL2 underexpression was significantly associated with DNA methylation and strong cytotoxic immune response. PIWIL2-4 were mainly associated with genes implicated in cell proliferation. As a result of this study, characterization of the PIWIL-piRNA pathway in IBCs opens interesting therapeutic perspectives using piRNAs, hypomethylating drugs, checkpoints immunotherapies and anti-PIWIL 1-3 antibodies.


Helminth genome analysis reveals conservation of extracellular vesicle biogenesis pathways but divergence of RNA loading machinery between phyla.
A comparative genomics approach was used to determine whether established extracellular vesicle biogenesis pathways are conserved in helminths. This revealed conservation of membrane and cytoskeletal organising proteins as well as the endosomal sorting complex required for transport previously described in mammalian cells. Domain level analysis of this complex in helminths, however, indicated that some species may rely on atypical proteins to support subunit interactions and cargo recruitment. Interestingly, helminths displayed phylum level divergence of proteins associated with loading RNA into extracellular vesicles. These findings provide a framework for functional studies of helminth extracellular vesicle biogenesis and cargo sorting.


Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles.
First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.


Aspiration cytology of salivary gland lesions advantages and pitfalls.
FNAC of the major salivary glands was performed on 72 patients during a period of two and a half years. In 64 patients samples were satisfactory. The cytologic diagnosis was correlated with histology available in 36 cases. 21 out of 22 benign lesions and 12 out 4 malignant lesions were correctly identified rendering a diagnostic accuracy of 91 percent. The pitfalls of FNAC of salivary gland lesions are reflected by the overall false positive rate of 5.5 percent of false negative rate of 2.7 percent. Diagnostic pitfalls are due to variability of tumor morphology which makes sampling & interpretation difficult. Multiple sampling and increasing experience help to minimize errors.


Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.
Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.


Location-selective growth of two-dimensional metallic/semiconducting transition metal dichalcogenide heterostructures.
An electrical contact between metallic electrodes and semiconductors is critical for the performance of electronic and optoelectronic devices. Two-dimensional (2D) transition metal dichalcogenides (TMDs) contain semiconducting, metallic and insulating material members, which enables the fabrication of highly integrated electronic devices fully based on 2D TMDs. However, location-selective synthesis of metallic/semiconducting heterostructures by a chemical vapor deposition (CVD) method has rarely been reported. In this study, a two-step CVD method was applied to fabricate 2D metallic/semiconducting heterostructures. Semiconducting WS2 was first synthesized and served as the template for the following CVD growth of metallic NbS2. In the growth process, NbS2 flakes selectively nucleate at the edges of WS2 monolayers, thus resulting in the formation of NbS2 islands circling around the WS2 monolayers. The as-grown NbS2/WS2 heterostructure was further systematically characterized by Raman spectroscopy, atomic force microscopy (AFM) and scanning transition electron microscopy (STEM). The NbS2 layers epitaxially grown on the WS2 monolayers exhibit a 3R phase and there was no discernible lattice strain in the NbS2/WS2 van der Waals (vdW) heterostructure. The growth of the metallic/semiconducting 2D heterostructures could benefit the nanoelectronic device fabrication and provide a platform for the 2D contact resistance study.


Valuing the past: The importance of an understanding of the history of psychiatry for healthcare professionals, service users and carers.
Drawing primarily on examples from the UK, this paper argues that an under-standing of the history of psychiatry can be of practical use to clinicians, service users and carers. It can provide a window on the present and an explanation of some aspects of current practice. In addition, a study of the past can provide a vision of how things might be done differently in the present and in the future. Moreover, knowledge of the past can also serve to remind us of psychiatry's potential for misuse and the dangers inherent in a view of the world in which psychiatry is simply seen as a benevolent science destined to find an answer to mental illness.


Long-term retention rates of adalimumab and infliximab in non-infectious intermediate, posterior, and panuveitis.
The aim of the present study was to compare long-term adalimumab (ADA) and infliximab (IFX) retention rates in patients with intermediate, posterior, or panuveitis. Additional aims are as follows: (i) to identify any difference in the causes of treatment discontinuation between patients treated with ADA and IFX; (ii) to assess any impact of demographic features, concomitant treatments, and different lines of biologic therapy on ADA and IFX retention rates; and (iii) to identify any correlation between ADA and IFX treatment duration and the age at uveitis onset, the age at onset of the associated systemic diseases, and the age at the start of treatment. Clinical, therapeutic, and demographic data from patients with non-infectious intermediate, posterior, or panuveitis treated with ADA or IFX were retrospectively collected. Kaplan-Meier plot and log-rank (Mantel-Cox) test were used to assess survival curves. One hundred eight patients (188 eyes) were enrolled; in 87 (80.6%) patients, uveitis was associated with a systemic disease. ADA and IFX were administered in 62 and 46 patients, respectively. No statistically significant differences were identified between ADA and IFX retention rates (p value = 0.22). Similarly, no differences were identified between ADA and IFX retention rates in relation to gender (p value = 0.61 for males, p value = 0.09 for females), monotherapy (p value = 0.08), combination therapy with conventional disease-modifying antirheumatic drugs (log-rank p value = 0.63), and different lines of biologic therapy (p value = 0.79 for biologic-naïve patients; p value = 0.81 for subjects previously treated with other biologics). In conclusion, ADA and IFX have similar long-term retention rates in patients with non-infectious intermediate, posterior, and panuveitis. Demographic, clinical, and therapeutic features do not affect their long-term effectiveness.


Acute gastrointestinal bleeding. Experience of a specialized management team.
The initial experience of a specialized management team organized to provide expedient care for all acute major gastrointestinal bleeding in protocolized fashion at a large referral center is presented. Of the 417 patients, 56% developed bleeding while hospitalized. Upper gastrointestinal bleeding accounted for 82%. The five most common etiologies included gastric ulcers (83 patients), duodenal ulcers (67 patients), erosions (41 patients), varices (35 patients), and diverticulosis (29 patients). Nonsteroidal anti-inflammatory drugs were implicated in 53% of gastroduodenal ulcers. The incidence of nonbleeding visible vessels was 42% in gastric and 54% in duodenal ulcers. The rates of rebleeding were 24% (20 patients) in gastric ulcers and 28% (19 patients) in duodenal ulcers. Predictive factors for rebleeding included copious bright red blood, active arterial streaming, spurting, or a densely adherent clot. The rebleeding rate for esophagogastric varices was 57%. The mortality rate overall was 6% (27 patients), with rates varying from 3% (five patients) for gastroduodenal ulcers to 40% (14 patients) for esophagogastric varices. The morbidity rate for the entire patient population was 18% (77 patients), dominated by myocardial events (34 patients). The average length of hospitalization for gastroduodenal ulcers was 5 days, for diverticulosis 8 days, and for varices 10 days. The major efforts of a specialized Gastrointestinal Bleeding Team would be best directed at both reducing the morbidity associated with acute bleeding and reducing the overall cost of care.


