Relations between PTSD and distress dimensions in an Indian child/adolescent sample following the 2008 Mumbai terrorist attacks.
Posttraumatic stress disorder's (PTSD) four-factor dysphoria model has substantial empirical support (reviewed in Elhai & Palmieri, Journal of Anxiety Disorders, 25, 849-854, 2011; Yufik & Simms, Journal of Abnormal Psychology, 119, 764-776, 2010). However, debatable is whether the model's dysphoria factor adequately captures all of PTSD's emotional distress (e.g., Marshall et al., Journal of Abnormal Psychology, 119(1), 126-135, 2010), which is relevant to understanding the assessment and psychopathology of PTSD. Thus, the present study assessed the factor-level relationship between PTSD and emotional distress in 818 children/adolescents attending school in the vicinity of the 2008 Mumbai terrorist attacks. The effective sample had a mean age of 12.85 years (SD = 1.33), with the majority being male (n = 435, 53.8 %). PTSD and emotional distress were measured by the UCLA PTSD Reaction Index (PTSD-RI) and Brief Symptom Inventory-18 (BSI-18) respectively. Confirmatory factor analyses (CFA) assessed the PTSD and BSI-18 model fit; Wald tests assessed hypothesized PTSD-distress latent-level relations; and invariance testing examined PTSD-distress parameter differences using age, gender and direct exposure as moderators. There were no moderating effects for the PTSD-distress structural parameters. BSI-18's depression and somatization factors related more to PTSD's dysphoria than PTSD's avoidance factor. The results emphasize assessing for specificity and distress variance of PTSD factors on a continuum, rather than assuming dysphoria factor's complete accountability for PTSD's inherent distress. Additionally, PTSD's dysphoria factor related more to BSI-18's depression than BSI-18's anxiety/somatization factors; this may explain PTSD's comorbidity mechanism with depressive disorders.


Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial.
Intermediate saphenous vein graft (SVG) lesions have high rates of progression. The purpose of this study was to examine the impact of extended-release niacin (ER-niacin) vs placebo on intermediate SVG lesions. Patients with intermediate (30%-60% diameter stenosis) SVG lesions were randomized to ER-niacin vs placebo for 12 months. Quantitative coronary angiography (QCA), intravascular ultrasonography (IVUS), and optical coherence tomography (OCT) were performed at baseline and at 12 months. The primary endpoint was change in percent atheroma volume (ΔPAV). Enrollment was planned for 138 patients for 90% power to detect ≥2.5% difference in the primary endpoint of ΔPAV, but stopped early after publication of two negative outcome trials of ER-niacin, with enrolled patients completing the 12-month trial protocol. Thirty-eight patients were randomized to niacin (n = 19) or placebo (n = 19), yielding power of 47% to detect the primary planned treatment effect of 2.5 ± 4.0% difference in ΔPAV. Between baseline and 12-month follow-up, no significant difference was found between study groups in ΔPAV (-1.31 ± 6.05% vs 1.05 ± 17.8%; P=.60). By OCT, the ER-niacin vs placebo group had less plaque rupture within the intermediate SVG lesion (0.0% vs 36.0%; P=.01). Administration of ER-niacin did not significantly impact intermediate SVG disease, with the notable limitation of compromised statistical power due to early termination of enrollment.


Regional long-term co-operation in the field of nuclear and radiation emergency preparedness.
Emergency preparedness is generally covered by methodical and coordinative activities of the International Atomic Energy Agency (IAEA) in Member States of the IAEA and by the European Commission (EC) in EU Member and EU Accession Countries. However, the regional harmonisation of emergency arrangements is an important trend of emergency preparedness. The present paper gives a couple of illustrative examples for a regional co-operation in the field of emergency preparedness in Central Europe and an overview on international exercises in this region. The penultimate section contains an outlook on future activities regarding regional co-operation in Central Europe. The following topics have been suggested inter alia: the harmonisation of intervention criteria and countermeasures, co-ordination in the field of information of the public, comprehensive bi lateral and multilateral exercises, exchange of experts between the national nuclear emergency centres and inter-comparison calculations of the computer codes.


Comparative genotoxicity evaluation of imidazolinone herbicides in somatic cells of Drosophila melanogaster.
In the present study, five analogous herbicides, namely Imazapyr (IMZR), Imazapic (IMZC), Imazethapyr (IMZT), Imazamox (IMZX) and Imazaquin (IMZQ), were evaluated for genotoxicity (mutagenic and recombinagenic activity) in the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. They are classified as imidazolinone (IMI) herbicides and their mode of action is to inhibit acetohydroxyacid synthase (AHAS), an enzyme involved in the biosynthesis of the amino acids leucine, isoleucine and valine. Two crosses were used: the standard (ST) cross and the high bioactivation (HB) cross. The latter is characterized by high levels of cytochrome P450 conferring increased sensitivity to promutagens and procarcinogens. Three-day-old larvae were exposed by chronic feeding (48 h) to four different concentrations of these herbicides (2.5, 5.0, 10.0 or 20.0 mM). For the evaluation of genotoxic effects, the frequencies of spots per individual in the treated series were compared to the concurrent negative control series (ultrapure water). Imazapyr, Imazapic and Imazethapyr gave negative results with both crosses of the wing spot test. In the ST cross, Imazamox showed positive results only for large single spots (20.0 mM IMZX) and weak positive results for total spots (10.0 and 20.0 mM IMZX), while Imazaquin showed positive results only for large single spots (5.0 and 20.0mM IMZQ) and a weak positive result for total spots (20.0 mM IMZQ). These positive results are mainly due to induced recombination and to a minor extent to mutations. In the HB cross, only Imazamox (5.0 mM IMZX) showed a weak positive result for small single spots. The positive control urethane, a promutagen, caused an increase in the number of all types of spots in both crosses. In conclusion, the results of chronic treatments performed at high doses (toxicity was observed at higher doses) shows the existence of a genotoxic risk for IMZX and IMZQ exposure under these experimental conditions, and indicate the need for further research to delineate the exact mechanisms involved.


A CZT-based blood counter for quantitative molecular imaging.
Robust quantitative analysis in positron emission tomography (PET) and in single-photon emission computed tomography (SPECT) typically requires the time-activity curve as an input function for the pharmacokinetic modeling of tracer uptake. For this purpose, a new automated tool for the determination of blood activity as a function of time is presented. The device, compact enough to be used on the patient bed, relies on a peristaltic pump for continuous blood withdrawal at user-defined rates. Gamma detection is based on a 20 × 20 × 15 mm3 cadmium zinc telluride (CZT) detector, read by custom-made electronics and a field-programmable gate array-based signal processing unit. A graphical user interface (GUI) allows users to select parameters and easily perform acquisitions. This paper presents the overall design of the device as well as the results related to the detector performance in terms of stability, sensitivity and energy resolution. Results from a patient study are also reported. The device achieved a sensitivity of 7.1 cps/(kBq/mL) and a minimum detectable activity of 2.5 kBq/ml for 18F. The gamma counter also demonstrated an excellent stability with a deviation in count rates inferior to 0.05% over 6 h. An energy resolution of 8% was achieved at 662 keV. The patient study was conclusive and demonstrated that the compact gamma blood counter developed has the sensitivity and the stability required to conduct quantitative molecular imaging studies in PET and SPECT.


Loss of heterozygosity on the short arm of chromosome 17 is associated with high proliferative capacity and DNA aneuploidy in primary human breast cancer.
Loss of heterozygosity (LOH) on the short arm of chromosome 17 (17p) was found in 27 of 52 (52%) previously untreated primary breast cancers. There was a significant correlation between this 17p allelic loss and two parameters associated with aggressive tumor behavior: high cellular proliferative fraction and DNA aneuploidy. These correlations with high cellular proliferative fraction and DNA aneuploidy were not found in tumors with LOH at nine other chromosome locations. The p53 gene, a putative tumor suppressor gene located at 17p13, was examined for aberrations to determine whether it is the target for the 17p LOH in breast cancer. Unlike other types of human cancer, there were no homozygous deletions or rearrangements of the p53 gene, and only 2 of 13 (15%) were mutated in the conserved region where mutational "hot spots" have been previously located. Therefore, we hypothesize that, in breast cancer, either loss or inactivation of gene(s) on chromosome 17p other than the p53 gene or a different mechanism of p53 gene inactivation may be responsible for the observed high labeling index and DNA aneuploidy associated with LOH at 17p.


Fatty Acids Increase GDF15 and Reduce Food Intake Through a GFRAL Signaling Axis.
In contrast to the well-defined biological feedback loops controlling glucose, the mechanisms by which the body responds to changes in fatty acid availability are less clearly defined. GDF15 suppresses the consumption of diets high in fat but is paradoxically increased in obese mice fed a high-fat diet. Given this interrelationship, we investigated whether diets high in fat could directly increase GDF15 independently of obesity. We found that fatty acids increase GDF15 levels dose-dependently with the greatest response observed with linolenic acid. GDF15 mRNA expression was modestly increased in the gastrointestinal tract, however, kidney GDF15 mRNA was ~1000-fold higher and was increased by over 3-fold with subsequent RNAscope analysis showing elevated expression within the cortex and outer medulla. Treatment of wildtype mice with linolenic acid reduced food intake and body mass, however, this effect was disappeared in mice lacking the GDF15 receptor GFRAL. An equal caloric load of glucose did not suppress food intake or reduce body mass in either WT or GFRAL KO mice. These data indicate that fatty acids such as linolenic acid increases GDF15 and suppresses food intake through a mechanism requiring GFRAL. These data suggest that a primary physiological function of GDF15 may be as a fatty acid sensor designed to protect cells from fatty acid overload.


