Cardiovascular risk after androgen deprivation therapy for prostate cancer: an Asian perspective.
Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer. However, ADT may result in major cardiovascular events and potentially lead to fatal consequences. Cardiovascular disease is the leading cause of mortality and it is a very important health condition to look into. Asians and Caucasians differ both physiologically and genetically, and they may have display different cardiovascular profiles. In this article, we reviewed the literature focusing on the cardiovascular risk after ADT for prostate cancer in the Asian population. We would discuss about the pathogenesis of ADT leading to cardiovascular events, summarize the findings concerning cardiac and stroke risks after ADT, compare between the different modalities of ADT and also provide genetic basics which are unique to Asians. We hope this article would provide more insights into the cardiovascular risk after ADT for prostate cancer in an Asian perspective.


Opinion: more mouse models and more translation needed for ALS.
Amyotrophic lateral sclerosis is a complex disorder most of which is 'sporadic' of unknown origin but approximately 10% is familial, arising from single mutations in any of more than 30 genes. Thus, there are more than 30 familial ALS subtypes, with different, often unknown, molecular pathologies leading to a complex constellation of clinical phenotypes. We have mouse models for many genetic forms of the disorder, but these do not, on their own, necessarily show us the key pathological pathways at work in human patients. To date, we have no models for the 90% of ALS that is 'sporadic'. Potential therapies have been developed mainly using a limited set of mouse models, and through lack of alternatives, in the past these have been tested on patients regardless of aetiology. Cancer researchers have undertaken therapy development with similar challenges; they have responded by producing complex mouse models that have transformed understanding of pathological processes, and they have implemented patient stratification in multi-centre trials, leading to the effective translation of basic research findings to the clinic. ALS researchers have successfully adopted this combined approach, and now to increase our understanding of key disease pathologies, and our rate of progress for moving from mouse models to mechanism to ALS therapies we need more, innovative, complex mouse models to address specific questions.


Effect of stress hyperglycaemia on acute kidney injury in non-diabetic critically ill patients?
Stress hyperglycaemia (SH) and acute kidney injury (AKI) occur frequently in critically ill patients, and particularly non-diabetics are associated with adverse outcome. Data is scarce on the effect of SH on AKI. We assessed whether SH (i) preceded AKI, (ii) was a risk factor of subsequent AKI, and (iii) how SH and tubular injury interacted in AKI development in critically ill, non-diabetics. Case-control study of 82 patients each with and without SH matched by propensity score for multiple demographic characteristics. AKI was defined by KDIGO criteria, SH either as blood glucose (BG) > 140 mg/dl (BG140), > 200 mg/dl (BG200), or stress hyperglycemia rate (SHR) ≥ 1.47 (SHR1.47) as measured 2 days before AKI. Urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) indicated tubular injury. In AKI, SH rates were frequent using all 3 definitions applied, but highest when BG140 was applied. SH by all 3 definitions was consistently associated with AKI. This was independent of established risk factors of AKI such as sepsis and shock. Increments of BG, urinary NGAL or cystatin C, and its products, were independently associated with the likelihood of subsequent AKI, demonstrating their reciprocal potentiating effects on AKI development. SH is frequent in critically ill, non-diabetics with AKI. SH was identified as an independent risk factor of AKI. Higher BG combined with tubular injury may potentiate their adverse effects on AKI.


[Interrelationship between immunomodulating action of essentiale and its protective effect on working capacity in vibration disease].
Vibration was indicated to act on the body by suppressing the development of an immune response and lowers the physical working capacity of Wistar rats. The administration of essential to the rats with vibration-induced abnormalities stimulated these processes. There was no relationship between the suppression of the body's immunological responsiveness and the decrease in its working capacity. There was a relationship between the immunostimulating effect of essential and its property to enhance the physical working capacity of rats with vibration-induced damage.


[Decrease in the tissue-specific resistance of gastric epithelium to acute cell death following inhibition of DNA synthesis].
Administration to mice of hydroxyurea caused an acute death of an insignificant number of DNA-synthesizing cells in the epithelium of the glandular stomach. When actinomycin D was injected 8 hours prior to hydroxyurea there occurred a sharp intensification of cell degeneration: about 80% of the cells which synthesized DNA during the hydroxyurea administration proved to degenerate. No intensifying action was produced when actinomycin D was injected simultaneously with hydroxyruea. It is supposed that actinomycin D intensified the protein synthesis in the cells of the stomach (the "superinduction" effect), this increasing their sensitivity to the inhibition of the DNA synthesis.


Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry-based study.
The proportion of women delivering with known HIV status in sub-Saharan Africa is not well described. Risk of HIV transmission to newborns is a major concern, but there may also be increased risks for other adverse pregnancy outcomes. Hospital registry. North East Tanzania (1999-2006). Singletons (n = 14,444). Births were grouped by maternal HIV status and socio-demographic factors predicting HIV status, and associations between status and pregnancy outcomes were studied. Maternal HIV status, perinatal mortality, prematurity, small for gestational age (SGA), birthweight and low Apgar score. The proportion of mothers with known HIV status increased from 7% before 2001 to 78% after 2004. Single motherhood, rural residence, low maternal education, maternal and paternal farming and higher paternal age were associated with unknown HIV status. About 7.4% (95% CI 6.7-8.1%) of women were HIV infected, with increased likelihood of infection with higher gravidity, single motherhood, rural residence, maternal business or farming occupations and paternal tribe. Compared with HIV-uninfected women, the untreated HIV-infected women had a higher risk of SGA births (adjusted risk ratio [ARR] 1.6; 95% CI 1.1-2.4), preterm birth (ARR 1.8; 95% CI 1.1-2.7) and perinatal death (ARR 1.9; 95% CI 0.95-3.8). Women with unknown HIV status had moderately increased risks. Treated HIV-infected women had a risk similar to that of the HIV-uninfected women for all outcomes, except for low Apgar score. HIV testing and infection were associated with socio-demographic factors. Untreated HIV-infected women had higher risks of adverse pregnancy outcomes, and risks were also increased for women with unknown HIV status. There is still a need to increase availability of HIV testing, education and adequate therapy for pregnant women.


Characteristics and management of flexor tendon graft disruption.
In order to define the proper management of patients with disruption of a flexor tendon graft, 220 consecutive flexor tendon grafts were reviewed. Patients were divided into two groups--those who did not require a silastic rod prior to tendon grafting (89 grafts) and those who did require a silastic rod prior to tendon grafting (131 grafts). The incidence of tendon graft disruption for these two groups was 1.1% and 7.6%, respectively. Based on an analysis of these 11 graft disruptions, a method of management was devised. The literature is reviewed regarding the incidence and method of management of disrupted flexor tendon grafts.


Post-Ebola sequelae among Ebola child survivors in Sierra Leone.
There are limited data regarding the long-term health effects of child survivors of the 2013-2016 West African Ebola virus disease (EVD) outbreak. Here, we assess post-Ebola sequelae among EVD child survivors by comparing the self-reported symptoms between EVD child survivors and their close household contacts over one year after the end of the outbreak. EVD child survivors(n=159) and their close contacts(n=303) were enrolled in Western and Eastern Sierra Leone. Demographics and self-reported symptoms data were collected using an interviewer-administered questionnaire. We compared a list of self-reported symptoms between EVD child survivors and their close household contacts using backward stepwise logistic regression. EVD child survivors were more likely to be orphans compared to their close contacts. Musculoskeletal, ocular, auditory and neurological symptoms were more prevalent among Ebola child survivors than their close contacts (p<0.001). Joint pain and headache were the most common self-reported symptoms in EVD child survivors and their close contacts. Joint pain (AOR=2.633; 95 % CI:1.31-5.28, p=0.006), eye pain (AOR=4.56;95 %CI: 2.16-9.64, p<0.001), hearing loss (AOR=3.85; 95 %CI: 1.15-12.87, p=0.029), memory impairment (AOR=7.76;0.95 %CI: 1.34-45.01 p=0.022), mood changes (AOR=5.07; 95 %CI: 2.35-10.94, p<0.001) were more common among survivors than their contacts. Our data suggest that EVD child survivors have higher odds than their close contacts of suffering from musculoskeletal, ophthalmic, auditory and neurological impairment more than a year after the end of the EVD outbreak. Routine screening, treatment and monitoring of these symptoms is required to prevent long-term disability among EVD child survivors.


The aspirin and heme-binding sites of ovine and murine prostaglandin endoperoxide synthases.
Acetylation of Ser-530 of sheep prostaglandin endoperoxide (PGG/H) synthase by aspirin causes irreversible inactivation of the cyclooxygenase activity of the enzyme. To determine the catalytic function of the hydroxyl group of Ser-530, we used site-directed mutagenesis to replace Ser-530 with an alanine. Cos-1 cells transfected with expression vectors containing the native (Ser-530) or mutant (Ala-530) cDNAs for sheep PGG/H synthase expressed comparable cyclooxygenase and hydroperoxidase activities. Km values for arachidonate (8 microM) and ID50 values for reversible inhibition by the cyclooxygenase inhibitors, flurbiprofen (5 microM), flufenamate (20 microM), and aspirin (20 mM), were also the same for both native and mutant PGG/H synthases; however, only the native enzyme was irreversibly inactivated by aspirin. Thus, the "active site" Ser-530 of PGG/H synthase is not essential for catalysis or substrate binding. Apparently, acetylation of native PGG/H synthase by aspirin introduces a bulky sidechain at position 530 which interferes with arachidonate binding. In related studies, a cDNA for mouse PGG/H synthase was cloned and sequenced. A sequence of 35 residues with Ser-530 at the midpoint was identical in the two proteins. Thus, Ser-530 does lie in a highly conserved region, probably involved in cyclooxygenase catalysis. Sequence comparisons of mouse and sheep PGG/H synthase also provided information about the heme-binding site of the enzyme. The sheep HYPR sequence (residues 274-277), which had been proposed to form a portion of the distal heme-binding site, is not conserved in the mouse PGG/H synthase, suggesting that this region is not the distal heme-binding site. One sequence, TIWLREHNRV (residues 303-312 of the sheep enzyme), is very closely related to the sequence TLW(L)LREHNRL common to thyroid peroxidase and myeloperoxidase. The histidine in this latter sequence is the putative axial heme ligand of these peroxidases. We suggest that the histidine (His-309) of sheep PGG/H synthase sequence is the axial heme ligand of this enzyme.


