Transarterial approach of the pulmonary artery in anatomically corrected malposition of the great arteries by manipulating a catheter inverted with balloon floating maneuver.
We describe two neonates with anatomically corrected malposition of the great arteries (ACM). A 1-day-old female newborn, who had the salient clinical findings of Goldenhar syndrome, behaved like a patient with the tetralogy of Fallot. The cardiac malformations included ACM, perimembranous inlet and outlet ventricular septal defect with tricuspid valve straddling, conoventricular septal malaligement, bilateral cori without aortic-mitral continuity, pulmonary stenosis at subvalvular, valvular, and supravalvular levels, and bicuspid semilunar valves. After the procedure of left Blalock-Taussig shunt at 3 months of age, cyanosis was alleviated. The other 1-month-old male newborn, who presented with prolonged feeding, tachypnea and tachycardia, likened to a patient with the hypoplastic left heart syndrome. He had a combination of ACM, mitral stenosis, hypoplastic left atrium and left ventricle, a restrictive patent foramen ovale, ventricular septal defect, subaortic conus without aortic-mitral continuity, subaortic stenosis, and a narrow ascending aortic root. Rashkind balloon atrioseptostomy was done with limited success. He survived a Norwood procedure. Transarterial entry of the catheter, which was inverted with the aid of balloon floating maneuver, to hook the retro-aortic pulmonary artery in ACM is recommended.


Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.
Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart Dmean), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRTDIBH decreased the Heart Dmean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRTFB. IMRT further lowered mean LAD dose by 18%. Heart Dmean was lower with 3DCRTDIBH over IMRTDIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V20 of ipsilateral lung were lower with 3DCRTDIBH over IMRTDIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRTDIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.


Presence, sources, and risk assessment of heavy metals in the upland soils of northern China using Monte Carlo simulation.
The spatial dynamics of heavy metal contamination in the upland soils of northern China are relatively unknown, despite the region's high contribution to the national grain output. In this study, the concentrations of As, Cd, Co, Cr, Cu, Mn, Pb, Sb, Sc, Ti, and Zn and subsequent ecological and human health risks were investigated in three major grain producing areas (Hexi Corridor, L1; Hetao irrigation area, L2; and eastern Inner Mongolia, L3) of northern China. Among the heavy metals, Ti had the highest average concentration of 3.02 g/kg, followed by Mn (470 mg/kg), Cr (56.6 mg/kg), Zn (34.3 mg/kg), Pb (19.4 mg/kg), Cu (17.8 mg/kg), Co (9.66 mg/kg), Sc (7.26 mg/kg), As (5.35 mg/kg), Sb (0.73 mg/kg), and Cd (0.17 mg/kg). Generally, the heavy metal concentrations decreased from west to east (L1 > L2 > L3) across northern China. Moreover, three potential sources of the heavy metal were distinguished, including natural process, anthropogenic activities (industrial development and agricultural cultivation), and atmospheric deposition. Although the contamination of the single metal (including Cd, Cr, Cu, and Pb) was moderate in L1 and L2, the combined contamination was low in the upland soils. It was noted that Cd posed a moderate to considerable ecological risk on the upland soils in northern China. This metal was the most sensitive factor in assessing the combined ecological risk, with a contribution rate of 91.56-94.84%. Considering the ingestion exposure, the current concentrations of the metals posed minimal risks to human health. Furthermore, children experienced higher health risks than adults. Present study analyzed the probabilistic distribution of contamination, ecological, and health risk of heavy metals in upland soils of northern China, providing fundamental information for better agricultural heavy metal pollution assessment in China.


Cadmium reduces 11 beta-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells.
Cadmium, a common environmental pollutant and a major constituent of tobacco smoke, has been identified as a new class of endocrine disruptors with a wide range of detrimental effects on mammalian reproduction. During human pregnancy, maternal cadmium exposure, via the environment and/or cigarette smoking, leads to fetal growth restriction (FGR), but the underlying mechanisms are unknown. Although a substantial amount of evidence suggests that cadmium may affect fetal growth indirectly via the placenta, the molecular targets remain to be identified. Given that reduced placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2, encoded by HSD11B2 gene) is causally linked to FGR, the present study was undertaken to examine the hypothesis that cadmium induces FGR in part by targeting placental HSD11B2. Using cultured human trophoblast cells as a model system, we showed that cadmium exposure resulted in a time- and concentration-dependent decrease in 11 beta-HSD2 activity, such that an 80% reduction was observed after 24-h treatment at 1 microM. It also led to a similar decrease in levels of 11 beta-HSD2 protein and mRNA, suggesting that cadmium reduced 11 beta-HSD2 expression. Furthermore, cadmium diminished HSD11B2 promoter activity, indicative of repression of HSD11B2 gene transcription. In addition, the effect of cadmium was highly specific, in that other divalent metals (Zn(2+), Mg(2+), and Mn(2+)) as well as nicotine and cotinine (a major metabolite of nicotine) did not alter 11 beta-HSD2 activity. Taken together, these findings demonstrate that cadmium reduces human placental 11 beta-HSD2 expression and activity by suppressing HSD11B2 gene transcription. Thus the present study identifies placental 11 beta-HSD2 as a novel molecular target of cadmium. It also reveals a molecular mechanism by which this endocrine disruptor may affect human placental function and, consequently, fetal growth and development.


A modular analysis of microglia gene expression, insights into the aged phenotype.
Microglia are multifunctional cells that are key players in brain development and homeostasis. Recent years have seen tremendous growth in our understanding of the role microglia play in neurodegeneration, CNS injury, and developmental disorders. Given that microglia show diverse functional phenotypes, there is a need for more precise tools to characterize microglial states. Here, we experimentally define gene modules as the foundation for describing microglial functional states. In an effort to develop a comprehensive classification scheme, we profiled transcriptomes of mouse microglia in a stimulus panel with 96 different conditions. Using the transcriptomic data, we generated fine-resolution gene modules that are robustly preserved across datasets. These modules served as the basis for a combinatorial code that we then used to characterize microglial activation under various inflammatory stimulus conditions. The microglial gene modules described here were robustly preserved, and could be applied to in vivo as well as in vitro conditions to dissociate the signaling pathways that distinguish acutely inflamed microglia from aged microglia. The microglial gene modules presented here are a novel resource for classifying and characterizing microglial states in health and disease.


Proposed rectal dose constraints for patients undergoing definitive whole pelvic radiotherapy for clinically localized prostate cancer.
Although several institutions have reported rectal dose constraints according to threshold toxicity, the plethora of trials has resulted in multiple, confusing dose-volume histogram recommendations. A set of standardized, literature-based constraints for patients undergoing whole pelvic radiotherapy (RT) for prostate cancer would help guide the practice of prostate RT. The purpose of this study was to develop these constraints, demonstrate that they are achievable, and assess the corresponding rectal toxicity. An extensive literature search identified eight key studies relating dose-volume histogram data to rectal toxicity. A correction factor was developed to address differences in the anatomic definition of the rectum across studies. The dose-volume histogram constraints recommended by each study were combined to generate the constraints. The data from all patients treated with definitive intensity-modulated RT were then compared against these constraints. Acute rectal toxicity was assessed. A continuous, proposed rectal dose-constraint curve was generated. Intensity-modulated RT not only met this constraint curve, but also was able to achieve at least 30-40% lower dose to the rectum. The preliminary clinical results were also positive: 50% of patients reported no acute bowel toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No patients reported Grade 3-4 acute rectal toxicity. In this study, we developed a set of proposed rectal dose constraints. This allowed for volumetric assessment of the dose-volume relationship compared with single dose-volume histogram points. Additional research will be performed to validate this threshold as a class solution for rectal dose constraints.


Outbreak of carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-23 in a tertiary care hospital of Papeete, French Polynesia.
Carbapenem-resistant Acinetobacter baumannii isolates were obtained from 24 patients between March and May 2004 at the Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia. The isolates were multidrug resistant, produced the carbapenemase OXA-23, and belonged to a single clone presenting several subtypes, suggesting an endemic situation. This study further illustrates the global spread of this kind of beta-lactamase-mediated resistance.


Overcoming recruitment challenges in construction safety intervention research.
Recruiting workers in small construction companies and securing their participation in voluntary safety programs or safety research poses unique challenges. Worker turnover and worksite changes contribute to difficulties in locating and enrolling participants. Economic pressures and time demands potentially threaten ongoing participation. Six simulation exercises designed to reduce back and fall injuries in small construction companies were developed based on data from focus groups of workers and company owners. Working with a workers' compensation insurer, we had access to owner-operators of general, heavy, and special trade construction companies reporting less than $10,000 in payroll expenses. Recruitment methods included a participation incentive, mailed invitations followed by phone contacts, and follow-up reminders. Despite using recruitment methods recommended in the literature, participation rates were low over a 2-year intervention period. Because of these difficulties, factors affecting participation or nonparticipation became an additional research focus. Owners' perceptions of already having a good safety record and of the time demands of participation were the most commonly cited reasons for not participating. Literature on recruitment emphasizes processes and procedures under investigator control rather than understanding potential participants' judgments about the adequacy of their existing practices and the potential benefits of intervention participation relative to potential time and productivity trade-offs. Greater attention to such judgments may enhance recruitment and participation in under-studied and difficult to access populations.


Early reoxygenation in tumors after irradiation: determining factors and consequences for radiotherapy regimens using daily multiple fractions.
To characterize changes in the tumor microenvironment early after irradiation and determine the factors responsible for early reoxygenation. Fibrosarcoma type II (FSaII) and hepatocarcinoma transplantable liver tumor tumor oxygenation were determined using electron paramagnetic resonance oximetry and a fiberoptic device. Perfusion was assessed by laser Doppler, dynamic contrast-enhanced MRI, and dye penetration. Oxygen consumption was determined by electron paramagnetic resonance. The interstitial fluid pressure was evaluated by the wick-in-needle technique. An increase in oxygen partial pressure was observed 3-4 h after irradiation. This increase resulted from a decrease in global oxygen consumption and an increase in oxygen delivery. The increase in oxygen delivery was due to radiation-induced acute inflammation (that was partially inhibited by the antiinflammatory agent diclofenac) and to a decrease in interstitial fluid pressure. The endothelial nitric oxide synthase pathway, identified as a contributing factor at 24 h after irradiation, did not play a role in the early stage after irradiation. We also observed that splitting a treatment of 18 Gy into two fractions separated by 4 h (time of maximal reoxygenation) had a greater effect on tumor regrowth delay than when applied as a single dose. Although the cell cycle redistribution effect is important for treatment protocols using multiple daily radiation fractions, the results of this work emphasize that the oxygen effect must be also considered to optimize the treatment strategy.