Effects of bilateral vagal cold block on vasopressin in conscious dogs.
Bilateral vagal cold block was used to interrupt afferent nerve traffic in the cervical vagi and thus to determine the tonic inhibitory influence of vagal afferents on plasma arginine vasopressin (AVP) concentrations in the conscious dog. Experiments were performed in conscious aortic baroreceptor-denervated dogs with carotid baroreflexes intact or with sinoaortic denervation. In the presence of intact carotid baroreflexes (n = 11) vagal cold block significantly increased arterial pressure (99 +/- 5 to 120 +/- 8 mmHg), heart rate (98 +/- 2 to 168 +/- 11 beats/min), and AVP (2.9 +/- 0.6 to 6.7 +/- 1.3 microU/ml). Chronic sinoaortic denervation did not significantly alter plasma AVP (4.4 +/- 1.0 microU/ml). However, vagal cold block in these totally denervated animals caused a significantly greater increase in arterial pressure (116 +/- 7 to 167 +/- 7 mmHg) and plasma AVP (4.4 +/- 1 to 33.4 +/- 4.8 microU/ml) compared with the responses observed in dogs with intact carotid baroreflexes. These results indicate that vagal afferent nerves exert a significant tonic inhibitory influence on the secretion of AVP in the conscious aortic baroreceptor-denervated dogs as well as in dogs with sinoaortic denervation.


Does collimation affect patient dose in antero-posterior thoraco-lumbar spine?
The purpose of this study is to determine the effect of collimation on the lifetime attributable risk (LAR) of cancer incidence in all body organs (effective risk) in patients undergoing antero-posterior (AP) examinations of the spine. This is of particular importance for patients suffering from scoliosis as in their case regular repeat examinations are required and also because such patients are usually young and more susceptible to the effects of ionising radiation than are older patients. High sensitivity thermo-luminescent dosimeters (TLDs) were used to measure radiation dose to all organs of an adult male dosimetry phantom, positioned for an AP projection of the thoraco-lumbar spine. Exposures were made, first applying tight collimation and then subsequently with loose collimation, using the same acquisition factors. In each case, the individual TLDs were measured to determine the local absorbed dose and those representing each organ averaged to calculate organ dose. This information was then used to calculate the effective risk of cancer incidence for each decade of life from 20 to 80, and to compare the likelihood of cancer incidence when using tight and loose collimation. The calculated figures for effective risk of cancer incidence suggest that the risk when using loose collimation compared to the use of tight collimation is over three times as high and this is the case across all age decades from 20 to 80. Tight collimation can greatly reduce radiation dose and risk of cancer incidence. However collimation in scoliotic patients can be necessarily limited.


Healthcare Workers and Nonhealthcare Workers Pro-Vaccination Attitude and Its Associated Factors towards COVID-19 Vaccine Globally: A Systematic Review and Meta-Analysis.
Coronavirus disease 2019 (COVID-19) pandemic has not been managed and controlled globally. The aim of this systematic review and meta-analysis were to determine the global pro-vaccination attitude and associated factors towards COVID-19 vaccine among healthcare workers (HCWs) and nonhealthcare workers (non-HCWs). Different databases such as PubMed, Scopus, EMBASE, and Google Scholar were used. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 flowchart diagram and PRISMA checklist were used for study screening, selection, and inclusion into this systematic review and meta-analysis. Newcastle-Ottawa Scale (NOS) quality assessment criteria for cross-sectional studies were used to assess the included articles. A total of 51 studies were included into this systematic review and meta-analysis. The meta-analysis revealed that the global pooled prevalence of pro-vaccination attitude towards COVID-19 vaccine among both HCWs and non-HCWs was 61.30% (95%CI: 56.12, 66.47, I 2 = 99.8%: p=0.000). Subgroup analysis showed that the global pooled prevalence of pro-vaccination attitude towards COVID-19 vaccine was the lowest (59.77%, 95%CI (51.56, 67.98); I 2 = 99.6%, p=0.000) among the HCWs participants and the highest (62.53%, 95%CI (55.39, 69.67); I 2 = 99.8%, p=0.000) among the non-HCWs participants and the lowest (54.31%, 95%CI (43, 65.63); I 2 = 99.5%, p=0.000) for sample size <700 and the highest (66.49%, 95%CI (60.01, 72.98); I 2 = 99.8%, p=0.000) for sample size >700; the lowest (60.70%, 95%CI (54.08, 67.44); I 2 = 93.0%, p=0.000) for studies published in 2020 year and the highest (61.31%, 95%CI (55.93, 66.70); I 2 = 99.8%, p=0.000) for the studies published after 2020 years. From this systematic review, factors significantly associated with pro-vaccination attitude towards COVID-19 vaccine among HCWs were such as age, gender, race, work experience, home location, having no fear of injections, being a non-smoker, profession, presence of chronic illnesses, allergies, confidence in pharmaceutical companies, history of taking influenza vaccine, vaccine recommendation, perceived risk of new vaccines, perceived utility of vaccine, receiving a seasonal flu vaccination in the last 5 years, working in a private hospital, a high perceived pandemic risk index, low vaccine harm index, high pro-socialness index, being in close contact with a high-risk group, knowledge about the virus, confidence in and expectations about personal protective equipment, and behaviors. The level of positive attitude towards COVID-19 vaccine among non-HCWs ranged from 21.40% to 91.99%. Factors associated with the attitude towards COVID-19 vaccine among non-HCWs were such as age, gender, educational level, occupation, marital status, residency, income, ethnicity, risk for severe course of COVID-19, direct contact with COVID-19 at work, being a health profession, being vaccinated against seasonal flu, perceived benefits, cues to actions, having previous history of vaccination, fear of passing on the disease to relatives, and the year of medical study, studying health-related courses, COVID-19 concern, adherence level to social distancing guidelines, history of chronic disease, being pregnant, perceived vaccine safety, having more information about vaccine effectiveness, mandatory vaccination, being recommended to be vaccinated, lack of confidence in the healthcare system to control epidemic, and belief in COVID-19 vaccines protection from COVID-19 infection. This meta-analysis revealed that the global estimated pooled prevalence of pro-vaccination attitude towards COVID-19 vaccine among both HCWs and non-HCWs was unsatisfactory. Globally, there is a need for a call for action to cease the crisis of this pandemic.


Adiposity cut-off points for cardiovascular disease and diabetes risk in the Portuguese population: The PORMETS study.
The contribution of adiposity to cardiovascular and diabetes risk justifies the inclusion of an adiposity measure, usually waist circumference, in the definition of metabolic syndrome. However, waist circumference thresholds differ across populations. Our aim was to assess which adiposity measure performs the best in identifying the metabolic syndrome in a sample of Portuguese participants and to estimate cut-off values for these measures. Data were obtained from a cross-sectional study (PORMETS study) conducted in Portugal between 2007 and 2009. A representative sample of non-institutionalized adults, comprising 3,956 participants, aged 18 years and older, was evaluated. A structured questionnaire was administered, collecting information on personal medical history, socio-demographics and behavioral characteristics. Anthropometrics, blood pressure and venous blood samples were also obtained. Metabolic syndrome was defined according to the Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology recommended criteria. Elevated cardiometabolic risk was considered when two or more of the four criteria of metabolic syndrome were present, excluding the waist circumference component. A receiver operating characteristic curve was used to estimate cut-off points. This study found that waist-to-height ratio, waist circumference and body adiposity index performed better than other adiposity measures, such as body mass index. The estimated cut-off points for waist-to-height ratio, waist circumference and body adiposity index in women and men were 0.564 / 89 cm / 27.4 and 0.571 / 93.5 cm / 25.5, respectively. As waist circumference is currently used as the adiposity measure in the definition of metabolic syndrome and as no relevant differences were observed between this measure and waist-to-height ratio, it is likely that no modification to the metabolic syndrome definition needs to be proposed. Moreover, this study also confirmed the applicability of European cut-off points in the Portuguese population.


Three-Dimensional Bioprinting Strategies for Tissue Engineering.
Over the past decades, many approaches have been developed to fabricate biomimetic extracellular matrices of desired properties for engineering functional tissues. However, the inability of these techniques to precisely control the spatial architecture has posed a significant challenge in producing complex tissues. 3D bioprinting technology has emerged as a potential solution by bringing unprecedented freedom and versatility in depositing biological materials and cells in a well-controlled manner in the 3D volumes, therefore achieving precision engineering of functional tissues. In this article, we review the application of 3D bioprinting to tissue engineering. We first discuss the general strategies for printing functional tissue constructs. We next describe different types of bioprinting with a focus on nozzle-based techniques and their respective advantages. Finally, we summarize the limitations of current technologies and propose challenges for future development of bioprinting.


Segmental colitis associated with diverticulosis syndrome.
An inflammatory process that involves the sigmoid colonic segment associated with diverticular disease (SCAD) appears to be a distinct clinical and pathological disorder. It has been described in older adults, often presenting with rectal bleeding. Most of the patients seem to respond to treatment only with a 5-aminosalicylate, but some spontaneously resolve with no treatment. Endoscopic evaluation usually shows a non-specific inflammatory process localized in the sigmoid colon alone that may resolve completely with histologically normal colonic mucosa. Repeated symptomatic events with discrete episodes of segmental colitis may occur, but most patients have an entirely benign clinical course. Definition of the underlying molecular events that occur with SCAD may be critically important in understanding the critical elements present in a colonic inflammatory process that can completely resolve without pharmacological or biological treatment.


Parkinson's disease: low-dose haloperidol increases dopamine receptor sensitivity and clinical response.
Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson's disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson's disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson's disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson's disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.