Reliability of a patient-rated forearm evaluation questionnaire for patients with lateral epicondylitis.
To determine the reliability of a questionnaire designed to assess forearm pain and function in patients with lateral epicondylitis. Forty-seven patients with unilateral lateral epicondylitis completed a patient-related forearm evaluation questionnaire (PRFEQ) on two occasions. Intraclass correlation coefficients (ICC 2,1), standard error of measurement (SEM), and 95% confidence intervals (CIs) were determined for the whole group and for three subgroup comparisons of male vs. female subjects, subacute vs. chronic lateral epicondylitis, and work-related vs. non-work-related lateral epicondylitis. The test-retest reliability for the overall PRFEQ (ICC, 0.89), and its pain (ICC, 0.89) and function (ICC, 0.83) subscales was excellent. Test-retest reliability for patients with work-related lateral epicondylitis (ICC, 0.80) was significantly (p = 0.018) less than for patients with non-work-related lateral epicondylitis (ICC, 0.94). The PRFEQ can provide a simple, quick, and reliable estimate of arm pain and function in patients with lateral epicondylitis. However, large SEM and 95% CIs limit its ability to accurately predict individual scores.


Surface topography of zirconia implants does not alter action potentials of isolated rat sciatic nerves.
The purpose of this study was to explore the effects of airborne-particle abrasion and selective infiltration etching of a yttrium-partially stabilized tetragonal zirconia polycrystal (Y-TZP) implant surfaces on nerve conduction. Particle-abraded Y-TZP (P/Y-TZP), selective infiltration etched Y-TZP (SIE/Y-TZP), and commercially pure titanium (CP-Ti) were used in the study (n = 5).The compound action potentials of the right and left sciatic nerves of eight sacrificed rats were quantified at the in vitro level. The implants were brought into intimate contact with the nerves and the time required for initiation of compound action potentials (TcAP), depolarization (Dp), repolarization (Rp), and amplitude of evoked compound action potentials (cAPs) were recorded before and after contact with the implants. The difference in cAPs between the basal response and after contact with CP-Ti implant was significant (p < 0.05). Time-dependent changes in cAPs of P/Y-TZP and SIE/Y-TZP groups and their basal nerve responses were similar (p > 0.05). Within- and between-subject comparisons revealed that TcAP, Dp, and Rp values for all groups were similar (p > 0.05). Particle-abraded and selective infiltration-etched zirconia implant surfaces do not alter nerve conduction beyond physiologic limits.


Expression of M-N#1, a histo-blood group B-like antigen, is strongly up-regulated in nonapoptosing mammary epithelial cells during rat mammary gland involution.
Antibodies against the histo-blood group B-like antigen M-N#1 efficiently block the growth in vivo of rat mammary carcinoma cells that bear the antigen (Sleeman et al., 1999, Oncogene 18, 4485--4494). To try to understand the function of the M-N#1 antigen, we investigated when and where the antigen is expressed during the normal function of the rat mammary gland. Expression was virtually only seen during mammary gland involution. Here, strong expression of the antigen was observed in mammary epithelial cells, beginning around 2 days postweaning and lasting throughout the involution process. Dexamethasone treatment of animals postlactation inhibited alveolar collapse and remodeling in the mammary gland but inhibited neither the apoptosis of mammary epithelial cells nor the expression of the M-N#1 antigen. We show that up-regulation of carbohydrate antigens is not a general phenomenon during mammary gland involution, and thus that M-N#1 antigen expression is specifically regulated. Up-regulation of alpha(1,2)fucosyltransferase A, an enzyme required for M-N#1 antigen synthesis, is at least partly responsible for regulated M-N#1 antigen expression postlactation. Most significantly, we observed that the M-N#1 antigen is virtually exclusively expressed on nonapoptosing epithelial cells in the involuting mammary gland. These data suggest that M-N#1 antigen expression might either provide a survival function and/or be expressed in epithelial cells that are destined to grow and remodel mammary duct structures.


An update to MitoTool: using a new scoring system for faster mtDNA haplogroup determination.
The determination of human mitochondrial DNA (mtDNA) haplogroups is not only crucial in anthropological and forensic studies, but is also helpful in the medical field to prevent establishment of wrong disease associations. In recent years, high-throughput technologies and the huge amounts of data they create, as well as the regular updates to the mtDNA phylogenetic tree, mean that there is a need for an automated approach which can make a speedier determination of haplogroups than can be made by using the traditional manual method. Here, we update the MitoTool (www.mitotool.org) by incorporating a novel scoring system for the determination of mtDNA into haplogroups, which has advantages on speed, accuracy and ease of implementation. In order to make the access to MitoTool easier, we also provide a stand-alone version of the program that will run on a local computer and this version is freely available at the MitoTool website.


EEG-Based Driving Fatigue Detection Using a Two-Level Learning Hierarchy Radial Basis Function.
Electroencephalography (EEG)-based driving fatigue detection has gained increasing attention recently due to the non-invasive, low-cost, and potable nature of the EEG technology, but it is still challenging to extract informative features from noisy EEG signals for driving fatigue detection. Radial basis function (RBF) neural network has drawn lots of attention as a promising classifier due to its linear-in-the-parameters network structure, strong non-linear approximation ability, and desired generalization property. The RBF network performance heavily relies on network parameters such as the number of the hidden nodes, number of the center vectors, width, and output weights. However, global optimization methods that directly optimize all the network parameters often result in high evaluation cost and slow convergence. To enhance the accuracy and efficiency of EEG-based driving fatigue detection model, this study aims to develop a two-level learning hierarchy RBF network (RBF-TLLH) which allows for global optimization of the key network parameters. Experimental EEG data were collected, at both fatigue and alert states, from six healthy participants in a simulated driving environment. Principal component analysis was first utilized to extract features from EEG signals, and the proposed RBF-TLLH was then employed for driving status (fatigue vs. alert) classification. The results demonstrated that the proposed RBF-TLLH approach achieved a better classification performance (mean accuracy: 92.71%; area under the receiver operating curve: 0.9199) compared to other widely used artificial neural networks. Moreover, only three core parameters need to be determined using the training datasets in the proposed RBF-TLLH classifier, which increases its reliability and applicability. The findings demonstrate that the proposed RBF-TLLH approach can be used as a promising framework for reliable EEG-based driving fatigue detection.


Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.
Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. Double-blind, placebo-controlled clinical trial. Multi-center at eight sites of the T1D Exchange Clinic Network. A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.