Hospitalwide adverse drug events before and after limiting weekly work hours of medical residents to 80.
Adverse drug events (ADEs) at a hospital before and after the weekly work hours of medical residents were limited to 80 were studied. The study population included all adults admitted to a 750-bed academic tertiary care hospital where resident physicians provide direct care under the supervision of faculty attending physicians. The six-month period after implementation of the 80-hour work limit (July 1 to December 31, 2003) was compared with the same six-month period one year before implementation (July 1 to December 31, 2002). There were no significant differences between study periods in any measured variables, including number of confirmed ADEs (194 before, 172 after), number of ADEs per 1000 patient days (1.3 before, 1.1 after), and number of preventable ADEs (21 before, 22 after). Hospitalwide ADEs remained constant despite limiting of resident physician weekly work hours to 80.


A new surgical approach for the correction of female stress urinary incontinence.
A new surgical approach for the correction of female urinary stress incontinence has been devised. The retropubic space is entered through a dome-shaped incision in front of the urethral meatus in the anterior vaginal vestibule. The incision does not extend beyond the lower edge of the symphysis pubis. With the tip of the hemostat or scissors the incision is opened longitudinally, and the lower legs of the incision are opened and freed up from the bulbocavernosus muscles. The bleeders are controlled. The layers of the genitourinary diaphragm are opened beginning from behind the symphysis pubis and the retropubic cavity is exposed. Then, the vesical neck and urethra are sutured to the back of the symphysis pubis in the midline. With this procedure there is no abdominal incision. The vesical neck and urethra are well exposed. The back of the symphysis pubis can be visualized with the patient in an exaggerated Trendelenburg position. All except 1 patient were cured. Hospitalization and postoperative recovery times were markedly reduced. The procedure affords easy access for drainage of the retropubic space. A new avenue is provided for insertion of an artificial sphincter to achieve urinary continence and for vesical neck colposuspension.


Maximal activation of skeletal muscle thin filaments requires both rigor myosin S1 and calcium.
The regulation by calcium and rigor-bound myosin-S1 of the rate of acceleration of 2'-deoxy-3'-O-(N-methylanthraniloyl)ADP (mdADP) release from myosin-mdADP-P(i) by skeletal muscle thin filaments (reconstituted from actin-tropomyosin-troponin) was measured using double mixing stopped-flow fluorescence with the nucleotide substrate 2'-deoxy-3'-O-(N-methylanthraniloyl). The predominant mechanism of regulation is the acceleration of product dissociation by a factor of approximately 200 by thin filaments in the fully activated conformation (bound calcium and rigor S1) relative to the inhibited conformation (no bound calcium or rigor S1). In contrast, only 2-3-fold regulation is due to a change in actin affinity such as would be expected by "steric blocking" of the myosin binding site of the thin filament by tropomyosin. The binding of one ligand (either calcium or rigor-S1) produces partial activation of the rate of product dissociation, but the binding of both is required to maximally accelerate product dissociation to a rate similar to that obtained with F-actin in the absence of regulatory proteins. The data support an allosteric regulation model in which the binding of either calcium or rigor S1 alone to the thin filament shifts the equilibrium in favor of the active conformation, but full activation requires binding of both ligands.


Eosinophil-specific biological activity of recombinant ovine interleukin-5.
Recombinant ovine interleukin-5 (rovIL-5) expressed from Chinese hamster ovary (CHO) cells was tested for cell-specific bioreactivity, in vitro, in a soft agar clonogenic assay and in an enzyme-based microassay for eosinophil potentiating activity (EPA). In soft agar assays, colony and cluster formation from sheep bone marrow cells (SBMC) incubated with rovIL-5 was significantly enhanced compared with SBMC incubated with control supernatants from mock-transfected CHO cells. Colony analysis at 14 days demonstrated that for three separate rovIL-5 preparations 45%, 61% and 66% of colonies were eosinophilic, as were 55%-71% of clusters. In contrast, no eosinophil colonies were detected in parallel control cultures. RovIL-5 was also shown to possess potent and dose-responsive EPA, on the basis of eosinophil peroxidase (EPO) and arylsulphatase (EAS) assay in 7 day SBMC cultures. This activity was inhibited in a dose-responsive manner by TRFK-5, a rat anti-murine IL-5 monoclonal antibody (MAb) previously shown to have cross-reactivity in the ovine EPA assay. The results demonstrate that rovIL-5 exhibited eosinophil-specific properties similar to those of IL-5 derived from other mammalian species.


Location and ion-binding of membrane-associated valinomycin, a proton nuclear magnetic resonance study.
Valinomycin, incorporated in small unilamellar vesicles of perdeuterated dimyristoylphosphatidylcholine, reveals several well-resolved 1H-NMR resonances. These resonances were used to examine the location, orientation and ion-binding of membrane-bound valinomycin. The order of affinity of membrane-bound valinomycin for cations is Rb+ greater than K+ greater than Cs+ greater than Ba2+, and binding is sensitive to surface change. The exchange between bound and free forms is fast on the NMR time scale. The intrinsic binding constants, extrapolated to zero anion concentration, are similar to those determined in aqueous solution. Rb+ and K+ show 1:1 binding to valinomycin, whereas the stoichiometry of Cs+ and Ba2+ is not certain. Paramagnetic chemical shift reagents and nitroxide spin label relaxation probes were used to study the location and orientation of valinomycin in the membrane. Despite relatively fast exchange of bound cations, the time average location of the cation-free form of valinomycin is deep within the bilayer under the conditions of these experiments. Upon complexation to K+, valinomycin moves closer to the interfacial region.


Towards complete eradication of hepatitis B infection from perinatal transmission: review of the mechanisms of in utero infection and the use of antiviral treatment during pregnancy.
Hepatitis B infection remains the most common form of chronic hepatitis. Mother to child transmission occurs despite immunoprophylaxis with vaccination and immunoglobulin. In utero infection is suggested to account for most of the cases with immunoprophylaxis failure. Infants who suffer from hepatitis B infection at birth have a higher risk of becoming chronic carriers and may develop liver cirrhosis or hepatocellular carcinoma in the future. Infected germ cells, transplacental infection, invasive prenatal diagnostic tests and various perinatal factors are possible factors leading to in utero infection and subsequent immunoprophylaxis failure. Hepatitis B e antigen positive status and high viral load increase the risk of immunoprophylaxis failure. Recent evidence shows promising results regarding the use of antiviral treatment in late gestation to suppress viral load, so as to decrease the risk of vertical transmission. This review discusses the possible mechanisms of in utero infection and the use of antiviral treatment during pregnancy.


Safety, immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis.
The safety, immunogenecity, and efficacy of two doses of an autoclaved-killed, whole cell Leishmania amazonensis vaccine (IFLA/BR/67/PH8) and BCG adjuvant (n = 750) against cutaneous leishmaniasis (CL) was compared with placebo (n = 756) in a randomized, placebo-controlled, blinded study. Systemic and local side-effects were more frequent in the vaccine than placebo group. Leishmanin skin test (LST) conversion was greater in the vaccine than placebo group 2 months after the second vaccination dose (74.4% versus 14.7%; P = 0.000001). The 26-month incidence of confirmed CL (n = 25) was similar between the vaccine (2.0%) and placebo groups (2.0% versus 1.3%; P > 0.05). LST conversion was not associated with CL protection and the vaccine did not offer significant protection against CL infection caused by L. Viannia spp. compared to placebo.


Intracellular starvation in the insulin resistance syndrome and type II diabetes mellitus.
Statistical associations of insulin resistance, type II diabetes, hypertension and hyperlipidemia have been well documented, but the pathophysiology of the 'insulin resistance syndrome' is unknown. This article explores the hypothesis that intracellular starvation plays a central role in the development of type II diabetes, hypertension and hyperlipidemia. According to this hypothesis, insulin resistance leads to inadequate intracellular glucose, which in turn leads to insufficient amounts of adenosine triphosphate needed for ion transfer, and to drive energy-requiring reactions. Indirect evidence supporting this hypothesis is presented. Intracellular starvation is also discussed as an alternative to the 'glucose hypothesis' to explain certain complications of diabetes.


Assessment of peripheral lung mechanics.
The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies.


[Effects of feeding deoxynivalenol contaminated wheat to piglets].
Effects of the mycotoxin deoxnivalenol (DON) on weaned piglets were investigated. Two feeding trials were conducted with naturally contaminated wheat in the ration. In the first trial as preliminary study weaned piglets were fed for one week with 7.7 mg DON per kg ration, intake of DON contaminated diets was not associated with any obvious negative health effects. Also in the main feeding trial with 3 mg DON per kg ration no vomiting and other negative clinical symptoms could be registered. The feed intake and the daily weight gains were significantly lower in the DON fed group when compared with control group, but the feed conversion rates were slightly improved in group fed DON.


Characterization of a Tigger1 element from the genome of the American mink (Neovison vison).
Tigger elements belong to the Tc1/Mariner family of DNA transposons which is remarkably widespread in nature with homologs present in organisms as diverse as fungi, plants and animals. In this report, we present the nucleotide sequence of a defragmented Tigger1 element from the genome of the American mink. The element is 2,274 bp long, carries 13 bp terminal inverted repeats (TIRs) and contains the vestiges of two open reading frames (ORFs), one of which is similar to the centromere associated protein CENP B. In addition, we estimate that the genome of the American mink contains approximately 1000 Tigger1 elements, but find no evidence for the transcription of extant elements in the mink.


Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia.
Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase. Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥ 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥ 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities. Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥ 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%. IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (≥ 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated.


Alanine dehydrogenases from four different microorganisms: characterization and their application in L-alanine production.
Alanine dehydrogenase (AlaDH) belongs to oxidoreductases, and it exists in several different bacteria species and plays a key role in microbial carbon and nitrogen metabolism, spore formation and photosynthesis. In addition, AlaDH can also be applied in biosynthesis of L-alanine from cheap carbon source, such as glucose. To achieve a better performance of L-alanine accumulation, system evaluation and comparison of different AlaDH with potential application value are essential. In this study, enzymatic properties of AlaDH from Bacillus subtilis 168 (BsAlaDH), Bacillus cereus (BcAlaDH), Mycobacterium smegmatis MC2 155 (MsAlaDH) and Geobacillus stearothermophilus (GsAlaDH) were firstly carefully investigated. Four different AlaDHs have few similarities in optimum temperature and optimum pH, while they also exhibited significant differences in enzyme activity, substrate affinity and enzymatic reaction rate. The wild E. coli BL21 with these four AlaDHs could produce 7.19 g/L, 7.81 g/L, 6.39 g/L and 6.52 g/L of L-alanine from 20 g/L glucose, respectively. To further increase the L-alanine titer, competitive pathways for L-alanine synthesis were completely blocked in E. coli. The final strain M-6 could produce 80.46 g/L of L-alanine with a yield of 1.02 g/g glucose after 63 h fed-batch fermentation, representing the highest yield for microbial L-alanine production. Enzyme assay, biochemical characterization and structure analysis of BsAlaDH, BcAlaDH, MsAlaDH and GsAlaDH were carried out. In addition, application potential of these four AlaDHs in L-alanine productions were explored. The strategies here can be applied for developing L-alanine producing strains with high titers.


Empyema necessitans complicating a mild COVID-19 infection in a young immunocompetent patient.
COVID-19 infection can be complicated by secondary bacterial infections including pneumonia and empyema resulting in worse outcomes. Empyema management includes empirical antibiotic therapy and drainage with a favorable prognosis in most cases. Empyema necessitans is a rare complication of poorly or uncontrolled empyema thoracis resulting in the dissection of pus through the soft tissues and skin of the chest wall resulting in a fistula between the pleural cavity and the skin. Previous reports indicate that secondary bacterial pneumonia can complicate the course of a COVID-19 infection even in immunocompetent patients resulting in worse outcomes. Management of empyema includes empirical antibiotic therapy and drainage with a favorable prognosis in most cases.


Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of Protein-Ligand Contacts.
Saturation transfer difference (STD) NMR spectroscopy is extensively used to obtain epitope maps of ligands binding to protein receptors, thereby revealing structural details of the interaction, which is key to direct lead optimization efforts in drug discovery. However, it does not give information about the nature of the amino acids surrounding the ligand in the binding pocket. Herein, we report the development of the novel method differential epitope mapping by STD NMR (DEEP-STD NMR) for identifying the type of protein residues contacting the ligand. The method produces differential epitope maps through 1) differential frequency STD NMR and/or 2) differential solvent (D2 O/H2 O) STD NMR experiments. The two approaches provide different complementary information on the binding pocket. We demonstrate that DEEP-STD NMR can be used to readily obtain pharmacophore information on the protein. Furthermore, if the 3D structure of the protein is known, this information also helps in orienting the ligand in the binding pocket.


"Individual Placement and Support" boosts employment for early psychosis clients, even when baseline rates are high.
Individual Placement and Support is an effective vocational intervention for increasing competitive employment for people with severe mental illness. Little is known, however, about its effectiveness in the context of early psychosis. This study assesses improvements in clients' employment in a phase of illness during which functional abilities often decline. The trial design is an assessor-blinded randomized clinical trial, set in the context of a population-based Early Psychosis Intervention program in British Columbia, Canada. Participants were randomized either to 1 year of employment support added to treatment-as-usual, or the latter alone. Interviews at intake captured data regarding demographics, symptom severity, and employment; assessments at 6 and 12 months repeated queries about employment activities. A total of 109 clients were recruited. Employment rates in the Individual Placement and Support group increased over time, unlike the control group. Further, the number of days worked over the 12-month intervention period, compared to the 6 months prior to the study, improved for both groups, but the increase was greater among clients receiving IPS. Sensitivity analysis indicated the advantage in days worked was evident in the second half of the intervention period (6-12 months), but not the first half. Employment rates, for younger clients in both early-psychosis groups, were high compared to older clients in later stages of illness. In this study, use of the Individual Placement and Support strategy further increased employment, despite the high baseline rates. Further research is needed to identify the optimal timing of employment support for these clients.


Effect of intratracheal and oral application of corticosteroids on the adrenal function test in beagle dogs after ACTH-stimulation.
The effect of synthetic corticosteroids given intratracheally or orally on the adrenal glands of beagle dogs was investigated. The adrenal function was evaluated using a standardized ACTH stimulation test. In addition, histological and morphometrical examinations of the adrenal cortex were performed at the end of the study. Beclomethasone dipropionate given intratracheally at daily dose levels of 0.05, 0.1 and 0.5 mg/kg body weight led to a dose dependent adrenal suppression on the basis of plasma cortisol concentration and eosinophil counts after ACTH stimulation and size of zona fasciculata and reticularis. A complete adrenal suppression was observed at the highest dose level of 0.5 mg/kg body weight. Also the oral administration of 0.1 mg/kg body weight/day of beclomethasone dipropionate had a definite adrenal suppressive effect comparaable to that of 0.1 mg/kg body weight given intratracheally. However, intratracheal administration of fluocortin butylester, a local antiinflammatory drug but systemically a nearly ineffective corticosteroid (2 X 8 mg/kg body weight/day) had no suppressive effect on the adrenal gland of the beagle dog, even after a 320 times higher dose.


An integrated approach of NMR experiments and MD simulations visualizes structural dynamics of a cyclic multi-domain protein.
Cyclization can stabilize the structure of proteins, as previously demonstrated in single-domain proteins. Although Lys48-linked polyubiquitin, a multi-domain protein, is also known to be cyclized in human cells, the structural effects of cyclization remain unclear. Here, we examined the impact of cyclization on the structural stability and dynamics of cyclic Lys48-linked diubiquitin (Ub2 ). As expected, cyclization increased the thermal stability of Ub2 and its resistance to proteolytic digestion, indicating that cyclization stabilized the structure of Ub2 . Furthermore, cyclization repressed the interdomain motion in Ub2 , but cyclic Ub2 still exhibited microsecond conformational exchange in NMR relaxation dispersion experiments. A series of long coarse-grained (CG) MD simulations visualized how cyclization slowed down the intrinsic nanosecond open-closed domain motion of Ub2 to microseconds. Thus, CG-MD analysis helped to explain the unexpected NMR relaxation results, thereby facilitating characterization of the structural stabilization of cyclic Ub2 .


Divorce Attitudes among Older Adults: Two Decades of Change.
The authors used data from the 1994, 2002, and 2012 General Social Survey (N = 1,450) to examine whether support for divorce has increased among adults aged 50 and older. Consistent with the rise in the gray divorce rate, today's older adults were more accepting of divorce than their predecessors were two decades ago. Attitudinal change was modest between 1994 and 2002 but accelerated after 2002. The acceleration was primarily due to period rather than cohort change, signaling the role of broader shifts in the meaning of marriage as it has become deinstitutionalized. Older birth cohorts and individuals who were either divorced or remarried were especially likely to hold supportive attitudes toward divorce.


Being Left Alone at Home and Dental Caries of Children Aged 6-7 Years.
Leaving children alone at home is considered child neglect in some countries but is not prohibited in Japan. We investigated the association between being left alone at home and dental caries of children aged 6-7 years in Japan. The data on first graders in all 69 public elementary schools in Adachi, Tokyo, obtained from repeated cross-sectional surveys in 2015, 2017, and 2019 were analyzed. Caregivers answered the questionnaire, and the data were linked to the information on children's dental caries evaluated in school dental health checkups (N = 12,029). Poisson regression analysis with propensity score matching (PSM) was applied to account for confounders. Leaving children alone at home for ≥1 hour during the weekdays was reported by 46.4% of the caregivers, which did not vary across years. The PSM analysis showed that, compared with children never being left alone at home, children being left alone at home for ≥1 time per week had more dental caries (mean ratio [MR] 1.11; 95% confidence interval (CI), 1.02-1.21; P = 0.016), while <1 time per week was not associated (MR 0.97; 95% CI, 0.92-1.03; P = 0.345). The difference between those being left alone at home for <1 time per week and those being left alone for ≥1 time per week was not significant after applying Bonferroni correction (MR 1.12; 95% CI, 1.00-1.26; P = 0.041). Leaving children alone at home for ≥1 hour every week might be a risk factor for dental caries of children aged 6-7 years.


The possible role of insulin-like growth factor-1 in osteosarcoma.
Osteosarcoma (OS) is a common malignant tumor of bone, of which clear understanding of molecular pathologic process is not yet possible. Insulin-like growth factor-1 (IGF-1) is a hormone that plays vital role in development and function of many tissues. Unfortunately, IGF-1 and its receptor (IGF-1R)'s over-expression have been implicated in carcinogenesis, and indicated to constitute a risk factor for the development of multiple human cancers, including OS. Increased levels of IGF-1 and IGF-1R have been reported in OS, leading to cancer progression through transformation, proliferation, pro-metastasis, and decreased susceptibility to apoptosis. Over-expression of IGF-1/IGF-1R signaling also contributes to tumor cell survival, metastasis, and resistance to chemotherapeutic drugs. IGF-1 has been included as an OS marker recently, and targeting IGF-1 is an interesting and promising approach in OS therapeutics. However more investigations with clinical trials are necessary to validate the use of drugs against IGF-1 that may provide a basis for new therapeutic approaches to treat this devastating disease. This review article focused on the role of IGF-1/IGF-1R in OS progression and therapeutic aspects of OS targeting IGF-1.


