[Updated human hematopoietic stem cell findings: purification of human hematopoietic stem cells and elucidation of their hierarchy].
Hematopoietic stem cell (HSC) biology is a current topic of interest having significant implications for clinical HSC transplantation and basic HSC research. It was long believed that the most primitive HSCs in mammals, including those in mice and humans, were CD34 antigen-positive (CD34+) cells. However, Nakauchi et al. reported that murine long-term lymphohematopoietic reconstituting HSCs were lineage marker-negative (Lin-) c-kit+Sca-1+CD34-low/negative (CD34low/-), known as CD34low/-KSL cells. We have previously identified very primitive human cord blood (CB) -derived CD34-negative (CD34-) severe combined immunodeficiency (SCID) -repopulating cells (SRCs) utilizing an intra-bone marrow injection method and have proposed a new concept that CD34-SRCs (HSCs) reside at the apex of human HSC hierarchy. Recently, we developed an ultra-high-resolution purification method using the two positive/enrichment markers CD133 and GPI-80 and succeeded in purifying CD34+/-HSCs on a single-cell level. On the basis of these data, we propose a revised roadmap for the commitment of human CD34-HSCs. This review updates the concept of the stem cell nature of human CB-derived primitive CD34+/-HSCs.


[Seminal duct abnormalities in cryptorchism: our experience with 334 cases].
Undescended testis is one of the most common anomalies in pediatric age; despite numerous theories offered to explain its etiology, the true mechanism of the anomaly seems not to have been fully elucidated. The purpose of this prospective study was to investigate the incidence of epididymal abnormalities in undescended testes, the potential role of these anomalies in testicular descent and in incidental infertility. All patients were submitted to orchidopexy during which the complete anatomical situation of the epididymis and vas deferens was detected. In a group of 334 testes the incidence of congenital defects was 68%. The severity of these abnormalities appeared to be strictly correlated to the level of undescended testis. The incidence was 85% when the testis was in the abdomen, 82% when in the inguinal canal, 63% when next to the external inguinal ring and 53% when the testis was ectopic. The epididymal detachment at the head was the most common anomaly (113 cases), followed by extended epididymis (91 cases) and by total detachment of epididymis from the testis (70 cases).


[Surgical technique for extravesical vesicoureteral neoimplantation].
The uneven relationship between length and diameter of the intramural ureter is essential for the development of vesicoureteral reflux (VUR). Surgical treatment should reconstruct that relationship. Several surgical techniques have been described to achieve this objective. After more than 30 years of experience, in our hands the Lich-Gregoir extra vesicoureteral reimplantation technique shows excellent results. We describe the technique step-by-step, emphasizing the modifications introduced, also in its laparoscopic version. The Lich-Gregoir extravesical ureteral reimplantation technique is completely described, reinforcing those technical details allowing the achievement of better results. We comment on the technical variations in the laparoscopic version. We also perform a retrospective review of the clinical records and imaging tests in patients who underwent vesicoureteral reimplantation in the period between 1974-2006 in the Hospital de Niños Dr. Exequiel Gonzalez Cortés. patients with primary VUR in which Lich-Gregoir extravesical ureteral reimplantation technique was performed. Secondary de VUR was excluded. We registered age, gender, radiological grade, bilateralism, surgical time, and development of complications such as persistent reflux, contralateral reflux, postoperative urinary tract infection, urinary retention, postoperative obstruction, reoperation, the degree of renal insufficiency, and long-term followup. Over the 33 years of the study period there were 267 patients with primary VUR who required surgery. 379 ureters were reimplanted in an extravesical fashion, 112 (42%) corresponded to bilateral VUR. Mean age at the time of surgery was 4 years (from three months to 16 years); 156 patients (58%) were girls and 111 boys (42%). All patients presented primary VUR, and 63% of them were high grade (grades IV-V). All ureters were reimplanted without modelling in a mean surgical time of 62 minutes for the open technique. After a mean follow-up of two years (2 months-5.5 yr.) 7% of the patients have presented complications. Our reoperation rate is 1.3%. There was not any postoperative urinary retention. Our success rate for VUR resolution with this technique is 98.5%. Based on the results the the authors think that extravesical ureteral reimplantation following the Lich-Gregoir technique is safe, simple, technically reproducible, efficient, and with a low morbidity to resolve primary unilateral and bilateral primary VUR.


Changes in the regulation of iodine crystals and chemical mixtures containing over 2.2 percent iodine. Final rule.
This rulemaking changes the regulation of the listed chemical iodine under the chemical regulatory provisions of the Controlled Substances Act (CSA). The Drug Enforcement Administration (DEA) believes that this action is necessary to remove deficiencies in the existing regulatory controls, which have been exploited by drug traffickers who divert iodine (in the form of iodine crystals and iodine tincture) for the illicit production of methamphetamine in clandestine drug laboratories. This rulemaking moves iodine from List II to List I; reduces the iodine threshold from 0.4 kilograms to zero kilograms; adds import and export regulatory controls; and controls chemical mixtures containing greater than 2.2 percent iodine. This rulemaking establishes regulatory controls that will apply to iodine crystals and iodine chemical mixtures that contain greater than 2.2 percent iodine. This regulation therefore controls iodine crystals and strong iodine tinctures/solutions (e.g., 7 percent iodine) that do not have common household uses and instead have limited application in livestock, horses, and for disinfection of equipment. Household products such as 2 percent iodine tincture/solution and household disinfectants containing iodine complexes will not be adversely impacted by this regulation. Additionally, the final rule exempts transactions of up to one-fluid-ounce (30 ml) of Lugol's Solution. Persons handling regulated iodine materials are required to register with DEA, are subject to the import/export notification requirements of the CSA, and are required to maintain records of all regulated transactions involving iodine regardless of size.


Topological structure and the H index in complex networks.
The generalized H(n) Hirsch index of order n has been recently introduced and shown to interpolate between the degree and the K-core centrality in networks. We provide a detailed analytic characterization of the properties of sets of nodes having the same H(n), within the annealed network approximation. The connection between the Hirsch indices and the degree is highlighted. Numerical tests in synthetic uncorrelated networks and real-world correlated ones validate the findings. We also test the use of the Hirsch index for the identification of influential spreaders in networks, finding that it is in general outperformed by the recently introduced nonbacktracking centrality.


The Brussels Statement on the Future Needs for Caries Epidemiology and Surveillance in Europe.
Following debate and discussion prompted by a focussed, day long pre-ORCA Symposium in July 2015, the Alliance for a Cavity-Free Future Pan-European Chapter, the Platform for Better Oral Health in Europe, and the European Association of Dental Public Health have agreed this statement on the future needs for caries epidemiology and surveillance in Europe. Each organisation agreed to support the planned publication of the Statement, and will make it available on their Organisation's websites and strive to implement its recommendations.


Nanosecond pulse electric field activation of platelet-rich plasma reduces myocardial infarct size and improves left ventricular mechanical function in the rabbit heart.
In the current study, we used the novel, nonchemical method of nanosecond pulsed electric fields (nsPEF) to investigate the efficiency of a protocol involving the in vivo treatment of the ischemic and reperfused heart and heart cells in culture with platelet-rich plasma (PRP). Associated with the restoration of blood flow to the ischemic tissue is a phenomenon referred to as "ischemic reperfusion injury." Clinically a type of reperfusion injury occurs during coronary bypass surgery once blood perfusion to the heart is restarted. Although the restoration of oxygen to ischemic myocardial cells is critical for tissue survival, reperfusion causes myocardial oxidative stress, attributable in part to the increased production of reactive oxygen species (ROS). Enhanced ROS production is associated with mitochondrial damage. Adult female New Zealand white rabbits were anesthetized and a left thoracotomy performed to expose the heart. The distal segment of the left anterior descending coronary artery was occluded for 15 minutes and then released so reperfusion of the tissue could occur. PRP (.21 mg/heart) or saline was injected into the ischemic area of the myocardium. Mechanical function of the left ventricle was analyzed using a Millar catheter attached to a Micro-Med Analysis System. H9c2 cells in culture were treated with 1 mL of nsPEF activated PRP (1.05 mg/flask) for 24 hours before analysis for ROS production or mitochondrial depolarization damage). The left ventricle contracted and relaxed faster and infarct size was reduced in hearts treated with PRP compared with saline. ROS production and mitochondrial depolarization were reduced in H9c2 cells treated with PRP and stimulated with hydrogen peroxide. These results provide evidence that nsPEFs can successfully be used to prepare PRP and that the PRP is functional in heart protection possibly by reducing ROS generation and stabilizing the mitochondria of the ischemic/reperfused heart.


Genetic and environmental influences on serum levels of human C4.
In a family study, levels of the C4 component of complement measured in 195 individuals show a continuous normal distribution. There is a slight but significant age effect, especially in females. Heritability is estimated at 62%. The effect of environment, however, remains substantial, and it is suggested that at some time during development the mechanism controlling the C4 levels establishes a general steady-state level whose effects remain after the divergence of sib environments with the approach of adulthood.


X-ray crystal structure of the opioid ligand naltrexonazine.
The anti-anti isomer of naltrexonazine (1) was synthesized, and its configuration was confirmed by X-ray crystallography. The syn-anti isomer is readily converted to 1 under acidic conditions. The apparent equal receptor binding of 1 and syn-anti isomer indicates that isomerization of the azine moiety may take place under the conditions of biological evaluation. Two possible explanations for wash-resistant binding of 1 to opioid receptors are presented. The first possibility involves a noncovalent interaction of the ligand with the opioid receptor, and the second considers covalent binding by a receptor-based sulfhydryl group.