Evaluation of Sexual Function Among Infertile Women and Their Sexual Self-Concept.
The present study was designed to assess the association between sexual self-concept and sexual function in infertile women. A study with a convenience sample of women attending a referral infertility center (Royan Institute) was conducted in Tehran, Iran, in 2017. The Multidimensional Sexual Self-Concept Questionnaire (MSSCQ) and the Female Sexual Function Index (FSFI) were used to collect data. Chi-Square, t-test, Mann-Whitney U test and logistic regression were applied to analyze the data. The significance level was set at p<0.05. The mean age of participants was 29.7±5.2 years. Overall, 152 women (60.8%) reported that they were experiencing sexual dysfunction. Comparing women with and without sexual dysfunction, there were significant differences between two groups on most measures such as sexual anxiety, sexual motivation, sexual satisfaction, and sexual depression (p<0.05). However, the results obtained from logistic regression indicated that women's and husband's age (OR for women's age=1.26, 95% CI=1.10-1.44, p<0.001; OR for husband's age=0.86, 95% CI=0.77-0.97, p=0.014), cause of infertility (OR for female factor=9.17, 95% CI=2.26-37.2, p=0.002; OR for male factor=3.90, 95% CI=1.26-12.1, p=0.018; OR for male and female factor=3.57, 95% CI=1.12-11.4, p=0.032), sexual motivation (OR=0.35, 95% CI=0.16-0.75, p= 0.007) and sexual satisfaction (OR=0.23, 95% CI=0.09-0.56, p=0.001) were significantly associated with sexual dysfunction. The findings suggest that sexual motivation and sexual satisfaction are important dimensions of sexual self-concept in infertile women. Indeed, it is essential to inform policy makers and stakeholders to provide more sexual health support for this population in the process of treatment.


Microfluidic vortex focusing for high throughput synthesis of size-tunable liposomes.
Control over vesicle size during nanoscale liposome synthesis is critical for defining the pharmaceutical properties of liposomal nanomedicines. Microfluidic technologies capable of size-tunable liposome generation have been widely explored, but scaling these microfluidic platforms for high production throughput without sacrificing size control has proven challenging. Here we describe a microfluidic-enabled process in which highly vortical flow is established around an axisymmetric stream of solvated lipids, simultaneously focusing the lipids while inducing rapid convective and diffusive mixing through application of the vortical flow field. By adjusting the individual buffer and lipid flow rates within the system, the microfluidic vortex focusing technique is capable of generating liposomes with precisely controlled size and low size variance, and may be operated up to the laminar flow limit for high throughput vesicle production. The reliable formation of liposomes as small as 27 nm and mass production rates over 20 g/h is demonstrated, offering a path toward production-scale liposome synthesis using a single continuous-flow vortex focusing device.


Frequency analysis of CD4+CD8+ T cells cloned with IL-4.
The coexpression of both CD4 and CD8 molecules on T cells occurs in the peripheral blood at a low frequency and can be generated transiently on CD4+ peripheral blood T cells by treatment with lectin which induces CD8 biosynthesis and cell surface expression. We have cloned T cells in a nonselective fashion from normal subjects in the presence of either IL-2, rIL-4 and IL-2, or rIL-4 and have examined the phenotypic expression of CD4 and CD8. The addition of excess rIL-4 increased the expression of CD8 on the surface of CD4+ T cell clones but did not increase CD4 expression on CD8+ T cell clones. There were three patterns of CD4 and CD8 expression observed: high density CD8 with no CD4 expression; high density CD4 with low CD8 expression; or high density CD4 with higher cell surface CD8 expression which was regulated by the presence of rIL-4. CD4+ T cell clones originally cultured in IL-2 and rIL-4 and subsequently grown in IL-2 alone exhibited decreased expression of the CD8 molecule. The increased expression of CD8 did not correlate with NK activity or lectin-dependent cytotoxicity in an antigen independent system. In addition, rIL-4 alone or in combination with IL-2 appeared to accelerate the growth curve of T cell clones as compared to IL-2 alone. These results show that IL-4 can upregulate CD8 expression on CD4+ T cell clones while not effecting CD4 expression on CD8+ T cell clones. As class I MHC is the ligand for the CD8 molecule, expression of CD8 induced by IL-4 on CD4+ T cells may allow for increased nonspecific cell to cell contact during the course of an inflammatory response.


NF-YA isoforms with alternative splicing of exon-5 in Aves.
NF-YA, the regulatory subunit of the trimeric CCAAT-binding transcription factor NF-Y, is present in vertebrates in two major alternative spliced isoforms: NF-YAl and NF-YAs, differing for the presence of exon-3. NF-YAx, a third isoform without exon-3/-5, was reported only in human neuronal cells and tumors. These events affect the Trans-Activation Domain. We provide here evidence for the expression of NF-YAx and for the existence of a new isoform, NF-YAg, skipping only exon-5. These isoforms are abundant in Aves, but not in reptiles, and are the prevalent transcripts in the initial phases of embryo development in chicken. Finally, we analyzed NF-YAg and NF-YAx amino acid sequence using AlphaFold: absence of exon-5 denotes a global reduction of β-stranded elements, while removal of the disordered exon-3 sequence has limited effects on TAD architecture. These data identify an expanded program of NF-YA isoforms within the TAD in Aves, implying a role during early development.


Saccharomyces cerevisiae Sepsis Following Probiotic Therapy in an Infant.
A 3.5-month-old infant with undiagnosed underlying combined immunodeficiency presented with S. ceravisiae fungemia following treatment with S. boulardii containing probiotic preparation. This case highlights that the use of probiotics in sick patients may be fraught with danger.


Recombinant study of the mouse molar cervical loop and dental papilla by renal transplantation.
Cervical loop tissues of the mandibular first molar germs were dissected from 18-day mouse embryos and recombined with the isochronal dental papilla mesenchyme. The recombinants were transplanted under the kidney capsule of syngeneic male mice. Five days later, proliferation of epithelial and mesenchymal cells was observed. At the junctional region between the internal dental epithelium and the dental papilla mesenchyme, extracellular organic matrix was deposited. By 10 days after, transplantation, the formation of dentine and enamel was initiated. Twenty days after transplantation, the recombinant developed into an almost intact molar tooth. The compensatory potential of the molar cervical loop, when recombined with the dental papilla mesenchyme, was indicated.


Plasma thrombin assay using a chromogenic substrate in disseminated intravascular coagulation due to snake bite envenomation.
Using the chromogenic substrate, Tos-Gly-Pro-Arg-pNA-HCl (Chromozym TH, Boehringer Mannheim) plasma thrombin was estimated in six cases of envenomation by Australian elapid snakes. All patients manifested findings characteristic of defibrination due to envenomation by these snakes. Fibrin-fibrinogen degradation products were grossly elevated, as was plasma thrombin in all cases. Following treatment with antivenene, all abnormal coagulation parameters returned rapidly towards normal by 24 hours and plasma thrombin disappeared.


DNA-binding proteins of mammalian mitochondria.
Acid-soluble proteins were isolated from liver and spleen mitochondria and their ability to form complexes with DNA was investigated. According to electrophoresis data, acid-soluble proteins include about 20 polypeptides ranging in the molecular mass from 10 to 120 kDa. It was found that acid-soluble proteins form stable DNA-protein complexes at a physiological NaCl concentration. Different polypeptides possess different degrees of DNA affinity. There is no significant difference between DNA-binding proteins of mitochondria from liver and those from spleen as to their ability to form complexes with mtDNA and nDNA. In the presence of 5 microg of DNA most polypeptides were bound to DNA, and further increase in DNA amount affected little the binding of proteins to DNA. There was no distinct difference in DNA-protein complex formation of liver mitochondrial acid-soluble proteins with nDNA or mtDNA. Also, it was detected that with these mitochondrial acid-soluble proteins, proteases that specifically cleave these proteins are associated. It was shown for the first time that these proteases are activated by DNA. DNA-binding proteins including DNA-activated mitochondrial proteases are likely to participate in the regulation of the structural organization and functional activity of mitochondrial DNA.


Separation and identification of 9-chloro-10-methoxy (9-methoxy-10-chloro)hexadecanoic and octadecanoic acids in adipocere.
Two homologs of 9-chloro-10-methoxy(9-methoxy-10-chloro) fatty acids were found in adipocere from the human neonate, and identified as 9-chloro-10-methoxy(9-methoxy-10-chloro)hexadecanoic acid and 9-chloro-10-methoxy(9-methoxy-10-chloro)-octadecanoic acid. The chemical structures of these compounds were confirmed by thin-layer chromatography, gas-liquid chromatography, gas chromatography--mass spectrometry, nuclear magnetic resonance spectrometry and elemental analysis. The adipocere contained approximately 7.2% 9-chloro-10-methoxy(9-methoxy-10-chloro) fatty acids in the total fatty acids.


A comparative study of lens gamma crystallins using isoelectric focusing.
The isoelectric points of gamma crystallins of the lenses of rats, dogfish, calves, and humans differ, with a range of pH 8.87-6.80. In each species, one gamma crystallin component with an isoelectric point at pH 7.5 is present, but at differing levels. Amino acid compositions of this component were similar among these four species. All pH 7.5 isoelectric point proteins crossreact immunochemically. A common messenger RNA must be present for this gamma crystallin in all of these species.