Microbial, physicochemical and proximate analysis of Tej collected from Amhara regional state of Ethiopia.
Tej is an Ethiopian traditional alcoholic beverage with significant social and economic importance. Due to the spontaneous fermentation process of Tej, several issues such as safety, quality, and physicochemical properties of the final products is rquired to be assessed. Thus, this study was aimed to assess the microbial quality, physicochemical, and proximate properties of Tej associated with different maturity time. The microbial, physicochemical and proximate analyses were carried out by standard protocol. Lactic acid bacteria (6.30 log CFU/mL) and yeast (6.22 log CFU/mL) were the dominat microorganisms of all Tej samples at different maturity time, with significant differences (p = 0.001) in mean microbial count among samples. The mean pH, titratable acidity and ethanol content of Tej samples were 3.51, 0.79 and 11.04% (v/v), respectively. There were significant differences (p = 0.001) among the mean pH and titratable acidity values. The mean proximate compositions (%) of Tej samples were as follows: moisture (91.88), ash (0.65), protein (1.38), fat (0.47) and carbohydrate (3.91). Statistically significant differences (p = 0.001) were observed in proximate compositions of Tej samples from different maturity time. Generally, Tej maturity time has a great impact on the improvement of nutrient composition and the increment of the acidic contents which in turn suppress the growth of unwanted microorganisms. Further evaluation of the biological, and chemical safety and development of yeast-LAB starter culture are strongly recommended to improve Tej fermentation in Ethiopia.


Do girls and boys perceive themselves as equally engaged in school? The results of an international study from 12 countries.
This study examined gender differences in student engagement and academic performance in school. Participants included 3420 students (7th, 8th, and 9th graders) from Austria, Canada, China, Cyprus, Estonia, Greece, Malta, Portugal, Romania, South Korea, the United Kingdom, and the United States. The results indicated that, compared to boys, girls reported higher levels of engagement in school and were rated higher by their teachers in academic performance. Student engagement accounted for gender differences in academic performance, but gender did not moderate the associations among student engagement, academic performance, or contextual supports. Analysis of multiple-group structural equation modeling revealed that perceptions of teacher support and parent support, but not peer support, were related indirectly to academic performance through student engagement. This partial mediation model was invariant across gender. The findings from this study enhance the understanding about the contextual and personal factors associated with girls' and boys' academic performance around the world.


Photodecomposition, photomutagenicity and photocytotoxicity of retinyl palmitate under He-Ne laser photoirradiation and its effects on photodynamic therapy of cancer cells in vitro.
Our aim was to study photodecomposition, photomutagenicity and cytotoxicity of retinyl palmitate (RP), a principal storage form of vitamin A in humans and animals, under He-Ne laser photoirradiation. Moreover, the effect of different concentrations and timing protocol of antioxidants on photodynamic therapy (PDT) is contradictory, so the effect of RP (as antioxidant) on the PDT cytotoxicity was studied. Photomutagenicity was tested by Ames test. Photodecomposition was studied by UV-vis spectroscopy. Cytotoxicity was measured with MTT-assay. Moreover, the effect of PDT, using hematoporphyrin derivatives (HpD) as photosensitizer under He-Ne laser irradiation (10 J/cm(2)), was studied on HeLa cells either with or without RP (1-100 μM) which incubated with the cells for short or long incubation period (1 h or 24 h) prior to PDT. No photodecomposition of RP alone was obseved whereas there is a little photodecomposition of RP only in presence of HpD under irradiation with He-Ne laser. Moreover, no photomutagenicity was observed in Salmonella typhimurium strains under laser irradiation in presence or absence of HpD. RP alone (1-100 μM) significantly decrease the viability of HeLa cells. Laser irradiation of HeLa cells pre-incubated with RP alone for 24 h showed further significant decrease in viability of the cells. While RP incubations for 1 h before PDT had slight effect on the cells, 24 h incubation before PDT enhanced the cytotoxicity of PDT on HeLa cells. RP can be used 24 h before PDT to enhance its effects. RP is not mutagenic under irradiation with He-Ne laser.


Chemical composition and health effects of Tartary buckwheat.
Tartary buckwheat (Fagopyrum tataricum) contains a range of nutrients including bioactive carbohydrates and proteins, polyphenols, phytosterols, vitamins, carotenoids, and minerals. The unique composition of Tartary buckwheat contributes to their various health benefits such as anti-oxidative, anti-cancer, anti-hypertension, anti-diabetic, cholesterol-lowering, and cognition-improving. Compared with the more widely cultivated and utilised common buckwheat (F. esculentum), Tartary buckwheat tends to contain higher amounts of certain bioactive components such as rutin, therefore, showing higher efficiency in preventing/treating various disorders. This review summarises the current knowledge of the chemical composition of Tartary buckwheat, and their bio-functions as studied by both in vitro and in vivo models. Tartary buckwheat can be further developed as a sustainable crop for functional food production to improve human health.


Spontaneous middle lobe torsion: An institutional case series.
Lobar torsion is a rare occurrence in which a portion of the lung is twisted on its bronchovascular pedicle. The vast majority are observed in the acute postoperative period often following right upper lobectomy. Spontaneous middle lobe torsion independent of pulmonary resection is exceptionally rarer; fewer than 15 cases have been recorded. We present an institutional case series of 2 patients postorthotopic liver transplantation who developed spontaneous middle lobe torsion due to large pleural effusions. We provide the medical course as well as intraoperative techniques for our 2 patients along with a review of the literature. Both patients in this case series underwent orthotopic liver transplant complicated postoperatively by a large pulmonary effusion. Patient one developed an abdominal hematoma requiring evacuation and repair, after which he developed progressive shortness of breath. Bronchoscopy revealed a right middle lobe obstruction; upon thoracotomy, 180-degree torsion with widespread necrosis was evident and the middle lobe was removed. He is doing well to date. Patient 2 experienced postoperative pleural effusion and mucus plugging; computed tomography revealed abrupt middle lobe arterial occlusion prompting urgent operative intervention. Again, the middle lobe was grossly ischemic and dissection revealed a 360-degree torsion around the pedicle. It was resected. He is doing well to date. As the result of its rarity, radiographic and clinical diagnosis of spontaneous pulmonary lobar torsion is challenging; a high index of suspicion for spontaneous middle lobe torsion must be maintained to avoid delays in diagnosis. Prompt surgical intervention is essential to improve patient outcomes.


Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids.
Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.


Potential enhancement of direct interspecies electron transfer for anaerobic degradation of coal gasification wastewater using up-flow anaerobic sludge blanket (UASB) with nitrogen doped sewage sludge carbon assisted.
Waste sewage sludge was converted into the novel conductive material of nitrogen doped sewage sludge carbon (N-SC) to enhance anaerobic degradation of coal gasification wastewater (CGW). The results indicated that N-SC played a significant role in enhanced efficiencies, with chemical oxygen demand (COD) removal efficiency increased by 25.4%, methane production rate improved by 68.1% and total volatile fatty acids (VFA) decreased by 37.5% than that of controlled reactor. The conductivity, activity of electron transport, and extracellular polymeric substances (EPS) of anaerobic sludge were remarkably enhanced with N-SC, which promoted sludge granulation and supplied better conductive environment for microorganisms. The microbial community analysis revealed that potential enhancement of direct interspecies electron transfer (DIET) was achieved by electrical connection between enriched Geobacter, Pseudomonas and Methanosaeta with N-SC assisted, which enhanced the anaerobic degradation of CGW. Moreover, anaerobic degradation with N-SC had higher capacity to resist acidic shocks, facilitating the process stability.


Challenges in determining perchlorate in biological tissues and fluids: implications for characterizing perchlorate exposure.
The ability to measure environmental contaminants in biological tissues and fluids is important in the characterization of exposure. However, the analysis of certain contaminants in these matrices presents significant challenges. Perchlorate (ClO4-) has emerged as a potential contaminant of concern primarily in drinking water and also in contaminated food. Significant advances have been made in the analysis of perchlorate in environmental matrices (water, soil) by ion chromatography (IC). In contrast, the analysis of perchlorate in extracts of biological tissues and fluids (vegetation, organs, milk, blood, urine, etc.) presents several challenges including small sample sizes, extracts with high matrix conductivity, and co-elution of other ions during IC analysis. To be able to detect low concentrations of perchlorate in biological samples, interferences must be removed or minimized, such as through the use of preparative chromatography cleanup techniques and/or alternative analytical methods less susceptible to common interferences (preconcentration or mass spectrometric detection). We present discussion and examples of the challenges encountered in the analysis of tissue extracts and fluids for perchlorate by IC and how some of those analytical challenges have been overcome.


[Activation of TLR3 pathway in the pathogenesis of nephrotic syndrome induced by respiratory syncytial virus in rat model].
To explore the activation of toll-like receptor 3 (TLR3) pathway on the process of respiratory syncytial virus (RSV) induced nephropathy. SD rats were inoculated intranasally and intraperitoneally with 6 X 10(6) plaque forming unit(PFU) RSV and sacrificed on days 4, 14, 30 postinoculation (RSV4, RSV14 and RSV30). The normal rats without intervention were set as control. Renal tissues were obtained, and the morphological changes were studied. The expressions of TLR3, NF-kappaB and IL-13 in the rats' kidney were measured with real-time quantitative RT-PCR, and indirect IF staining. After the inoculation of RSV, the rats had proteinuria and the fusion of foot processes of glomerular epithelial cells, resembling human minimal changed nephrotic syndrome (MCNS). The expressions of TLR3, NF-kappaB and IL-13 in renal tissues increased obviously at Day 4 and Day 14 postinoculation, the differences were significant when compared with normal control rats (P < 0.05). The expressions of these three factors decreased at Day 30, which were not significantly different to those of normal control group (P > 0.05). TLR3 signal pathway may play an important role in early stage of RSV nephropathy.