Changes in cardiac output, rhythm regularity, and symptom severity after electrical cardioversion of atrial fibrillation.
Symptoms in atrial fibrillation (AF) range from none to disabling. The physiological correlates of AF symptoms are not well characterized. This study investigated the association between physiological parameters and symptom severity before and after electrical cardioversion (EC) of AF. We studied 44 patients with persistent AF (age 66.2 ± 7.9 years, 16% females) 4 ± 2 days before and 5 ± 2 days after EC. Physiological parameters included cardiac output (CO; non-invasive inert gas rebreathing), heart rate (HR), RR variability and resting and ambulatory blood pressure (BP). Symptoms and quality of life (QoL) were assessed by the modified European Heart Rhythm Association score (mEHRA), the Atrial Fibrillation Effect on Quality of Life (AFEQT) and the Symptom Checklist for frequency and severity of symptoms (SCL). 28 of 44 patients were still in sinus rhythm (SR) at post EC evaluation. Those in SR had a decreased HR (-15.4 ± 13.1 bpm, p < 0.001), and an increased CO (+0.8 ± 0.7 L/min, p < 0.001) as compared to those with recurrent AF. Changes in CO after EC correlated with symptom improvement as scored by AFEQT (r = 0.36; p < 0.05), AFEQT symptoms subscore (r = 0.46; p < 0.01), SCL for frequency (r = 0.62; p < 0.01) and severity (r = 0.33; p < 0.05) of symptoms, and the mEHRA score (r = 0.50; p < 0.01). A decrease in RR variability showed similar correlations with these measures of symptom improvement. Improvements in symptoms and quality of life experienced by patients after electrical conversion of atrial fibrillation are correlated with an increase in CO and a decreased RR variability.


Effect of Interferon-Free Regimens on Disparities in Hepatitis C Treatment of US Veterans.
To determine whether implementation of interferon-free treatment for hepatitis C virus (HCV) reached groups less likely to benefit from earlier therapies, including patients with genotype 1 virus or contraindications to interferon treatment, and groups that faced treatment disparities: African Americans, patients with HIV co-infection, and those with drug use disorder. Electronic medical records of the US Veterans Health Administration (VHA) were used to characterize patients with chronic HCV infection and the treatments they received. Initiation of treatment in 206,544 patients with chronic HCV characterized by viral genotype, demographic characteristics, and comorbid medical and mental illness was studied using a competing events Cox regression over 6 years. With the advent of interferon-free regimens, the proportion treated increased from 2.4% in 2010 to 18.1% in 2015, an absolute increase of 15.7%. Patients with genotype 1 virus, poor response to previous treatment, and liver disease had the greatest increase. Large absolute increases in the proportion treated were observed in patients with HIV co-infection (18.6%), alcohol use disorder (11.9%), and drug use disorder (12.6%) and in African American (13.7%) and Hispanic (13.5%) patients, groups that were less likely to receive interferon-containing treatment. The VHA spent $962 million on interferon-free treatments in 2015, 1.5% of its operating budget. The proportion of patients with HCV treated in VHA increased sevenfold. The VHA was successful in implementing interferon treatment in previously undertreated populations, and this may become the community standard of care.


The voltage-gated calcium channel functions as the molecular switch of synaptic transmission.
Transmitter release is a fast Ca(2+)-dependent process triggered in response to membrane depolarization. It involves two major calcium-binding proteins, the voltage-gated calcium channel (VGCC) and the vesicular protein synaptotagmin (syt1). Ca(2+) binding triggers transmitter release with a time response of conformational changes that are too fast to be accounted for by Ca(2+) binding to syt1. In contrast, conformation-triggered release, which engages Ca(2+) binding to VGCC, better accounts for the fast rate of the release process. Here, we summarize findings obtained from heterologous expression systems, neuroendocrine cells, and reconstituted systems, which reveal the molecular mechanism by which Ca(2+) binding to VGCC triggers exocytosis prior to Ca(2+) entry into the cell. This review highlights the molecular aspects of an intramembrane signaling mechanism in which a signal is propagated from the channel transmembrane (TM) domain to the TM domain of syntaxin 1A to trigger transmitter release. It discusses fundamental problems of triggering transmitter release by syt1 and suggests a classification of docked vesicles that might explain synchronous transmitter release, spontaneous release, and facilitation of transmitter release.


Mechanism of versatile catalytic activities of quaternary CuZnFeS nanocrystals designed by a rapid synthesis route.
Quaternary alloyed nanocrystals (NCs) composed of earth abundant, environment friendly elements are of interest for energy-harvesting applications. These complex NCs are useful as catalysts for the degradation of multiple refractory organic pollutants as well as nitro-organic reduction at a rapid rate. Here, a remarkably fast (∼30 s) and facile synthesis of crystalline quaternary chalcopyrite copper-zinc-iron-sulfide (CZIS) NCs is reported. These NCs show excellent catalytic properties by degrading a number of refractory organic dyes and converting nitro-compounds at a rapid rate. The valence and conduction band information of the newly designed NCs are extracted using scanning tunneling spectroscopy and ultraviolet photoelectron spectroscopy, which reveal energy levels suitable for performing redox chemistry by generating reactive radicals establishing NCs as efficient catalyst with multiple uses. Rapid synthesis of high quality phase-controlled CZIS NCs with robust catalytic activities could be useful for organic waste treatment.


Online use statistics.
Online use statistics can provide libraries with a tool to be used when developing an online collection of resources. Statistics can provide information on overall use of a collection, individual print and electronic journal use, and collection use by specific user populations. They can also be used to determine the number of user licenses to purchase. This paper focuses on the issue of use statistics made available for one collection of online resources.


Effects of different intra canal medicaments on the push out bond strength of endodontic sealers.
One of the essential properties of the root canal sealers is the adhesion to root canal dentin and their higher bond strength decreases the microleakage. The aim of the present study was to compare the effect of Different Intracanal medicaments on the push out bond strength of AH26 and MTA Fillapex sealers. A total of 104 one-rooted extracted human teeth were divided into 4 (n=26) experimental groups. After the cleaning and shaping, the root canals were filled with Ca(OH)2, triantibiotic paste (TAP), Metapex or 2% chlorhexidine gel for two weeks. Then, intracanal medicaments were rinsed away and the samples in the sub-groups were obturated with gutta-percha and AH26 or MTA Fillapex sealers. After two weeks incubation, 2-mm-thick middle section of each root was then subjected to push-out testing. Data were analyzed with two-way ANOVA and LSD test. With all the intracanal medicaments, the overall mean of bond strength values were significantly higher with AH26 compared to MTA Fillapex (p<0.05). With the use of MTA Fillapex the maximum and minimum means of bond strength values were recorded with CHX and Metapex and for AH26 were recorded with Ca(OH)2 and chlorhexidine, respectively. The bond strengths of sealers to dentin are under the influence of pre-treatment with intracanal medicaments. Under the limitations of the present study, the effect of TAP on the bond strength of endodontic sealers was not negative. Key words:AH26, medicament, MTA Fillapex, push-out bond.


Custom neck orthosis in combination with onabotulinumtoxinA for the treatment of refractory congenital muscular torticollis: A case report.
This case report examines the use of a custom neck orthosis following onabotulinumtoxinA (BoNT-A) injections for the treatment of congenital muscular torticollis (CMT) that has not been responsive to conservative treatment or previous injections. The patient was fitted for a custom neck orthosis following BoNT-A injections for refractory CMT. Clinical outcomes were evaluated with head tilt, cervical rotation, and neck passive range of motion (PROM) measurements. Parental reports of patient tolerance of the orthosis and family satisfaction of results were obtained through survey. With use of the orthosis following BoNT-A injections, the patient's head tilt improved from 45° to an intermittent tilt of 10° and neck PROM to the left improved from 70° to 90°. He wore the neck orthosis for 8 to 10 hours per day for 3 months, experienced no major complications, and tolerated it well. On follow-up survey, the family reported satisfaction with the results. This case provides evidence that a custom neck orthosis after BoNT-A injection may be an effective treatment of refractory CMT before or replacing surgical intervention.


Diabetes Research and Resource Sharing During the COVID-19 Pandemic: A Systematic Review and Experience from an Academic/Non-Profit Resource Website.
The magnitude of the response of the diabetes professional community to the COVID-19 pandemic is not known. We aimed to examine diabetes technology research trends and resources offered by professional organizations during this period. We explored patterns of the response from the professional diabetes community to the pandemic by (1) systematically searching for articles related to diabetes, COVID-19, and diabetes technologies; (2) examining publication trends of research protocols (clinicaltrials.gov) and preprints (medRxiv); and (3) reviewing online resources from professional organizations including our website (COVIDinDiabetes.org; an Emory University-Diabetes Technology Society collaboration). We identified 492 articles published between December 2019 and December 2022 meeting our inclusion criteria. Telemedicine and continuous glucose monitoring were the most common reported technologies from most parts of the world. The largest number of preprint articles was published in 2020, with a decline in 2021 and 2022. The number of research protocols related to COVID-19 was the highest in 2020 and declined in 2021 and 2022. Resources from organizations included protocols adapted to treat patients with diabetes and COVID-19, training programs, emergency preparedness, and literature on diabetes and COVID-19. On our website (COVIDinDiabetes.org), there were 12 236 visits and 18 149 pageviews, with 1.6 actions per visits, with most visits coming from North America (N = 7233, 54.2%), South America (N = 2663, 21.8%), and Europe (N = 1219). We conclude that the COVID-19 pandemic promoted unprecedented global research productivity related to diabetes and COVID-19 and that the transition to the use of technology resources has been evident during this period.


Engaging individuals recently released from prison into primary care: a randomized trial.
Individuals released from prison have high rates of chronic conditions but minimal engagement in primary care. We compared 2 interventions designed to improve primary care engagement and reduce acute care utilization: Transitions Clinic, a primary care-based care management program with a community health worker, versus expedited primary care. We performed a randomized controlled trial from 2007 to 2009 among 200 recently released prisoners who had a chronic medical condition or were older than 50 years. We abstracted 12-month outcomes from an electronic repository available from the safety-net health care system. Main outcomes were (1) primary care utilization (2 or more visits to the assigned primary care clinic) and (2) emergency department (ED) utilization (the proportion of participants making any ED visit). Both groups had similar rates of primary care utilization (37.7% vs 47.1%; P = .18). Transitions Clinic participants had lower rates of ED utilization (25.5% vs 39.2%; P = .04). Chronically ill patients leaving prison will engage in primary care if provided early access. The addition of a primary care-based care management program tailored for returning prisoners reduces ED utilization over expedited primary care.