A potential role for cannabichromene in modulating TRP channels during acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome whose potential to become one of the most grievous challenges of the healthcare system evidenced by the COVID-19 pandemic. Considering the lack of target-specific treatment for ARDS, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve quality of life and outcomes for ARDS patients. ARDS is a systemic inflammatory disease starting with the pulmonary system and involves all other organs in a morbid bidirectional fashion. Mounting evidence including our findings supporting the notion that cannabinoids have potential to be targeted as regulatory therapeutic modalities in the treatment of inflammatory diseases. Therefore, it is plausible to test their capabilities as alternative therapies in the treatment of ARDS. In this study, we investigated the potential protective effects of cannabichromene (CBC) in an experimental model of ARDS. We used, for the first time, an inhalant CBC treatment as a potential therapeutic target in a murine model of ARDS-like symptoms. ARDS was induced by intranasal administration of Poly(I:C), a synthetic mismatched double-stranded RNA, into the C57BL/6 mice (6-10 male mice/group, including sham, placebo, and CBC treated), three once-daily doses followed by a daily dose of inhalant CBC or placebo for the period of 8 days starting the first dose 2 h after the second Poly(I:C) treatment. We employed histologic, immunohistochemistry, and flow cytometry methods to assess the findings. Statistical analysis was performed by using one way analysis of variance (ANOVA) followed by Newman-Keuls post hoc test to determine the differences among the means of all experimental groups and to establish significance (p < 0.05) among all groups. Our data showed that CBC was able to reverse the hypoxia (increasing blood O2 saturation by 8%), ameliorate the symptoms of ARDS (reducing the pro-inflammatory cytokines by 50% in lung and blood), and protect the lung tissues from further destruction. Further analysis showed that CBC may wield its protective effects through transient receptor potential (TRP) cation channels, TRPA1 and TRPV1, increasing their expression by 5-folds in lung tissues compared to sham and untreated mice, re-establishing the homeostasis and immune balance. Our findings suggest that inhalant CBC may be an effective alternative therapeutic target in the treatment of ARDS. In addition, Increased expression of TRPs cation channels after CBC treatment proposes a novel role for TRPs (TRPA1 and TRPV2) as new potential mechanism to interpret the beneficial effects of CBC as well as other cannabinoids in the treatment of ARDS as well as other inflammatory diseases. Importantly, delivering CBC through an inhaler device is a translational model supporting the feasibility of trial with human subjects, authorizing further research.


Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.
The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet.


Amitochondriate amoebae and the evolution of DNA-dependent RNA polymerase II.
Unlike parasitic protist groups that are defined by the absence of mitochondria, the Pelobiontida is composed mostly of free-living species. Because of the presence of ultrastructural and cellular features that set them apart from all other eukaryotic organisms, it has been suggested that pelobionts are primitively amitochondriate and may represent the earliest-evolved lineage of extant protists. Analyses of rRNA genes, however, have suggested that the group arose well after the diversification of the earliest-evolved protists. Here we report the sequence of the gene encoding the largest subunit of DNA-dependent RNA polymerase II (RPB1) from the pelobiont Mastigamoeba invertens. Sequences within RPB1 encompass several of the conserved catalytic domains that are common to eubacterial, archaeal, and eukaryotic nuclear-encoded RNA polymerases. In RNA polymerase II, these domains catalyze the transcription of all nuclear pre-mRNAs, as well as the majority of small nuclear RNAs. In contrast with rDNA-based trees, phylogenetic analyses of RPB1 sequences indicate that Mastigamoeba represents an early branch of eukaryotic evolution. Unlike sequences from parasitic amitochondriate protists that were included in our study, there is no indication that Mastigamoeba RPB1 is attracted to the base of the eukaryotic tree artifactually. In addition, the presence of introns and a heptapeptide C-terminal repeat in the Mastigamoeba RPB1 sequence, features that are typically associated with more recently derived eukaryotic groups, raise provocative questions regarding models of protist evolution that depend almost exclusively on rDNA sequence analyses.


[Genetic variants of acid erythrocytic phosphatase as a risk factor of rheumatic fever].
A study was made of the genetic variants (isoenzymes, phenotypes) of acid erythrocytic phosphatase (AcP) in 120 patients with rheumatic fever. There were 78 women and 42 men aged 16 to 57 years. The population data concerned with distribution of the AcP variants among the population of Moscow were used as control. As compared with control, the patients suffering from rheumatic fever demonstrated the accumulation of the rarely occurring variants of AcP (AC, BC and CC, in particular). A significant direct correlation was established between the activity of isoenzymes and relative risk of rheumatic fever incidence. The definite regularities in the distribution of AcP variants were found to depend on the disease clinical patterns (the articular syndrome, the times of the formation of heart diseases, the character of recurrent rheumocarditis). The data obtained can used for distinguishing the rheumatic fever risk groups and forecasting the rheumatic process (to a certain degree of probability).


Can Residential Greenspace Exposure Improve Pain Experience? A Comparison between Physical Visit and Image Viewing.
Reducing the burden of pain via greenspace exposure is a rising research topic. However, insufficient evidence has been found in relation to the environmental effect itself. Residential greenspace, as a convenient but limited natural environment for urban dwellers, has benefits and services yet to be discovered. Therefore, the current study recruited 24 young adults to evaluate the effects of physical visit to, or image viewing of, residential greenspace on pain perception and related psychophysiological outcomes, via simulated pain. Pain threshold and tolerance were recorded via the level of pain stimuli, and pain intensity was evaluated using the Visual Analog Scale (VAS). The state scale of the State-Trait Anxiety Inventory (STAI-S) and two adjective pairs were employed to measure the state anxiety and subjective stress, respectively. Meanwhile, heart rate (HR), heart rate variability (HRV), and blood pressure (BP) were measured to investigate physiological responses. Besides, Scenic Beauty Estimation (SBE) was also employed to assess participants' preference regarding the experimental environments. The results revealed that visiting the greenspace significantly increased the pain threshold and tolerance, while no significant effect was observed for image viewing. On the other hand, no significant difference was observed in pain-related psychophysiological indices between the experimental settings, but significantly negative associations were found between the scores of SBE and subjective stress and state anxiety. In conclusion, the current study brings experimental evidence of improving pain experience via residential greenspace exposure, while the related psychophysiological benefits require further investigation.


The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism.
A body of work has emerged over the past decade demonstrating a relationship between mutations in glucocerebrosidase gene (GBA), the gene implicated in Gaucher disease (GD), and the development of parkinsonism. Several different lines of research support this relationship. First, patients with GD who are homozygous for mutations in GBA have a higher than expected propensity to develop Parkinson's disease (PD). Furthermore, carriers of GBA mutations, particularly family members of patients with GD, have displayed an increased rate of parkinsonism. Subsequently, investigators from centers around the world screened cohorts of patients with parkinsonism for GBA mutations and found that overall, subjects with PD, as well as other Lewy body disorders, have at least a fivefold increase in the number of carriers of GBA mutations as compared to age-matched controls. In addition, neuropathologic studies of subjects with parkinsonism carrying GBA mutations demonstrate Lewy bodies, depletion of neurons of the substantia nigra, and involvement of hippocampal layers CA2-4. Although the basis for this association has yet to be elucidated, evidence continues to support the role of GBA as a PD risk factor across different centers, synucleinopathies, and ethnicities. Further studies of the association between GD and parkinsonism will stimulate new insights into the pathophysiology of the two disorders and will prove crucial for both genetic counseling of patients and family members and the design of relevant therapeutic strategies for specific patients with parkinsonism.


