ROCK inhibitor fasudil attenuated high glucose-induced MCP-1 and VCAM-1 expression and monocyte-endothelial cell adhesion.
Previous studies suggested that the RhoA/ROCK pathway may contribute to vascular complications in diabetes. The present study was designed to investigate whether ROCK inhibitor fasudil could prevent high glucose-induced monocyte-endothelial cells adhesion, and whether this was related to fasudil effects on vascular endothelial cell expression of chemotactic factors, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1). HUVECs were stimulated with high glucose (HG) or HG + fasudil in different concentration or different time. Monocyte-endothelial cell adhesion was determined using fluorescence-labeled monocytes. The mRNA and protein expression of VCAM-1 and MCP-1 were measured using real-time PCR and western blot. The protein levels of RhoA, ROCKI and p-MYPT were determined using western blot analysis. ELISA was employed to measure the expression of soluble VCAM-1 and MCP-1 in cell supernatants and human serum samples. Fasudil significantly suppressed HG-induced adhesion of THP-1 to HUVECs. Fasudil reduced Rho/ROCK activity (as indicated by lower p-MYPT/MYPT ratio), and prevented HG induced increases in VCAM-1 and MCP-1 mRNA and protein levels. Fasudil also decreased MCP-1 concentration in HUVEC supernatants, but increased sVCAM-1 shedding into the media. In human diabetic subjects, 2 weeks of fasudil treatment significantly decreased serum MCP-1 level from 27.9 ± 10.6 pg/ml to 13.8 ± 7.0 pg/ml (P < 0.05), while sVCAM-1 increased from 23.2 ± 7.5 ng/ml to 39.7 ± 5.6 ng/ml after fasudil treatment (P < 0.05). Treatment with the Rho/ROCK pathway inhibitor fasudil attenuated HG-induced monocyte-endothelial cell adhesion, possibly by reducing endothelial expression of VCAM-1 and MCP-1. These results suggest inhibition of Rho/ROCK signaling may have therapeutic potential in preventing diabetes associated vascular inflammation and atherogenesis.


[The "aphasia" article in Villaret's Handwörterbuch].
Freud's authorship is founded on three arguments: 1) the reasoning of the article is close to Charcot's lectures which Freud had just translated; 2) there is a specific Freudian core thesis, common to the article and his later writings, namely the notion of an associative speech area extending between the "motor fields of the cortex and those of the optic and auditory nerves" and touching them like "corners" of a continuous field; 3) general observations on the revision or non- revision of articles taken over from the 1st to the 2nd edition of Villaret.


Diffusion Behavior of Drug Molecules in Acrylic Pressure-Sensitive Adhesive.
Acrylic pressure-sensitive adhesive (PSA) is widely used in transdermal drug delivery systems, while the diffusion behavior of drug molecules in PSA is of great importance. In this paper, PSAs with different cross-link densities were prepared by adjusting the ratio of cross-linkers. The effects of cross-link density and temperature on the diffusion of drugs in PSA were investigated by Fourier transform infrared attenuated total reflectance and molecular dynamics simulation. The consistency between the experimental and simulation results demonstrated that molecular dynamics simulation could be used to predict the diffusion behavior of drugs in PSA. The results showed that free volume and the wriggling of polymer chains are positively related to the diffusion coefficient of drug molecules, while hydrogen bonds hinder drug diffusion.


Li3Al(MoO4)3, a lyonsite molybdate.
Trilithium aluminium trimolybdate(VI), Li(3)Al(MoO(4))(3), has been grown as single crystals from α-Al(2)O(3) and MoO(3) in an Li(2)MoO(4) flux at 998 K. This compound is an example of the well known lyonsite structure type, the general formula of which can be written as A(16)B(12)O(48). Because this structure can accomodate cationic mixing as well as cationic vacancies, a wide range of chemical compositions can adopt this structure type. This has led to instances in the literature where membership in the lyonsite family has been overlooked when assigning the structure type to novel compounds. In the title compound, there are two octahedral sites with substitutional disorder between Li(+) and Al(3+), as well as a trigonal prismatic site fully occupied by Li(+). The (Li,Al)O(6) octahedra and LiO(6) trigonal prisms are linked to form hexagonal tunnels along the [100] axis. These polyhedra are connected by isolated MoO(4) tetrahedra. Infinite chains of face-sharing (Li,Al)O(6) octahedra extend through the centers of the tunnels. A mixed Li/Al site, an Li, an Mo, and two O atoms are located on mirror planes.


miR-142-3p attenuates breast cancer stem cell characteristics and decreases radioresistance in vitro.
Effectively targeting cancer stem cells, a subpopulation of tumorigenic, aggressive, and radioresistant cells, holds therapeutic promise. However, the effects of the microRNA miR-142-3p, a small endogenous regulator of gene expression on breast cancer stem cells, have not been investigated. This study identifies the influence of miR-142-3p on mammary stemness properties and breast cancer radioresistance to establish its role in this setting. miR-142-3p precursor transfection was performed in MDA-MB-468, HCC1806, and MCF-7 cells, and stem cell markers CD44, CD133, ALDH1 activity and mammosphere formation were measured. β-catenin, the canonical wnt signaling effector protein, was quantified by Western blots and cell fluorescence assays both in miR-142-3p-overexpressing and anti-miR-142-3p-treated cells. Radiation response was investigated by colony formation assays. Levels of BRCA1, BRCA2, and Bod1 in miR-142-3p-overexpressing cells as well as expression of miR-142-3p, Bod1, KLF4, and Oct4 in sorted CD44+/CD24-/low cells were determined by quantitative polymerase chain reaction. miR-142-3p overexpression resulted in a strong decline in breast cancer stem cell characteristics with a decrease in CD44, CD133, ALDH1, Bod1, BRCA2, and mammosphere formation as well as reduced survival after irradiation. miR-142-3p expression was strongly reduced in sorted CD44+/CD24-/low stem cells, while Bod1, Oct4, and KLF4 were overexpressed. β-catenin levels strongly decreased after miR-142-3p overexpression, but not after anti-miR-142-3p treatment. We conclude that miR-142-3p downregulates cancer stem cell characteristics and radioresistance in breast cancer, mediated by a reduced role of β-catenin in miR-142-3p-overexpressing cells. miR-142-3p might therefore help to target cancer stem cells.


The desirability of a Ph.D. program in forensic science.
The results of a national survey to determine the need for and desirability of a Ph.D. program in forensic science revealed that crime laboratory scientists and administrators favor the establishment of such a program by a margin of almost three to one. Seventy-nine percent of laboratory personnel who had already received doctoral degrees also favored establishment of Ph.D. program. Forty-five percent of all those responding to the questionnaire who do not already hold a Ph.D. indicated interest in such a program, but only 6.1% would consider leaving their present positions to matriculate.


Predictors of Adherence to Antiretroviral Therapy among HIV/AIDS Patients in the Upper West Region of Ghana.
Background. The effectiveness of ART interventions is only realized in maximal levels of adherence. A near perfect adherence level of >95% is required for the effective suppression of HIV/AIDS virus. The main objective of this study was to identify the sociodemographic and socioeconomic factors that facilitate adherence to antiretroviral therapy among HIV/AIDS patients. Methods. This descriptive cross-sectional study was conducted between March and May 2013 at the Upper West Regional Hospital, Wa. A total of 201 confirmed HIV 1 seropositive subjects (mean age 36.6 ± 9.9 years) receiving antiretroviral therapy were interviewed using a structured questionnaire. The collected data was analyzed using GraphPad Prism version 5. A P value of <0.05 was considered statistically significant for all statistical analyses. Results. Overall lifetime adherence was found to be 62.2% while medication adherence in the last six months, last three months, last month, and last week were 73.6%, 87.1%, 91.0%, and 86.0%, respectively. The study revealed a positive association between adherence to ART and immunological success, with nonadherence increasing the risk (OR (95% CI): 9.2 (3.2-26.9)) of immunological failure. Univariate logistic regression analysis of the data showed that other ailments and side effects of drug were negatively associated with adherence to ART whereas self-perceived wellness, family support, and regular followup were positively associated with adherence to ART. Conclusion. Regular attendance at followup and family support are vital factors for 100% lifetime medication adherence. Effective counseling sessions on adherence for patients on antiretroviral therapy are paramount for the realization of the purpose of antiretroviral therapy programmes in Ghana.


The local intrinsic curvature of wavefronts allows to detect optical vortices.
We describe a method for effectively distinguishing the radiation endowed with optical angular momentum, also known as optical vortex, from ordinary light. We show that by detecting the inversion of the transverse intrinsic curvature sign (ITICS) an optical vortex can be locally recognized. The method is effective under conditions of huge importance for the exploitation of optical vortices, such as the far field of the source and access to a small fraction of the wavefront only. The validity of the method has been verified with table-top experiments with visible light, and the results show that a measurement performed over a transverse distance smaller than 4% of the beam diameter distinguishes a vortex from a Gaussian beam with a significance of 93.4%. New perspectives are considered for the characterization of vortices, with potential impact on the detection of extra-terrestrial radiation as well as on broadcast communication techniques.


