Transperitoneal laparoscopic nephroureterectomy for native upper tract urothelial carcinoma in renal transplant recipients.
To analyze the safety and clinical outcome of laparoscopic nephroureterectomy (LNUT) for native upper tract urothelial carcinoma (UC) in renal transplant (RT) recipients. We conducted a retrospective analysis of 956 RT recipients from January 2003 to December 2010 to evaluate the benefit of LNUT for patients who were diagnosed with de novo UC after renal transplantation. Women predominated (10/11, 91 %) in the 11 patients with upper tract UC who underwent LNUT. Five patients underwent LNUT ipsilateral to the transplanted kidney, 4 patients underwent contralateral LNUT, and 2 patients underwent bilateral LNUT. Nine were operated with LNUT combining resection of bladder cuff, 2 with right ureteral cancer underwent open ureterectomy with bladder cuff due to severe adhesions attached to the lesion. The mean surgical duration was 184.2 min (105-305), the mean blood loss was 182.3 ml (20-500), and the mean hospitalization time was 6.7 days (5-9). The mean levels of preoperative and postoperative serum creatinine were 0.99 mg/dl (0.78-1.16) and 1.01 mg/dl (0.89-1.18), respectively. No intraoperative complications occurred. One patient died of multiple metastases at 13 months after LNUT. The mean follow-up of the remaining 10 patients after diagnosis was 21.7 months (3-48). Two patients had recurrent bladder cancer and underwent transurethral resection of the tumor. Eight patients showed no evidence of disease during the follow-up. LNUT is a safe and effective approach with low morbidity in transplant recipients, and this therapy provides less trauma, quicker recovery, and acceptable oncological outcomes.


Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene.
C(72)-Macrocyclic systems functionalized with nitroaryl and arylamino groups were synthesized from the bisdioxine diacid dichloride 1,3,5,7-tetra-tert-butyl-2,6,9-trioxabicyclo[3.3.1]nona-3,7-diene-4,8-dicarbonyl dichloride (3).


Structure of the zebrafish fasciclin I-related extracellular matrix protein (betaig-h3) and its characteristic expression during embryogenesis.
betaig-h3, which is structurally related to the insect fasciclin I, is assumed to act as a cell adhesion molecule through binding to cell-surface integrins. In this study, we obtained cDNA clones for the zebrafish orthologue of betaig-h3 and examined the expression of the gene (betaig-h3) in zebrafish embryos using in situ hybridization. Expression is first seen at the bud stage in the presomitic mesoderm. Throughout the somitogenesis stage, betaig-h3 is expressed in all the segmented somites, as well as in the presomitic mesoderm (S0 and S-I). High expression is observed in the dorsolateral part of the somite until the mid-somitogenesis stage. At late somitogenesis stages, the betaig-h3 expression in the dorsolateral somite fades away, while expression is upregulated in the ventromedial part of the somite that corresponds to the sclerotome. In embryos after completion of somitogenesis and fry after hatching, betaig-h3 continues to be expressed in the sclerotome. In addition, new expression starts in the mesenchyme cells in the head, pharyngeal arches, and pectoral fins. In the embryonic brain, expression is observed along the anterior and postoptic commissures, as well as along the optic nerve.


Antimicrobial properties of diethylamine NONOate, a nitric oxide donor, against Escherichia coli: a pilot study.
The emergence of SARS-CoV-2, the causative agent of COVID-19, highlights the increasing need for new and effective antiviral and antimicrobial agents. The FDA has recently banned several active ingredients used in hand sanitizers, including triclosan and benzethonium chloride. Nitric oxide (NO) is involved in the innate immune response and is a major component of macrophage-mediated attack on foreign viruses and bacteria. The specific aim of this study was to assess the antibacterial effects of 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NONOate) against Escherichia coli (E. coli). A bacterial growth assay was compared to an adenosine triphosphate (ATP) activity assay at various time points to assess effects of DEA-NONOate on E. coli growth. A UV/Vis spectrophotometer was used to determine concentration of E. coli by measuring optical density (OD) at 630 nm. A luminescent assay was used to measure ATP activity correlating to viable cells. DEA-NONOate at a concentration of 65 mM was able to inhibit the growth of E. coli with the same efficacy as 1 μg ml-1 concentration of ciprofloxacin. Both the OD and ATP assays demonstrated a 99.9% reduction in E. coli. Both a 1 μg ml-1 concentration of ciprofloxacin and a 65 mM concentration of DEA-NONOate achieved 99.9% inhibition of E. coli, verified using both optical density measurement of bacterial cultures in 96 well plates and a luminescent ATP activity assay. The bactericidal effects of DEA-NONOate against E. coli is proof-of-concept to pursue evaluation of nitric oxide-based formulations as antimicrobial and antiviral agents as hand sanitizers.


Adherence to antiretroviral therapy: an update of current concepts.
The remarkable effectiveness of combination antiretroviral therapy (CART) in the treatment of HIV infection has placed a high premium on long-term adherence to therapy. Adherence levels to CART among HIV-infected individuals are similar to adherence levels with chronic medical conditions, such as diabetes and hypertension. However, unlike chronic medical conditions, medication adherence that is insufficient to maintain suppression of HIV replication will lead to drug resistance. Combination antiretroviral therapy regimen complexity and side-effect burden are clearly linked to adherence and are likely to be the factors most amenable to intervention. Adherence interventions that are multifaceted, flexible, and protracted are the most likely to be successful. Owing to the great benefits of CART even the small to modest gains in adherence that are achievable with adherence programs may prove to be cost effective.


Juvenile arthritis: a nursing perspective.
Juvenile arthritis is the fifth most common chronic illness in children. When a child is diagnosed with juvenile arthritis, the family must adjust in many ways in order to cope with the demands of this illness. This article provides an overview of the disease, presents the case history of two sisters with polyarticular arthritis, and discusses how nurses and other health team members can empower a family to manage more successfully with this disease and thereby enhance quality of life. Professional resources that aid families coping including educating the family about the disease, providing psychologic support, as well as knowledge and assistance for optimal physical functioning and maintaining energy reserves, and suggesting strategies to sustain self esteem, motivation and hope.


Cadmium tolerance in Elodea canadensis Michx: Subcellular distribution and metabolomic analysis.
The aquatic plant Elodea canadensis is considered a good candidate for ecotoxicological investigations. Cadmium (Cd) is a widespread contaminant in aquatic systems. In this study, to better elucidate the underlying tolerance mechanism and molecular impact of environmentally relevant Cd concentration in aquatic plants, subcellular distribution, chemical forms, and gas chromatography-mass spectrometry-based non-targeted metabolomics profiles were comprehensively analyzed in E. canadensis subjected to 0 and 10 µM Cd treatment for 5 d. Subcellular fractionation analysis of Cd-containing leaves showed that 67% of Cd was compartmentalized in cell wall followed by the soluble fraction (24 %) and organelles (9 %). The majority of Cd (90 %) was found in the extraction using 1 M NaCl. Metabolomic analysis using unsupervised principal component analyses and a supervised partial least squares discriminant analysis revealed clear differences in metabolic profiles between the two groups, demonstrating the metabolic effects of Cd. The 155 identified compounds altered by Cd were mainly from primary metabolism, including sugars, amino acids, organic acids, and their derivatives. Secondary metabolites such as polyphenols and phenolamides were also detected. The massive up-regulation of metabolites, including trehalose, proline, sarcosine, nicotianamine, putrescine, α-ketoglutaric acid, citric acid, and phytol might represent a detoxification mechanism. These findings highlighted the mechanistic strategies that E. canadensis employs to defend against Cd toxicity.


Distribution of thyrotropin-releasing hormone (TRH) in the hippocampal formation as determined by radioimmunoassay.
The distribution of thyrotropin-releasing hormone (TRH) in the hippocampal formation was determined using a radioimmunoassay (RIA) specific for TRH. RIA of hippocampal subregions revealed that the CA3 region of the hippocampal formation contained the highest amount of TRH, followed by intermediate levels in region CA1 and the dentate gyrus. The hilus and subiculum contained the lowest levels. The issue of whether hippocampal TRH is derived from extrinsic and/or intrinsic sources was evaluated by making lesions of the major subcortical afferent to the hippocampus, the fornix pathway. Analysis of the hippocampal formation by RIA revealed that the ventral hippocampus contains higher levels of TRH than the dorsal hippocampus (6.01 +/- 0.62 pg/mg tissue weight vs 1.11 +/- 0.19 pg/mg tissue weight). Lesions of the fornix produced significant decreases in ventral TRH to 52.9% of its control level and in dorsal TRH to 28.8% of its control level. The results from these studies suggest that (1) there is a differential distribution of TRH in the hippocampal formation, (2) the hippocampal formation might be composed of extrinsic and intrinsic sources of TRH, and (3) extrinsic sources of TRH might enter the hippocampus via the fornix pathway. In addition (4) the greater post-lesion decrement in ventral vs dorsal hippocampal TRH suggests that TRH fibers traversing the fornix innervate the ventral hippocampal formation in preference to its dorsal counterpart.


Examination of the associations between young children's trauma exposure, trauma-symptomatology, and executive function.
The present study used a bioecological framework to examine associations between trauma exposure, trauma-related symptomatology, and executive function (EF) in an urban sample of 88 predominantly ethnic-minority, low-income preschoolers (age 2-5) exposed to interpersonal trauma. Contrary to hypotheses based on past literature documenting associations between trauma exposure and EF deficits in childhood, in regressions adjusting for child gender, family income, and caregiver education, neither trauma exposure or trauma-related symptoms (post-traumatic stress symptoms, internalizing behaviors, or externalizing behaviors) were significantly associated with children's EF performance. Associations between child trauma exposure, symptomatology, and executive function were not moderated by parental PTSD symptomatology; and EF was not differentially predicted by type of trauma. Results suggest that, within an ethnically-diverse sample of preschool-aged children exposed to multiple traumas, associations between trauma exposure, symptomatology, and EF may be particularly nuanced. Keywords: child trauma, posttraumatic stress, executive function, preschool-age children, child mental health.


