Emerging technologies to support independent living of older adults at risk.
The aging of the population is expected to place an unprecedented strain on health care systems over the next two decades and beyond. Emerging electronic monitoring technologies provide opportunities to learn about the aging process, age-related diseases, and contribute to new, cost effective care models that preserve independence at home for older adults at risk. The goals of this article are to familiarize the reader with emerging technologies and potential applications to older adults' at-risk, review the current literature about the clinical and economic outcomes of emerging technologies, and to outline future directions and challenges.


Pulmonary function in school-age children following intravitreal injection of bevacizumab for retinopathy of prematurity.
The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25-75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.


Temperature, Doping, and Chemical Potential Tuning Intrinsic Defects Concentration in Bi2MoO6: GGA + U Method.
Using the GGA + U method, the formation energy and concentration of intrinsic defects in Bi2MoO6 are explored under different chemical conditions, with/without doping, from 120 to 900 K. We find that the intrinsic defect and carrier concentration can be deduced from the small range of calculated Fermi levels in the diagram of formation energy vs Fermi level under different conditions. Once the doping conditions or/and temperature are determined, the corresponding EF is only limited to a special region in the diagram of formation energy vs Fermi level, from which the magnitude relationship of defects concentration can be directly derived from their formation energy. The lower the defect formation energy is, the higher the defect concentration is. With EF moving under different doping conditions, the intrinsic defect concentration changes accordingly. At the same time, the highest electron concentration at the relative O-poor (point HU) with only intrinsic defects confirms its intrinsic n-type behavior. Moreover, upon A-/D+ doping, EF moves closer to VBM/CBM for the increasing concentration of holes/electrons. The electron concentration can also be further improved after D+ doping, indicating that D+ doping under O-poor chemical growth conditions is positive to improve its photogenerated carriers. This provides us with a method to adjust the intrinsic defect concentration and deepens our knowledge about comprehension and application of the diagram of formation energy vs Fermi level.


Association between vitamin D deficiency and diabetic foot ulcer wound in diabetic subjects: A meta-analysis.
A meta-analysis was performed to evaluate the association between vitamin D deficiency and diabetic foot ulcer wounds in diabetic subjects. A systematic literature search up to March 2022 incorporated 7586 subjects with diabetes mellitus at the beginning of the study; 1565 were using diabetic subjects with foot ulcer wounds, and 6021 were non-ulcerated diabetic subjects. Statistical tools like the dichotomous and contentious method were used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of vitamin D deficiency in managing diabetic foot ulcer wound. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels (MD, -6.48; 95% CI, -10.84 to -2.11, P < .004), higher prevalence of vitamin D deficiency (<50 nmoL/L) (OR, 1.82; 95% CI, 1.32-2.52, P < .001), and higher prevalence of severe vitamin D deficiency (OR, 2.53; 95% CI, 1.65-3.89, P < .001) compared with non-ulcerated diabetic subjects. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels, higher prevalence of vitamin D deficiency, and higher prevalence of severe vitamin D deficiency compared with non-ulcerated diabetic subjects. Further studies are required to validate these findings.


E2F and cell survival: context really is key.
Our understanding of roles for the E2F transcription factor in regulating apoptosis has progressed from asking what E2F can do based on overexpression studies to what E2F actually does based on analyses of loss-of-function mutants. A paper in this issue of Developmental Cell implicates Drosophila E2F1 in context-dependent pro- as well as anti-apoptotic roles in the same tissue following genotoxic stress.


Discovery, purification and characterization of the angiotensin converting enzyme inhibitor, L-681,176, produced by Streptomyces sp. MA 5143a.
L-681,176, an inhibitor of angiotensin converting enzyme was found in the culture filtrate of Streptomyces sp. MA 5143. The I50 of the crystalline inhibitor is about 1.3 micrograms/ml and the inhibition is reversed by zinc sulfate. In rats, L-681,176 exhibits a dose-related inhibition of the pressor response to angiotensin I with an ID50 of 142 mg/kg when administered intravenously. The structure of L-681,176 is similar to that of marasmine but lacking one carboxyl group. The maximum yield of L-681,176 occurs after three to four days growth at 28 degrees C.


Role and nature of an interview in the selection of CUP applicants.
The purposes of this research were to study the role of an interview in the selection of applicants in coordinated undergraduate programs (CUPs) in dietetics and to ascertain the nature of the interview in those programs in which it was used. A questionnaire sent to all CUP directors asked why they did or did not use an interview, the criteria used to determine which applicants would be interviewed, and the makeup of the interviewing team. Furthermore, the directors were asked to state the types of questions asked most frequently, the rationale for asking those questions, and the procedure used to evaluate applicants' responses. Finally, the directors were asked to rate the level of influence of selected factors that might be used in the decision regarding admission to CUP. The overall response rate was 81%. Results indicated that an interview is used in 80% of the programs. Difficulty in scheduling and in achieving a standardized method of evaluating an interview were the most frequently cited reasons for not using one. Thirty-seven percent of the respondents ranked an interview as high in influencing the decision regarding admission to CUP. In contrast, 90% of the respondents ranked completion of prerequisite courses and 86% ranked overall GPA as highly influential factors.


Sparfloxacin pharmacokinetics in healthy volunteers: the influence of acidification and alkalinization.
To investigate the effect of acidification and alkalinization on the pharmacokinetics of sparfloxacin in healthy subjects. A single 200-mg oral dose of sparfloxacin was given to nine healthy Japanese volunteers on three separate occasions under different conditions of urinary pH. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride and sodium bicarbonate, respectively. The concentrations of sparfloxacin and its metabolite in plasma and urine were determined by high-performance liquid chromatography assays. The difference between treatments for Cmax, AUCinfinity, and CL x f(-1) were found to be significant. The relative bioavailability of sparfloxacin was 84.4% and 122.3% after ammonium chloride and sodium bicarbonate treatments, respectively. The amount of unchanged sparfloxacin in urine samples collected 0-48 h after sparfloxacin administration represented 10.1% of the dose in the control, 14.3% of the dose in urine acidification and 8.4% of the dose with alkalinization of urine. Renal clearance was found to depend on urinary pH. However, the plasma elimination and the metabolism of sparfloxacin were not significantly altered by acidification or alkalinization of the urine. The urinary pH dependence of the renal clearance of sparfloxacin will be of minor clinical importance with regard to the low contribution of renal excretion to the overall elimination of sparfloxacin. On the other hand, the alteration in the environmental pH in the gastrointestinal tract, produced by the concomitant ingestion of ammonium chloride or sodium bicarbonate, influences the absorption and bioavailability of sparfloxacin. This effect is likely to be clinically significant.


An Ethical (Descriptive) Framework for Judgment of Actions and Decisions in the Construction Industry and Engineering-Part I.
The construction industry is usually characterized as a fragmented system of multiple-organizational entities in which members from different technical backgrounds and moral values join together to develop a particular business or project. The greatest challenge in the construction process for the achievement of a successful practice is the development of an outstanding reputation, which is built on identifying and applying an ethical framework. This framework should reflect a common ethical ground for myriad people involved in this process to survive and compete ethically in today's turbulent construction market. This study establishes a framework for ethical judgment of behavior and actions conducted in the construction process. The framework was primarily developed based on the essential attributes of business management identified in the literature review and subsequently incorporates additional attributes identified to prevent breaches in the construction industry and common ethical values related to professional engineering. The proposed judgment framework is based primarily on the ethical dimension of professional responsibility. The Ethical Judgment Framework consists of descriptive approaches involving technical, professional, administrative, and miscellaneous terms. The framework provides the basis for judging actions as either ethical or unethical. Furthermore, the framework can be implemented as a form of preventive ethics, which would help avoid ethical dilemmas and moral allegations. The framework can be considered a decision-making model to guide actions and improve the ethical reasoning process that would help individuals think through possible implications and consequences of ethical dilemmas in the construction industry.


Identification of ethanol-inducible P450 isozyme 3a (P450IIE1) as a benzene and phenol hydroxylase.
In this report, the identity of the cytochrome P450 isozyme(s) catalyzing the hydroxylation of benzene and the major hydroxylated metabolite of benzene, phenol, was investigated using rabbit hepatic microsomes and six purified isozymes of hepatic P450. Microsomes from acetone-treated rabbits showed about a 5-fold induction of benzene hydroxylation to phenol and hydroquinone. This increase correlated with the increase in form 3a determined immunochemically (about 7-fold). Antibody to isozyme 3a inhibited greater than 90% of the benzene and phenol hydroxylase activity of hepatic microsomes from acetone-treated rabbits. At high benzene concentrations (2 mM) in the presence of cytochrome b5, form 3a was 1.3 times more active than form 2 and 7- to 10-fold more active than forms 3b, 3c, 4, and 6. At lower benzene concentrations (about 0.3 mM) form 3a was 5-fold more active than form 2. Furthermore, form 3a was the only isozyme to produce significant quantities of hydroquinone as did microsomes from acetone-treated rabbits. When phenol was used as the substrate, hydroquinone was the only product detected, and acetone treatment induced its formation 4- to 5-fold. Purified form 3a was 20- to 30-fold more active than the next most active isozyme, form 6, depending on the presence or absence of cytochrome b5. These results suggest that isozyme 3a (P450IIE1) is a low-Km benzene hydroxylase and the principal phenol hydroxylase in rabbit hepatic microsomes. As a result, the induction of isozyme 3a could potentiate the toxicity of benzene by catalyzing an increase in the formation of both phenol and hydroquinone.


miR-196b-5p inhibits proliferation of Wharton's jelly umbilical cord stem cells.
Human umbilical cord mesenchymal stem cells can be obtained from different parts of the umbilical cord, including Wharton's jelly. Transplantation of Wharton's jelly umbilical cord stem cells (WJCMSCs) is a promising strategy for the treatment of various diseases. However, the molecular mechanisms underlying the proliferation of WJCMSCs are incompletely understood. Here, we report that overexpression of miR-196b-5p in WJCMSCs suppresses proliferation and arrests the cell cycle in G0/G1 phase, whereas knockdown of miR-196b-5p promotes WJCMSC proliferation and cell-cycle progression. Moreover, miR-196b-5p overexpression resulted in decreased levels of Cyclin A, Cyclin D, Cyclin E and cyclin-dependent kinases 2 and increased levels of p15INK4b , whereas miR-196b-5p knockdown had the opposite effects. In conclusion, our data suggests that miR-196b-5p inhibits WJCMSC proliferation by enhancing G0/G1-phase arrest.