Suppression of tumor growth by designed dimeric epidithiodiketopiperazine targeting hypoxia-inducible transcription factor complex.
Hypoxia is a hallmark of solid tumors, is associated with local invasion, metastatic spread, resistance to chemo- and radiotherapy, and is an independent, negative prognostic factor for a diverse range of malignant neoplasms. The cellular response to hypoxia is primarily mediated by a family of transcription factors, among which hypoxia-inducible factor 1 (HIF1) plays a major role. Under normoxia, the oxygen-sensitive α subunit of HIF1 is rapidly and constitutively degraded but is stabilized and accumulates under hypoxia. Upon nuclear translocation, HIF1 controls the expression of over 100 genes involved in angiogenesis, altered energy metabolism, antiapoptotic, and pro-proliferative mechanisms that promote tumor growth. A designed transcriptional antagonist, dimeric epidithiodiketopiperazine (ETP 2), selectively disrupts the interaction of HIF1α with p300/CBP coactivators and downregulates the expression of hypoxia-inducible genes. ETP 2 was synthesized via a novel homo-oxidative coupling of the aliphatic primary carbons of the dithioacetal precursor. It effectively inhibits HIF1-induced activation of VEGFA, LOX, Glut1, and c-Met genes in a panel of cell lines representing breast and lung cancers. We observed an outstanding antitumor efficacy of both (±)-ETP 2 and meso-ETP 2 in a fully established breast carcinoma model by intravital microscopy. Treatment with either form of ETP 2 (1 mg/kg) resulted in a rapid regression of tumor growth that lasted for up to 14 days. These results suggest that inhibition of HIF1 transcriptional activity by designed dimeric ETPs could offer an innovative approach to cancer therapy with the potential to overcome hypoxia-induced tumor growth and resistance.


Needleless electrospinning with twisted wire spinneret.
A needleless electrospinning setup named 'Needleless Twisted Wire Electrospinning' was developed. The polymer solution is electrospun from the surface of a twisted wire set to a high voltage and collected on a cylindrical collector around the wire. Multiple Taylor cones are simultaneously self-formed on the downward flowing solution. The system is robust and simple with no moving parts aside from the syringe pump used to transport the solution to the top of the wire. The structure and process parameters of the setup and the results on the preparation of polyvinyl pyrrolidone (PVP), hydroxyapatite (HA) and bioglass fibers with the setup are presented. PVP fiber sheets with areas of 40 × 120 cm(2) and masses up to 1.15 g were prepared. High production rates of 5.23 g h(-1) and 1.40 g h(-1) were achieved for PVP and HA respectively. The major limiting factor of the setup is drying of the polymer solution on the wire during the electrospinning process which will eventually force to interrupt the process for cleaning of the wire. Possible solutions to this problem and other ways to develop the setup are discussed. The presented system provides a simple way to increase the production rate and area of fiber sheet as compared with the conventional needle electrospinning.


Efficacy and safety of tranexamic acid as an emetic in dogs.
To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. 10 Beagles. In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.


The effects of the El Niño Southern Oscillation on skin and skin-related diseases: a message from the International Society of Dermatology Climate Change Task Force.
The El Niño Southern Oscillation (ENSO) is a complex climate phenomenon occurring in the Pacific Ocean at intervals of 2-7 years. The term refers to fluctuations in ocean temperatures in the tropical eastern Pacific Ocean (El Niño [the warm phase of ENSO] and La Niña [the cool phase of ENSO]) and in atmospheric pressure across the Pacific basin (Southern Oscillation). This weather pattern is attributed with causing climate change in certain parts of the world and is associated with disease outbreaks. The question of how ENSO affects skin and skin-related disease is relatively unanswered. We aimed to review the literature describing the effects of this complex weather pattern on skin. El Niño has been associated with increases in the occurrence of actinic keratosis, tinea, pityriasis versicolor, miliaria, folliculitis, rosacea, dermatitis by Paederus irritans and Paederus sabaeus, and certain vector-borne and waterborne diseases, such as dengue fever, leishmaniasis, Chagas' disease, Barmah Forest virus, and leptospirosis, and with decreases in the occurrence of dermatitis, scabies, psoriasis, and papular urticaria. La Niña has been associated with increases in the occurrence of varicella, hand, foot, and mouth disease, and Ross River virus (in certain areas), and decreases in viral warts and leishmaniasis. Reports on the effects of ENSO on skin and skin-related disease are limited, and more studies could be helpful in the future.


Factors predisposing to perinatal death related to uterine rupture during attempted vaginal birth after caesarean section: retrospective cohort study.
To determine the factors associated with an increased risk of perinatal death related to uterine rupture during attempted vaginal birth after caesarean section. Population based retrospective cohort study. Data from the linked Scottish Morbidity Record and Stillbirth and Infant Death Survey of births in Scotland, 1985-98. All women with one previous caesarean delivery who gave birth to a singleton infant at term by a means other than planned repeat caesarean section (n = 35 854). All intrapartum uterine rupture and uterine rupture resulting in perinatal death (that is, death of the fetus or neonate). The overall proportion of vaginal births was 74.2% and of uterine rupture was 0.35%. The risk of intrapartum uterine rupture was higher among women who had not previously given birth vaginally (adjusted odds ratio 2.5, 95% confidence interval 1.6 to 3.9, P < 0.001) and those whose labour was induced with prostaglandin (2.9, 2.0 to 4.3, P < 0.001). Both factors were also associated with an increased risk of perinatal death due to uterine rupture. Delivery in a hospital with < 3000 births a year did not increase the overall risk of uterine rupture (1.1, 0.8 to 1.5, P = 0.67). However, the risk of perinatal death due to uterine rupture was significantly higher in hospitals with < 3000 births a year (one per 1300 births) than in hospitals with >or= 3000 births a year (one per 4700; 3.4, 1.0 to 14.3, P = 0.04). Women who have not previously given birth vaginally and those whose labour is induced with prostaglandin are at increased risk of uterine rupture when attempting vaginal birth after caesarean section. The risk of consequent death of the infant is higher in units with lower annual numbers of births.


[A case of pyogenic osteomyelitis of the cervical spine following stellate ganglion block].
A 56-year-old woman had been treated with stellate ganglion block (SGB) for pigmentation degeneration retinopathy over 6 years. She had no history of diabetes mellitus or immunodeficiency. She complained of high back pain but was afebrile. She was diagnosed as pyogenic osteomyelitis by the MRI findings and hematological examination. Antibiotics was administerd for 3 weeks and inflammatory signs disappeared. We should bear in mind that pyogenic osteomyelitis is very rare but one of the most serious complications with SGB.


Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis is associated with a reduction in polar auxin transport and diverse morphological defects.
Polar auxin transport plays a key role in the regulation of plant growth and development. To identify genes involved in this process, we have developed a genetic procedure to screen for mutants of Arabidopsis that are altered in their response to auxin transport inhibitors. We recovered a total of 16 independent mutants that defined seven genes, called TRANSPORT INHIBITOR RESPONSE (TIR) genes. Recessive mutations in one of these genes, TIR3, result in altered responses to transport inhibitors, a reduction in polar auxin transport, and a variety of morphological defects that can be ascribed to changes in indole-3-acetic acid distribution. Most dramatically, tir3 seedlings are strongly deficient in lateral root production, a process that is known to depend on polar auxin transport from the shoot into the root. In addition, tir3 plants display a reduction in apical dominance as well as decreased elongation of siliques, pedicels, roots, and the inflorescence. Biochemical studies indicate that tir3 plants have a reduced number of N-1-naphthylphthalamic (NPA) binding sites, suggesting that the TIR3 gene is required for expression, localization, or stabilization of the NPA binding protein (NBP). Alternatively, the TIR3 gene may encode the NBP. Because the tir3 mutants have a substantial defect in NPA binding, their phenotype provides genetic evidence for a role for the NBP in plant growth and development.


Diabetic ketoacidosis in pregnancy.
Episodes of diabetic ketoacidosis (DKA) can represent a life-threatening emergency for mother and fetus. The cornerstones of treatment of DKA are aggressive fluid replacement and insulin administration while ascertaining which precipitating factors brought about the current episode of DKA, and then treating accordingly to mitigate those factors. The incidence of DKA and factors unique to pregnancy are discussed in this article, along with the effects of the disease process on pregnancy. Clinical presentation, diagnosis, and treatment modalities are covered in detail to offer ideas to improve maternal and fetal outcome.


Differential regulation of symmetry genes and the evolution of floral morphologies.
Shifts in flower symmetry have occurred frequently during the diversification of angiosperms, and it is thought that such shifts play important roles in plant-pollinator interactions. In the model developmental system Antirrhinum majus (snapdragon), the closely related genes CYCLOIDEA (CYC) and DICHOTOMA (DICH) are needed for the development of zygomorphic flowers and the determination of adaxial (dorsal) identity of floral organs, including adaxial stamen abortion and asymmetry of adaxial petals. However, it is not known whether these genes played a role in the divergence of species differing in flower morphology and pollination mode. We compared A. majus with a close relative, Mohavea confertiflora (desert ghost flower), which differs from Antirrhinum in corolla (petal) symmetry and pollination mode. In addition, Mohavea has undergone a homeotic-like transformation in stamen number relative to Antirrhinum, aborting the lateral and adaxial stamens during flower development. Here we show that the patterns of expression of CYC and DICH orthologs have shifted in concert with changes in floral morphology. Specifically, lateral stamen abortion in Mohavea is correlated with an expansion of CYC and DICH expression, and internal symmetry of Mohavea adaxial petals is correlated with a reduction in DICH expression during petal differentiation. We propose that changes in the pattern of CYC and DICH expression have contributed to the derived flower morphology of Mohavea and may reflect adaptations to a pollination strategy resulting from a mimetic relationship, linking the genetic basis for morphological evolution to the ecological context in which the morphology arose.


Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.
Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.


SuperSAGE as an analytical tool for host and viral gene expression.
SuperSAGE is a tag-based transcript profiling method, which allows to analyze the expression of thousands of genes at a time. In SuperSAGE, 26 bp tags are extracted from cDNA using the type III restriction enzyme, EcoP15I. In SuperSAGE, the amount of transcripts was represented by tag counts. Taking advantage of uniqueness of the 26 bp tags, host and virus transcripts can be monitored in virus-infected cells. Combining next generation sequencing technology, we established High-throughput SuperSAGE (Ht-SuperSAGE), which allows the analysis of multiple samples with reduced time and cost. In this chapter, we present the protocol of Ht-SuperSAGE involving a recently available benchtop type next generation sequencer.