Azo polymer microspherical cap array: soft-lithographic fabrication and photoinduced shape deformation behavior.
In this work, azo polymer microspherical cap arrays possessing unique photoprocessible properties have been fabricated through a soft-lithographic contact printing approach. In the process, hexagonal polystyrene (PS) colloidal arrays, obtained by the vertical deposition method, were used as masters. Poly(dimethylsiloxane) (PDMS) stamps with aligned hemisphere air voids on the surfaces were obtained by casting the precursor against the colloidal arrays. By using the stamps and a solution of an epoxy-based azo polymer (BP-AZ-CA) as "ink", the microspherical cap arrays were fabricated by pressing the "inked" surfaces against substrates. Uniform 2D arrays of the submicrometer spherical caps could be obtained on the substrates after peeling off the stamps and drying. The characteristic sizes of the arrays depended on some adjustable features, such as the diameters of PS spheres and concentrations of the "inks" used in the process. After exposure to a linearly polarized Ar+ laser single beam, the spherical caps could be stretched along the polarization direction, and the arrays were consequently transformed into ellipsoidal cap arrays. Upon irradiation of interfering p-polarized Ar+ laser beams, only the spherical caps in the bright fringes were deformed by the light irradiation, which resulted in more complicated surface relief patterns. The observation gives another well-defined example of the photoinduced mass migration in the submicrometer scale. The approach can potentially be applied to fabrication of microlens arrays with different converging rate in two directions.


H2-M3, a full-service class Ib histocompatibility antigen.
H2-M3 is an MHC class Ib molecule of the mouse with a unique preference for N-formylated peptides, which may come from the N-termini of endogenous, mitochondrial proteins or foreign, bacterial proteins. The crystal structure of M3 revealed a hydrophobic peptide-binding groove with an occluded A pocket and the peptide shifted one residue relative to class Ia structures. The formyl group is held by a novel hydrogen bonding network, involving His9 on the bottom of the groove, and the side chain of the P1 methionine is lodged in the B pocket. M3 is a full-service histocompatibility (H) antigen, i.e. self-M3 can present endogenous peptides as minor H antigens and foreign, bacterial antigens in a defensive immune response to infection; and foreign M3 complexed with endogenous self-peptides.


Further studies on difluoromethylornithine in African trypanosomes.
DL-alpha-Difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC) was previously shown to cure mice infected with Trypanosoma brucei brucei, a parasite of game and cattle in Africa and Trypanosoma brucei rhodesiense, a human African Sleeping Sickness pathogen. Our studies now indicate that DFMO blocks ornithine decarboxylase and lowers trypanosome polyamine levels in vivo. Polyamine uptake in T.b. brucei also resembles that previously described for mammalian cells. The therapeutic potential of DFMO can now also be extended to another human pathogen, Trypanosoma brucei gambiense. Finally, DFMO acts synergistically with another drug, bleomycin, to cure acute trypanosome infections, and furthermore, this same drug combination provides a new approach to the treatment of trypanosomal infections of the central nervous system.


(99M)Tc-ciprofloxacin in imaging of clinical infections in camelids and a goat.
(99M)Tc-ciprofloxacin was used to image five adult camelids and a juvenile goat with clinical and/or radiographic signs of infection. (99m)Tc-ciprofloxacin (range 10-33 MBq/kg) was injected intravenously and a series of 2-min static images were acquired at 1- and 4-h postinjection. At 24-h postinjection, 5-min static images were acquired. Only the skull or abdomen was imaged in the adults; the whole body was imaged in the goat. The quality of the 1-, 4-, and 24-h studies was evaluated subjectively. Normal and abnormal areas of (99m)Tc-ciprofloxacin uptake were recorded and subjectively graded as mild, moderate or intense. Image quality was best 4-h postinjection. Twenty-four-hour images were poor because of insufficient radioactivity. (99m)Tc-ciprofloxacin imaging resulted in true positive or true negative scans in four of six animals. Two false-negative studies occurred. Intense (99m)Tc-cirofloxacin activity was seen in the lungs and urinary bladder, moderate/intense activity in the kidneys, and mild activity in the physes/epiphyses, liver and intermittently in the gastrointestinal tract. The normal distribution of (99m)Tc-ciprofloxacin in camelids/small ruminants differed from people. Further studies to determine the sensitivity and specificity of infection detection using (99m)Tc-ciprofloxacin in animals are warranted.


The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster.
We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.


[Role of full-time nurses in reception of sperm donors in the sperm bank].
To explore the necessity of reception of sperm donors by full-time nurses in the sperm bank by analyzing the efficiency of sperm donation before and after staffing Guangdong Sperm Bank (GSB) with full-time nurses. We selected 9 712 qualified sperm donors in GSB from January 1, 2016 to December 31, 2021 and compared the efficiency of sperm donation before and after staffing GSB with full-time nurses. After staffing GSB with full-time nurses, the proportion of qualified sperm donors screened from the quasi-qualified ones was dramatically increased from 66.2% (1 230/1 858) to 77.1% (3 252/4 218) (P < 0.01), that of HIV re-examinees after 6-month suspension from sperm donation increased from 84.6% (137/162) to 93.4% (599/641) (P < 0.01), and that of the candidate donors lost to follow-up during the screening period decreased from 23.2% (831/3 583) to 21.3% (1 308/6 129) (P = 0.034). After Guangdong Sperm Bank was staffed with full-time nurses for reception of sperm donors, the proportion of the candidate donors lost to follow-up was reduced and the efficiency of sperm donation was significantly improved. Individualized psychological intervention for the sperm donors by the nurses could dispel the worries of the donors and improve the compliance and efficiency of sperm donation.


GoM DE: interpreting structure in sequence count data with differential expression analysis allowing for grades of membership.
Parts-based representations, such as non-negative matrix factorization and topic modeling, have been used to identify structure from single-cell sequencing data sets, in particular structure that is not as well captured by clustering or other dimensionality reduction methods. However, interpreting the individual parts remains a challenge. To address this challenge, we extend methods for differential expression analysis by allowing cells to have partial membership to multiple groups. We call this grade of membership differential expression (GoM DE). We illustrate the benefits of GoM DE for annotating topics identified in several single-cell RNA-seq and ATAC-seq data sets.


EphrinA2 regulates clathrin mediated KSHV endocytosis in fibroblast cells by coordinating integrin-associated signaling and c-Cbl directed polyubiquitination.
Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with human dermal endothelial cell surface tyrosine kinase EphrinA2 (EphA2) and integrins (α3β1 and αVβ3) in the lipid raft (LR) region, and EphA2 regulates macropinocytic virus entry by coordinating integrin-c-Cbl associated signaling. In contrast, KSHV enters human foreskin fibroblast (HFF) cells by LR-independent clathrin mediated endocytosis. The present studies conducted to identify the key molecules regulating KSHV entry in HFF cells showed that KSHV induces association with integrins (αVβ5, αVβ3 and α3β1) and EphA2 in non-LR regions early during infection and activates EphA2, which in turn associates with phosphorylated c-Cbl, myosin IIA, FAK, Src, and PI3-K, as well as clathrin and its adaptor AP2 and effector Epsin-15 proteins. EphA2 knockdown significantly reduced these signal inductions, virus internalization and gene expression. c-Cbl knockdown ablated the c-Cbl mediated K63 type polyubiquitination of EphA2 and clathrin association with EphA2 and KSHV. Mutations in EphA2's tyrosine kinase domain (TKD) or sterile alpha motif (SAM) abolished its interaction with c-Cbl. Mutations in tyrosine kinase binding (TKB) or RING finger (RF) domains of c-Cbl resulted in very poor association of c-Cbl with EphA2 and decreased EphA2 polyubiquitination. These studies demonstrated the contributions of these domains in EphA2 and c-Cbl association, EphA2 polyubiquitination and virus-EphA2 internalization. Collectively, these results revealed for the first time that EphA2 influences the tyrosine phosphorylation of clathrin, the role of EphA2 in clathrin mediated endocytosis of a virus, and c-Cbl mediated EphA2 polyubiquitination directing KSHV entry in HFF cells via coordinated signal induction and progression of endocytic events, all of which suggest that targeting EphA2 and c-Cbl could block KSHV entry and infection.


ATP hydrolytic activity of purified Spf1p correlate with micellar lipid fluidity and is dependent on conserved residues in transmembrane helix M1.
P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in pleiotropic phenotypes related to severe ER stress. They were recently proposed to function in peptide translocation although their specificity have yet to be confirmed in reconstituted assays using the purified enzyme. A general theme for P-type ATPases is that binding and transport of substrates is coupled to hydrolysis of ATP in a conserved allosteric mechanism, however several independent reports have shown purified Spf1p to display intrinsic spontaneous ATP hydrolytic activity after purification. It has never been determined to what extend this spontaneous activity is caused by uncoupling of the enzyme. In this work we have purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and have observed that the intrinsic ATP hydrolytic activity of the purified and re-lipidated protein can be stimulated by specific detergents (C12E8, C12E10 and Tween20) in mixed lipid/detergent micelles in the absence of any apparent substrate. We further show that this increase in activity correlate with the reaction temperature and the anisotropic state of the mixed lipid/detergent micelles and further that this correlation relies on three highly conserved phenylalanine residues in M1. This suggests that at least part of the intrinsic ATP hydrolytic activity is allosterically coupled to movements in the TM domain in the purified preparations. It is suggested that free movement of the M1 helix represent an energetic constraint on catalysis and that this constraint likely is lost in the purified preparations resulting in protein with intrinsic spontaneous ATP hydrolytic activity. Removal of the N-terminal part of the protein apparently removes this activity.