The interrelationships between antimicrobial resistance, COVID-19, past, and future pandemics.
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China in December 2019 and is associated with high levels of morbidity and mortality. Various types of bacterial and fungal infections occur in patients with COVID-19 with some resistant to antimicrobials that are associated with significantly worse outcomes and deaths. Besides, antimicrobial-resistant (AMR) co-infections are responsible for clinically significant mortality in past pandemics. There is evidence to suggest that factors such as the proliferation of adulterated antimicrobials in some developing countries, international travels, issues with healthcare financing, use/misuse by humans, and in agricultural production and climate change are determinants of AMR at various levels of society. These complex interrelated determinants intersect with AMR in current and past pandemics and could amplify the potential of a future antimicrobial resistance pandemic. Therefore, global concerted interventions targeted at all levels of society to reduce the use/misuse of antimicrobials and disrupt these multifaceted, interrelated, and interdependent factors are urgently needed. This paper leverages prior research to describe complex major determinants of antimicrobial resistance and provides fresh insights into possible intervention strategies to tackle antimicrobial resistance including in the current and future pandemics.


Memory search for the first target modulates the magnitude of the attentional blink.
The resolution of temporal attention is limited in a manner that makes it difficult to identify two targets in short succession. This limitation produces the phenomenon known as the attentional blink (AB), in which processing of a first target (T1) impairs identification of a second target (T2). In the AB literature, there is broad agreement that increasing the time it takes to process T1 leads to a larger AB. One might, therefore, predict that increasing the number of possible T1 identities, or target set, from 1 to 16 would lead to a larger AB. We were surprised to find that this manipulation of T1 difficulty had no influence on AB magnitude. In subsequent experiments, we found that AB magnitude interacts with T1 processing time only under certain circumstances. Specifically, when the T1 task was either well masked or had to be completed online, we found a reliable interaction between AB magnitude and the target set size. When neither of these conditions was fulfilled, there was no interaction between target set size and the AB. Previous research found that when the target set changes from trial to trial, trials with more possible targets elicited a larger AB. In the present study, the target set is held constant, reducing the demands on working memory. Nevertheless, AB magnitude still interacts with target set size, as long as the T1 task cannot be processed offline. Thus, the act of searching memory delays subsequent processing, even when the role of working memory has been minimized.


Ethnic concentration in the neighbourhood and majority and minority language: A study of first and second-generation immigrants.
Ethnic residential concentration is often found to hamper immigrants' majority language proficiency. However, there are still several gaps in our understanding of the relationship between ethnic concentration and ethnic minorities' language practices. This study examines the extent to which ethnic concentration also constrains immigrants' majority language use, whether contact with natives and co-ethnics mediates these relationships, and whether ethnic concentration relates to second-generation minorities' minority language proficiency. Structural equation models on data for people of Turkish and Moroccan origin living in the Netherlands (N=2163) showed that ethnic concentration is indirectly related to weaker majority language proficiency and less majority language use through contact with natives and co-ethnics. For second-generation minorities, ethnic concentration is related to better minority language proficiency.


A practical guide for the use of contour locking plates for the repair of humeral diaphyseal fractures with proximal extension.
The emergence of minimally invasive techniques has expanded the use of plates and improved their safety for the repair of humeral diaphyseal fractures with proximal extension. In this study, we aimed to determine the best contouring method for long locking plates in the repair of humeral fractures using this approach. Comparative observations were performed between helical and spiral modelling in plastic models to identify which shape best fits the contours of the humerus. To determine the best shape, we attempted to assess the torsion required for the plate to settle laterally in the greater tuberosity and anteriorly in the diaphyseal region of the humerus. After establishing the best approach, we transferred the method to two anatomical specimens and confirmed the viability of the method and pathways. Additionally, to confirm the clinical applicability of the method, we applied the method in ten patients. After placing the plates in the bone models, it was found that the helical plate was more distant from the bone. On the other hand, the spiral plate achieved better accommodation along the contours of the humerus. The amount of twist was tested at 50°, 70° and 90°. When the plate was twisted at 70°, it maintained contact with the greater tuberosity proximally and the anterior cortical diaphyseal region. Eight patients completed the follow-up. Radiographic consolidation and good functional outcomes were achieved in all patients. Spiral modelling at 70° allows anatomical accommodation at the greater tuberosity proximally and in the diaphyseal region.


Characterization of a strong covalent Th3+-Th3+ bond inside an Ih(7)-C80 fullerene cage.
The nature of the actinide-actinide bonds is of fundamental importance to understand the electronic structure of the 5f elements. It has attracted considerable theoretical attention, but little is known experimentally as the synthesis of these chemical bonds remains extremely challenging. Herein, we report a strong covalent Th-Th bond formed between two rarely accessible Th3+ ions, stabilized inside a fullerene cage nanocontainer as Th2@Ih(7)-C80. This compound is synthesized using the arc-discharge method and fully characterized using several techniques. The single-crystal X-Ray diffraction analysis determines that the two Th atoms are separated by 3.816 Å. Both experimental and quantum-chemical results show that the two Th atoms have formal charges of +3 and confirm the presence of a strong covalent Th-Th bond inside Ih(7)-C80. Moreover, density functional theory and ab initio multireference calculations suggest that the overlap between the 7s/6d hybrid thorium orbitals is so large that the bond still exists at Th-Th separations larger than 6 Å. This work demonstrates the authenticity of covalent actinide metal-metal bonds in a stable compound and deepens our fundamental understanding of f element metal bonds.


Intrapartum maternal glucose infusion reduces umbilical cord acidemia.
Our purpose was to compare the effects of intrapartum 5% glucose in the intravenous fluid on umbilical cord acid-base and glucose status after spontaneous vaginal delivery. This was a prospective randomized clinical trial in which gravid women with low-risk pregnancies at term were randomized by computer to receive lactated Ringer's solution, either with 5% glucose or without, as the maintenance intravenous fluid during active labor. Antepartum and intrapartum factors that might influence fetal-neonatal glucose levels were recorded. Umbilical arterial cord blood was assessed for glucose level and acid-base status. Of the 106 parturient patients who consented, 15 were excluded because of operative delivery (n = 8), preeclampsia (n = 2), shoulder dystocia (n = 1), intravenous fluid infusion duration of < 1 hour (n = 1), and cord blood data not available (n = 3). There were no statistical differences between the two groups regarding maternal age, parity, maternal weight at term, epidural placement, intravenous fluid duration, or gestational age. Infant birth weight, gender, Apgar scores, and incidence of meconium were not statistically different. Neonatal hypoglycemic episodes and intrapartum fetal heart rate tracing parameters were similar between groups. The difference between the umbilical artery pH values of those who were treated with lactated Ringer's solution with 5% glucose (n = 48) versus those treated with the solution without glucose (n = 43) approached significance, with a p value of 0.08 (mean +/- SD, 7.30 +/- 0.07 and 7.27 +/- 0.09, respectively). The PCO2 value of those treated with lactated Ringer's solution without glucose was higher (mean +/- SD, 50.6 +/- 12.9 mm Hg vs 44.8 +/- 9.9 mm Hg) (p = 0.02). Base excess (in milliequivalents per deciliter) and cord glucose (in milligrams per deciliter) levels, as well as the incidence of neonatal hypoglycemic episodes within the first 8 hours of life, were not statistically different. Despite failure of mean pH differences to achieve significance, the relative risk (0.22) for an umbilical arterial pH < or = 7.20 was significantly reduced (95% confidence interval 0.1 to 0.7) with lactated Ringer's solution containing 5% glucose. The relative risk (0.42) of having an umbilical artery cord blood PCO2 value > or = 55 mm Hg was also significantly lowered (95% confidence interval 0.19 to 0.93) when lactated Ringer's solution containing 5% glucose was used. Intrapartum intravenous fluid consisting of lactated Ringer's solution containing 5% glucose reduces umbilical cord acidemia and hypercarbia but does not change cord levels of glucose or base excess. Lactated Ringer's solution containing 5% glucose may be a preferable solution than without glucose as an intravenous fluid during labor.


Cell-free synthesis of rat parotid preamylase.
Poly(A)-containing RNA from rat parotid gland directs the cell-free synthesis of several products in the reticulocyte lysate translation system including a very prominent 58,000-dalton polypeptide which is immunoreactive with anti-alpha-amylase. Purified alpha-amylase has a molecular weight estimated as 56,000 daltons. The 58,000-dalton, cell-free product and alpha-amylase share common peptides as determined by analysis of their limited proteolysis digests. The cross-reactivity and peptide homology suggest that the cell-free product may be a precursor of mature alpha-amylase. While the NH2 terminus of alpha-amylase is blocked, that of the 58,000-dalton product evidently is not, and automated sequence analysis has yielded its partial sequence as: Met-X-Phe-Phe-Leu-Leu-Leu-X-Leu-Ile-X-Leu-X-X-X-X-X-X-X-X-X-Phe-X-X-X-X-X-Ile-X-X-Leu-Phe. The highly hydrophobic nature of the NH2 terminus of the 58,000-dalton, cell-free product suggests that, like other secreted polypeptides, the extra piece may play a role in the transport and secretion of the mature alpha-amylase.


5G in healthcare: how fast will be the transformation?
The 5G technology, with its low latency, high speed, enhanced high-resolution bandwidth, superior reliability, and less energy consumption, is bound to transform telemedicine and the healthcare industry as a whole. This next-generation wireless networking technology has many far-reaching implications in both preventive and therapeutic care of the patients. Remote monitoring of patients is possible with wearables facilitated by robust sensors coupled to 5G network. Virtual patient consultation; augmented reality (AR) and virtual reality (VR)-based simulated surgeries; artificial intelligence (AI)-powered robotic surgeries; real-time maintenance of ambulances and other medical devices; and dynamic huge data repository are some of the other applications of 5G technology in the health sector.


Hydrophobic interaction between DNP-HSA and different tissue structures in vivo assessed by indirect immunofluorescence microscopy.
Circulating dinitrophenylated human serum albumin (DNP-HSA) was shown by indirect immunofluorescence microscopy to adhere to non-parenchymal liver cells and capillaries of striated muscle in mice. The DNP-HSA at these sites could be removed by surface-tension-lowering agents such as Triton X-100 and ethylene glycol. The adherence of DNP-HSA to white blood cells in vitro was inhibited in the presence of 0.3 M ethylene glycol. The findings support the hypothesis that hydrophobic interaction with different tissue structures may be important for the fate of circulating antigens and immune complexes. Indirect immunofluorescence microscopy offers a simple means of checking the role of hydrophobic bonding for the tissue adherence of various substances in vivo.


Quantitative analysis of carbon content in cementite in steel by atom probe tomography.
Atom probe performance in the quantitative analysis of carbon atoms in steel was investigated through analysis of stoichiometric spherical cementite (Fe(3)C) in steel. The carbon concentration was estimated by determining the mean carbon number of molecular ions having a mass-to-charge ratio of 24. The apparent carbon concentration of cementite increased as the specimen temperature decreased, and it was several at% higher than the stoichiometric value (25 at%) under the preferable condition of low specimen temperature. On the other hand, the apparent carbon concentration was not changed by pulse fraction. These results indicate that the large deviation from the stoichiometric value did not arise from the preferential retention and evaporation between carbon and iron. The other mechanisms explaining the phenomenon have been discussed.