[Poisoning with cholinesterase inhibitors].
A 32-year-old woman who had ingested 300 ml of a potent cholinesterase inhibitor insecticide (Fonofos) with suicidal intent became progressively comatose and finally suffered respiratory arrest. Tracheal intubation, mechanical ventilation, vigorous gastric lavage and intravenous administration of atropine and obidoxime brought about complete clinical recovery within 24 hours of ingestion of this potentially fatal dose of Fonofos.


Prognostic significance and clinical utility of left atrial reservoir strain in transcatheter aortic valve replacement.
Patients with diastolic dysfunction (DD) experience worse outcomes after transcatheter aortic valve replacement (TAVR). We investigated the prognostic value and clinical utility of left atrial reservoir strain (LARS) in patients undergoing TAVR for aortic stenosis (AS). All consecutive patients undergoing TAVR between 01/2018 and 12/2018 were included if discharge echocardiography and follow-up were available. LARS was derived from 2-D-speckle-tracking. Patients were grouped into 3 tertiles according to LARS. DD was analyzed using the ASE/EACVI-algorithm. The primary outcome was a composite of all-cause death and readmission for worsening heart failure 12 months after TAVR. Overall, 606 patients were available (age 80 years, interquartile range [IQR] 77-84), including 53% women. Median LARS was 13.0% (IQR 8.4-18.3). Patients were classified by LARS tertiles (mildly-impaired 21.4% [IQR 18.3-24.5], moderately-impaired 13.0% [IQR 11.3-14.6], severely-impaired 7.1% [IQR 5.4-8.4], p<0.0001). The primary outcome occurred more often in patients with impaired LARS (mildly-impaired 7.4%, moderately-impaired 13.4%, severely-impaired 25.7%, p<0.0001). On adjusted multivariable Cox-regression analysis, LARS-tertiles (HR 0.62, 95% CI 0.44-0.86, p=0.005) and higher degree of tricuspid regurgitation (HR 1.82, 95% CI 1.23-2.98, p=0.003) were the only significant predictors of the primary endpoint. Importantly, DD was unavailable in 56% of patients, but LARS-assessment allowed for reliable prognostication regarding the primary endpoint in subgroups without DD assessment (HR 0.64, 95% CI 0.47-0.87, p=0.003). Impaired LARS is independently associated with worse outcomes in patients undergoing TAVR. LARS allows for risk-stratification at discharge even in patients where DD cannot be assessed by conventional echocardiographic means.


Ligand binding affinity prediction with fusion of graph neural networks and 3D structure-based complex graph.
Accurate prediction of protein-ligand binding affinity is pivotal for drug design and discovery. Here, we proposed a novel deep fusion graph neural networks framework named FGNN to learn the protein-ligand interactions from the 3D structures of protein-ligand complexes. Unlike 1D sequences for proteins or 2D graphs for ligands, the 3D graph of protein-ligand complex enables the more accurate representations of the protein-ligand interactions. Benchmark studies have shown that our fusion models FGNN can achieve more accurate prediction of binding affinity than any individual algorithm. The advantages of fusion strategies have been demonstrated in terms of expressive power of data, learning efficiency and model interpretability. Our fusion models show satisfactory performances on diverse data sets, demonstrating their generalization ability. Given the good performances in both binding affinity prediction and virtual screening, our fusion models are expected to be practically applied for drug screening and design. Our work highlights the potential of the fusion graph neural network algorithm in solving complex prediction problems in computational biology and chemistry. The fusion graph neural networks (FGNN) model is freely available in https://github.com/LinaDongXMU/FGNN.


Age-Related Brood Parasitism and Egg Rejection in Magpie Hosts.
When the strength or nature of a host-parasite interaction changes over the host life cycle, the consequences of parasitism can depend on host population age structure. Avian brood parasites reduce hosts' breeding success, and host age may play a role in this interaction if younger hosts are more likely parasitized and/or less able to defend themselves. We analyzed whether the age of female magpie (Pica pica) hosts is associated with parasite attack or their ability to reject foreign eggs. We recorded parasitism and model egg rejection of known-age individuals over their lifetime and established whether the likelihood of parasitism or egg rejection changed with age or longevity. Parasitism probability did not change with female age, and there was a trend toward longer-lived females being less likely to be parasitized. However, model egg rejection probability increased with age for each individual female, and longer-lived females were more prone to reject model eggs. Most females in the population were young, and the majority of them accepted model eggs, suggesting that brood parasites exploiting younger host individuals are benefitting from a lower defense level of their hosts. Our results stress that the intensity of selection by brood parasites may be mediated by the age structure of host populations, a to-date neglected aspect in brood parasite-host research.


Improved Estimation of Human Lipoprotein Kinetics with Mixed Effects Models.
Mathematical models may help the analysis of biological systems by providing estimates of otherwise un-measurable quantities such as concentrations and fluxes. The variability in such systems makes it difficult to translate individual characteristics to group behavior. Mixed effects models offer a tool to simultaneously assess individual and population behavior from experimental data. Lipoproteins and plasma lipids are key mediators for cardiovascular disease in metabolic disorders such as diabetes mellitus type 2. By the use of mathematical models and tracer experiments fluxes and production rates of lipoproteins may be estimated. We developed a mixed effects model to study lipoprotein kinetics in a data set of 15 healthy individuals and 15 patients with type 2 diabetes. We compare the traditional and the mixed effects approach in terms of group estimates at various sample and data set sizes. We conclude that the mixed effects approach provided better estimates using the full data set as well as with both sparse and truncated data sets. Sample size estimates showed that to compare lipoprotein secretion the mixed effects approach needed almost half the sample size as the traditional method.


Identifying the effects of education on the ability to cope with a disability among individuals with disabilities.
The literature on disability has suggested that an educated individual with a disability is more likely to better cope with her/his disability than those without education. However, few published studies explore whether the relationship between education and ability to cope with a disability is anything more than an association. Using data on disability and accommodation from a large Danish survey from 2012-13 and exploiting a major Danish schooling reform as a natural experiment, we identified a potential causal effect of education on both economic (holding a job) as well as social (cultural activities, visiting clubs/associations, etc.) dimensions of coping among individuals with a disability, controlling for background factors, functioning, and disability characteristics. We found that endogeneity bias was only present in the case of economic participation and more educated individuals with a disability indeed had higher levels of both economic and social coping. To some extent, having more knowledge of public support systems and higher motivation explained the better coping among the group of individuals with disabilities who were educated. Our results indicated, however, that a large part of the effect of education on the ability to cope with a disability among individuals with disabilities was suggestive of a causal relationship.


Impulse oscillometry: reference values in children 100 to 150 cm in height and 3 to 10 years of age.
To generate reference equations in North American children to be used for assessing respiratory function through the forced oscillation (Rfo) technique, and to determine the changes in oscillatory resistance, reactance, and resonant frequency (Fres) in relation to age, body height, and weight. A prospective cross-sectional study performed on healthy children selected according to strict criteria of American Thoracic Society and European Respiratory Society recommendations. Triplicate measures were obtained of resistance and reactance at 5, 10, 15, 20, 25, and 35 Hz as well as Fres through the impulse oscillometer (MasterScreen IOS; Jaeger/Toennies; Höchberg, Germany). Two hundred twenty-two white children--normally distributed within the 3- to 10-year age range and 100 to 150 cm in height--were recruited in Montreal, Canada. We used regression analysis to generate multiple predictive equations separately per gender and frequency on age, height, and body weight. Stepwise multiple regression in both natural and logarithmic forms for height, weight, age, and gender showed that standing height was the only significant predictor for all variables. Minimal variability was noted in each subject among the triplicate measurements (p = 0.68 to 0.96). Coherence was > 0.9 at all oscillating frequencies except 5 Hz (< 0.72), with tendencies to lower values in young children. Resistance and Fres decrease by height, but also by age; and reactance increases. As opposed to our past experience with spirometry in compatible age groups, the Rfo technique was well accepted by preschool children.


Investigating the Association between Sociodemographic Factors and Chronic Disease Risk in Adults Aged 50 and above in the Hungarian Population.
Chronic diseases are a major cause of mortality and morbidity globally, with non-communicable diseases being responsible for most deaths. Older adults are at a higher risk of developing chronic diseases due to various sociodemographic and lifestyle factors such as age, sex, income, education, employment, place of residence, dietary supplementation, tobacco use, and alcohol consumption. Understanding the relationship between these factors and chronic diseases is crucial for identifying vulnerable populations and improving healthcare delivery. Through both an online and an interview-based survey, this cross-sectional study aimed to examine these associations, focusing on adults aged 50 and above, with the goal of identifying potential areas for intervention and prevention. The study found that gender, area of residence, education status, employment status, nutritional supplementation, body mass index (BMI), alcohol usage, and age are associated with the risk of chronic disease, cardiovascular disease, and diabetes. Female gender, higher educational level, employment, normal BMI, and younger age were found to be protective factors, while living in rural areas, alcohol consumption, and older age were identified as risk factors. The study recommends targeted interventions and improved access to healthcare to reduce risk factors and enhance healthcare delivery for better health outcomes.


Probiotic Improves Skin Oxidation, Elasticity, and Structural Properties in Aging Rats.
Skin aging, which affects all living organisms, is associated with oxidative stress. Probiotics exhibit antioxidant properties by producing reactive metabolites that counter oxidative stress. We hypothesized that Limosilactobacillus fermentum USM 4189 (LF 4189) has antioxidative properties and may prevent skin aging. In the present study, we used a D-galactose senescence-induced rat model to evaluate the potential antioxidative capability of LF 4189. The results indicated that rats administered LF 4189 exhibited increased plasma antioxidative activity (P=0.004), lipid peroxidation capacity (P=0.007), and skin elasticity compared with untreated aged rats (P=0.005). LF 4189 prevented telomere length shortening (P<0.05), indicating the potential to prevent senescence. A higher apoptotic activity was observed in old rats compared with young rats, whereas LF 4189 reduced the expression of four antioxidative enzyme genes that function as radical scavengers (all P<0.05), suggesting that the LF 4189 group had a reduced need to scavenge free radicals. Our findings indicate the potential of probiotics, such as LF 4189, as an anti-aging dietary intervention with antioxidant potential to improve skin health.