Chlorpromazine reduces UV-induced squamous cell carcinogenesis in hairless mice and enhances UV-induced DNA damage in cultured cells.
Administration of the photoactivable compound chlorpromazine (CPZ) to SKH-1 hairless mice via their drinking water (CPZ, 0.01%) significantly reduced the rates of accumulation and yields of squamous cell carcinomas induced by long-term repeated exposures of these animals to solar UV radiation. This protective effect of CPZ was partially reversed in mice given a single injection of ethyl nitrosourea at birth. In in vitro studies, the presence of CPZ (0.2 mM) in mammalian cell cultures enhanced the yield of DNA single-strand breaks induced in the cells by exposure to monochromatic UVA radiation at 334 nm. Collectively, the results suggest that CPZ may exert antineoplastic effects against UV-induced skin tumours by the induction of DNA damage.


Reliability and validity of the modified preverbal, early verbal pediatric pain scale in emergency department pediatric patients.
Research has demonstrated that children are at particular risk for oligoanalgesia due to assessment difficulties when they are unable to self-report. We sought to evaluate the psychometric properties of the Modified Preverbal, Early Verbal Pediatric Pain Scale (M-PEPPS) when used in an emergency department pediatric population. We conducted a secondary analysis of data from a prospective, observational study of pain in emergency patients to evaluate the M-PEPPS tool. Data from 118 pediatric patients was subjected to item analysis, reliability analysis, and common factor analysis. Item difficulties suggest that the items capture the range of pain states from mild to severe. Corrected item-total correlations indicate that the instrument discriminates between various levels of pain. Common factor analysis yielded a single, unrotated common factor solution providing evidence that the M-PEPPS measures the single construct of pain. Cronbach's alpha for the scale (0.954) suggests excellent reliability. Findings indicate that the M-PEPPS instrument is reliable when used by emergency nurses to measure pediatric pain. The single-factor common factor solution provides support for the scale as measuring the single construct of pain. Additional research is necessary to establish the degree of change in score required for a clinically meaningful reduction in pain to be present.


MicroPulse Transscleral Laser Therapy with Kahook Dual Blade Excisional Goniotomy and Goniosynechialysis Combined with Phacoemulsification for Angle-Closure Glaucoma: A Case Report.
To report the efficacy and safety of MicroPulse transscleral laser therapy (TLT) and Kahook Dual Blade excisional goniotomy and goniosynechialysis combined with phacoemulsification for chronic angle-closure glaucoma (ACG). A 39-year-old hyperopic female with a known history of ACG presented with a 2-week history of blurry vision, headache, and photophobia in the right eye (RE) following surgical peripheral iridectomy at another hospital. On examination, her uncorrected visual acuity was 20/50 in the RE, and 20/25 in the left eye (LE). Goldman applanation tonometry revealed an intraocular pressure (IOP) of 51 mmHg in the RE and 12 mmHg in the LE. Ocular examination of the RE revealed conjunctival hyperemia, corneal edema, shallow anterior chamber, posterior synechia, mid-dilated non-reactive pupil, and early cataractous changes. Anterior segment examination findings in the LE were normal except for a shallow anterior chamber. Gonioscopy revealed a closed angle (Schaffer grade 0) with 360° peripheral anterior synechia in the RE and a narrow angle (Schaffer grade 2) in the LE. The cup-to-disc ratios were 0.5 RE and 0.3 LE. The patient underwent MicroPulse TLT with phacoemulsification, Kahook Dual Blade-assisted goniosynechialysis, and excisional goniotomy in the RE. At the 1-year follow-up, her IOP remained stable without the need for antiglaucoma medications. No further optic nerve or visual field deterioration was noted. MicroPulse TLT combined with phacoemulsification and Kahook Dual Blade-assisted goniosynechialysis and excisional goniotomy safely reduced IOP and the need for antiglaucoma medications in chronic ACG, avoiding the complications associated with incisional glaucoma surgery.


Skin changes in hairy cell leukemia.
Skin lesions have been reported in about 10-12% of hairy cell leukemia (HCL) patients. Most are etiologically related to autoimmune or infectious processes, although secondary cutaneous neoplasms and drug-induced lesions are also reported. However, leukemia cutis with the direct infiltration of the skin by leukemic cells is extremely rare in HCL patients. This paper reviews the epidemiology, pathogenesis, clinical symptoms, diagnosis, and approach to treating skin lesions in HCL. A literature review of the MEDLINE database for articles in English concerning hairy cell leukemia, skin lesions, leukemia cutis, adverse events, infectious, cutaneous, drug reactions, neutrophilic dermatoses, secondary neoplasms, and vasculitis was conducted via PubMed. Publications from January 1980 to September 2020 were scrutinized. Additional relevant publications were obtained by reviewing the references from the chosen articles.


Intraoperative radiation therapy in advanced thyroid cancer.
An intraoperative radiation therapy (IORT)-protocol was designed for poorly differentiated non-anaplastic thyroid carcinoma. Out of 155 cases of differentiated thyroid tumours, 12 showed marked vascular/capsular invasion. Five entered the study (three primarily local invasive tumours, two local recurring). IORT was administered after tumour surgery (4-10 GY) and combined with post-operative percutaneous irradiation. The tumour control rate in the thyroid bed was achieved in all five patients, 1/5 developed mediastinal nodes and 1/5 with primary mediastinal tumour extension showed tumour progression. No specific complications occurred.


Trichinella spiralis a new alien parasite in Italy and the increased risk of infection for domestic and wild swine.
In Europe, Trichinella spiralis, the most dangerous species for humans of the genus Trichinella, has a patchy distribution with important foci in Eastern countries and Spain. This zoonotic pathogen was apparently not circulating among wild and domestic animals of Italy. In 2016, muscle larvae belonging to this nematode species were detected in a red fox (Vulpes vulpes) shot in the Piacenza province (Northern Italy). This parasite may have been introduced into northern Italy from eastern Europe by hunters, by a hunting dog, or by immigrants, who illegally carried infected meat in their personal baggage. In the same year, T. spiralis infected sausages illegally introduced by personal baggage into Italy from Romania, were inadequately disposed of in the garbage of a central Italian town. Even though these two episodes may not be connected in time and space, they represent an increased risk of infection for domestic and wild swine, which are highly susceptible to this pathogen. In these animals, T. spiralis shows a higher larval burden and a longer survival time than other Trichinella species. Since most of the Italian pig production plants are in northern Italy, the circulation of T. spiralis should be strictly monitored in wildlife living in these areas.


The preparation of CaCO3-polyalkoxysilane porous nanocomposites as effective sorbent for oil spill removal.
The novel porous nanocomposite sorbent was synthesized by the condensation of the diol monomer with the alkoxysilane cross-linker at moderately high temperatures in the presence of nano-CaCO3 particles. The structural, thermal, and morphological properties of the nanocomposite sorbents were determined by using Fourier transform infrared spectroscopy (FTIR), solid-state CPMAS 13C and 29Si NMR, scanning electron microscope (SEM), and thermal gravimetric analysis (TGA). Adding nano-CaCO3 to the network structure of the polymer not only provided pores to the sorbent but also enhanced its sorption capacity towards various oils and toxic organic solvents. The nanocomposite sorbent exhibited excellent absorption capacity for different toxic organic solvents and oils and great reusability for ten cycles. Moreover, the obtained sorbent material selectively absorbed organic liquids from the surface and bottom of the water without any capacity change owing to their hydrophobicity and oleophilicity. These features of the nanocomposite make it a potential sorbent for the cleaning of oils and oil derivative organic contaminants from the environment.


Embryonic remnants of the umbilical cord: morphologic and clinical aspects.
Embryonic vestiges of the umbilical cord are classic findings in routine morphologic examination of the placenta. In order to evaluate their clinicopathologic significance, we examined samples from the fetal and placental ends of 1,000 umbilical cords and collected the principal clinical findings of the corresponding newborns. Microscopic evidence of embryonic remnants were found in 231 cases (23.1%) divided into remnants of the allantoic duct (63%), the omphalomesenteric duct (6.6%), and the embryonic vessels (30.4%), including one case of hemangioma and an accessory small artery. There were no significant clinical differences between the three vestigial groups, and no particular association with congenital malformations or perinatal complications. In 70.9% of the cases, the embryonic remnants were found at the fetal end of the umbilical cord, where most tumors of the cord develop.


Sirolimus-eluting stent implantation in diabetic patients with multivessel coronary artery disease.
Restenosis rate is lower after sirolimus-eluting stent (SES) implantation than after bare metal stent (BS) implantation. We evaluated the impact of SES implantation on immediate and 12-month outcome in diabetic patients with multivessel coronary artery disease (MVD). From April 2002 to September 2003, 100 consecutive diabetic patients with MVD without previous myocardial revascularization underwent successful elective percutaneous coronary intervention (PCI) with SES on native coronary arteries at our institutions. A group (n = 122) of consecutive diabetic patients with MVD treated with BS implantation (BS group) for de novo lesions was selected from our database and matched with the SES group. Major adverse cardiac events (MACEs) during hospital stay and at follow-up included nonfatal myocardial infarction, death, bypass surgery, and re-PCI. At 12 +/- 4 months, MACEs occurred in 25% of patients in the SES group and in 44% of those in the BS group (P = .003, OR .72, 95% CI 0.57-0.91). Need for repeat intervention (re-PCI or bypass surgery) occurred in 17% of patients in the SES group and in 41% of those in the BS group (P < .001, OR .67, 95% CI 0.52-0.86). No significant difference in the rate of death and myocardial infarction was observed. In the SES group, the independent predictors of MACEs at follow-up were premature clopidogrel discontinuation (hazard ratio 20.62, 95% CI 1.60-264.97, P = .020) and chronic renal insufficiency (hazard ratio 4.73, 95% CI 1.99-11.25, P = .0004). As compared with BS implantation, SES implantation favorably influences outcome in diabetic patients with MVD, mainly by reducing the need for new revascularization.