Effects of heat exposure on the thermoregulatory responses of young children.
The purpose of this study was to determine whether young children's thermoregulation during heat exposure varies with age and body size. A total of 34 young children (aged 6 months-8 years)-18 boys and 16 girls-participated in the study. They were divided into five groups according to age (<1 year, 1 year, 2-3 years, 4-5 years, and 8 years). The participants sat for 30 min in a 27°C, 50% rh room, then moved to a 35°C, 70% rh room and remained seated for at least 30 min. They then returned to the first 27°C room and remained stationary for 30 min. Rectal temperature (Tre) and skin temperature (Tsk) were continuously recorded, and the amount of whole-body sweat rate (SR) was measured. Local SR of the back and upper arm were collected with filter paper to calculate local sweating volume, and Na + concentration was measured later. The smaller the age, the significantly greater the increase in Tre. There was no significant difference in the amount of whole-body SR and the increase in Tsk during the heating among the five groups. Furthermore, there was no significant difference in whole-body SR per increase in Tre during heating between the five groups, but a significant difference was found in back local SR per increase in Tre with age. Difference in local SR between upper arm and back was observed at age 2 years and above, and difference in Na+ concentrations in sweat was observed at age 8 years. The development of thermoregulatory responses with growth was observed. The results indicate that the thermoregulatory response is disadvantaged by immature mechanisms and small body size in younger children.


Near fatal ventricular fibrillation in Brugada syndrome despite presence of an implanted implantable cardioverter defibrillator.
A 38-year-old man with Brugada syndrome and aborted cardiac arrest was treated with quinidine only, based on the results of electrophysiologic drug testing. Six months later, after suffering a vaso-vagal syncope, he opted to receive an implantable cardioverter defibrillator and decided to discontinue quinidine against our recommendation. Sixty-seven months later, he had recurrent ventricular fibrillation that was terminated only by the sixth maximal energy shock delivered by the device (which has the capability to deliver a maximum of 8 shocks). This case suggests the possible risk in only relying on an implantable cardioverter defibrillator in the management of cardiac arrest survivors with Brugada syndrome.


Ropivacaine produces sensory blockade in the lumbar sacral region more frequently than mepivacaine in lower thoracic epidural anesthesia.
The first sacral nerve has the largest diameter among the spinal nerves and is resistant to local anesthetics. Ropivacaine is a newly developed local anesthetic. There is a possibility that a difference in chemical properties between ropivacaine and other local anesthetics produces a difference in the blockade of the S1 dermatome by lower thoracic epidural anesthesia. Mepivacaine, 2%, is frequently used for epidural anesthesia and produces a level of blockade similar to that of bupivacaine, 0.5%. The purpose of this study was to examine the sensory blockade in the sacral region induced by ropivacaine with that induced by mepivacaine administered in the lower thoracic epidural space. Eighteen adults undergoing lower thoracic epidural anesthesia (thoracic 11/12 interspace) were studied in a double-blind fashion. Patients were assigned to one of two groups: those who received 2% mepivacaine, 18 ml (group M; n = 9), and those who received 1% ropivacaine, 12 ml (group R; n = 9). The cephalad levels of sensory blockade to cold, pinprick, and touch in the L2, S1, and S3 dermatomes were assessed at 10, 20, and 35 min after injection. There were no differences in the cephalad levels of sensory block to cold (T4 [range, T4-T2] and T4 [range, T6-T2]), pinprick (T4 [range, T6-T4] and T4 [range, T6-T4]), or touch (T6 [range, T6-T4] and T6 [range, T6-T4]) between group M and group R respectively, at 35 min (P > 0.05). In the L2 and S3 dermatomes, there were no significant differences in the numbers of patients who obtained sensory block to cold or pinprick at 20 and 35 min after study drug administration. However, in the S1 dermatome, significantly higher numbers of patients in group R obtained sensory block to cold at 20 and 35 min after study drug administration than in group M (8 and 0; 9 and 0; P = 0.001 and P < 0.001; 20 min and 35 min after administration, respectively). Also in the S1 dermatome, significantly higher numbers of patients in group R obtained sensory block to pinprick at 20 and 35 min after study drug administration than in group M (6 and 0; 9 and 0; P = 0.027 and P < 0.001; 20 min and 35 min after administration, respectively). A significantly higher number of patients in group R had sensory block to touch in the S3 dermatome at 35 min (7 and 2; group R and group M, respectively; P = 0.01). Ropivacaine, 1%, administered in the lower thoracic epidural space, induces sensory blockade to cold and pinprick in the S1 dermatome more frequently than 2% mepivacaine.


Establishment and application of minigene models for studying pre-mRNA alternative splicing.
The objective of the present study is to establish a minigene model for studying pre-mRNA alternative splicing. To prepare the minigene DNA constructs, with human or mouse genomic DNA as templates, GluR-B, FGF-2R and Zis "minigene" fragments were amplified using PCR and cloned to the eukaryotic expression vectors. The three constructed minigenes and the expression vectors of Tra2beta1 and Zis2 were co-transfected in Hela cells. RT-PCR analysis was performed to semi-quantitatively determine the spliced products from the minigenes. The results demonstrated that the constructed minigenes are useful in studying the pre-mRNA alternative splicing in cultured cells. With the established Zis minigene, we for the first time found that Zis2 isoform regulates the alternative splicing of Zis minigene.


A hop, skip and a jump towards evaluating social interaction and learning through play at a child and adolescent inpatient treatment program.
The number of inpatient mental health facilities for children and adolescents in the United States is growing rapidly. While undergoing inpatient treatment, children and adolescents can benefit from innovative play opportunities designed to foster social interaction and learning. The Playful Learning Landscapes (PLL) initiative is a group of projects designed to transform everyday spaces into opportunities for playful learning. As a part of this initiative, two designs-Lifesize Ruler and Jumping Feet-were installed in an inpatient mental health facility for children and adolescents in the Mid-Atlantic region of the United States. Results of pre-installation and post-installation naturalistic observations suggested that social interactions, the use of STEM-related language and 21st century skills, including confidence, increased after interacting with the installations. While previous research on PLL projects has demonstrated the efficacy of transforming public spaces into places for playful learning, this research provides support that, even in private, targeted settings, using a trauma-informed approach, children and adolescents, can reap the benefits of playful learning.


Knee arthroscopy in the military population: an analysis of 600 knee arthroscopies.
Six hundred knee arthroscopies in a military population were analyzed. Similarities in types of injuries encountered in the military and civilian populations were noted. The important role of arthroscopy in the practice of orthopedics in the military was emphasized.


[Intracoronary fracture of a guidewire tip in percutaneous coronary angioplasty].
The authors report a case of intracoronary rupture of the tip of a guidewire used for angioplasty. They discuss its mechanism and management. The hazards involved in re-using coronary dilatation material are underlined.


Development of cranial nerve palsy shortly after endosaccular embolization for asymptomatic cerebral aneurysm: report of two cases and literature review.
We report two cases of asymptomatic cerebral aneurysm in which cranial nerve palsy (CNP) developed shortly after symbolization. The CNP occurred immediately in case 1, but case 2 showed the CNP 30 h after symbolization. Although both aneurysms had increased in size on follow-up angiography, case 2 who showed dome re canalization resulted in progressive CNP deterioration. These findings suggest that the CNP may result not only from mechanical compression by coils but also from inflammation induced by perpendicular thrombosis, and that the prognosis of the CNP may be influenced by dome re canalization. This complication should be kept in mind in treatment for asymptomatic aneurysms adjacent to the cranial nerves.


Subsequent, unplanned spine surgery and life survival of patients operated for neuropathic spine deformity.
Retrospective study of a prospectively assembled cohort. To characterize the survival from subsequent spine surgery and the life survival of patients treated surgically for severe spinal deformity due to neuropathic diseases. Survivorship analysis is widely used to study the natural history of disease processes and of treatments provided, but has very seldom been used to study patients' course after surgery for spinal deformity associated with neuropathic diseases. Patients with neuropathic spinal deformity treated with primary posterior instrumentation and arthrodesis from 1989 through 2002 were identified and studied by review of charts and radiographs, and by mail survey. Subsequent spine surgery and death events, and the time interval from surgery were identified. Fifteen variables possibly influencing survivorship were studied. There were no perioperative deaths, spinal cord injuries, or acute wound infections in the 117 eligible patients. Reoperation and life survival statuses were available for 110 patients (94%) at an average follow-up of 11.89 years (±5.3; range: 2-20.9 yr). Twelve patients (11%) had subsequent spine surgery. Survival from subsequent spine surgery was 91% at 5 years, 90% at 10 and 15 years, and 72% at 20 years. Proximal fixation problems occurred in 4 patients. Twenty-two patients (20%) had died from 4 to 20 years postoperative. Life survival was 98% at 5 years, 89% at 10 years, 81% at 15 years, and 56% at 20 years. The only variable associated with life survival was the occurrence of one or more perioperative complications, P = 0.0032. The younger half of the series at operation (<13.75 yr) was significantly more likely to have one or more perioperative complications, P = 0.0068. Spinal deformity type and magnitude were similar for the younger and older halves of the patients. Life survival of the patients with cerebral-palsy and not-cerebral-palsy upper motor neuron disease was not different. One-hundred-two of 105 were at least satisfied or would have the surgery again for the same condition. Survival from subsequent spine operation was similar to adolescent idiopathic scoliosis series studied in the same manner. Life survival decline began at 4 years postoperative and was significantly associated with the occurrence of one or more perioperative complications. Even after successful spine deformity surgery, this population's health status is often precarious.


Transplant medications.
This article discusses the medications used most commonly to keep the lung transplant patient free of rejection and infection. Medications used in the treatment of rejection are categorized by their use; therefore, the most common three- and four-drug regimens used for induction, maintenance, and treatment of rejection are discussed. The most commonly used antibacterial, antiviral, and antifungal drugs also are identified. Tables listing the characteristics of the medications are included to make it easier for the reader to quickly identify the indications, mechanisms of action, major adverse reactions, and nursing implications of these medications.