Towards an improved estimate of antimicrobial use in animals: Adjusting the "population correction unit" calculation.
International comparisons of animal antimicrobial use (AMU) have typically been based on total national estimates of antimicrobials sales standardized by the national animal biomass calculated as the population correction unit (PCU). The objective of this paper was to compare the currently accepted PCU calculation with that of the adjusted population correction unit (APCU), which re-evaluates the standard animal weights used in the calculation and accounts for animal lifespan. The APCU calculation resulted in substantial changes to the 2009 national biomass estimates for cattle, pigs, and poultry in 8 European countries and Canada. The estimated national biomass for cattle increased 35% to 43%, while the estimated national biomass of pigs and poultry typically decreased by approximately 51% and 87%, respectively. Among the 9 countries, the total national APCU ranged from an increase of 1% to a decrease of 40% relative to PCU, and these differences were statistically significant. Adjusted population correction unit is preferred over PCU in comparing and contrasting AMU among animals with different lifespans because it is more transparently derived and is a reasonable approximation of the animal biomass at risk of antimicrobial treatment.


Analysis of inactivation of AcMNPV under various conditions by the ELVA method.
Inactivation of baculoviruses was examined under various conditions by ELVA, which enzymatically labels the virus envelope with radioisotopes and detects the labeled viruses by host cell-specific binding. When baculoviruses were incubated in a 50-ml culture tube, they rapidly lost infective ability by more than 75% of the initial titer in 2 h even at an insect cell cultivation temperature of 27 degrees C. Altering pH from neutral significantly decreased the virus titer. Repetition of freezing and thawing of baculovirus solutions decreased the virus titer, but the addition of DMSO and glycerol prevented inactivation to some extent.


[Not Available].
Reference is made to the medical assistance in Gabrovo during the epic Shipka battles of the Liberation war (1877-1878). With the common efforts of the Russian military medical personnel and of the population of Gabrovo, medical aid was organized and secured for the Russian soldiers, Bulgarian volunteers as well as for the refugees and local population.


[Isolation, identification and over- siderophores production of Pseudomonas fluorescens sp-f].
Strain sp-f was isolated, a siderophores over producing bacterium, using an improved universal Chrome Azurol S(CAS)-agar plate method from Donghu Lake. The result of the CAS solution siderophores quantitative determination showed the lowest As/Ar (OD680) ratio could be as low as 0.09 with Su (Siderophore Unit) of 90%. Some more experiments were made to make out the pertinence between its growth and siderophores production, indicating that its siderophores quantity reached maximum amount during the prophase of logarithmic growth. After then, siderophores concentration stopped accumulating and turned to be stable at stationary phase. Based on the characteristics of morphology, cultivation, physiology, (G + C) mol % content, 16S rDNA sequence and BIOLOG Station system analysis, it was identified as Pseudomonas fluorescens sp-f strain. RP-HPLC analysis showed there exist at least 3 kinds of catecholate siderophores, including fluorescent and non-fluorescent pyoverdins. But only fluorescent pyoverdin's excretion was completely repressed by the 200 micromol/L Fe2+ in the medium. And the non-pyoverdin siderophores excretion was induced at the same time, contrarily.


Nanohybrids of silver particles immobilized on silicate platelet for infected wound healing.
Silver nanoparticles supported on nanoscale silicate platelets (AgNP/NSP) possess interesting properties, including a large surface area and high biocide effectiveness. The nanohybrid of AgNP/NSP at a weight ratio 7/93 contains 5-nm Ag particles supported on the surface of platelets with dimensions of approximately 80×80×1 nm(3). The nanohybrid expresses a trend of lower cytotoxicity at the concentration of 8.75 ppm Ag and low genotoxicity. Compared with conventional silver ions and the organically dispersed AgNPs, the nanohybrid promotes wound healing. We investigated overall wound healing by using acute burn and excision wound healing models. Tests on both infected wound models of mice were compared among the AgNP/NSP, polymer-dispersed AgNPs, the commercially available Aquacel, and silver sulfadiazine. The AgNP/NSP nanohybrid was superior for wound appearance, but had similar wound healing rates, vascular endothelial growth factor (VEGF)-A levels and transforming growth factor (TGF)-β1 expressions to Aquacel and silver sulfadiazine.


Aberrant Gray Matter Networks in Non-comorbid Medication-Naive Patients With Major Depressive Disorder and Those With Social Anxiety Disorder.
Major depressive disorder (MDD) and social anxiety disorder (SAD) are among the most prevalent and frequently co-occurring psychiatric disorders in adults and may have, at least in part, a common etiology. However, the unique and the shared neuroanatomical characteristics of the two disorders have not been fully identified. The aim of this study was to compare the topological organization of gray matter networks between non-comorbid medication-naive MDD patients and SAD patients. High-resolution T1-weighted images were acquired from 37 non-comorbid medication-naive MDD patients, 24 non-comorbid medication-naive SAD patients, and 41 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the three groups. The relationships between brain network measures and clinical characteristics were analyzed. Relative to healthy controls, both the MDD and the SAD patients showed global decreases in clustering coefficient, normalized clustering coefficient, and small-worldness and locally decreased nodal centralities and morphological connections in the left insular, lingual, and calcarine cortices. Compared with healthy controls, the SAD patients exhibited increased nodal centralities and morphological connections mainly involving the prefrontal cortex and the sensorimotor network. Furthermore, compared to the SAD patients, the MDD patients showed increased characteristic path length, reduced global efficiency, and decreased nodal centralities and morphological connections in the right middle occipital gyrus and the right postcentral gyrus. Our findings provide new evidence for shared and specific similarity-based gray matter network alterations in MDD and SAD and emphasize that the psychopathological changes in the right middle occipital gyrus and the right postcentral gyrus might be different between the two disorders.


Noninvasive monitoring of photodynamic therapy on skin neoplastic lesions using the optical attenuation coefficient measured by optical coherence tomography.
Photodynamic therapy (PDT) has become a promising alternative for treatment of skin lesions such as squamous cell carcinoma. We propose a method to monitor the effects of PDT in a noninvasive way by using the optical attenuation coefficient (OAC) calculated from optical coherence tomography (OCT) images. We conducted a study on mice with chemically induced neoplastic lesions and performed PDT on these lesions using homemade photosensitizers. The response of neoplastic lesions to therapy was monitored using, at the same time, macroscopic clinical visualization, histopathological analysis, OCT imaging, and OCT-based attenuation coefficient measurement. Results with all four modalities demonstrated a positive response to treatment. The attenuation coefficient was found to be 1.4 higher in skin lesions than in healthy tissue and it decreased after therapy. This study shows that the OAC is a potential tool to noninvasively assess the evolution of skin neoplastic lesions with time after treatment.


The atomic and electronic structure of nitrogen- and boron-doped phosphorene.
First principles modeling of nitrogen- and boron-doped phosphorene demonstrates the tendency toward the formation of highly ordered structures. Nitrogen doping leads to the formation of -N-P-P-P-N- lines. Further transformation into -P-N-P-N- lines across the chains of phosphorene occurs with increasing band gap and increasing nitrogen concentration, which coincides with the decreasing chemical activity of N-doped phosphorene. In contrast to the case of nitrogen, boron atoms prefer to form -B-B- pairs with the further formation of -P-P-B-B-P-P- patterns along the phosphorene chains. The low concentration of boron dopants converts the phosphorene from a semiconductor into a semimetal with the simultaneous enhancement of its chemical activity. Co-doping of phosphorene by both boron and nitrogen starts from the formation of -B-N- pairs, which provides flat bands and further transformation of these pairs into hexagonal BN lines and ribbons across the phosphorene chains.


Underwater blast injury: a review of standards.
The first cases of underwater blast injury appeared in the scientific literature in 1917, and thousands of service members and civilians were injured or killed by underwater blast during WWII. The prevalence of underwater blast injuries and occupational blasting needs led to the development of many safety standards to prevent injury or death. Most of these standards were not supported by experimental data or testing. In this review, we describe existing standards, discuss their origins, and we comprehensively compare their prescriptions across standards. Surprisingly, we found that most safety standards had little or no scientific basis, and prescriptions across standards often varied by at least an order of magnitude. Many published standards traced back to a US Navy 500 psi guideline, which was intended to provide a peak pressure at which injuries were likely to occur. This standard itself seems to have been based upon a completely unfounded assertion that has propagated throughout the literature in subsequent years. Based on the limitations of the standards discussed, we outline future directions for underwater blast injury research, such as the compilation of epidemiological data to examine actual injury risk by human beings subjected to underwater blasts.


Human X-autosome translocations: differential inactivation of the X chromosome in a kindred with an X-9 translocation.
A kindred with an X-autosome translocation and differential inactivation of the X chromosome is described. The phenotypically normal mother has a reciprocal translocation [46,X,rcp(X;9) (q11;q32)] while the daughter's karyotype is unbalanced [46,X,--X,+der(9),rcp(X;9) (q11;q32)mat], indicating adjacent-two type of segregation in the mother. In the mother's cells the normal X is late replicating, while in the daughter's cells almost the entire der(9) is late replicating, indicating the presence of autosomal inactivation. The daughter's abnormal phenotype can be explained by her sex chromosomal complement and the absence of effective trisomy 9. At this stage there is no simple explanation to account for all types of inactivation patterns encountered in the 14 balanced and 15 unbalanced cases of X-autosome translocations reported to date. Selection of X inactivation is not an inherent characteristic of the X chromosome per se, and it is not dependent on the direction of chromosomal exchange, as was suggested previously. Correlation of the phenotypic and cytogenetic features of these patients suggests a pattern of X and autosomal inactivation consistent with the least amount of genotypic and phenotypic imbalance in most cases. The data are most consistent with random X inactivation followed by selection of the most viable cell line.


