Tallysomycin S10b: experimental antitumor activity and toxicity.
Tallysomycin S10b (TLM S10b), a structural analog of bleomycin (BLM), was evaluated and compared with BLM for antitumor activity in several murine tumor systems and for toxic effects in mice and rats. Neither TLM S10b nor BLM was effective against IP P388 and L1210 leukemias, whereas both drugs were active against IP P388/J leukemia (a BLM-sensitive subline). TLM S10b and BLM were both active against murine solid tumors, including SC B16 melanoma, IV Lewis lung carcinoma, SC Madison 109 lung carcinoma, SC CD8F1 mammary carcinoma and SC Colon 38 carcinoma. In human tumor xenograft models, TLM S10b was active against a colon tumor and had slight activity against breast and lung tumors. Compared with TLM S10b, BLM had less activity against the colon tumor, comparable activity against the breast tumor, and no effect against the lung tumor. A consensus of the antitumor data indicated that compared with BLM, TLM S10b had comparable or greater activity and was about twice as potent. TLM S10b and BLM had approximately equivalent LD50 values in mice. TLM S10b had minimal effects on WBC counts, blood urea nitrogen levels, and serum glutamic pyruvic transaminase levels in mice during the time periods monitored. These effects were comparable to or less pronounced than those of BLM. Both drugs caused dose-related increases in the whole-lung hydroxyproline content in mice, but the dose-response curves were not parallel. TLM S10b caused a larger increase than BLM at the lower doses and a smaller increase than BLM at the highest doses. In rats, TLM S10b and BLM caused comparable, significant decreases in lung mechanics; however, histopathological examination of the lungs indicated that TLM S10b caused less evidence of pulmonary toxicity than did BLM at comparable dose levels. TLM S10b was, therefore, generally comparable to BLM in causing pulmonary toxicity in mice and showed possibly less pulmonary toxicity in rats, while demonstrating approximately equivalent to four-fold greater potency, depending on the test system. It also appeared that TLM S10b caused less pulmonary toxicity than BLM in both mice and rats at doses approaching maximally tolerated levels. TLM S10b is currently undergoing phase I clinical evaluation.


Effects of standard treatments on depressive/anxiety symptoms in patients with inflammatory bowel disease: A systematic review and meta-analysis.
A combination of inflammatory bowel disease (IBD) and psychological comorbidities can influence the natural course of IBD. A systematic review and meta-analysis was performed to examine whether a standard IBD medical therapy without any antipsychotic intervention has beneficial effects on depression/anxiety in IBD patients. PubMed and Web of Science databases were systematically searched for related literature from their inception to March 2020. The random-effects model was used to calculate the standardized mean difference (SMD). A total of 16 eligible studies were included in the present meta-analysis. Compared with baseline assessments, IBD patients with standard IBD medication had significantly reduced depression assessment scores (pooled SMD = 0.500; 95% confidence interval: 0.207, 0.793; P = 0.001). These results were obtained without any psychological interventions. Additionally, no significant differences in anxiety-related scores were detected between the baseline assessments and the end of therapy assessments (pooled SMD = 0.083; 95% confidence interval: -0.120, 0.285; P = 0.425). The meta-regression and subgroup analyses revealed that differences in assessment tools and medications might be the main source of heterogeneity. Standard IBD treatments can significantly alleviate the depressive symptoms in IBD patients. However, more studies are needed to analyze this association.


Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells.
Pulmonary epithelial cells may be responsible for regulating airway smooth muscle function, in part by release of fatty acid-derived mediators. Incubation of isolated guinea pig tracheal epithelial cells with radiolabeled arachidonic acid (AA) leads to the production of 5- and 15-hydroxyeicosatetraenoic acid (5- and 15-HETE) and smaller amounts of leukotriene (LT) B4 and C4 and 12-hydroxyheptadecatrienoic acid (HHT). Epithelial cells also are able to release linoleic acid (LA) metabolites. Incubation with radiolabeled linoleic acid leads to the formation of 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE). The biological significance of these mediators produced by epithelial cells is discussed.


The effect of thyrotrophin on oxidative activity in thyroid follicle cells.
Biochemical evidence, based on supra-physiological concentrations of thyrotrophin (TSH), has indicated that this hormone increases the NADP concentration in thyroid follicle cells. The hormone is believed to act both to enhance the reoxidation of the reduced coenzyme and to generate NADP from NAD. The latter effect, mediated by NAD-+-kinase, could be a major control mechanism in thyroid metabolism. In the present study increased sensitivity has been obtained by the use of maintenance culture and of microdensitometry for measuring enzyme activity in the follicle cells. Using low physiological (0.1 muU/ml), and sub-physiological concentrations of the hormone as are used in the cytochemical bioassay systems, it has been shown that the rate of reoxidation of NADPH is enhanced by TSH. Moreover the NAD-+-kinase activity is also greatly increased, and shows a direct relationship to the concentration of the hormone acting on the segments of the gland in vitro. It is possible that this phenomenon could be used to assay TSH. The results indicate that NAD-+-kinase activity may play a significant part in the control of pentose-shunt oxidation in thyroid follicle cells.


Arrhythmia and prognosis in infants, children and adolescents with hypertrophic cardiomyopathy.
In adults with hypertrophic cardiomyopathy, the annual mortality rate from sudden death is 2 to 3%, and the finding of nonsustained ventricular tachycardia during electrocardiographic (ECG) monitoring provides a marker of the patient who is at increased risk. In the young, the annual mortality rate from sudden death is even higher, approximately 6%, but the prognostic significance of arrhythmia is unknown. To determine the prevalence of arrhythmia and its relation to prognosis, 2 days of ECG monitoring was performed in 6 infants, 14 children and 33 adolescents with hypertrophic cardiomyopathy receiving no cardioactive medications. An additional 1 to 9 days (median 2) of monitoring was performed in 29 patients. All patients had sinus rhythm; 4 adolescents had episodes of paroxysmal supraventricular tachycardia, a child with the Wolff-Parkinson-White syndrome had symptomatic reentrant atrioventricular tachycardia and 5 adolescents had asymptomatic nonsustained ventricular tachycardia. During follow-up of 1 week to 7 years (median 3 years), five patients died suddenly and two had successful resuscitation from out-of-hospital ventricular fibrillation; none of these seven patients had ventricular arrhythmias during 2 to 7 days (median 3) of ECG monitoring. The two patients with ventricular fibrillation, the five with ventricular tachycardia, the one with Wolff-Parkinson-White syndrome and the seven with recurrent syncope or adverse family history, or both, received low dose amiodarone. None of these "high risk" patients died during 6 months to 6 years (median 3 years) of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis of coreless, probably defective virus particles in cell cultures infected with rotaviruses.
PK-15 cells infected with pig and lamb rotavirus strains which were not adapted to serial growth in cell cultures were examined by electron microscopy. A major difference between virus morphogenesis in the initial passage in PK-15 cells and in intestinal epithelial cells was the generation of large numbers of coreless virus particles in PK-15 cells. The numbers of coreless particles increased with increasing multiplicity of infection. Infectious virus was synthesized in PK-15 cells, but a variable decrease in infectivity titre occurred between 12 and 24 hours after infection. It is suggested that synthesis of defective interfering particles or an inhibitory substance such as interferon might account for this decrease.


A Case Series of Amoebic Liver Abscess in Patients With COVID-19 Infection.
Globally, amoebiasis is the second leading cause of death due to parasitic diseases. Amoebic liver abscess (ALA) as an opportunistic infection in recently recovered COVID 19 disease patients has not been reported earlier. We present here a case series of 13 patients of ALA admitted during the month of May 2021 in BLK hospital, New Delhi, and had recently recovered from COVID 19 disease. Out of 13, eight patients had moderate, and one had severe COVID 19 disease. All these patients had received steroids for the management of COVID 19 disease. The remaining 4 (30%) patients had mild disease. The mean age of our patients was 50 years (37-81 years). Out of 13 patients, nine (70%) were male, 5 were diabetic, 2 were hypertensive, and none were alcoholic. The most common presentation was fever (11/13) followed by upper abdomen pain (10/13). The mean time of symptom (fever or pain abdomen) onset from COVID 19 positivity date was 19 days (range 15-23 days). A complication the in form of localized intraperitoneal rupture was common in these patients and was seen in more than 50% (7/13) of patients. All the patients were managed with IV Metronidazole and abscess aspiration. All the patients were discharged, and the mean hospital stay was 6.6 days. We report here an increase in the incidence of ALA in recently recovered COVID 19 patients and propose that it is most likely due to alteration in the immune state of these patients. It is important for physicians to investigate for liver abscess in patients who present again with fever and/or pain abdomen within 2 weeks of COVID 19 recovery.


Toward the atomic structure of the nuclear pore complex: when top down meets bottom up.
Elucidating the structure of the nuclear pore complex (NPC) is a prerequisite for understanding the molecular mechanism of nucleocytoplasmic transport. However, owing to its sheer size and flexibility, the NPC is unapproachable by classical structure determination techniques and requires a joint effort of complementary methods. Whereas bottom-up approaches rely on biochemical interaction studies and crystal-structure determination of NPC components, top-down approaches attempt to determine the structure of the intact NPC in situ. Recently, both approaches have converged, thereby bridging the resolution gap from the higher-order scaffold structure to near-atomic resolution and opening the door for structure-guided experimental interrogations of NPC function.