START-Play Physical Therapy Intervention Impacts Motor and Cognitive Outcomes in Infants With Neuromotor Disorders: A Multisite Randomized Clinical Trial.
Our objective was to evaluate the efficacy of the Sitting Together and Reaching to Play (START-Play) intervention in young infants with neuromotor disorders. This randomized controlled trial compared usual care early intervention (UC-EI) with START-Play plus UC-EI. Analyses included 112 infants with motor delay (55 UC-EI, 57 START-Play) recruited at 7 to 16 months of age across 5 sites. START-Play included twice-weekly home visits with the infant and caregiver for 12 weeks provided by physical therapists trained in the START-Play intervention; UC-EI was not disrupted. Outcome measures were the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley); the Gross Motor Function Measure; reaching frequency; and the Assessment of Problem Solving in Play (APSP). Comparisons for the full group as well as separate comparisons for infants with mild motor delay and infants with significant motor delay were conducted. Piecewise linear mixed modeling estimated short- and long-term effects. For infants with significant motor delay, positive effects of START-Play were observed at 3 months for Bayley cognition, Bayley fine motor, and APSP and at 12 months for Bayley fine motor and reaching frequency outcomes. For infants with mild motor delay, positive effects of START-Play for the Bayley receptive communication outcome were found. For the UC-EI group, the only difference between groups was a positive effect for the APSP outcome, observed at 3 months. START-Play may advance reaching, problem solving, cognitive, and fine motor skills for young infants with significant motor delay over UC-EI in the short term. START-Play in addition to UC-EI may not improve motor/cognitive outcomes for infants with milder motor delays over and above usual care. Concepts of embodied cognition, applied to early intervention in the START-Play intervention, may serve to advance cognition and motor skills in young infants with significant motor delays over usual care early intervention. If you have a young infant with significant delays in motor skills, your physical therapist can work with you to develop play opportunities to enhance your child's problem solving, such as that used in the START-Play intervention, in addition to usual care to help your child advance cognitive and motor skills.


Passively Q-switched Tm(3+)-doped silica fiber lasers.
By splicing on a length of Ho(3+)-doped silica fiber onto a diode-pumped double-clad Tm(3+)-doped silica fiber, stable passive Q switching of the Tm(3+)-doped silica fiber laser is demonstrated. The formation of Q-switched pulses was found to depend on both the length and the position of the Ho(3+)-doped silica fiber that was inserted into the fiber laser cavity. For stable Q-switched pulse generation, Ho(3+)-doped silica fiber lengths shorter than twice the absorption depth must be used. For long Ho(3+)-doped silica fiber lengths, randomly generated pulses are observed at operating wavelengths longer than 2090 nm, which are attributed to intracavity pumping of the Ho(3+)-doped silica fiber.


Heterogeneous origin of hyperacidity in duodenal ulcer.
Recent advances in the medical therapy of duodenal ulcer support the long held concept that acid hypersecretion is an important pathophysiological abnormality in the majority of patients with duodenal ulcer. The origin of acid hypersecretion is heterogeneous (Table 1). Certain specific physiologic abnormalities that lead to acid hypersecretion may have a genetic basis. The various physiologic abnormalities, alone or in combination, may lead to two final common pathways: abnormally large meal-stimulated and nocturnal acid secretion. Indeed, the success of medical therapy aimed at the control of postprandial acid secretion alone or that of nocturnal acid secretion alone strongly support the significance of these two final acid hypersecretory pathways.


Hypsibius vaskelae, a new species of Tardigrada (Eutardigrada, Hypsibiidae) from Russia.
Hypsibius vaskelae sp. nov. (Tardigrada, Eutardigrada, Hypsibiidae) is described from a freshwater sample collected in the vicinity of Saint-Petersburg. The new species has wrinkled cuticle, bucco-pharyngeal apparatus with two elongate macroplacoids and septulum, and cuticular bars between the bases of inner and outer claw and near the base of the inner claw on legs I-IV. Hypsibius vaskelae sp. nov. is most similar to Hypsibius marcelli Pilato, 1990 and H. septulatus Pilato, Binda, Napolitano Moncada, 2004, but differs from both in having wrinkled dorsal cuticle, thinner claws, and presence of lunules on the claws of all legs.


Discovery Viewer (DV): Web-Based Medical AI Model Development Platform and Deployment Hub.
The rapid rise of artificial intelligence (AI) in medicine in the last few years highlights the importance of developing bigger and better systems for data and model sharing. However, the presence of Protected Health Information (PHI) in medical data poses a challenge when it comes to sharing. One potential solution to mitigate the risk of PHI breaches is to exclusively share pre-trained models developed using private datasets. Despite the availability of these pre-trained networks, there remains a need for an adaptable environment to test and fine-tune specific models tailored for clinical tasks. This environment should be open for peer testing, feedback, and continuous model refinement, allowing dynamic model updates that are especially important in the medical field, where diseases and scanning techniques evolve rapidly. In this context, the Discovery Viewer (DV) platform was developed in-house at the Biomedical Engineering and Imaging Institute at Mount Sinai (BMEII) to facilitate the creation and distribution of cutting-edge medical AI models that remain accessible after their development. The all-in-one platform offers a unique environment for non-AI experts to learn, develop, and share their own deep learning (DL) concepts. This paper presents various use cases of the platform, with its primary goal being to demonstrate how DV holds the potential to empower individuals without expertise in AI to create high-performing DL models. We tasked three non-AI experts to develop different musculoskeletal AI projects that encompassed segmentation, regression, and classification tasks. In each project, 80% of the samples were provided with a subset of these samples annotated to aid the volunteers in understanding the expected annotation task. Subsequently, they were responsible for annotating the remaining samples and training their models through the platform's "Training Module". The resulting models were then tested on the separate 20% hold-off dataset to assess their performance. The classification model achieved an accuracy of 0.94, a sensitivity of 0.92, and a specificity of 1. The regression model yielded a mean absolute error of 14.27 pixels. And the segmentation model attained a Dice Score of 0.93, with a sensitivity of 0.9 and a specificity of 0.99. This initiative seeks to broaden the community of medical AI model developers and democratize the access of this technology to all stakeholders. The ultimate goal is to facilitate the transition of medical AI models from research to clinical settings.


Family caregiving in a pediatric renal transplant population.
Twenty parents (3 fathers and 17 mothers) engaged in caring for a child 2 to 14 months after renal transplant were studied to: (a) determine the kinds of caregiving tasks required and how difficult they are; and (b) explore the relationships among caregiver characteristics, caregiving burden, appraisal, and mood state. Increased housework, errands, providing emotional support, transportation, and monitoring/reporting symptoms were the most demanding tasks; housework, emotional support, and managing behavior problems were the most difficult. Overall, caregiving was perceived as moderately demanding and not particularly difficult, and the caregiving situation was not appraised as being very threatening. Mood dysfunction scores were quite low, but were associated with perceptions of caregiving difficulty. Caregiving demands and difficulty were greater with adolescent children, when the parent had other dependents to care for, and when the parent was working. This suggests the need for careful assessment of the family environment to identify parents at risk of caregiving burden.