The risk of use small matrices to measure specialization in host-parasite interaction networks: a comment to Rivera-García et al. (2016).
In the last years, there were a growing number of studies using the metric H 2' to calculate complementary specialization in host-parasite interaction networks. However, only a few studies have explored the sensitivity of H 2' to network dimensions (i.e. species richness and number of interactions), which consequently could generate studies that are not comparable among them or lead to biased conclusions. In this study, we used the recent published study conducted by Rivera-García et al. in 2016 involving host-bat fly networks as an example to call attention to the risk of using H 2' to calculate specialization for small matrices. After conducting analyses based on both empirical and simulated data, we show that H 2' values are strongly affected by randomly allocation of species interactions to another cell in the matrix for small networks and that therefore the results and conclusions presented in Rivera-García et al. in 2016 are only an artefact of the dataset used. Therefore, we fully recommended taking into account the careful use of small networks to measuring specialization in host-parasite interactions.


The Influence of pH on the Scleroglucan and Scleroglucan/Borax Systems.
The effects that an increase of environmental pH has on the triple helix of scleroglucan (Sclg) and on the Sclg/borax hydrogel are reported. Rheological experiments show that the hydrogel is less sensitive to pH increase than Sclg alone, while at pH = 14 a dramatic viscosity decrease takes place for both systems. This effect is evidenced also by the reduced water uptake and anisotropic elongation detected, at pH = 14, by the swelling behaviour of tablets prepared with the Sclg/borax system. On the opposite, a different behaviour was observed with guar gum and locust bean gum tablets, tested as reference polysaccharides. The effect of pH on the structure of Sclg and Sclg/borax was investigated also by means of spectroscopic approaches based on the interaction between Congo red (CR) and the Sclg triple helix. Obtained results indicated that the CR absorbance maximum is shifted as a function of pH and by the presence of borax. Principal component analysis allowed very precise identification of the pH value at which the Sclg helix collapses. Molecular dynamics simulations of the Sclg/borax-CR complex indicated that, at physiological pH, only a few ordered configurations are populated, according to the induced circular dichroism (CD) spectrum evidence.


[A case involving long-term survival following bile duct cancer with para-aortic lymph node metastasis that was treated by multidisciplinary therapy].
Complete resection of advanced bile duct cancer is difficult due to the anatomical location of the tumor and invasion into other organs. Even if a complete resection is achieved, the survival rates of patients with bile duct cancer after surgery are lower as compared to those associated with other gastrointestinal tumors. Certain cases with para-aortic lymph node metastasis have a poor prognosis. In the present report, we describe a case involving long-term survival following bile duct cancer that was treated by multidisciplinary therapy (particle radiotherapy, surgical resection, chemotherapy). In the present case, we detected lymph node (LN) metastasis only in LN#16, but not in LN#13 or LN#17. We believe that particle radiotherapy, consisting of proton and carbon-ion, can be used to control the lymphatic metastasis around the pancreas head and hepatoduodenal ligament. Our findings suggest that particle radiotherapy can be a standard neoadjuvant therapy for bile duct cancer.


Serum albumin and mortality in acutely decompensated heart failure.
Although hypoalbuminemia has been associated with decreased survival in chronic systolic heart failure (HF), its role for prognosticating outcomes in those with acutely decompensated heart failure (ADHF) has not been established. 438 consecutive patients with ADHF (mean age 75±13 years, mean left ventricular ejection fraction 41%±20%) admitted to a large community hospital were studied. The mean serum albumin level for the group was 3.4 g/dL; quintile analysis demonstrated an inflection of risk for death below this value. Patients with hypoalbuminemia (defined as a serum albumin<3.4 g/dL; N=236, 54% overall) were more likely to have prior HF, more severe HF symptoms, more likely to be edematous, and had more prevalent prognostically meaningful laboratory abnormalities, such as a higher frequency of renal dysfunction and elevated B-type natriuretic peptide. Independent associations between anemia, hyponatremia, lack of therapy with vasodilators at presentation, prior history of obstructive airways disease, severe tricuspid regurgitation, low serum cholesterol, and the presence of a pleural effusion on chest radiography were found with reduced serum albumin; interestingly, body mass index was not predictive of albumin levels. In Cox proportional hazards analysis, hypoalbuminemia predicted 1-year mortality (hazard ratio [HR]adjusted=2.05, 95% CI 1.10-3.81, P=.001). Reduced serum albumin concentrations were prognostic across a wide range of body mass index but had highest HR in obese patients (HRadjusted=4.39 [95% CI=1.66 to 11.60], P=.003). As well, hypoalbuminemia was mainly predictive of outcomes among those with systolic HF (HRadjusted=5.00, 95% CI=2.17-11.5, P<.001). Hypoalbuminemia is common among patients with ADHF and is independently associated with increased one year mortality in patients admitted with ADHF.


Effects of nifedipine, verapamil and diltiazem on renal function.
Eight healthy female volunteers were given single doses of nifedipine 10 mg, verapamil 80 mg, diltiazem 120 mg or placebo on 4 different study days. Urine and sodium output increased after all four drugs, but the increase after nifedipine was significantly greater than after verapamil or placebo. Nifedipine caused a significant increase in heart rate; none of the drugs caused any change in blood pressure. Potassium excretion, creatinine clearance, free water clearance and plasma renin activity did not change with any drug. The mechanism of the natriuresis and diuresis has still to be elucidated.


Exosomal miR-17-5p from human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease characterized by pulmonary fibrosis and lung dysfunction, ultimately leading to respiratory failure. Many preclinical studies have investigated the therapeutic potential of stem cell-derived exosomes in this disease, particularly mesenchymal stem cell-derived exosomes. However, the effects of embryonic stem cell-derived exosomes in IPF remain unclear. We established a bleomycin (BLM)-induced pulmonary fibrosis mice model and administered human embryonic stem cell exosomes (hESC-exo) from the first day after BLM treatment. The effects of hESC-exo were assessed by pulmonary function tests, biochemical analysis, histochemistry, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). RNA-seq was used to screen for the potential therapeutic targets of hESC-exo in fibrotic lungs; the identified signaling axis was characterized using a luciferase assay, qPCR, and WB. Results indicated hESC-exo administration notably alleviated inflammation, removed deposited collagen, and rescued alveolar architecture in the lungs of BLM-induced mice. In vivo and in vitro tests revealed that hESC-exo-derived miR-17-5p directly bound thrombospondin-2 (Thbs2) to regulate inflammation and fibrosis; thus, hESC-exo protected against BLM toxicity in the lungs via the miR-17-5p/Thbs2 axis. These results suggest a promising new treatment for fibrosis-associated diseases.


Femoral nerve lesion subsequent to renal transplantation.
Severe femoral neuropathy subsequent to renal transplantation is described in a patient who died in the 5th postoperative week. Postmortem examination revealed a compression of the femoral nerve by an older hematoma of the iliac muscle, ipsilateral to the transplantation, and severe Wallerian degeneration of the nerve beginning at the site of the hematoma. It is postulated that the hematoma resulted from surgical trauma on the iliac muscle and was facilitated by previous anticoagulation and hypertensive vasculopathy. We suggest that every patient with similar symptoms occurring after renal transplantation should be investigated for a retroperitoneal hematoma. If such a hematoma is diagnosed, immediate decompression neurolysis should be performed in order to prevent prolonged recovery time or permanent disability.


Interactions between mature Der p 1 and its free prodomain indicate membership of a new family of C1 peptidases.
Studies in vivo have shown that the cysteine peptidase activity of group 1 house dust mite allergens contributes to their allergenicity. These allergens are synthesized initially as proenzymes and removal of the propiece is necessary to unmask their proteolytic activity. In related C1 family cysteine peptidases of enzyme clan CA, liberated propieces continue to inhibit the mature peptidase as tight binding inhibitors. As it is not known whether mite peptidase allergens behave similarly, our objective was to investigate the effect of the Der p 1 propiece on the catalytic activity of Der p 1 and Der f 1. Enzymatic activity of natural Der p 1 and Der f 1 was assessed using a specific substrate and the effect of the recombinant propiece on its enzyme kinetics defined. The integrity of the propiece during these interactions was studied functionally and by analysis of the reaction mixtures. Der p 1 propiece was a potent competitive inhibitor of Der p 1 and Der f 1. In contrast to other cysteine peptidase prodomains, which are cognate tight binding inhibitors, the Der p 1 propiece behaves as a substrate and is fully degraded during this interaction. Mature Der p 1-prodomain interactions differ from other C1 family cysteine peptidases, suggesting that group 1 mite allergens are a new subgroup among C1 family cysteine peptidases. The rapid inactivation of Der p 1 prodomain is a newly identified mechanism that may contribute to the potency of this allergen.


Rheumatoid-factor-reactive sites on CH2 established by analysis of overlapping peptides of primary sequence.
Polyclonal IgM rheumatoid factors (RF) from ten patients with rheumatoid arthritis (RA) isolated on IgG affinity columns were studied for their reactivity with overlapping 7-mer peptides representative of solvent accessible regions of the CH2 domains of IgG using a pin-ELISA assay. A panel of nine monoclonal RF from RA patients' B cells were studied in parallel. Four peptides SVFLFPP (239-245), KFNWYVD (274-280), NSTYRVVSV (297-305) and VLTVLHQNWL (305-314) reacted with most RF. Glycine substitution showed that tryptophanes at 277 and 313, tyrosine at 278, valines at 279 and 305, and leucine 314 represented important residues for RF reactivity. Assays using monoclonal IgM RF produced from RA synovial B cells or peripheral blood B cells frequently showed a restricted spectrum of reactivity for CH2 epitopes, which often were identical to those binding to polyclonal IgM RF. Combinations of synthetic 7-mer peptides representing RF-reactive CH2 or CH3 epitopes produced as much as 60-90% inhibition of RF binding to IgG when peptides were preincubated with RF in free solution before completion of the reaction of RF with IgG on the ELISA plate.