Review: F-Actin remodelling during plant signal transduction via biomolecular assembly.
During signal transduction, multivalent interactions establish dynamic molecular connectivities that propagate molecular cascades throughout the entire signaling pathway. Such multivalent interactions include the initial activation, cascade signal transduction, and the amplification and assembly of structural machinery. For example, plants rapidly remodel the actin cytoskeleton during signal transduction by perceiving a wide range of mechanical and chemical cues from developmental and defense pathways. Actin treadmilling is stepwise-regulated by interactions between actin and actin-binding proteins (ABPs). Emerging evidence shows that intrinsically disordered regions (IDRs) enable flexible and promiscuous interactions that serve as the functional hub for generating cellular interactomes underlying various signaling events. Though IDRs are present in a majority of ABPs, few of the functional roles of IDR in the interaction and functions of ABPs have been defined. The distinct features of IDRs create diverse and dynamic molecular interactions that introduce a new paradigm to our understanding of the structure-function relationships for actin assembly. In this review, we will create a snapshot of recent advances in IDR-mediated plant actin remodeling and discuss future research directions in studying the complexity of actin assembly via multifaceted biomolecular assembly during signal transduction.


Naringenin and proanthocyanidins pre-treatment decreases synthesis and activity of gelatinases induced by zoledronic acid in a dental implant surface in vitro model.
To assess the effects of pre-treatment with proanthocyanidins (PA) flavonoids, from grape seed extract, and synthetic naringenin (NA) on the synthesis of matrix metalloproteinases (MMPs) gelatinases and their tissue inhibitors (TIMPs), as well as the gelatinolytic activity of MMPs by human gingival fibroblasts (HGF) and osteoblasts (Ob) exposed to zoledronic acid (ZA) in a dental implant surface in vitro model. The highest non-cytotoxic concentrations of NA and PA were determined for HGF (10 μg/mL; defined by previous study) and Ob (0.5 μg/mL; defined by prestoBlue assay). Then, HFG and Ob were individually seeded onto titanium discs, and after 24 h, cells were pre-treated (or not) with NA or PA, followed (or not) by exposure to ZA. Next, MMP-2, MMP-9, TIMP-1, TIMP-2 synthesis (ELISA), and gelatinolytic activity (in situ zymography) was evaluated. Data were analyzed by one-way ANOVA and Tukey tests (α = 0.05). ZA treatment increased the synthesis (p < 0.05) and activity of MMPs; flavonoids pre-treatment controlled ZA-induced gelatinolytic effects, down-regulating MMPs synthesis (p < 0.05) and activity by HGF and Ob. For HGF, NA and PA pre-treatment did not up-regulate TIMP synthesis after ZA exposure (p > 0.05); for Ob, TIMP-2 was up-regulated (p < 0.05) by flavonoids, followed by ZA. NA and PA pre-treatment provides interesting results in the modulation of ZA deleterious effects, down-regulating MMP-2 and MMP-9 synthesis and activity by HGF and Ob and up-regulating TIMP-2 by Ob.


Applied physiology of marathon running.
Performance in marathon running is influenced by a variety of factors, most of which are of a physiological nature. Accordingly, the marathon runner must rely to a large extent on a high aerobic capacity. But great variations in maximal oxygen uptake (VO2 max) have been observed among runners with a similar performance capacity, indicating complementary factors are of importance for performance. The oxygen cost of running or the running economy (expressed, e.g. as VO2 15 at 15 km/h) as well as the fractional utilisation of VO2 max at marathon race pace (%VO2 Ma X VO2 max-1) [where Ma = mean marathon velocity] are additional factors which are known to affect the performance capacity. Together VO2 max, VO2 15 and %VO2 Ma X VO2 max-1 can almost entirely explain the variation in marathon performance. To a similar degree, these variables have also been found to explain the variations in the 'anaerobic threshold'. This factor, which is closely related to the metabolic response to increasing exercise intensities, is the single variable that has the highest predictive power for marathon performance. But a major limiting factor to marathon performance is probably the choice of fuels for the exercising muscles, which factor is related to the %VO2 Ma X VO2 max-1. Present indications are that marathon runners, compared with normal individuals, have a higher turnover rate in fat metabolism at given high exercise intensities expressed both in absolute (m/sec) and relative (%VO2 max) terms. The selection of fat for oxidation by the muscles is important since the stores of the most efficient fuel, the carbohydrates, are limited. The large amount of endurance training done by marathon runners is probably responsible for similar metabolic adaptations, which contribute to a delayed onset of fatigue and raise the VO2 Ma X VO2max-1. There is probably an upper limit in training kilometrage above which there are no improvements in the fractional utilisation of VO2 max at the marathon race pace. The influence of training on VO2 max and, to some extent, on the running economy appears, however, to be limited by genetic factors.


Intraoperative Fluorescent Angiography Predicts Pharyngocutaneous Fistula After Salvage Laryngectomy.
Technology to assess tissue perfusion is exciting with translational potential, although data supporting its clinical applications have been lagging. Patients who have undergone radiation are at particular risk of poor tissue perfusion and would benefit from this expanding technology. We designed a prospective clinical trial using intraoperative indocyanine green angiography to evaluate for wound-healing complications in patients undergoing salvage laryngectomy after radiation failure. This prospective trial included patients undergoing salvage laryngectomy at a National Cancer Institute-designated tertiary cancer center between 2016 and 2018. After tumor extirpation and prior to reconstruction, 10 mg indocyanine green dye was infused and the fluorescence (FHYPO) and ingress rate of the pharyngeal mucosa recorded. The primary outcome measure was formation of a pharyngocutaneous fistula (PCF). Patients who developed a PCF had significantly lower FHYPO (87 vs 172, p < 0.001) and ingress rates (6.7 vs 15.8, p = 0.043) compared with those who did not develop a fistula. There were no fistulas in patients with FHYPO > 150 (n = 21) or ingress > 15 (n = 15). There was a 50% fistula rate in patients with FHYPO ≤ 103 (n = 10) and ingress rate ≤ 6 (n = 6). Intraoperative indocyanine green angiography can assess hypoperfusion in patients and predict risk of PCFs after salvage laryngectomy, and can thus intraoperatively risk-stratify patients for postoperative wound-healing complications.


The relation between prepregnancy maternal body mass index and total gestational weight gain with the characteristics of the newborns.
To evaluate the relationship between the maternal body mass index (BMI) and total gestational weight gain (GWG) with the characteristics of newborns, taking into consideration the birth weight (BW), weight for age score (WfA), length for age (LfA), and weight for length (WfL), APGAR score, and premature delivery. We conducted a study, from March 2015 to 2016. We included a number of 1218 pregnant women who delivered single babies, from three different hospitals that serve the entire Mures County and who met our inclusion criteria. We did not find significant differences regarding weight, length at birth, and gestational age, between girls and boys, neither between total GWG during pregnancy and the measured anthropometric parameters of the newborns, or between maternal GWG and gestational age of the newborns. We found a positive correlation between the mothers' BMI and the BW of the newborns (p =.03, r = 0.06, 95% CI = 0.0036-0.1169), but not between BMI and the birth length and nor with APGAR score. The statistical analysis showed a positive correlation between BMI and LfA (p = .01, r = 0.07, 95%CI = 0.0141-0.1269), but not with WfA and WfL. Women with higher BMI before getting pregnant showed significantly higher frequency of preterm delivery (p = .0078). We found a statistically significant correlation between GWG and BW (p<.0001). Excessive GWG correlates statistically significant with BW (p < .0001). We found a positive correlation between the mothers' BMI and excessive GWG and the BW of their newborns in women delivering a single baby. Women with higher BMI showed significantly higher frequency of preterm delivery.


Design of Customized Mobile Application for Patient Adherence to Oral Anticancer Medications Utilizing User-Centered Design.
Adherence and compliance to oral anticancer medications (OAMs) can be challenging for patients due to their complex regimens. The goal of this research project was to design an effective and engaging user interface (UI), based on user-centered design (UCD) and incorporate animations, to reinforce and improve patient's understanding of the key aspects of taking OAMs. This current paper encompasses the development process and describes the initial phase of the project, which focused on the design and development of the tablet-based educational application (app). A UCD approach was implemented by consulting with oncology clinicians and patients at an early stage of development. Animations were developed and incorporated to convey complex medical concepts and information. An iterative design process will help ensure that the tool is customized for patient engagement.


The role of thoracic computed tomography in staging newly-diagnosed oral squamous cell carcinoma.
Patients who present with squamous cell carcinoma (SCC) in the head and neck have a serious risk of coincident thoracic malignancy. The aim of this study was to identify the incidence of thoracic malignancy in newly diagnosed, previously untreated, oral and oro-pharyngeal SCC, and to evaluate the role of thoracic computed tomography (CT) in its management. Of 116 consecutive patients who were identified prospectively 81(70%) had oral and 35 (30%) oropharyngeal SCC. Ten patients (9%) had suspicious thoracic CT findings. After investigation or follow up, four (3.5%) of these patients were shown to have coincident thoracic malignancies. This large prospective series of newly diagnosed oral and oropharyngeal SCC had a lower incidence of coincident thoracic malignancy than had previously been shown.