Patient controlled analgesia and intramuscular injections: a comparisons of patient pain experiences and postoperative outcomes.
Despite relatively widespread use of various forms of patient controlled analgesia (PCA), there remain conflicting results in the literature as to the efficacy of PCA. This study was conducted to assess the efficacy and postoperative outcomes of intravenous PCA compared to intramuscular (IM) injections in 73 patients who received major abdominal surgery. These patients were randomly selected and randomly assigned preoperatively to receiving IM or PCA modes of analgesia postoperatively. The following factors were compared: amount of pain; amount of analgesia use; degree of patient satisfaction with pain control both while on parenteral analgesia and after switching to oral; length of time to first ambulation; and length of stay in hospital. Results of the study did not demonstrate a statistically significant difference in any of these, using a P-value of 0.01. The PCA patients took an average of 4.5 hours longer than the IM patients to ambulate postoperatively and the IM patients received at least three times as much antiemetic (P = 0.001). Locus of control was not found to be a major factor in satisfaction or pain levels. Subsequent meta-analyses have also failed to yield significant differences between IM and PCA groups except in patient satisfaction. It is recommended that expansion of PCA programmes with abdominal surgery patients be considered only in cases where there is fiscal advantage or where patient satisfaction can be a driving force.


Overload: impact of incident stressful events on antiretroviral medication adherence and virologic failure in a longitudinal, multisite human immunodeficiency virus cohort study.
To examine the influence of incident stressful experiences on antiretroviral medication adherence and treatment outcomes. Past trauma history predicts poorer medication adherence and health outcomes. Human immunodeficiency virus (HIV)-infected individuals experience frequently traumatic and stressful events, such as sexual and physical assault, housing instability, and major financial, employment, and legal difficulties. We measured prospectively incident stressful and traumatic events, medication adherence, and viral load over 27 months in an eight-site, five-state study. Using multivariable logistic and generalized estimating equation modeling, we assessed the impact of incident stressful events on 27-month changes in self-reported medication adherence and virologic failure (viral load = >or=400 c/mL). Of 474 participants on antiretroviral therapy at baseline, 289 persons were interviewed and still received treatment at 27 months. Participants experiencing the median number of incident stressful events (n = 9) had over twice the predicted odds (odds ratio = 2.32) of antiretroviral medication nonadherence at follow-up compared with those with no events. Stressful events also predicted increased odds of virologic failure during follow-up (odds ratio = 1.09 per event). Incident stressful events are exceedingly common in the lives of HIV-infected individuals and negatively affect antiretroviral medication adherence and treatment outcomes. Interventions to address stress and trauma are needed to improve HIV outcomes.


Traditional Chinese medicine method of tonifying kidney for hypertension: Clinical evidence and molecular mechanisms.
Hypertension is the most common chronic disease. A large amount of evidence showed that traditional Chinese medicine (TCM) method of tonifying kidney (TK) combined with routine treatment is more effective and safer in the treatment of hypertension. This study integrated meta-analysis, data mining, and network pharmacology to explore the efficacy and potential mechanisms of TK in the treatment of hypertension. Meta-analysis was performed to explore the efficacy and safety of TK combined with routine treatment in the treatment of hypertension. Data mining was used to screen the core herbs of the TK. Network pharmacology was used to predict the antihypertensive mechanism of TK core herbs. A total of 18 studies with 2,024 patients were included in this study. Meta-analysis showed that TK combined with routine treatment was superior to routine treatment alone in lowering blood pressure (systolic and diastolic blood pressures), lowering blood lipids (total cholesterol, triglyceride, low-density lipoprotein cholesterol), improving vascular endothelial functions (nitric oxide, endothelin) and TCM symptoms (headache dizziness, soreness, and weakness of waist and knees). In addition, TK was safe and has no obvious adverse reactions. Data mining showed that the core herbs of TK were Eucommia ulmoides Oliv. (Duzhong), Vitex negundo L. (Huangjing), Taxillus chinensis (DC.) Danser (Sangjisheng), Ligustrum lucidum W.T.Aiton (Nuzhenzi), Astragalus mongholicus Bunge (Huangqi), Rehmannia glutinosa (Gaertn.) DC. (Shudihuang). Network pharmacology predicted that core herbs antihypertensive components were oleanolic acid, ursolic acid, and civetone, and the antihypertensive targets were NOS3, NOS2, MMP9, TNF, PTGS2, HMOX1. In addition, the antihypertensive targets were enriched in cGMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption, HIF-1 signaling pathway. In conclusion, TK combined with routine treatment for hypertension is effective and safe. The mechanism of TK may be related to GMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption. On the premise of syndrome differentiation and treatment, it is promising to treat hypertension with TK. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022358276].


Utility of the Conners' Adult ADHD Rating Scale validity scales in identifying simulated attention-deficit hyperactivity disorder and random responding.
Recent concern about malingered self-report of symptoms of attention-deficit hyperactivity disorder (ADHD) in college students has resulted in an urgent need for scales that can detect feigning of this disorder. The present study provided further validation data for a recently developed validity scale for the Conners' Adult ADHD Rating Scale (CAARS), the CAARS Infrequency Index (CII), as well as for the Inconsistency Index (INC). The sample included 139 undergraduate students: 21 individuals with diagnoses of ADHD, 29 individuals responding honestly, 54 individuals responding randomly (full or half), and 35 individuals instructed to feign. Overall, the INC showed moderate sensitivity to random responding (.44-.63) and fairly high specificity to ADHD (.86-.91). The CII demonstrated modest sensitivity to feigning (.31-.46) and excellent specificity to ADHD (.91-.95). Sequential application of validity scales had correct classification rates of honest (93.1%), ADHD (81.0%), feigning (57.1%), half random (42.3%), and full random (92.9%). The present study suggests that the CII is modestly sensitive (true positive rate) to feigned ADHD symptoms, and highly specific (true negative rate) to ADHD. Additionally, this study highlights the utility of applying the CAARS validity scales in a sequential manner for identifying feigning. (PsycINFO Database Record


Structural Ultrasound of the Medial Temporal Lobe in Alzheimer's Disease.
Purpose One of the anatomical hallmarks of Alzheimer's disease (AD) is the atrophy of the medial temporal lobe (MTL), yet cost-effective and broadly available methodological alternatives to the current imaging tools for screening of this brain area are not currently available. Materials and Methods Using structural transcranial ultrasound (TCS), we attempted to visualize and measure the MTL, and compared the results of 32 AD patients and 84 healthy controls (HC). The MTL and the surrounding space were defined in the coronal plane on TCS. A ratio of the height of the MTL/height of the choroidal fissure (M/F) was calculated in order to obtain a regional proportion. Results An insufficient temporal bone window was identified in 22 % of the AD patients and 12 % of the HCs. The results showed that the ratio of M/F was significantly smaller in the AD group on both sides (p = 0.004 right, p = 0.007 left side). Furthermore, the M/F ratio made it possible to discriminate AD patients from HCs with a sensitivity of 83 % (right)/73 % (left) and a specificity of 76 % (right)/72 % (left) which is basically comparable to results published for magnetic resonance imaging. The measurements showed substantial intra/interrater reliability (ICC:0.79/0.69). Conclusion These results suggest that utilization of structural TCS may possibly constitute a cheap and easy-to-use supplement to other techniques for the diagnosis of AD. It may be especially useful as a screening tool in the large population of individuals with cognitive decline. Further studies are needed to validate this novel method.