Nonsteroidal anti-inflammatory therapy and recurrent acute anterior uveitis.
To investigate oral nonsteroidal anti-inflammatory drug (NSAID) therapy in the prevention of recurrences of uveitis in patients with recurrent nongranulomatous, idiopathic, or HLA-B27-associated acute anterior uveitis (AAU). Retrospective case series of 59 patients with recurrent AAU treated with celecoxib or diflunisal. The average duration of NSAID therapy was 21.2 +/- 5.7 months. The average number of relapses for all patients prior to systemic NSAID therapy was 2.84 per person-year follow-up. These relapses declined to 0.53 per person-year follow-up with NSAID therapy (p < .001). The relapse rates prior to and after treatment in the HLA-B27-positive group (n = 21) were compared with the relapse rates prior to and after treatment in the HLA-B27-negative group (n = 38) and were also statistically significant (p < .001). Morbid attacks and the cumulative exposure to corticosteroids can be prevented with systemic NSAID therapy in patients with recurrent AAU.


Brain stem reticular units: synaptic responses to stimulation within the ascending reticular pathways.
When the ascending reticular axonal system is stimulated, the responses of distal structures (e.g., the cerebral cortex) appear to outlast the stimulus; these longlasting effects could reflect the intrinsic nature of the distal structure, or the response could reflect an interaction among the reticular cells which tends to prolong the effects of stimulation. To examine the latter hypothesis, single units with ascending axons (projecting units) were recorded in the cat rostral rhombencephalon in acute experiments conducted under halothane-nitrous oxide anesthesia. Stimulation of areas to or through which axons of reticular neurons projected (midbrain tegmentum and lower tectum, medial thalamus, and basal forebrain) produced a consistent and specific response which was elicited only from these areas: suppression of spontaneous activity which was typically elicited from several areas having ascending axons. One-half of these responses were accompanied by a short latency-single spike synaptic excitation. Stimulating areas more than 1.0 mm from the ascending trajectory never produced this response, whereas the number of responses was directly related to the number of projecting axons identified in any one experiment from a given site. Thus, the predominant effect of stimulating within the ascending axonal trajectory was suppression of spontaneous activity in the projecting units, not an 'en cascade' activation of these units; on the contrary, the only type of excitation encountered was a single, short latency spike. Therefore, any effects of stimulation within the ascending reticular pathway which appear to outlast the stimulus (as previously described in the literature) cannot be ascribed to a reverberating (excitatory) circuit among projecting units. A possible source of the synaptic responses of projecting units is a retrograde activation of collaterals interconnecting the reticular cells. If such interaction exists, it is specifically distributed among cells with ascending axons, as the responses were only observed in a very few units not identified by antidromic excitation; however, other evidence is adduced to support the belief that these few units were projecting units whose axons were beyond the reach of the stimulating electrodes. Futhermore, the axons may be bundled such that units with axons nearest that of a given projecting unit give rise to the most extensive synaptic interactions; the activation of these nearby axons suppresses spontaneous activity, while axons farther away have a greater possibility of being excitatory in nature. Should such a medium for interaction exist, reticular collateral interactions might be seen to exist specifically for the purpose of decreasing the activity of cells destined for similar rostral target structures.


Potential Application of Bacteriophages in Enrichment Culture for Improved Prenatal Streptococcus agalactiae Screening.
Vertical transmission of Streptococcus agalactiae can cause neonatal infections. A culture test in the late stage of pregnancy is used to screen for the presence of maternal S. agalactiae for intrapartum antibiotic prophylaxis. For the test, a vaginal⁻rectal sample is recommended to be enriched, followed by bacterial identification. In some cases, Enterococcus faecalis overgrows in the enrichment culture. Consequently, the identification test yields false-negative results. Bacteriophages (phages) can be used as antimicrobial materials. Here, we explored the feasibility of using phages to minimize false-negative results in an experimental setting. Phage mixture was prepared using three phages that specifically infect E. faecalis: phiEF24C, phiEF17H, and phiM1EF22. The mixture inhibited the growth of 86.7% (26/30) of vaginal E. faecalis strains. The simple coculture of E. faecalis and S. agalactiae was used as an experimental enrichment model. Phage mixture treatment led to suppression of E. faecalis growth and facilitation of S. agalactiae growth. In addition, testing several sets of S. agalactiae and E. faecalis strains, the treatment with phage mixture in the enrichment improved S. agalactiae detection on chromogenic agar. Our results suggest that the phage mixture can be usefully employed in the S. agalactiae culture test to increase test accuracy.


Lipofuscinogenesis in a model system of cultured cardiac myocytes.
Lipofuscin, or age pigment, is a yellowish-brown, autofluorescent, protein, and lipid containing pigment that accumulates in the lysosomal vacuome of a variety of post-mitotic cells in man and animals during aging. Lipofuscin seems to be an end product of peroxidation, fragmentation and polymerization of proteins and lipids. Protein and lipid containing materials are regularly sequestered to the lysosomal system by means of endocytosis and autophagocytosis. Lysosomes and acidified endosomes constitute cellular compartments where iron for short periods of time may exist in reactive form allowing for peroxidative processes. The importance was demonstrated in model systems of cultured cells subjected to oxidative stress and augmented amounts of FeCl3 in the culture medium. This combination was considered to result in increased intracellular, mainly mitochondrial, production of hydrogen peroxide as well as increased intralysosomal concentration of iron. One of the results of this situation was dramatically increased lipofuscinogenesis.


Combining Multifunctional Delivery System with Blood Brain Barrier Reversible Opening Strategy for The Enhanced Treatment of Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative illness characterized by intracellular tau phosphorylation, β-amyloid (Aβ) plaques accumulation, neuroinflammation and impaired behavioral ability. Owing to the lack of effective brain delivery approaches and the presence of the blood brain barrier (BBB), current AD therapeutic endeavors are severely limited. Herein, we elaborately combined a multifunctional delivery system (RVG-DDQ/PDP@siBACE1) with an AKT agonist (SC79) for facilitating RVG-DDQ/PDP@siBACE1 to target and penetrate BBB, enter brain parenchyma, and further accumulate in AD brain lesion. Moreover, compared with the unitary dose of RVG-DDQ/PDP@siBACE1, this collaborative therapy strategy exhibited a distinctive synergistic function including scavenging reactive oxygen species (ROS), decreasing of Aβ production, alleviating neuroinflammation by promoting the polarized microglia into the anti-inflammatory M2-like phenotype and significantly enhancing the cognitive functions of AD mice. More strikingly, according to our results, we found an innovative signaling pathway "lncRNA MALAT1/miR-181c/BCL2L11" that can mediate the neuronal apoptosis of AD. Taken together, combining brain targeted delivery system with non-invasive BBB opening can provide a promising strategy and platform for targeting treatment of AD and other neurodegenerative diseases. This article is protected by copyright. All rights reserved.


Preoperative chemoradiation in rectal cancer: Retrospective comparison between capecitabine and continuous infusion of 5-fluorouracil.
We compared the efficacy and toxicity of oral capecitabine and continuous infusion of 5-fluorouracil (5-FU) in the preoperative chemoradiation treatment of patients with rectal cancer. The files of 89 patients with rectal cancer, 43 treated preoperatively with oral capecitabine and 46 with intravenous 5-FU, were reviewed, and the outcome of the groups was compared. There was no statistically significant difference in the complete pathological response rate between the capecitabine and the 5-FU groups (30% vs. 17%, P = 0.15). The downstaging rate was higher in the capecitabine group (77% vs. 50%, P = 0.009). Toxicity was mild in both groups. The rate of Grade 3 gastrointestinal toxicity was similar in the two groups (diarrhea 2% vs. 4%, proctitis 5% vs. 7%), except for one patient in the 5-FU group (2%) who developed a rectovaginal fistula. In the capecitabine group, one patient (2%) had Grade 3 hand-foot syndrome, and another had an acute myocardial infarction. In the 5-FU group, two patients (4%) had Grade 3 hematological toxicity, and three (6%) had complications from Port-a-Cath insertion. Preoperative chemoradiation with oral capecitabine appears to be safe and well tolerated, and at least as good as continuous 5-FU.


Spectral analysis of laser light scattered from motile microorganisms.
The theoretical basis of laser scattering from motile microorganisms is examined. Spectra of swimming particles are compared with spectra arising from brownian motion. For mixtures of motile and resting organisms, that part of the spectrum related to the motile organisms is enhanced when V(s)/|k|D is large, where V(s) is the mean swimming speed of the motile microorganisms,|k| is the Bragg wave vector, and D is the diffusion coefficient of the nonmotile particles. When the directed motion of swimming microorganisms persists for periods which are much longer than tau = (|k|V(s))(-1), the scattering spectrum is given as S(k, omega) infinity P(| [omega - omega(0)]/k|), where P is the probability distribution obtained by two-dimensional integration over the swimming speed distribution. A computation of scattering from bull spermatozoa, based on published velocity distributions, is investigated in detail.


Acrylic resins reinforced with highly drawn linear polyethylene woven fibres. 1. Construction of upper denture bases.
This paper presents a detailed description of the construction of complete acrylic upper dentures reinforced with highly drawn linear polyethylene fibres. The work forms part of a continuing project to elucidate the properties and potential of the new system.


Ulcerative colitis-associated rectal cancer resected and diagnosed by rectovesical fistula: a case report.
Ulcerative colitis (UC), which mainly consists of mucosal lesions, rarely form colovesical or rectovesical fistulas, although few cases of fistula formation associated with comorbidities have been reported. We report a case of UC-associated rectal cancer diagnosed following symptoms associated with rectovesical fistula. A 40-year-old man with a 31-year history of extensive UC presented with difficulty in defecation. Two years before the current presentation, he had experienced pneumaturia, and the examination then had revealed a rectal neoplastic lesion and rectovesical fistula; however, tissue biopsy showed no malignancy. Therefore, he requested for observation with no further treatment. Current examination suggested the rectal tumor had grown to invade the bladder. Tissue biopsy showed no malignancy. However, the clinical symptoms and examination findings strongly indicated UC-associated rectal cancer with bladder invasion; thus, open total proctocolectomy with partial cystectomy was performed. Histopathological evaluation of the rectal neoplastic lesion revealed UC-associated rectal cancer originating from the inflammatory mucosa, and the rectovesical fistula was found to be caused by the rectal cancer invading the bladder. Therefore, other colorectal cancers should be considered even though tissue biopsy does not reveal malignant lesions in UC patients with fistula.