Twinning and intertwined microcrystals in an intriguing, yet elusive, mineral.
After a hundred years with no solution, the seemingly simple but actually very complex mineral kaliophilite, KAlSiO4, is finally revealed by electron crystallography.


In vitro production of synthetic viral RNAs and their delivery into mammalian cells and the application of viral RNAs in the study of innate interferon responses.
Mammalian cells express different types of RNA molecules that can be classified as protein coding RNAs (mRNA) and non-coding RNAs (ncRNAs) the latter of which have housekeeping and regulatory functions in cells. Cellular RNAs are not recognized by cellular pattern recognition receptors (PRRs) and innate immunity is not activated. RNA viruses encode and express RNA molecules that usually differ from cell-specific RNAs and they include for instance 5'capped and 5'mono- and triphosphorylated RNAs, small viral RNAs and viral RNA-protein complexes called vRNPs. These molecules are recognized by certain members of Toll-like receptor (TLR) and RIG-I-like receptor (RLR) families leading to activation of innate immune responses and the production of antiviral cytokines, such as type I and type III interferons (IFNs). Virus-specific ssRNA and dsRNA molecules that mimic the viral genomic RNAs or their replication intermediates can efficiently be produced by bacteriophage T7 DNA-dependent RNA polymerase and bacteriophage phi6 RNA-dependent RNA polymerase, respectively. These molecules can then be delivered into mammalian cells and the mechanisms of activation of innate immune responses can be studied. In addition, synthetic viral dsRNAs can be processed to small interfering RNAs (siRNAs) by a Dicer enzyme to produce a swarm of antiviral siRNAs. Here we describe the biology of RNAs, their in vitro production and delivery into mammalian cells as well as how these molecules can be used to inhibit virus replication and to study the mechanisms of activation of the innate immune system.


An electrochemical impedimetric platform formed by a CNT@UiO-66 nanocomposite for quantitative analysis of oxytetracycline.
Functional materials are considered one of the most critical factors in constructing high-performance electrochemical aptasensors in the sensing field. In this work, the microporous Zr-MOF UiO-66 (UiO = Universitetet i Oslo) is selected for assembly with carbon nanotubes (CNTs) to prepare a CNT@UiO-66 composite. The as-synthesized CNT@UiO-66 composite has a high surface area, excellent stability, good electrical conductivity, and abundant Zr(IV) sites, conferring it great potential for application in fabricating high-performance electrochemical aptasensors. It is gratifying that this electrochemical impedimetric aptasensor can detect trace oxytetracycline (OTC) from 0.01 to 0.7 pg mL-1 with a low limit of detection (LOD) of 1.48 fg mL-1. Meanwhile, this fabricated sensor based on CNT@UiO-66 has fine stability, excellent selectivity, and available reproducibility. In particular, the CNT@UiO-66-based aptasensor can quantitatively detect the OTC concentration in real samples.


Detection of HCV core antigen in human serum and plasma with an automated chemiluminescent immunoassay.
Currently, the detection of HCV infection in blood donors relies on the ability of immunoassays to detect circulating HCV antibodies. However, a significant delay exists between the time of infection and the development of antibodies. This delay (window period) can last up to 70 days. The introduction of NAT for the detection of HCV RNA has reduced this window period dramatically. However, NAT is labor intensive, prone to contamination, and expensive as compared with standard serologic tests. An automated, microparticle-based chemiluminescent assay for the detection of HCV core antigen in human serum and plasma was developed. The specificity and sensitivity of this prototype assay were evaluated by testing a population of normal blood donors and commercially available seroconversion panels. The HCV core antigen assay exhibited a 99.9-percent specificity by detecting a single repeatably reactive sample out of 1004 normal donors tested. Assay sensitivity was determined by comparing the HCV core antigen detection rate with the antibody seroconversion profile and the rate of HCV RNA detection. Among 15 seroconversion panels examined, core antigen was detected in 69 of 70 antibody-negative and/or RNA-positive samples for a sensitivity relative to NAT of 98.6 percent. These data indicate that the automated, microparticle-based chemiluminescent HCV core antigen assay can reduce the window period for detection of potentially infected blood donors by 32.7 days, and it represents a viable alternative to HCV RNA testing.


TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid tumor with a poor prognosis. However, there are limited choices for ATC treatment. Recently, the effectiveness of antibody-drug conjugates has been demonstrated in various carcinomas. Whether the targets of antibody-drug conjugates are expressed in anaplastic thyroid carcinoma remains unclear. Fifty-four patients with ATC were enrolled in this study. Tissue microarrays were constructed using the archives of formalin-fixed paraffin-embedded tissue blocks. All sections were stained with the following antibody-drug conjugate targets: human epidermal growth factor receptor 2 (HER2), nectin-4, trophoblast cell surface antigen 2 (TROP-2), glycoprotein non-metastatic B (GPNMB), and B7-H3. HER2 was negative in all tissues, whereas GPNMB and B7-H3 were expressed in most ATC tissues. TROP-2 and nectin-4 were expressed in 65% and 59% of ATC tissues, respectively. TROP-2 was expressed at significantly higher levels in ATC undifferentiated from papillary thyroid carcinoma than in ATC undifferentiated from follicular thyroid carcinoma and de novo ATC. In contrast, nectin-4 expression was markedly higher in patients with de novo ATC than in those with papillary and follicular thyroid carcinoma. TROP-2 and nectin-4 are potential therapeutic targets for ATC undifferentiated from papillary thyroid carcinoma and de novo ATC, respectively. GPNMB and B7-H3 potential for treating all types of ATC.


Does percutaneous cholecystostomy timing in high anaesthetic-risk patients impact on outcome?
The optimal timing for percutaneous cholecystostomy (PCT) in patients with acute biliary sepsis, who are high-risk for cholecystectomy, requires further investigation. We aimed to study local factors influencing the timing to PCT placement, and investigate patient outcomes in early (≤ 48 h) vs. delayed PCT over a six-year period. A retrospective observational study investigating patients who required a PCT at a single hospital in the UK between January 2014 and December 2019. Placement of a PCT was at the discretion of the on-call surgical consultant according to their own personal experience and not based on a standard local protocol. Clinical outcomes, hospital statistics and details of any subsequent bridging surgery were analysed using multivariate logistic regression models adjusting for age, sex, Charlson Comorbidity Index (CCI) and American Society of Anaesthesiologists (ASA) grade. There were 72 patients with 35/72 (48.6%) classed as TG18 AC grade 3; 26/72 (36.1%) had an early PCT placed and 46/72 (63.9%) delayed. Median age was 76 (65-83) years, 52.8% were female, and 51.4% were classed ASA ≥ 3 with 94.0% scoring CCI > 2. Trial on antibiotic therapy was the primary reason for delayed PCT. In adjusted models, early PCT was associated with a shorter length in hospital stay (OR 3.02, p = 0.044), successful definitive treatment (OR 6.26, p = 0.009); and reduced likelihood for catheter dislodgment (OR 0.12, p = 0.004) with fewer patients bridging to later emergency open surgery (OR 0.19, p = 0.024). Clinical outcomes may be superior in urgent or early PCT for high anaesthetic-risk patients following acute biliary sepsis.


(-)-Epicatechin in vitro ameliorates erythrocyte protein carbonyl content in hypertensive patients: comparison with L-ascorbic acid.
Oxidative stress plays a key role in the patho-physiology of hypertension. (-)-Epicatechin has many important biological properties. The present study was undertaken to evaluate effect of (-)-epicatechin on protein carbonyl content in gender-based hypertensive patients and normal subjects. The study was carried out on 83 normal (male: 42; female: 41) and 62 hypertensive subjects (male: 32; female: 30). In vitro effect on (-)-epicatechin and L-ascorbic acid was estimated on protein carbonyl content. Result showed a significant (p < 0.001) increase in protein carbonyl content in hypertensive patients but no gender-based difference was observed. (-)-epicatechin shows significant (p < 0.001) dose-dependent effect as compared to L-ascorbic acid, which is manifested as decrease in protein carbonyl content. We hypothesizes that a higher intake of (-)-epicatechin may provide protection against hypertension in males and females.


Bound states in the continuum in anisotropic photonic crystal slabs.
We investigate the bound states in the continuum (BICs) in photonic crystal slabs composed of alternating anisotropic and isotropic dielectric materials. According to the orientation of optical axis plane, three different configurations are proposed for analyzing various types of BICs, associated with extremely large quality factors and vanishing spectral linewidths. In particular, symmetry-protected (SP) BICs exist at the Brillouin zone center for zero rotation angle of the optical axis, which exhibit antisymmetric field patterns that are decoupled from the symmetric radiating fields. Accidental BICs and Friedrich-Wintgen (FW) BICs also occur at the Brillouin zone center for particular rotation angles of the optical axis. The former emerge on isolated bands with quasi-symmetric or quasi-antisymmetric field patterns, while the latter appear near the avoided crossing between two dispersion bands. At off the Brillouin zone center, SP BICs do not exist while accidental BICs and FW BICs appear at particular optical axis rotation angles, with similar features but somewhat more asymmetric field patterns than those at the Brillouin zone center.


Digestion in the soil predatory mite Pergamasus longicornis (Berlese) (Acari: Mesostigmata: Parasitidae)--detectable hydrolases.
Nineteen hydrolytic enzymes were detected in individual adult Pergamasus longicornis (Berlese) mites--amylase, hide protease, alkali phosphatase, esterase (C4), esterase lipase (C8), lipase (C14), leucine arylamidase, valine arylamidase, cystine arylamidase, acid phosphatase, phosphoamidase, alpha-galactosidase, beta-galactosidase, beta-glucuronidase, alpha-glucosidase, beta-glucosidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, and alpha-fucosidase. All but the phosphatases were detected for the first time. Tryptic and chymotryptic activity were consistently not demonstrable. Comparisons are made with saprophagous mites. No clear enzymic specialization for predation was found.