Post-operative complications following masculinizing genitoplasty in moderate to severe genital atypia: results from a multicenter, observational prospective cohort study.
Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of Mϋllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children's hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3-6 in those with a 46, XY or 45,X/46, XY chromosome complement, age <3 years with no previous genitoplasty; patients were included independent of whether genitoplasty was performed. Cosmesis was graded according to a 4-point Likert scale and complications per the Clavian-Dindo classification. Of the 31 participants, 30 underwent hypospadias repair and 1 patient did not undergo a genitoplasty procedure. The majority of participants (22) received a staged hypospadias repair. Seventeen complications were identified in 12 of the 31 children (41%) at 12 months of follow up. Glans dehiscence and urethrocutaneous fistula were the most common complications. Orchiopexy was performed in 14 (44%) and streak gonads were removed in 4 (13%) participants. Both parents and surgeons reported improved cosmesis after surgery when compared to baseline. Genitoplasty was chosen by parents for the majority of children eligible for study. No single surgical approach for masculinizing moderate to severe genital ambiguity in young patients with 46, XY or 45,X/46, XY DSD was adopted by all surgeons. Complications occurred in 41% of those who underwent genitoplasty for severe hypospadias. Overall, appearance of the genitals, as determined by parents and surgeons, improved following genitoplasty. Outcomes of early genitoplasty are needed to guide families when making decisions about such procedures for their young children.


A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Therapeutic Potential.
Interleukin-6 (IL-6), a pleiotropic cytokine that regulates immune responses and inflammatory reactions, plays a pivotal role in the development of rheumatoid arthritis (RA). Blockade of IL-6 signaling with the monoclonal antibody (mAb) represents an important advancement in RA treatment. Although two IL-6 receptor antibodies are already available in the clinic, there is no mAb specifically targeting the human IL-6 to block IL-6 signaling for RA treatment. In this study, we have developed a novel humanized anti-IL-6 mAb HZ-0408b with potent binding and neutralizing activity to human IL-6. We demonstrated that HZ-0408b has a high species specificity and low cross-reactivity. Moreover, HZ-0408b showed a more potent inhibitory effect on IL-6 signaling than Siltuximab, an FDA-approved anti-IL-6 chimeric mAb. HZ-0408b is comparable to Olokizumab, a humanized mAb against IL-6 that is already in phase III studies. We observed that HZ-0408b is well tolerated at doses that can achieve therapeutic serum levels in cynomolgus monkey. Most importantly, we proved that HZ-0408b treatment significantly ameliorated joint swelling after the onset of arthritis and dramatically reduced plasma C-reactive protein (CRP) levels in a monkey collagen-induced arthritis (CIA) model. Collectively, our findings using non-human primates indicate that humanized anti-IL-6 mAb HZ-0408b has excellent safety and efficacy profiles for RA therapy.


Flickering of fetal erythrocytes membrane under gestational diabetes observed with dual time resolved membrane fluctuation spectroscopy.
The membrane flickering of human fetal red blood cells (RBCs) affected by gestational diabetes mellitus (GDM) was studied with dual time resolved membrane fluctuation spectroscopy (D-TRMFS). This new technique is a modified version of the dual optical tweezers method that has been adapted to measure the mechanical properties of RBCs at two distant membrane points simultaneously. The micro-rheological parameters were obtained from direct membrane flickering measurements, followed by Fourier decomposition and cell membrane model adjustment. Our results show a significant decrease of 6.01 ± 1.19 nm in membrane fluctuations amplitude in healthy fetal, compared with healthy adult RBCs, meanwhile the amplitude in GDM cells increased 3.22 ± 1.10 nm compared with healthy fetal RBCs. Between GDM and healthy fetal RBCs, there are significant differences, especially in the bending modulus. Considering the mean of the two membrane points measured, the tension for GDM RBCs increased by 6.431 ± 3.57 (10-7 [N/m]) compared with healthy fetal RBCs, meanwhile, the bending was increased by 2.483 ± 0.58 (10-19 [J]) in GDM compared with healthy fetal RBCs. These results showed significant increment of 1.23 ± 0.07-fold and 3.29 ± 0.36-fold in tension and bending modulus in GDM, respectively. The strong impact of GDM on bending modulus could be associated with oxidative stress and lipid peroxidation, previously reported in fetal plasma of GDM cases.


Granulocyte-macrophage colony-stimulating factor is neuroprotective in experimental traumatic brain injury.
Traumatic brain injury (TBI) is an international health concern with a complex pathogenesis resulting in major long-term neurological, neurocognitive, and neuropsychiatric outcomes. Although neuroinflammation has been identified as an important pathophysiological process resulting from TBI, the function of specific inflammatory mediators in the aftermath of TBI remains poorly understood. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an inflammatory cytokine that has been reported to have neuroprotective effects in various animal models of neurodegenerative disease that share pathological similarities with TBI. The importance of GM-CSF in TBI has yet to be studied, however. We examined the role of GM-CSF in TBI by comparing the effects of a lateral fluid percussion (LFP) injury or sham injury in GM-CSF gene deficient (GM-CSF(-/-)) versus wild-type (WT) mice. After a 3-month recovery interval, mice were assessed using neuroimaging and behavioral outcomes. All mice given a LFP injury displayed significant brain atrophy and behavioral impairments compared with those given sham-injuries; however, this was significantly worse in the GM-CSF(-/-) mice compared with the WT mice. GM-CSF(-/-) mice given LFP injury also had reduced astrogliosis compared with their WT counterparts. These novel findings indicate that the inflammatory mediator, GM-CSF, may have significant protective properties in the chronic sequelae of experimental TBI and suggest that further research investigating GM-CSF and its potential benefits in the injured brain is warranted.


Innovative non-targeted liquid chromatography fingerprinting approach for authenticating tigernuts under Protected Designation of Origin quality seal.
Tigernut is a typical foodstuff from a specific region of Valencia (Spain) called 'L'Horta Nord', where it is commercialized under a Protected Designation of Origin (PDO) as Chufa de Valencia ('Valencia's tigernut'). PDO-recognized tigernuts present unique characteristics associated with their particular production region. Increasing demand and the associated expansion of its cultivation area has made necessary an exhaustive quality control to check the geographical origin and quality seal. In this work, a new multivariate analytical method capable of authenticating the PDO quality seal of tigernut samples was developed. Tigernut fat fraction was extracted under optimal conditions, applying the methodology of design of experiments. The analytical method combined fingerprinting methodology and chemometric tools to observe the natural grouping of samples using the exploratory analysis method and to develop classification models (partial least squares-discriminatory analysis; PLS-DA) to discriminate between two sample categories: (i) PDO tigernuts; and (ii) NON-PDO tigernuts. The built PLS-DA model demonstrated 100% accuracy, high sensitivity and specificity, revealing that the tigernut fat fraction can be applied to authenticate the PDO quality seal. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Examining school-based pedometer step counts among children in grades 3 to 6 using different timetables.
Advocates for the implementation of the Balanced School Day (BSD) schedule argue that this schedule will increase opportunities for physical activity. However, the relationship between this scheduling change and its impact on physical activity has not been examined. Thus, this study assessed levels of physical activity in students attending 2 different schools: 1 using the BSD and the other using the Traditional School Day (TSD) schedule. Participation of students between grades 3 and 6 was sought. Data were collected over 4 school days using pedometers. Independent Sample t tests and 1-way analysis of variance (ANOVA) were performed. A total of 117 students participated. Overall, average daily step counts for boys (6972 ± 1952) were significantly higher than girls (5742 ± 1495; p < .001). These average step counts represent 47% and 48% of the recommended amount of steps needed for health benefits for children between the ages of 6 and 12. The average daily step count for students using the BSD schedule was 6017 (±1666), while the average daily step count for students using the TSD schedule was 6788 (±1987). The difference in steps (771) was statistically significant (p = .03). These results do not support claims that the BSD offers increased physical activity. In fact, these results suggest that students enrolled in schools using the BSD schedule may have reduced daily physical activity. In addition, these results demonstrate that overall school-based physical activity is less than half of the recommended level; independent of school scheduling.


Highly specific substrates of proteinase 3 containing 3-(2-benzoxazol-5-yl)-l-alanine and their application for detection of this enzyme in human serum.
A set of benzoxazolyl-l-alanine derivates along with the MCA moiety (donors of fluorescence) were introduced into a proteinase 3 (PR3) substrate with a C-terminal ANB-NH(2) that serves as a fluorescence acceptor. Five substrates with general formula X-Tyr-Tyr-Abu-ANB-NH(2) were synthesized, and their kinetic parameters against proteinase 3 were determined. The highest k(cat)/K(M) value, 1.5 x 10(6) M(-1) s(-1), was obtained for (Pyr)Box-Ala-Tyr-Tyr-Abu-NH(2) where (Pyr)Box-Ala stands for N-methylpyrrole benzoxazole-l-alanine. Titration of this peptide with proteinase 3 resulted in measurable fluorescence at an enzyme amount equal to 29 pmol. This substrate was selected used to detect quantifiable levels of proteinase 3 in serum samples, including those of normal subjects. For all c-ANCA-positive samples (diagnosed Wegener granulomatosis), a significant increase of PR3 concentration was observed. Wegener granulomatosis is a severe autoimmune disease causing inflammation of the blood vessels. Our results clearly show that this substrate can be used for the construction of a very reliable, inexpensive, and easy to use diagnostic test for PR3 determination.