Protein modeling and molecular dynamics simulation of SlWRKY4 protein cloned from drought tolerant tomato (Solanum habrochaites) line EC520061.
WRKY genes are members of one of the largest families of plant transcription factors and play an important role in response to biotic and abiotic stresses, and overall growth and development. Understanding the interaction of WRKY proteins with other proteins/ligands in plant cells is of utmost importance to develop plants having tolerance to biotic and abiotic stresses. The SlWRKY4 gene was cloned from a drought tolerant wild species of tomato (Solanum habrochaites) and the secondary structure and 3D modeling of this protein were predicted using Schrödinger Suite-Prime. Predicted structures were also subjected to plot against Ramachandran's conformation, and the modeled structure was minimized using Macromodel. Finally, the minimized structure was simulated in the water environment to check the protein stability. The behavior of the modeled structure was well-simulated and analyzed through RMSD and RMSF of the protein. The present work provides the modeled 3D structure of SlWRKY4 that will help in understanding the mechanism of gene regulation by further in silico interaction studies.


Nestin expression after experimental intracerebral hemorrhage.
The current study examines nestin expression after intracerebral hemorrhage (ICH), the role of different blood components in nestin upregulation, and the possibility that low doses of thrombin that induce tolerance to brain injury (thrombin preconditioning) might also induce nestin expression. Adult male Sprague-Dawley rats received an intracaudate injection of either whole blood, thrombin (1 or 5 U) or red blood cells (RBCs). Animals were sacrificed for single and double labeling immunohistochemistry to identify which cells express nestin, and for Western blotting to quantify nestin expression. By immunohistochemistry, nestin immunoreactivity was present in large numbers of astrocytes, surrounding the hematoma from day 3 to 1 week after ICH. After 2 weeks, nestin immunoreactivity was co-localized with a neuronal marker (neuronal specific enolase). By Western blot analysis, nestin was strongly expressed at day 3 (P<0.01) and 1 week (P<0.01), and expression persisted for at least 1 month (P<0.05). Intracerebral injection of thrombin or lysed RBCs resulted in a marked increase in nestin expression. Interestingly, injection of a low dose of thrombin that induces brain tolerance also upregulated nestin. The ICH-induced nestin expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury perhaps leading to recovery of function. Nestin induction by a low dose of thrombin suggests that specific receptor-mediated pathways are involved in inducing nestin expression and that nestin may play a role in thrombin preconditioning.


LAVH for large uteri by various strategies.
To study if there are specific problems in laparoscopically assisted vaginal hysterectomy (LAVH) for a certain weight of bulky uteri and the strategies to overcome such problems. One hundred and eighty-one women with myoma or adenomyosis, weighing 350-1,590 g, underwent LAVH between August 2002 and December 2005. Key surgical strategies were special sites for trocar insertion, uterine artery or adnexal collateral pre-ligation, laparoscopic and transvaginal volume reduction technique. The basic clinical and operative parameters were recorded for analysis. Based on significant differences in the operative time and estimated blood loss, the patients were divided into medium uteri weighing 350-749 g, n=138 (76%), and large uteri weighing > or =750 g, n=43 (24%). There was no significant difference in terms of age, body mass index, preoperative diagnoses, complications and duration of hospital stay among groups. The operative time and estimated blood loss increased with larger uterine size (p<0.001). The operative time (196+/-53, 115-395 min), estimated blood loss (234+/-200, 50-1,000 ml) and frequency of excessive bleeding (14%) or transfusion (5%) were significantly greater, but in acceptable ranges, for those with large uteri. Conversion to laparotomy was required in a patient (2%) with a large uterus, and the overall conversion rate was 0.6%. There was no re-operation or surgical mortality. Using various combinations of special strategies, most experienced gynecologic surgeons can conduct LAVH for most large uteri with minimal rates of complications and conversion to laparotomy.


Co-administration of fresh grape fruit juice (GFJ) and bergamottin prevented paracetamol induced hepatotoxicity after paracetamol overdose in rats.
The aim of this study was to evaluate small doses of known cytochrome P450 enzyme inhibitors, grapefruit juice (GFJ) and one of its components, bergamottin (BGT), for the prevention of paracetamol (PAR)-induced hepatotoxicity after overdose in rats. Six groups of 15 Sprague Dawley (SD) rats each were treated with single oral doses of either saline, PAR only 1725 mg/kg, PAR + GFJ low dose (2 ml) and PAR + GFJ high dose (3 ml), PAR + BGT 0.05 mg/kg (BGT-low) and PAR + BGT 0.22 mg/kg (BGT-high). Thereafter, 5 rats from each group were sacrificed after 24, 48 and 72 h and, on each occasion, blood samples were collected for determination of liver and renal function, full blood count (FBC) and PAR concentration. A piece of liver was sent for histopathology. By 48 h the liver enzymes in the PAR-only group were significantly (P < 0.05) higher than in the PAR + GFJ and PAR + BGT groups, i.e., alanine transaminase (ALT) 837 ± 268 u/L and aspertate transaminase (AST) 1359 ± 405 for PAR only; versus ALT 34 ± 48.8 u/L and AST 238 ± 221 for PAR + GFJ-high; ALT 22 ± 13.9 and AST168 ± 49.6 for PAR + BGT-high; and ALT 52 ± 7.2 u/L and AST 147 ± 153 for the control group. The results correlated with the histopathology findings where livers of the PAR-only group exhibited severe centrilobular and hepatocyte necrosis. In conclusion, GFJ and BGT prevented PAR-induced hepatotoxicity after PAR overdose in rats, and this calls for appropriate observation studies in humans.


Does the timing of intake matter? Association between caffeine intake and depression: Evidence from the National Health and Nutrition Examination Survey.
Recent research suggests that caffeine intake is associated with a reduced risk of depression. However, the relationship between caffeine intake during different periods of the day and depression is still unclear. This cross-sectional study analyzed noninstitutionalized adults from the National Health and Nutrition Examination Survey, with a weighted representation of approximately 218 million US adults. Covariate-adjusted sample-weighted regressions were used to examine associations between caffeine intake and depression in different periods. Caffeine intake during non-early morning periods (outside of 5:00-8:00 AM) is associated with a high prevalence of depression (unadjusted OR: 1.08, 95%CI: 1.05-1.11; adjusted OR: 1.03, 95 % CI: 1.00-1.06). Participants who consumed caffeine in the early morning (5:00-8:00 AM) had a lower prevalence of depression compared to participants who did not consume caffeine in the early morning (unadjusted OR: 0.75, 95%CI: 0.67-0.85; adjusted OR: 0.86, 95 % CI: 0.75-0.99). Cross-sectional study could not determine the temporal association; patients with depression in this study were not clinically diagnosed with Major Depressive Disorder. Among US adults, early morning caffeine consumers had a lower prevalence of depression than non-consumers; caffeine intake during non-early morning periods is associated with a high prevalence of depression. Our results may suggest the importance of caffeine intake time for depression.


Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells.
In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.


Intracardiac metastasis from germ cell testicular tumor.
Intracardiac metastases of germ cell testicular tumors are not commonly seen in clinical practice. The clinical presentation of right-sided heart metastases ranges widely. Depending upon its size and intracardiac location, it could be highly symptomatic, leading to a congestive heart failure, pulmonary embolism, and death, or completely asymptomatic. Improved imaging techniques and treatment strategies demonstrate that right-sided heart metastasis should be considered a potentially dangerous but treatable disease. Presented is the case of a 24-year-old man with a testicular nonseminomatous germ cell tumor, which after metastasizing in the right atrium differentiated into a teratoma and resulted in an inflow obstruction of the right ventricle.


Testing the monophyly of Aesculus L. and Billia Peyr., woody genera of tribe Hippocastaneae of the Sapindaceae.
Hippocastaneae is a well-supported clade in Sapindaceae that comprises 15+ species; 12+ in Aesculus, two in Billia, and one in Handeliodendron Rehder. The monophyly of Aesculus and Billia were widely assumed, but a recent molecular phylogenetic study of Sapindanceae used seven species of Aesculus and one each of Billia and Handeliodendron and showed that Billia and Handeliodendron were nested within Aesculus. Here, we tested the hypothesis that Aesculus and Billia are mutually monophyletic using phylogenetic analyses of seven molecular markers and 31 accessions of Hippocastaneae representing 14 species. We performed phylogenetic analyses using a dataset of concatenated genes as well as with coalescent method for constructing a species tree from individual gene trees. The analysis of seven concatenated markers and the species tree strongly supported the mutual monophyly of Aesculus and Billia. We also recovered support for the traditional arrangement of genera within Hippocastaneae: Aesculus and Billia comprising a clade that is sister to Handeliodendron. However, the relationships among the genera remain incompletely resolved.


The effects of stretch on vascular smooth muscle cell phenotype in vitro.
Vascular smooth muscle cells (VSMC) situated in the tunica media of veins and arteries are central to maintaining conduit integrity in the face of mechanical forces inherent within the cardiovascular system. The predominant mechanical force influencing VSMC structural organisation and signalling is cyclic stretch. VSMC phenotype is manipulated by externally applied stretch which regulates the activity of their contractile apparatus. Stretch modulates cell shape, cytoplasmic organisation, and intracellular processes leading to migration, proliferation, or contraction. Drug therapy directed at the components of the signalling pathways influenced by stretch may ultimately prevent cardiovascular pathology such as myointimal hyperplasia.


Subarachnoid dissemination of a pituitary adenoma.
The authors present an unusual case of a pituitary adenoma that developed into intracranial and intraspinal dissemination following intracranial surgery with adjunctive radiation, and review metastasis of pituitary adenomas in the central nervous system briefly in light of other reported cases.