Shared care management of patients with type 2 diabetes across the primary and secondary healthcare sectors: study protocol for a randomised controlled trial.
The prevalence of type 2 diabetes (T2D) is growing globally and hospital-based outpatient clinics are burdened with increasing numbers of patients. To ensure high quality treatment and care, it is necessary to structurally reorganise the management of patients with T2D. The objective of this study is to test if T2D patients (who are at intermediate risk of or are already having incipient diabetic complications) jointly managed by a hospital-based outpatient clinic and general practitioners (shared care programme) have a non-inferior outcome compared to an established programme in a specialised (hospital based) outpatient diabetes clinic. The study is designed as a randomised controlled trial. The shared care model will be tested during a period of 3 years, with data collection at baseline and at 12, 24 and 36 months. All patients will be offered four medical visits a year; the shared care intervention consists of one annual comprehensive check-up at the outpatient clinic and three quarterly visits at the general practitioners' office. The control group will be followed with four quarterly visits at the outpatient clinic, including an annual comprehensive check-up. In the outpatient clinic, the patients will be treated by a specialised diabetes team, including an endocrinologist. On the basis of a predefined stratification model, we will recruit patients stratified to be at intermediate risk of or already having incipient diabetic complications. We plan to include 140 patients. The primary outcome is glycated haemoglobin. Other outcome measures include (1) the proportion of patients who meet the Danish standard indicators reflecting quality of care; (2) quality of life measured by Short Form 36; and (3) the functionality of the patients' families measured by Family Assessment Measure III. The experiences of the patients and families when participating in the shared care program will be explored by collecting dyadic interviews. This study will evaluate the quality of a shared care programme for patients with T2D, and provide evidence about advantages and disadvantages compared with a programme in a specialised outpatient clinic. The results may provide important information on how to organise the care for patients with T2D in the future. This trial was registered with Clinicaltrials.gov on 21 October 2015, registration number: NCT02586545 .


The use of microwave irradiation with low formalin concentrations to enhance the conversion of dopamine into norsalsolinol in rat brain: a pilot study.
The fixation of the neurotransmitter dopamine in the central nervous system by perfusion with formalin solutions seems to take place mainly via the formalin-induced condensation product norsalsolinol. In the present investigation the influence of microwave irradiation of the formalin-induced condensation of dopamine was studied in vitro and in vivo by making use of different, relatively low, formalin concentrations. It appeared that in vitro and in vivo the dopamine conversion was complete with 4% formalin and no influence of microwaves was noted. However, by making use of much lower formalin concentrations (0.2% and 0.4%) the condensation of dopamine was strongly augmented, in vitro (200%) and in vivo (at least 500%) using microwave techniques. There was a considerable loss in non-microwaved tissue (30%) after perfusion in vivo. This was lower (10%) in microwaved tissue. In experiments with perfused brain tissue which allowed a more complete calculation, a loss was found. This might be caused by a strong binding of dopamine and/or norsalsolinol to tissue components or to side reactions that could not be traced by the present experimental techniques.


[The testing of bulls for the polledness gene].
Main regularities have been stated concerning the poll gene inheritance by the progeny of breeding bulls mated with cows of various (homozygous and heterozygous) genotypes by the "poll" or "hornedness" genes.


Heat wave hazard classification and risk assessment using artificial intelligence fuzzy logic.
The average summer temperatures as well as the frequency and intensity of hot days and heat waves are expected to increase due to climate change. Motivated by this consequence, we propose a methodology to evaluate the monthly heat wave hazard and risk and its spatial distribution within large cities. A simple urban climate model with assimilated satellite-derived land surface temperature images was used to generate a historic database of urban air temperature fields. Heat wave hazard was then estimated from the analysis of these hourly air temperatures distributed at a 1-km grid over Athens, Greece, by identifying the areas that are more likely to suffer higher temperatures in the case of a heat wave event. Innovation lies in the artificial intelligence fuzzy logic model that was used to classify the heat waves from mild to extreme by taking into consideration their duration, intensity and time of occurrence. The monthly hazard was subsequently estimated as the cumulative effect from the individual heat waves that occurred at each grid cell during a month. Finally, monthly heat wave risk maps were produced integrating geospatial information on the population vulnerability to heat waves calculated from socio-economic variables.


Nipponium as a new element (Z=75) separated by the Japanese chemist, Masataka Ogawa: a scientific and science historical re-evaluation.
This review article deals with a new element 'nipponium' reported by Masataka Ogawa in 1908, and with its scientific and science historical background. Ogawa positioned nipponium between molybdenum and ruthenium in the periodic table. From a modern chemical viewpoint, however, nipponium is ascribable to the element with Z=75, namely rhenium, which was unknown in 1908. The reasons for this corrected assignment of nipponium are (1) its optical spectra, (2) its atomic weight when corrected, (3) its relative abundance in molybdenite, the same being true with rhenium. Recently some important evidence was found among the Ogawa's personal collection preserved by his family. Deciphering the X-ray spectra revealed that the measured spectra of the nipponium sample that Ogawa brought from University College, London clearly showed the presence of the element 75 (rhenium). Thus was resolved the mysterious story of nipponium, which had continued for almost a century. It is concluded that nipponium was identical to rhenium.


Effect of pH on tumor cell uptake of radiogallium in vitro and in vivo.
When injected at tracer levels into the blood, radiogallium as 67Ga-citrate binds to, and it transported to the site of the tumor by, transferrin. The process by which transferrin-bound Ga is converted to tumor-bound Ga is not fully understood, but may involve the differential physiology of neoplasms compared with normal tissues. Based on the slight acidity known to be exhibited by the extracellular fluid of many animal and human tumors, we have studied the effect of pH on stability and dissociation of the Ga-transferrin complex and on the uptake of Ga by tumor cells in vitro and animal tumors in vivo. When plasma from rabbits injection 67Ga-citrate was dialyzed at pH 6.5-7.5, dissociation of Ga from transferrin showed an inverse pH-dependence. A similar inverse dependence on pH was observed for the uptake of Ga by L1210 leukemia cells and Ehrlich ascites cells incubated with Ga-transferrin complex. Tumor uptake of Ga in rats bearing Walker-256 carcinosarcoma or Murphystum lymphosarcoma whose tumor pH had been further lowered by administration of glucose showed a statistically significant increase over control rats receiving no glucose. These results demonstrate that the stability of the Ga-transferrin complex is pH-dependent and suggest that dissociation of this complex due to decreased pH at the tumor site may be one factor involved in tumor localization and binding of Ga.


Genetic variation in the schizophrenia-risk gene neuregulin1 correlates with personality traits in healthy individuals.
Differences in personality traits have long been acknowledged as potential risk factors in developing psychiatric disorders. Lately, several susceptibility genes of different psychiatric disorders have been linked to personality traits. This has not been done for schizophrenia yet. Neuregulin1 has been repeatedly shown to be associated with schizophrenia and is involved in numerous neurodevelopmental functions such as neuronal migration and myelination. The impact of this gene might also modulate personality traits in healthy subjects. The NRG1 status of 523 healthy subjects was determined with a single nucleotide polymorphism (SNP8NRG221533) which has been described as a tagging marker being part of the core at-risk haplotype for schizophrenia. Genotype was correlated with personality traits using the NEO-FFI questionnaire. Subjects with the NRG1 risk allele scored higher on neuroticism (p<.05) and lower on conscientiousness (p<.05). Further, interactions of genotype by gender for extraversion (p<.05), openness (p<.05) and conscientiousness (p<.05) were found with men carrying the risk allele scoring the lowest. The data indicate that the NRG1 gene which has found to be associated with schizophrenia may also influence personality differences in healthy subjects.


Sex and hemispheric differences in the recall of verbal and spatial information.
Arrays of four digits were presented in a 3 X 3 matrix for 80 msec to either the left or right visual field. Women recalled digits presented to the left and right visual fields equally well, while men recalled digits more accurately after presentation to the right visual field. Both men and women recalled the positions of the digits presented to the left and right visual fields equally well. Overall, men's recall of positions was superior to that of women. Handedness correlated only with recall of positions presented to the right visual field, positively for women and negatively for men.


Anti-hypertensive treatment in the immediate post-operative period and 1 year after pediatric heart transplantation.
Hypertension is a known complication of pediatric heart transplantation. We sought to identify factors associated with anti-hypertensive use in pediatric heart transplant recipients immediately post-transplant and oral anti-hypertensive use at discharge and 1-year post-transplant. Retrospective chart review was conducted of patients ≤18 years who underwent heart transplantation at two major heart transplant centers between August 1, 2009 and December 31, 2017 with ≥1-year follow-up. Exclusion criteria included re-transplant, multi-organ recipients, survival <1 year, and comorbidities associated with hypertension. Anti-hypertensive use was recorded during initial ICU stay, at discharge, and 1-year post-transplant. Univariate and multivariate analyses determined associations of demographic and diagnostic factors and need for anti-hypertensives. There were 188 patients that met inclusion criteria. Anti-hypertensive infusions were required in the ICU post-transplant in 46 patients (24.5%) for a median of 3 days (1-21 days). Oral anti-hypertensives were required in 58 patients (30.9%) at discharge and 1-year post-transplant. Anti-hypertensive infusion in the ICU post-transplant was associated with donor-to-recipient weight ratio. Oral anti-hypertensive use at discharge was associated with weight ratio and pretransplant VAD use, and at 1-year, post-transplant was associated with age at transplant, steroid use at discharge, and oral anti-hypertensive use at discharge. Hypertension is common immediately following and 1-year post-transplant. Weight ratio was the only independent predictor of anti-hypertensive use in the early post-transplant period, whereas VAD use was also associated with anti-hypertensive use at discharge. Anti-hypertensive use 1-year post-transplant was not associated with those factors, but rather with age at transplant and steroid use.