Cytokines and VEGF induction in orthodontic movement in animal models.
Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor.


Influence of the large grid size used in a multimedia mass balance model (POPsME) on the exposure assessment of polychlorinated dibenzo-p-dioxins and dibenzofurans.
A multimedia mass balance model (MMM), POPsME, was evaluated for its performance to assess the fate and transport of 2,3,7,8-substituted PCDD/Fs in Seoul and a neighboring area (150 km x 150 km) in Korea. As part of the evaluation, the effects of the grid size with the homogeneous mixing assumption were estimated on the sign and magnitude of the prediction bias. The prediction compared with the monitoring data generally within 1 order of magnitude. In the presence of a concentration gradient within individual cells of 30 km x 30 km,the prediction bias for air and soil tended to increase with the distance from the sources. It was observed that the ratio of the predicted to the measured values could vary more than 4 times with the location of the monitoring site. Use of the large grid size in POPsME (and perhaps other MMMs) resulted in overpredictions for a major portion of the model domain at the cost of underprediction for limited areas nearthe sources. Beyond the source areas, a substantial contribution of the total prediction bias originated from the congeners with a large atmospheric loss rate and small TEF value. On a TEQ basis, therefore, the magnitude of the overpredictions could be significantly reduced as compared to that of the underprediction for the source areas.


Review article: controversy in the therapy of gastro-oesophageal reflux disease--long-term proton pump inhibition or laparoscopic anti-reflux surgery?
The treatment of gastro-oesophageal reflux disease is controversial. Whilst medical treatment is successful in patients with mild to moderate disease, the threshold of severity above which an operation should be contemplated remains a matter for debate. Laparoscopic anti-reflux surgery may be lowering this threshold, as this form of therapy provides several advantages over its open counterpart, but it is not without risk, and few long-term results are available. This article reviews treatment options for reflux disease and examines the relative position of current medical and surgical therapies.


Decreased level of endogenous secretory receptor for advanced glycation end-products in diabetes with concomitant hyperlipidemia.
Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an association of esRAGE and methylglyoxal-adducts serum level, as well as AGE-to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipidemia and macrovascular disease in history. In diabetes with concomitant hyperlipidemia esRAGE was significantly decreased compared to hyperlipidemia with normal glucose metabolism (0.306+/-0.2 vs. 0.367+/-0.1; p=0.019) or diabetes alone (0.306+/-0.2 vs. 0.404+/-0.1; p=0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipidemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was recognized as a high risk for vascular disease outcomes.


Ultrashort laser pulses and electromagnetic pulse generation in air and on dielectric surfaces.
Intense, ultrashort laser pulses propagating in the atmosphere have been observed to emit sub-THz electromagnetic pulses (EMPS). The purpose of this paper is to analyze EMP generation from the interaction of ultrashort laser pulses with air and with dielectric surfaces and to determine the efficiency of conversion of laser energy to EMP energy. In our self-consistent model the laser pulse partially ionizes the medium, forms a plasma filament, and through the ponderomotive forces associated with the laser pulse, drives plasma currents which are the source of the EMP. The propagating laser pulse evolves under the influence of diffraction, Kerr focusing, plasma defocusing, and energy depletion due to electron collisions and ionization. Collective effects and recombination processes are also included in the model. The duration of the EMP in air, at a fixed point, is found to be a few hundred femtoseconds, i.e., on the order of the laser pulse duration plus the electron collision time. For steady state laser pulse propagation the flux of EMP energy is nonradiative and axially directed. Radiative EMP energy is present only for nonsteady state or transient laser pulse propagation. The analysis also considers the generation of EMP on the surface of a dielectric on which an ultrashort laser pulse is incident. For typical laser parameters, the power and energy conversion efficiency from laser radiation to EMP radiation in both air and from dielectric surfaces is found to be extremely small, < 10(-8). Results of full-scale, self-consistent, numerical simulations of atmospheric and dielectric surface EMP generation are presented. A recent experiment on atmospheric EMP generation is also simulated.


[Electroacupuncture Intervention Improves Physical Power of Aged Rats with Low Testosterone by Reducing Chronic Inflammatory Response of Leydig Cells].
To assess the effect of electroacupuncture (EA) on chronic inflammatory response of Leydig cells in aged rats with low testosterone, so as to investigate its underlying mechanism of anti-male reproductive aging. Twenty-four 20 months old SD rats were randomly divided into EA, medication and aged control groups (n= 8 in each), and other 8 young SD rats (2 months of age) were used as the youth control group. EA (2 Hz/100 Hz, 1 mA) was applied to "Guanyuan"(CV 4) and bilate-ral "Shenshu"(BL 23) for 15 min, once daily for 8 weeks except the weekends. The medication group received abdominal subcutaneous injection of testosterone propionate (7 mg• kg-1• 3 d-1) for 8 weeks. The aged control group and the youth control group received subcutaneous injection of 0.9% normal saline, with the same dose and same treatment frequency as those of the medication group. The rats' physical power was assessed according to the exhausted swimming duration, and the levels of serum total testosterone (TT) and free testosterone(FT) were determined by ELISA. The pathological changes of the testis tissue were detected by using H.E.staining, and the immunoactivity of cyclooxygenase-2 (COX-2) in Leydig cells was detected by immunohisto-chemistry. The expression levels of nuclear factor-κB p 65 (NF-κB p 65), COX-2, interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) proteins in the testis tissues were determined by Western blot. Before and after treatment, the exhaustive swimming duration and the levels of serum TT and FT in the aged control group were significantly lower than those of the youth control group (P < 0.01). After the treatment, the exhaustive swimming duration and serum TT and FT in the EA and medication groups were notably higher than those in the aged control group (P<0.01). HE staining showed that the incompleteness of basement membrane of spermatogenic tubules, reduction of spermatogenic cells and supporting cells and irregularity of Leydig cells in the testis tissue of the aged rats were relatively milder after EA intervention. Compared with the youth control group, the expression levels of NF-κB p 65 and COX-2, IL-1 β and TNF-α in the testicular tissue were significantly higher in the aged control group (P<0.01),while in compared with the aged control group, the expression levels of NF-κB p 65, COX-2, IL-1 β and TNF-α proteins were significantly down-regulated in the EA group (P<0.01). EA intervention can improve the physical power of the aged rats with low testosterone, which may be related to its effects in up-regulating TT and FT levels, and in reducing chronic inflammatory response in the testis tissue.


Molecular evolution, functional variation, and proposed nomenclature of the gene family that includes sphingomyelinase D in sicariid spider venoms.
The venom enzyme sphingomyelinase D (SMase D) in the spider family Sicariidae (brown or fiddleback spiders [Loxosceles] and six-eyed sand spiders [Sicarius]) causes dermonecrosis in mammals. SMase D is in a gene family with multiple venom-expressed members that vary in functional specificity. We analyze molecular evolution of this family and variation in SMase D activity among crude venoms using a data set that represents the phylogenetic breadth of Loxosceles and Sicarius. We isolated a total of 190 nonredundant nucleotide sequences encoding 168 nonredundant amino acid sequences of SMase D homologs from 21 species. Bayesian phylogenies support two major clades that we name alpha and beta, within which we define seven and three subclades, respectively. Sequences in the alpha clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have SMase D and dermonecrotic activity. The beta clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Gene duplications are frequent, consistent with a birth-and-death model, and there is evidence of purifying selection with episodic positive directional selection. Despite having venom-expressed SMase D homologs, venoms from New World Sicarius have reduced, or no, detectable SMase D activity, and Loxosceles in the Southern African spinulosa group have low SMase D activity. Sequence conservation mapping shows >98% conservation of proposed catalytic residues of the active site and around a plug motif at the opposite end of the TIM barrel, but alpha and beta clades differ in conservation of key residues surrounding the apparent substrate binding pocket. Based on these combined results, we propose an inclusive nomenclature for the gene family, renaming it SicTox, and discuss emerging patterns of functional diversification.


"Truman syndrome" induced by online education: A case report in adolescent-Onset psychosis.
Early-onset schizophrenia (EOS) is an important psychiatric problem characterized by the onset of psychotic symptoms before the age of 18 years. We present the case of a 14-year-old girl who had social anxiety symptoms in the premorbid period and whose psychotic symptoms increased with pandemic restrictions and online education. Our patient's distance from the peer environment and school as well as the fact that she used webcams and online education more frequently in her daily life were risk factors for EOS. In accordance with the case of Truman syndrome, she has delusions that her daily life is secretly filmed and that she is a "TV star." Anti-anxiety treatments were initiated during the pre-pandemic period. After a diagnosis of schizophrenia was made, antipsychotic treatment was initiated. A significant response was observed after paliperidone (extended release) treatment. Close follow-ups revealed decreased delusions and increased functionality. Further studies are required to elucidate whether Truman syndrome and social anxiety are different aspects of a similar spectrum. With increasing digitalization, the direction of psychiatric diseases, including EOS, and measures that can be taken for adolescent mental health in crisis, such as pandemics, should be discussed in future research.