Maximum androgen blockade: a clinical update.
Maximal androgen blockade (MAB) therapy for metastatic prostate cancer has advanced in recent years with the discovery of luteinizing hormone-releasing hormone agonists (LHRH), the development of LHRH analogues, and the discovery of antiandrogens. Of 36 studies of MAB therapy performed from 1980 to 1991, 3 showed a statistically significant increase in survival with MAB versus castration alone. Because of the large number of studies showing no benefit from MAB, a meta-analysis was performed on 27 studies. This meta-analysis demonstrated a survival benefit from MAB of only 3%; however, a critical review of the analysis revealed major flaws that raise serious questions regarding the validity of its findings. In addition, the fact remains that the longest survival reported for patients with stage M1 prostate cancer was 35 to 36 months, whereas the longest survival for castration alone was 32 to 33 months. Therefore, when physicians discuss treatment choices for patients with metastatic disease, MAB should remain a reasonable option.


Ventilatory behavior after hypoxia in C57BL/6J and A/J mice.
Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (VE), respiratory frequency (f), tidal volume (VT), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease in VE on reoxygenation with either air (-11%) or 100% O2 (-20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in VE (-28.4 vs. -38.7%, air vs. 100% O2) and f (-13.8 vs. -22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase in VE (+116%) and f (+62.2%) during air reoxygenation and significant increase in VE (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.


Terahertz absorber based on vanadium dioxide with high sensitivity and switching capability between ultra-wideband and ultra-narrowband.
The terahertz perfect absorber can be applied in the control, sensing and modulation of optical fields in micro- and nanostructures. However, they are only single function, complex device structure and low sensing sensitivity. Based on this, by introducing the bound state in the continuum (BIC) with infinite quality factor and field enhancement effect, and taking advantage of the phase transition characteristics of vanadium dioxide (VO2), we designed a terahertz perfect absorber device which can actively switch between ultra-wideband and ultra-narrowband. The absorption mechanism is explained by multipole analysis theory, impedance matching theory and electromagnetic field distribution. The broadband absorption is mainly due to the electric dipole resonance on metallic VO2 materials, and the absorption is more than 99% across 3.64-6.96 THz, and it has excellent characteristics such as robustness. Ultra-narrowband perfect absorption has a quality factor greater than 2200 due mainly to the implementation of symmetrically protected BIC with a sensing sensitivity of 2.575 THz per RIU. Therefore, this research could be widely used in the fields of integrated optical circuits, optoelectronic sensing and perceptual modulation of energy, as well as providing additional design ideas for the design of terahertz multifunctional devices.


Influence of artificial intelligence in education on adolescents' social adaptability: The mediatory role of social support.
Artificial intelligence (AI) is widely used in the field of education at present, but people know little about its possible impacts, especially on the physical and mental development of the educated. It is important to explore the possible impacts of the application of artificial intelligence in education (AIEd) in order to avoid the possible adverse effects. Prior research has focused on theory to the exclusion of the psychological impact of AIEd, and the empirical research was relatively lacking. This study aimed to identify the influence of AIEd on adolescents' social adaptability via social support. A total of 1332 students were recruited using random sampling from 13 Artificial Intelligence Curriculum Reform Experimental Schools in Guangzhou, Southern China, completed the survey. There were 342 primary school students (Meanage = 10.6), 351 junior high school students (Meanage = 13.1), and 639 senior high school students (Meanage = 15.8). Results showed that AIEd has a negative impact on adolescents' social adaptability, and is significantly negatively correlated with social adaptability and family support, but there is no significant correlation with school support. AIEd could not only affect social adaptability directly, but also could affected it through the family support.


Perspective: micoarrays and differential display PCR-tools for studying transcript levels of genes in neuroendocrine systems.
A central goal of neuroendocrinology is the understanding of how hormones modulate a variety of neurobiological functions including releasing factors for anterior pituitary secretions and behavior. We know that mechanisms of hormone actions clearly include the activation and repression of genes either directly through nuclear hormone receptors or indirectly, through a series of transduced signals originating from membrane receptors. Until recently, identification of the differentially expressed genes has been a "gene-at-a-time" proposition. With the advent of the completion of sequencing of several genomes including those of the human and mouse, new methods for the simultaneous assessment of many genes' expression are proving especially timely. Two such methods, differential display PCR and gene microarrays, are based on the well-established principles of DNA amplification and nucleic acid hybridization, respectively. With properly designed and well-executed experiments, these methods are powerful tools in the assessment of differentially expressed genes yielding results both expected and unanticipated.


The Evaluation of Laboratory Parameters as Predictors of Disease Severity and Mortality in COVID-19 Patients: A Retrospective Study From a Tertiary Care Hospital in India.
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects and alters various laboratory parameters that are predictors of disease severity and mortality, and hence, their prompt identification can aid in patient triaging and resource allocation. Objectives A retrospective study was conducted on 7416 admitted coronavirus disease 2019 (COVID-19) patients from 20 March 2020 to 9 August 2021 to identify crucial laboratory biomarkers as predictors of disease severity and outcome; also, their optimal cutoffs were also calculated. A comparison of laboratory markers between both COVID-19 waves was also performed. Results The majority of patients had mild disease (4295/7416, 57.92%), whereas 1262/7416 (17.02%) had severe disease. The overall fatal outcome was reported in 461 (6.22%) patients. Predictors for mortality were age (>52 years), albumin/globulin (A/G) ratio (≤1.47), chloride (≤101 mmol/L), ferritin (>483.89 ng/mL), lactate dehydrogenase (LDH) (>393 U/L), procalcitonin (>0.10 ng/mL), interleukin-6 (IL-6) (>8.8 pg/mL), fibrinogen (>403 mg/dL), international normalized ratio (INR) (>1.18), and D-dimer (>268 ng/mL). Disease severity predictors were neutrophils (>81%), lymphocyte (≤25.4%), absolute lymphocyte count (ALC) (≤1.38×103/µL), absolute eosinophil count (AEC) (≤0.03×103/µL), total bilirubin (TBIL) (≥0.51 mg/dL), A/G ratio (≤1.49), albumin (≤4.2 g/dL), ferritin (≥445.4 mg/dL), LDH (≥479 U/L), IL-6 (≥28.6 pg/mL), C-reactive protein/albumin (CRP/ALB) ratio (≥1.78), D-dimer (≥237 ng/mL), and fibrinogen (≥425 mg/dL). The majority of patients admitted in the second wave were older and had severe disease, increased fatality, and significantly deranged laboratory parameters than first wave patients. Conclusion Our findings suggested that several biomarkers are crucial for both severe disease and mortality in COVID-19 patients. Ferritin, LDH, IL-6, A/G ratio, fibrinogen, and D-dimer are important biomarkers for both severity and mortality, and when combined, they provide valuable information for patient monitoring and triaging. In addition to these, older age, INR, chloride, and procalcitonin are also significant risk factors for mortality. For severe COVID-19, TBIL, CRP/ALB, albumin, neutrophil percentage, lymphocyte percentage, ALC, and AEC are also important biomarkers. According to the study, the majority of the baseline laboratory parameters associated with COVID-19 mortality and severe disease were significantly higher during the second wave, which could be one of the possible causes for the high mortality rate in India during the second wave. So, the combination of all these parameters can be a powerful tool in emergency settings to improve the efficacy of treatment and prevent mortality, and the planning of subsequent waves should be done accordingly.


Live birth resulting from in-office vas deferens sperm retrieval combined with natural-cycle insemination.
In-office retrieval of spermatozoa from the vas deferens was successfully combined with intra-uterine insemination of the wife during her natural cycle in the case of a man with azoospermia due to a non-correctable obstruction of the vas deferens. The combined cost of both procedures (sperm retrieval and intra-uterine insemination with processed spermatozoa) was less than $1000. The cost and convenience compare quite favourably with that of epididymis sperm aspiration combined with in-vitro fertilization, which is the currently recommended alternative treatment in such cases. These alternative therapies are compared and discussed relative to their advantages and disadvantages. Our technique for in-office vas deferens sperm retrieval is also presented.


Maternal genotype and gestational diabetes.
To determine whether genetic variants associated with glucose homeostasis are associated with gestational diabetes (GDM). We genotyped 899 self-identified Caucasian women and 386 self-identified African-American women in the Pregnancy, Infection and Nutrition (PIN) Studies cohorts for 38 single-nucleotide polymorphisms (SNPs) associated with type II diabetes (T2DM) and/or glucose homeostasis in European populations. GDM was diagnosed in 56 of 899 (6.2%) Caucasian and 24 of 386 (6.2%) African-American women. Among Caucasian women, GDM was associated with carriage of TCF7L2 rs7901695, MTNR1B rs10830963 and GCKR rs780094 alleles that are associated with T2DM and fasting glucose in nonpregnant populations. Among African-American participants, we found an increased risk among TSPAN8 rs7961581 C allele homozygotes and reduced risk among carriers of the JAZF1 rs864745 T allele. We found several SNPs that are associated with GDM risk in the PIN cohorts. Maternal genotyping may identify women at risk for impaired gestational glucose tolerance.


[Preventive effect of 5-fluorouracil on post-ERCP pancreatitis].
To investigate the preventive effect of 5-fluorouracil (5-FU) on post-ERCP (endoscopic retrograde cholangiopancreatography) hyperamy-lasemia and pancreatitis. One hundred and sixty patients who underwent ERCP were divided at random into 2 groups: group A (n = 80) was given meglumine diatrizoate with 5-FU; and group B (n = 80) was used contrast medium without 5-FU. Blood was drawn in each group the day before, 6 hours and 24 hours following ERCP for amylase. Post-ERCP hyperamylasemia occurred in 9 patients in group A (11. 25%) and 45 in B (56.25%). The difference of both groups was notable. Pancreatitis ensued in 2 instances in group A (2.50%) and 8 in group B (10.00%). Their difference was significant. 5-FU added in meglumine diatrizoate is helpful to prevent post-ERCP hyperamylasemia and pancreatitis.