Safety and Efficacy of Tranexamic Acid in Total Knee Arthroplasty.
The prevalence of total knee arthroplasty (TKA) is increasing, which is one of the most frequent operations in orthopedic practice. To further investigate the safe and effective role of using tranexamic acid (TA) in reducing transfusion rate and blood loss in total knee arthroplasty. This meta-analysis was conducted according to the Cochrane methodology. Twenty-eight superior quality and well designed randomized controlled trials (RCT) were collected to analyze for this study. Patients who had undergone primary unilateral TKA were chosen. The software, RevMan 5.2, was used to analyze collected data. Finally, 28 RCTs were collected to analyze for this study. Total blood loss was dramatically decreased via the application of TA, by a mean of 420 ml [95% CI: -514 to -327]. A significant reduction about blood transfusion rate was also found in patients who received TA. [RD: -0.26, 95%CI: -0.33 to -0.19]. Moreover, no significant differences were found between TA and control groups in incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE). This meta-analysis demonstrates that the application of TA in TKA could decrease total blood loss and transfusion rate. On the other hand, the application of TA is not associated with high incidence of DVT or other adverse events. TA should be taken into account in routine use in primary knee arthroplasty to benefit the patients.


Preoperative and postoperative evaluation by manometric study of the anal sphincter after coloanal anastomosis for carcinoma.
The purpose of the present study was to pre- and postoperatively evaluate the anal sphincter after coloanal anastomosis in 20 patients with carcinoma of the rectum at 5.5 to 8 cm from the anal verge. The 20 patients matched age and sex with the controlled subjects. Of the 20 patients, 17 with normal preoperative manometric studies when compared with control subjects underwent a coloanal anastomosis as described by Castrini, and three patients with preoperative incontinence underwent abdominoperineal resection. Manometric studies preoperatively, and postoperatively at three and 12 months, indicated a statistically significant decrease in squeezing pressure, and rectal compliance at three months that almost normalized by 12 months. The rectal compliance correlated with the number of bowel movements per day at three months (four to five per day) and at 12 months (two to three per day). The rectoanal reflex and length of pressure zone have remained unchanged. Results seem to indicate that anal continence can be preserved after coloanal anastomosis.


Predictors of renal impairment and proteinuria after commencement of antiretroviral therapy in a Zimbabwean HIV cohort.
Renal disease prevalence varies widely amongst reported cohorts of people living with HIV (PLWHIV) in sub-Saharan Africa. Renal function testing is not routine in those commencing antiretroviral therapy (ART) in the region, however. Further data on renal disease prevalence and the change associated with ART use are therefore needed. To explore changes in renal function and associated predictors after 1 year of ART in an adult cohort of PLWHIV from Zimbabwe. A retrospective analysis of patients who attended the Newlands Clinic between January 2007 and September 2019. Eligible patients were aged ≥18 years and had measures of serum creatinine at baseline and after 1 year of ART. Predictors of renal function change were assessed by multiple linear regression. 1729 patients were eligible for inclusion. Median age was 36 years (IQR 30-43) and 62.8% were female. After 1 year of ART, the proportion of patients with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.732 did not significantly change (2.0% vs. 1.2%; p = 0.094), but there was a decrease in the proportion of patients with proteinuria (11.0% vs. 5.6%; p < 0.001). Hypertension (B = -6.43; 95% CI -8.97 to -3.89; p < 0.001) and baseline proteinuria (B = -7.33; 95% CI -10.25 to -4.42; p < 0.001) were negative predictors of change in eGFR from baseline, whereas diabetes status was not associated (p = 0.476). Proteinuria was common, but its prevalence halved after 1 year of ART. Screening for hypertension could be a simple way to identify patients at risk of renal function decline.


Pepper pectin methylesterase inhibitor protein CaPMEI1 is required for antifungal activity, basal disease resistance and abiotic stress tolerance.
Pectin is one of the main components of the plant cell wall that functions as the primary barrier against pathogens. Among the extracellular pectinolytic enzymes, pectin methylesterase (PME) demethylesterifies pectin, which is secreted into the cell wall in a highly methylesterified form. Here, we isolated and functionally characterized the pepper (Capsicum annuum L.) gene CaPMEI1, which encodes a pectin methylesterase inhibitor protein (PMEI), in pepper leaves infected by Xanthomonas campestris pv. vesicatoria (Xcv). CaPMEI1 transcripts are localized in the xylem of vascular bundles in leaf tissues, and pathogens and abiotic stresses can induce differential expression of this gene. Purified recombinant CaPMEI1 protein not only inhibits PME, but also exhibits antifungal activity against some plant pathogenic fungi. Virus-induced gene silencing of CaPMEI1 in pepper confers enhanced susceptibility to Xcv, accompanied by suppressed expression of some defense-related genes. Transgenic Arabidopsis CaPMEI1-overexpression lines exhibit enhanced resistance to Pseudomonas syringae pv. tomato, mannitol and methyl viologen, but not to the biotrophic pathogen Hyaloperonospora parasitica. Together, these results suggest that CaPMEI1, an antifungal protein, may be involved in basal disease resistance, as well as in drought and oxidative stress tolerance in plants.


Changes in metal-binding peptides due to acclimation to cadmium transferred between ramets of Salvinia minima.
Different ramets of a clonal plant exploiting a patchily metal-contaminated habitat may be exposed to different levels of toxic metals. This study investigated whether the exposure of older ("parent") ramets to Cd affected the levels of metal-binding peptides and essential elements in younger ("daughter") ramets which were not exposed to ambient Cd. Pre-treatment of parent ramets of Salvinia minima with 50 μg Cd·l-1 increased the levels of thiols and phytochelatins (PCs), decreased Mg and increased Cu, Zn and S in daughter ramets growing in a Cd-free medium. Acclimation of parents to lower Cd levels (10 and 25 μg Cd·l-1) increased thiols and decreased cysteine and glutathione in daughters, but did not increase PCs. Parental acclimation to all Cd concentrations tested reduced PC production in daughter ramets during subsequent Cd exposure. Daughter ramets from parents pre-treated with 25 μg Cd·l-1 were more Cd tolerant than controls. Although the tolerant daughters contained 35% more thiols than controls, fractionation of tissue Cd showed no difference between the control and tolerant ramets in the fraction of Cd bound by thiol compounds. Thus, while the acclimation of parent plants to Cd increased levels of metal-binding peptides and thiols in daughter ramets, the relationship between these compounds and the Cd tolerance of daughters is unclear.


Considerations of the Posterior Tibial Slope in Anterior Cruciate Ligament Reconstruction: a Scoping Review.
The significance of posterior tibial slope (PTS) in the setting of anterior cruciate ligament (ACL) injury and reconstruction has been increasingly recognized in recent years. The purpose of this article is to review the biomechanical and clinical studies of PTS in conjunction with ACL injuries, providing an evidence-based approach for the evaluation and management of this patient population. Several biomechanical and clinical studies suggest that PTS > 12° may be considered with increased strain on the native ACL fibers (or reconstructed graft) and greater anterior tibial translation, predisposing patients to a recurrent ACL injury. The increased rates of ACL injury and graft failure seen in those with increased PTS have garnered attention to diagnose and surgically address increased PTS in the revision ACL setting; however, the role of a slope-reducing high tibial osteotomy (HTO) in primary ACL reconstruction (ACL-R) has yet to be defined. Various HTO techniques to decrease PTS during revision ACL-R have demonstrated promising outcomes, though conclusions are limited by the multifactorial nature of revision surgery and concomitant procedures performed. Recent evidence suggests that increased PTS is a risk factor for failure following ACL-R, which may be mitigated by a slope-reducing HTO. Further investigation is needed to elucidate abnormal PTS values and to determine appropriate indications for a slope-reducing HTO in primary ACL-R.


Productive Performance, Serum Antioxidant Status, Tissue Selenium Deposition, and Gut Health Analysis of Broiler Chickens Supplemented with Selenium and Probiotics-A Pilot Study.
The effect and interaction of dietary selenium (Se) and probiotics on three yellow chicken growth performance, tissue Se content, antioxidant capacity, and gut health were studied from 0 to 70 days of age. A total of 400 one-day-old broilers were distributed into four groups (I-Se, O-Se, I-Se + pros, and O-Se + pros groups) consisting of a 2 × 2 factorial design. The main factors were the source of Se (I-Se = inorganic Se: 0.2 mg/kg sodium selenite; O-Se = organic Se: 0.2 mg/kg Selenium yeast) and the level of probiotics (0.5% EM or 0% EM, the component of EM mainly includes Lactobacillus and Yeast at the dose of 2 × 108 cfu/kg and 3 × 107 cfu/kg, respectively). Each treatment had 5 duplicates consisting of 20 broilers. The results showed that the I-Se group had a greater (p < 0.05) ratio of feed: weight gain (F/G) of broilers at Starter (0−35 d) than the other treatments. Compared to the I-Se group, the O-Se group increased (p < 0.05) Se concentrations in the liver, pancreas, breast muscles, thigh muscle, and the activity of total antioxidative capacity (T-AOC) in serum, as well as the relative abundance of Barnesiella and Lactobacillus in cecum. Meanwhile, probiotics enhanced (p < 0.05) Se concentrations in the pancreas, thigh muscle, serum, and the activity of T-AOC and glutathione peroxidase (GSH-Px), the duodenum's ratio of villi height to crypt depth (V/C), the jejunum villus height and V/C, and the ileum's villus height. Furthermore, the significant interactions (p < 0.05) between Se sources and the level of probiotics were observed in Se concentrations in the pancreas, thigh muscle, serum, crypt depth of duodenum, and villus height of jejunum of birds, and Barnesiella abundance in the cecal. In conclusion, our results demonstrate that the combination of O-Se + pros can improve broiler early growth performance, tissue Se content in the pancreas, thigh muscle, and serum, promote intestinal development, and regulate the composition of intestinal flora, suggesting a better combination. These findings provide an effective method of nutrient combination addition to improving the performance of three yellow chickens.


Cistanches Herba enhances learning and memory by inducing nerve growth factor.
Nerve growth factor (NGF) has potent biological activities such as preventing neuronal death, promoting neurite outgrowth, supporting synapse formation, and enhancing memory function. NGF and NGF-like molecules can potentially be used to treat neurodegenerative disorders, such as dementia. This study investigated the effects of Cistanches Herba, a widely used medicinal herb, on NGF regulation and its neuronal actions, including neurite outgrowth, synapse formation, and learning and memory enhancement. Cistanches Herba extract (CHE; 250 μg/ml) increased NGF induction in C6 cells and led to neurite extension in PC12 cells. It also stimulated NGF secretion in the cortex and hippocampus of the mouse brain at 5 and 20mg/kg/day (3 days, p.o.). Furthermore, CHE increased neuronal cell differentiation, neurite length, and synapse formation in the mouse hippocampus. CHE significantly enhanced learning and memory, as demonstrated by passive avoidance test and novel object recognition test. These results suggest that CHE is useful for improving memory function via its action in upregulating NGF.