Serum cytokine, chemokine and hormone levels in Saudi adults with pre-diabetes: a one-year prospective study.
Approximately 5-10% of subjects with pre-diabetes eventually progress to diabetes every year. While inflammation is thought to be involved in the development of obesity-related type 2 diabetes mellitus (T2DM), the relation between inflammation and pre-diabetes remains largely unexplored. In this study we examined a comprehensive panel of 10 serum biomarkers involved in overweight and obese subjects with pre-diabetes. A total of 98 subjects (23 males, 75 females) were advised to reduce total intake of fat, increase fiber intake and physical activity. Serum cytokines, MCP and other hormones were assessed by multiplex cytokine profiling. Results show that CRP, IL-6, leptin, IL-10, MCP, resistin, serpin, and TNF-α were significantly lower after 12-months than baseline. Serum concentrations of other adipocytokines, including adipsin and leptin were modestly lower in the 12-month follow-up than baseline, but failed to reach statistical significance. Changes in HbA1c was found to be positively correlated with adipsin, CRP, IL-6, IL-10, resistin, serpin, and TNF-α. The results suggest that promotion of lifestyle changes for one year among overweight and obese subjects modestly changes several circulating inflammatory biomarkers which maybe favorable in reducing risk for T2DM progression.


Do urine dipsticks reliably predict microhematuria? The bloody truth!
Some literature has cast doubt on the reliability of urine dipsticks in the search for microhematuria. In our study, 2,000 urine dipsticks (two brands) were tested on urine samples containing 0, 0 to 5, 5 to 10, 10 to 20, and 20 to 50 red blood cells per high-power field. The same samples were retested four hours later and the same sticks were tested after four months of aging. Variables controlled for included observer, lighting, performance according to package insert, pH, specific gravity, white blood cells, ascorbic acid, protein, age of dipstick, and exposure of urine to povidine or cleaning solutions. Results obtained using both N-Multistix and Chemstrip 9 urine dipsticks correlated closely with the degree of hematuria. Overall sensitivity was 100%, and specificity was 99.3%. We conclude that these urine dipsticks are reliable and are not affected when tested on urine four hours after void, and that Chemstrips 9 are much more reliable than are N-Multistix if aged in air for four months.


Differential decerebrate control of depolarization in the central terminals of cutaneous afferents in the sacral cord.
Presynaptic depolarization of cutaneous afferents has been investigated in the sacral cord of decerebrate cats before and after spinal cord transection. In the decerebrate state the central terminals of caudal femoral cutaneous nerve are depolarized by ipsilateral volleys entering the cord via sacral and lumbar dorsal roots. A significant increase of depolarization occurring after severing the cord indicates that there is tonic decerebrate inhibition of presynaptic depolarization in terminals of caudal femoral cutaneous nerve. In contrast to this finding, presynaptic depolarization evoked in the central terminals of the pudendal nerve by ipsilateral volleys entering the cord through sacral and lumbar dorsal roots is not subjected to decerebrate inhibitory control. It is suggested that differential inhibitory control of depolarization in the central terminals of cutaneous nerves in the sacral cord is related to the intraspinal course of their fibres, to differences in the receptor types involved, and to the location of their innervation fields. In more than half of the decerebrate preparations stimulation of the central terminals of cutaneous afferents through microelectrodes evokes antidromic spikes appearing simultaneously in ipsi- and contralateral nerves. The time course of bilateral excitability changes is similar on both sides of the cord. It is assumed that presynaptic effects are transmitted to the contralateral side by collaterals of ipsilateral cutaneous afferents.


Lobular endocervical glandular hyperplasia might become a precursor of adenocarcinoma with pyloric gland features.
We report a case of adenocarcinoma with pyloric gland features, which appears to have originated from lobular endocervical glandular hyperplasia (LEGH). Hematoxylin and eosin staining, as well as histochemical and immunohistochemical stainings were performed on formalin-fixed and paraffin-embedded specimens. LEGH was observed in the conization specimens. In the hysterectomy specimens, LEGH, atypical LEGH, and mucinous adenocarcinoma coexisted. The adenocarcinoma was located at a site distant from the transition zone. p16(INK4a) immunopositivity was extremely rare. Front formation was observed, and a transition from benign-looking columnar cells of LEGH to adenocarcinoma was recognized. These findings suggested that the adenocarcinoma with pyloric gland features arose from LEGH. LEGH is no longer regarded as a pseudoneoplastic lesion, and it is necessary to consider that LEGH is able to transform into a precursor lesion and to develop into an adenocarcinoma with pyloric gland features.


Depression Symptoms Among Homeless Smokers: Effect of Motivational Interviewing.
Tobacco use is higher among homeless individuals than the general population. Homeless individuals are also more likely to have symptoms of depression. Depression symptoms may add to the burden of homelessness by increasing psychological distress and serve as a barrier to quitting smoking. The primary goal of this study is to assess the impact of depression symptoms on psychological distress in homeless smokers. The effect of depression symptoms on abstinence and the effect of Motivational Interviewing (MI) on cessation among smokers is also explored. Homeless smokers (N = 430) enrolled in a smoking cessation study were randomized to Motivational Interviewing (MI) or standard care (SC). Participants received nicotine replacement therapy and were followed for 26 weeks. Participants were categorized into a depression symptoms (DS) group or control group using the Patient Health Questionnaire-9. Between group differences of perceived stress, hopelessness, confidence, craving and abstinence were assessed at weeks 8 and 26. The interaction between depression symptoms (levels: DS and control) and the intervention (levels: MI and SC) was also assessed. Homeless smokers in the DS group reported higher levels of hopelessness, perceived stress, and craving. There was no effect of DS status on abstinence at week 8 or week 26. There was no significant interaction between depression symptoms (DS vs. Control) and the intervention (MI vs. SC). Despite reporting greater psychological distress, homeless smokers with depression symptoms in this sample had abstinence levels similar to the control group. Future research should explore protective factors among depressed smokers.


Disease burden of congenital cytomegalovirus infection in Japan.
Cytomegalovirus is the most frequently acquired congenital infectious agent that causes malformation in newborns in developed countries. Although there are many discussions worldwide about neonatal screening and treatment, there is scarce information relating to the lifetime economic burden of this disease, which is essential for calculating the cost-effectiveness of any screening and treatment programs. Economic and lifetime health burdens of congenital cytomegalovirus infection in the Japanese annual birth cohort in 2019 were calculated, using demographic, epidemiologic, health value, and economic indicators. The economic burden was divided into medical and social costs. Sensitivity analysis was performed, using high and low values for some indicators. Our model estimated that the overall cost due to congenital cytomegalovirus infection in 2019 was 27.6 billion JPY. Acute care costs comprised a small portion of the medical costs. Social costs were much higher than medical costs. Our study revealed the economic burden of congenital cytomegalovirus infection in Japan, which highlighted the significance of this disease. Our study will be helpful for guiding national strategies in Japan, including neonatal screening and early treatment.


Automatic diagnosis for cysts and tumors of both jaws on panoramic radiographs using a deep convolution neural network.
The purpose of this study was to automatically diagnose odontogenic cysts and tumors of both jaws on panoramic radiographs using deep learning. We proposed a novel framework of deep convolution neural network (CNN) with data augmentation for detection and classification of the multiple diseases. We developed a deep CNN modified from YOLOv3 for detecting and classifying odontogenic cysts and tumors of both jaws. Our data set of 1282 panoramic radiographs comprised 350 dentigerous cysts (DCs), 302 periapical cysts (PCs), 300 odontogenic keratocysts (OKCs), 230 ameloblastomas (ABs), and 100 normal jaws with no disease. In addition, the number of radiographs was augmented 12-fold by flip, rotation, and intensity changes. We evaluated the classification performance of the developed CNN by calculating sensitivity, specificity, accuracy, and area under the curve (AUC) for diseases of both jaws. The overall classification performance for the diseases improved from 78.2% sensitivity, 93.9% specificity,91.3% accuracy, and 0.86 AUC using the CNN with unaugmented data set to 88.9% sensitivity, 97.2% specificity, 95.6% accuracy, and 0.94 AUC using the CNN with augmented data set. CNN using augmented data set had the following sensitivities, specificities, accuracies, and AUCs: 91.4%, 99.2%, 97.8%, and 0.96 for DCs, 82.8%, 99.2%, 96.2%, and 0.92 for PCs, 98.4%,92.3%,94.0%, and 0.97 for OKCs, 71.7%, 100%, 94.3%, and 0.86 for ABs, and 100.0%, 95.1%, 96.0%, and 0.97 for normal jaws, respectively. The CNN method we developed for automatically diagnosing odontogenic cysts and tumors of both jaws on panoramic radiographs using data augmentation showed high sensitivity, specificity, accuracy, and AUC despite the limited number of panoramic images involved.


Adult coarctation of the aorta: Anaesthesia and postoperative management.
The complications following surgery for the correction of aortic coarctation are reviewed. The immediate postoperative increase in blood pressure is associated with a very high (750%) increase in plasma noradrenaline concentrations. The pre-operative management and preparation of the patient, the use of induced hypotension during surgery with careful haemodynamic control to prevent the hypoperfusion of the lower segment of the aorta, and the postoperative management with special reference to adequate control of blood pressure are discussed.


Poly(styrene-divinylbenzene)-based strong anion-exchange packing material for high-performance liquid chromatography of proteins.
An adsorbed polyethyleneimine coating was applied to sulfonated macroporous, microparticulate poly(styrene-divinylbenzene). The chemical, physical and chromatographic properties of the resulting strong anion-exchange packing material were thoroughly characterized. The dynamic load capacity of the experimental packing was comparable to that of large-pore diameter silica. Good recoveries of protein mass and enzyme activity were achieved. The new column withstood a variety of cleaning procedures and prolonged exposure to aqueous base. The retention times on the polystyrene-based column were similar to those on a silica and a commercial, polymeric, strong anion-exchange column. Chromatographic resolution of the new packing material was equal or superior to that provided by the other two packings.