Parental uveitis causes elevated hair loss in offspring of C57BL/6J mice.
Our previous study demonstrated that parental uveitis in a susceptible population can cause hair loss and increase the susceptibility to experimental autoimmune uveitis (EAU) in offspring. However, it is unclear whether parental uveitis affects the development of offspring in an EAU-moderate-susceptible population. Herein, moderate-susceptible C57BL/6J mice were immunized with inter-photoreceptor retinoid binding protein (IRBP) 651-670 to develop EAU and were kept together for mating. Gross examination and histopathological changes of the offspring gestated with parental uveitis were observed to evaluate the impact of parental uveitis on the development of the offspring. Differentially expressed genes (DEGs) were screened by RNA sequencing in the affected skin and eyeball of the offspring on postnatal day 27. Adult offspring were injected 75 μg IRBP651-670 to evaluate their susceptibility to EAU. Gross examination in the offspring revealed hair loss on postnatal days 11-31. Histopathological observation showed increased melanin granules and hair follicles of skin in the affected offspring with hair loss. Gene Ontology (GO) analysis in the skin revealed differential expression of genes involved in the mitotic cell cycle, response to endogenous stimulus, hair follicle development, and hair cycle. The DEGs in the skin were predominately associated with the cell cycle and peroxisome proliferator-activated receptor (PPAR) signaling pathway. The GO enrichment analysis in the eyeball showed differential expression of genes involved in the nervous system development, camera-type eye photoreceptor cell differentiation, neuron projection morphogenesis, axon development, and calcium-induced calcium release activity; enriched pathways included the circadian entrainment and glutamatergic synapses. No increased susceptibility to EAU in offspring gestated from parental remitting EAU was observed at a low-dose 75 μg IRBP induction. These results suggested that parental uveitis in a moderate-susceptible population could affect the skin development and DEG profiles of skin and eyeball related to the response to endogenous stimulus, the PPAR signaling pathway, and glutamatergic synapse, which provides the molecular evidence to explain the influence of parental uveitis on offspring development.


Maturing from embryonic to adult policy on stem cell therapeutics.
The National Institutes of Health (NIH) closure of the agency's Center for Regenerative Medicine (CRM), which focused on therapeutic development of induced pluripotent stem cells (iPS), was caused by the lack of progress in practical development of the iPSs for use in human therapies. As the NIH evaluates priorities in future stem cell therapeutic development, adult stem cell processes in the human body need to be prioritized for a number of key reasons, including (1) adult stem cells release many types of molecules that provide much of the therapeutic benefit of stem cells and (2) adult stem cells and somatic cells exist in a state of dynamic transition between different potency levels and can be naturally driven by the microenvironment to a state of pluripotency. Thus, the study and development of adult stems for therapeutic use can include naturally induced pluripotent stem cells (NiPSs) that lack the problematic genetic and epigenetic reprogramming errors found in iPSs.


Spontaneous creation of macroscopic flow and metachronal waves in an array of cilia.
Cells carrying cilia on their surface show many striking features: alignment of cilia in an array, two-phase asymmetric beating for each cilium, and existence of metachronal coordination with a constant phase difference between two adjacent cilia. We give simple theoretical arguments based on hydrodynamic coupling and an internal mechanism of the cilium derived from the behavior of a collection of molecular motors to account qualitatively for these cooperative features. Hydrodynamic interactions can lead to the alignment of an array of cilia. We study the effect of a transverse external flow and obtain a two-phase asymmetrical beating, faster along the flow and slower against the flow, proceeding around an average curved position. We show that an aligned array of cilia is able to spontaneously break the left-right symmetry and to create a global average flow. Metachronal coordination arises as a consequence of the internal mechanism of the cilia and their hydrodynamic couplings, with a wavelength comparable to that found in experiments. It allows the cilia to start beating at a lower adenosine-triphosphate threshold and at a higher frequency than for a single cilium. It also leads to a rather stationary flow, which might be its major advantage.


Cardiovascular toxic effects of targeted cancer therapy.
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established. Vascular endothelial growth factor pathway inhibitors decrease vascular tone, leading to hypertension. After drug initiation, the early detection and aggressive pharmacological management of hypertension are necessary to avoid severe complications. Cardiovascular safety is an emerging challenge in patients treated with newer generations of BCR-ABL inhibitors. Although rare, dasatinib-induced pulmonary hypertension is potentially fatal. Vascular events including cardiac and cerebral ischemic events and peripheral arterial occlusive disease have emerged as a new type of toxicity in patients treated with ponatinib and nilotinib. Thus, a wide variety of cardiovascular toxicities have been observed in patients treated with targeted drugs and have become a critically important topic of discussion for the practicing oncologist and cardiologists. Awareness of the potential side effects, recognition of signs and symptoms, and the establishment of therapeutic strategies are all crucial to providing quality patient care.


Dysmenorrhea.
Dysmenorrhea is one of the most common gynecologic complaints of young women, affecting approximately half of menstruating females. Although most patients have primary dysmenorrhea, which although creating much discomfort does not lead to significant physical problems, it is very important to rule out secondary dysmenorrhea to prevent problems with health and fertility. Primary dysmenorrhea is seen only in ovulatory cycles, usually developing within 6 to 12 months of menarche and is characterized by lower midabdominal colicky pain that may radiate to the back and upper thighs. The pain of primary dysmenorrhea starts with the onset of menstrual flow or a few hours following onset and may last for a few hours up to 2 days. The pain of secondary dysmenorrhea usually begins several days before the start of menstrual flow and may be present during much of the menstrual cycle. Pain that occurs with the first menses or after the age of 25 or is associated with anovulatory cycles is more likely to be secondary dysmenorrhea. The causes of secondary dysmenorrhea, such as endometriosis, adenomyosis, complications of intrauterine devices, and congenital abnormalities, will often be associated with abnormalities noted on pelvic examination, and whenever dysmenorrheic patients have any abnormalities, further evaluation is necessary.


Agaribacter flavus sp. nov., isolated from red algae.
A Gram-stain-negative, non-motile, aerobic, curved-rod bacterium, designated as strain 2p52T, was isolated from the marine algae Gracilaria blodgettii collected off the coast of Lingshui county, in Hainan province, China. Strain 2p52T grew at 15-42 °C (optimally at 30-33 °C), at pH 6.0-10.0 (7.5-8.0) and in the presence of 1.0-8.0 % (w/v) NaCl (2.0-3.0 %). The most closely related species was Agaribacter marinus (96.5 % 16S rRNA gene sequence similarity). Phylogenetic analysis based on the sequence of the 16S rRNA gene revealed that strain 2p52T belonged to the genus Agaribacter. The novel strain contained phophatidylethanolamine and phosphatidylglycerol as the major polar lipids. The predominant isoprenoid quinine was Q-8, and the DNA G+C content was 43.2 mol%. The major cellular fatty acids were C16 : 1ω7c and/or iso-C15 : 0 2-OH, C16 : 0, and C18 : 1ω7c. The phenotypic and systematic comparative analyses indicated that the isolate is representative of a novel species of the genus Agaribacter, and the name Agaribacter flavus sp. nov. is proposed. The type strain is 2p52T (=KCTC 52473T=MCCC 1H00151T).


Remote and cross-stack measurement of stack gas concentrations using a mobile FT-IR system.
The EPA remote optical sensing of emissions (ROSE) system consists of a commercial FT-IR system and associated components installed in a van. The ROSE system was recently used to make both single-ended measurements of the emission spectra of the gas plume exiting a cement plant smokestack and also cross-stack measurements of the absorption spectra of the stack gases. The stack gases were also analyzed by conventional extractive techniques. The species NO, CO, CO(2), and NH(3) were observed in emission and absorption at concentrations of the order of 400, 50, 120,000, and 10 ppm, respectively. The species HC1, H(2)CO, HF, and SO(2) (typical concentrations of 20, 6, 0.5, and 40 ppm, respectively) were observed in absorption. Stack plume temperatures determined from the emission spectra agreed with in-stack temperature measurements to within +/-10%; concentration measurements agreed to within about +/-20%. This paper discusses the measurement and calibration procedures and shows the spectral signatures for the various species observed in the emission and absorption measurements.


Mutant PCNA alleles are associated with cdc phenotypes and sensitivity to DNA damage in fission yeast.
Twenty-eight site-directed mutations were introduced into the fission yeast gene (pcn1+) that encodes proliferating cell nuclear antigen (PCNA) and their in vivo effects analyzed in a strain with a null pcn1 background. Mutants defective in enhancing processivity of DNA polymerase delta have previously been identified. In this study, we assessed all of the mutants for their sensitivities to temperature, hydroxyurea, UV irradiation and methyl methanesulfonate (MMS), and specific mutants were also tested for sensitivity to gamma irradiation. One cold-sensitive allele, pcn1-3, was characterized in detail. This mutant had a recessive cold-sensitive cdc phenotype and showed sensitivity to hydroxyurea, UV, and gamma irradiation. At the non-permissive temperature pcn1-3 protein was able to form homotrimers in solution and showed increased stimulation of both synthetic activity and processivity of DNA polymerase delta relative to the wild-type Pcn1+ protein. Epistasis analyses indicated that pcn1-3 is defective in the repair pathway involving rad2+ but not defective in the classical nucleotide excision repair pathway involving rad13+. Furthermore, pcn1-3 is either synthetically or conditionally lethal in null checkpoint rad backgrounds and displays a mitotic catastrophe phenotype in these backgrounds. A model for how pcn1-3 defects may affect DNA repair and replication is presented.


Automated staining of bone marrow and peripheral blood by a modified Wright's technic.
A Wright's stain provided for the automatic staining of routine peripheral blood smears is recommended for use in the Hematrak instrument. This stain at a pH range of 6.5-7.15 shows a dull and bluish coloration of erythrocytes, a finding not readily acceptable for visual microscopy of cell morphology or for photomicroscopy. In order to achieve a desirable erythrocyte color, but still retain the staining intensity of leukocyte chromatin, a two-stage staining method was devised. This involves the use of a mixture of Eosin y and a buffered Wright's solution to secondarily stain Wright-stained smears. This modification of Wright's technic offers a stain of high quality for both bone marrow and peripheral blood films with the advantage of little or no day-to-day variability. In comparison to the frequently advocated dual staining methods, it is cheap and easy to automate. The total staining time for peripheral blood films is about 12 minutes and about 20 minutes for bone marrow smears.


Intracranial hemorrhage in COVID-19 patients during extracorporeal membrane oxygenation for acute respiratory failure: a nationwide register study report.
In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.


Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma.
Clear cell, mesenchymal, and dedifferentiated chondrosarcoma are rare, cartilaginous tumors with limited treatment options other than surgery. Conventional chondrosarcomas have been extensively studied at the genetic level, but for rare chondrosarcoma subtypes, this is merely restricted to case reports. Information on the genetics of rare chondrosarcomas may provide insight into the etiology of these specific disease subtypes and possible alternative treatment strategies. Therefore, the aim of this study was to genetically characterize this subset of rare tumors. Using array CGH, we gathered genomic information of 30 rare cartilaginous tumors. In addition, we constructed tissue microarrays with 2 mm cores of 23 clear cell, 23 mesenchymal, and 45 dedifferentiated chondrosarcomas, in triplicate. Using immunohistochemistry, we investigated expression of R132H IDH1, and p53 and retinoblastoma pathways. Results were verified and further investigated with a methylation assay and MLPA for CDKN2A/p16, and IDH1/2, and TP53 mutation analysis. Array-CGH showed numerous genomic alterations in all subtypes. However, only a limited number of recurrent alterations were detected, none of which seemed to be associated with the subtypes. The IDH1/2, p53, and retinoblastoma pathways were affected in 0, 9, and 95% of clear cell chondrosarcomas, in 0, 39, and 70% in mesenchymal chondrosarcomas, and in 50, 59, and 85% of dedifferentiated chondrosarcomas, respectively. Our results suggest an important role for the retinoblastoma pathway in all three rare chondrosarcoma subtypes investigated.


A discrete Cu2(Pd-bpy)2L2 heterometallic compound with superoxide dismutase enzyme like activity.
A discrete heterometallic compound consisting of Cu(ii) and Pd(ii) units which mimicks Bovine Cu-ZnSOD has been synthesised in aqueous medium. Its superoxide radical ion scavenging activity is higher than the SOD activity of Scylla serrata tissues and comparable with the liver of Gallus domesticus.


Kinetics of the gas phase reaction CH3 + HO2.
Reaction of methyl radicals with hydroperoxy radicals, CH3 + HO2 → products (1) was studied using pulsed laser photolysis coupled to transient UV-vis absorption spectroscopy at 295 K and 1 bar (He). Photolysis of N2O/H2O2/CH4/H2O/He mixtures at 193.3 nm (ArF excimer laser) was used to simultaneously produce methyl radicals and hydroperoxy radicals in reactions of electronically excited oxygen atoms O((1)D) with CH4 and OH radicals with H2O2, respectively. Temporal profiles of CH3 and HO2 were recorded via absorption at 216.4 and 224 nm. The absolute intensity of the photolysis light inside the reactor was determined by an accurate in situ actinometry based on the ozone formation in the presence of molecular oxygen. The measured rate constant of reaction 1 is k1 = (3.7 ± 1.8 × 10(-11) cm(3) molecule(-1) s(-1) (295 K, 1 bar, He).


Larva of Halesus nurag Malicky 1974 (Trichoptera: Limnephilidae) and diagnostic key for the limnephilid larvae of Sardinia.
This paper gives a description of the hitherto unknown larva of Halesus nurag Malicky 1974 (Trichoptera: Limnephilidae). Information on the morphology of the larva is given, and the most important diagnostic features are figured. In the context of the European Halesus species, the larva of H. nurag is morphologically close to H. appenninus Moretti Spinelli Batta 1979, H. digitatus (Schrank 1781), H. radiatus (Curtis 1834), and H. tessellatus (Rambur 1842). This new morphological dataset was used for providing a key to the Sardinian limnephilid larvae. In this context, H. nurag can be separated from the other Sardinian species with single-filament gills described so far by chaetotaxonomical characters, mandible morphology, and details of the lateral protuberance of abdominal segment I.


Fine structure of mammalian renal cilia.
Studies were carried out, using transmission electron microscopy, of the cilia of the nephrons of rat and human kidneys. Cilia were observed in the parietal layer of Bowman's capsule, in the proximal tubule, the distal tubule, including the macula densa, and the collecting duct. They had a number of characteristic features, including the presence of a centriole adjacent to the basal body, long, slender cross-striated rootlets, and a typically organized basal body. The shaft of the cilia differed from the typical 9 + 2 pattern of organization. Near the base of the cilia the pattern was 9 + 0. In the middle portion, one or more of the peripheral doublets had been displaced centrally to give an 8 + 1 or a 7 + 2 pattern, while towards the tip the pattern became more irregular and the doublets were reduced to single microtubules. We have hypothesized that these cilia may be vestigial. They may, if motile, have some minor stirring function, or they may play a sensory role, as has been postulated for similarly structured cilia in other sites.


The gut microbiome in the fight against obesity: The potential of dietary factors.
Obesity as a global public health burden has experienced a drastic growing trend recently. The management of obesity is challenging because of its complex etiology, and various factors are involved in its development, such as genetic and environmental factors. Different approaches are available to treat and/or manage obesity, including diet, physical activity, lifestyle changes, medications, and surgery. However, some of these approaches have inherent limitations and are closely associated with adverse effects. Therefore, probing into a novel/safe approach to treat and/or manage obesity is of fundamental importance. One such approach gaining renewed interest is the potential role of gut microbiota in obesity and its effectiveness in treating this condition. However, there is a dearth of comprehensive compilation of data on the potential role of the gut microbiome in obesity, particularly regarding dietary factors as a therapeutic approach. Therefore, this review aims to provide an updated overview of the role of gut microbiota in obesity, further highlighting the importance of dietary factors, particularly diet, prebiotics, and probiotics, as potential complementary and/or alternative therapeutic options. Moreover, the association of gut microbiota with obese or lean individuals has also been discussed.


Rh(III)-Catalyzed C8-Spiroannulation of 1-Aminonaphthalenes with Maleimides.
The rhodium(III)-catalyzed C8-spiroannulation of 1-aminonaphthalenes with maleimides is described herein. Initially formed C8-alkenylated 1-aminonaphthalenes can intercept nucleophilic 1-amino groups through the intramolecular aza-Michael reaction, resulting in the formation of spirofused tetracyclic frameworks. This protocol displayed a wide substrate scope and a broad functional group compatibility. The synthetic utility of this process is demonstrated by the gram-scale synthesis, late-stage modification, and synthetic transformations.


What's behind RN turnover?
Examine the results of a qualitative study designed to enhance your understanding of RNs' perceptions of the factors prompting them to leave employment in acute care settings.


[New approaches to the pathogenesis, clinic, and treatment of hepatic encephalopathy].
This review article presents new approaches to the assessment of key pathogenesis factors, clinical features, and treatment of hepatic encephalopathy (HE) associated with liver cirrhosis. Various clinical variants of the course of HE in patients with cirrhosis of the liver areconsidered, which are important for the choice of treatment and prevention of repeated relapses of HE. Analyzed the ammonia hypothesis of pathogenesis and associated hyperammonemia, which is the basis of most modern treatment methods. These data on the activation of the adaptive pathway for removing ammonia in the form of glutamine are used in the further study of drugs that enhance the clearance of ammonia. The possibility of reducing GABA-ergic tone due to the effect of the antagonist on the neurosteroid site in the GABA receptor complex is emphasized.


Cross-amplification and validation of SNPs conserved over 44 million years between seals and dogs.
High-density SNP arrays developed for humans and their companion species provide a rapid and convenient tool for generating SNP data in closely-related non-model organisms, but have not yet been widely applied to phylogenetically divergent taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur seal (Arctocephalus gazella) individuals. Despite seals and dogs having diverged around 44 million years ago, 33,324 out of 173,662 loci (19.2%) could be genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were validated using KASP genotyping assays, with the resulting genotypes being 100% concordant with those obtained from the high-density array. Two loci were also confirmed through in silico visualisation after mapping them to the fur seal transcriptome. Polymorphic SNPs were distributed broadly throughout the dog genome and did not differ significantly in proximity to genes from either monomorphic SNPs or those that failed to cross-amplify in seals. However, the nearest genes to polymorphic SNPs were significantly enriched for functional annotations relating to energy metabolism, suggesting a possible bias towards conserved regions of the genome.


Lipidomic characterization and localization of phospholipids in the human lung.
Lipids play a central role in lung physiology and pathology; however, a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed. The cells involved in lung host defense, including alveolar macrophages (AMs), bronchial epithelial cells (BECs), and alveolar type II cells (ATIIs), were isolated from human subjects and lipidomic analysis by LC-MS and LC-MS/MS was performed. Additionally, pieces of lung tissue from the same donors were analyzed by MALDI imaging MS in order to determine lipid localization in the tissue. The unique distribution of phospholipids in ATIIs, BECs, and AMs from human subjects was accomplished by subjecting the large number of identified phospholipid molecular species to univariant statistical analysis. Specific MALDI images were generated based on the univariant statistical analysis data to reveal the location of specific cell types within the human lung slice. While the complex composition and function of the lipidome in various disease states is currently poorly understood, this method could be useful for the characterization of lipid alterations in pulmonary disease and may aid in a better understanding of disease pathogenesis.


Comparison of the experimental intestinal anastomoses performed by different surgeons.
This study was designed to determine the effects of different surgeons on the experimental anastomosis studied in rats. Sixteen Wistar-albino rats were equally separated into two groups. The rats operated on by the first surgeon were coded Group 1 and operated on by the other surgeon were coded Group 2. Both surgeons were trained on the gastrointestinal surgery. The procedure of the study were standardized and dictated to the surgeons. Bursting pressure and tissue hydroxyproline content were determined as parameters of the anastomotic strength and healing on the seventh day postoperatively. The bursting pressures were measured with a digital manometer and anastomotic lines were removed to measure tissue hydroxyproline level. While hydroxyproline value in the first group was 105.60 +/- 9.43 microg/mg dry tissue, it was found to be 104.02 +/- 17.26 microg/mg dry tissue in the second group and this difference was not statistically significant (p=0.521). The bursting pressure was determined as 240.71 +/- 11.65 mmHg in the first group, 190.75 +/- 14.09 mmHg in the second group and the difference was statistically significant (p=0.002). The anastomotic resistances to intraluminal pressure were found statistically different whereas tissue hydroxyproline levels were normal between the groups. These results make us to consider mechanical differences occur related to the surgeons in the studies performed with the same technical detail.