Alcoholism and drug abuse in three groups--bipolar I, unipolars and their acquaintances.
Previous work has shown that manic-depressive illness and alcohol abuse are linked. This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method. Diagnosis was accomplished according to Research Diagnostic Criteria (RDC): controls = 469; bipolars = 277; unipolar depressives = 678. Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism. Both patients and comparison subjects were then followed prospectively for 10 years. First degree family members were interviewed using the RDC family history method. The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined. However, primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group. In contrast, primary bipolar patients had higher rates of alcoholism, stimulant abuse, and ever having abused a drug than the primary unipolar group and the control group. In an evaluation of the bipolar patients, drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder. There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients. As in all adult samples of patients with affective illness, the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively. (1) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients. (2) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs. (3) In a bipolar patient, familial diathesis for mania is significantly associated with the abuse of alcohol and drugs. (4) More provocatively, these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I, alcohol and stimulant abuse. The present analyses, coupled with two previous ones from the CDS, suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania. Furthermore, in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history, mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems, and should be studied in systematic controlled trials.


Subchronic elevation of brain kynurenic acid augments amphetamine-induced locomotor response in mice.
The neuromodulating tryptophan metabolite kynurenic acid (KYNA) is increased in the brain of patients with schizophrenia. In the present study we investigate the spontaneous locomotor activity as well as the locomotor response to d-amphetamine [5 mg/kg, administered intraperitoneal (i.p.)] after increasing endogenous levels of brain KYNA in mice by acute (10 mg/kg, i.p., 60 min) or subchronic (100 mg/kg i.p., twice daily for 6 days) pretreatment with the blood-brain crossing precursor, L: -kynurenine. We found that an acute increase in the brain KYNA levels caused increased corner time and percent peripheral activity but did not change the d-amphetamine-induced locomotor response. In contrast, subchronic elevation of KYNA did not change the spontaneous locomotor activity but produced an exaggerated d-amphetamine-induced hyperlocomotion. These results cohere with clinical studies of patients with schizophrenia, where a potentiated DA release associated with exacerbation of positive symptoms has been observed following d-amphetamine administration. Present results further underscore KYNA as a possible mediator of the aberrant dopaminergic neurotransmission seen in schizophrenia.


Sustained recovery of Na(+)-K(+)-ATPase activity in sciatic nerve of diabetic mice by administration of H7 or calphostin C, inhibitors of PKC.
We have previously shown that intraperitoneal injection of H-7, an inhibitor of PKC, restores completely the activity of Na(+)-K(+)-ATPase in sciatic nerve of diabetic mice; however, the effect was transient, with a half-life of approximately 1 h under the conditions used. This work assessed whether calphostin C, a new more potent and specific inhibitor of PKC, is also able to restore the activity of Na(+)-K(+)-ATPase in sciatic nerve of ALX-induced diabetic mice and also assessed if continuous administration of H-7 or calphostin C can afford sustained recovery of the ATPase. Small amounts of calphostin C (i.e., 2 micrograms/kg) restore entirely the activity of the enzyme. Larger doses (e.g., 30 micrograms/kg) can be administered with equal results. The ED50 was approximately 0.5 micrograms/kg. This indicates that calphostin C is approximately 20,000 times more potent than H-7 in restoring the ATPase activity in diabetic mice. A single intraperitoneal injection of 1 or 10 micrograms/kg of calphostin C maintains the enzyme for 4 and 8 h, respectively. Administration of H-7 by continuous delivery from micro-osmotic pumps implanted in the back of the mice maintains the Na(+)-K(+)-ATPase for 24 h, although the activity decreases thereafter. This is the result of instability of H-7 in solution. Continous administration of calphostin C maintains the activity of the ATPase at nearly normal values for at least 2 wk. The results support the hypothesis that, in sciatic nerve tissue of diabetic animals, the activity of PKC is increased, leading to higher phosphorylation of Na(+)-K(+)-ATPase, which results in the decreased activity observed.(ABSTRACT TRUNCATED AT 250 WORDS)


A role for the anteromedial thalamic nucleus in the acquisition of contextual fear memory to predatory threats.
Previous studies from our group have shown that cytotoxic lesions in the ventral portion of the anteromedial thalamic nucleus (AMv), one of the main targets of the hypothalamic predator-responsive circuit, strongly impairs contextual fear responses to an environment previously associated with a predator. The AMv is in a position to convey information to cortico-hippocampal-amygdalar circuits involved in the processing of fear memory. However, it remains to be determined whether the nucleus is involved in the acquisition or subsequent expression of contextual fear. In the present investigation, we addressed this question by inactivating the rat AMv with muscimol either prior to cat exposure or prior to exposure to the cat-related context. Accordingly, AMv pharmacological inactivation prior to cat exposure did not interfere with innate fear responses, but it drastically reduced contextual conditioning to the predator-associated environment. On the other hand, AMv inactivation prior to exposure to the environment associated with the predator threat did not affect contextual fear responses. The behavioral results were further supported by the demonstration that AMv inactivation prior to cat exposure also blocked the activation of sites critically involved in the expression of anti-predatory contextual defensive responses (i.e., the dorsal premammillary nucleus and the dorsolateral periaqueductal gray) in animals exposed to the predator-associated context. The AMv projections were also examined, and the results of this investigation outline important paths that can influence hippocampal circuitry and raise new ideas for anterior thalamic-hippocampal paths involved in emotional learning.


PIK3CA somatic mutations in breast cancer: Mechanistic insights from Langevin dynamics simulations.
Somatic mutations in PIK3CA (phosphatidylinositol-3 kinase, catalytic subunit, alpha isoform) are reported in breast and other human cancers to concentrate at hotspots within its kinase and helical domains. Most of these mutations cause kinase gain of function in vitro and are associated with oncogenicity in vivo. However, little is known about the mechanisms driving tumor development. We have performed computational structural studies on a homology model of wildtype PIK3CA plus recurrent H1047R, H1047L, and P539R mutations, located in the kinase and helical domains, respectively. The time evolution of the structures show that H1047R/L mutants exhibit a larger area of the catalytic cleft between the kinase N- and C-lobes compared with the wildtype that could facilitate the entrance of substrates. This larger area might yield enhanced substrate-to-product turnover associated with oncogenicity. In addition, the H1047R/L mutants display increased kinase activation loop mobility, compared with the wildtype. The P539R mutant forms more hydrogen bonds and salt-bridge interactions than the wildtype, properties that are associated with enhanced thermostability. Mutant-specific differences in the catalytic cleft and activation loop behavior suggest that structure-based mutant-specific inhibitors can be designed for PIK3CA-positive breast cancers.


Synthesis and characterization of crosslinked gellan/PVA nanofibers for tissue engineering application.
Electrospun nanofibers based on gellan are considered as promising biomaterial for tissue engineering and wound healing applications. However, major hurdles in usage of these nanofibers are their poor stability and deprived structural consistency in aqueous medium which is a prerequisite for their application in the biomedical sector. In this investigation, three dimensional nanofibers, consisting of gellan and PVA have been fabricated and then stabilized under various crosslinking conditions in order to improve their physiochemical stability. The impacts of different crosslinking procedures on the gellan/PVA nanofibers were examined in terms of changes in morphological, mechanical, swelling and biological properties. Superior tensile strength and strain was recorded in case of crosslinked nanofibers as compared to non-crosslinked nanofibers. Contact angles and swelling properties of fabricated gellan/PVA nanofibers were found to vary with the crosslinking method. All crosslinking conditions were evaluated with regard to their response towards human dermal fibroblast (3T3L1) cells. Biocompatibility studies suggested that the fabricated crosslinked gellan/PVA nanofibers hold a great prospective in the biomedical engineering arena.


Influence of intraluminal brachytherapy dose on complications in the treatment of esophageal cancer.
Demonstration of the influence of intraluminal brachytherapy dose on complications in the treatment of esophageal carcinoma. Between January 1990 and June 1991, 75 patients with esophageal cancer were treated with external radiotherapy followed by intraluminal brachytherapy. Patients had a Karnofsky score of over 70, with no supra-clavicular nodal or distant disease. An external radiotherapy dose between 40 and 55 Gy (mean 52 Gy), 5 times a week, 2 to 2.06 Gy/fraction, followed by a single session of Intraluminal brachytherapy using a locally developed, manual, afterloading applicator with Cs-137 sources with dose ranges of 8-10 Gy (Group 1: 42 patients), 10-12 Gy (Group 2: 11 patients), and 12-15 Gy (Group 3: 22 patients) at a mean dose rate of 2.09 Gy/hr was delivered. The actuarial figures at 1 year were 39% for overall survival, 29% for disease-free survival, and 38% for local control. Fourteen patients (18.6%) developed complications of either an esophageal stricture or fistula. These were dependent on intra-luminal brachytherapy dose, whereas external radiotherapy and intra-luminal brachytherapy doses did not contribute significantly to local control. For Groups 1, 2, and 3, actuarial local control were 28%, 45%, and 63% (p < 0.1) and of complications were 6%, 20%, and 70% (p < 0.001), respectively. Also, on applying the Time/Dose/Fractionation formula on brachytherapy doses, it was found that the complication rate was 6% for TDF of < 31, 25% for TDF of 32-37, and 70% for TDF of > 38 (p < 0.001). External radiotherapy doses in the range of 50 to 55 Gy followed by a dose of 10-12 Gy of intraluminal brachytherapy was found optimal with respect to complications and local control in the radiotherapeutic management of esophageal cancer.


Incorporation of autopsy case-based learning into PhD graduate education: a novel approach to bridging the "bench-to-bedside" gap.
Given the current rapid expansion of biological knowledge and the challenges of translating that knowledge into clinical practice, finding effective methods of teaching graduate students clinical medicine concepts has become even more critical. The utility of autopsy in medical student and resident education has been well established. Multiple studies have reported it to be a helpful means of teaching anatomy, pathophysiology, clinical problem-solving skills, and medical diagnostic techniques. Although various models of training PhD candidates in clinical medicine have been reported, an autopsy-based curriculum has not been previously described. For over 4 years, our pathology department has offered a novel semester-long autopsy-based course to educate future Cellular and Molecular Pathology scientists about clinical medicine. Our results indicate that this "hands-on" approach is a popular as well as effective means of teaching the pathogenesis of disease at the level of the cell, organ, and patient. The course reputation has recently led to requests to open registration to graduate students from other university programs as well as undergraduate students. Additionally, it has played an important role in our Cellular and Molecular Pathology program's recent receipt of a 5-year renewal National Institutes of Health-funded T32 award. Overall, this course model has been successful at our own institution and could provide a useful template for other institutions seeking to provide graduate investigators with in-depth exposure to clinical medicine.