Parathyroid hormone-related protein is a gravisensor in lung and bone cell biology.
Parathyroid Hormone-related Protein (PTHrP) has been shown to be essential for the development and homeostatic regulation of lung and bone. Since both lung and bone structure and function are affected by microgravity, we hypothesized that 0 x g down-regulates PTHrP signaling. To test this hypothesis, we suspended lung and bone cells in the simulated microgravity environment of a Rotating Wall Vessel Bioreactor, which simulates microgravity, for up to 72 hours. During the first 8 hours of exposure to simulated 0 x g, PTHrP expression fell precipitously, decreasing by 80-90%; during the subsequent 64 hours, PTHrP expression remained at this newly established level of expression. PTHrP production decreased from 12 pg/ml/hour to 1 pg/ml/hour in culture medium from microgravity-exposed cells. The cells were then recultured at unit gravity for 24 hours, and PTHrP expression and production returned to normal levels. Based on these findings, we have obtained bones from rats flown in space for 2 weeks (Mission STS-58, SL-2). Analysis of PTHrP expression by femurs and tibias from these animals (n=5) revealed that PTHrP expression was 60% lower than in bones from control ground-based rats. Interestingly, there were no differences in PTHrP expression by parietal bone from space-exposed versus ground-based animals, indicating that the effect of weightlessness on PTHrP expression is due to the unweighting of weight-bearing bones. This finding is consistent with other studies of microgravity-induced osteoporosis. The loss of the PTHrP signaling mechanism may be corrected using chemical agents that up-regulate this pathway. In conclusion, PTHrP represents a stretch-sensitive paracrine signaling mechanism that may sense gravity.


Newly synthesized small nuclear RNAs appear transiently in the cytoplasm.
Newly synthesized small nuclear RNA (snRNA) species U1 and U2 are easily identified in cytoplasmic fractions prepared by standard aqueous cell fractionation. However, because the mature stable snRNA species leak from isolated nuclei during cell fractionation, the possibility exists that these newly synthesized species also leak from the nucleus. To overcome the problems of nuclear leakage, mouse L929 cells were fractionated by cell enucleation. Enucleation extrudes the nuclei from cytochalasin-treated cells and produces cytoplasts that, by several criteria, are a bona fide cytoplasmic fraction uncontaminated by nuclear material. All six of the major snRNAs are present in the cytoplasts (c-snRNAs) shortly after synthesis. The species are identified by immunoprecipitation with specific antisera against the ribonucleoproteins and by Northern blotting and hybrid selection using cloned probes. This confirms and extends similar studies that used non-aqueous cell fractionation and manual dissection to overcome nuclear leakage. Kinetic studies demonstrate that the c-snRNAs return to the interphase nucleus after approximately 20 minutes in the cytoplasm. The U2 precursor U2' is processed to mature-sized U2 in the cytoplast fractions before returning to the nucleus. The c-snRNAs occur in ribonucleoprotein particles with similar antigenicity to the mature nuclear particles within six minutes of transcription. This suggests that in mammalian cells, important steps in the assembly of these ribonucleoproteins occur in the cytoplasm.


Pattern of covariation between life-history traits of European birds.
A large amount of variation is found in most reproductive traits of birds. Clutch size for instance, can vary from 1 to 15 between species of similar body weight. The adaptive significance of this variation is only poorly understood. According to life-history theory, large clutch size and early onset of reproduction are expected when the chances of survival are low. There is some support for the existence of such a relationship from studies of single species. Here I present evidence that, in European birds, clutch size is increased, and onset of reproduction occurs earlier in life, when the probability of survival is low.


Interspecies scaling of renally secreted drugs.
The objective of this study is to predict pharmacokinetic parameters (clearance, volume of distribution at steady state, and elimination half-life) in humans from animal data for drugs which are renally secreted in humans. Pharmacokinetic parameters of ten drugs were scaled-up from animal data obtained from the literature. Using simple allometry (pharmacokinetic parameter of interest vs body weight), total, renal and nonrenal clearances, volume of distribution and half-life were predicted in humans. The predicted parameters were compared with the observed parameters. The results of the study indicated that it is likely that the predicted total and renal clearances from animal data will be underestimated in humans for renally secreted drugs. The prediction of renal clearance was improved by normalizing the renal clearance by a 'correction factor' for animals who exhibited renal secretion. The predicted volume and half-life were comparable with the observed values in man. Overall, the results of this study indicate that caution should be employed in interpreting the total and renal clearance of renally secreted drugs predicted by the allometric approach.


Comparison of vascularity and angiogenesis in primary invasive mammary carcinomas and in their respective axillary lymph node metastases.
It is well established that the ability of a neoplasm to induce a blood supply from a pre-existing circulation (angiogenesis) is a major factor in tumour growth, invasion and metastasis. However, the angiogenic potential of metastases and their subsequent growth have not been extensively studied. The question arises: can metastatic clones induce the same level of angiogenesis as in the primary neoplasm they emanated from? In this study it is hypothesised that in the same patient the level of vascularity and angiogenesis is the same in both the primary invasive ductal carcinoma and in the axillary lymph node metastasis at the time of surgery, according to Kerbels theory of clonal-dominance. To directly address the hypothesis, morphological measures of the established blood/lymphatic circulation (vascularity) as well as estimates of angiogenesis (endothelial cell proliferation) were measured in primary tumours and directly compared to the same parameters in the corresponding lymph node metastasis in a case by case basis (n = 17). The results demonstrate varying associations between the level of vascularity and angiogenesis between matched individual tumours and their metastatic lymph nodal deposits. It is possible that either variations in the angiogenic characteristics of the metastasising clone or local or systemic promoters or inhibitors of angiogenesis influence tumour angiogenesis at the different sites.


Effect of positional change and inhalant anesthesia on parameters of acoustic reflectometry.
Purpose of this study was to find out the effect of positional change and inhalant anesthesia on acoustic reflectometry (AR) parameters (reflectivity and curve angle). AR parameters were measured on 58 ears with otitis media in sitting position before anesthesia and in supine position under inhalant anesthesia, subsequently. Under anesthesia, ears with effusion disclosed more changes in reflectivity (Chi-squared analysis, chi2-test; P<0.05) and curve angle (P>0.1) than those without effusion. Further, inhalant anesthesia caused more changes in the false negative ears (63.63%) than in those with effusion having positive test before anesthesia (12.90%) (P<0.001). From the data of this study, it could be said that reflectivity shows changes according to the amount of effusion which is in contact with the tympanic membrane under anesthesia, and that curve angle becomes more sensitive to detect effusion when anesthetic gas diffuses into the middle ear with effusion, probably due to the pushing of effusion towards the tympanic membrane.


Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity.
The hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. Rectal or vaginal mucosal administration of 10(4)-10(7) unmatched mononuclear cells induced significant dose-dependent T-cell proliferation stimulated by the allogeneic cells in rhesus macaques. This was associated with a significant upregulation of CD8(+) T-cell-derived suppressor factor, as well as the CC chemokines CCL3, CCL4 and CCL5. In addition, there was a dose-dependent increase in antibodies to CCR5. These responses were associated with decreased in vitro simian immunodeficiency virus (SIV) infectivity of CD4(+) T cells. A further investigation of SIV infectivity of CD4(+) T cells separated from multiparous macaques also showed significant inhibition compared with male macaques. It is suggested that vaginal or rectal exposure to allogeneic stimulation by a partner's HLA antigens in seminal fluid, as occurs during sexual intercourse, or immunization by semi-allogeneic fetuses in multiparous females may elicit protection against SIV or human immunodeficiency virus infection.


Evolution of surgical techniques for atrial septal defect repair in adults: a 10-year single-institution experience.
We retrospectively analyzed our experience in atrial septal defect repair with varied minimally invasive surgical approaches. From 1997 to 2006, 64 patients underwent surgical repair of atrial septal defects in our center. Patients were grouped into four groups according to the approach used; group 1 (n = 16), partial lower sternotomy; group 2 (n = 20), right anterior small thoracotomy with transthoracic clamping; group 3 (n = 4), right anterior small thoracotomy with endoaortic balloon clamping; and group 4 (n = 24), totally endoscopic approach with the use of the da Vinci surgical system (Intuitive Surgical, Mountain View, Calif). Preoperative diagnosis was a large secundum type atrial septal defect in 60 patients, primum type in 3 patients, and sinus venosus type in 1 patient. Complete atrial septal defect closure was verified by intraoperative transesophageal echocardiography in all patients. There was neither perioperative mortality nor major complication. Groups 3 and 4 had significantly longer aortic crossclamp, cardiopulmonary bypass, and skin-to-skin operative times than had groups 1 and 2 (P = .000). All groups had similar ventilation time, postoperative drainage, and intensive care unit and hospital stays. Only 2 patients in group 4 were converted to the minithoracotomy owing to endoaortic balloon failure. During the follow-up of 30 +/- 24.3 months, 1 patient in group 3 was reoperated on owing to significant residual shunting. All types of atrial septal defects can be repaired via those four different approaches as safely as can be done by the conventional technique. General complications during surgical procedures are negligible. These approaches may be considered a standard treatment and an adjunct to transcatheter treatment options in atrial septal defect repair.


Relationships between blood and follicular fluid urea nitrogen concentrations and between blood urea nitrogen and embryo survival in mares.
High blood urea nitrogen (BUN) concentration is linked to low fertility in cows and ewes; however, this relationship has not been reported in mares. The study characterized the relationship between BUN and follicular fluid urea nitrogen (FUN) during follicle growth (Experiment 1) and the impact of BUN from embryo donors on the pregnancy outcome of recipient mares (Experiment 2). In experiment one, follicular fluid and blood samples were collected from mares during diestrus with growing follicles and during estrus with pre-ovulatory follicles (n = 16 and 10 mares, respectively). In experiment two, BUN concentrations of embryo donors were related to pregnancy outcome after embryo transfer. In experiment one, there was a strong positive correlation between BUN and FUN (R = 0.83; P < 0.0001), with higher BUN in mares with growing follicles than with preovulatory follicles (P = 0.004) and higher FUN in growing follicles than in preovulatory follicles (P = 0.031). In experiment two, BUN was higher in donor mares that produced unsuccessful embryos compared to donor mares that produced embryos resulting in successful pregnancies at D14 (P < 0.03). Additionally, there was an effect of age (P = 0.01) and interaction between age and lactation (P = 0.009) in donor mares for embryo survival after embryo transfer. Donor mares with unsuccessful embryos were older than donor mares with successful embryos. Therefore, these experiments showed that BUN was related to follicular fluid environment as well as to the survival of Day 7-8 embryos after transfer to recipient mares.