Topologically-Enhanced Thermoelectric Properties in Bi2Te3-Based Compounds: Effects of Grain Size and Misorientation.
Topological insulators (TIs) and thermoelectric (TE) materials seem to belong to distinct physical realms; however, in practice, they both share common characteristics. Introducing concepts from TIs into TE materials to enhance their performance and achieve better understanding of electronic transport requires extensive research. Particularly, grain size, misorientation, and grain boundary (GB) character are of utmost importance to attain effective charge carrier transport in TE polycrystals; these factors, however, have not been thoroughly explored. Herein, we investigate the correlation between grain size, misorientation, and lattice strain in Bi2Te3 and its TI signature, aiming to improve its TE performance. We reveal an unusual behavior showing that electron mobility increases upon the increase of grain size, reaching at a maximum value of 495 cm2/V·s for an optimum grain size of 600 nm and most-frequent GB misorientation angle of 60° and then decreases with increasing grain size. It is also indicated that the combined effects of grain size reduction and point defects induce lattice strain in the Bi2Te3-matrix that is essential to trigger the TI contribution to TE transport. This trend is corroborated by first-principles calculations showing that compressive strains form multiple valleys in the valence band and opens the TI band gap. Such a combination of physical phenomena in a well-known TE material is unique and can promote our understanding of the nature of TE transport with implications for TE energy conversion.


Interplay between inflammatory bowel disease therapeutics and the gut microbiome reveals opportunities for novel treatment approaches.
Inflammatory bowel disease (IBD) is a complex heterogeneous disorder defined by recurring chronic inflammation of the gastrointestinal tract, attributed to a combination of factors including genetic susceptibility, altered immune response, a shift in microbial composition/microbial insults (infection/exposure), and environmental influences. Therapeutics generally used to treat IBD mainly focus on the immune response and include non-specific anti-inflammatory and immunosuppressive therapeutics and targeted therapeutics aimed at specific components of the immune system. Other therapies include exclusive enteral nutrition and emerging stem cell therapies. However, in recent years, scientists have begun to examine the interplay between these therapeutics and the gut microbiome, and we present this information here. Many of these therapeutics are associated with alterations to gut microbiome composition and functionality, often driving it toward a "healthier profile" and preclinical studies have revealed that such alterations can play an important role in therapeutic efficacy. The gut microbiome can also improve or hinder IBD therapeutic efficacy or generate undesirable metabolites. For certain IBD therapeutics, the microbiome composition, particularly before treatment, may serve as a biomarker of therapeutic efficacy. Utilising this information and manipulating the interactions between the gut microbiome and IBD therapeutics may enhance treatment outcomes in the future and bring about new opportunities for personalised, precision medicine.


[Parasitic appendicitis. Apropos of 4 cases of acute appendicitis].
The authors present 4 observations of acute appendicitis with the presence of parasites at the micropathological examination. To this end, they study the literature in order to try to show the frequency of parasitic appendicitis on the one hand and what it does on the other, which is still controversial in the physiopathological of appendicitis. According to the authors, an aetiology of parasitic involvement is evident in 1.9% to 25% cases of appendicitis. The most frequent intestinal parasites in this area are the pinworms (54.78%), the whipworms (13%) and the ascaris (9%).


Studies on heat inactivation of hepatitis A virus with special reference to shellfish. Part 1. Procedures for infection and recovery of virus from laboratory-maintained cockles.
The consumption of bi-valve molluscan shellfish has been associated with outbreaks of viral gastroenteritis and hepatitis A. Investigations were undertaken to determine the heat inactivation conditions necessary to render shellfish such as cockles safe for the consumer. Conditions for the laboratory maintenance of live cockles are described. In preliminary experiments either poliovirus (10(6) TCID50/ml seawater) or hepatitis A virus (HAV) (approx. 10(4) RFU/ml seawater) was introduced into the shellfish tank. Following 48 h filter feeding, virus was recovered from cockles using an adsorption-elution extraction procedure. Titres of virus recovered ranged from 10(4) to 10(5) TCID50/ml of shellfish extract for poliovirus and from 10(3) to 10(5) RFU/ml of shellfish extract for HAV. Active ingestion of the virus from the seawater was demonstrated by recovering virus from within cockle guts. To quantify recovered HAV, end-point dilutions and an adaptation of a radioimmunofocus assay (RIFA) were compared. The tests were of similar sensitivity but the RIFA has the advantage of being relatively rapid, shortening the time taken to complete an experiment by as much as 4 weeks.


[Radiation-induced esophageal carcinoma: report of 11 cases].
Radiation-induced oesophageal carcinoma can occur several years after mediastinal irradiation. The aim of this study was to report 11 cases of this rare entity with analysis of its diagnostic, therapeutic and prognostic special features. From 1983 to 2001, 10 female and one male patients, aged 47 to 76 years, were treated for an oesophageal squamous cell carcinoma which was diagnosed 5 to 25 years after mediastinal irradiation. This irradiation (30 to 78 Gy) was administered in 8 women for breast carcinoma and in other patients for lymphoma. Only one patient had alcoholic consumption and 2 were smokers. An oesophagectomy was performed whenever possible. All (but one) oesophageal tumors were symptomatic. Ten patients underwent an oesophagectomy, including 2 without thoracotomy. Postoperative course was uneventful in 6 cases, 3 patients developed transient respiratory failure and one patient died postoperatively. At late follow-up, 6 patients developed distant metastases (mainly hepatic and pulmonary). These metastases were associated with mediastinal recurrences in 2 cases. No isolated mediastinal recurrence occurred. Median survival was 13 months. Clinical presentation and surgical treatment of radiation-induced oesophageal carcinoma are similar to those of other oesophageal squamous cell carcinomas. After oesophagectomy, isolated mediastinal recurrences seem to be rarer than with other cancers. These cancers, which are almost all symptomatic, have a poor prognosis.


Glucose fatty acid interactions and the regulation of glucose disposal.
Glucose is essential for the energy metabolism of some cells and conservation of glucose is obligatory for survival during starvation. The principal site of this glucose conservation is the mitochondrial pyruvate dehydrogenase (PDH) complex, which is regulated by reversible phosphorylation (phosphorylation is inactivating). In cells in which glucose oxidation is switched off during starvation, fatty acids are used as fuel, and acetyl CoA and NADH formed by beta-oxidation promote phosphorylation of PDH complex by activation of PDH kinase. A longer-term mechanism further increases PDH kinase activity in response to cAMP and products of beta-oxidation of fatty acids. Coordinated inhibition of glycolytic flux mediated by effects of citrate on PFK1 and PFK2 in muscles and liver results in an associated inhibition of glucose uptake. Similar mechanisms lead to impaired glucose oxidation in diabetes.


The Influence of Obstetric Factors on the Occurrence of Pelvic Floor Dysfunction in Women in the Early Postpartum Period.
This study aimed to analyze the effect of obstetric factors on the development of pelvic floor dysfunction (PFD) in women in the early postpartum period. Clinical data of 300 women who were reviewed in our outpatient clinic from July 2016 to December 2019 in the postpartum period were retrospectively analyzed. The occurrence of pelvic organ prolapse (POP) and stress urinary incontinence (SUI) was assessed using the Pelvic Organ Prolapse Quantification System and International Consultation on Incontinence Questionnaire Short Form. Factors affecting the occurrence of PFD in women in the early postpartum period were analyzed using univariate and multifactorial logistic regression models. A total of 46 cases of POP (15.33%) and 82 of SUI (27.33%) occurred in 300 women at 6-8 weeks after birth. Unconditional logistic regression confirmed that age ≥35 years, vaginal delivery, BMI before delivery ≥ 25 kg/m2, perineal tear, protracted or prolonged second stage of labor, and fetal macrosomia were risk factors influencing the occurrence of POP (OR > 1, P < 0.05), whereas age ≥ 35 years, vaginal delivery, perineal tear, protracted or prolonged second stage of labor, fetal macrosomia, and SUI during pregnancy were risk factors influencing the occurrence of SUI (OR> 1, P< 0.05). Obstetric factors such as age, mode of delivery, perineal tear, protracted or prolonged second stage of labor, and fetal macrosomia may increase the risk of developing PFD in women in the early postpartum period; hence, these risk factors should be correctly identified and promptly addressed to prevent the development of PFD.


Spin trapping of precursors of thymine damage in X-irradiated DNA.
A spin-trapping method combined with ESR spectroscopy was utilized to obtain evidence for the presence of precursor radicals leading to damage in X-irradiated DNA. Two technical improvements were introduced to the conventional spin-trapping method to make possible its application to large molecules such as DNA: prior to X irradiation, sonolysis of aqueous DNA solution by 19.5-kHz ultrasound was made to get a highly concentrated DNA solution and to lower the viscosity of the solution; after precursor radicals in X-irradiated DNA were trapped by a spin-trapping reagent, the DNA was digested to oligonucleotides by DNase I to get an ESR spectrum with a well-resolved hyperfine structure. Thus, it was recognized that the ESR spectrum obtained after X irradiation of the aqueous solution containing DNA and the nitroso spin-trapping reagent 2-methyl-2-nitrosopropane consisted of at least three sets of signals in the DNA. Identification of free radicals was made by comparing the spectrum with that of thymidine, which was precisely examined by a spin-trapping method combining two kinds of spin traps (nitroso and nitrone compounds) with liquid chromatography. As a result, all the signals were identified as the spin adducts of radicals produced at the thymine base moiety of DNA. The 5-hydroxy-5,6-dihydrothymin-6-yl radical was identified as a precursor of 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol), the 6-hydroxy-5,6-dihydrothymin-5-yl radical as a precursor of 6-hydroxy-5,6-dihydrothymine, and the 5-methyleneuracil radical as a precursor of 5-(hydroxymethyl) uracil.