Patient with CATSPER3 mutations-related failure of sperm acrosome reaction with successful pregnancy outcome from intracytoplasmic sperm injection (ICSI).
This study is intended to investigate the candidate pathogenic gene in a patient with primary infertility but without the defect in routine semen parameters from a consanguineous family and explore the potential impacts of mutations on assisted reproductive technology outcome. Whole-exome sequencing (WES) was carried out. A variant in his family found by WES was verified by Sanger sequencing. Intracytoplasmic sperm injection (ICSI) was applied to obtain a successful outcome. A Cation Channel of Sperm 3(CATSPER3) homozygous variant (NM_ 178019.3:exon5:c.707T>A, p.L236*) was identified for the first time. The anti-CD46 immunofluorescence analysis revealed the failure of sperm acrosome reaction (AR) caused by the mutation. ICSI treatment was successful. This is the first report of a homozygous pathogenic CATSPER3 mutation. This mutation may cause male infertility with the failure of AR but without the defect in routine semen parameters. ICSI was supposed to be the most appropriate therapy.


Acetyl-l-carnitine enhances myelination of regenerated fibers of the lateral olfactory tract.
It is well known that acetyl-l-carnitine (ALC) has various neuroprotective effects against neurodegenerative diseases. In addition, it has been reported that ALC facilitates myelination of regenerated axons after peripheral nerve injuries. We previously reported that spontaneous regeneration of the lateral olfactory tract (LOT), the main fiber tract of the central olfactory system, consistently occurred in newborn rats and a majority of these regenerated fibers were unmyelinated in neonatally LOT-transected young adult rats. To investigate the effects of ALC treatment on myelination in LOT, neonatal rats were treated with ALC after LOT transection. Immunohistochemistry for myelin basic protein showed more positive areas in ALC-treated rats than in control rats. Moreover, the number of myelinated axons of regenerated fibers was assessed using electron microscopy and was found to be statistically higher in ALC-treated rats compared to control rats. The study revealed that ALC accelerates myelination of regenerated fibers in neonatally LOT-injured young adult rats.


Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients.
Sleep complaints are common in end-stage renal disease. We aimed to investigate the relationship between sleep-related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels. Predialysis serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels in nine patients with sleep complaints were compared with those of nine patients without sleep complaints and nine healthy controls. Patients with sleep complaints underwent polysomnography the night after HD and the following night. Patients with sleep complaints had significantly higher predialysis IL-1beta levels compared with those without and healthy controls (P=0.004 and P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha levels than those without sleep complaints; however, the difference was not significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha and similar mean IL-1beta levels compared with healthy controls (P=0.001, P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was found in six out of nine (66%) patients with sleep complaints. Sleep architecture and cytokine levels did not differ between the two nights. The mean serum IL-1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post-polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF-alpha levels and the apnoea-hypopnoea index. Proinflammatory cytokines, IL-1beta in particular, might be associated with sleep complaints in HD patients. OSAS is not uncommon in HD patients with sleep-related complaints and sleep architecture does not appear to be effected by the HD procedure itself.


Efficient Identification for Alcohol Homologues and Hyperthermy Based on Coordination Polymer Multiple Structural Transformations.
Recently, coordination polymer materials are of high interest due to the potential applications for chemical sensing and luminescent materials. In this work, we designed a photofluorescence coordination polymer material based on a donor-metal-acceptor structure. The donor-metal-acceptor architecture showed unusual multiple environmental responsiveness accompanied by a great change of fluorescence behaviors. Generally, organic homologue molecules are not easily distinguished by coordination polymer sensors because they have similar molecular structures and interaction sites. However, using the feature of multiple structural transformations, the accurate identification for organic homologue molecules can be realized, especially in a short time to quickly identify MeOH in other alcohol homologues (even in mixed atmospheres with only 10% MeOH). The visualization transformation of fluorescence can also be realized by single crystal to single crystal thermal-induced coordination bond ON/OFF behavior. The reversible structure conversion strategy provides new ideas for the accurate identification of organic homolog molecules or external environmental stimuli.


Bacteremia and sternal infection after coronary artery bypass grafting.
Sternal wound infection remains a source of substantial morbidity and mortality after coronary artery bypass grafting. We noted an association between bacteremias and sternal wound complications in these patients. A review of 835 consecutive coronary bypass patients showed a 3.2% incidence of bacteremia and a 1.9% incidence of deep and superficial sternal wound infection. The sternal wound was the most common source of bacteremia, accounting for 59% of the infections. Coagulase-negative Staphylococcus was responsible for one half of the sternal wound infections. Often, a positive blood culture was the first manifestation of wound infection, occurring before local signs were manifest. We recommend multiple blood cultures in postoperative coronary bypass patients with pronounced fever. If no source of infection can be identified, sternal wound aspirate may be revealing. Appropriate early wound management can then be carried out, maximizing chances for good recovery.


Work-family enrichment: A potential buffer of inflammation among black adults?
Inflammation plays a known role in the development of cardiovascular disease (CVD), the leading cause of death in the United States and a condition that disproportionately affects Blacks. Although social stressors are frequently studied, the role of positive experiences in inflammation and its potential for CVD remains understudied. To address this gap, we examined the relationship between work family enrichment and inflammation in a population-based sample of working adults. Participants were 447 working adults from Refresher Cohort of the National Study of Midlife Development in the United States (MIDUS) and the oversample of Blacks from the Milwaukee, WI. Serum concentration of pro-inflammatory biomarkers (IL-6/sIL-6r; CPR; Fibrinogen) were obtained via blood draw. Family-to-work enrichment (FtoWE) and work-to-family enrichment (WtoFE) were each assessed with four established survey questions. Blacks had higher concentrations of IL-6, CRP and Fibrinogen, and lower levels of sIL-6r than whites. A significant inverse relationship was observed between WtoFE and systemic inflammation as well as WtoFE and serum IL-6 concentration. Individuals who perceived a stronger enhancing effect from work onto family showed lower levels of systemic inflammation and decreased concentrations of the pro-inflammatory cytokine IL-6; highlighting the potential work-family enrichment or other positive experiences may have in buffering the negative cardiovascular effects of inflammation. However, variation between racial groups remain undetermined.


Mutagenicity of nitrophenanthrene derivatives for Salmonella typhimurium: effects of nitroreductase and acetyltransferase.
To determine the mutagenicity of nitrophenanthrenes, three mononitrophenanthrenes (NPhs), 11 dinitrophenanthrenes (diNPhs) and eight trinitrophenanthrenes (tiNPhs) were synthesized, and their mutagenicity was investigated by using Salmonella typhimurium his- strains TA98, TA100, and TA98NR, nitroreductase-deficient, and TA98/1,8-DNP6, O-acetyltransferase-deficient mutants, and strains YG1021 and YG1026, nitroreductase-overproducing mutants of TA98 and TA100, respectively, and strains YG1024 and YG1029, O-acetyltransferase-overproducing mutants of TA98 and TA100, respectively. 1-, 3- and 9-NPhis induced 329, 620 and 438 revertants per nmol in strain TA100, respectively, and 4,839, 11,309 and 16728 revertants per nmol, respectively, in strain YG1029. Mutagenicity of 1,6-, 2,6-, 2,9-, 2,10-, 3,5-, 3,6- and 3,10-diNPh was elevated in strains YG1021, YG1024, YG1026 and YG1029. Among these derivatives, 1,6-, 2,6-, 3,6- and 3,10-diNPhs were more mutagenic in strains YG1024 and YG1029 than YG1021 and YG1026, and they showed a structure-activity relationship between mutagenicity and NO2-substitution. Nitro derivatives substituted at the 3 and 6 positions of their chemical structure strongly mutated both strains YG1024 and YG1029, whereas those substituted at the 9 and 10 positions showed weak mutagenicity. In addition, nitro substituents at positions 4 and 5 were perpendicular while those on positions 2,3,6 and 7 were nearly coplanar to the aromatic ring. Furthermore, 2,6,9-, 3,6,9- and 1,6,9-trinitrophenanthrenes (triNPhs) were mutagenic for strain TA100, and their mutagenicity was more enhanced in YG1024 and YG1029 than in YG1021 and YG1026. Of the eight triNPhs all except 1,5,10-triNP were mutagenic in TA98 and TA100, and their mutagenicity was more enhanced in YG1024 and YG1029 than in YG1021 and YG1026. These results suggest that these compounds are mutagens that are activated by O-acetyltransferase esterification following nitroreductase. The nitrated derivatives substituted at the 2(7) and 3(6) positions of the phenanthrene ring were highly mutagenic. The relationship between chemical structure and the mutagenicity of NPh derivatives is discussed.


Structure of vesicles formed from non-ionic dialkylglycerol poly(oxyethylene) ether surfactants: effect of electrolyte and cholesterol.
Five non-ionic dialkylglycerol poly(oxyethylene) ether surfactants, designated 2C(m)E(n) (where m, the number of carbons in each alkyl chain=16 or 18, and n, the number of oxyethylene units=12, 16 or 17) have been examined for their ability to form vesicles when dispersed in water or in an aqueous solution of 154 mM NaCl, alone or in the presence of 50 mol% cholesterol. Freeze fracture electron microscopy and light scattering showed that regardless of the hydrating fluid, all the non-ionic surfactants, with the exception of 2C(16)E(17) and 2C(18)E(17), formed vesicles in the absence of cholesterol - 2C(16)E(17) and 2C(18)E(17) instead formed micellar aggregates. All surfactants, however, formed vesicles in the presence of 50 mol% cholesterol. Small angle neutron scattering studies of the surfactant vesicles enabled the bilayer thickness and repeat distance (d-spacing) to be determined. The bilayers formed by all the non-ionic surfactants in the absence of cholesterol were surprisingly thin (∼50 Å for the E(12) containing surfactants and ∼64 Å for 2C(18)E(16)) most likely due to the intrusion of oxyethylene groups into the hydrophobic core of the bilayers. In contrast, however, the non-ionic surfactants exhibited a relatively large d-spacing of around ∼130-150 Å. The addition of 50 mol% cholesterol had a dramatic effect on the thickness of the vesicle bilayer, increasing its size by 10-20 Å, most probably because of an extrusion of oxyethylene from the hydrophobic region of the bilayer and/or a reduction in the tilt on the surfactant alkyl chains. Additionally the presence of cholesterol in a vesicle tended to reduce slightly both the d-spacing and the thickness of the water layer separating the bilayers. The presence of NaCl, even at the low concentrations used in the study, did affect the properties of the bilayer such that it reduced the d-spacing and, in the case of cholesterol-containing systems, also reduced bilayer thickness.