Adsorption of pesticides from water by functionalized organobentonites.
Replacement of natural inorganic cations of clay minerals with organic cations has been proposed as a strategy to improve the adsorptive capacity of clay minerals for organic compounds, including pesticides. The organic cations most commonly used for this purpose have been quaternary ammonium ions containing alkyl or aryl chains without specific functional groups. In this work, we evaluated the ability of two bentonites (SWy-2 and SAz-1) exchanged with four natural organic cations containing diverse functional groups (L-carnitine, L-cysteine ethyl ester, L-cystine dimethyl ester, and thiamine) as adsorbents of pesticides varying in their chemical structures (simazine, hexazinone, triadimefon, alachlor, carbaryl, and imazethapyr). For comparison purposes, the adsorptive properties of two "classical" organobentonites, hexadecyltrimethylammonium- and phenyltrimethylammonium-exchanged bentonites, were also determined. Most organobentonites displayed higher affinity for the pesticides than the untreated bentonites, but the improvement in adsorption capacity varied depending on the characteristics of the pesticide and the interlayer organic cation. Triadimefon, carbaryl, and imazethapyr displayed the highest affinity for carnitine (K(f) = 229-2377)-, thiamine (K(f) = 83-354)-, and cystine (K(f) = 96-100)-treated bentonites, respectively, whereas alachlor was adsorbed similarly by all organobentonites. In general, pesticide adsorption-desorption hysteresis was greater for adsorbents with the highest adsorption capacities. The results demonstrate that selective modification of smectitic clay minerals with natural organic cations containing appropriate functional groups can be a useful strategy to improve their performance for the removal of specific pesticides from the environment.


Electronic Excitations of Polythiophene within Many-Body Perturbation Theory with and without the Tamm-Dancoff Approximation.
Excited electronic states of small and large π-conjugated organic molecules can be described within ab initio many-body perturbation theory, notably by the GW approximation for the electron self-energy operator combined with the Bethe-Salpeter equation for correlated electron-hole excitations. In this context, the Tamm-Dancoff approximation is routinely employed to reduce the computational effort. It is known that the use of this approximation introduces errors of several 100 meV for small organic molecules but is negligible for extended systems. In this paper, we investigate how exactly the transition between these two regimes happens, by calculating the optical excitation energies of a series of polythiophene molecules of different sizes. We determine which parts of the electron-hole interaction are responsible for the deviation and show that the quantitative effects of the Tamm-Dancoff approximation depend sensitively on the size of the electronic system, in particular on the electronic conjugation length.


Supporting the management of type 2 diabetes with pharmacist-led reviews: an observational analysis.
Describe and assess the impact of a pharmacist-led patient review programme on the management and control of type 2 diabetes (T2D). Uncontrolled prospective cohort study with before and after intervention data collection. General practices within NHS Slough Clinical Commissioning Group (CCG). 5910 patients with T2D. Pharmacists reviewed 5910 patients and worked with general practice teams to schedule any of the 9 key care processes recommended by the National Institute for Health and Care Excellence (NICE) that the patients were lacking, to optimise medication and to make other interventions such as providing lifestyle advice. The proportion of patients receiving the NICE-recommended 9 key care processes and proportion of patients whose glycated haemoglobin (HbA1c), blood pressure (BP) or total cholesterol (TC) readings were over target before and after the intervention period. The proportion of patients receiving all of the NICE-recommended 9 key care processes increased from 46% at project outset in April 2013 to 58% on completion in April 2014 and the percentage of patients achieving HbA1c, BP and TC targets all increased (65% to 70%, 70% to 76%, 78% to 82%, respectively). Quality Outcomes Framework (QOF) data for Slough CCG showed the percentage of diabetic patients achieving target HbA1c, BP and TC readings increased from April 2013 to April 2014, but then diminished in the year after project completion. The pharmacist-led review increased the number of key care processes administered and improved diabetic control during the year of programme delivery. The improvement abated during the year after, suggesting that such programmes should be ongoing rather than fixed term. The programme combined the strategic drive and project facilitation skills of Slough CCG, the general practice teams' knowledge of their patients and the clinical and information technology skills of an experienced pharmacist team.


CG gene body DNA methylation changes and evolution of duplicated genes in cassava.
DNA methylation is important for the regulation of gene expression and the silencing of transposons in plants. Here we present genome-wide methylation patterns at single-base pair resolution for cassava (Manihot esculenta, cultivar TME 7), a crop with a substantial impact in the agriculture of subtropical and tropical regions. On average, DNA methylation levels were higher in all three DNA sequence contexts (CG, CHG, and CHH, where H equals A, T, or C) than those of the most well-studied model plant Arabidopsis thaliana. As in other plants, DNA methylation was found both on transposons and in the transcribed regions (bodies) of many genes. Consistent with these patterns, at least one cassava gene copy of all of the known components of Arabidopsis DNA methylation pathways was identified. Methylation of LTR transposons (GYPSY and COPIA) was found to be unusually high compared with other types of transposons, suggesting that the control of the activity of these two types of transposons may be especially important. Analysis of duplicated gene pairs resulting from whole-genome duplication showed that gene body DNA methylation and gene expression levels have coevolved over short evolutionary time scales, reinforcing the positive relationship between gene body methylation and high levels of gene expression. Duplicated genes with the most divergent gene body methylation and expression patterns were found to have distinct biological functions and may have been under natural or human selection for cassava traits.


Noncontact longitudinal shear wave imaging for the evaluation of heterogeneous porcine brain biomechanical properties using optical coherence elastography.
High-resolution quantification of heterogeneous brain biomechanical properties has long been an important topic. Longitudinal shear waves (LSWs) can be used to assess the longitudinal Young's modulus, but contact excitation methods have been used in most previous studies. We propose an air-coupled ultrasound transducer-based optical coherence elastography (AcUT-OCE) technique for noncontact excitation and detection of LSWs in samples and assessment of the nonuniformity of the brain's biomechanical properties. The air-coupled ultrasonic transducer (AcUT) for noncontact excitation of LSWs in the sample has a center frequency of 250 kHz. Phase-resolved Doppler optical coherence tomography (OCT) was used to image and reconstruct the propagation behavior of LSWs and surface ultrasound waves at high resolution. An agar phantom model was used to verify the feasibility of the experimental protocol, and experiments with ex vivo porcine brain samples were used to assess the nonuniformity of the brain biomechanical properties. LSWs with velocities of 0.83 ± 0.11 m/s were successfully excited in the agar phantom model. The perivascular elastography results in the prefrontal cortex (PFC) of the ex vivo porcine brains showed that the Young's modulus was significantly higher in the longitudinal and transverse directions on the left side of the cerebral vessels than on the right side and that the Young's modulus of the PFC decreased with increasing depth. The AcUT-OCE technique, as a new scheme for LSW applications in in vivo elastography, can be used for noncontact excitation of LSWs in brain tissue and high-resolution detection of heterogeneous brain biomechanical properties.


Prenatal diagnosis of anhidrotic ectodermal dysplasia.
This paper reports on successful prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia (AED) by means of light and electron microscopy on fetal skin biopsies obtained under fetoscopy. In the present family two brothers of the proband were severely affected with the full symptomatology of AED, the pregnant female and her mother revealed minor symptoms with patches of skin lacking vellus hair. Control of lesional skin of the affected family members by electron microscopy revealed no ultrastructural abnormalities. However, all biopsies lacked skin appendages including hair follicles, sebaceous glands, and sweat glands. The lack of pilosebaceous follicles can be used as a diagnostic criterion since these structures are fully developed in normal fetuses of 20 weeks whereas the development of sweat glands does not start before week 20 to 24 of fetal life. Skin biopsies were taken from various regions of the fetus at risk via fetoscopy in week 20 and processed for light and electron microscopy. All samples revealed complete absence of all skin appendages in contrast to a total of 61 non-AED fetuses. Thus positive prenatal diagnosis of AED was made and the pregnancy was terminated. Control investigations after abortion confirmed the diagnosis.


Supradiaphragmatic accessory liver tissue mimicking pleural tumour: excision by transdiaphragmatic uniportal video-assisted thoracoscopic surgery (U-VATS).
We describe a case of an extremely rare intrathoracic supradiaphragmatic accessory liver tissue that was excised via transdiaphragmatic uniportal video-assisted thoracoscopic surgery. The intrathoracic mass that was radiologically detected was found to be mimicking a pleural tumour because of its supradiaphragmatic location as well as the presence of a clear cleavage plane separating the mass and the liver completely. This, to our knowledge, is the first described case that was resected via transdiaphragmatic uniportal approach in the literature.


Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons.
The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L-1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L-1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L-1 (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L-1 and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca2+ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.


Patient and staff exposure during endoscopic retrograde cholangiopancreatography.
Despite a number of efforts being put into the radiological protection of both patient and staff during interventional radiological (IR) procedures during recent years, information about radiation exposure during endoscopic retrograde cholangiopancreatography (ERCP) procedures remains scarce. The purpose of this study was to estimate both patient and staff radiation doses during therapeutic ERCP procedures by direct measurement and to compare these results with data from other IR procedures. For 54 patients, effective dose and skin dose were estimated by measuring the dose-area product. For staff, entrance surface doses to the lens of the eye, thyroid and hands were estimated by thermoluminescent dosemeters. A median effective dose of 7.3 mSv and a median entrance surface dose of 271 mGy per procedure were estimated for patients. The gastroenterologist received a median dose of 0.34 mGy to the lens of the eye, 0.30 mGy to the skin at the level of the thyroid and 0.44 mGy to the skin of the hands, per procedure. When comparing the dosimetric quantities presented in this study with data from other IR procedures, it is clear that patient skin doses and doses to staff are high owing to the use of inappropriate X-ray equipment. ERCP requires the same radiation protection practice as all IR procedures. It should be consistently included in future multicentre IR patient and staff dose survey studies at national or international level.