Effect of pre- and post-partum supplementation with lipid-encapsulated conjugated linoleic acid on milk yield and metabolic status in multiparous high-producing dairy cows.
We evaluated the lactation performance, liver lipid content and plasma metabolites indicating the energy balance of dairy cows supplemented with conjugated linoleic acid (CLA) pre- and post-partum (PP) vs. only PP. A total of 60 cows were divided into three groups (n = 20). Daily diet of cows was supplemented with 14 g of CLA (7 g cis-9, trans-11 and 7 g trans-10, cis-12 isomers) from week 3 before the expected date of calving (group CLA1), or from the day of calving (group CLA2) until 77-91 days PP. Control cows were fed an isocaloric, isonitrogenous and isolipidic diet without CLA. Between week 3 and week 6 PP, the milk yield of cows in both CLA-treated groups was approximately 4.5 kg higher (p < 0.05) than in control. Milk fat concentrations decreased from week 3 and were lower in both CLA groups than in control (p < 0.01). Body condition score loss was lower (p < 0.05) in the CLA1 than in the control group on week 5 PP. By week 11 PP, the body condition of both CLA1 and CLA2 groups exceeded that of control. Plasma non-esterified fatty acid was lower in CLA1 compared to CLA2 and control during the early PP period (p < 0.05), while this difference faded away by the late PP period. Beta-hydroxybutyrate (BHBA) increased rapidly in all groups following calving. In CLA1 group, it began to decrease sooner than in CLA2 and control. The prevalence of subclinical ketosis (BHBA > 1.2 mm) was lower in CLA1 group than in CLA2 and control (p < 0.05). Liver biopsy analyses showed that CLA1 treatment decreased (p < 0.05) the total lipid content of liver compared to control at week 5 after calving. Our results show that CLA supplementation is more efficient in alleviating body mass mobilization and decreasing the incidence of subclinical ketosis when applied as early as 3 weeks before calving than started feeding after calving.


The gp120 protein is a second determinant of decreased neurovirulence of Indian HIV-1C isolates compared to southern African HIV-1C isolates.
Regional differences in neurovirulence have been documented among subtype/clade-C HIV-1 isolates in India and Southern Africa. We previously demonstrated that a C31S substitution in Clade-C Tat dicysteine motif reduces monocyte recruitment, cytokine induction and direct neurotoxicity. Therefore, this polymorphism is considered to be a causative factor for these differences in neurovirulence. We previously reported on the genotypic differences in Tat protein between clade-C and rest of the clades showing that approximately 90% of clade-C HIV-1 Tat sequences worldwide contained this C31S polymorphism, while 99% of non-clade C isolates lacked this Tat polymorphism at C31 residue (Ranga et al. (2004) J Virol 78:2586-2590). Subsequently, we documented intra-clade-C differences in the frequency of Tat dicysteine variants between India and Southern Africa, as the basis for differential disease severity and showed the importance of the Tat dicysteine motif for neuropathogenesis using small animal models. We have now examined if determinants of neurovirulence besides Tat are different between the clade-C HIV-1 isolates from Southern Africa and India. Envelope glycoprotein gp120 is a well-documented contributor to neurotoxicity. We found that gp120 sequences of HIV-1 isolates from these two regions are genetically distinct. In order to delineate the contribution of gp120 to neurovirulence, we compared direct in vitro neurotoxicity of HIV-infected supernatants of a representative neurovirulent US clade-B isolate with two isolates each from Southern Africa and India using primary human neurons and SH-SY5Y neuroblastoma cells. Immunodepletion of gp120 of both US clade B and the Southern African clade C isolates revealed robust decreases in neurotoxicity, while that of the Indian isolates showed minimal effect on neurotoxicity. The gp120 as a cause of differential neurotoxicity was further confirmed using purified recombinant gp120 from HIV isolates from these regions. We conclude that gp120 is one of the key factors responsible for the decreased neurovirulence of Indian clade C HIV-1 isolates when compared to South African clade C HIV-1.


Effect of dehydroepiandrosterone on growth in lean and obese Zucker rats.
Several studies were undertaken to determine the effect of dehydroepiandrosterone (DHEA) on growth in Zucker rats. In experiment 1, 3 weeks of DHEA treatment in lean rats resulted in decreased body weight gain in comparison to control rats. In experiment 2, both lean and obese rats were treated with DHEA from 6 to 21 weeks of age. Significant decreases in body weight were found for both lean and obese DHEA-treated rats. The food efficiency ratio (FER) was significantly decreased in both DHEA-treated groups. Significant decreases in parametrial and retroperitoneal fat pads were found in both lean and obese DHEA-treated rats. This was primarily attributed to a decrease in fat cell number in lean rats and to decreases in both number and size of fat cells in obese rats. In experiment 3 obese female rats were treated with DHEA from 6 to 21 weeks of age followed by 15 weeks with DHEA removed from the diet. Significantly more weight was gained by the rats previously treated than by the control rats, but body weight remained significantly lower than in the control groups. These data indicate DHEA has an effect on altering body weight and body fat in lean and obese Zucker rats.


The effect of wortmannin on the localisation of lysosomal type I integral membrane glycoproteins suggests a role for phosphoinositide 3-kinase activity in regulating membrane traffic late in the endocytic pathway.
Addition of wortmannin to normal rat kidney cells caused a redistribution of the lysosomal type I integral membrane proteins Igp110 and Igp120 to a swollen vacuolar compartment. This compartment did not contain the cation independent mannose 6-phosphate receptor and was depleted in acid hydrolases. It was distinct from another swollen vacuolar compartment containing the cation independent mannose 6-phosphate receptor. The swollen Igp110-positive compartment was accessible to a monoclonal antibody against Igp120 added extracellularly, showing that it had the characteristics of an endosomal compartment. Wortmannin had no gross morphological effect on the trans-Golgi network or lysosomes nor any effect on the delivery to the trans-Golgi network of endocytosed antibodies against the type I membrane protein TGN38. We propose that the observed effects of wortmannin were due to inhibition of membrane traffic between cation independent mannose 6-phosphate receptor-positive late endosomes and the trans-Golgi network and to inhibition of membrane traffic between a novel Igp120-positive, cation independent mannose 6-phosphate receptor-negative late endosomal compartment and lysosomes. The effects of wortmannin suggest a function for a phosphatidylinositol 3-kinase(s) in regulating membrane traffic in the late endocytic pathway.