Calcium prescription by Indian orthopaedic surgeons: A survey and a review of literature.
Orthopaedic surgeons prefer calcium supplement for various pathologies like fracture, osteoporosis, chronic musculoskeletal pain, yet there is no proper evidence to support the benefits of taking them regularly. The average requirement for calcium is around 500-1000 mg/day for a healthy adult, this amount of calcium is not achieved by diet, especially in developing countries like India. Despite this, the serum calcium level remains unaltered, due to the well-controlled absorption and excretion of calcium by the human body. As there is no clarity over the dose, duration and the prefered calcium salts, we constructed a survey to find the preferred dose, duration, the preferred calcium salts among orthopaedic surgeons, and to give an in-depth review of literature about dose, duration, timing, preferred calcium salt and various other calcium-related queries. The survey included 15 pre-structured questionnaires; these questions were formatted and validated by senior surgeons and other specialists after a through a review of calcium-related literature. These questionnaires were used in a pilot study conducted within the department and were later modified and separated into 7 sections. Data were collected by both online survey (google forms) and direct interviews. 128 Orthopedic surgeons responded. The total number of response obtained was 2355. Unanswered questions were 152. From the survey, it was found that most orthopaedic surgeons prefer to prescribe calcium routinely (55.46%). The commonly used calcium salt was calcium carbonate (47.65%), followed by citrate (32.8%). 42.18% were not aware of the efficiency of prescribing calcium in divided doses. Most responded that calcium is not to be given for patients with renal stones, but literature shows that calcium prescribed reduces the recurrence of commonest kidney stones, calcium oxalate stones.


An unusual clinical case of haemoptysis in spontaneous pneumothorax: blood clots within emphysematous bulla.
We report an unusual case of spontaneous haemopneumothorax associated with haemoptysis due to blood clots within emphysematous bulla in a 42-year-old man. Haemoptysis disappeared after surgery.


Role of insulin in Cr(VI)-mediated genotoxicity in Neurospora crassa.
Chromium (III) is an insulinomimetic agent whose biological and/or environmental availability is frequently in the form of Cr(VI), which is known to be toxic. Wall-less mutant of Neurospora crassa (FGSC stock no. 4761) is known to possess insulin receptor in its cell membrane and hence is a good model for Cr toxicity studies. This study explores the toxicity of Cr(VI) and the possible consequences on simultaneous exposure to insulin in N. crassa. Comet assay of N. crassa cells treated with 100 μmol l⁻¹ Cr(VI) showed up to 50% reduction in comet tail lengths when incubated simultaneously with 0.4 U insulin. Fluorescence measurement in Cr(VI)-treated cells using DCFH-DA showed six- to eightfold increase in free radical generation, which was reduced to fourfold by 0.4 U insulin. Annexin-V/PI Flow cytometry analysis indicated necrotic cell death up to 28.7 ± 3.6% and 68.6 ± 2.5% on Cr(VI) exposure at concentrations 100 and 500 μmol l⁻¹ which was reduced by 68.3 ± 3.2% and 48.9 ± 3.6%, respectively, upon addition of insulin. Insulin-mediated protection from DNA damage by Cr(VI) is because of scavenging of free radicals liberated during exposure to Cr(VI). Overall, Cr(VI) toxicity depends upon available insulin, indicating that Cr(VI) toxicity may be a serious issue in insulin-deficient individuals with diabetes.


Solubilization, purification and reconstitution of Ca(2+)-ATPase from bovine pulmonary artery smooth muscle microsomes by different detergents: preservation of native structure and function of the enzyme by DHPC.
The properties of Ca(2+)-ATPase purified and reconstituted from bovine pulmonary artery smooth muscle microsomes {enriched with endoplasmic reticulum (ER)} were studied using the detergents 1,2-diheptanoyl-sn-phosphatidylcholine (DHPC), poly(oxy-ethylene)8-lauryl ether (C(12)E(8)) and Triton X-100 as the solubilizing agents. Solubilization with DHPC consistently gave higher yields of purified Ca(2+)-ATPase with a greater specific activity than solubilization with C(12)E(8) or Triton X-100. DHPC was determined to be superior to C(12)E(8); while that the C(12)E(8) was determined to be better than Triton X-100 in active enzyme yields and specific activity. DHPC solubilized and purified Ca(2+)-ATPase retained the E1Ca-E1*Ca conformational transition as that observed for native microsomes; whereas the C(12)E(8) and Triton X-100 solubilized preparations did not fully retain this transition. The coupling of Ca(2+) transported to ATP hydrolyzed in the DHPC purified enzyme reconstituted in liposomes was similar to that of the native micosomes, whereas that the coupling was much lower for the C(12)E(8) and Triton X-100 purified enzyme reconstituted in liposomes. The specific activity of Ca(2+)-ATPase reconstituted into dioleoyl-phosphatidylcholine (DOPC) vesicles with DHPC was 2.5-fold and 3-fold greater than that achieved with C(12)E(8) and Triton X-100, respectively. Addition of the protonophore, FCCP caused a marked increase in Ca(2+) uptake in the reconstituted proteoliposomes compared with the untreated liposomes. Circular dichroism analysis of the three detergents solubilized and purified enzyme preparations showed that the increased negative ellipticity at 223 nm is well correlated with decreased specific activity. It, therefore, appears that the DHPC purified Ca(2+)-ATPase retained more organized and native secondary conformation compared to C(12)E(8) and Triton X-100 solubilized and purified preparations. The size distribution of the reconstituted liposomes measured by quasi-elastic light scattering indicated that DHPC preparation has nearly similar size to that of the native microsomal vesicles whereas C(12)E(8) and Triton X-100 preparations have to some extent smaller size. These studies suggest that the Ca(2+)-ATPase solubilized, purified and reconstituted with DHPC is superior to that obtained with C(12)E(8) and Triton X-100 in many ways, which is suitable for detailed studies on the mechanism of ion transport and the role of protein-lipid interactions in the function of the membrane-bound enzyme.


Mechanism of dopachrome tautomerization into 5,6-dihydroxyindole-2-carboxylic acid catalyzed by Cu(II) based on quantum chemical calculations.
Tautomerization of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) is a biologically crucial reaction relevant to melanin synthesis, cellular antioxidation, and cross-talk among epidermal cells. Since dopachrome spontaneously converts into 5,6-dihydroxyindole (DHI) via decarboxylation without any enzymes at physiologically usual pH, the mechanism of how tautomerization to DHICA occurs in physiological system is a subject of intense debate. A previous work has found that Cu(II) is an important factor to catalyze the tautomerization of dopachrome to DHICA. However, the effect of Cu(II) on the tautomerization has not been clarified at the atomic level. We propose the reaction mechanism of the tautomerization to DHICA by Cu(II) from density functional theory-based calculation. We clarified that the activation barriers of α-deprotonation, β-deprotonation, and decarboxylation from dopachrome are significantly reduced by coordination of Cu(II) to quinonoid oxygens (5,6-oxygens) of dopachrome, with the lowest activation barrier of β-deprotonation among them. In contrast to our previous work, in which β-deprotonation and quinonoid protonation (O5/O6-protonation) were shown to be important to form DHI, our results show that the Cu(II) coordination to quinonoid oxygens inhibits the quinonoid protonation, leading to the preference of proton rearrangement from β-carbon to carboxylate group but not to the quinonoid oxygens. Integrating these results, we conclude that dopachrome tautomerization first proceeds via proton rearrangement from β-carbon to carboxylate group and subsequently undergoes α-deprotonation to form DHICA. This study would provide the biochemical basis of DHICA metabolism and the generalized view of dopachrome conversion which is important to understand melanogenesis.


Stimuli-responsive DNA-based hydrogels for biosensing applications.
The base sequences of DNA are endowed with the rich structural and functional information and are available for the precise construction of the 2D and 3D macro products. The hydrogels formed by DNA are biocompatible, stable, tunable and biologically versatile, thus, these have a wide range of promising applications in bioanalysis and biomedicine. In particular, the stimuli-responsive DNA hydrogels (smart DNA hydrogels), which exhibit a reversible and switchable hydrogel to sol transition under different triggers, have emerged as smart materials for sensing. Thus far, the combination of the stimuli-responsive DNA hydrogels and multiple sensing platforms is considered as biocompatible and is useful as the flexible recognition components. A review of the stimuli-responsive DNA hydrogels and their biosensing applications has been presented in this study. The synthesis methods to prepare the DNA hydrogels have been introduced. Subsequently, the current status of the stimuli-responsive DNA hydrogels in biosensing has been described. The analytical mechanisms are further elaborated by the combination of the stimuli-responsive DNA hydrogels with the optical, electrochemical, point-of-care testing (POCT) and other detection platforms. In addition, the prospects of the application of the stimuli-responsive DNA hydrogels in biosensing are presented.


Circannual changes in immune function.
Adrenocortical activity varies on a circannual basis with increased secretion in the winter and decreased secretion in the summer. One consequence of this variation is a circannual pattern in immune function. Adrenal corticosteroids, especially glucocorticoids, depress cellular immune function and seem to be more effective against T-suppressor cells. Thus, when adrenocortical activity is elevated, T-cell activity is depressed and B-cell activity is elevated. To the extent that T-cell "surveillance" is depressed in winter, there should be increased lymphoproliferative cancer risk during winter and in regions characterized by cold climates. This article presents data which suggest: (1) a winter, adrenal-corticoid induced, depression of T-cell function which is accompanied by elevated B-cell function; (2) elevated serum immunoglobulin levels in the winter; and (3) an inverse relationship between ambient temperature and serum immunoglobulin levels. The circannual pattern in immune function could help explain increased lymphoproliferative cancer risk, as a side effect of immunosuppression therapy during organ transplants, and as a function of latitude.


The discriminative ability of Prostate Health Index to detect prostate cancer is enhanced in combination with miR-222-3p.
There is an urgent need for better prostate cancer (PCa) biomarkers due to the low specificity of prostate specific antigen (PSA). Prostate Health Index (PHI) is an advanced PSA-based test for early detection of PCa. The present study aim was to investigate the potential improvement of diagnostic accuracy of PHI by its combination with suitable discriminative microRNAs (miRNAs). A two-phase study was performed. In a discovery phase, a panel of 177 miRNAs was measured in ten men with biopsy proven PCa and ten men with histologically no evidence of malignancy (NEM). These results were validated in a second phase including 25 patients in each group. The patients of all groups were matched regarding their PSA values and PHI were measured. Based on data in the discovery phase, four elevated miRNAs were selected as potential miRNA candidates for further validation. A combination of miR-222-3p as the best discriminative miRNA with PHI extended the diagnostic accuracy of PHI from an AUC value of 0.690 to 0.787 and resulted in a sensitivity of 72.0% and a specificity of 84.0%. Circulating microRNAs show useful diagnostic potential in combination with common used biomarkers to enhance their diagnostic power.