Polychlorinated biphenyl (PCBs) in rice grains and straw; risk surveillance, congener specific analysis, distribution and source apportionment from selected districts of Punjab Province, Pakistan.
The current study presents health risk surveillance by investigating the levels of polychlorinated biphenyls (PCBs) in rice (Oryza sativa L.) grains and rice straw. Samples were collected from four districts (Okara, Sahiwal, Lahore and Sheikhpura) of Punjab Province, Pakistan for congener specific analysis of PCBs, and to observe the spatial distribution pattern and point sources. Level of Σ30 PCB (ng g(-1)) in rice grains and rice straw ranged from 4.31 to 29.68 and 6.11-25.35, respectively. Tetra-CBs were found predominant in rice straw (49%) and grains (38%) over other PCB homologs. No significant variation (P>0.005) was observed for most of the screened PCBs congeners except, PCB-66, -77, -60, -101, -74, -138, -153 and -105 in rice grains and PCB-66 in rice straw. Reported toxicity equivalency (TEQ) values for dioxin like PCBs in rice grains were found lower than the previously published reports from Asian countries, however higher TEQ values are reported for rice straw in this study. Health was found at risk of cancer among one in million by consumption of the study area food stuffs, though no considerable carcinogenic risks to human health was found.


Lithium discriminates between muscarinic receptor subtypes on guinea pig hippocampal neurons in vitro.
In CA3 pyramidal neurons of guinea pig hippocampal slices an outward current activated by the GABAB agonist, baclofen (0.3 microM, Ibac) was reduced by low concentrations of carbachol (Cch, 0.1-0.3 microM). The effect of Cch desensitized suggesting that the receptor subtype involved in this muscarinic effect of Cch was of the M1 subtype. The receptor subtype was also characterized by its equilibrium dissociation constant for pirenzepine (10 nM) as an M1 receptor. Li+ applied extracellularly (1 mM) or intracellularly blocked the suppression of Ibac by Cch without affecting the Cch blockade of a current termed IAHP, which is mediated by M2 receptors. While the effect of intracellular Li+ application was immediate, it developed very slowly with extracellular application. Since Li+-salts are used effectively in the treatment of mania and depression, the selective effect of Li+ on M1-mediated muscarinic neurotransmission might be important for the cholinergic hypothesis of affective disorders.


The surgical management of the lid changes of Graves' disease.
There are three areas of surgical intervention available to patients with the eye changes of Graves' disease-lids, extraocular muscles, and orbital decompression. The lid changes may be managed by lateral tarsorrhaphy, levator tenotomy, recession of the levator with or without graft, "tenotomy" of the retractors of the lower lid, or recession with graft. The success of these procedures is dependent on proper patient selection and surgical execution, and when these are achieved, definite benefits result.


Determination of calcium stearate in polyolefin samples by gas chromatographic technique after performing dispersive liquid-liquid microextraction.
In this study, a gas chromatographic method is presented for the determination of calcium stearate after its conversion to stearic acid in a polymeric matrix. A solution of hydrochloric acid in 2-propanol is used as an extracting solvent of calcium stearate and its converter to stearic acid. For stearic acid preconcentration before its injection to a separation system, a recently presented extraction method, dispersive liquid-liquid microextraction, using carbon tetrachloride as an extracting solvent is used. Finally, 1 microL of the organic phase collected at the bottom of a conical test tube after centrifuging is injected into a gas chromatograph (GC) for quantification. This method has a relatively broad linear dynamic range (50 - 2000 mg/L) with a limit of detection (LOD) of 15 mg/L for stearic acid in solution. The LOD of the proposed method in a polymeric sample using 10 mg of polymer is 60 ppm as calcium stearate. Some effective parameters, such as the time and temperature of heating, the concentration of hydrochloric acid and the volume of distilled water, were studied.


Adapting the 24-hr. recall for epidemiologic studies of school children.
Chemical analysis of food actually eaten would be the most accurate method for analyzing the diets of children, but this technique is not feasible for most nutrition staffs. An improved 24-hr. dietary recall can be used by a small, well trained staff to collect more reliable data on a large number of school children. Vigilant monitoring of school lunch operations, incorporation of known recipes in the ETNV, and organizing probing techniques are necessary to insure the reliability of the tool. The low coefficients of variation of duplicate recalls noted in the study indicate that the error of measurement between interviewers is small, if the tool is carefully tested and sophisticated before use in the field and if observers are carefully trained by a written protocol.


A Chitosanase mutant from Streptomyces sp. N174 prefers to produce functional chitopentasaccharide.
The Chitosanase (Genbank No. AAA19865.1, SsCsn46) from Streptomyces sp. N174 was mutated via the deletion of 198A, 199A, 200H and 201D. Mutant chitosanase (m-SsCsn46) and wild chitosanase (SsCsn46) were secretory expressed at high level and purity in Pichia pastoris GS115. The activity of m-SsCsn46 was 30,000 U/mg and reduced by almost 40% of the maximum activity of wild type SsCsn46 (50,000 U/mg). Both enzymes had a high maximum activity at pH 6.0 and 50 °C, and maintained 40% of maximum activity at temperature 40-60 °C at pH 6.0 and or pH 5-7 at 50 °C after 2-hour treatment. The hydrolysis of chitosan by SsCsn46 yielded predominantly chitooligosaccharides with degree of polymerization (DP) 3-5 while m-SsCsn46 preferred to produce chitopentasaccharide from chitosan. Chitopentasaccharide improved gut microbiota significantly (by reducing the proportion of harmful pathogen population and increasing the proportion of the probiotic population) in mice when compared with the chitooligosaccharides with DPs 3-5. Thus, the mutant chitosanase from Streptomyces sp. N174 prefers to produce functional chitopentasaccharide from chitosan and m-SsCsn46 provides a potential tool for producing high-purity functional chitooligosaccharides.


Structural and functional insight into the nuclear pore complex and nuclear transport receptors in plant stress signaling.
Nuclear pore complexes (NPC) are highly conserved mega protein complexes that penetrate the double-layered nuclear membrane and form channels to allow bi-directional transport of macromolecules between the nucleus and the cytosol. Non-passive nucleocytoplasmic transport also requires nuclear transport receptors (NTR), which bind cargo molecules and shuttle them across the NPC. The NPC and NTRs constitute two fundamental layers of regulatory mechanisms that together determine the selective nuclear translocation of signal molecules and play essential roles in activating the precise response of a cell to environmental stimuli. Here we discuss recent findings in the NPC made by advanced structural biology approaches, and dissect distinct functions of different NPC components and NTRs in plants' responses to various biotic and abiotic stresses.


Extra-articular distal radial fracture malunion.
With the increase in surgical options for the treatment of distal radius fractures, the authors anticipate that distal radial fracture malunions will be a less frequently seen problem. Nevertheless, they will still occur. Although patient selection has been weighted toward the younger patient, we believe that surgery should be based on patient activity level, functional needs, and disability related to the malunion. With advances in biotechnology and improved anesthetics, surgical intervention even in the older and osteopenic population is now more promising. Surgical intervention still requires appropriate patient selection, careful preoperative planning, and meticulous surgical technique. The appropriate surgical procedure should be tailored to the patient's symptoms, age, needs, and radiographic findings.


Metabolic implications and safety of dolutegravir use in pregnancy.
Dolutegravir is recommended for all people living with HIV because of its efficacy, high barrier to resistance, favourable safety and tolerability profile, and affordability. Dolutegravir has the highest rates of viral suppression in pregnancy, therefore preventing perinatal HIV transmission. In view of these benefits, particularly for pregnant women, an important question is if dolutegravir is safe in pregnancy. Dolutegravir has been associated with metabolic complications, including weight gain and rare events of hyperglycaemia, that could affect maternal, fetal, and postnatal health. We review the current clinically and experimentally based literature on the implications of dolutegravir use for pregnant women and for developing embryos and fetuses. Possible effects on folate status, energy metabolism, adipogenesis, and oxidative stress are considered. In many instances, insufficient data are available, pointing to the need for additional research in this important area of HIV treatment.


Short-term memory and the EEG: effects of instructions to rehearse.
Transoccipital EEG was analyzed during the performance of a task involving the presentation and recall of auditorily presented nine-digit strings. Three strategies of processing were imposed by instruction: (i) passive listening without recall; (ii) passive listening followed by attempted recall; (iii) active rehersal followed by attempted recall. Phasic EEG arousal (8.5-12.5 Hz), inferred from the decline in abundance during string presentation, was found to be a function of the level of 'engagement' in the task. This finding was viewed as supporting an earlier phenomenological description of the task demands involved in recall. Tonic levels of arousal were found to be frequency dependent. At low frequencies (8.5-10.5 Hz) EEG abundance was inversely related to engagement but at higher frequencies (10.5-12.5 Hz) abundance was directly related to the level of engagement. The results are discussed in terms of a possible functional dissociation of EEG arousal within the alpha frequency band.


Are regulatory molecules for T cells involved in the development of autoimmune pancreatitis?
Impaired regulatory functions such as CTLA4 on T cells and naive regulatory T cells may be involved in the development of AIP.


Prevention of visual loss in older adults.
The major causes of visual loss in older adults are cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. Intensive research is ongoing for the prevention of these diseases. The present article updates different research studies and clinical trials aimed at prevention of visual loss in older adults.


Synthesis, characterization, and computational study of a new heteroaryl chalcone.
This work presents the synthesis of the chalcone (E)-3-(2,6-difluorophenyl)-1-(furan-2-yl)-prop-2-en-1-one molecule through the equimolar reaction between 1-(furan-2-yl)-ethenone and 2,6-difluorobenzaldehyde. The crystallographic characterization and the extensive theoretical study regarding electronic properties were obtained. The supramolecular arrangement was described by X-ray diffraction and Hirshfeld surfaces. Optimized geometrical structure was obtained by density functional theory, and the electronic study for differences between the solid and gas phases was carried out with M062-X at 6-311++G(2d,2p) basis set. Natural bond orbital, frontier molecular orbitals (HOMO-LUMO), and molecular electrostatic potential map were determined to elucidate the information related to the charge transfer in the molecule. The theoretical and experimental vibrational spectra were plotted, which included the IR intensities, the calculated and experimental vibrational frequencies, and the assigned vibrational modes for the main groups of DTP.