Cryopreservation and long-term in vitro maintenance of second-stage larvae of Toxocara canis.
Second stage larvae of Toxocara canis were isolated from developed eggs, frozen in Eagle's Minimal Essential Medium with 5% dimethyl sulfoxide or 10% glycerol as cryoprotectants according to two cooling schedules and maintained in liquid nitrogen for 1 week. After thawing, the previously frozen larvae (FL) and unfrozen controls (CL) were maintained in a chemically defined medium in vitro for 35 weeks. While CL had motility rates around 95% to 97% throughout the experiment, previously frozen larvae (FL) exhibited rates of 48%-58% at the beginning and of 19%-39% at the end of the 35 week in vitro maintenance period. The surviving FL and CL larvae proved to be infective for mice. Excretory/secretory (ES) antigens isolated from several batches of culture medium in which FL and CL had been maintained reacted in the ELISA with human sera containing antibodies against Toxocara. Antigens from FL and CL separated by SDS-PAGE and silver-stained showed some differences in polypeptide patterns. Western-blot analysis revealed that these differences were not related to antigenic polypeptides but were most likely caused by substances without antigenic properties originating from dead and/or degenerating larvae. It can be concluded that ES antigens produced by previously frozen larvae are essentially the same as those derived from unfrozen controls. The value of cryopreservation of T. canis larvae for routine production of ES antigens will be further evaluated.


Discordant Reporting of Partner Labels, HIV Testing and Sexual Behavior Among a Sample of Partnered Men Who have Sex with Men in the US.
There is growing evidence that sexual behaviors among male couples are strongly shaped by emotional and quality characteristics of the relationship, and that the labels that men attach to their relationships may indicate how men perceive and engage in risk taking. There has been a lack of attention to how male couples label their relationships, and how discordant understandings of relationship labels may shape HIV risk behavior. Using data from a sample of 804 partnered men who have sex with men, this analysis examines associations between discordant relationship labeling and participation in HIV testing and sexual behavior. Men who labeled their relationship differently from their partners were less likely to have been recently tested for HIV and more likely to engage in sexual risk. The results underscore the need to develop interventions that provide spaces and skills for men to learn how to effectively navigate HIV risks in their relationships.


Effect of central administration of prolactin-releasing peptide on feeding in chicks.
Prolactin-releasing peptide (PrRP) is one of the inhibitory factors in feeding regulation of mammals. However, no information is available for avian species. The present study was done to clarify the effect of intracerebroventricular (ICV) injection of PrRP on feeding in chicks. Firstly, we found that ICV injection of PrRP (94-1500 pmol) significantly increased food intake in chicks. The result was completely different from those obtained in mammals. The orexigenic effect of PrRP was significantly weaker than that of neuropeptide Y (NPY), a potent orexigenic peptide, on an equimolar basis. The orexigenic effect of NPY was further enhanced with coinjection of PrRP. These results suggest the existence of a novel orexigenic mechanism in the chick brain, which might differ from NPY-involved feeding regulatory pathway. In addition, ICV injection of PrRP significantly decreased the rectal temperature, but the effect was weaker than that of NPY, suggesting that PrRP may inhibit energy expenditure in chicks. Taken together, we showed here that PrRP may be involved in the regulation of both feeding behavior and energy metabolism in the chick brain.


An observational study of emotionally disturbed and learning-disabled children in school settings.
It has been alleged that populations of learning-disabled (LD) and emotionally disturbed (ED) children are essentially indistinguishable on important intervention-related symptoms. To examine this claim, a direct observation study of social interactions during class, lunch, and recess settings in two public schools was conducted. Teacher ratings of school behavior were also collected. The results indicated that the ED boys exhibited significantly more nonphysical aggression and noncompliance than the LD boys across settings, and that the LD boys had significantly higher rates of physical and nonphysical aggression and immature behavior than the LD girls. The correlations between the observations and teachers' ratings were modest but consistent with previous studies. The results are discussed with regard to their assessment and treatment implications.


The Remote Food Photography Method Accurately Estimates Dry Powdered Foods-The Source of Calories for Many Infants.
Infant formula is a major source of nutrition for infants, with more than half of all infants in the United States consuming infant formula exclusively or in combination with breast milk. The energy in infant powdered formula is derived from the powder and not the water, making it necessary to develop methods that can accurately estimate the amount of powder used before reconstitution. Our aim was to assess the use of the Remote Food Photography Method to accurately estimate the weight of infant powdered formula before reconstitution among the standard serving sizes. For each serving size (1 scoop, 2 scoops, 3 scoops, and 4 scoops), a set of seven test bottles and photographs were prepared as follow: recommended gram weight of powdered formula of the respective serving size by the manufacturer; three bottles and photographs containing 15%, 10%, and 5% less powdered formula than recommended; and three bottles and photographs containing 5%, 10%, and 15% more powdered formula than recommended (n=28). Ratio estimates of the test photographs as compared to standard photographs were obtained using standard Remote Food Photography Method analysis procedures. The ratio estimates and the US Department of Agriculture data tables were used to generate food and nutrient information to provide the Remote Food Photography Method estimates. Equivalence testing using the two one-sided t tests approach was used to determine equivalence between the actual gram weights and the Remote Food Photography Method estimated weights for all samples, within each serving size, and within underprepared and overprepared bottles. For all bottles, the gram weights estimated by the Remote Food Photography Method were within 5% equivalence bounds with a slight underestimation of 0.05 g (90% CI -0.49 to 0.40; P<0.001) and mean percent error ranging between 0.32% and 1.58% among the four serving sizes. The maximum observed mean error was an overestimation of 1.58% of powdered formula by the Remote Food Photography Method under controlled laboratory conditions, indicating that the Remote Food Photography Method accurately estimated infant powdered formula.


Hepatic fibrosis changes in patients with chronic hepatitis C infection who respond to direct-acting antivirals.
Clearance of hepatitis C virus (HCV) can potentially slow or reverse liver fibrosis and cirrhosis. Studies of fibrosis changes after treatment with direct-acting antivirals (DAAs) are limited. We aimed to assess the impact of DAAs on fibrosis in HCV treatment responders. Retrospective cohort study. Tertiary care centers. This study included adult patients who received DAA treatment for HCV (naïve and experienced) from June 2015 to January 2019 who were treatment responders. Biochemical and hematological data and noninvasive fibrosis markers were recorded at baseline and follow-up. Aspartate aminotransferase/platelet ratio index (APRI), fibrosis-4 score (FIB-4) and liver stiffness measurements (LSM) at baseline and follow-up. 172 HCV treatment responders, mean (SD) age 54.1 (14.1) and body mass index 28.8 (6.5) kg/m2 at baseline; 96 (55.8%) were females. Fifty-eight (33.7%) patients were HCV treatment-experienced. Most patients were genotype 4 (n=125, 73%) and the mean follow-up was 141 (57.9) weeks. Compared with baseline, changes in alanine aminotransferase (P<.001), aspartate aminotransferase (P<.001), and albumin (P=.01) were statistically significant. Changes in LSM (15.09 kPa [11.4] vs. 10.19 kPa [7.4], P<.001), APRI (0.81 [0.7] vs. 0.34 [0.2], P<.001), and FIB-4 (1.99 [1.4) vs.1.35 [0.9], P<.001), and AST/ALT ratio (0.86 [0.32] vs. 0.95 [0.41], P=.015) were statistically significant. Differences in many of the same parameters were statistically significant between patients with low fibrosis (F0-F1) (n=59, 34.3%) and significant fibrosis (≥F2) (n=113, 65.7%). Our findings confirm that clearance of HCV with DAAs is associated with significant improvement in fibrosis as assessed by noninvasive liver fibrosis measures, which supports the concept of post-treatment fibrosis regression. Long follow-up studies are needed to assess the impact on morbidity and mortality. Absence of histological correlation with these noninvasive scores. No assessment of fibrosis changes based on HCV geno-type or treatment regimen. None.


Role of Spin-Orbit Coupling in Long Range Energy Transfer in Metal-Organic Frameworks.
Metal-organic frameworks (MOFs) are emerging as a promising platform for solar energy conversion applications. Their potential utilization as efficient chromophores in artificial photosynthesis is closely related to the understanding of light-harvesting and energy transfer processes that occur within these molecular scaffolds. Herein, we present the photophysical investigation of Ru(II), Ir(III), and Os(II) polypyridyl complexes incorporated into the backbone of UiO-67. In this work, we systematically study the effect of spin-orbit coupling on dipole-dipole energy transfer in MOFs using steady-state and time-resolved spectroscopic techniques. The results of our work indicate successful triplet-to-singlet energy transfer and a sizable increase in the transfer kinetics and critical distance, as direct consequences of strong spin-orbit couplings. Remarkably, the reported R0 value for OsDCBPY (R0 = 88 ± 10 Å) represents one of the largest Förster distances observed in an MOF. Collectively, this work contributes to the general knowledge of energy transfer in materials and provides groundwork for efficient utilization in artificial photosynthetic assemblies.