Inhibitory effects of fluoroquinolone antibiotics on Babesia divergens and Babesia microti, blood parasites of veterinary and zoonotic importance.
This study aimed to evaluate the inhibitory effects of fluoroquinolone antibiotics, including enrofloxacin, enoxacin, trovafloxacin, norfloxacin, and ofloxacin, on the in vitro and in vivo growth of Babesia divergens and Babesia microti parasites, respectively. The in vitro and in vivo inhibitory effects of fluoroquinolone antibiotics against B. divergens and B. microti, respectively were evaluated using fluorescence-based assay. Additionally, combination therapies of highly effective fluoroquinolone antibiotics (enrofloxacin, enoxacin, and trovafloxacin) with diminazene aceturate, luteolin, or pyronaridine tetraphosphate were tested on the in vitro cultures of B. divergens. Enrofloxacin, trovafloxacin, and enoxacin were the most effective fluoroquinolones against the in vitro growth of B. divergens, followed by norfloxacin and ofloxacin. Furthermore, a combination of enoxacin or trovafloxacin with either diminazene aceturate, luteolin, or pyronaridine tetraphosphate significantly enhanced the inhibitory effect on the growth of B. divergens in in vitro cultures. In mice infected by B. microti, enoxacin and diminazene aceturate combination therapy exhibited a potential antibabesial effect. These results suggest that safe and cheap fluoroquinolone, such as enoxacin, might be used for the treatment of clinical cases caused by Babesia spp. in animals or humans.


In situ calibration of an infrared imaging video bolometer in the Large Helical Device.
The InfraRed imaging Video Bolometer (IRVB) is a powerful diagnostic to measure multi-dimensional radiation profiles in plasma fusion devices. In the Large Helical Device (LHD), four IRVBs have been installed with different fields of view to reconstruct three-dimensional profiles using a tomography technique. For the application of the measurement to plasma experiments using deuterium gas in LHD in the near future, the long-term effect of the neutron irradiation on the heat characteristics of an IRVB foil should be taken into account by regular in situ calibration measurements. Therefore, in this study, an in situ calibration system was designed.


Incidence and risk factors of postnatal growth restriction in preterm infants.
Preterm infants are often significantly underweight at the time of hospital discharge. Growth impairment during early infancy can have permanent detrimental effects. We aimed to evaluate the incidence and risk factors of postnatal growth restriction (PNGR) in preterm infants. This prospective study included 124 preterm infants in neonatal intensive care unit between January 2015 and June 2016. Of 140 preterm infants screened, postnatal growth retardation was detected in 46 babies (37%). Low gestational age was independent risk factors for PNGR. Clinicians should be aware of the presence of this morbidity when caring for preterm infants and to provide optimal enteral nutrition.


Investigation on the Stability of Derivative Melam from Melamine Pyrolysis under High Pressure.
Although various kinds of carbon nitride precursors have been proposed, s-triazine-based structures are hardly reported because of their unfavorable energy, higher than that of heptazine-based ones. In this study, we investigate the thermal stability of s-triazine-based melam processed at a high pressure of 5 GPa and a temperature of 400-700 °C and complete the analyses of the composition and structure of the treated samples through X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and elemental analyses (EA). Results show that melam can stably exist up to 600 °C at 5 GPa. XRD and FTIR analyses reveal that residual melamine can be pyrolyzed into melam as temperature increases from 400 °C to 600 °C at a high pressure, suggesting that melam may be purified through high-pressure pyrolysis. Further melam polymerization at a higher pressure is a promising strategy for the preparation of s-triazine-based carbon nitride precursors used for bulk carbon nitride synthesis.


1,3-Dibenzyl-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione.
The mol-ecule of the title compound, C(29)H(20)N(2)O(3), contains four fused rings, three are six-membered rings and one is the five-membered imidazole ring. The fused-ring system is linked to two benzyl groups. The four fused rings are folded around the O=C⋯C=O direction of the anthraquinone, with a dihedral angle of 16.36 (8)° between the two terminal rings (A and D). The imidazole ring (D) is almost perpendicular to the two benzyl groups (E and F) with dihedral angles of 86.69 (17) and 83.15 (13)°, respectively. In the crystal, adjacent mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonding.


Approaches to combat with confounding by indication in observational studies of intended drug effects.
There has been a resurgence of controversy about the usefulness of observational data to study the efficacy of drugs. Nearly every week a researcher makes some criticism of clinical trials or justifies observational research into intended effects, with other researchers offering a contradictory viewpoint. Literature reviews are not useful in this regard because the contradictory studies will not usually be carried out. Some methods are discussed which may have potential utility in the study of intended effects. There may be a marginal role for statistical techniques such as propensity scores and confounder scores. More promising techniques may include ecological analyses, restriction of subjects and blinded prospective review. Because it is currently unknown when the observational study of drug efficacy is possible, we should arguably always carry out a study of the determinants of prescribing first, and possibly consider using the various techniques that are outlined in this article.


Marfan Syndrome.
Marfan syndrome (MFS) is the autosomal dominant-inherited multisystem connective-tissue disorder, with a reported incidence of 1 in 10,000 individuals and equal distribution in both genders. The main clinical manifestation of this disorder consists of an exaggerated length of the upper and lower limbs, hyperlaxity, scoliosis, alterations in the cardiovascular and pulmonary systems, and atypical bone overgrowth. Orofacial manifestations such as high-arched palate, hypodontia, long narrow teeth, bifid uvula, mandibular prognathism, and temporomandibular disorders are also common. Early diagnosis of MFS is essential to prevent the cardiovascular complications and treatment of orofacial manifestations, thus to increase the quality of life of the patient.


Establishment of multidrug resistant human colorectal carcinoma HCT-15 cell lines and their properties.
A series of MDR cell lines with various levels of P-glycoprotein have been established from a human colorectal carcinoma cell line, HCT-15, by stepwise exposure to adriamycin. The relative drug resistance of these cell lines correlated directly with both MDR1 mRNA levels and P-glycoprotein expression levels. Intracellular accumulation of adriamycin decreased inversely to their resistance. Drug sensitivities of these lines were reversed using verapamil. Since these cell lines are transplantable to nude mice, they may provide a useful animal model of MDR solid tumors for therapeutic experiments.


A study of the communicating branch between the medial and lateral plantar nerves.
A study of the communicating branch between the medial and lateral plantar nerves was carried out on the feet of 20 cadavers. The nerve was found to be present in all the feet examined, but in two women it was considerably enlarged bilaterally. It is suggested that this enlarged communicating branch may be a factor responsible for the frequent involvement of the nerve to the third interspace by Morton's neuroma.


Immunohistochemical investigation of parainfluenza 3 virus in sheep pneumonia.
The aim of this study was to determine the prevalence of parainfluenza 3 (PI3) virus antigen through histopathological and immunohistochemical (IHC) methods in sheep lung samples collected from Erzurum province, Türkiye. Between August and November 2017, 1462 sheep were dissected in the slaughterhouse and their lungs were examined macroscopically. In total, 100 of the lung samples with pneumonia were selected. Routine histopathological and IHC analyses of the collected lung tissues with pneumonia were performed. Pneumonia observed through macroscopical and histopathological examinations of the lung samples was classified as purulent-catarrhal bronchopneumonia (14.00%), fibrinous bronchopneumonia (23.00%), interstitial pneumonia (69.00%), granulomatous pneumonia (7.00%), verminous pneumonia (19.00%) and pulmonary adenomatosis (6.00%). Two or three types of pneumonia were observed in many of the same cases. The PI3 virus antigen positivity rate in the IHC analysis of sheep lung samples was 19.00%. In the IHC tracing, positivities were found mostly in the alveolar macrophages and cytoplasm of bronchial, bronchiolar and alveolar epithelial cells. As a result, the prevalence of PI3 virus in sheep in Erzurum province, Türkiye, was determined to be 19.00% using KLN BVB IHC method.


Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells.
NK cells express both inhibitory and activatory receptors that allow them to recognize target cells through HLA class I Ag expression. KIR3DL1 is a receptor that recognizes the HLA-Bw4 public epitope of HLA-B alleles. We demonstrate that polymorphism within the KIR3DL1 receptor has functional consequences in terms of NK cell recognition of target. Inhibitory alleles of KIR3DL1 differ in their ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand reactivity can be defined. KIR3DS1, which segregates as an allele of KIR3DL1, has a short cytoplasmic tail characteristic of activatory receptors. Because it is very similar to KIR3DL1 in the extracellular domains, it has been assumed that KIR3DS1 will recognize a HLA-Bw4 ligand. In this study, we demonstrate that KIR3DS1 is expressed as a protein at the cell surface of NK cells, where it is recognized by the Z27 Ab. Using this Ab, we found that KIR3DS1 is expressed on a higher percentage of NK cells in KIR3DS1 homozygous compared with heterozygous donors. In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not recognize HLA-Bw4 on EBV-transformed cell lines.


Cardiac hydatid cysts: surgical treatment and results.
From 1991 to 2000 six patients with intracardiac echinococcosis underwent surgical treatment. Four patients were females and two were males, age of the patients ranged from 20 to 68 years. Two patients had symptoms, all patients were diagnosed as a component of multi-organ echinococcosis and three of them underwent operation before. They were examined serologically and echocardiographically. Cardiac hydatidosis were diagnosed in right ventricle (in three cases), left ventricle (in one case), and interventricular septum (in two cases). Sternotomy was the approach used and all patients were operated on using cardiopulmonary bypass. Intraoperative rupture did not occur. There was no operative mortality, the only morbidity was complete atrioventricular block necessitating VVD pacemaker implantation in the patient with hydatid cyst involving the basal interventricular septum. All patients were followed by medical treatment with albendazole (400 mg/day) and no recurrences were reported in the late follow-up.