Multi-parameters of Magnetic Resonance Imaging to Estimate Ischemia-Reperfusion Injury after Stroke in Hyperglycemic Rats.
The aim of the study is to verify the effect of hyperglycemia on ischemia-reperfusion injury and to explore the feasibility of noninvasive observation of ischemic-reperfusion injury in hyperglycemic ischemic stroke by MRI technique. According to the duration of ischemia and blood glucose levels, 40 rats were divided into hyperglycemic ischemic 2-hr (H-I2h), hyperglycemic ischemic 6-hr (H-I6h), non- hyperglycemic ischemic 2-hr (NH-I2h), and non- hyperglycemic ischemic 6-hr (NH-I6h) groups. T2W imaging, DW imaging, T2 mapping, T2* mapping, DCE, and T1 mapping after enhancement sequences were acquired before reperfusion and approximately 3-hr after reperfusion. ADC, T1, T2, T2*, and Ktrans values of ischemic lesion were obtained in different groups. After reperfusion, the variation of ADC values showed no significant difference between groups with diabetes and groups without diabetes and between different recanalization time-points (2-hr vs 6-hr). After reperfusion, T2, T2*, and Ktrans values increased in different degrees in all four groups. Only the T1 value decreased in all groups. The change of all parameters in groups with hyperglycemia was more obvious than that in groups without hyperglycemia and was more obvious in groups with H-I6h versus those with H-I2h. This study confirms that hyperglycemia aggravates ischemia-reperfusion injury and may be an important risk factor for the prognosis of ischemic stroke. The Ktrans values should be noninvasive imaging indicators to monitor blood brain barrier permeability and ischemic-reperfusion injury in ischemic stroke.


A C-terminally truncated form of β-catenin acts as a novel regulator of Wnt/β-catenin signaling in planarians.
β-Catenin, the core element of the Wnt/β-catenin pathway, is a multifunctional and evolutionarily conserved protein which performs essential roles in a variety of developmental and homeostatic processes. Despite its crucial roles, the mechanisms that control its context-specific functions in time and space remain largely unknown. The Wnt/β-catenin pathway has been extensively studied in planarians, flatworms with the ability to regenerate and remodel the whole body, providing a 'whole animal' developmental framework to approach this question. Here we identify a C-terminally truncated β-catenin (β-catenin4), generated by gene duplication, that is required for planarian photoreceptor cell specification. Our results indicate that the role of β-catenin4 is to modulate the activity of β-catenin1, the planarian β-catenin involved in Wnt signal transduction in the nucleus, mediated by the transcription factor TCF-2. This inhibitory form of β-catenin, expressed in specific cell types, would provide a novel mechanism to modulate nuclear β-catenin signaling levels. Genomic searches and in vitro analysis suggest that the existence of a C-terminally truncated form of β-catenin could be an evolutionarily conserved mechanism to achieve a fine-tuned regulation of Wnt/β-catenin signaling in specific cellular contexts.


MVIL6: Accurate identification of IL-6-induced peptides using multi-view feature learning.
Interleukin-6 (IL-6) is a potential therapeutic target for many diseases, and it is of great significance in accurately predicting IL-6-induced peptides for IL-6 research. However, the cost of traditional wet experiments to detect IL-6-induced peptides is huge, and the discovery and design of peptides by computer before the experimental stage have become a promising technology. In this study, we developed a deep learning model called MVIL6 for predicting IL-6-inducing peptides. Comparative results demonstrated the outstanding performance and robustness of MVIL6. Specifically, we employ a pre-trained protein language model MG-BERT and the Transformer model to process two different sequence-based descriptors and integrate them with a fusion module to improve the prediction performance. The ablation experiment demonstrated the effectiveness of our fusion strategy for the two models. In addition, to provide good interpretability of our model, we explored and visualized the amino acids considered important for IL-6-induced peptide prediction by our model. Finally, a case study presented using MVIL6 to predict IL-6-induced peptides in the SARS-CoV-2 spike protein shows that MVIL6 achieves higher performance than existing methods and can be useful for identifying potential IL-6-induced peptides in viral proteins.


Biotech value chain and technologies for COVID-19 research areas for collaboration on cost quality tradeoff with tool companies.
Technologies for COVID-19 are in high demand, and supply chains from biotech and pharma industries face critical supply issues. This paper discusses the case on mRNA technologies and quality assurance issues. Interviews with managers of biotech companies were performed. These helped to prepare biotech panels at a roundtable on quality of medicine, organized by the Polish Academy of Sciences in Paris (PAN) in 2021. This paper analyzes the new mRNA technology and shows the importance of emerging new biotech firms, especially tool companies providing services in quality assurance. It highlights research areas and types of survey instruments with academic collaborators, to better understand the economics of mRNA technology platforms. A future research agenda for collaboration with academic communities is proposed on cost-quality tradeoffs and clinical quality attributes for such genomic technologies.


Initial multicentre experience of high-speed myocardial perfusion imaging: comparison between high-speed and conventional single-photon emission computed tomography with angiographic validation.
High-speed (HS) single-photon emission computed tomography (SPECT) with a recently developed solid-state camera shows comparable myocardial perfusion abnormalities to those seen in conventional SPECT. We aimed to compare HS and conventional SPECT images from multiple centres with coronary angiographic findings. The study included 50 patients who had sequential conventional SPECT and HS SPECT myocardial perfusion studies and coronary angiography within 3 months. Stress and rest perfusion images were visually analysed and scored semiquantitatively using a 17-segment model by two experienced blinded readers. Global and coronary territorial summed stress scores (SSS) and summed rest scores (SRS) were calculated. Global SSS ≥3 or coronary territorial SSS ≥2 was considered abnormal. In addition the total perfusion deficit (TPD) was automatically derived. TPD >5% and coronary territorial TPD ≥3% were defined as abnormal. Coronary angiograms were analysed for site and severity of coronary stenosis; ≥50% was considered significant. Of the 50 patients, 13 (26%) had no stenosis, 22 (44%) had single-vessel disease, 6 (12%) had double-vessel disease and 9 (18%) had triple-vessel disease. There was a good linear correlation between the visual global SSS and SRS (Spearman's ρ 0.897 and 0.866, respectively; p < 0.001). In relation to coronary angiography, the sensitivities, specificities and accuracies of HS SPECT and conventional SPECT by visual assessment were 92% (35/38), 83% (10/12) and 90% (45/50) vs. 84% (32/38), 50% (6/12) and 76% (38/50), respectively (p < 0.001). The sensitivities, specificities and accuracies of HS SPECT and conventional SPECT in relation to automated TPD assessment were 89% (31/35), 57% (8/14) and 80% (39/49) vs. 86% (31/36), 77% (10/13) and 84% (41/49), respectively. HS SPECT allows fast acquisition of myocardial perfusion images that correlate well with angiographic findings with overall accuracy by visual assessment better than conventional SPECT. Further assessment in a larger patient population may be needed to confirm this observation.


Renalase, a catecholamine-metabolizing hormone from the kidney.
A novel flavin adenine dinucleotide-dependent amine oxidase that is secreted by the kidney, circulates in the blood, and modulates cardiac function and systemic blood pressure has recently been discovered. Renalase appears to be a hormone that metabolizes catecholamines, and its discovery will facilitate our understanding of sympathetic regulation.


The role of multi-modality imaging for sinus of Valsalva aneurysms.
Sinus of Valsalva aneurysms (SVAs) are uncommon but important entities. They are most often congenital in origin, resulting from incomplete fusion of the aortic media to the aortic valve annulus. Less frequently, they may be acquired, usually secondary to infective endocarditis. Unruptured aneurysms may be clinically silent and diagnosed incidentally, but can also produce symptoms as a consequence of mass effect on related structures. Rupture may present with sudden hemodynamic collapse but can have a more insidious onset depending upon the site and size of the perforation. Early diagnosis is imperative and can usually be made reliably by transthoracic echocardiography. However, transesophageal echocardiography may sometimes be required for confirmation. Cardiovascular magnetic resonance imaging (CMRI) and multi-detector computed tomography are being increasingly utilized for evaluation of SVAs and can offer valuable complimentary information. CMRI in particular enables a comprehensive assessment of anatomy, function and flow in a single sitting. Surgical repair forms the mainstay of treatment for both ruptured and unruptured aneurysms and has low complication rates. This article provides an overview of the pathological and clinical aspects of SVAs and discusses in detail the role of advanced imaging modalities in their evaluation.


The digital child: A cross-sectional survey study on the access to electronic devices in paediatrics.
To explore the use of electronic devices in children and possible risk factors for smartphone ownership and cyberbullying. A cross-sectional survey study was conducted involving 62 Italian general paediatricians who administered a close-ended questionnaire about the use of electronic devices to 1732 parents/caregivers. Data of 2563 children aged 0-14 years were collected. Investigating the electronic device use by parents/caregivers of children aged 0-1 years, 72.5% of mothers were revealed to have the habit to use a smartphone during breastfeeding and bottle-feeding. The ownership of a smartphone was found in 29.5% of children aged 2-14 years, 68.1% considering only children aged 10-14. A higher parental degree level was identified as a protective factor for smartphone ownership by children (OR 0.59; 95% CI 0.36-0.98; p = 0.04 for father; OR 0.51; 95% CI 0.33-0.78; p = 0.002 for mother). A higher risk of cyberbullying was found when caregivers did not use any restrictions on smartphone use (OR 11.92; 95% CI 3.41-41.68; p < 0.001). The absence of rules for smartphone use represents a risk factor for cyberbullying. In this context, the general paediatrician might play an important role in helping parents/caregivers and their children adopt safer use of electronic devices.