Survival According to Primary Tumor Location, Stage, and Treatment Patterns in Locoregional Gastroenteropancreatic High-grade Neuroendocrine Carcinomas.
Although the gastrointestinal tract (including the pancreas, gastroenteropancreatic (GEP) is the most common site for extrapulmonary neuroendocrine carcinoma (NEC), the current treatment patterns of locoregional GEP NEC and in particular, the role of surgical resection is unclear. Data from the National Cancer Database between 2004 and 2016 were used for this study. Of 2314 GEP NEC cases (stages I-III), 52.5% were stage III. Colon was the most common site (30%); 30.9% of all cases were small cell morphology. Age, morphology, stage, and primary site were associated with significant differences in treatment patterns. Management of NEC mimicked that of adenocarcinomas arising at the respective sites: colon NEC most likely to be treated with surgery and chemotherapy; anal and esophageal NEC was primarily likely to receive chemotherapy and radiation, and rectal NEC mostly likely to receive trimodality therapy. However, 25%-40% of patients did not undergo surgical resection even at sites typically managed with curative resection, and there was a trend toward lesser resection over time. The prognostic impact of surgical resection was significant across all stages and correlated with variations in survival across primary sites. Even in patients undergoing chemoradiation, surgery was the only prognostic variable that significantly affected survival in stages I-II patients (HR 0.63) and showed a strong trend in stage III (HR 0.77) patients. Treatment patterns in GEP NEC vary considerably according to stage and primary tumor site. Surgery significantly improved survival in stages I-II patients and showed a strong trend in stage III patients regardless of primary tumor location and other perioperative therapies.


Comparative study of enterostatin sequence in five rat strains and enterostatin binding proteins in rat and chicken serum.
Enterostatin, a pentapeptide derived from the precursor protein procolipase has been shown to inhibit dietary fat intake and to reduce body fat after chronic administration in rats. We repeat that the enterostatin amino acid sequence from the genomic DNA of 5 different rat strains is APGPR. 125I-APGPR bound to three proteins (300, 205 and 60 kDa) in rat serum and one 60 kDa protein in chicken serum. These serum binding proteins were also eluted by APGPR affinity chromatography. Western blot analysis of serum protein identified enterostatin-like immunoreactivity associated with the same molecular weight bands. Our results demonstrate the enterostatin sequence in rat is APGPR and suggest the presence of enterostatin binding proteins in rat and chicken serum.


Catalytic Activation of Polyethylene Model Compounds Over Metal-Exchanged Beta Zeolites.
Decomposition of polymers by heterogeneous catalysts presents a promising approach for reuse of waste plastics. We demonstrated non-hydrogenative decomposition of model polyolefins over proton-form and metal (Cu, Ni) ion-exchanged beta (BEA) zeolites at moderate temperatures (around 300 °C). Near complete polyolefin decomposition was observed in batch reactions monitored by thermogravimetric analysis, while decomposition at partial conversion was studied in flow reactions. Ni-exchanged zeolites produced H2 at substantially higher rates (>10x) than other catalysts while also uniquely resisting deactivation over time. Application of the delplot formalism offered insights into the reaction network for polyolefin decomposition over Ni/BEA most notably that H2 is solely a primary product. We deduce that H2 production is catalyzed by activation of C-H bonds at ionic Ni sites, and H2 prevents buildup of polyaromatic coke species in Ni-exchanged zeolites that deactivate Cu-exchanged and protonic zeolites.


Effect and mechanism of Fisetin on myocardial damage induced by Patulin.
The aim of this study is to investigate whether fisetin can effectively reduce the myocardial damage induced by patulin. This study also aims to reveal the mechanism and target of fisetin in inhibiting myocardial damage. Network pharmacology was used to screen the targets of fisetin on myocardial damage and the regulatory network of active ingredients-drug targets was constructed. GO and KEGG enrichment analyses were performed to screen out the key pathways and targets of fisetin on myocardial damage. Patulin induced apoptosis in H9c2 cardiomyocytes to verify the key targets. The mechanism of fisetin in inhibiting myocardial damage was determined. FIS can reduce the apoptosis of cardiomyocytes by protecting cardiomyocytes from PAT injury. According to the results of network pharmacology analysis, combined with enzyme activity detection and WB experiment, it was found that the mechanism of FIS to reduce myocardial damage may be related to the P53 signaling pathway, Caspase3/8/9 and Bax/Bcl-2. FIS plays a protective role in PAT-induced myocardial damage. On the one hand, FIS inhibits the protein overexpression of P53, Caspase-9 and Bax. On the other hand, FIS enhances the protein expression of Bcl-2.


The prevalence of microalbuminuria in diabetic children and adolescents and its relation to puberty.
The albumin excretion rate (AER) was studied in two groups of diabetic children and adolescents. Twenty-four-hour AER was studied in 75 children with diabetes for 5 years, in 49 children with diabetes for 10 years, in 55 children with diabetes for 10-20 years and in 21 age matched healthy controls. Overnight AER was studied in 129 diabetic children and adolescents with a duration of diabetes varying from 1-14 years. Diabetics exhibited a wide range of AER-values and when expressed per body surface area, diabetic children had significantly higher AER compared to controls. Log transformed AER-values were significantly correlated to age and body surface area in diabetics but not in controls. In the diabetics, log AER was also correlated to systolic and diastolic blood pressure but not to HbA1c. 20% of the diabetics had AER values exceeding the upper value for healthy controls which was 18.5 micrograms/min. 31/35 of them were older than 12 years. In both groups of diabetics, 5% had AER-values exceeding those reported to be predictive for later development of overt nephropathy, the youngest being 16 years old. When comparing diabetic children 0-12 years (i.e. before the maximal growth spurt of puberty) to those older than 12 years, at the same duration of diabetes, the latter group had significantly higher AER-values. No sex difference was found in either age group. It is concluded that after puberty diabetic patients also show evidence of incipient diabetic nephropathy. Thus, routine screening for microalbuminuria is recommended also in pediatric diabetes care after 12 years of age.


A randomization test for comparison of groups of growth curves with different polynomial design matrices.
Well defined methods for comparing mean polynomial growth curves exist when subjects are measured at identical times, modeled with polynomials of identical degree and when multivariate normality of the measurements can be assumed. Relaxing these conditions creates problems solved here for the special case of a completely randomized design by developing a randomization test which is both practical and interval specific. The procedure is applied to longitudinal data from a study of human growth.


Stability-indicating assay for mecillinam using high-pressure liquid chromatography.
A high-pressure liquid chromatographic method has been developed for use as a stability-indicating assay for mecillinam. Seven related compounds and at least one unknown degradation product are well separated and easily determined. The accuracy of the method is in good agreement with the published UV assay and the precision of a series of seven replicate determinations is +/- 1.0% R.S.D.


How to confirm occupational asthma.
A methodological overview is provided on the important question of how to confirm occupational asthma in routine work. Recent knowledge gained in immunology and occupational allergy has been utilized, supplemented by an overview of recent publications on the diagnosis and pathophysiology of occupational asthma. The aim of the paper is to facilitate decision making for an investigator dealing with individual cases of occupational asthma. Moreover, by presenting stepping-stones in the diagnostic cascade, the author hopes to encourage the less experienced to conduct a comprehensive and cause-oriented diagnostic procedure. Methods which are being worked on at present (standardization) are discussed in more detail. Finally, the research goals in the understanding, confirmation, and prevention of occupational asthma are listed.


Novel quad-rotor-shaped photovoltaic materials: first example of fused-ring non-fullerene acceptors with proficient photovoltaic properties for high-performance solar cells.
Development of novel materials for organic solar cells is a booming area of current research. Fused-ring electron accepters are the potential agents of revolution in organic photovoltaic devices and revealing high efficiency in organic solar cells. This study highlights the novel quad-rotor-shaped molecules as first example of efficient fused-ring non-fullerene acceptor materials with proficient photovoltaic parameters for their utilization in high-performance organic solar cells. First time, eight quad-rotor-shaped fused-ring electron accepters (QRFR-1-QRFR-8) are developed via modulating end-caps of experimentally synthesized (BFTT-TN) molecule (QRFR). Optoelectronic properties of proposed molecules are determined using frontier molecular orbitals (FMO), UV-Visible, density of state (DOS), overlap DOS (ODOS), transition density matrix (TDM) heat maps, open circuit voltage (Voc), binding energies (Eb), reorganization energy of electron (λe), hole (λh), charge transfer analysis, and compared with reference QRFR. All proposed fused-ring electron accepters disclose less energy gap and λmax in near IR region than QRFR after end-capped engineering. Highest Voc with respect to HOMOPM6-LUMOacceptor is found 1.66 V in QRFR-6 than QRFR (1.63 V). Eb values of QRFR-1-QRFR-8 are found better and comparable with QRFR. The λe is found smaller than QRFR in all molecules except QRFR-5. The proposed quad-rotor-shaped molecules exhibit proficient photovoltaic features and can serve as best candidate for organic solar cells when blended with PM6 film. This study not only enlightens the researchers to use end-capped reforms as effective tactic for designing materials, but also provides novel quad-rotor-shaped materials to experimentalist for synthesis and their usage in future application of organic solar cells.


Dual-role self-assembling nanoplexes for efficient gene transfection and sustained gene delivery.
Novel cationic pentablock copolymers with poly(diethylamino ethyl methacrylate) blocks covalently attached to parent triblock Pluronic copolymers have been designed and developed as sustained release non-viral gene delivery vectors. These copolymers electrostatically condense plasmid DNA into nanostructures (nanoplexes) and further self-assemble above critical concentration to form thermoreversible hydrogels at physiological temperatures. Unlike other sustained gene delivery systems of non-ionic copolymers that release naked DNA, hydrogels of pentablock copolymer/DNA nanoplexes dissolve in excess buffers to release DNA compacted inside the nanoplexes. These hydrogels permit aqueous pharmaceutical formulations that do not involve organic solvents and are non-invasively injectable with syringes into localized tissues where they instantly form hydrogels in situ. The hydrogels were found to have better mechanical strength than Pluronic gels. Hydrogels of nanoplexes containing 15wt% copolymer dissolved to release nanoplexes up to 5 days in vitro, compared to rapid release of up to 90% entrapped naked DNA from only Pluronic gels by day 1. The release profile of the nanoplexes from the hydrogels could be modulated by changing the concentration of copolymer or plasmid DNA in the hydrogel formulation. Since DNA is electrostatically bound to copolymer molecules, it does not freely diffuse out of the polymeric network, preventing initial release bursts observed with other such controlled release gels/matrices/microspheres. The released nanoplexes were colloidally stable, preserved the integrity of supercoiled plasmid DNA, and gave good transfection efficiencies in vitro upon dissolution. These novel copolymers, thus, act as both nanoscale gene delivery vectors and macroscale sustained delivery agents, and make a clinically viable long-term sustained gene delivery system.