MYD88L265P and CD79B double mutations type (MCD type) of diffuse large B-cell lymphoma: mechanism, clinical characteristics, and targeted therapy.
MYD88/CD79B-mutated (MCD) genotype is a genetic subgroup of diffuse large B-cell lymphoma (DLBCL) with the co-occurrence of MYD88L265P and CD79B mutations. MCD genotype is characterized by poor prognosis and extranodal involvement especially in immune-privileged sites. MCD model is dominated by activated B-cell (ABC)-like subtype of DLBCLs. It is generally accepted that the pathogenesis of MCD DLBCL mainly includes chronic active B-cell receptor (BCR) signaling and oncogenic MYD88 mutations, which drives pathological nuclear factor kappa B (NF-κB) activation in MCD lymphoid malignancies. CD79B and MYD88L265P mutations are frequently and contemporaneously founded in B-cell malignancies. The collaboration of the two mutations may explain the unique biology of MCD. Meanwhile, standard immunochemotherapy combine with different targeted therapies worth further study to improve the prognosis of MCD, according to genetic, phenotypic, and clinical features of MCD type. In this review, we systematically described mechanism, clinical characteristics, and targeted therapy of MCD DLBCL.


Late-onset hypogonadism.
In Poland, the number of men over the age of 50 years exceeds 6 million. It is estimated that about 2-6% of this population develops symptoms of late-onset hypogonadism (LOH). In men, testosterone deficiency increases slightly with age. LOH is a clinically and biochemically defined disease of older men with serum testosterone level below the reference parameters of younger healthy men and with symptoms of testosterone deficiency, manifested by pronounced disturbances of quality of life and harmful effects on multiple organ systems. Testosterone replacement therapy may give several benefits regarding body composition, metabolic control, and psychological and sexual parameters.


Plasma bupivacaine concentrations during combined regional and general anaesthesia for resection and reconstruction of head and neck carcinomata.
Venous plasma bupivacaine concentrations were measured in patients undergoing resection and reconstruction surgery for intra-oral malignancy. Vth cranial nerve and cervical plexus blocks were performed using 0.5% bupivacaine. Total dosage was higher than recommended by U.K. manufacturers. Mean peak venous plasma concentrations were higher than previously recorded. A significant different was found in the peak concentrations when adrenaline was included. The significance of these results in relation to systemic toxicity and recommended dosage is discussed.


Induction of alpha-calcitonin gene-related peptide mRNA expression in rat dorsal root ganglia by heat stress involves the heme oxygenase-1/carbon monoxide pathway.
SD rats were pretreated with whole body hyperthermia (rectal 42 degrees C) for 15 min. The level of calcitonin gene-related peptide (CGRP) in plasma, and alpha- and beta-CGRP mRNA as well as heme oxygenease-1 and heme oxygenase-2 mRNA in dorsal root ganglia were determined by radioimmunoassay and semi-quantitative reverse-transcription polymerase chain reaction, respectively. Heat stress induced only the expression of alpha-CGRP or heme oxygenease-1 but not beta-CGRP or heme oxygenase-2 mRNA, and the release of CGRP and induction of alpha-CGRP mRNA expression were abolished by pretreatment with Zinc protoporphyrin IX, the heme oxygenase inhibitor, or methylene blue, the inhibitor of soluble guanylate cyclase. These results indicate that induction of alpha-CGRP mRNA expression in rat DRG by heat stress involves the heme oxygenase-1/carbon monoxide pathway.


Yellow Subthreshold Micropulse Laser in Retinal Diseases: An In-Depth Analysis and Review of the Literature.
Yellow subthreshold micropulse laser (YSML) is a retinal laser capable of inducing a biologic response without causing thermal damage to the targeted tissue. The 577-nm YSML is delivered to the retina abiding by different protocols in which wavelength, power, duration, spot size and number of spots can be properly set to achieve the most effective and safe treatment response in various chorioretinal disorders. The ultrashort trains of power modulate the activation of the retinal pigment epithelium cells and intraretinal cells, such as Müller cells, causing no visible retinal scars. Subthreshold energy delivered by YSML stimulates the production of the heat-shock proteins, highly conserved molecules that protect cells against any sort of stress by blocking apoptotic and inflammatory pathways that cause cell damage. YSML treatment allows resorption of the subretinal fluid in central serous chorioretinopathy and intraretinal fluid in various conditions including diabetic macular edema, postoperative cystoid macular edema and other miscellaneous conditions. YSML also seems to modulate the development and progression of reticular pseudodrusen in dry age-related macular degeneration. The aim of this review is to discuss and summarize the safety and efficacy of YSML treatment in retinal diseases.


Large heterogeneous nuclear ribonucleic acid has three times as many 5' caps as polyadenylic acid segments, and most caps do not enter polyribosomes.
The rate of synthesis in Chinese hamster cells of 5' cap structures, m7 GpppNmp, in large (greater than 700 bases) heterogeneous nuclear ribonucleic acid (RNA) molecules is two to three times faster than the synthesis of 3'-terminal polyadenylic acid segments. As judged by presence of caps, newly synthesized polysomal messenger RNA, exclusive of messenger RNA the size of histone messenger RNA, is more than 90% in the polyadenylated category. It appears, therefore, that between half and two-thirds of the long capped heterogeneous nuclear RNA molecules do not contribute a capped polysomal derivative to the cytoplasm. There are capped, nonpolysomal, non-polyadenylated molecules with a rapid turnover rate that fractionate with the cytoplasm. These metabolically unstable molecules either could represent leakage into the cytoplasm during fractionation or could truly spend a brief time in the cytoplasm before decay.


A review of current practice for boys undergoing hypospadias repair: from pre-operative work up to removal of dressing post-surgery.
The aim of this article was to examine an area from dinical practice, in this instance, paediatric urology and to look at the information needs of families prior to their young sons' having surgery to correct a hypospadias. Involving families and promoting informed decision-making with families prior to hypospadias repair for their child is important. To be able to facilitate real involvement the information has to be shared and parents and families given adequate support and opportunity to seek answers to questions. Providing an environment to undertake this, to then learn from the families for the future and to support the development of a National Support group, www.hypospadias.co.uk have been outcomes from setting up a pre-admission clinic. Literature in respect of after-care is very sparse. It became evident from clinical practice that the rationale for applying a dressing postoperatively needed to be explored. Furthermore limited evidence about dressing removal, coupled with the anxiety and upset this caused parents, identified the need to consider two issues (i) a better method of removal of dressings and (ii) the effects on pain scores. A blinded randomized controlled feasibility study was developed and implemented, with completion due at the end of 2001.


Age effects on rat hindlimb muscle atrophy during suspension unloading.
Disuse can induce numerous adaptive alterations in skeletal muscle. In the present study the effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450 g) and juvenile (200 g) rats after 1, 7, or 14 days of whole body suspension. Quantitatively and qualitatively the soleus (S), gastrocnemius (G), plantaris (P), and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicated a less rapid rate of response in adult muscles. This was corroborated by assessment of muscle alpha-actin mRNA levels, which indicated a rapid (within 1 day) and significant (P less than 0.05) effect in juveniles but not in adults. The results of this investigation indicate 1) a qualitatively similar differential effect of unloading on muscles of adults and juveniles, 2) a quantitatively reduced and less rapid effect of suspension on adult muscles, and 3) a close similarity of adult and juvenile muscle responses during suspension and spaceflight, suggesting that this ground-based model simulates many of the unloading effects of weightlessness.


Atherosclerotic plaque characterization by quantitative analysis using intravascular ultrasound: correlation with histological and immunohistochemical findings.
The aim of this study was to clarify whether atherosclerotic plaque morphology, as defined by quantitative analysis with intravascular ultrasound (IVUS) images, was related to the immunohistochemical findings. Twenty-five coronary lesions in 25 patients who had ultrasound guidance during directional coronary atherectomy (DCA) were enrolled. The lesions retrieved by DCA were analyzed and divided into 3 groups (lesions infiltrated with both macrophages and lymphocytes: group IML; lesions infiltrated with macrophages but not lymphocytes: group IM; and non-infiltrated lesions: group NI). The mean plaque echo level divided by the mean adventitia echo level (MPEL/MAEL) and the heterogeneity of the distribution of plaque echo levels (HDPEL) were calculated. The proportion of patients with acute coronary syndromes was significantly different among the groups: IML (n=14), IM (n=5), and NI (71%, 0% and 17%, respectively; p<0.01). The pre-DCA HDPEL value was highest in group IML and lowest in group NI; however, no significant differences in MPEL/MAEL values were found. The results suggest that plaque morphology, as defined by IVUS images, was related to the immunohistochemical findings. The increase in HDPEL correlated with the presence of immune inflammation.


Indirect Electrosynthesis with Halogen Ions as Mediators.
Organic electrosynthesis has gained increasing research interest as it harvests electric current as redox regents, thereby providing a sustainable alternative to conventional approaches. Compared with direct electrosynthesis, indirect electrosynthesis employs mediator(s) to lower the overpotentials for substrate activation, and enhance the reaction efficiency and functional group compatibility by shifting the heterogenous electron transfer process to be homogenous. As one of the most versatile and cost-efficient mediators, halogen mediators are always combined with an irreversible halogenation reaction. Thus, the electrochemical reaction between halogen mediators and substrates doesn't directly controlled by the two standard potentials difference. In this account, our recent developments in the area of halogen-mediated indirect electrosynthesis are summarized. The anodically generated halogen species from halogenide salts have the abilities to undergo electron-transfer (ET) or hydrogen-atom- transfer (HAT) processes. The reaction features, scopes, limitations, and mechanistic rationalisations are discussed in this account. We hope our studies will contribute to the future developments to broaden the scope of halogen-mediated electrosynthesis.