Perturbation Electrochemiluminescence Imaging to Observe the Fluctuation of Charge-Transfer Resistance in Individual Graphene Microsheets with Redox-Induced Defects.
Here, the fluctuation of charge-transfer resistance in individual reduced graphene oxide (rGO) microsheets with more redox-induced defects is unprecedentedly visualized using a perturbation electrochemiluminescence (ECL) imaging. This perturbation uses a short and low potential to recover defect-covered rGO microsheets slightly and then introduces a high potential to form more redox-induced defects resulting in an increase of charge-transfer resistance. Also, these defects at rGO microsheets enhance their catalytic feature and the resultant ECL intensity so that the temporal resolution in ECL imaging is improved to 30 ms. Aided by this fast imaging approach, the exponential decrease of ECL intensity at individual graphene microsheets after the oxidation is observed, which reflects the increase of their charge-transfer resistances. Since the charge-transfer resistance at electrode surfaces is mainly affected by the conductivity of electrode materials, the result provides the dynamic information to support the reduction of the electrical conductivity in graphene with more defects.


Is a shorter atrioventricular septal length an intermediate phenotype in the spectrum of nonsyndromic atrioventricular septal defects?
Atrioventricular septal defects (AVSDs) account for 7% of all congenital cardiovascular malformations. The atrioventricular septum (AVS) is the portion of the septal tissue that separates the right atrium from the left ventricle; deficiency of the AVS contributes to the AVSD phenotype. A study of case and control families was performed to identify whether an intermediate phenotype consisting of a shortened AVS existed in relatives of children with AVSDs. AVS length (AVSL) was measured on the echocardiograms of clinically unaffected parents and siblings from families that were identified through children with nonsyndromic AVSDs and in families with no histories of congenital heart disease. No significant differences were seen between case and control family members in terms of gender, age, weight, and height. AVSLs were significantly shorter in case parents compared with control parents. Similar findings were noted within the sibling groups. There was significant evidence for two-component distributions in the case parent, case sibling, and control sibling groups after standardizing AVSL for age and body surface area. Heritability of AVSL standardized for age and body surface area was 0.82 and 0.71 in nonsyndromic case and control families, respectively. Evidence for two-component distributions from the analysis of AVSL standardized for age and body surface area for case parents and case siblings suggests the presence of an intermediate phenotype for nonsyndromic AVSD. The high heritability in the control families suggests that there may be polygenic involvement in the determination of AVSL. Broadening the definition of AVSD to include those with shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes for AVSD.


Comparative evaluation of influence of aging, soil properties and structural characteristics on bioaccessibility of polychlorinated biphenyls in soil.
Though bioaccessibility commonly recognized as a guideline for risk assessment is closely related with pollution occurrence and chemical species of compounds, the mechanistic links are barely evaluated particularly for widespread polychlorinated biphenyls (PCBs) in soil. With the biomimetic extraction of hydroxypropyl-β-cyclodextrin (β-HPCD), the temporal and spatial influences of soil properties, aging and structural characteristics, e.g. polarity of PCB congeners on bioaccessibility were investigated for PCBs. Sensitive variation of bioaccessibility with aging, soil organic matter (SOM), particle size and soil moisture were clearly evidenced for different PCB congeners. Due to aging, the bioaccessibility decreased in the long term after stabilization for 36 h. In concert with the first-order kinetics, the decay rates of bioaccessibility were shown with congener-specificity and were well correlated with dipoles of PCBs. The increment of SOM diminished the bioaccessibility for the strengthened adsorption while the increased particle size and soil moisture elevated it possibly due to the less adsorption on soil particles and more accommodation of PCBs in soil pore water. Except the positive correlations with particle size, soil moisture and dipole moment, the greater dependency on aging and SOM was highlighted for bioaccessibility by partial least squares (PLS) analysis. The mutual relationship with influential factors was quantitatively formulated for accelerative prediction of bioaccessibility, and the comparative evaluation and detailed insights into the mechanistic links would thus help enhance the precise determination of bioaccessibility and risk assessment of PCBs in soil.


Copper and zinc generated by the Aquascape IonGen pond clarifier system can be detrimental to koi (Cyprinus carpio) health.
Copper is frequently used as an algicide, and copper ion generators such as the Aquascape IonGen claim to be safe for use in systems containing fish. In 2012, a die-off of koi (Cyprinus carpio) in a pond in Raleigh, North Carolina, occurred after the IonGen was added to the system. Physical and postmortem examinations suggested that heavy metal toxicity was the likely cause of morbidity and mortality. This was supported by a heavy metal screening of the owners' pond. Additional experiments were performed to determine if the IonGen produced toxic levels of copper and zinc. The tank containing the IonGen had higher concentrations of copper and zinc, and copper levels exceeded those associated with toxicity in both hard and soft water. The results of this study indicate that ion generators might not be safe for fish, and copper should only be used as an algicide if concentrations are closely monitored.


An expert system on the diagnosis of ascites.
We constructed an expert system on the diagnosis of ascites, using a combination of case reports and unpublished patient data. Rule production was by induction from examples, and the program operated on an algorithm which was a modification of Quinlan's ID3. The result was a small, but formally complete expert system. When tested against a new data set of patients, our expert system predicted the clinical diagnosis 82% of the time.


Evaluation and Management of Arterial Thoracic Outlet Syndrome.
Arterial thoracic outlet syndrome is rare and may be associated with a bony anomaly. Patient presentation can range from mild arm discoloration and claudication to severe limb-threatening ischemia. For patients with subclavian artery dilation without secondary complications, thoracic outlet decompression and arterial surveillance is sufficient. Patients with subclavian artery aneurysms or distal embolization require decompression with reconstruction or thromboembolectomy and distal bypass respectively.


Evaluating the efficacy of vaccine storage in the general practice setting.
To describe the implementation of guidelines for vaccine storage in general practice, and their effectiveness in achieving optimum vaccine storage temperatures in fridges. Repeated cross-sectional surveys over time--phase 1 1996/97, phase 2 1998/99, phase 3 1999/2000. Central Coast, New South Wales. Phase 1--all general practices on the Central Coast. Phases 2 and 3--samples of practices. Each practice was surveyed about how they stored vaccines. A datalogger recorded fridge temperatures over six days. Individual feedback and advice were given. Proportion of: 1. fridges maintaining a temperature in the 2-8 degrees C range; 2. fridges freezing; 3. practices with one person responsible for vaccine storage; 4. bridge temperature checked daily; 5. fridges storing no items other than vaccines; 6. bridges with thermometers; and 7. associations between storage practices and fridge temperatures. In phase 1, 102 fridges, and in phase 3, a random sample of 36 practices was surveyed. The findings for phase 1 and phase 3 respectively were: 31% and 50% of fridges were in the 2-8 degrees C range; 36% and 25% were <0 degrees C; one person was responsible in 52% and 53% of cases; 20% and 38% reported daily checks; 74% and 94% of fridges had no extraneous items and 53% and 86% of fridges had thermometers. No statistically significant associations were found between vaccine storage practices and bridge temperatures. Despite improvements in vaccine storage practices, a quarter of fridges were freezing, thereby compromising the potency of many of the immunisation schedule vaccines.


Germination ecology and seed population dynamics of Digitalis purpurea.
The germination ecology and the dynamics of the generative reproduction in populations of Digitalis purpurea L. were investigated in the field as well as in experiments. Germination of fresh seeds in the dark on moist filter paper appeared to differ between populations. These differences were eliminated when a moist natural soil functioned as germination substrate. An interaction between the spectral composition of light and the germination substrate was present. Germination in gradients of light, temperature and soil moisture revealed some clear-cut results. Germination proved to be strongly dependent on the percentage of vegetation cover. During two years of burial in litter bags, the number of buried viable seeds did not decrease. From one generation of seeds produced in a natural population, 18% was introduced into the buried seed bank, 10% germinated in autumn and 24% was present as a enforced dormant surface seed bank in late autumn.The results are discussed in relation to secondary succession. can be derived from Milton (1936), Salisbury (1942) and Thompson and Grime (1979). Soil disturbance and germination seem to be correlated in D. purpurea (Grime 1979). The purpose of this study is to analyse the dormancy and germination behaviour of D. purpurea in relation to the relevant environmental factors in order to explain the mechanisms of entry into, and the escape of D. purpurea seeds from a seed bank. Furthermore, an attempt will be made to quantify seed rain as well as the fate of different germinating and non-germinating seed rain fractions in space and time per unit area, in different stages of succession.


Best-practice protocols: preventing adverse drug events.
Analysis of Stanford's electronic Patient Safety Net revealed a pattern of unrecognized, widespread, low-frequency I.V.-PCA adverse events. A performance improvement-failure modes and effects analysis identified causes, and a multidisciplinary team developed solutions.


Kinetics of drug action in disease states. IX. Effect of experimental fever on phenobarbital concentrations at onset of loss of righting reflex in rats.
The purpose of this investigation was to determine the effect of fever on the concentration-pharmacologic activity relationship of phenobarbital (PB). Fever was produced in adult female Lewis rats by either bacterial endotoxin or brewer's yeast. Endotoxin elevated body temperature by 0.9 +/- 0.6 degrees C in one study and by 1.0 +/- 0.4 degrees C in another. Brewer's yeast caused a more pronounced and protracted elevation of temperature averaging 1.8 +/- 0.3 degrees C at the time of the pharmacodynamic measurements. PB was administered by slow i.v. infusion until the rats lost their righting reflex. The concentrations of PB at that time in serum, cerebrospinal fluid and brain were appreciably lower in the hyperpyrexic than in control (saline-treated) animals, irrespective of the method used to produce fever. Thus, fever is associated with an increased sensitivity of the central nervous system to the depressant effect of PB. This observation may be of particular relevance to the use of PB for the treatment and prevention of febrile convulsions.