Evaluation of retention time for temperature-programmed gas chromatography by use of a closed-form integral.
A closed-form integral for the Arrhenius exponential was obtained by using an approximate relation instead of the usual one in a linear temperature program. The closed-form integral can be applied to predict the retention time very well both for a packed column and for a capillary column, in constant the velocity mode.


HIV-related discrimination in New Brunswick increasing.
In February 2000, AIDS New Brunswick, AIDS Saint John, and SIDA AIDS Moncton released findings of a study on the needs of people with HIV/AIDS in New Brunswick.


A rare case of primary spinal cord oligodendroglioma.
Primary spinal cord oligodendroglioma is a rare tumor that originates from oligodendrocytes. Oligodendroglioma itself is commonly found in the cerebral hemisphere and spinal oligodendroglioma is an unusual presentation of this disease. Here, we present a case of a 48-year-old patient with low back pain, weakness of the lower extremities, and numbness. Spinal magnetic resonance imaging (MRI) showed an intradural intramedullary vertebral mass at level T4-T5 which proved to be an oligodendroglioma after histopathological examination.


Analysis of Strychnos alkaloids in traditional Chinese medicines with improved sensitivity by sweeping micellar electrokinetic chromatography.
The application of an on-line sweeping preconcentration method in micellar electrokinetic chromatography (MEKC) for the determination of Strychnos alkaloids, namely strychnine and brucine, has been investigated in this work. After experimental optimizations, the best separation was achieved in 50 mmol l(-1) H3PO4 (pH 2.0) containing 100 mmol l(-1) SDS and acetonitrile in a ratio of 4:1 (v/v), with an applied voltage of -20 kV at 20 degrees C. The sample matrix consisted of 100 mmol l(-1) H3PO4 (pH 2.0), and sample introduction was performed at 0.5 psi for 270 s, with photodiode array detection at 203 nm. Compared with the conventional MEKC injection method, up to 100-fold improvement in concentration sensitivity was achieved in terms of peak height by using this sweeping injection technique. In the method, the compound berberine was used as the internal standard for the improvement of the experimental reproducibility. The calibration curve was linear over a range of 0.5-15 microg ml(-1) for both strychnine and brucine, with a correlation coefficient of 0.998 and 0.997, respectively. The detection limits (S/N=3:1) for strychnine and brucine were 0.05 and 0.07 microg ml(-1), respectively. The sweeping-MEKC method has been successfully applied to the analysis of strychnine and brucine in Strychnos nux-vomica L. and its Chinese medicinal preparations.


The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.
Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models.


Origin of blood cells and HSC production in the embryo.
Hematopoietic stem cells (HSCs) are capable of self-renewal and differentiation into all blood cell types. During adult life, they reside in the bone marrow in a quiescent state. By contrast, in the growing embryo hematopoiesis is sequentially found in several developmental niches. This review provides an overview of the still controversial contribution of each of these embryonic sites to the final pool of adult HSCs and discusses new insights into the cellular origin and the molecular regulation implicated in the generation of blood progenitor cells. A better understanding of HSC development during ontogeny is essential to develop new strategies to amplify HSCs or to generate them from embryonic stem cells or by somatic cell reprogramming.


[Gender-related aspects of family caregiving].
Most people in need of care and assistance are currently still being cared for at home by family members. The majority of family caregivers are women. However, the percentage of men assuming the role of main caregiver at home is increasing. This may point to a change in the distribution of caregiving within the family. The health-related and social stresses and strains affecting cargiving persons also show gender-specific differences and are experienced more frequently and with a higher intensity by female caregivers than caregiving men. Men approach the challenge of caring differently to women and also organize care differently to female family caregivers. Although a high percentage of those providing informal care to family members at home are now men, this fact is hardly appreciated by society. In the specialist literature, caring men are often seen from the perspective of women. This article aims to portray gender-specific perspectives concerning the situation of providing informal care and assistance to elderly people and the stresses and strains that are associated with it.


Intravenous immunoglobulins reduce skin thickness in systemic sclerosis: evidence from Systematic Literature Review and from real life experience.
Intravenous immunoglobulins (IVIG) are a new therapeutic approach in systemic sclerosis SSc. An immunomodulatory and antifibrotic activity has been postulated. IVIG are generally well tolerated and have only rare side effects. Our retrospective study focused its attention on SSc, an autoimmune connective tissue disease, characterized by several complications which has a significant impact on patient's quality of life. The pathophysiology comprises fibrotic, vascular and immunological aspects. The aim of this study was to verify the effectiveness of IVIG on SSc skin involvement. Moreover, a systematic review of the literature (SLR) of the results obtained to date on the use of Intravenous immunoglobulin (IVIG) in SSc has been also performed. The data of 24 patients (21 women, 3 male) with refractory diffuse SSc skin involvement were evaluated (mean age was 52.13 years). IVIG infusion at a dosage of 2 g/Kg body weight for 4 consecutive days/month, was started between 2002 and 2019. Skin involvement was evaluated with the modified Rodnan Skin Score (mRSS) before therapy and then again after 6 and 12 months. To perform the SLR, the PubMed, Medline, Embase, and Web of Science database were searched from 1990 to 2020 (keywords: IVIG, systemic sclerosis). Three assessors (E.A., C.B. & M.M.C) identified the criteria to scan all papers. From the total SLR (106 results), 17 papers were identified after the separation of the clinical cases from the studies (total number of treated patients 183). The studies were classified according to the organ involvement considered in each study, as well as the prescribed dose (high or low doses), and the therapeutic regimens. In the selected papers, the organs mainly involved were the skin, the gastrointestinal, the joint and the cardiovascular systems. Only in one case, plasmapheresis was associated to IVIG. All papers reported significant reduction of the skin involvement, although generally the strength of the works was limited the lack of control cases or by the low number of patients involved. From the real life experience, a statistically significant reduction of mRSS was obtained at 6 months follow-up (average value of -6.61 ± 5.2, p < 0.001), and it was further maintained with a significant stabilization after 12-months (-11.45 ± 9.63, p < 0.002). This SLR and the data of the retrospective study suggest that IVIG may improve skin involvement reducing mRSS in particular in those patients that were refractory to other standard of care therapies and represents a therapeutic option in patients with concomitant myositis. The literature review revealed encouraging perspectives on the use of this therapy, given the effectiveness found in the selected works.


A neural network for glomerulus classification based on histological images of kidney biopsy.
Computer-aided diagnosis (CAD) systems based on medical images could support physicians in the decision-making process. During the last decades, researchers have proposed CAD systems in several medical domains achieving promising results. CAD systems play an important role in digital pathology supporting pathologists in analyzing biopsy slides by means of standardized and objective workflows. In the proposed work, we designed and tested a novel CAD system module based on image processing techniques and machine learning, whose objective was to classify the condition affecting renal corpuscles (glomeruli) between sclerotic and non-sclerotic. Such discrimination is useful for the biopsy slides evaluation performed by pathologists. We collected 26 digital slides taken from the kidneys of 19 donors with Periodic Acid-Schiff staining. Expert pathologists have conducted the slides preparation, digital acquisition and glomeruli annotations. Before setting the classifiers, we evaluated several feature extraction techniques from the annotated regions. Then, a feature reduction procedure followed by a shallow artificial neural network allowed discriminating between the glomeruli classes. We evaluated the workflow considering an independent dataset (i.e., processing images not used in the training procedure). Ten independent runs of the training algorithm, and evaluation, allowed achieving MCC and Accuracy of 0.95 (± 0.01) and 0.99 (standard deviation < 0.00), respectively. We also obtained good precision (0.9844 ± 0.0111) and recall (0.9310 ± 0.0153). Results on the test set confirm that the proposed workflow is consistent and reliable for the investigated domain, and it can support the clinical practice of discriminating the two classes of glomeruli. Analyses on misclassifications show that the involved images are usually affected by staining artefacts or present partial sections due to slice preparation and staining processes. In clinical practice, however, pathologists discard images showing such artefacts.


Factors Associated With Secondary Traumatic Stress Among Nurses in Regional Trauma Centers in South Korea: A Descriptive Correlational Study.
Trauma is a leading cause of death in South Korea. This study aimed to identify the factors associated with secondary traumatic stress of nurses working at regional trauma centers. A survey-based cross-sectional design was utilized. Data were collected through a structured questionnaire consisting of 5 rating scales and demographic data. Data were analyzed via descriptive statistics, t test, analysis of variance, Pearson's correlation, and multiple regression. One hundred eighty-six nurses participated, and most (84.4%) reported moderate to severe secondary traumatic stress. Exposure to traumatic events averaged 34.33 (SD = 6.25) out of 65 points. Average problem-focused coping was 3.00 (SD = 0.37), emotion-focused coping was 2.57 (SD = 0.26), and dysfunctional coping was 2.17 (SD = 0.41) out of 4 points. Social support from family and friends averaged 5.85 (SD = 0.75), social support from coworkers was 5.78 (SD = 0.83), and social support from supervisors was 4.65 (SD = 1.18) out of 7 points. The factors affecting the respondents' secondary traumatic stress were type D personality (β = 0.39, P < .001), dysfunctional coping (β = 0.28, P < .001), problem-focused coping (β = 0.19, P < .01), desire for job rotation (β = 0.17, P < .01), and social support from supervisors (β = -0.12, P = < .05). This regression model was statistically significant and the explanatory power was 46.7% (F = 33.47, P < .001, Adj R2 = 0.47). Along with a personal effort to engage in stress management programs, administrators, managers, and supervisors should prioritize developing practical strategies for reducing secondary traumatic stress of nurses.