A case of intradiaphragmatic bronchogenic cyst with an abnormally high serum level of CA19-9.
Bronchogenic cysts that occur within the diaphragm are rare and difficult to diagnose preoperatively. We experienced the case of a patient with an abnormally high serum carbohydrate antigen 19-9 (CA19-9) level before surgery. The diagnosis of intradiaphragmatic bronchogenic cyst was made at the time of surgery. The patient was a 50-year-old woman with upper abdominal pain with an incidentally elevated serum CA19-9. Although the tumour location could not be established on images, a tumour within the diaphragm was confirmed during the operation. The diaphragm was incised and the tumour was removed together with the capsule. Bronchial cysts were diagnosed histopathologically, and immunohistochemical examination revealed that the bronchial epithelial cells were positive for CA19-9. When managing patients with bronchogenic cysts in the diaphragm, it is difficult to make a preoperative diagnosis or determine the location of the tumour; thus, careful planning is required before surgery.


A biomimetic triple-layered biocomposite with effective multifunction for dura repair.
Dura mater defect and subsequent cerebrospinal fluid (CSF) leakage usually appear in trauma or neurosurgical procedures and are followed by a series of serious complications and even death. The use of a qualified dura mater substitute with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is one of the promising treatment methods. However, even though some products have been used in the clinic, none of the substitutes achieved the required multifunction. In this study, we aimed to design and fabricate a dura repair composite with the ideal multifunction. By biomimicking the structure and component of natural dura, we applied poly(L-lactic acid) (PLLA), chitosan (CS), gelatin, and acellular small intestinal submucosa (SIS) powders to successfully prepare a triple-layered composite. Then, a series of specific devices and techniques were developed to investigate the performance. The results revealed that satisfactory structural stability could be realized under good synergistic interactions among the components. In addition, all the findings suggested that the bionic triple-layered composite showed satisfactory multifunction of leakage blockade, adhesion prevention, antibacterial property, and dura reconstruction potential, and thus, it might be a promising candidate for dura repair. STATEMENT OF SIGNIFICANCE: Developing qualified dura mater substitutes with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is crucial for treating dura mater defect and subsequent cerebrospinal fluid (CSF) leakage that appear in trauma or neurosurgical procedures. In this study, we designed and fabricated a triple-layered dura repair biocomposite with satisfactory structural stability and desired multifunction based on biomimicking of the structure and component of natural dura. Moreover, a series of specific devices and techniques were developed to investigate the relevant performance. Overall, the developed hydrogel electrospinning system exhibited excellent advantages in achieving multifunction and could be applied widely in the future to achieve multifunctional tissue repair materials.


[Transient hyperphosphatasemia in childhood. 4 new cases and review of the literature].
Transient hyperphosphatasemia of infancy is a biochemical syndrome characterized by a striking, transient increase in serum alkaline phosphatase in children without any evidence of bone or liver disease and of a familial occurrence. The abnormal isoenzyme pattern frequently observed in this syndrome may represent an excessively sialylated form of the liver isoenzyme, not normally removed from circulation. Here are described four new cases of this syndrome, followed biochemically and clinically until normalization of the serum abnormalities; a review of literature is also presented.


Growth abnormalities of cultured human skin fibroblasts derived from individuals with hereditary adenomatosis of the colon and rectum.
A heritable propensity to develop malignant lesions is found in individuals with familial adenomatosis of the colon an rectum (ACR) and the Gardner's syndrome variant, an autosomal dominant trait. In the present study, the growth characteristics of cultured skin fibroblasts (SF) derived from normal-appearing flat skin biopsies of ACR families, representing all phenotypes, and appropriate controls were investigated. SF were obtained from stocks between the second and fifth passages and growth to confluency in Eagle's Minimal Essential Medium (EMEM) supplemented with 15% fetal calf serum (FCS). Following trypsinization, cells were replanted in EMEM supplemented with either 1% or 15% FCS at an initial density of 4 x 10(3) cells/cm2 and counted daily for five days. Normal SF representing several age groups (both sexes) and those obtained from non-afflicted individuals of ACR families grew only in 15% FCS. In contrast, SF from ACR subjects and from embryonal skin grew both in 1% and 15% FCS. SF from several clinically asymptomatic adults, children or ACR patients, grew in 1% FCS as well. Cell cultures from ACR individuals showed regions of criss-crossed arrays and multilayered pattern. These growth properties were not observed in normal cell cultures. The SF from ACR individuals did not grow in methocel, nor did they form tumors in athymic mice. These results suggest the occurrence of previously undetected biochemical alterations in SF taken from ACR genotypes.


Stroke in Takayasu arteritis with concomitant tuberculosis: an unusual pediatric case report.
Stroke is a lethal complication of polyarteritis in children. Takayasu arteritis is a rare disease with an unknown etiology and is known to mainly affect young women. In this report, we present the case of a Chinese boy diagnosed with TA results in stroke, originally presenting in the context of latent tuberculosis infection and then developing active tuberculosis. The patient was a 14-year-old child who developed a latent tuberculosis infection at age 5 after coming in close contact with his grandfather, who had tuberculosis. However, he did not receive any anti-tuberculosis medications at that time. At age 9, he was hospitalized for symptoms of "dizziness and headache" and was diagnosed with Takayasu arteritis and hypertension; however, tuberculosis was not diagnosed. Only antihypertensive drugs were administered without considering the possible pathogenic factors of tuberculosis infection. At age 14, he was rehospitalized for "fever and cough" and was diagnosed with active pulmonary tuberculosis as an analysis of his fiberoptic bronchoscopy sample using the Gene-Xpert assay was positive for Mycobacterium tuberculosis. However, after 2 months of taking oral anti-tuberculosis drugs, his blood pressure continued to rise, and he presented with numbness and weakness of the right limb and a deviation of the right side of his mouth. Computed tomography angiography of his head and neck revealed that the walls of the left subclavian artery and bilateral vertebral arteries were thickened, and the lumen was significantly narrowed. In a recent examination, magnetic resonance imaging and diffusion-weighted imaging of the head showed infarctions in the right basal ganglia area close to the left lateral ventricle. Our patient was treated with methotrexate, tocilizumab and glucocorticoids to control he continued active vasculitis. The possible association of tuberculosis and Takayasu arteritis complicated by stroke needs to be considered, especially in children who had prior contact with a family member with tuberculosis infection. The temporal relationship between TA and infection with Mycobacterium tuberculosis in our patient suggests a compelling link that demands further investigation.


Estimating the impacts of lockdown on Covid-19 cases in Nigeria.
The study examines the extent to which lockdown measures impact on COVID-19 confirmed cases in Nigeria. Six indicators of lockdown entailing retail and recreation, grocery and pharmacy, parks, transit stations, workplaces, and residential, are considered. The empirical evidence is anchored on the negative binomial regression estimator, due to the count nature of the dataset on the daily cases of the virus. The study established the key following findings: First, retail and recreation, grocery and pharmacy, parks, transit stations, and workplaces are statistically significant and negatively signed as relevant predictors of the virus. Second, the impact of residential is positive and statistically significant at the conventional level. Lastly, the results are robust to an alternative estimator of Poisson Regression. The emanated policy message centres on the need to direct efforts toward ensuring total compliance to the lockdown rules as it holds the key to keeping the virus under check.


A critical analysis of Swanson ulnar head replacement arthroplasty: rheumatoid versus nonrheumatoid.
Clinical and radiographic assessment of the results of 40 Swanson silicone ulnar head prosthesis implants in three different patient groups is presented. Twenty-eight were done for treatment of rheumatoid arthritis, eight for ulnoradial impingement after the Darrach procedure, and four for ulnocarpal impingement resulting from malunited Colles' fractures. Patients were reviewed 12 to 48 months after operation (mean, 29 months). Seventy-eight percent of patients reported relief of pain and improved function. Radiologic examination showed that all patients exhibited resorption of the distal ulna (mean 4.4 mm) and that resorption was worst in the group with rheumatoid arthritis. Bone resorption about the implant predisposed the cap to both side-to-side tilt and pistoning of the prosthesis on supination and pronation. There was a 10% revision rate because of silicone synovitis. Although clinical results remain satisfactory for patients with rheumatoid arthritis and ulnocarpal impingement, the radiologic results suggest that Swanson ulnar head replacement should be restricted to elderly patients with rheumatoid arthritis.


Differential autonomic nervous system activity in multiple personality disorder.
The cardinal feature of multiple personality disorder (MPD) is the existence of two or more alter personality states that exchange control over the behaviour of an individual. Numerous clinical reports suggest that these alter personality states exhibit distinct physiological differences. We investigated differential autonomic nervous system (ANS) activity across nine subjects with MPD and five controls, who produced "alter" personality states by simulation and by hypnosis or deep relaxation. Eight of the nine MPD subjects consistently manifested physiologically distinct alter personality states. Three of the five controls were also produced physiologically distinct states, but these differed from those of the MPD subjects. A habituation paradigm demonstrated carryover effects at the ANS levels from one state to the next for both groups.


Inverse relationship between the changes in trunk lean and fat mass during gonadotropin-releasing hormone agonist therapy.
The aim of the present study was to investigate the relationship between the changes in lean and fat mass during gonadotropin-releasing hormone agonist (GnRH agonist) therapy. Subjects were 24 premenopausal women (mean age, 39.5+/-9.4 years; range, 32-52 years) with uterine leiomyomas. They were given GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Age and height were recorded. Body weight, regional and total body composition, and the ratio of trunk fat mass to leg fat mass (trunk-leg fat ratio) were assessed by whole body scanning with dual-energy X-ray absorptiometry. Changes in these variables were investigated. Relationships between the changes in regional lean and fat mass were investigated using Pearson's correlation test. Trunk fat mass significantly increased from 8616+/-3538 to 9265+/-3526 g (P<0.01) and trunk-leg fat ratio significantly increased (1.02+/-0.39 to 1.07+/-0.39, P<0.05). Trunk lean mass significantly decreased from 18,509+/-2602 to 17,916+/-2402 g (P<0.01). However, body weight, and lean and fat mass component in the extremities did not change. Change in trunk fat mass was inversely correlated with change in trunk lean mass (r=-0.439, P<0.05), but such relationships were not observed in arm and leg regions. Inverse relationship between the changes in trunk lean and fat mass is observed during GnRH agonist therapy.