The whole experience of public hospital physicians from several specialties with biopharmaceutical effectiveness, safety, adverse drug reactions and interchangeability: A qualitative study.
Although there is increasing support for biosimilar medicines by the Iraqi Ministry of Health (MOH), there is scarce information about whether physicians accept these medicines and support movement toward replacing reference medicines with their biosimilar counterparts. The study objectives were to 1) explore in-depth the perceptions of Iraqi physicians working in public hospitals about the difference in effectiveness and safety between biosimilar medicines and their reference biological counterparts, 2) evaluate physicians' barriers to prescribing biosimilar medicines, 3) assess the adherence of physicians to the new pharmacovigilance regulations on reporting biopharmaceutical adverse drug reactions (ADRs) and 4) identify any barriers facing physicians to reporting biopharmaceutical- ADRs. This qualitative study included face-to-face and virtual semi-structured interviews involving physicians from different disciplines who had experience with biological or biosimilar medicines. The interviews were conducted between November 6, 2020, and February 7, 2021. Thematic analyses were used to analyze qualitative data generated from the interviews. The study sample included 36 physicians (6 women and 30 men) from seven different specialties at ten governmental hospitals mainly in Baghdad, and one physician was from Mosul, Iraq. Because most physicians had insufficient experience with biosimilar medications and were not sure about their effectiveness, the majority were hesitant to prescribe them. Most physicians preferred to prescribe reference biological medicines initially. However, the initial prescribing and switching between a reference and counterpart biosimilar relies on its availability. They chose biosimilar medications that have been approved by the U.S. FDA or EMA. Most physicians were unaware about the new pharmacovigilance regulations to report adverse biopharmaceutical reactions. The physicians tended to underreport biopharmaceutical ADRs and believed that inadequate physician-pharmacist collaboration negatively impacts preventing and reporting ADRs. Medicine procurement in healthcare settings should focus on sustainably securing high-quality biopharmaceuticals rather than looking only at costs to enhance physician experience and patient clinical outcomes. Promoting documentation, monitoring, and physician-pharmacist collaboration is pivotal to prevent, monitor, and treat biopharmaceutical ADRs.


Prevention of pacemaker mediated arrhythmias.
Pacemaker mediated re-entry tachyarrhythmias and their causes are discussed. Several methods to prevent these arrhythmias are presented. It is shown that the most efficient method incorporates a long refractory period of the atrial detection after ventricular depolarization. The benefits of a short A-V delay after atrial sensing are discussed.


TGFBI promoter hypermethylation correlating with paclitaxel chemoresistance in ovarian cancer.
The purpose of this study is to determine the methylation status of Transforming growth factor-beta-inducible gene-h3 (TGFBI) and its correlation with paclitaxel chemoresistance in ovarian cancer. The methylation status of TGFBI was examined in ovarian cancer and control groups by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). The TGFBI expression and cell viability were compared by Quantitative Real-Time PCR, Western Blotting and MTT assay before and after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment in 6 cell lines (SKOV3, SKOV3/TR, SKOV3/DDP, A2780, 2780/TR, OVCAR8). In our results, TGFBI methylation was detected in 29/40 (72.5%) of ovarian cancer and 1/10 (10%) of benign ovarian tumors. No methylation was detected in normal ovarian tissues (P < 0.001). No statistical correlation between RUNX3 methylation and clinicopathological characteristics was observed. A significant correlation between TGFBI methylation and loss of TGFBI mRNA expression was found (P < 0.001). The methylation level of TGFBI was significantly higher in paclitaxel resistant cell lines (SKOV3/TR and 2780/TR) than that in the sensitive pairs (P < 0.001). After 5-aza-dc treatment, the relative expression of TGFBI mRNA and protein increased significantly in SKOV3/TR and A2780/TR cells. However, no statistical differences of relative TGFBI mRNA expression and protein were found in other cells (all P > 0.05), which showed that re-expression of TGFBI could reverse paclitaxel chemoresistance. Our results show that TGFBI is frequently methylated and associated with paclitaxel-resistance in ovarian cancer. TGFBI might be a potential therapeutic target for the enhancement of responses to chemotherapy in ovarian cancer patients.


Treatment of adult neural progenitor cells prior to transplantation affects graft survival and integration in a neonatal and adult rat model of selective retinal ganglion cell depletion.
We tested whether microenvironmental changes surrounding apoptotic neural degeneration, cellular pre-treatment and timing of transplant can influence the survival and differentiation of transplanted cells. This was done by transplanting adult hippocampal precursor cells (AHPCs) into normal and retinal ganglion cell (RGC) depleted rat retinae. Apoptotic RGC death was induced in neonates by removal of the contralateral superior colliculus (SC) and in adults by unilateral optic nerve transection, with or without a peripheral nerve (PN) graft. AHPCs were transplanted 24 h after SC ablation, or 5, 7 or 14 days following optic nerve (ON) transection. Hosts received untreated grafts, or grafts treated by co-culture with embryonic retinal explants or the neuropeptide somatostatin. AHPCs integrated within all neonatal and 65% of adult retinae. Greater numbers of AHPCs were observed within the ganglion cell layer (GCL) in SC lesioned hosts. Explant co-culture induced proliferation of grafted AHPCs within host retinae. Somatostatin-treatment resulted in reduced overall engraftment but increased integration within the GCL. In lesioned adults, greatest GCL engraftment was observed following 7 or 14 day grafts. Some AHPCs in the inner retina expressed neuronal antigens and extended processes into the ON. These data indicate that various factors can influence the behaviour of grafted cells and work towards encouraging the functional restoration of retinal circuitry.


Erratum: The mediating role of Perceived Stress in the Relationship between Neuroticism and Death Anxiety among Women in Isfahan during the Coronavirus Pandemic.
[This corrects the article on p. 78 in vol. 12, PMID: 37288392.].


Prognostic implications of the response of arterial ketone body ratio and insulin secretion to glucose load in major hepatectomy.
Impaired glucose tolerance is a serious obstacle to major hepatic resection. To assess the predictability of surgical risk in major hepatectomy for patients with chronic liver diseases from the viewpoint of glucose metabolism, we evaluated the insulinogenic index (II) and redox tolerance index (RTI) in 48 patients who underwent major hepatectomy at our university hospital due to hepatocellular carcinoma. Patients with low II and low RTI fell into the high risk group. Based on this finding, the Z score was developed as an index of patient risk for major hepatectomy: Z = 3.11 x [II] + 1.43 x [RTI] - 2.27. When the Z score was negative, mortality reached 33.3%, but when it was positive the mortality was only 3.2%. Intraportal insulin supplementation after hepatectomy to patients with a negative Z score could reduce mortality. Preoperative evaluation of surgical risk by Z score seems to be useful for predicting patient prognosis after hepatectomy.


Follicular lymphoma: clinical features and treatment.
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin's lymphoma (NHL) in the Western world, constituting up to 22% of the total cases of NHL. This article describes the clinical characteristics of FL, its prognostic indicators, and its clinical course, including transformation to an aggressive lymphoma. Primary management and therapies for recurrent FL are detailed.


Kinetic activity of spermatozoa from fertile subjects and asthenozoospermic infertile patients.
The motility characteristics of spermatozoa from asthenozoospermic semen were investigated and compared to the same parameters in fertile semen. The motility characteristics assessed by the CellSoft semen analyser (CRYO Resources Ltd, NY) were the following: curvilinear velocity (VCL), straight line velocity (VSL), amplitude of lateral head displacement (ALH), linearity (%LIN), and beat cross frequency (BCF). Analysis of the data indicated a decreased kinetic activity in the spermatozoa from the asthenozoospermic group which is expressed as a highly significant decrease (P < 0.002) in the VCL and VSL compared to velocities from normospermic samples. Moreover, percentage linearity and ALH were also statistically lower (P < 0.05) in this group. However, no difference was evidenced for the BCF.


Cognitive Restructuring Before Versus After Exposure: Effect on Expectancy and Outcome in Individuals With Claustrophobia.
Maximizing the discrepancy between expected and actual outcomes during exposure (i.e., expectancy violation) is thought to optimize inhibitory learning. The current study examined Craske et al.'s suggestion that engaging in cognitive restructuring (CR) before exposure prematurely reduces expectancy and mitigates outcomes. Participants (N = 93) with claustrophobia were randomly assigned to either 15 minutes of CR before exposure (CR Before) or 15 minutes of CR after exposure (CR After). Although the CR Before condition experienced greater expectancy reduction before exposure than the CR After condition, both groups experienced similar overall expectancy reduction by the end of the intervention. Groups experienced similar gains, with large significant improvement at posttreatment and follow-up. Results suggest that both cognitive therapy and exposure therapy lead to expectancy reduction, but that the order of these interventions does not impact outcome. Clinicaltrials.org registration #NCT03628105.


HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic Stress-Induced major depressive disorder.
Neuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. Here, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. Bioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. The differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. Our study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.


The development of a physical therapy service to treat urinary incontinence: Results of a RE-AIM evaluation.
A conservative physiotherapy service development addressed to treat urinary incontinence for older women was studied using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. We conducted a pragmatic case study design based on RE-AIM. Included women ≥ 60 years of age, with self-reported UI symptoms. A total of 34 older women were enrolled in the service with a mean age of 61.53 years. There was a significant improvement in the strength of the pelvic floor muscles, power, endurance, and fast contraction capacity after the intervention, however, it was observed a high dropout rate. Program implementation was supported by Physical Therapy teams who engaged in care coordination. The program has been maintained for over 4 years. Our findings demonstrate that UI patients would benefit from physiotherapy treatment and that this intervention is feasible. This RE-AIM evaluation provides lessons learned and strategies for future adoption, implementation, and maintenance of a Physical Therapy pelvic service.