Perioperative Surgical Home: Perspective II.
Healthcare delivery and payment systems in the United States must continue to be reformed to address currently untenably increasing healthcare expenditures, while increasing the quality of care. The Perioperative Surgical Home is a highly patient-centered approach to care, focusing on the standardization, coordination, transitions, and value of care, throughout the perioperative continuum, including after hospital discharge. To increase the value of surgical care, any Perioperative Surgical Home model must translate, implement, and sustain improvements in quality, safety, and satisfaction, plus cost reduction strategies, throughout the perioperative continuum. Healthcare informatics, analytics, decision support, and practice change are central to this effort.


Prognostic Value of Neutrophil to Lymphocyte Ratio for Predicting 90-Day Poor Outcomes in Hospitalized Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
This study aimed to evaluate the predictive value of neutrophil to lymphocyte ratio (NLR) for poor outcomes within 90-day in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A retrospective study including 503 AECOPD patients was performed, and the subjects' clinical characteristics were collected. Binary logistic regression analysis was used to identify risk factors for 90-day poor outcomes in patients with AECOPD. Receiver-operating characteristic curves (ROC) and areas under the curves (AUC) were used to assess the ability of different biomarkers to predict the risk of 90-day mortality, readmission and re-exacerbation in patients with AECOPD. During the follow-up, 188 patients (38.4%) redeveloped exacerbations, 112 patients (22.9%) were readmitted, and 20 patients (4.1%) died directly resulted from COPD or COPD-related causes. Multivariate analysis demonstrated that age>72 years (OR: 14.817, 95% CI: 1.561-140.647), NLR>14.17 (OR: 9.611, 95% CI: 2.303-40.113), EOS<0.15% (OR: 8.621, 95% CI: 3.465-34.913) and BNP>2840ng/L (OR: 5.291, 95% CI: 1.367-20.474) at discharge were independent risk factors for 90-day mortality in AECOPD patients. NLR was the optimal biomarker for predicting 90-day mortality with an AUC of 0.802 (95% CI: 0.631-0.973). Using 14.17 as the critical value of NLR, the sensitivity was 76.7%, and the specificity was 88.9%. Compared with mortality, NLR had no significant advantage in predicting risk of short-term re-exacerbation (AUC=0.580, 95% CI:0.529-0.632, p=0.001) and readmission (AUC=0.555, 95% CI:0.497-0.614, p=0.045), with AUCs less than 0.6. In contrast, the predictive value of EOS (AUC=0.561, 95% CI:0.502-0.621, p=0.038) was slightly better than NLR in terms of readmission within 90 days. CRP did not serve as a well predictive biomarker for the risk of readmission and re-deterioration (p>0.05). NLR is of great value in predicting the risk of poor outcomes, especially COPD associated mortality, in hospitalized patients with AECOPD within 90 days after discharge.


Preliminary Study of Confounder-Corrected Fat Fraction and R2* Mapping of Bone Marrow in Children With Acute Leukemia.
The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. Prospective. Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). Independent sample t-tests, variance analysis, Spearman correlation. BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. 1 Technical Efficacy: 2.


[Preoperative factors influencing visual acuity following vitrectomy for exudative age-related macular degeneration].
We investigated the relations between ingrowth site and visual results in patients undergoing surgical removal of subfoveal choroidal neovascular membranes (CNV) caused by age-related macular degeneration (AMD). The subjects were 70 eyes(69 patients), which underwent surgical removal of CNV for AMD and were followed up for 6 months or more. The eligibility criteria were active subfoveal choroidal neovascular membrane 3 disc diameters (DD) or less in size located above the retinal pigment epithelium, and visual acuity of 0.3 or worse. We analyzed the relationships between postoperative best-corrected visual acuity and preoperative factors: ingrowth site of CNV, distance between the fovea and the CNV edge, CNV size, and fluorescence pattern in indocyanine green angiography (IA). Patients 1) with feeder vessels located outside the foveal avascular zone (FAZ) rather than inside the FAZ and/or unknown feeder vessels, 2) with a distance between the fovea and the CNV edge 0.2 DD or less than 0.2 DD versus larger, than 0.2 DD 3) with a 1 DD or smaller CNV versus 1.5 DD or larger, and 4) type I, II, or III findings in IA rather than type IV had good postoperative best-corrected visual acuity. To achieve better postoperative visual acuity after surgical removal of CNV associated with AMD, it is important to select CNV with ingrowth sites outside the FAZ, small and large CNV with a relatively short distance between the fovea and the CNV edge closest to the fovea, and type I, II, and III findings in IA.


Haem synthesis during cytochrome P-450 induction in higher plants. 5-Aminolaevulinic acid synthesis through a five-carbon pathway in Helianthus tuberosus tuber tissues aged in the dark.
Chlorophyll and haem synthesis in illuminated Jerusalem artichoke tuber tissues were very efficiently inhibited by gabaculine (3-amino-2,3-dihydrobenzoic acid). This inhibition seems to be due specifically to a blockade of the pathway for 5-aminolaevulinate biosynthesis which used glutamate as a substrate (the so-called C5 pathway) since we could not detect any inhibition of protein synthesis in the treated tissues and there was no effect of gabaculine on the glycine-dependent yeast 5-aminolaevulinate synthase used as a model. In dark-aged artichoke tissues, gabaculine also effectively blocked cytochrome P-450 induction, peroxidase activity and 5-aminolaevulinic acid synthesis, thus suggesting the involvement of a C5 pathway in cytoplasmic and microsomal haemoprotein synthesis in this higher plant. Allylglycine and (2-amino-ethyloxyvinyl)glycine, two olefinic glycine analogues which are potential suicide inhibitors of pyridoxal phosphate enzymes, were also demonstrated to be effective blockers of chlorophyll synthesis in artichoke tuber and Euglena cells exposed to light.


Angiotensin and the renal circulation in hypertension.
Converting-enzyme inhibition, whether teprotide, captopril, or enalapril is used, produces a larger increase in renal blood flow in patients with essential hypertension than in normal subjects when they are on a low-salt diet, a quantitative difference. When studies were performed in individuals on a high-salt diet, normal subjects showed little or no response, whereas a substantial number of patients with essential hypertension displayed an increase in renal blood flow with these agents, a qualitative difference. The individuals that show this potentiated response we now are coming to recognize, have a number of features that suggest a distinct subgroup, the "nonmodulators." Normotensive offspring of hypertensive patients show a directionally similar but smaller renal vascular response to converting-enzyme inhibition. These hypertensive patients also show a blunted natriuresis in response to a sodium loading, which is corrected by converting-enzyme inhibition. Several lines of evidence suggest that the locus of action is intrarenal rather than systemic. Plasma renin activity and plasma angiotensin II concentration are not higher in these subjects, and thus cannot account for their potentiated response to converting-enzyme inhibition. Moreover, the infusion of captopril directly into the renal artery in doses far too low to induce a systemic effect increases renal blood flow specifically in these subjects. They also show a blunted rate of renin suppression after a sodium load, although plasma renin activity falls to the same low level at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)


Facilitating and motivating factors for reporting reprehensible conduct in care: A study among nurse practitioners and physician assistants in the Netherlands.
The aims of this study are as follows: (a) to establish whether a relationship exists between the importance that healthcare professionals attach to ethics in care and their likelihood to report reprehensible conduct committed by colleagues, and (b) to assess whether this relationship is moderated by behavioural control targeted at preventing harm. In this cross-sectional study, which was based on a convenience sample (n = 155) of nurse practitioners (NPs) and physician assistants (PAs) in the Netherlands, we measured ethics advocacy (EA) as a motivating factor (reflecting the importance that healthcare professionals attach to ethics and care) and "behavioral control targeted at preventing harm" (BCPH) as a facilitating factor. "Reporting reprehensible conduct" (RRC) was measured as a context-specific indicator of whistleblowing intentions, consisting of two vignettes describing morally questionable behaviour committed by colleagues. The propensity to report reprehensible conduct was a function of the interaction between EA and BCPH. The only group for which EA predicted RRC consisted of individuals with above-average levels of perceived BCPH. The results suggest that the importance that healthcare professionals attach to ethical aspects in care is not sufficient to ensure that they will report reprehensible conduct. Such importance does not induce reporting behaviour unless the professionals also perceive themselves as having a high level of BCPH. We suggest that these insights could be helpful in training healthcare providers to cope with ethical dilemmas that they are likely to encounter in their work.


Acquired aqueductal stenosis in preterm infants: an indication for neuroendoscopic third ventriculostomy.
The object of this study is to demonstrate the delayed occurrence of aqueductal stenosis in preterm infants who have suffered from intraventricular hemorrhage (IVH) and to try to explain the mechanisms of this stenosis. From January 1996 to June 2002, 1,046 premature infants were admitted to our institution. Thirty-six neonates suffered from grade 3 or 4 intraventricular hemorrhage (Papile grading), of whom 16 died. Twenty patients survived and a ventriculoperitoneal shunt was inserted in 7 infants. Four patients underwent a neuroendoscopic third ventriculostomy. Follow-up was carried out, twice a month during the first 2 months and subsequently twice a year. In 2 children NTV was an effective treatment for hydrocephalus with an average follow-up of 29 months. The specific pattern concerning these patients is the long delay before obstructive hydrocephalus and the visualization of de novo obstruction with MRI. The biological explanation must be investigated.