Cold Cas: reevaluating the occurrence of CRISPR/Cas systems in Mycobacteriaceae.
Bacterial CRISPR/Cas systems target foreign genetic elements such as phages and regulate gene expression by some pathogens, even in the host. The system is a marker for evolutionary history and has been used for inferences in Mycobacterium tuberculosis for 30 years. However, knowledge about mycobacterial CRISPR/Cas systems remains limited. It is believed that Type III-A Cas systems are exclusive to Mycobacterium canettii and the M. tuberculosis complex (MTBC) of organisms and that very few of the >200 diverse species of non-tuberculous mycobacteria (NTM) possess any CRISPR/Cas system. This study sought unreported CRISPR/Cas loci across NTM to better understand mycobacterial evolution, particularly in species phylogenetically near the MTBC. An analysis of available mycobacterial genomes revealed that Cas systems are widespread across Mycobacteriaceae and that some species contain multiple types. The phylogeny of Cas loci shows scattered presence in many NTM, with variation even within species, suggesting gains/losses of these loci occur frequently. Cas Type III-A systems were identified in pathogenic Mycobacterium heckeshornense and the geological environmental isolate Mycobacterium SM1. In summary, mycobacterial CRISPR/Cas systems are numerous, Type III-A systems are unreliable as markers for MTBC evolution, and mycobacterial horizontal gene transfer appears to be a frequent source of genetic variation.


Modeling extreme mass ratio inspirals within the effective-one-body approach.
We present the first models of extreme-mass-ratio inspirals within the effective-one-body (EOB) formalism, focusing on quasicircular orbits into nonrotating black holes. We show that the phase difference and (Newtonian-normalized) amplitude difference between analytical EOB and numerical Teukolsky-based gravitational waveforms can be reduced to less than or approximately 10{-1} rad and less than or approximately 2x10{-3}, respectively, after a 2-year evolution. The inclusion of post-Newtonian self-force terms in the EOB approach leads to a phase disagreement of approximately 6-27 rad after a 2-year evolution. Such inclusion could also allow for the EOB modeling of waveforms from intermediate-mass-ratio, quasicircular inspirals.


The homophone meaning generation test: psychometric properties and a method for estimating premorbid performance.
The Homophone Meaning Generation Test (HMGT; Warrington, 2000) is a new measure of verbal fluency that has been demonstrated to be sensitive to the presence of anterior lesions. In the present study we used the HMGT healthy standardization sample (N = 170) and demonstrate that scores on the HMGT do not differ significantly from a normal distribution and that the test has adequate reliability (alpha = .82). A table for obtaining confidence limits on an individual's score is presented. A regression equation for the estimation of premorbid HMGT performance was constructed using the National Adult Reading Test as the predictor variable. In a sample of 36 cases with anterior lesions estimated premorbid scores were significantly higher than obtained scores (p < .001). Premorbid ability acted to suppress group differences on the HMGT; the partial correlation between neurological status (healthy vs. anterior lesion) and HMGT performance controlling for premorbid ability (.53) was significantly higher than the raw correlation (.44). In addition, hierarchical discriminant function analysis demonstrated that the inclusion of premorbid ability improved classification over that achieved by HMGT scores alone. These results support both the underlying rationale and the clinical utility of controlling for premorbid performance when interpreting verbal fluency scores.


Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes.
This paper describes the synthesis of a series of organic liquid crystals (LCs) containing selectively fluorinated cyclopropanes at their termini. The syntheses used difluorocarbene additions to olefin precursors, an approach which proved straightforward such that these liquid crystal candidates could be efficiently prepared. Their physical and thermodynamic properties were evaluated and depending on individual structures, they either displayed positive or negative dielectric anisotropy. The study gives some guidance into effective structure-property relationships for the design of LCs containing selectively fluorinated cyclopropane motifs.


Induction of nephrotoxic serum nephritis in inbred mice and suppressive effect of colchicine on the development of this nephritis.
Accelerated nephrotoxic serum (NTS) nephritis is successfully produced in C57BL/6 mice, using anti-murine glomerular basement membrane (GBM) rabbit antiserum. Anti-murine GBM rabbits antiserum was obtained by immunization of New Zealand white rabbit with trypsinized GBM antigen from normal C57BL/6 mice. Preimmunization with normal rabbit IgG and injection with 150 microl of NTS induced typical NTS nephritis with cellular proliferation in glomeruli, occlusion of glomerular loops, crescents, tubulointerstitial changes and hyperazotemia within 14 days. Polymorphonuclear leucocytes (PMN) have an important role in induction and development of NTS nephritis. Furthermore, clinically used colchicine is thought to suppress functions of PMN. Therefore, the therapeutic effect of colchicine on NTS nephritis was examined. The histological score (HS) of the group treated with 60 microg kg (-1) of colchicine (2.8 +/- 0.5) was significantly lower than that of positive control group (4.03 +/- 0.3).The direct immunofluorescent microscopic study revealed that there is no quantitative difference in the deposition of rabbit IgG, mouse IgG and C3 in GBM between these two groups. Urinary protein excretion and hyperazotemia were significantly suppressed by treatment with 60 microg kg (-1) of colchicine. A NTS nephritis model was established, it was found that colchicine may have a suppressive effect on the development of glomerular nephritis.


Simultaneous immunophenotyping and FISH on fetal cells from maternal blood.
Current methods for the prenatal diagnosis of genetic disorders from fetal cells in the maternal circulation are restricted by maternal cell contamination and therefore must rely on the presence of features (such as Y-specific DNA sequences) absent from maternal cells. We have used density gradient centrifugation and magnetic-activated cell sorting to enrich maternal blood samples for fetal nucleated red cells. Mouse monoclonal antibodies for CD45 and CD32 were used to reduce the proportion of leukocytes. Unequivocal identification of fetal cells was achieved using an immunophenotypic test for fetal hemoglobin that allowed the simultaneous application of a diagnostic FISH analysis with chromosome-specific DNA probes. A positive diagnosis of female fetal sex (among other diagnoses) is thus possible even in the presence of an excess of maternal cells. The method, which appears to represent an advance over previous techniques, has considerable application in the development of noninvasive prenatal diagnosis from maternal blood.


Radiofrequency Ablation for the Treatment of Painful Neuroma.
Mechanical compression of interdigital nerves beneath the deep transverse intermetatarsal ligament and between the metatarsal heads leads to painful irritation and possible fibrosis. Conservative measures of padding and injections often fail to provide long-term relief. Surgical excision provides definitive relief, but the procedure is not without risk. Incomplete excision and stump neuroma formation are a few of the possible complications associate with open excision. This retrospective cohort study was performed to provide a review of the available literature on the identification and treatment of interdigital neuromas and to examine the overall incidence of patient satisfaction after radiofrequency ablation as definitive treatment for interdigital neuroma formation. This study population consisted of 32 patients (25 females and 7 males with 1 patient having bilateral procedures) with a mean age of 46.3 ± 17 (range 31 to 65) years. For all procedures, the median patient satisfaction score was 92.5 (interquartile range 50 to 100) of 100, with a mean follow-up period of > 2.5 years. Only 1 patient in the study population reported no relief after 3 total procedures. Radiofrequency ablation offers a minimally invasive alternative with a short postoperative recovery course and considerably fewer complications compared with surgical excision of the intermetatarsal neuroma as described in prior reports.


Method for multiplex cellular detection of mRNAs using quantum dot fluorescent in situ hybridization.
The photostability and narrow emission spectra of non-organic quantum dot fluorophores (QDs) make them desirable candidates for fluorescent in situ hybridization (FISH) to study the expression of specific mRNA transcripts. We developed a novel method for direct QD labeling of modified oligonucleotide probes through streptavidin and biotin interactions, as well as protocols for their use in multiple-label FISH. We validated this technique in mouse brainstem sections. The subcellular localization of the vesicular monoamine transporter (Vmat2) mRNA corresponds when using probes labeled with two different QDs in the same hybridization. We developed protocols for combined direct QD FISH and QD immunohistochemical labeling within the same neurons as well as for simultaneous study of the subcellular distribution of multiple mRNA targets. We demonstrated increased sensitivity of FISH using QDs in comparison with organic fluorophores. These techniques gave excellent histological results both for multiplex FISH and combined FISH and immunohistochemistry. This approach can facilitate the ultrasensitive simultaneous study of multiple mRNA and protein markers in tissue culture and histological section.


Recombinant Fusion Protein Vaccine Containing Clostridioides difficile FliC and FliD Protects Mice against C. difficile Infection.
Bacterial flagella are involved in infection through their roles in host cell adhesion, cell invasion, auto-agglutination, colonization, the formation of biofilms, and the regulation and secretion of nonflagellar bacterial proteins that are involved in the virulence process. In this study, we constructed a fusion protein vaccine (FliCD) containing the Clostridioides difficile flagellar proteins FliC and FliD. The immunization of mice with FliCD induced potent IgG and IgA antibody responses against FliCD, protected mice against C. difficile infection (CDI), and decreased the C. difficile spore and toxin levels in the feces after infection. Additionally, the anti-FliCD serum inhibited the binding of C. difficile vegetative cells to HCT8 cells. These results suggest that FliCD may represent an effective vaccine candidate against CDI.


Implant-guided supracrestal alveolar bone growth using scaffolds, BMP-2, and novel scaffold-retaining device.
To evaluate the efficacy of various scaffold systems and a Ti scaffold-retaining device with and without non-glycosylated rhBMP-2 (BMP-2) for increasing the vertical alveolar bone growth in the intra-oral mini-pig model. Forty-eight Straumann Bone Level implants with hydrophilic (SLActive) surfaces were partially embedded in mandibles of 12 adult mini-pigs with the shoulder of the implant located 3 mm above the bone crest. Twenty-four implants were placed in conjunction with BMP-2 (50 μg) incorporated within resorbable scaffolds. Twenty-four additional control implants were placed with scaffolds only. Scaffolds were placed around the implant and stabilized with a newly developed Ti "umbrella" scaffold retainer. Scaffolds included (i) HA-coated collagen (Healos); (ii) biphasic HA/β-TCP crystals (Straumann Bone Ceramic, SBC); and (iii) SBC crystals infused with polyethylene glycol (PEG) hydrogel. Eight test and control pairs for each scaffold group were implanted. At 9 weeks, soft tissue healing was assessed and the extent of new vertical bone was evaluated with microCT and histomorphometry. microCT analysis revealed a mean of 167 ± 47 mm3 new supracrestal mineralized tissue volume formation around the test sites where BMP-2 was released from the scaffold whereas the control group (no BMP-2) showed a significantly lower mineralized tissue volume of 106 ± 55 mm3 . The SBC+BMP-2 group had the highest mineralized tissue volume of 189 ± 36 mm3 . Histomorphometry showed bone-to-implant contact of 54.5% for the test groups and 33.3% for the control groups and new vertical bone growth of 2.2 ± 1.0 and 1.0 ± 0.9 mm, respectively. The SBC+BMP-2 group again demonstrated the best outcome (2.7 ± 0.4 mm). The qualitative scoring of soft tissue dehiscence showed that the presence of BMP-2 yielded far superior outcomes, 0.63 vs. 1.75 for all control implant sites (with scores ranging from 0, reflecting no soft dehiscence, to 4, showing a completely exposed umbrella). The release of BMP-2 from a SBC scaffold adjacent to a hydrophilic, rough Ti implant and scaffold retention umbrella consistently regenerated the greatest volume and height of new vertical bone along the length of the implant.