A Comprehensive Cardiovascular-Renal-Metabolic Risk Reduction Approach to Patients with Type 2 Diabetes Mellitus.
Despite decades of research into risk-reduction strategies, cardiovascular disease and renal disease remain leading causes of morbidity and mortality among patients with type 2 diabetes mellitus. Given the tight clustering of cardiovascular and renal disease with the metabolic abnormalities of type 2 diabetes mellitus, we can think of these conditions together as cardiovascular-renal-metabolic disease states. A holistic view of cardiovascular-renal-metabolic disease states is critical to provide integrated patient-centered care to individuals with these disease states. Here, we explore the cardiovascular and renal risks associated with type 2 diabetes mellitus and highlight the importance of reducing cardiovascular-renal-metabolic disease risk in a comprehensive manner. We advocate a cross-disciplinary, team-based model to manage cardiovascular-renal-metabolic disease risk among patients with type 2 diabetes mellitus.


USe of tissue culture medium for in vitro studies on the ion transport capacity of amphibian epithelia.
The sodium transport capacity across frog skin and toad bladder in vitro is enhanced when a tissue culture medium is used to mount the preparations, instead of the classic Ringer solution. The response to antidiuretic hormone used 24 h after isolating the tissues is also higher in preparations incubated in the same culture medium.


[Driver genes and its clinical significance in non-small cell lung cancer].
With the development of molecular biology technology and the transforming patterns of drug research, guiding molecular targeted therapy according to the drive gene mutation spectrum in lung cancer has gradually become a reality. Definition of the mutation incidence and whether existing advantage population groups in non-small cell lung cancer (NSCLC) have important guiding significance in clinical practice. The purpose of this paper will draw a summary on the general characteristics, demographic features and clinical significance of driver genes in NSCLC.


Molecular dynamics simulations, docking and MMGBSA studies of newly designed peptide-conjugated glucosyloxy stilbene derivatives with tumor cell receptors.
In this work, for the first time, we designed derivatives of beta-D-glucosyloxy-3-hydroxy-trans-stiblene-2-carboxylic acid (GHS), by conjugating GHS with tumor targeting peptides RPARPAR and GGKRPAR to target over-expressed receptors in tumor cells. The sequences RPARPAR and GGKRPAR are known to target the neuropilin1 (NRP1) receptor due to the C-terminal Arg domain; however, their effectiveness has never been examined with other commonly over-expressed receptors in tumor cells, particularly of chronic lymphocytic leukemia that include integrin α1β1 and CD22. By conjugating these peptides with GHS, which is known for its inherent anti-cancer properties, the goal is to further enhance tumor cell targeting by developing compounds that can target multiple receptors. The physicochemical properties of the conjugates and individual peptides were analyzed using Turbomole and COSMOthermX20 in order to determine their hydrogen bond accepting and donating capabilities. The web server POCASA was used in order to determine the surface cavities and binding pockets of the three receptors. To explore the binding affinities, we conducted molecular docking studies with the peptides and the conjugates with each of the receptors. After molecular docking, the complexes were analyzed using Protein-Ligand Interaction Profiler to determine the types of interactions involved. Molecular dynamics simulation studies were conducted to explore the stability of the receptor-ligand complexes. Our results indicated that in most cases the conjugates showed higher binding and stability with the receptors. Additionally, highly stable complexes of conjugates were obtained with CD22, NRP1 and in most cases with the integrin α1β1 receptor as well. The binding energies were calculated for each of the receptor ligand complexes through trajectory analysis using MMGBSA studies. SwissADME studies revealed that the compounds showed low GI absorption and were not found to be CYP inhibitors and had bioavailability score that would allow them to be considered as potential drug candidates. Overall, our results for the first time show that the designed conjugates can target multiple over-expressed receptors in tumor cells and may be potentially developed as future therapeutics for targeting tumor cells.


Analysis of voiding disorders in patients with cerebrovascular accidents.
Urodynamic evaluation was undertaken in 33 patients (15 males and 18 females, age range 48-90 years) with voiding problems following cerebrovascular accidents. In the majority of these patients (26) cystometry revealed involuntary contractions of the bladder. The critical volume for involuntary bladder contractions was approximately 200 mL. The majority of patients with cerebral cortex and/or internal capsule lesions had uninhibited relaxation of the sphincter during involuntary bladder contractions, while all of the patients with lesions only in the basal ganglia or thalamus had normal sphincter function. The remaining 7 patients had poor bladder contractions. Correlation of bladder dysfunction with the area of brain injury was not conclusive, but was suggestive of directions to be taken in future research.


Serine 204 phosphorylation and O-β-GlcNAC interplay of IGFBP-6 as therapeutic indicator to regulate IGF-II functions in viral mediated hepatocellular carcinoma.
Hepatocellular carcinoma is mainly associated with viral hepatitis B and C. Activation of cell growth stimulator IGF-II gene is observed in tumor formation especially in viral associated hepatocellular carcinoma. Elevated IGF-II levels are indicator of increased risk for cholangiocellular and hepatocellular carcinomas through over saturation of IGF-II binding capacities with IGF receptors leading to cellular dedifferentiation. In HCV, core protein is believed to trans-activate host IGF-II receptor through PKC pathway and the inhibition of tumor cell growth can be achieved by blocking IGF-II pathway either at transcriptional level or increasing its binding with IGFBPs (Insulin like growth factor proteins) at C-terminal, so that it is not available in free form. IGFBP-6 is a specific inhibitor of IGF-II actions. Affinity of IGFBPs with IGFs is controlled by post-translational modifications. Phosphorylation of IGFBPs inhibits IGFs action on target cells while O-glycosylation prevents binding of IGFBP-6 to glycosaminoglycans and cell membranes and resulting in a 10-fold higher affinity for IGF-II. O-glycosylation and phosphorylation operate the functional expression of cellular proteins, this switching on and off the protein expression is difficult to monitor in vivo. By using neural network based prediction methods, we propose that alternate O-β-GlcNAc modification and phosphorylation on Ser 204 control the binding of IGFBP-6 with IGF-II. This information may be used for developing new therapies by regulating IGFBP-6 assembly with IGF-II to minimize the risk of viral associated hepatocellular carcinoma. We can conclude that during HCV/HBV infection, O-β-GlcNAc of IGFBP-6 at Ser 204 diminish their binding with IGF-II, increase IGF-II cellular expression and promote cancer progression which can lead to hepatocellular carcinoma. Furthermore, this site can be used for developing new therapies to control the IGF-II actions during viral infection to minimize the risk of hepatocellular carcinoma.


Machine Learning Protocol for Surface-Enhanced Raman Spectroscopy.
Surface-enhanced Raman spectroscopy (SERS) is a powerful technique that can capture the electronic-vibrational "fingerprint" of molecules on surfaces. Ab initio prediction of Raman response is a long-standing challenge because of the diversified interfacial structures. Here we show that a cost-effective machine learning (ML) random forest method can predict SERS signals of a trans-1,2-bis (4-pyridyl) ethylene (BPE) molecule adsorbed on a gold substrate. Using geometric descriptors extracted from quantum chemistry simulations of thousands of ab initio molecular dynamics conformations, the ML protocol predicts vibrational frequencies and Raman intensities. The resulting spectra agree with density functional theory calculations and experiment. Predicted SERS responses of the molecule on different surfaces, or under external fields of electric fields and solvent environment, demonstrate the good transferability of the protocol.


The metabolism in vivo and in vitro of plasma low-density lipoprotein from a subject with inherited hypercholesterolaemia.
1. The metabolism in vivo and in vitro of an abnormal low-density lipoprotein (LDL) obtained from a patient with an inherited form of hypercholesterolaemia was compared with that of LDL obtained from a normal subject. 2. The rates of turnover of the apoprotein of the two types of LDL in a normal subject, and their uptake and catabolism by normal lymphocytes in vitro, were similar. 3. It is concluded that the abnormal behaviour of the patient's LDL may not be due to an abnormality in the apoprotein component.


Benzo[b]selenophene/thieno[3,2-b]indole-Based N,S,Se-Heteroacenes for Hole-Transporting Layers.
Two series of new N,S,Se-heteroacenes, namely, 6H-benzo[4',5']selenopheno[2',3':4,5]thieno[3,2-b]indoles and 12H-benzo[4″,5″]selenopheno[2″,3″:4',5']thieno[2',3'4,5]thieno[3,2-b]indoles, were successfully obtained using an effective strategy based on Fiesselmann thiophene and Fischer indole synthesis. The new molecules exhibit a large optical band gap (2.82 eV < E g opt < 3.23 eV) and their highest occupied molecular orbital (HOMO) energy formed by the plane π-core ranges between -5.2 and -5.6 eV, with the narrower optical band gap and lower HOMO level corresponding to selenated heteroacenes. In thin solid films of the heteroacenes, hole mobility measured using the conventional CELIV technique ranges between 10-5 and 10-4 cm2·V-1·s-1. All these make the proposed condensed-ring compounds a promising platform for the development of hole-transporting materials applicable in organic electronics.


Evidence of increased platelet reactivity in the first six months after acute ST segment elevation myocardial infarction.
Platelets play a crucial role in the pathogenesis of acute coronary syndromes. Accordingly, previous studies showed increased platelet reactivity on admission in these patients. In this study we assessed platelet reactivity at short-medium term follow-up in patients with ST-segment elevation acute myocardial infarction (STEMI). Fifty-nine patients (58 ± 11 years, 45 men), treated with primary angioplasty, were studied 1 month after STEMI. Thirty-five patients were retested at 6 months. Twenty matched patients with stable coronary artery disease served as controls. Platelet reactivity was assessed by flow cyometry at rest and at peak exercise, with and without adenosine diphosphate (ADP) stimulation, by measuring monocyte-platelet aggregates (MPAs) and glycoprotein IIb/IIIa (CD41) expression in the MPA gate, and CD41 and fibrinogen receptor (PAC-1) expression in the platelet gate. Compared to controls, basal MPAs and CD41 in the MPA gate were higher in STEMI patients both at 1 month (p = 0.001 and p = 0.002, respectively) and at 6 months (p = 0.03 and p = 0.01, respectively). Basal CD41 and PAC-1 expression was also higher in STEMI patients at the two assessments compared to controls (P<0.001 for both). Exercise induced a similar increase in platelet reactivity in patients and controls. ADP induced a higher increase in CD41 platelet expression in STEMI patients compared to controls both at 1 and 6 months (P < 0.001). Platelet reactivity is increased in the first 6 months after STEMI. The persistence of increased platelet reactivity in this time period may play a role in the early recurrence of coronary events after STEMI.