Immunoregulation of IL-6 secretion by endogenous and exogenous adenosine and by exogenous purinergic agonists in splenic tissue slices.
In recent years, the role of norepinephrine, opioids, and neuropeptide Y for sympathetic regulation of murine spleen cells has been characterised. In this study, we describe the role of exogenous and endogenous adenosine and exogenous P2X(1) and P2Y(1) agonists for spontaneous splenic IL-6 secretion from spleen slices. The P2X(1) agonist beta,gamma-methylene ATP inhibited IL-6 secretion at 10(-5) M, whereas the P2Y(1) agonist 2-methylthio ATP increased IL-6 secretion at 10(-6) to 10(-8) M. Furthermore, adenosine (at 5 x 10(-8), 10(-7), 5 x 10(-7) M) inhibited IL-6 secretion via A1 adenosine receptors, whereas an A2(A) adenosine receptor agonist increased IL-6 secretion in the presence of 10(-7) M cortisol. To determine the effects of endogenous adenosine, electrical field stimulation was applied in order to release endogenous ATP, which yields adenosine after conversion from ATP. Electrical field stimulation markedly reduced IL-6 secretion, which was attenuated by the A1 antagonist DPCPX but not by the A2 antagonist 8-(3-Chlorostyryl)caffeine. Thus, via A1 adenosine receptors, adenosine was found to be a strong inhibitor of splenic IL-6 secretion. This study further expands our earlier description of the complexity of the local dialogue of sympathetic nerves and macrophages in lymphoid organs.


Decoding the organization of spinal circuits that control locomotion.
Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait.


Effect of propentofylline on hippocampal brain energy state and amyloid precursor protein concentration in a rat model of cerebral hypoperfusion.
An animal model of graded cerebral hypoperfusion achieved by way of 2- and 4-brain vessel occlusion (vo) was used to test the effect of chronic propentofylline (PPF) administration on hippocampal energy state and amyloid precursor protein (APP) concentration. For this purpose, forty adult rats were subjected to stepwise and permanent 2 vo and 4 vo and PPF in a dose of 25 mg/day per kilogram body weight was continuously administered intraperitoneally for 1 week or 3 weeks, respectively. During the final steady-state experiment arterial blood parameters and blood gases (mean arterial blood pressure, PO2, pCO2, pH, hematocrit, hemoglobin, body temperature) were measured. Brain tissue concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine were measured in rat hippocampus by high-pressure liquid chromatography (HPLC) analysis; APP concentration was determined using Western blot techniques. In adult rat brain, long-term PPF treatment induced a striking increase in hippocampal ATP concentration which was paralleled by an enhancement of the ATP/ADP-ratio. Specifically, after 2 vo with 1 week of PPF treatment the ATP concentration in hippocampus was enhanced by 18% when compared with 2 vo without PPF treatment, whereas after 3 weeks PPF administration with 4 vo the concentration of ATP was enhanced by 31%. Furthermore, PPF reduced the tissue concentration of adenosine from 17.75 +/- 2.79 to 8.83 +/- 3.68 pmol/mg wet weight during 4 vo if compared with animals without PPF. In addition, the APP concentration was enhanced by 35% after 1 week PPF administration when compared with non PPF treated animals. In summary, the results demonstrated that chronic administration of PPF induced an enhancement in ATP concentration in adult rat hippocampus under conditions of long-term brain vessel occlusion. Interestingly, 1 week PPF seems to have a stimulating effect on APP which may act neuroprotectively. Thus, PPF may protect hippocampal neurons from chronic ischemic damage. In conclusion, PPF may have some beneficial effects and could be used in the treatment of patients with chronic cerebrovascular disorders or neurodegenerative diseases such as vascular dementia.


Localization of the high molecular weight kininogen binding site in the heavy chain of human factor XI to amino acids phenylalanine 56 through serine 86.
We have previously demonstrated that a monoclonal antibody (5F7) directed against the heavy chain region of factor XI inhibits the binding of factor XI to high molecular weight kininogen (high Mr kininogen) and the surface-mediated proteolytic activation of factor XI by factor XIIa in the presence of high Mr kininogen. In order to identify the structural domain of factor XI that binds high Mr kininogen, CNBr-digested factor XI was passed over a 5F7 antibody affinity column. One of two CNBr peptides that bound to this 5F7 affinity column inhibited binding of 125I-factor XI to high Mr kininogen, as did intact factor XI. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate of an inhibitory peptide purified by high performance liquid chromatography revealed an Mr of 10,000-15,000. Gas-phase sequencing of this peptide revealed the following amino-terminal sequence: X-X-Val-Thr-Gln-Leu-Leu-Lys-Asp-Thr. These data together with the amino acid composition of the isolated peptide indicate that both the epitope recognized by antibody 5F7 and at least a portion of the high Mr kininogen binding site are contained within the amino-terminal portion of factor XI comprising residues Glu-1 through Met-102. Further cleavage of this peptide with o-iodosobenzoic acid at a tryptophanyl peptide bond revealed that an Mr 5,000 peptide (with the amino-terminal sequence Trp-Phe-Thr-Cys-Val-Leu) bound to a high Mr kininogen affinity column and inhibited binding of 125I-factor XI to high Mr kininogen. Finally, a synthetic peptide comprising residues Phe-56 through Ser-86 inhibited 125I-factor XI binding to high Mr kininogen. These experiments strongly suggest that the high Mr kininogen binding site is contained within the domain in the heavy chain region of factor XI comprising residues Phe-56 through Ser-86.


A possible cause of heterogeneity of mammalian apurinic/apyrimidinic endonuclease.
1. Mammalian major apurinic/apyrimidinic (AP) endonuclease, APEX nuclease (M(r) 35.4 kDa) was purified from HeLa cells. A hybrid protein (M(r) 36.4 kDa), which was expressed in BW2001 strain cells of E. coli, comprising human APEX nuclease headed by 10 additional amino acids was also purified. 2. The purified preparations were frequently associated with 31-, 33- and 35-kDa peptides having AP endonuclease activity. 3. The 33- and 35-kDa peptides were suggested to be formed from the hybrid protein or APEX nuclease during their purification processes by proteolytic cleavage with subtilisin-like protease. The 31-kDa peptide was thought to be produced by chemical cleavage of the aspartyl-prolyl bond of APEX nuclease. 4. The results support the notion that some of AP endonuclease heterogeneity based on the molecular weight difference are caused by proteolytic (and chemical) cleavage of a species of AP endonucleases during the extraction and purification.


Removal of polybrominated diphenyl ethers in high impact polystyrene (HIPS) from waste TV sets.
Most studies have shown that improper disposal of e-waste can accelerate the release of high concentrations of polybrominated diphenyl ethers (PBDEs), and this situation causes environmental pollution and human health risks. The recycling technology of waste electronic plastics based on solvent processes can reduce environmental pollution and health risks from PBDEs. In this study, high impact polystyrene (HIPS) from waste TV sets was taken as the research object, and d-limonene and n-propanol were used as solvent and precipitant, respectively. We studied the relationship between the precipitation conditions and the size of precipitate particles, and the effect laws of precipitation conditions on the removal percentage of PBDEs were discussed. Transferring behavior of PBDEs during precipitation was investigated, and the parameters suitable for removing PBDEs from HIPS solution were confirmed. Results showed that lower HIPS concentration in d-limonene, lower precipitation temperature, higher mass ratio of n-propanol to HIPS solution, and greater stirring speed were conducive to form smaller and more uniform precipitate particles. All conditions (concentration, temperature, mass ratio, and stirring rate) that could increase the solubility of PBDEs in the mixed solvent of limonene and n-propanol or decrease the swelling degree of HIPS precipitate particles, or reduce the size of particles could improve the removal percentage of PBDEs. The investigated results indicated that insoluble PBDEs (e.g., decabromodiphenyl ether) transferred into the HIPS precipitate mainly through the generated crystals and then precipitated together with the HIPS particles, and soluble PBDEs (e.g., octabromodiphenyl ether) migrated into the precipitate by the solution entrained. The precipitate particles, which measured approximately 1.0 mm (on average), were obtained when the solution containing 10% of HIPS from waste TV shell was precipitated by adding n-propanol equivalent to twice the mass of the solution at 40 °C and 3000 r/min stirring speed. The total concentration of PBDEs in the precipitate particles (dried) was reduced to 2369 mg/kg, and 88.06% of the PBDEs in the original plastic solution was successfully removed by this process.


Data on interaction between adeno-associated virus and U87 cell via cRGD chemical modification.
RGD tripeptide is a specific, high-affinity ligand for integrin, which is highly expressed in cancer cells. We previously reported that cRGD chemically modified AAV2 (AAV2(N587+1/azido+RGD)) showed significantly enhanced infectivity compared to RGD genetically inserted AAV2 (AAV2(N587+RGD)) (10.1016/j.biomaterials.2015.11.066) [1]. Herein we provide the binding ability analysis of RGD modified AAV2 and U87 cell by flow cytometry and the theoretical working model of RGD-αvβ3 integrin interaction.


Corrigendum to "Adoption of knowledge-graph best development practices for scalable and optimized manufacturing processes" [MethodsX Volume 10(2023) 102124].
[This corrects the article DOI: 10.1016/j.mex.2023.102124.].


Concentration dependent SERS, DFT and molecular docking studies of a ureido derivative with antitubercular properties.
Spectroscopic analysis, density functional theory (DFT) studies and surface enhanced Raman scattering (SERS) of antimycobactetial 4-[3-(4-acetylphenyl)ureido]-2-hydroxybenzoic acid (AUHB) have been studied on different silver sols. For Raman and SERS wavenumbers, very large changes are observed. Observed variations in the modes of ring may be due to surface π-electron interactions and presence of this indicated that poly substituted ring is more inclined than para substituted phenyl ring and assumes a inclined position for concentration 10-3 M. Changes in orientation are seen in SERS spectra depending on concentration. In order to find electron-rich and poor sites of AUHB, molecular electrostatic potential was also constructed. The molecular docking results show that binding affinity and interactions with the receptor DprE1 may be supporting evidence for further studies in design further AUHB pharmaceutical applications. Based on antitubercular activity of 4-aminosalicylic acid (PAS) and urea derivatives we designed, synthesized and investigated mutual PAS-urea derivatives as potential antimycobacterial agents.