What is the role of epsilon in the Escherichia coli ATP synthase?
The ATP synthase from Escherichia coli is a prototype of the ATP synthases that are found in many bacteria, in the mitochondria of eukaryotes, and in the chloroplasts of plants. It contains eight different types of subunits that have traditionally been divided into F(1), a water-soluble catalytic sector, and F(o), a membrane-bound ion transporting sector. In the current rotary model for ATP synthesis, the subunits can be divided into rotor and stator subunits. Several lines of evidence indicate that epsilon is one of the three rotor subunits, which rotate through 360 degrees. The three-dimensional structure of epsilon is known and its interactions with other subunits have been explored by several approaches. In light of recent work by our group and that of others, the role of epsilon in the ATP synthase from E. coli is discussed.


Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts.
MR-guided focused ultrasound (MRgFUS) is increasingly being used to treat patients with essential tremor (ET) and Parkinson's disease (PD) with thalamotomy and pallidotomy, respectively. Pallidotomy is performed off-center within the cranium compared to thalamotomy and may present challenges to therapeutic lesioning due to this location. However, the impact of target location on treatment efficiency and ability to create therapeutic lesions has not been studied. This study aimed to compare the physical efficiency of MRgFUS thalamotomy and pallidotomy. Treatment characteristics were compared between patients treated with thalamotomy (n = 20) or pallidotomy (n = 20), matched by skull density ratios (SDR). Aspects of treatment efficiency were compared between these groups. Demographic and comparative statistics were conducted to assess these differences. Acoustic field simulations were performed to compare and validate the simulated temperature profile for VIM and GPi ablation. Lower SDR values were associated with greater energy requirement for thalamotomy (R2 = 0.197, p = 0.049) and pallidotomy (R2 = 0.342, p = 0.007). The impact of low SDR on efficiency reduction was greater for pallidotomy, approaching significance (p = 0.061). A nearly two-fold increase in energy was needed to reach 50°C in pallidotomy (10.9kJ) than in thalamotomy (5.7kJ), (p = 0.002). Despite lower energy requirement, the maximum average temperature reached was higher in thalamotomy (56.7°C) than in pallidotomy (55.0°C), (p = 0.017). Mean incident angle of acoustic beams was lesser in thalamotomy (12.7°) than in pallidotomy (18.6°), (p < 0.001). For all patients, a lesser mean incident angle correlated with a higher maximum average temperature reached (R2 = 0.124, p = 0.026), and less energy needed to reach 50°C (R2=0.134, p = 0.020). Greater skull thickness was associated with a higher maximum energy for a single sonication for thalamotomy (R2 = 0.206, p = 0.045) and pallidotomy (R2 = 0.403, p = 0.003). An acoustic and temperature field simulation validated similar findings for thalamotomy and pallidotomy in a single patient. The centrally located VIM offers a more efficient location for therapeutic lesioning compared to GPi pallidotomy in SDR matched cohort of patients. The impact on therapeutic lesioning with lower SDR may be greater for pallidotomy patients. As newer off-center targets are investigated, these findings can inform patient selection and treatment requirements for lesion production.


First-Line Helicobacter pylori Eradication in Patients with Chronic Kidney Diseases in Taiwan.
Patients with chronic kidney disease (CKD) and Helicobacter pylori (H. pylori) infection have a higher incidence of gastroduodenal diseases and therefore are recommended to receive eradication therapies. This study aimed to assess the efficacy of a 7-day standard triple therapy in patients with CKD (eGFR < 60 ml/min/1.73 m2) and to investigate the clinical factors influencing the success of eradication. A total of 758 patients with H. pylori infection receiving a 7-day standard first-line triple therapy between January 1, 2013, and December 31, 2014, were recruited. Patients were divided into two groups: CKD group (N = 130) and non-CKD group (N = 628). The eradication rates attained by the CKD and non-CKD groups were 85.4% and 85.7%, respectively, in the per-protocol analysis (p = 0.933). The eradication rate in CKD stage 3 was 84.5% (82/97), in stage 4 was 88.2% (15/17), and in those who received hemodialysis was 87.5% (14/16). There were no significant differences in the various stages of CKD (p = 0.982). The adverse events were similar between the two groups (3.1% versus 4.6%, p = 0.433). Compliance between the two groups was good (100.0% versus 99.8%, p = 0.649). There was no significant clinical factor influencing the H. pylori eradication rate in the non-CKD and CKD groups. This study suggests that the H. pylori eradication rate and adverse rate in patients with CKD are comparable to those of non-CKD patients.


Biochemical Analysis of Ferritin and D-dimer in COVID-19 Survivors and Non-survivors.
Background COVID-19 is a major cause of illness and mortality. The management of COVID-19-related illnesses might change if variables connected to their severity and the requirement for ICU admission could be found. The severity of COVID-19 might be efficiently predicted with several laboratory measures, such as ferritin levels and D-dimer analysis. Objectives This study aimed to evaluate the association between serum D-dimer and ferritin levels and their effects on mortality in patients with COVID-19. Methods This retrospective observational study included all patients with positive real-time polymerase chain reaction (RT-PCR) results for COVID-19 who were hospitalized in the Ministry of Health South Al-Qunfudah General Hospital between March and September 30, 2020. Their laboratory parameters, serum D-dimer, and ferritin levels were evaluated. IBM SPSS Statistics for Windows, Version 26.0 (released 2019; IBM Corp., Armonk, New York, United States) was used to analyze the data. Results A total of 318 COVID-19 patients were analyzed; 56.9% (n=181) were male and 43.1% (n=137) were female. Of these, 78.6% (n=250) survived, including 58% of men and 42% of women. The mean D-dimer was 2.1 mcg/mL (SD=3.16) and the mean ferritin was 698.59 ng/mL (SD=603.11). Non-recovered patients were substantially older (66.16 years old) and had higher D-dimer (5.46) mcg/mL and ferritin levels (992.96) ng/mL. Intubation length and gender did not affect survival. Of the non-survivors, 95.6% (n=239) were admitted to the ICU, and 50% (n=34) required mechanical ventilation. Conclusions COVID-19 infection mortality dramatically increased with older age and increased mean ferritin and plasma D-dimer values, which were significantly higher in COVID-19 non-survivors than in survivors. Therefore, assessing and monitoring these laboratory markers in the early stages of the disease may have a significant impact on preventing disease progression and death.


Comparative study of three short-chain neurotoxins from the venom of Naja kaouthia (Yunnan, China).
Three short-chain neurotoxins named NT-1, NT-II, and NT-III were purified from the venom of Naja kaouthia, a snake distributed throughout the south of Yunnan province, China, by a series of chromatographic steps, including an FPLC Resource S column. Their molecular weights, determined by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MS, were 6952.19 Da, 6854.92 Da, and 6828.80 Da, respectively. NT-I consisted of 62 amino acid residues, and the other two consisted of 61 amino acid residues, including 8 cysteines. After hydrolysis by endoproteinase Glu-C, their primary sequences were determined. A test of their activities demonstrated that they effectively inhibited muscle contractions induced by electric stimulation. Furthermore, the extent of inhibition caused by NT-II and NT-III was less than that of NT-I. The IC50s were 0.04 microg/ml, 0.20 microg/ml, and 0.23 microg/ml for NT-I, NT-II, and NT-III, respectively. Compared with NT-II and NT-III, the higher activity of NT-I may be a result of the amino acid residue substitution Ile36 to Arg36.


Automatic Perception of Chemical Similarities Between Metabolic Pathways.
Metabolic pathways are at the crossroad between the chemical world of small molecules and the biological world of enzymes, genes and regulation. Methods for their processing are therefore required for a great variety of applications. The work presented here reports a new method to encode metabolic pathways and reactomes of organisms based on the MOLMAP approach. Pathways are represented from features of the metabolites involved in their reactions enabling to automatically perceive chemical similarities, and making no use of EC numbers. MOLMAP descriptors are based on atomic topological and physicochemical features of the bonds involved in reactions. The results show that self-organizing maps (SOM) can be trained with MOLMAPs of pathways to automatically recognize similarities between pathways of the same type of metabolism. The study also illustrates the possibility of applying the MOLMAP methodology at progressively higher levels of complexity, bridging chemical and biological information, and going all the way from atomic properties to the classification of organisms.


Cephalosporins: an update.
The cephalosporins are the largest and most diverse family of antimicrobial agents available. Although they rarely are considered drugs of first choice for the therapy of bacterial infections, they are the most commonly prescribed agents for both ambulatory and hospitalized patients. The first-generation agents have the most limited spectrum of bactericidal activity, but they are the most potent against Gram-positive microbes. The third- and fourth-generation agents have a broad spectrum of activity that includes the majority of Gram-negative pathogens. However, they are less active than their first-generation counterparts against Gram-positive bacteria, especially S aureus. The cephalosporins generally are well tolerated, and the oral agents are palatable. However, their use is limited by increasing resistance among certain groups of bacteria and high cost, especially of the parenteral and recently licensed oral agents. The prudent physician need not be familiar with all cephalosporins, but should be knowledgeable about a select few.


Causal Inference in Developmental Origins of Health and Disease (DOHaD) Research.
Studies of the developmental origins of health and disease (DOHaD) often rely on prospective observational data, from which associations between developmental exposures and outcomes in later life can be identified. Typically, conventional statistical methods are used in an attempt to mitigate problems inherent in observational data, such as confounding and reverse causality, but these have serious limitations. In this review, we discuss a variety of methods that are increasingly being used in observational epidemiological studies to help strengthen causal inference. These methods include negative controls, cross-contextual designs, instrumental variables (including Mendelian randomization), family-based studies, and natural experiments. Applications within the DOHaD framework, and in relation to behavioral, psychiatric, and psychological domains, are considered, and the considerable potential for expanding the use of these methods is outlined.