Determination of the ascorbate content of photographic developer solutions using miniaturised isotachophoresis on a planar chip.
The use of miniaturised isotachophoresis, performed on a planar poly(methyl methacrylate) device with integrated platinum conductivity electrodes, for the analysis of the ascorbate content of photographic developer solutions has been investigated. An electrolyte system has been developed which enabled the analysis to be made without interference from any of the other components in the developer solution, a number of which were present at significantly higher concentrations than that of the ascorbate ions. Using this system, the ascorbate content of the developer solutions could be analysed in under 6 min. The limit of detection for ascorbate using miniaturised isotachophoresis was calculated to be 0.011 mmol dm(-3).


Evolving trends: hyperbilirubinemia among newborns delivered to rh negative mothers in southern India.
Neonatal jaundice is the commonest abnormal physical finding in the new born nursery and hemolytic disease of the newborn (HDN) among babies born to Rh negative mothers is the most formidable etiology. During last few decades considerable evolution has been observed in this entity secondary to development of several novel preventive, diagnostic and therapeutic modalities. To study the current trends in presentation, management and outcome of hyperbilirubinemia among newborns delivered to Rh negative mothers. This observational descriptive study with prospective data collection included one hundred live born term babies born to Rh negative mothers in our hospital. A predesigned proforma was used to record antenatal and postnatal data .Cord blood collected during delivery for assessment of bilirubin,hematocrit and direct coombs test.Serum bilirubin levels were estimated in babies with clinical jaundice and treated for the same if required.All babies were regularly followed up weekly for one month. Chi square test/Fisher Exact test and Student "t" test has been used to find the significant association of jaundice(incidence,treatment) and study characteristics. Out of 100 babies enrolled, 57 babies developed jaundice. Jaundice is 2.7 times more likely associated with babies born to multiparous Rh-ve mothers with p=0.017*. Jaundice is 3 times more likely associated with Rh+ve babies born to multiparous mothers with p=0.020*. Jaundice is 3.97 times more likely associated with Rh+ve babies born to multiparous mothers who have not received Anti-D with p=0.154. Treatment of jaundice is 2.75 times more likely in Rh+ve babies born to multiparous mothers who have not received Anti-D with p=0.162. Duration of phototherapy is significantly more in Rh+ve babies born to multiparous mothers who had not received Anti-D with p=0.0097*.Exchange transfusion was required in two babies. Although the incidence of Rh isoimmunization has declined dramatically over the years ,it is still an important cause of neonatal morbidity and mortality emphasizing the need for more vigorous preventive efforts and up-to-date management skills.


Genetic regulation of variable Vi antigen expression in a strain of Citrobacter freundii.
Certain strains of the genus Citrobacter exhibit a variable expression of the Vi surface antigen that appears to involve a special mechanism for regulation of gene expression. Two nonlinked chromosomal loci, viaA and viaB, are known to determine nonvariable Vi antigen expression in strains of Salmonella. To confirm the presence of analogous loci in Citrobacter and to ascertain whether either of them is involved in variable Vi antigen expression in this organism, donor strains were constructed from Citrobacter freundii WR7004 and used to transfer their Vi antigen-determining genes to ViaA- and ViaB- Salmonella typhi recipient strains. Vi antigen expression in C. freundii was found to be controlled by loci analogous to the Salmonella via genes. S. typhi recipients of the C. freundii viaA+ genes were restored to the full, continuous expression of the Vi antigen normally seen in S. typhi. Thus, the C. freundii viaA genes appeared to play no role in the variable expression of the Vi antigen. In contrast, S. typhi recipients of the C. freundii viaB+ genes exhibited the rapid, reversible alternation between full Vi antigen expression and markedly reduced Vi antigen expression that was seen to occur in the C. freundii parent. The C. freundii viaB locus was thus identified as the one whose genes are regulated so as to produce variable Vi antigen expression. Genes determining another C. freundii surface antigen, the synthesis of which is not affected by the mechanism regulating Vi expression, were coinherited with the C. freundii viaB+ genes. An invertible, insertion sequence element located within the C. freundii viaB locus is proposed to account for the regulation of variable Vi antigen expression.


Alterations in megakaryocyte and platelet compartments following in vivo IL-1 beta administration to normal mice.
IL-1 has been shown to stimulate the release of granulocyte-macrophage CSF, granulocyte-CSF, and macrophage-CSF from "accessory cell populations" in vitro, and it stimulates the appearance of colony-stimulating activity in the sera of mice in vivo. This cytokine has also been proposed to act on primitive hematopoietic progenitor cells to stimulate expression of receptors for the CSF. We sought to determine whether IL-1 beta could influence platelet and/or megakaryocytes and their progenitor cells following in vivo administration to normal mice. Our results demonstrated that, although administration of IL-1 beta clearly expands the pool of megakaryocyte-CFU and acetylcholinesterase-positive megakaryocytic cells (primarily in the spleen), it causes a transient and dose-dependent reduction of circulating platelets. The associated thrombocytopenia can be abolished by splenectomy before IL-1 beta administration, and is not temporally associated with the development of splenomegaly.


Immune infertility in men.
Male factors are implicated as the cause of roughly half of cases of infertility, and the presence of antisperm antibodies (ASA) may be responsible for some of these. Their presence is associated with a reduction in natural conception and live birth and impacts the success of assisted reproductive technologies. Interpretation of the data regarding ASAs and fertility is complicated by a lack of standardization in testing methodology and test thresholds and a lack of data on their prevalence in the healthy fertile population. Although their pathogenesis remains elusive, and many cases are idiopathic, a disruption in the immunologic blood-testis barrier (BTB) appears to contribute to the formation of ASA. As delineation of the specific antigen targets of ASA advances, it has been recognized that they may affect almost all aspects of sperm function, and ASA against different targets likely have specific mechanisms of impairing fertility. Intracytoplasmic sperm injection (ICSI) appears to be the most reliable method by which to overcome fertility impairment due to ASA, achieving similar outcomes to ASA-negative patients with regard to fertilization rates, embryonic development, clinical pregnancy rates, and live birth rates. The lack of consistency in testing for and reporting ASA remains a substantial barrier to achieving clarity in describing their role in infertility and the optimal management approach, and future research should use a unified approach to the detection and description of ASA. Determination of the specific antigens targeted by ASA, and their function and clinical relevance, would contribute to improving the understanding of ASA-mediated impacts on fertility and tailoring treatment appropriately to achieve the best outcomes for patients.


[The heterochromatin regions of the mitotic chromosomes in cattle].
Cytochemical and molecular peculiarities of heterochromatic regions of bovine chromosomes have been studied, using specific fluorochrome staining induced decondensation, in situ hybridization, pretreatment of restriction enzymes. The heterochromatin of autosomes demonstrated a strong homogeneity. In chromosome Y two small specific heterochromatic regions were found lacking a long repeated tandem block of nucleotides enriched in GC base pairs and having no tandem block of Bkm repeats (10(4) b.p.). This class repeats are probably interspersed in the bovine genome. A rather seldom character of mammalian karyotypes is the absence of cytochemical heterochromatin in the X chromosome.


Exposure of mares to processionary caterpillars (Ochrogaster lunifer) in early pregnancy: an additional dimension to equine amnionitis and fetal loss.
Equine amnionitis and fetal loss (EAFL) is an unusual form of abortion in mid- to late-gestation mares, first identified in Australia in 2004. It has been shown that both whole processionary caterpillars (Ochrogaster lunifer) and their shed exoskeletons can induce abortion in mares during midgestation. These abortions exhibited gross pathology and bacteriology results consistent with field cases of EAFL. To determine whether exposure of mares to the shed exoskeletons of processionary caterpillars can induce abortion in the preplacentation (<35 days' gestation) and early placentation (45-60 days) stages of pregnancy. In vivo experimental study. Mares less than 35 days' gestation and between 45 and 60 days' gestation were exposed to a slurry of shed processionary caterpillar exoskeletons by nasogastric intubation. Mares were monitored by clinical examination daily. Transrectal ultrasonography was performed daily (control and treated preplacentation mares, treated early placentation mares) or every second day (control early placentation mares). Uterine swabs were collected from mares that aborted. All live foals underwent a clinical examination. Placentas were examined, with sampling for bacteriology and histopathology if appropriate. Abortions occurred in treated mares in both experiments without signs of impending abortion. One mare aborted in the embryonic stage experiment and 2 in the early placentation experiment. Embryonic and fetal death was detected on transrectal ultrasonography prior to abortion. In the early placentation experiment, one foal was born 5 weeks preterm and was very small, with laxity of the tendons in all limbs. Enteric or environmental bacteria, consistent with EAFL, were isolated from the mares that aborted. Focal mucoid placentitis lesions were present on the placentas of 2 treated mares, one from each experiment. Processionary caterpillar exposure may be associated with EAFL-related embryonic and early fetal loss in mares. Processionary caterpillars may also play a role in the occurrence of focal mucoid placentitis.