Hydrographic and sediment characteristics of seagrass meadows of the Gulf of Mannar Marine Biosphere Reserve, South India.
The aim of the study was to examine the spatial and temporal variations in the physicochemical parameters of seagrass meadows of the Gulf of Mannar, South India using multivariate statistical techniques, namely, cluster analysis (CA) and principal component analysis (PCA), to explore the relationship. There were clear spatial and temporal variations in physicochemical variables of the seagrass meadow of the Gulf of Mannar, but such changes were subjected to seasonal variations especially during monsoon and post-monsoon seasons. The multivariate statistical techniques, viz., CA and PCA helped in the discrimination of islands according to the physicochemical parameters of the seagrass meadows. It was inferred that electrical conductivity, nitrate, particulate organic carbon, and phosphate strongly determined the discrimination of 19 islands, respectively, upon physicochemical characteristics of their seagrass meadows. These results highlight the important role of seagrasses in the Gulf of Mannar Marine Biosphere Reserve.


Osteomyelitis infection disguised as Reiter's syndrome in a child: A case report.
Reiter's syndrome (reactive arthritis) should always prompt a thorough clinical investigation of a potentially more serious disease condition in every pediatric patient and adults. It should always be regarded as a warning sign and not a disease. This is a case of a 16-year-old African boy with osteomyelitis presenting with symptoms of reactive arthritis (Reiter's syndrome).


Effect of reduced oxygen tension and long-term mechanical stimulation on chondrocyte-polymer constructs.
We have investigated the influence of long-term confined dynamic compression and surface motion under low oxygen tension on tissue-engineered cell-scaffold constructs. Porous polyurethane scaffolds (8 mm x 4 mm) were seeded with bovine articular chondrocytes and cultured under normoxic (21% O(2)) or hypoxic (5% O(2)) conditions for up to 4 weeks. By means of our joint-simulating bioreactor, cyclic axial compression (10-20%; 0.5 Hz) was applied for 1 h daily with a ceramic ball, which simultaneously oscillated over the construct surface (+/-25 degrees; 0.5 Hz). Culture under reduced oxygen tension resulted in an increase in mRNA levels of type II collagen and aggrecan, whereas the expression of type I collagen was down-regulated at early time points. A higher glycosaminoglycan content was found in hypoxic than in normoxic constructs. Immunohistochemical analysis showed more intense type II and weaker type I collagen staining in hypoxic than in normoxic cultures. Type II collagen gene expression was slightly elevated after short-term loading, whereas aggrecan mRNA levels were not influenced by the applied mechanical stimuli. Of importance, the combination of loading and low oxygen tension resulted in a further down-regulation of collagen type I mRNA expression, contributing to the stabilization of the chondrocytic phenotype. Histological results confirmed the beneficial effect of mechanical loading on chondrocyte matrix synthesis. Thus, mechanical stimulation combined with low oxygen tension is an effective tool for modulating the chondrocytic phenotype and should be considered when chondrocytes or mesenchymal stem cells are cultured and differentiated with the aim of generating cartilage-like tissue in vitro.


Synthesis, fluorescence and biodistribution of a bone-targeted near-infrared conjugate.
Enhanced imaging of early-stage bone abnormalities, such as primary tumors or metastases is highly required as the widely-used bone scan frequently lacks the desired sensitivity. Near IR (NIR) fluorescence imaging affords high contrast and enhanced sensitivity, as body tissue expresses minimal autofluorescence at NIR range (600-1200 nm). Indocyanine green (ICG), a biocompatible NIR dye, is widely used in the imaging of various organs, such as liver, heart and blood circulation. We report the preparation and in-vivo testing of a bone-targeting ICG derivative, in comparison to the parent molecule(s). Since ICG itself is chemically unreactive, and could not form conjugates, we prepared two novel ICG conjugatable derivatives. The overall ICG structure was maintained while only a replacement of one or two sulfonate groups with carboxylic acids resulted in new linkers for covalent binding to biomolecules. These derivatives were evaluated for their fluorescence and biodistribution in comparison to ICG and were found to be comparable. One of the novel ICG-derivatives was conjugated to a bone-targeting moiety and this new compound was found to bind to growing regions of the skeleton, and emit fluorescence for as long as two weeks in young mice.


Establishing community services for the mentally ill: a summary of lessons learned.
In summary, the development of programs in the community serving the severely and chronically mentally ill is a political-sociological activity requiring a detailed working knowledge of the community to be involved, a clear understanding of objectives and specific agreements related to the program to be developed, adequate and stable funding, appropriate supportive and ancillary resources, significant bureaucratic skill and flexibility, adequate time for appropriate community education and feedback from key community leaders, a certain amount of clairvoyance in anticipating difficulties and unexpected problems, an immense amount of perseverance and, finally--and probably as important as any other single element--timing and luck.


Minor but key chlorophylls in photosystem II.
A 'metal-free' chlorophyll (Chl) a, pheophytin (Phe) a, functions as the primary electron acceptor in PS II. On the basis of Phe a/PS II = 2, Phe a content is postulated as an index for estimation of the stoichiometry of pigments and photosystems. We found Phe a in a Chl d-dominant cyanobacterium Acaryochloris marina, whereas Phe d was absent. The minimum Chl a:Phe a ratio was 2:2, indicating that the primary electron donor is Chl a, accessory is Chl d, and the primary electron acceptor is Phe a in PS II of A. marina. Chl d was artificially formed by the treatment of Chl a with papain in aqueous organic solvents. Further, we will raise a key question on the mechanisms of water oxidation in PS II.


Effects of hypoxia caused by mussel farming on benthic foraminifera in semi-closed Gamak Bay, South Korea.
Seawater monitoring and geochemical and benthic foraminiferal analysis of sediments were conducted to identify the effects of hypoxia created by a mussel farm on benthic foraminifera in a semi-closed bay. Extremely polluted reductive conditions with a high content of organic matter (OM) at >12.0% and oxygen minimum zones (OMZs) with dissolved oxygen (DO) <0.4mg∙L(-1) were formed below the mussel farm in the northwest area of Gamak Bay, and gradually diffused toward the south. Highly similar patterns of variation were observed in species diversity, abundance frequency, and benthic foraminiferal assemblage distributed from Elphidium subarcticum-Ammonia beccarii in the northwest area through E. subarcticum-A. beccarii-Trochammina hadai, E. subarcticum-A. beccarii-Elphidiumclavatum, and E. clavatum-Ammonia ketienziensis in the southern area. These phenomena were caused by hydrodynamics in the current water mass. It was thought that E. subarcticum is a bioindicator of organic pollution caused by the mussel farm.


Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow-derived human mesenchymal stem cells for bone tissue regeneration.
Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow-derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non-stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up-regulation of Collagen-I, ALP, and Runx-2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629-640, 2018.


Teaching and assessing family medicine clerks' use of medical interpreters.
Academic health centers must develop strategies to prepare health care providers to meet the needs of an increasingly diverse population. We designed a curriculum module, including didactic presentation and a standardized patient experience, to teach and evaluate the knowledge and skills necessary for third-year family medicine clerks to effectively communicate with non-English-speaking patients when using interpreters in clinical settings. Analyses indicated improvement both in students' knowledge and skills following participation in the curriculum module. The instructional intervention was successful in improving students' effective use of interpreters in a simulated clinical setting.


Antibodies elicited by N2,N2-7-trimethylguanosine react with small nuclear RNAs and ribonucleoproteins.
The 5' ends of U1, U2, U3, U4, and U5 small nuclear RNAs (snRNA) are capped by a structure which contains N2,N2-7-trimethylguanosine (m2,2,7 G). m2,2,7 G was used as hapten to raise antibodies in rabbits, and these antibodies were linked to Sepharose. When deproteinized RNA was passed through this antibody column, these snRNA species were retained by the column. Conversely, 4 S, 5 S, 5.8 S, U6, and 7 S RNA, whose 5' termini do not contain m2,2,7 G, were not recognized. After a nuclear extract was loaded on the column, U1 RNA and some U2 RNA were retained. Therefore, the 5' ends of at least U1 RNA are accessible when this RNA species is in small nuclear ribonucleoprotein particle (snRNP) form. This is of interest, since it has been proposed that the 5' terminus sequence of U1 RNA may hybridize with splice junctions in heterogeneous nuclear ribonucleoprotein particles (hnRNP) during mRNA splicing. The retention of m2,2,7 G-containing RNA species by these antibodies is not due to association of snRNAs or snRNPs with heterogeneous nuclear RNA (hnRNA) or hnRNP (and antibody recognition of 7-monomethylguanosine residues in hnRNA), since the reaction still occurs after removal of hnRNA or hnRNP by sucrose gradient centrifugation.


Male Hormonal Contraception: Where Are We Now?
Hormonal male contraception clinical trials began in the 1970s. The method is based on the use of exogenous testosterone alone or in combination with a progestin to suppress the endogenous production of testosterone and spermatogenesis. Studies using testosterone alone showed that the method was very effective with few adverse effects. Addition of a progestin increases the rate and extent of suppression of spermatogenesis. Common adverse effects include acne, injection site pain, mood change including depression, and changes in libido that are usually mild and rarely lead to discontinuation. Current development includes long-acting injectables and transdermal gels and novel androgens that may have both androgenic and progestational activities. Surveys showed that over 50 % of men will accept a new male method and female partners will trust their partner to take oral "male pills." Partnership between government, nongovernment agencies, academia, and industry may generate adequate interest and collaboration to develop and market the first male hormonal contraception.