Bis-intercalative dinuclear platinum(II) 6-phenyl-2,2'-bipyridine complexes exhibit enhanced DNA affinity but similar cytotoxicity compared to the mononuclear unit.
The interactions between a series of platinum complexes, including (pyridyl)(6-phenyl-2,2'-bipyridine)platinum(II) hexafluorophosphate (1), three dinuclear bis[(6-phenyl-2,2'-bipyridine)platinum(II)] complexes (2-4), and (4-aminopyridine)(4,6-diphenyl-2,2'-bipyridine)platinum(II) perchlorate (5) with DNA have been investigated. All Pt(II) complexes, except 5, were demonstrated to be DNA intercalators, based on viscosity measurements. Absorption and fluorescence titration results indicated that the addition of a phenyl ring to the 6-phenyl-2,2'-bipyridine ligand dramatically reduced the DNA binding of the Pt(II) complex 5. The dinuclear complexes 2-4 exhibited multiple binding modes of mono/bisintercalation and groove binding, as revealed by viscosity and fluorescence titration measurements. While complexes 2-4 bound to DNA with significantly enhanced affinities as compared to 1, compounds 1 and 2-4 showed similar IC(50) values against a panel of cancer cell lines. In addition, these complexes showed similar cellular uptakes. The results indicated that the cytotoxicity of these (6-phenyl-2,2'-bipyridine)platinum compounds may not be mediated through DNA binding but may involve interacting mechanisms with cellular components other than DNA.


Evaluation of structure-reactivity descriptors and biological activity spectra of 4-(6-methoxy-2-naphthyl)-2-butanone using spectroscopic techniques.
The structure and several spectroscopic features along with reactivity parameters of the compound 4-(6-methoxy-2-naphthyl)-2-butanone (Nabumetone) have been studied using experimental techniques and tools derived from quantum chemical calculations. Structure optimization is followed by force field calculations based on density functional theory (DFT) at the B3LYP/6-311++G(d,p) level of theory. The vibrational spectra have been interpreted with the aid of normal coordinate analysis. UV-visible spectrum and the effect of solvent have been discussed. The electronic properties such as HOMO and LUMO energies have been determined by TD-DFT approach. In order to understand various aspects of pharmacological sciences several new chemical reactivity descriptors - chemical potential, global hardness and electrophilicity have been evaluated. Local reactivity descriptors - Fukui functions and local softnesses have also been calculated to find out the reactive sites within molecule. Aqueous solubility and lipophilicity have been calculated which are crucial for estimating transport properties of organic molecules in drug development. Estimation of biological effects, toxic/side effects has been made on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by Pharma Expert software. Using the THz-TDS technique, the frequency-dependent absorptions of NBM have been measured in the frequency range up to 3THz.


Heart rate before ICU discharge: a simple and readily available predictor of short- and long-term mortality from critical illness.
A heart rate >90 bpm serves as one of four characteristics defining the systemic inflammatory response syndrome and is used in scoring systems to predict in-hospital mortality of intensive care unit (ICU) patients. Despite its central role in critical illness, specific data regarding the relationship between heart rate and outcome are rare. In this post hoc analysis of a prospectively collected database, we analyzed the value of heart rate averaged from four predefined time points during the last 24 h before ICU discharge as a predictor of post-ICU in-hospital and post-hospital mortality in medical ICU patients. Furthermore, the relationship between heart rate and inflammation, as well as the influence of rate control medications on the association between heart rate and outcome were identified. Among the 702 ICU patients discharged from the ICU, 7.1 % died before hospital discharge. At 4 years of follow-up, post-hospital mortality was 14.4 %. Multivariate Cox proportional hazards models revealed heart rate before ICU discharge (HR 5.95; 95 % CI 1.24-28.63; p = 0.03) as an independent predictor of post-ICU in-hospital mortality. Both heart rate (HR 2.56; 95 % CI, 1.05-6.34; p = 0.04) and the C-reactive protein serum concentration before ICU discharge (HR, 1.26; 95 % CI, 1.09-1.46; p = 0.002) were independently associated with post-hospital mortality. Heart rate control therapy reduced the risk of post-ICU in-hospital (HR 0.38; 95 % CI, 0.18-0.81; p = 0.01) and post-hospital (HR, 0.47; 95 % CI, 0.22-1.00; p = 0.05) mortality. Heart rate evaluated 24 h before ICU discharge was independently associated with post-ICU in-hospital and post-hospital mortality. Pharmacological interventions to control heart rate may beneficially influence post-ICU mortality.


Subclavian artery occlusion and pseudoaneurysm caused by lung apex mucormycosis: successful treatment with transcatheter embolization.
Subclavian artery pseudoaneurysm and occlusion in young patients are usually post-traumatic. We report the case of a 33-year-old diabetic woman with subclavian artery occlusion and pseudoaneurysm formation caused by pulmonary mucormycosis infection. The patient presented with diabetic ketoacidosis, Horner's syndrome, and absent left arm pulses. A cystic lesion of the left lung apex was found by imaging, was surgically resected, and was histologically diagnosed as mucormycosis infection. Magnetic resonance angiography depicted a left subclavian artery pseudoaneurysm and occlusion adjacent to the mucormycosis lesion. To protect against thromboembolic complications and rupture, the pseudoaneurysm was embolized with coils. The patient is clinically well 1 year after the intervention with no perfusion of the pseudoaneurysm.


Evaluation of DNA Binding, Radicals Scavenging and Antimicrobial Studies of Newly Synthesized N-Substituted Naphthalimides: Spectroscopic and Molecular Docking Investigations.
In this study, we investigated a new series of naphthalimide based Schiff base compounds as potential DNA binding, antioxidant and antimicrobial agents. The structural characterization of synthesized compounds was carried out with the aid of elemental analysis and spectroscopic techniques (UV-vis., IR, (1)H and (13)C NMR). The DNA binding properties of target compounds against Ct-DNA (calf thymus) have been investigated in detail by numerous biophysical techniques (UV-vis, fluorescence, ethidium bromide displacement assay, Time resolved fluorescence, viscosity, cyclic voltammetry and circular dichorism) and the evidences have suggested that the test compounds could interact with DNA via intercalative binding. The extent of DNA binding (Kb) of these compounds follow the order of 3b (3.33 × 10(4) M(-1)) > 3a (2.25 × 10(4) M(-1)) > 3c (2 × 10(4) M(-1)), suggesting that compound 3b binds more strongly to Ct- DNA than the compounds 3a and 3c. Molecular docking results further support intercalative binding of test compounds with DNA. The binding energies of docked compounds (3a-3c) were found to be -8.20 to -8.69 kcal/ mol, suggesting greater binding affinity to Ct-DNA. The synthesized compounds displayed potential antimicrobial activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Salmonella typhimurium. Compound 3c has emerged as most active against all the four tested bacterial strains with MIC value in the range of 0.031-0.062 mg/mL. In the mutagenicity studies, all the test compounds were found to be non-mutagenic both in the presence and absence of metabolic activation. Furthermore, the antioxidant activity experiments show that these compounds exhibited potential scavenging activities against DPPH and H2O2 radicals.


Modafinil improves attentional performance in healthy, non-sleep deprived humans at doses not inducing hyperarousal across species.
The wake-promoting drug modafinil is frequently used off-label to improve cognition in psychiatric and academic populations alike. The domain-specific attentional benefits of modafinil have yet to be quantified objectively in healthy human volunteers using tasks validated for comparison across species. Further, given that modafinil is a low-affinity inhibitor for the dopamine and norepinephrine transporters (DAT/NET respectively) it is unclear if any effects are attributable to a non-specific increase in arousal, a feature of many catecholamine reuptake inhibitors (e.g., cocaine, amphetamine). These experiments were designed to test for domain-specific enhancement of attention and cognitive control by modafinil (200 and 400 mg) in healthy volunteers using the 5-choice continuous performance task (5C-CPT) and Wisconsin Card Sort Task (WCST). An additional cross-species assessment of arousal and hyperactivity was performed in this group and in mice (3.2, 10, or 32 mg/kg) using species-specific versions of the behavioral pattern monitor (BPM). Modafinil significantly enhanced attention (d prime) in humans performing the 5C-CPT at doses that did not affect WCST performance or induce hyperactivity in the BPM. In mice, only the highest dose elicited increased activity in the BPM. These results indicate that modafinil produces domain-specific enhancement of attention in humans not driven by hyperarousal, unlike other drugs in this class, and higher equivalent doses were required for hyperarousal in mice. Further, these data support the utility of using the 5C-CPT across species to more precisely determine the mechanism(s) underlying the pro-cognitive effects of modafinil and potentially other pharmacological treatments.


Switching the Stiffness of Polyelectrolyte Assembly by Light to Control Behavior of Supported Cells.
Polyelectrolyte block copolymer micelles assembled thin film is switched in response to local photocatalytic reactions on titanium dioxide, resulting in a layer of variable height, stiffness in response to visible light irradiation. Preosteoblasts migrate toward stiffer side of the substrates.


Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells.
Peripheral B cell depletion strategies have been employed recently in the treatment of systemic autoimmune diseases and the initial clinical results have been encouraging. Although the major target of rituximab-based treatments was to reduce the levels of circulating autoantibodies, additional mechanisms of action may operate. Recent studies have addressed the question of potential effects of transient B cell depletion on other, non-B cell populations. The data, albeit uncontrolled, suggest that anti-CD20 monoclonal antibody treatment is associated with significant effects in the T cell pool, whereas individual clinical responses do not always correlate with changes in autoantibody titers. More specifically, it has been reported that rituximab administration may decrease the activated phenotype of peripheral and tissue-resident T cells by abolishing antigen presentation by B cells, and may enhance the numbers and function of regulatory T cells. In this review we analyze and discuss available data emerging from B cell depletion studies in patients with systemic lupus erythematosus, rheumatoid arthritis and other autoimmune conditions. Further controlled studies are needed to confirm the role of B cell depletion in modifying T cell function in vivo.