Applicability of Control Materials To Support Gene Promoter Characterization and Expression in Engineered Cells Using Digital PCR.
The use of standardized components and processes in engineering underpins the design-build-test model, and the engineering of biological systems is no different. Substantial efforts to standardize both the components and the methods to validate the engineered biological systems is ongoing. This study has developed a panel of control materials encoding the commonly used reporter genes GFP and RFP as DNA or RNA molecules. Each panel contained up to six samples with increasingly small copy number differences between the two reporter genes that ranged from 1- to 2-fold differences. These copy number differences represent the magnitude of changes that may need to be measured to validate an engineered system. Using digital PCR (dPCR), we demonstrated that it is possible to quantify changes in both gene and gene transcript numbers both within and between samples down to 1.05-fold. We corroborated these findings using a simple gene circuit within a bacterial model to demonstrate that dPCR was able to precisely identify small changes in gene expression of two transcripts in response to promoter stimulation. Finally, we used our findings to highlight sources of error that can contributed to the measurement uncertainty in the measurement of small ratios in biological systems. Together, the development of a panel of control materials and validation of a high accuracy method for the measurement of small changes in gene expression, this study can contribute to the engineering biology "toolkit" of methods and materials to support the current standardization efforts.


Extracellular Vesicle RNA: A Universal Mediator of Microbial Communication?
Both extracellular RNAs and extracellular vesicles (EVs) have recently garnered attention as novel mediators of intercellular communication in eukaryotes and prokaryotes alike. EVs not only permit export of RNA, but also facilitate delivery and trans-kingdom exchange of these and other biomolecules, for instance between microbes and their hosts. In this Opinion article, we propose that EV-mediated export of RNA represents a universal mechanism for interkingdom and intrakingdom communication that is conserved among bacterial, archaeal, and eukaryotic microbes. We speculate how microbes might use EV RNA to influence target cell gene expression or manipulate host immune responses.


Prevalence of preterm birth in Scandinavian countries: a systematic review and meta-analysis.
As welfare societies, Scandinavian countries share characteristics of equality related to healthcare access, gender, and social services. However, cultural and lifestyle variations create country-specific health differences. This meta-analysis assessed the prevalence of preterm birth (PTB) and its categories in Scandinavian countries. A systematic search in key databases of literature published between 1990 and 2021 identified studies of the prevalence of PTB and its categories. Following the use of the Freeman-Tukey double arcsine transformation, a meta-analysis of weighted data was performed using the random-effects model and meta-prop method. We identified 109 observational studies that involved 86,420,188 live births. The overall pooled prevalence (PP) of PTB was 5.3% (PP = 5.3%, 95% confidence interval [CI] 5.1%, 5.5%). The highest prevalence was in Norway (PP = 6.2%, 95% CI 5.3%, 7.0%), followed by Sweden (PP = 5.3%, 95% CI 5.1%, 5.4%), Denmark (PP = 5.2%, 95% CI 4.9%, 5.3%), and Iceland (PP = 5.0%, 95% CI 4.4%, 5.7%). Finland had the lowest PTB rate (PP = 4.9%, 95% CI 4.7%, 5.1%). The overall PP of PTB was 5.3%, with small variations among countries (4.9%-6.2%). The highest and lowest PPs of PTB were in Norway and Finland, respectively.


Pregnancy with bilateral tubercular pleural effusion: challenges.
Pulmonary tuberculosis (TB) during pregnancy mimics some of the physiological changes that occur during pregnancy. Diagnosis is challenging, especially when the patient presents with acute respiratory distress. The incidence of pleural effusion in TB is 3-25% and in the majority of patients, is unilateral. We describe the intensive care management of a 27-year-old pregnant woman admitted to our hospital with life threatening respiratory distress and circulatory shock. She continued to have severe metabolic and respiratory acidosis with shock in spite of the resuscitative measures undertaken. At that point, a bedside lung ultrasonography showed bilateral pleural effusion which was followed with therapeutic thoracocentesis of the right side. This resulted in the stabilization of the respiratory mechanics and haemodynamics of the patient. The pleural fluid culture tested positive for acid fast bacilli after 4 weeks in the intensive care unit. Anti-TB therapy was started and she made a rapid recovery with liberation from mechanical ventilation. The early use of bedside lung ultrasonography was instrumental in the successful management of this patient.


Applications of acceptorless dehydrogenation and related transformations in chemical synthesis.
Conventional oxidations of organic compounds formally transfer hydrogen atoms from the substrate to an acceptor molecule such as oxygen, a metal oxide, or a sacrificial olefin. In acceptorless dehydrogenation (AD) reactions, catalytic scission of C-H, N-H, and/or O-H bonds liberates hydrogen gas with no need for a stoichiometric oxidant, thereby providing efficient, nonpolluting activation of substrates. In addition, the hydrogen gas is valuable in itself as a high-energy, clean fuel. Here, we review AD reactions selectively catalyzed by transition metal complexes, as well as related transformations that rely on intermediates derived from reversible dehydrogenation. We delineate the methodologies evolving from this recent concept and highlight the effect of these reactions on chemical synthesis.


CDNF rescues motor neurons in models of amyotrophic lateral sclerosis by targeting endoplasmic reticulum stress.
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects motor neurons in the spinal cord, brainstem and motor cortex, leading to paralysis and eventually to death within 3-5 years of symptom onset. To date, no cure or effective therapy is available. The role of chronic endoplasmic reticulum stress in the pathophysiology of amyotrophic lateral sclerosis, as well as a potential drug target, has received increasing attention. Here, we investigated the mode of action and therapeutic effect of the endoplasmic reticulum-resident protein cerebral dopamine neurotrophic factor in three preclinical models of amyotrophic lateral sclerosis, exhibiting different disease development and aetiology: (i) the conditional choline acetyltransferase-tTA/TRE-hTDP43-M337V rat model previously described; (ii) the widely used SOD1-G93A mouse model; and (iii) a novel slow-progressive TDP43-M337V mouse model. To specifically analyse the endoplasmic reticulum stress response in motor neurons, we used three main methods: (i) primary cultures of motor neurons derived from embryonic Day 13 embryos; (ii) immunohistochemical analyses of spinal cord sections with choline acetyltransferase as spinal motor neuron marker; and (iii) quantitative polymerase chain reaction analyses of lumbar motor neurons isolated via laser microdissection. We show that intracerebroventricular administration of cerebral dopamine neurotrophic factor significantly halts the progression of the disease and improves motor behaviour in TDP43-M337V and SOD1-G93A rodent models of amyotrophic lateral sclerosis. Cerebral dopamine neurotrophic factor rescues motor neurons in vitro and in vivo from endoplasmic reticulum stress-associated cell death and its beneficial effect is independent of genetic disease aetiology. Notably, cerebral dopamine neurotrophic factor regulates the unfolded protein response initiated by transducers IRE1α, PERK and ATF6, thereby enhancing motor neuron survival. Thus, cerebral dopamine neurotrophic factor holds great promise for the design of new rational treatments for amyotrophic lateral sclerosis.


Locking it down: The privacy and security of mobile medication apps.
To explore the privacy and security of free medication applications (apps) available to Canadian consumers. The authors searched the Canadian iTunes store for iOS apps and the Canadian Google Play store for Android apps related to medication use and management. Using an Apple iPad Air 2 and a Google Nexus 7 tablet, 2 reviewers generated a list of apps that met the following inclusion criteria: free, available in English, intended for consumer use and related to medication management. Using a standard data collection form, 2 reviewers independently coded each app for the presence/absence of passwords, the storage of personal health information, a privacy statement, encryption, remote wipe and third-party sharing. A Cohen's Kappa statistic was used to measure interrater agreement. Of the 184 apps evaluated, 70.1% had no password protection or sign-in system. Personal information, including name, date of birth and gender, was requested by 41.8% (77/184) of apps. Contact information, such as address, phone number and email, was requested by 25% (46/184) of apps. Finally, personal health information, other than medication name, was requested by 89.1% (164/184) of apps. Only 34.2% (63/184) of apps had a privacy policy in place. Most free medication apps offer very limited authentication and privacy protocols. As a result, the onus currently falls on patients to input information in these apps selectively and to be aware of the potential privacy issues. Until more secure systems are built, health care practitioners cannot fully support patients wanting to use such apps.


[Molecular genetic study of a family featuring cardiac conduction block].
OBJECTIVE To explore the genetic mechanism for a family affected with cardiac conduction block. METHODS Affected family members were screened for potential mutations of known candidate genes. As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation was analyzed using bioinformatics software. RESULTS Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family. Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site is highly conserved and becomes pathogenic with the mutation. CONCLUSION The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.


The Efficacy of Levobupivacaine Hydrochloride-Dexamethasone Infiltration for Post-Tonsillectomy Pain in Adults.
The aim of the study is to evaluate the efficacy of peritonsillar infiltration of a levobupivacaine hydrochloride and dexamethasone combination for post-tonsillectomy pain in adult patients. A total of 40 patients were included in this double-blind, randomized, and placebo-controlled study. The patients were equally randomized into 2 groups by means of sealed envelopes. The study group (SG) received peritonsillar levobupivacaine hydrochloride and dexamethasone infiltration and the control group (CG) received peritonsillar saline infiltration. Pain scores at the second, fourth, eighth, 12th, 16th, and 24th hours and the second to seventh days after operation were recorded by the patients in each group using a visual analog scale. Duration of surgery and the total amount of blood loss during the surgery were also recorded for each patient. All pain scores in the SG were lower than those in the CG; however, the difference was significant at the second, 12th, and 16th hours, and the second and third day (P < 0.05). Postoperative morbidity parameters, including otalgia, nausea, vomiting, fever, halitosis, and bleeding were similar between the 2 groups. Total amount of analgesic consumption in the SG was significantly lower than in the CG on each day of the week after tonsillectomy. Peritonsillar infiltration of a levobupivacaine hydrochloride and dexamethasone combination may provide pain reduction and decrease analgesic consumption in the postoperative period after adult tonsillectomy.