A midline nasopharyngeal heterotopic neuroglial tissue.
Glial heterotopia is a rare disorder. However, it must be considered in the differential diagnosis of airway obstruction in the newborn. Differentiation of this lesion from nasal glioma and encephalocele is important. In this paper we report a midline glial heterotopia, which presented with upper airway obstruction in a newborn. The origin of a glial heterotopia from the midline of the nasopharynx has not been reported before. We present a review of the literature and discuss the clinical, radiological and pathological features of nasopharyngeal brain heterotopia in an infant.


Circulating extracellular vesicles activate the pyroptosis pathway in the brain following ventilation-induced lung injury.
Mechanical ventilation of preterm newborns causes lung injury and is associated with poor neurodevelopmental outcomes. However, the mechanistic links between ventilation-induced lung injury (VILI) and brain injury is not well defined. Since circulating extracellular vesicles (EVs) are known to link distant organs by transferring their cargos, we hypothesized that EVs mediate inflammatory brain injury associated with VILI. Neonatal rats were mechanically ventilated with low (10 mL/kg) or high (25 mL/kg) tidal volume for 1 h on post-natal day 7 followed by recovery for 2 weeks. Exosomes were isolated from the plasma of these rats and adoptively transferred into normal newborn rats. We assessed the effect of mechanical ventilation or exosome transfer on brain inflammation and activation of the pyroptosis pathway by western blot and histology. Injurious mechanical ventilation induced similar markers of inflammation and pyroptosis, such as increased IL-1β and activated caspase-1/gasdermin D (GSDMD) in both lung and brain, in addition to inducing microglial activation and cell death in the brain. Isolated EVs were enriched for the exosomal markers CD9 and CD81, suggesting enrichment for exosomes. EVs isolated from neonatal rats with VILI had increased caspase-1 but not GSDMD. Adoptive transfer of these EVs led to neuroinflammation with microglial activation and activation of caspase-1 and GSDMD in the brain similar to that observed in neonatal rats that were mechanically ventilated. These findings suggest that circulating EVs can contribute to the brain injury and poor neurodevelopmental outcomes in preterm infants with VILI through activation of GSDMD.


Renal Pelvis Metastasis From Prostatic Adenocarcinoma Missed by PSMA PET: A Case Report.
Metastasis of prostate cancer to renal pelvis is extremely rare. A 64-year-old man was hospitalized for increased prostate-specific antigen after radical prostatectomy. 68Ga-PSMA-11 PET/CT showed hydronephrosis caused by a mass in the left renal pelvis without significant uptake of prostate-specific membrane antigen tracer. The histopathology indicated metastatic prostate cancer with a Gleason score of 5 + 5 but negative for prostate-specific membrane antigen following nephroureterectomy. Although metastasis to renal pelvis is rare, the occurrence possibility could not be ignored when with hydronephrosis is found in prostate cancer patients.


Preventing Type 2 Diabetes with Home Cooking: Current Evidence and Future Potential.
Various dietary regimes have proven effective in preventing diabetes, yet its prevalence is growing. This review's goals are to examine the relationship between home cooking and diabetes and to present the literature on home cooking education programs as a novel strategy to improve adherence to healthy nutrition, thus decreasing the risk of diabetes. Consumption of home-cooked food is linked to healthier nutrition and decreased risk of diabetes. Further, home cooking interventions have a short-term positive impact on nutritional intake of both children and adults, and on diabetes prevention. Well-designed randomized controlled studies are needed to rigorously evaluate the long-term impact of home cooking interventions on cooking behavior, dietary intake, diabetes, and healthcare costs. Culinary education is an emerging field that aims to change nutrition education paradigms. Clinicians can empower patients to adopt home cooking by role modeling home cooking themselves, including home cooking content in their medical encounters, and through comprehensive lifestyle medicine interventions.


Spectroscopic, Thermal, Microbiological, and Antioxidant Study of Alkali Metal 2-Hydroxyphenylacetates.
The structural, spectral, thermal, and biological properties of hydroxyphenylacetic acid and lithium, sodium, potassium, rubidium, and cesium 2-hydroxyphenylacetates were analyzed by means of infrared spectroscopy FT-IR, electronic absorption spectroscopy UV-VIS, nuclear magnetic resonance 1H and 13C NMR, thermogravimetric analysis (TG/DSC), and quantum-chemical calculations at B3LYP/6-311++G** level. Moreover, the antioxidant (ABTS, FRAP, and CUPRAC assays), antibacterial (against E. coli, K. aerogenes, P. fluorescens, and B. subtilis) and antifungal (against C. albicans) properties of studied compounds were measured. The effect of alkali metal ions on the structure, thermal, and biological properties of 2-hydroxyphenylacetates was discussed.


Quantifying the policy-driven large scale vegetation restoration effects on evapotranspiration over drylands in China.
Evapotranspiration (ET) is a key variable in the water cycle and reflects the ecosystem's feedback into the climate system. However, quantitative studies on the response of ET to large-scale vegetation restoration projects and climate change are still lacking, especially in drylands. To address this deficiency, this research examined the variation in ET since the implementation of restoration projects in the drylands of China in 2000-2018, and utilized quantitative analysis methods to investigate the effects of six environmental factors, including temperature (TEM), precipitation (PRE), solar radiation (RAD), vapour pressure deficit (VPD), soil moisture (SM), and leaf area index (LAI) on ET. Furthermore, a new method was proposed to detect the ET change caused by land use and land cover change (LUCC). The results indicated that ET showed a significant increasing trend (3.54 mm yr-1) during 2000-2018, and PRE was identified as a main influential factor with an ET contribution rate of more than 50%, especially in areas with insignificant vegetation greening. Additionally, the LAI had a major positive impact on ET in the areas of significant vegetation greening, and the contribution rate was nearly 40%. Furthermore, large-scale vegetation restoration expanded the area of high-transpiration vegetation types, and the ΔET (net variable quantity of ET caused by LUCC) increased obviously especially for the changes from cropland and grassland to forest, and barren land to grassland. These findings provide a new perspective for future assessments and further decision making regarding vegetation restoration projects in drylands.


Correction to: TDZ-induced direct shoot organogenesis and somatic embryogenesis on cotyledonary node explants of lentil (Lens culinaris Medik.).
[This corrects the article DOI: 10.1007/s12298-008-0033-z.].


Skeletal anatomy of the early Permian parareptile Delorhynchus with new information provided by neutron tomography.
Detailed description of the holotype skeleton of Delorhynchus cifellii, made possible through the use of neutron tomography, has yielded important new information about the cranial and postcranial anatomy of this early Permian acleistorhinid parareptile. Hitherto unknown features of the skull include a sphenethmoid, paired epipterygoids and a complete neurocranium. In addition, the stapes has been exposed in three dimensions for the first time in an early parareptile. Postcranial material found in articulation with the skull in this holotype allows for the first detailed description of vertebrae, ribs, shoulder girdle and humerus of an acleistorhinid parareptile, allowing for a reevaluation of the phylogenetic relationships of this taxon with other acleistorhinids, and more broadly among parareptiles. Results show that Delorhynchus is recovered as the sister taxon of Colobomycter, and 'acleistorhinids' now include Lanthanosuchus.


The agreement in isolation of Salmonella enterica IIIb 61:k:1,5,(7) from rectal swabs, faecal samples and ileo-caecal lymph nodes from sheep.
The agreements between various culturing-method combinations and specimens to detect sheep naturally infected by Salmonella enterica IIIb 61:k:1,5,(7) were tested. Rectal swabs, faecal samples and ileo-caecal lymph nodes were collected from each individual. Rectal swabs called "group I" (n = 54) were cultured directly on selective media (selenite cysteine, SC). Rectal swabs called "group II" (n = 47) were pre-incubated in buffered peptone water. The four other combinations of culturing-method and specimen (one lymph node and three faecal) in each of the two groups were cultured directly on SC. The results from all the combinations of method and specimens were compared to the result from the rectal-swab test by kappa and McNemar's chi-square. Kappas for the agreement between rectal swabs and faecal sample tests were only 0.4. The lymph-node test agreed even-more poorly, with mean kappa value -0.02. The McNemar's test revealed that the discordancies between the rectal-swab test and all of the other tests went in both directions but sometimes did show bias (directionality) in the discordancies.


First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh.
We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98-99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.


Quantified superiority of cognitive behaviour therapy to antidepressant drugs: a challenge to an earlier meta-analysis.
The study aimed to review the conclusion of a previously published meta-analysis which quantified distinct superiority of cognitive therapy to antidepressant drug-therapy (P < 0.0001). We sought to include all studies used in the original meta-analysis. Adopting both that study's inclusion criteria and additional criteria resulted in a reduced set of studies. We analysed both 'completer' and 'intention to treat' data, using effect size and odds ratio quantification. There was an overall trend for cognitive therapy to be superior to antidepressant drug-therapy, but this was significant for only one of the four meta-analyses (an intention to treat analysis). We demonstrated considerable heterogeneity between studies, and a significantly higher drop-out rate in the antidepressant groups. The previous interpretation--cognitive therapy being distinctly superior to antidepressant medication--cannot be sustained from the currently analysed data set.


A myopathy-related actin mutation increases contractile function.
Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. Despite increasing clinical and scientific interest, the contractile consequences of these subtle amino acid substitutions remain obscure. To decipher them, in the present study, we originally recorded and analysed the mechanics as well as the X-ray diffraction patterns of human membrane-permeabilized single muscle fibres with a particular peptide substitution in actin, i.e. p.Phe352Ser. Results unravelled an unexpected cascade of molecular and cellular events. During contraction, p.Phe352Ser greatly enhances the strain of individual cross-bridges. Paradoxically, p.Phe352Ser also slightly lowers the number of cross-bridges by altering the rate of myosin head attachment to actin monomers. Overall, at the cell level, these divergent mechanisms conduct to an improved steady-state force production. Such results provide new surprising scientific insights and crucial information for future therapeutic strategies.