Impact of Lockdown Measures on Health Outcomes of Adults with Type 2 Diabetes Mellitus in Bangladesh.
COVID-19 lockdown measures appreciably affected patients' lifestyles, negatively impacting on their health. This includes patients with Type 2 Diabetes Mellitus (T2DM). Care of these patients was also negatively impacted due to a priority to treat patients with COVID-19, certainly initially, within hospitals and clinics in Bangladesh, combined with a lack of access to clinics and physicians due to lockdown and other measures. This is a concern in Bangladesh with growing rates of T2DM and subsequent complications. Consequently, we sought to critically analyze the situation among patients with T2DM in Bangladesh during the initial stages of the pandemic to address this information gap and provide future direction. Overall, 731 patients were recruited by a simple random sampling method among patients attending hospitals in Bangladesh, with data collected over 3 timescales: before lockdown, during the pandemic, and after lockdown. Data extracted from patients' notes included current prescribed medicines and key parameters, including blood sugar levels, blood pressure, and comorbidities. In addition, the extent of record keeping. The glycemic status of patients deteriorated during lockdown, and comorbidities as well as complications related to T2DM increased during this period. Overall, a significant proportion of key datasets were not recorded in patients' notes by their physician before and during lockdown. This started to change after lockdown measures eased. In conclusion, lockdown measures critically affected the management of patients with T2DM in Bangladesh, building on previous concerns. Extending internet coverage for telemedicine, introduction of structured guidelines, and appreciably increasing data recording during consultations is of the utmost priority to improve the care of T2DM patients in Bangladesh.


A Review of Probiotic Supplementation and Feasibility of Topical Application for the Treatment of Pediatric Atopic Dermatitis.
Atopic dermatitis is a chronic inflammatory skin disease that commonly occurs in early childhood. To date, the pharmacological treatment of atopic dermatitis is far from ideal, poses several limitations, and constantly requires novel approaches. The theory that appropriate colonization of gut bacteria during infancy influences the development of the immune system has prompted numerous clinical trials that have evaluated the effectiveness of probiotic supplementation for the prevention and treatment of atopic eczema in children. In addition, topical application of probiotics has been demonstrated to improve the skin's barrier function, which might contribute to reduce the severity of atopic dermatitis. In this article, we review the literature and data regarding the use of probiotics, both by oral administration and topical application, for the treatment of atopic dermatitis. We also summarize the knowledge on the potential mechanisms by which probiotics influence the gut and exert their skin effects. Probiotic supplementation seems to be an attractive strategy to prevent and treat pediatric atopic dermatitis. However, to enable the treatment to be fully effective, the period of supplementation should be considered. Moreover, in future studies, a combination of probiotic supplementation and simultaneous topical application of creams containing probiotics might also be considered.


Development of Chinese chestnut whiskey: yeast strains isolation, fermentation system optimization, and scale-up fermentation.
In this study, we used Chinese chestnut as the main raw material to develop a novel type of whiskey. First, 16 yeasts were isolated and identified for producing aroma using olfactory plate assay. Of these, we screened nine yeast strains based on their fermentation capacity, aroma profile, and sensory evaluation. The results demonstrated the combination of strains HN006 (Saccharomyces cerevisiae) and HN010 (Wickerhamomyces anomalus) provided satisfactory wine fermentation with an interesting flavor profile, as strain HN010 was highly aromatic and had elevated sensory scores with comparatively low ethanol yield, while strain HN006 had a poor flavor profile but produced the largest amount of ethanol. Subsequently, we co-cultured strains HN006 and HN010 to optimize the fermentation system. The results revealed the following optimum parameters: a mixed inoculum of 6% (v/v) at an HN006/HN010 ratio of 1:2 (v/v), a raw material ratio of 5:3:2 (chestnut: malt: glutinous rice), and yeast extract concentration of 6 g/L. Additionally, this fermentation system was successfully scaled-up to a 1000 L pilot-scale system. The results of this study showed that strains HN006 and HN010 could be used as alternatives for whiskey fermentation, as well as provided a generalized experimental scheme to assess other microorganisms.


Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: implications for sudden infant death syndrome.
Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.


Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.
A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.


Design for broadband high-efficiency grating couplers.
In this Letter, we propose general optimization methods to design broadband high-efficiency grating couplers for planar waveguides. We attribute the coupling bandwidth to the mismatch of effective indices between the diffracted beam and the actual grating structure around the operation wavelength for fiber to waveguide excitation. The coupling bandwidth formula is deduced. A simple parameter-separate optimization procedure is proposed for general layered grating couplers for high coupling efficiency. Using our principle, we optimized a grating coupler for a horizontal slot waveguide operating at wavelength 1.55 μm for TM polarization. The grating coupler has 1 dB bandwidth of 60 nm and coupling efficiency of 65% with incident light from single-mode optical fiber (SMF) at 8°.


Evidence for metabolism of o-xylene by simultaneous ring and methyl group oxidation in a new soil isolate.
An o-xylene-utilizing Rhodococcus, strain B3, was isolated from enrichments with o-xylene. The pathway for o-xylene degradation was investigated by simultaneous adaptation experiments, studies of product formation by a mutant and fortuitous oxidation studies using trimethylbenzene isomers as substrates. Two pathways were found to operate simultaneously and both were inducible. The first pathway involved the oxidation of a methyl group to form 2-methylbenzyl alcohol, followed by oxidation via the corresponding acid to 3-methylcatechol. The second pathway involved oxidation of the aromatic ring to form a dimethylcatechol. The bulk of the evidence suggests that the initial reaction was catalysed by a monooxygenase rather than a dioxygenase, and that 2,3-dimethylphenol was produced as an intermediate.


'Rallying around the flag': Can an intergroup contact intervention promote national unity?
A longitudinal study evaluated the success of a contact-based nation-building intervention (the Malaysian National Service Programme) in promoting various facets of national unity. The study assessed how post-test measures of quality of intergroup contact, outgroup evaluations, and levels of identification changed compared to their respective pre-test levels, for both National Service and control group participants. The intervention did not lead to a worsening of any of the constructs related to intergroup relations, which is noteworthy given the novelty for many participants of mixing in a multi-ethnic setting. Furthermore, all rater groups (Malays, Chinese, and Indians) maintained their ethnic identity, even in the presence of high levels of national identity, which we discuss with respect to past research on the effects of positive intergroup contact on minority group identification. However, the changes associated with the intervention yielded only small effect sizes, and, on the whole, National Service participants did not show significantly greater improvement than that experienced by control participants. We discuss the value of intergroup contact in this novel setting, considering various features of this programme that may have limited its effectiveness and discuss how such interventions can more successfully meet their goals.


Assessment of instrumental activities of daily living in dementia: diagnostic value of the Amsterdam Instrumental Activities of Daily Living Questionnaire.
Measuring impairments in "instrumental activities of daily living" (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting. Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and "disability assessment of dementia" (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses. Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63-0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A-IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not. In this study, we showed a fair diagnostic accuracy for A-IADL-Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool.