Lung and liver transplantation in patients with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin (AAT) augmentation is effective in slowing the progression of emphysema due to AAT deficiency (AATD) but cannot prevent eventual progression to end-stage lung disease and complete respiratory failure, which is the leading cause of death for individuals with severe AATD. When patients develop end-stage lung disease, lung transplantation is the only treatment option available, and this can improve lung physiology and patient health status. The available data suggest that survival rates for lung transplantation are significantly higher for patients with AATD-related chronic obstructive pulmonary disease (COPD) compared with non-AATD-related COPD, but, conversely, there is a higher risk of common post-lung transplant complications in patients with AATD versus non-AATD COPD. Nevertheless, lung transplantation (single and bilateral) is favorable for patients with AATD. After respiratory failure, the second leading cause of death in patients with AATD is liver disease, for example, cirrhosis and hepatocellular carcinoma, caused by the accumulation of mutant forms of AAT retained within the liver. As with lung disease, the only treatment option for end-stage liver disease is liver transplantation. Survival rates for patients with AATD undergoing liver transplantation are also favorable, and patients, particularly pediatric patients, have benefitted from advancements in peri-/post-surgical care. As the majority of AAT is produced by the liver, the AAT phenotype of the recipient becomes that of the donor, meaning that AAT serum levels should be normalized (if the donor is AAT-replete), halting further lung and liver disease progression. However, post-liver transplant respiratory function may continue to decline in line with normal age-related lung function decline. In the most severe cases, where patients have simultaneous end-stage lung and liver disease, combined lung and liver transplantation is a treatment option with favorable outcomes. However, there is very little information available on this procedure in patients with AATD.


Drug-induced lupus.
Drug-induced lupus (DIL) is a rare adverse reaction to a large variety of drugs with features resembling those of idiopathic systemic lupus erythematosus (SLE). It usually develops only after months and, quite commonly, years of treatment with the offending agent, although latencies of days or weeks have been described in some instances. There are some indications that the risk of DIL can increase with higher daily and cumulative doses and with longer duration of therapy. There are no definitive and commonly accepted diagnostic criteria for DIL, but the following guidelines have been proposed: (a) sufficient and continuing exposure to a specific drug, (b) at least one symptom compatible with SLE, (c) no history suggestive of SLE before starting the drug, and (d) resolution of symptoms within weeks (sometimes months) after discontinuation of the putative offending agent. In addition, it is frequently suggested that the presence of ANA is required for the diagnosis of DIL. However, negative ANA test results should not automatically preclude such a diagnosis, particularly if a patient has other autoantibodies associated with SLE/DIL.


Photosynthetic responses of the tropical spiny shrub Lycium nodosum (Solanaceae) to drought, soil salinity and saline spray.
Water relations and photosynthetic characteristics of plants of Lycium nodosum grown under increasing water deficit (WD), saline spray (SS) or saline irrigation (SI) were studied. Plants of this perennial, deciduous shrub growing in the coastal thorn scrubs of Venezuela show succulent leaves which persist for approx. 1 month after the beginning of the dry season; leaf succulence is higher in populations closer to the sea. These observations suggested that L. nodosum is tolerant both to WD and salinity. In the glasshouse, WD caused a marked decrease in the xylem water potential (psi), leaf osmotic potential (psi(s)) and relative water content (RWC) after 21 d; additionally, photosynthetic rate (A), carboxylation efficiency (CE) and stomatal conductance (gs) decreased by more than 90 %. In contrast, in plants treated for 21 d with a foliar spray with 35 per thousand NaCl or irrigation with a 10 % NaCl solution, psi and RWC remained nearly constant, while psi(s) decreased by 30 %, and A, CE and gs decreased by more than 80 %. An osmotic adjustment of 0.60 (SS) and 0.94 MPa (SI) was measured. Relative stomatal and mesophyll limitations to A increased with both WD and SS, but were not determined for SI-treated plants. No evidence of chronic photoinhibition due to any treatment was observed, since maximum quantum yield of PSII, Fv/Fm, did not change with either drought in the field or water or salinity stress in the glasshouse. Nevertheless, WD and SI treatments caused a decrease in the photochemical (qP) and an increase in the non-photochemical (qN) quenching coefficients relative to controls; qN was unaffected by the SS treatment. The occurrence of co-limitation of A by stomatal and non-stomatal factors in plants of L. nodosum may be associated with the extended leaf duration under water or saline stress. Additionally, osmotic adjustment may partly explain the relative maintenance of A and gs in the SS and SI treatments and the tolerance to salinity of plants of this species in coastal habitats.


Biological monitoring of wood dust exposure in nasal lavage by high-performance liquid chromatography.
A high-performance liquid chromatography (HPLC) method for biomonitoring of occupational wood dust exposure based on nasal lavage as a biomonitoring matrix was developed. Gallic acid (GA) was chosen as the indicator compound for oak dust exposure. From the chromatographic profile of ash dust, four peaks were chosen as indicator compounds. Phenolic indicator compounds were analysed by HPLC. Personal dust samples and corresponding nasal lavage samples were collected from 16 workers exposed to oak dust and six to ash dust. The dust concentrations in the workers' breathing zone varied between 0.7 and 13.8 mg m(-3). The indicators revealed the nature of the wood dust inhaled. For the workers who did not use respirators, the correlation between the dust and corresponding indicator compound in their nasal lavage was significant; r2 = 0.59 (n = 12) for oak dust and r2 = 0.58 (n = 6) for ash dust, respectively. Further, the correlation for oak dust workers who used respirators was r = 0.67 (n = 4). Nasal lavage sampling and HPLC analysis of polyphenol indicator compounds are promising tools for measuring wood dust exposure. Although further validation is necessary, determination of the individual dose may prove invaluable in prospective epidemiological studies.


An environmental monitoring system for managing spatiotemporal sensor data over sensor networks.
In a wireless sensor network, sensors collect data about natural phenomena and transmit them to a server in real-time. Many studies have been conducted focusing on the processing of continuous queries in an approximate form. However, this approach is difficult to apply to environmental applications which require the correct data to be stored. In this paper, we propose a weather monitoring system for handling and storing the sensor data stream in real-time in order to support continuous spatial and/or temporal queries. In our system, we exploit two time-based insertion methods to store the sensor data stream and reduce the number of managed tuples, without losing any of the raw data which are useful for queries, by using the sensors' temporal attributes. In addition, we offer a method for reducing the cost of the join operations used in processing spatiotemporal queries by filtering out a list of irrelevant sensors from query range before making a join operation. In the results of the performance evaluation, the number of tuples obtained from the data stream is reduced by about 30% in comparison to a naïve approach, thereby decreasing the query execution time.


A patent review of ubiquitin-specific protease 7 (USP7) inhibitors (2014-present).
Ubiquitin-specific protease 7 (USP7) plays a critical role in multiple signaling pathways, and many recent studies have proved its association with many diseases. The USP7-murine double minute 2-p53 pathway and the relationship between USP7 and the important immune protein PD-L1 in cancer progression and metastasis have been clarified. Recently, USP7 has emerged as a promising and potent therapeutic target for cancer and has attracted both academic and industrial attention. This review focuses on the structure, activity, and applications of USP7 inhibitors in cancer therapy. It also focuses on patents reported since 2014. Recently, USP7 has attracted considerable attention owing to its physiological and pathophysiological roles in cancer progression, and few studies have focused on the development of USP7 inhibitors. Compared with micromolar first-generation USP7 inhibitors, second-generation USP7 inhibitors exhibit higher potency (at nanomolar level for both USP7 and cell inhibitory activities), higher selectivity, and better pharmacokinetic properties, and they largely broaden the range of candidates for further clinical tests. However, there is still a need for a more precise description of compounds with receptors, the structural diversity of these compounds, and screening methods.


Adaptive carbonyl umpolung involving a carbanionic carbene Breslow intermediate: an alternative mechanism for NHC-mediated organocatalysis.
Herein, we propose a novel mechanistic model for NHC-mediated carbonyl umpolung which involves the formation of a carbanionic carbene Breslow intermediate (CCBI). We have demonstrated theoretically that this reactive intermediate can be formed by inserting an aldehyde into the C4-H position of an N-aryl-substituted imidazolium-derived NHC via the generation of an H-bonded ditopic carbanionic NHC (dcNHC). Our DFT study on benzoin condensation has revealed that the mechanism of polarity inversion proceeding through the CCBI may be more energetically favorable than the classical mechanism of umpolung that uses the C2 carbene position in NHC. The potential existence of the CCBI highlights the dynamic and adaptive nature of NHC-mediated organocatalysis, particularly in relation to carbonyl umpolung. This finding also sheds light on new pathways in organocatalytic transformations employing the ambident reactivity of NHC, which may be particularly attractive for reactions involving furanic aldehydes and sterically encumbered N-aryl-substituted carbenes.


Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction.
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PX:IncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5. Mutagenesis of the SNX5-PX:IncE binding surface disrupts a previously unsuspected interaction between SNX5 and the cation-independent mannose-6-phosphate receptor (CI-MPR). Addition of IncE peptide inhibits the interaction of CI-MPR with SNX5. Finally, C. trachomatis infection interferes with the SNX5:CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5. Our results provide new insights into retromer assembly and underscore the power of using pathogens to discover disease-related cell biology.