Potential Use of SGLT-2 Inhibitors in Obstructive Sleep Apnea: A new treatment on the horizon.
Obstructive sleep apnea (OSA) is characterized by hypoxic episodes due to collapse of the airway during sleep and is frequently associated with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). There is currently no pharmacological agent approved for the treatment of OSA. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to both increase life expectancy and quality of life of these patients making them promising agents for this role. There are relatively few studies investigating this possible beneficial relationship between these drugs and OSA. We aimed to increase awareness on the potential benefits of SGLT2 inhibitors in OSA patients by describing the current evidence on the effectiveness of these inhibitors in both overall and cardiovascular morbidity and mortality. We performed a literature search for articles reporting on the use of SGLT2 inhibitors in patients with OSA and T2DM. We identified 4 manuscripts studying the use of SGLT2 inhibitors in 475 OSA patients with T2DM. Among them, 332 patients were administered SGLT2 inhibitors, and 143 patients were in a control group. SGLT2 inhibitors have many potential positive impacts on OSA patients by targeting various mechanisms involved in OSA pathogenesis. SGLT2 inhibitors are prime pharmacological candidates for the treatment of OSA, and additional studies are needed to better explore mechanisms and outcomes unique to this population. Additionally, patients with OSA often have multiple comorbidities that are clinical indications for SGLT2 inhibitor therapy. Physicians should recognize and encourage the use of these agents in such patients.


Regulation by extracellular Na+ of cytosolic Mg2+ concentration in Mg(2+)-loaded rat sublingual acini.
The regulation of cytosolic free Mg2+ concentration ([Mg2+]i) in Mg(2+)-loaded rat sublingual mucous acini was examined using the Mg(2+)-sensitive fluorescent indicator mag-fura-2. Loading sublingual acini with 5 mM Mg2+ elevated the [Mg2+]i from 0.35 +/- 0.01 mM to 0.66 +/- 0.01 mM. Removal of extracellular Mg2+ resulted in a significantly faster [Mg2+]i decrease in Mg(2+)-loaded acini than in unloaded acini. Membrane depolarization with high extracellular [K+] and inhibition of P-type ATPases by vanadate did not alter the [Mg2+]i decrease, indicating that the Mg2+ efflux mechanism is not electrogenic. Na(+)-free medium inhibited 80% of the [Mg2+]i decrease suggesting that a Na(+)-dependent Mg2+ efflux pathway mediates the [Mg2+]i decrease. Accordingly, the Na(+)-dependent antiport inhibitor quinidine reduced > 80% of the [Mg2+]i decrease, suggesting that the Na(+)-dependent Mg2+ efflux is mediated by the Na+/Mg2+ antiport system. Mg2+ efflux was also partly driven by K+. The [Mg2+]i decreased was significantly inhibited by carbachol, a muscarinic agonist, but not by cAMP. These results indicate that in sublingual acinar cells a Na(+)-dependent pathway mediates Mg2+ efflux and that muscarinic stimulation may regulate Mg2+ extrusion.


Relationship between serum asymmetric dimethylarginine and left ventricular structure and function in patients with end‑stage renal disease treated with hemodialysis.
Asymmetric dimethylarginin (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase, considered an effector of endothelial dysfunction. Among multiple diseases associated with elevated ADMA, chronic renal disease is often mentioned. ADMA is thought to be related to certain adverse cardiovascular effects of chronic uremia. The association between left ventricular (LV) structure and function and ADMA has been studied in numerous papers, but only few of them addressed this issue in end‑stage renal disease (ESRD). The aim of the study was to analyze associations between serum ADMA (sADMA) levels and LV geometry and function in patients with ESRD treated with hemodialysis (HD). The study group included 56 patients (31 women, 25 men) aged 59.0 ±13.1 years, treated with HD for 70 ±67 months. sADMA and biochemical parameters were measured and echocardiography was performed. sADMA levels were also measured in the control group of healthy individuals matched for age. Mean sADMA levels in patients were 2.39 ±1.0 μmol/ and were significantly higher compared with controls (0.55 ±0.12 μmol/l; P <0.01). Based on echocardiography, patients were classified into the following groups: normal LV geometry (17.8%), concentric remodeling (8.9%), concentric hypertrophy (35.7%), excentric hypertrophy (37.5%), impaired systolic function (10.7%), and impaired diastolic function (71.4%) (1 patient could be in 1 or more groups). sADMA correlated with mean (r = 0.78; P <0.05) and relative (r = 0.64; P <0.05) LV wall thickness and with the LV mass index (r = 0.65; P <0.05), but not with the indexes of systolic and diastolic function. sADMA was significantly higher in patients with excentric hypertrophy, concentric remodeling, and concentric hypertrophy compared with patients with normal LV geometry, and the highest was in patients with concentric hypertrophy. Our study demonstrated an association between sADMA and disturbances in LV geometry in patients with ESRD treated with HD.


Plasmodium berghei: influence of infection on the oxidant and antioxidants levels in pregnant BALB/c mice.
Malarial infection during pregnancy has been associated with maternal anemia and death, abortion, still-birth and is a major cause of low birth weight, an important risk factor for infant morbidity and mortality in endemic areas. The present study was designed to delineate the oxidative stress in various organs (liver, spleen, kidney, brain and placenta) of pregnant Plasmodium berghei infected BALB/c mice. It was observed that pregnant-infected mice had higher parasitaemia than nonpregnant-infected mice. Most notably, levels of malondialdehyde (MDA), a measure of lipid peroxidation, reduced glutathione (GSH) and superoxide dismutase (SOD) levels were significantly higher in the liver, spleen, kidney and brain of pregnant-infected mice compared with pregnant mice. Although MDA levels were significantly higher, GSH and SOD levels remained unaltered in the placenta of pregnant-infected mice compared with pregnant mice. Furthermore, catalase activity was significantly lower in all the organs of pregnant-infected mice compared with pregnant mice. Histopathological observations in the organs clearly show the cellular and morphological alterations that may be occurring due to increased lipid peroxidation. Taken together, the data suggest that the increased severity of malarial infection during pregnancy may be due to accentuated oxidative stress.


Mutagenicity of isoniazid: testing for somatic chromosome aberrations in mouse embryos.
Isonicotinic acid hydrazide (INH) were given by peroral intubation to pregnant mice of strain C57BL/6Ffm on day 9 of pregnancy, INH was given in the following doses: 0, 5, 25, and 125 mg/kg solved in physiological saline. Cytogenetic analysis of homogenized embryos 6, 12, 24, and 48 h, resp., after treatment of the females did not show any increase of the rate of gaps or chromosomal aberrations.


Olsenella timonensis sp. nov., a new bacteria species isolated from the human gut microbiota.
Olsenella timonensis sp. nov., strain Marseille-P2300T (= CSUR P2300; =DSM102072), is a new bacterial species from the phylum Firmicutes in the family Atopobiaceae.This bacteria species was isolated from the human gut microbiota.


Comparative Activity of Carbapenem Testing (COMPACT) study in Germany.
The aim of this study was to determine the current susceptibility of hospital isolates of contemporary Gram-negative pathogens to the carbapenems doripenem, imipenem and meropenem. Between May and October 2008, seven centres in Germany were invited to collect and submit Pseudomonas aeruginosa, Enterobacteriaceae and other Gram-negative bacterial Intensive Care Unit (ICU)/non-ICU isolates from patients with complicated intra-abdominal infections (cIAIs), bloodstream infections (BSIs) or nosocomial pneumonia (NP). Susceptibility was determined at each centre by Etest. A central laboratory performed species confirmation as well as limited susceptibility and quality control testing. In total, 363 isolates were collected, comprising 46.0% Enterobacteriaceae, 45.2% P. aeruginosa, 4.7% Acinetobacter spp. and 4.1% other Gram-negatives. Most isolates (47.9%) were collected from NP, 32.8% were from cIAIs and 19.3% from BSIs; 57.3% were obtained from ICU patients. The MIC(90) values (minimum inhibitory concentration for 90% of the isolates) for doripenem, meropenem and imipenem were, respectively, 4, 16 and 32 mg/L against P. aeruginosa, 0.06, 0.06 and 0.5mg/L against Enterobacteriaceae and ≥ 64 mg/L for each carbapenem against other Gram-negative isolates. Using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 81.1%, 75.6% and 79.3% of P. aeruginosa were susceptible to doripenem, imipenem and meropenem, respectively. Against all pathogens combined, MIC(90) values for ICU versus non-ICU isolates, respectively, were 4 mg/L vs. 1mg/L for doripenem, 8 mg/L vs. 1mg/L for meropenem and ≥ 64 mg/L vs. 8 mg/L for imipenem. Doripenem showed comparable activity against P. aeruginosa from patients with BSIs, cIAIs or NP. Similar findings were observed for Enterobacteriaceae and other Gram-negatives, including Acinetobacter spp. Doripenem generally showed similar or slightly better activity than meropenem and better activity than imipenem against Gram-negative pathogens collected in Germany.


Optic nerve decompression.
Post-traumatic deterioration of vision requires thorough ophthalmologic evaluation, as well as computed tomographic scanning of the orbits and central visual pathways if no obvious ocular origins of the visual decrement are detected. When optic nerve trauma is a suspected etiology, the patient should be treated with megadose intravenous steroids, as well as optic nerve decompression performed after 12 to 24 hours if improvement of vision fails to occur.


Factors affecting the growth and titration by immunofluorescence of simian foamy virus.
This paper presents some observations concerned with the growth of simian foamy virus and some modifications which should be introduced to the fluorescence assay of foamy virus. The modified procedure is the most sensitive method described for the titration of foamy virus. Examination of the optimal conditions for the growth and titration by fluorescence assay of simian foamy virus showed that the virus was particularly sensitive to changes in virus and cell concentration. At the low cell concentrations employed previously a "saturation-type" response was obtained with high titre virus and virus adsorption efficiency was decreased as input virus was diluted. Maximum virus production was obtained with high cell concentrations at input multiplicities of 5 and 10. At high multiplicities of infection more than 90 per cent of the cells adsorbed virus but only 45 per cent became infected, this appeared to be related to cell DNA synthesis.