Direct Electrophysiological Evidence for Prefrontal Control of Hippocampal Processing during Voluntary Forgetting.
Forgetting does not necessarily reflect failure to encode information but can, to some extent, also be voluntarily controlled. Previous studies have suggested that voluntary forgetting relies on active inhibition of encoding processes in the hippocampus by the dorsolateral prefrontal cortex (DLPFC) [1-4]. During attentional and sensorimotor processing, enhanced DLPFC theta power alongside increased alpha/beta oscillations are a neural signature of an inhibitory top-down mechanism, with theta oscillations reflecting prefrontal control and alpha/beta oscillations occurring in areas targeted by inhibition [5-12]. Here, we used intracranial EEG recordings in presurgical epilepsy patients implanted in DLPFC (n = 13) and hippocampus (n = 15) during an item-method directed forgetting paradigm. We found that voluntary forgetting is associated with increased neural oscillations in the low theta band (3-5 Hz) in DLPFC and in a broad theta/alpha/beta (6-18 Hz) frequency range in hippocampus. Combining time-lagged correlation analysis, phase synchronization, and Granger causality in 6 patients with electrodes in both DLPFC and hippocampus, we obtained converging evidence for a top-down control of hippocampal activity by the DLPFC. Together, our results provide strong support for a model in which voluntary forgetting relies on enhanced inhibition of the hippocampus by the DLPFC.


Multi-omics to predict changes during cold pressor test.
The cold pressor test (CPT) is a widely used pain provocation test to investigate both pain tolerance and cardiovascular responses. We hypothesize, that performing multi-omic analyses during CPT gives the opportunity to home in on molecular mechanisms involved. Twenty-two females were phenotypically assessed before and after a CPT, and blood samples were taken. RNA-Sequencing, steroid profiling and untargeted metabolomics were performed. Each 'omic level was analyzed separately at both single-feature and systems-level (principal component [PCA] and partial least squares [PLS] regression analysis) and all 'omic levels were combined using an integrative multi-omics approach, all using the paired-sample design. We showed that PCA was not able to discriminate time points, while PLS did significantly distinguish time points using metabolomics and/or transcriptomic data, but not using conventional physiological measures. Transcriptomic and metabolomic data revealed at feature-, systems- and integrative- level biologically relevant processes involved during CPT, e.g. lipid metabolism and stress response. Multi-omics strategies have a great potential in pain research, both at feature- and systems- level. Therefore, they should be exploited in intervention studies, such as pain provocation tests, to gain knowledge on the biological mechanisms involved in complex traits.


LncRNA MALAT1 promotes neuropathic pain progression through the miR‑154‑5p/AQP9 axis in CCI rat models.
The present study investigated the role and molecular mechanism of long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript (MALAT)1 in neuropathic pain in rat chronic constriction injury (CCI) model. Reverse transcription‑quantitative PCR and western blot analysis were used to detect the expression levels of MALAT1, microRNA (miR)‑154‑5p and aquaporin (AQP)9 in spinal cord tissue and microglia of CCI rats. ELISA and pain behavioral assays were used to observe the effect of MALAT1 on neuropathic pain and neuroinflammation in model rats, and to verify its molecular mechanism through bioinformatics and luciferase experiments. The results of the present study identified that the expression levels of MALAT1 and AQP9 were upregulated, while miR‑154‑5p was downregulated in spinal cord tissue and microglia of CCI rats. MALAT1 knockdown in CCI model rats significantly induced the occurrence of neuropathic pain, while the upregulation of miR‑154‑5p could reverse this process. The present study also identified that miR‑154‑5p was the target gene of MALAT1, and AQP9 was the target gene of miR‑154‑5p. AQP9 knockdown promoted the occurrence of neuropathic pain. In conclusion, lncRNA MALAT1 promotes the progression of neuropathic pain in rats by reducing miR‑154‑5p and increasing AQP9. The MALAT1/miR‑154‑5p/AQP9 axis can be used as a new therapeutic target for neuropathic pain.


Dataset for life cycle assessment of strawberry-package supply chain with considering food loss during transportation.
This dataset includes two kinds of data (for inventory analysis in Table A1 to A13, and precondition of waste and recycle for plastic and cardboard in Table A14) for conducting life cycle assessment (LCA) of strawberry-package supply chain with considering food loss during transportation Inventory analysis includes input data for LCA analysis. The data in the inventory was referenced from the publication of Plastic Waste Management Institute Plastic Waste Management Institute, (2017) and calculated based on the damage area ratio measured in our co-submitted article (Sasaki et al., 2022). This data helps to reproduce the article (Sasaki et al., 2022) for inventory analysis and re-analyze the environmental impact through the life cycle of strawberry assessed in the co-submitted article. Data of waste (incineration and landfill) and recycle ratios for plastic was collected from the previous reports of the publication Basic Knowledge of Plastic Recycle 2021 (Plastic Waste Management Institute, 2021), and data of the ratios for cardboard was referenced from Transition of Collect Rate on Cardboard (Ministry of the Environment (MOE), 2016). Ratios in this data show Japan-specialized values and is useful for creating the inventory.


Inhaling alcohol vapour or mist: An international study of use, effects and harms.
To determine the prevalence, patterns of use and consequences of inhaling alcohol vapour or mist. Cross-sectional survey recruiting an international non-probability sample of people who use alcohol and other drugs as part of the annual Global Drug Survey (GDS). Online questionnaire translated into 19 languages. 110,557 people took part in GDS2020 and 88,124 completed a question about inhaling alcohol in the last 12 months. The focus of this study is GDS2020 respondents who reported inhaling alcohol mist/vapour from a balloon in the last 12 months. Last 12-month use of alcohol vapour, onset duration, intensity of effects, value for money compared with alcohol, and incidence of falls/injuries. A total of 803 people reported the use of alcohol vapour in the last 12 months, with 51% of the sample coming from 3 countries: Australia, Denmark and England. Two-thirds were male, and they were more likely to be under 25. 45.7% reported that they were a bit/very drunk before they inhaled alcohol. 51.3% reported that the effects lasted for less than 5 mins. Both the intensity of effect and perceived value for money showed a normal distribution on a 10-point scale. 12.7% of respondents reported falling/injuring themselves. Inhaling alcohol vapour appears to be more common amongst younger, higher-risk drinkers. The rapid onset of action and inability to titrate consumption to effect is a risk for acute injury. We consider that alcohol is harmful enough through oral consumption without adding to the risk of injury by offering such a potentially risky additional administration method.


A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer.
PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, predominantly surgically treated cohort. In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided. On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors. PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.


Serological reactivity of sera from scrub typhus patients against Weil-Felix test antigens.
Sera from 17 patients of scrub typhus in the acute and convalescent phases were tested by indirect immunoperoxidase test, Weil-Felix (WF) test, enzyme-linked immunosorbent assay (ELISA), and immunoblotting. In the comparison of antibody titers between acute- and convalescent-phase sera, we recognized a parallelism of increment between the titers in WF test and titers of immunoglobulin M (IgM) in ELISA against Proteus mirabilis strain OXK-whole cells and OXK-lipopolysaccharides (Proteus OXK-LPS). Furthermore, IgM antibodies from almost all of WF test-positive sera recognized LPS from Proteus OXK in immunoblotting. Based on these results, it was concluded that IgM antibody rather than IgG may participate in WF test, and that Proteus OXK-LPS may have one of antigenic epitopes common to the components of R. tsutsugamushi.


Hospital admission unnecessary for successful uncomplicated radiographic reduction of pediatric intussusception.
After radiologic reduction, patients with ileocolic intussusception are often admitted. We hypothesize that discharge of stable patients after 4 h of emergency department (ED) observation does not result in an increase of adverse outcomes. We retrospectively reviewed pediatric patients with ileocolic intussusception between 2011 and 2016, managed with either 24-h inpatient or 4-h ED observation. Outcomes included length of stay, adverse outcomes, and total hospital charges. Fifty-one patients were managed with ED observation and 79 with inpatient observation. Recurrence rates, time to recurrence, and adverse outcomes were similar in both protocols. Total recurrence rates for ED observation was 15% versus 14% for inpatient observation. ED observation reduced time in the hospital by 26.8 h (4.9 versus 31.7 h). Discharging patients following uncomplicated hydrostatic reduction of ileocolic intussusception after a 4-h observation period does not result in an increase in adverse outcomes.


Serum level of vitamin A in febrile children with and without seizure: A comparative study.
The role of vitamins and antioxidants in the febrile seizure (FS) has recently become of interest. The role of Vitamin A in seizure is remained controversial. It may suppress or provoke the seizure. In present study, the serum vitamin A level in febrile patients was compared with febrile seizure children for the first time. In a cross-sectional study, eighty children aged 6-60 months including 40 febrile children and 40 children with FS were included. Blood samples were obtained, and the serum level of vitamin A and other blood parameters were measured. Patients were similar in demographic characteristics (p = 0.06 for age and p = 0.41 for sex). The serum vitamin A level was 0.19 (0.12, 0.25) and 0.22 (0.17, 0.29) milligram per liter (mg/L) in febrile and FS group respectively (p = 0.33). In children aged less than 24 months the serum vitamin A level in FS and febrile group was 0.22 ± 0.07 and 0.24 ± 0.12 mg/L respectively (p = 0.56). In children aged more than 24 months the serum vitamin A level in FS group was higher significantly in comparison with febrile group (0.25 ± 0.11 and 0.16 ± 0.07 mg/L respectively, p = 0.01). Serum vitamin A level was not different in febrile children with and without seizure. Surprisingly in children aged more than 24 months, the serum level of vitamin A was higher in FS group than in the febrile children. More studies are needed to confirm the present observation.