[Influence of the high peak serum estradiol on the outcome of in vitro fertilization cycles].
For the use of assisted reproductive technologies of high complexity (IVF-ET and ICSI) is essential to proper ovarian stimulation with recombinant FSH drugs menotropins, as well as the use of GnRH analogues. To correlate serum estradiol level on day 10th with the outcome of in vitro fertilization cycles. Retrospective study of 523 IVF cycles, selected and analyzed from 2005 to 2009. Patients underwent individualized stimulation protocols with gonadotropins and agonist (late luteal phase). The patients were divided into three groups according with the serum level of estradiol on day 10th of stimulation: Group I, patients with serum level of Estradiol below 1,000 pg/mL; Group II, with levels between 1,000-4,000 pg/mL; and Group III, with levels above 4,000 pg/mL. Peak serum estradiol levels, oocyte number, fertilization rates, implantation rates, and pregnancy rates were compared among groups. The fertilization rate was 62.8 in Group I; 60.6% in Group II, and 54.2% in Group III. The pregnancy rate in Group I was 29.8%; in Group II, 37.3%; and 24% for Group III. The implantation rates were 14, 22 and 14% for each group respectively (I, II and III). There is an inverse relationship between high peak serum estradiol levels and pregnancy rate; the implantation rate seems affected by the extreme levels of serum estradiol. The percent of total mature oocytes and fertilization rate improve with serum levels of estradiol at physiologic values.


Does antenatal care matter in the use of skilled birth attendance in rural Africa: a multi-country analysis.
While the importance of antenatal care for maternal and child health continues to be debated, several researchers have documented its impact on intermediate variables affecting survival such as birth weight. These studies have also highlighted the problems of causality that are typically not taken into account when estimating the effects of antenatal care on skilled birth attendance. In this study, we revisit this relation in the rural areas of four countries: Ghana, Kenya, Uganda and Tanzania. Using a structural equation modeling approach that corrects for endogeneity, in all four countries we find that the usual simpler probit (or logit) models tend to underestimate the direct effect of antenatal care on skilled birth attendance. Furthermore, in two of the countries, this estimated effect is mediated by the range of services offered to women during antenatal care. These results suggest that governments and NGOs should place more importance on the role of antenatal care providers and on the services they offer, in efforts to promote skilled birth attendance.


Safety and efficacy of clonazepam in patients with hemifacial spasm: A double-blind, randomized, placebo-controlled trial.
Hemifacial spasm (HFS) is an involuntary intermittent twitching of the facial muscles. Medical and surgical treatments can be considered for HFS. Among medical treatments, clonazepam is a benzodiazepine used to treat epilepsy, psychiatric symptoms, and movement disorders. This study aimed to investigate the efficacy and safety of clonazepam for the treatment of HFS. This randomized double-blind placebo-controlled trial prospectively enrolled patients with HFS aged 20-79 years. The patients were randomly assigned in a 1:1 ratio to receive either clonazepam (0.5 mg twice daily) or a placebo for 4 weeks. All participants underwent clinical assessment and laboratory tests at baseline and visit 2. The primary endpoint was the clinical global impression-improvement (CGI-I) score at visit 2. A total of 34 patients with HFS assessed for eligibility were enrolled between April 2015 and November 2016. Among them, two patients were withdrawn before randomization. Thus, the intention-to-treat analysis included 32 patients with HFS. The median CGI-I scores at visit 2 did not differ significantly between the clonazepam (3; range 1-6) and placebo (3.5; range 3-5) groups. In the safety analysis, only mild or no serious adverse events were observed. The results of this study demonstrated the safety of clonazepam in patients with HFS. However, clonazepam did not show a statistically significant effect on HFS. Further studies are needed to provide evidence of the clinical benefits in patients with HFS.


Problems and challenges in providing feedback to clinical teachers on their educational performance: A mixed-methods study.
Given the importance of feedback to improve teachers' educational performance, the current study aimed to identify the challenges and problems involved in providing feedback to clinical teachers on their educational performance. In the first phase of this mixed-methods study, the clinical teachers, students, and university officials were interviewed on feedback problems and challenges. After an inductive content analysis, and based on the problems enlisted, a ten-item questionnaire was developed. Subsequently, 25 clinical teachers completed the questionnaire by scoring the importance and urgency of each problem. Overall, 18 individual and group interviews were conducted with 24 people. A total of ten themes and five categories emerged, including "lack of transparency of feedback system," "absence of criticizability culture," "lack of motivation to improve performance," "failure to consider factors affecting teacher's performance," "lack of formative evaluation," "inappropriate data obtained on teacher's performance," "inappropriate feedback providers," "inappropriate feedback recipients," "inappropriate feedback provision," and "no feedback follow-up." Three items of priority involved "inappropriate feedback providers," "inappropriate data," and "failure to consider factors affecting the teacher's performance." All the raised problems obtained high scores; nevertheless, the interviewees had more problems with the feedback provider, the data collected on the performance, and inattention of university officials to the factors influencing performance than feedback presentation methods. Hence, gaining the trust of teachers on the collected data, providing feedback by their trustworthy individuals, and paying attention to the factors influencing teachers' performance are associated with an increased possibility of feedback acceptance.


[Xq;Yq translocation in a patient with premature ovarian insufficiency].
To explore the genetic basis for a patient with premature ovarian insufficiency. Chromosomal G-banding and C-banding, single nucleotide polymorphism array (SNP-array), fluorescence in situ hybridization (FISH) and Y chromosome microdeletion assay were used for the analysis. With the combined techniques, the patient was found to carry a Xq;Yq translocation, with a karyotype of 46,X,der(X)t(X;Y)(q25;q12).ish der(X)(Tel XYp+,Tel XYq+,Yq12+). Unbalanced Xq;Yq translocation probably underlay the premature ovarian insufficiency in this patient.


Fibroblast monolayer cultures in scintillation counting vials: metabolic and growth experiments using radioisotopes and a microfluoremetric DNA assay.
We have developed a simple technique for the investigation of cellular metabolism and growth in cultured human fibroblasts which facilitates experiments using up to 3 x 10(5) cells in each of 100 or more culture vessels. The method has been used to study cell growth, glucose utilization and oxidation, and protein, RNA and DNA sysnthesis. The use of radiolabeled substrates in tracer experiments is simplified since transfer of cell material is not required. Methods for measuring both total cellular protein and DNA have been adapted to this culture system. Although we have used this tecnique for fibroblast cultures, it also can be easily applied to experiments on any other type of cell that can be grown in a monolayer.


Use of microfiltration as first step in recovery of protein A from fermentation broth.
The flux and transmission of protein A during microfiltration have been studied. We studied the performance of two commercial membranes: one made of nylon (Pall Ultipore Nylon66, 0.2 microm) and one of polyether sulfone (Pall Omega, 0.16 microm). The Nylon66 membrane had by far the best transmission of protein A although a previous study showed that bovine serum albumin (BSA), often used to characterize membranes, had much better transmission through the Omega membrane. The membrane manufacturer also states that the Omega membrane is the best membrane for this kind of application because it is a low-protein-binding membrane. The lower transmission of the Omega membrane for protein A was assumed to be owing to its smaller pores and higher charge density in combination with the larger Stokes radius for protein A. When the pH was lowered, the Nylon66 membrane still had the higher transmission. It can thus be concluded that a membrane that is found suitable for the recovery process of one protein is not always the best choice for the recovery process for other proteins even though the membrane is low protein binding.


Tuberculosis Supranational Reference Laboratories: A Global Approach.
The World Health Organization Supranational TB Reference Laboratory Network (SRLN) has served as the backbone for TB drug-resistance surveillance and diagnosis since 1994 and remains a key WHO programme for antimicrobial resistance (AMR) surveillance at the global level. SRLN is a great technical resource for proficiency testing to ensure accuracy of drug-susceptibility testing, scale-up, capacity development in countries and provides unique support to the reliable detection of drug resistance. Technical assistance from individual SRLs has been supported by a variety of mechanisms but funding for the SRLN has become increasingly challenging.


Age and sex differences on anti-hyperglycemic medication exposure and risk of newly diagnosed multiple sclerosis in propensity score matched type 2 diabetics.
The association between exposure to anti-hyperglycemic medications (A-HgM) for Type 2 Diabetes Mellitus (T2D) treatment and Multiple Sclerosis (MS) in T2D patients is unclear. This retrospective cohort analysis used the Mariner claims database. Patient records were surveyed for a diagnosis of MS starting 12 months after diagnosis of T2D. Patients were required to be actively enrolled in the Mariner claims records for six months prior and at least three years after the diagnosis of T2D without a history of previous neurodegenerative disease. Survival analysis was used to determine the association between A-HgM exposure and diagnosis of MS. A propensity score approach was used to minimize measured and unmeasured selection bias. The analyses were conducted between January 1st and April 28th, 2021. In T2D patients younger than 45, A-HgM exposure was associated with a reduced risk of developing MS (RR: 0.22, 95%CI: 0.17-0.29, p-value <0.001). In contrast, A-HgM exposure in patients older than 45 was associated with an increased risk of MS with women exhibiting greater risk (RR: 1.53, 95%CI: 1.39-1.69, p < 0.001) than men (RR: 1.17, 95%CI: 1.01-1.37, p = 0 · 04). Patients who developed MS had a higher incidence of baseline comorbidities. Mean follow-up was 6.2 years with a standard deviation of 1.8 years. In this study, A-HgM exposure in patients with T2D was associated with reduced risk of MS in patients younger than 45 whereas in patients older than 45, exposure to A-HgM was associated with an increased risk of newly diagnosed MS, particularly in women.


The role of oral semaglutide in managing type 2 diabetes in Indian clinical settings: Addressing the unmet needs.
Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population. We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation. Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population. Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents.


The management of diabetic macular oedema.
Diabetic macular oedema (DMO) is a significant cause of visual loss in the working population. Focal/grid photocoagulation remains an effective treatment for DMO and the benchmark to which clinicians compare other newer treatment modalities. There are, however, patients who do not respond adequately or who are refractory to laser photocoagulation. This has led to the development of newer treatments such as the intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing delivery systems. Cataract formation and raised intraocular pressure remain the major disadvantages of corticosteroid use. There is mounting evidence that intravitreal VEGF inhibitors with or without combined laser photocoagulation will become the gold standard treatment for DMO.