Sensory nerve recovery following median nerve provocation in carpal tunnel syndrome.
The purpose of this study was to evaluate the recovery of median nerve sensory nerve action potentials (SNAP) following median nerve provocation in hands with carpal tunnel syndrome (CTS). Repeated nerve conduction measurements were performed before and after wrist flexion combined with resisted finger flexion in 35 hands with a clinical diagnosis of CTS and in 25 asymptomatic control hands. Orthodromic sensory median nerve potentials were recorded over an 8 cm segment between the palm and wrist. Hands with CTS had significant reductions in nerve potential amplitude and latency following median nerve provocation. Hands with mild to moderate CTS, had the greatest reductions in nerve potential amplitude and the longest amplitude recovery times following median nerve provocation. Determination of changes in amplitude and amplitude recovery time of the median nerve SNAP following median nerve provocation has the potential to improve the accuracy of the electrophysiological diagnosis of CTS.


Burden of illness, visual impairment and health resource utilisation of patients with neovascular age-related macular degeneration: results from the UK cohort of a five-country cross-sectional study.
Quantitative data regarding the impact of neovascular age-related macular degeneration (NV-AMD) on individuals and society is a prerequisite for rational decision-making processes when evaluating alternative treatments for the disease. 75 bilateral NV-AMD (patients) and 91 elderly non-AMD (controls) subjects forming the UK cohort of an international cross-sectional, observational study were independently analysed. Subjects completed a telephone survey including the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), history of falls and health resource utilisation. Patients with NV-AMD reported substantially worse vision-related functioning and overall well-being, including higher depression scores, than controls after adjusting for age, gender and co-morbidities (adjusted mean scores: NEI-VFQ-25 overall 52.7 vs 90.7, p<0.0001; EQ-5D 0.67 vs 0.77, p = 0.0273; HADS depression 6.8 vs 4.0, p = 0.0026). Significantly more patients reported a need for assistance with daily activities compared with controls (25.3% vs 6.6%, p = 0.003). Total annual healthcare utilisation costs were more than sevenfold higher for patients with AMD compared with controls ( pound 3,823.89 vs pound 517.05, respectively; p<0.0001) Patients with NV-AMD show a significant decline in quality of life and increased need for daily living assistance compared to a control population without AMD. With the availability of effective new therapies there is a need for improved early access to treatment.


Influence of independent and proximate variables on condom use in selected states in Nigeria.
The study examined the influence of individual and proximate factors in determining condom use. Current use of condom and condom use during last sex were used as proxies for consistent condom use. Data on 3,797 sexually active respondents of reproductive age were analyzed from the 2007 USAID-COMPASS midline evaluation on basic family planning and reproductive health outcomes in five Nigerian states. About 9% of respondents were current users, while 11% used a condom during last sex. Younger and more educated respondents were more likely to report condom use. Of the 23 variables, four were statistically significant (p < 0.05) in predicting current use for females, and five for males; six were statistically significant in predicting condom use during last sex for females and seven for males. The paper concluded that understanding the determinants and predictors of condom use is critical to improving family planning and reproductive health indicators in Nigeria.


The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression.
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression.Significance: We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic. Cancer Discov; 8(4); 403-16. ©2018 AACR.See related commentary by Riquelme et al., p. 386This article is highlighted in the In This Issue feature, p. 371.


Follow-up results of synthetic vascular grafts in children undergoing hemodialysis.
Polytetrafluoroethylene (PTFE) grafts were inserted in the thigh of 14 children (7 boys and 7 girls, age 12 +/- 1.8 years) who were undergoing chronic hemodialysis for endstage renal disease. Removal of grafts was necessary in three patients within three months of implantation. In a fourth case it was indicated in the fifteenth month. In two cases thrombectomy was necessary. Echocardiography was performed in 10 patients before and three and 12 months after surgery. Cardiac performance followed by echocardiography did not change after one year. After two years the survival of grafts was 71%. It appears that synthetic grafts offer advantages for pediatric hemodialysis patients with arteriovenous fistula failure. On the other hand, this technique entails serious risks.


Addressing the challenges of cardiorenal syndrome.
In heart failure, as the heart gets worse, often so do the kidneys, complicating the treatment of heart failure and worsening the prognosis. This article addresses challenges in the use of diuretics, angiotensin-converting enzyme (ACE) inhibitors, and other therapies in the cardiorenal syndrome, as well as novel therapies that hold promise, such as arginine vasopressin antagonists, adenosine A1 receptor antagonists, and ultrafiltration.


Post-epidemic Schmallenberg virus circulation: parallel bovine serological and Culicoides virological surveillance studies in Ireland.
Schmallenberg virus (SBV) emerged in northern-Europe in 2011 resulting in an epidemic of ruminant abortions and congenital malformations throughout the continent. In the years following the epidemic there have been reports of SBV overwintering and continued circulation in several European countries. When the population-level of immunity declines in exposed regions, re-introduction of SBV could result in further outbreaks of Schmallenberg disease. The aims of this study were to determine the SBV seroprevalence in previously exposed Irish dairy herds in 2014 and to investigate if SBV continued to circulate in these herds in the three years (2013-2015) following the Irish Schmallenberg epidemic. Whole-herd SBV serosurveillance was conducted in 26 herds before (spring) and following the 2014 vector-season (winter), and following the 2015 vector-season (winter). In spring 2014, 5,531 blood samples were collected from 4,070 cows and 1,461 heifers. In winter 2014, 2,483 blood samples were collected from 1,550 youngstock (8-10 months old) and a subsample (n = 933; 288 cows, 645 heifers) of the seronegative animals identified in the spring. Youngstock were resampled in winter 2015. Culicoides spp. were collected in 10 herds during the 2014 vector-season and analysed for SBV; a total of 138 pools (3,048 Culicoides) from 6 SBV vector species were tested for SBV RNA using real-time PCR. In spring 2014, animal-level seroprevalence was 62.5 % (cows = 84.7 %; heifers = 0.6 %). Within-herd seroprevalence ranged widely from 8.5 %-84.1 % in the 26 herds. In winter 2014, 22 animals (0.9 %; 10 cows, 5 heifers, 7 youngstock) originating in 17 herds (range 1-4 animals/herd) tested seropositive. In winter 2015 all youngstock, including the 7 seropositive animals in winter 2014, tested seronegative suggesting their initial positive result was due to persistence of maternal antibodies. All of the Culicoides pools examined tested negative for SBV-RNA. SBV appears to have recirculated at a very low level in these herds during 2013 and 2014, while there was no evidence of SBV infection in naïve youngstock during 2015. A large population of naïve animals was identified and may be at risk of infection in future years should SBV re-emerge and recirculate as it has done in continental Europe.


Current Status of Organ Preservation in Carcinoma Larynx.
Organ preservation in carcinoma larynx is a long debated topic. There are multiple organ preserving approaches in the management of carcinoma larynx depending on various factors. Radical radiotherapy (RT) and conservation laryngeal surgery have shown equivalent results in early laryngeal cancer. Concurrent chemoradiation (CTRT) is the standard treatment in stage III and IV laryngeal cancer with intact cartilage and functional larynx. Patients with cartilage destruction or dysfunctional larynx are not the candidates for organ preservation. This systematic review is aimed at discussing the evolution of different organ preserving approaches, their efficacy, impact on voice quality, their pitfalls and future directions.