"False negative" CSF cryptococcal antigen with clinical meningitis: Case reports and review of literature.
There is an increasing recognition of patients presenting with cryptococcal meningitis despite having a negative CSF cryptococcal antigen (CrAg). In this report, we describe three cases of patients with advanced immunosuppression who presented to hospital with "false negative" CSF cryptococcal antigen, two of whom had a positive fungal culture. We describe the challenge of CSF-CrAg negative cryptococcal meningitis and explore ways to overcome this challenge using newer diagnostic techniques.


Phylogenetic relationships of rat lungworm, Angiostrongylus cantonensis, isolated from different geographical regions revealed widespread multiple lineages.
We conducted a pilot survey of genetic variation of A. cantonensis using small subunit (SSU) ribosomal (r) RNA and mitochondrial cytochrome c oxidase subunit I (coxI) gene sequences. Two distinct SSU genotypes (G1 and G2) were identified among 17 individual A. cantonensis worms from 17 different geographical localities in Japan, Mainland China, Taiwan, and Thailand. The partial coxI sequences were determined for 83 worms from 18 different geographical localities from Japan, Mainland China, Taiwan, and Thailand. Phylogenetic analysis showed eight distinct coxI haplotypes (ac1 to ac8). In 16 out of 18 localities, only a single coxI haplotype was found. However, in two localities, two coxI haplotypes coexisted. The common haplotypes found were: haplotype ac1 (Tokyo, Chiba, Kanagawa, Amamioshima Island, and Taichung), haplotype ac2 (Ishikawa, Shenzhen, and Lianjiang), haplotype ac5 (the Okinawa and the Ogasawara Islands), and haplotype ac7 (Miyagi, Aichi, and Kanagawa). Each of these regions is separated from the others by high mountain ranges or oceans. In addition, the lower genetic variation and particular geographical distribution of A. cantonensis in each location could indicate a founder effect, which may have resulted from multiple independent origins, and suggests that haplotypes migrated from endemic areas via human-related transportation.


[Localization diagnosis of chyluria by radionuclide lymphoscintigraphy].
To study the effect of radionuclide lymphoscintigraphy, a new method of localization diagnosis of chyluria. Radionuclide lymphoscintigraphy was used to examine 34 patients with chyluria and the results of radionuclide lymphoscintigraphy was compared with those of cystoscopy and lymphangiography. Among the 34 patients 85.3% of unilateral localization diagnosis by radionuclide lymphoscintigraphy was coincident with that by cystoscopy. The positive rate of bilateral localization diagnosis was higher than that by cystoscopy. A less invasive technique, radionuclide lymphoscintigraphy can be used as a new option for the localization diagnosis of chyluria.


CMTM3 overexpression promotes cell apoptosis while DHT promotes cell proliferation in hair follicle stem cells (HFSCs).
In Yangtze River Delta white goat, hypermethylation of CMTM3 leads to a decreased expression level in high quality brush hair. However, the regulation of CMTM3 expression and its function in hair follicle stem cells (HFSCs) remains largely unknown. In this study, we investigated the regulation of CMTM3 expression, function, and molecular mechanism in HFSCs. The re-expression of CMTM3 significantly suppressed the proliferation of HFSCs by inducing G1 cell cycle arrest and promoting apoptosis. Moreover, the downregulation of CMTM3 promoted HFSC proliferation. Treatment with sh_CMTM3 and incubation in a DHT culture medium had the most significant growth-promoting effect. It was hypothesized that transcriptome analysis using RNA sequencing (RNA-seq) in samples would enable the identification of unique protein-coding and non-coding genes that may help uncover the role of CMTM3. Multiple genes and pathways were involved in this process, including 168 common DEGs, such as CXCL8 and E-selectin, which is reportedly involved in multiple regulatory pathways. These results indicated that CMTM3 can function as HFSCs through the induction of a G1 cell cycle arrest and promoted apoptosis by mediating crosstalk between several pathways and transcription factors. Our data is available in the National Center for Biotechnology Information (NCBI) database with the accession number PRJNA657430.


Thrombophilia and fetal germinal matrix-intraventricular hemorrhage: does it matter?
Germinal matrix-intraventricular hemorrhage (GMH-IVH) in the fetus is very rare and the role of thrombophilia in its pathogenesis is unclear. We report on the prenatal diagnosis by magnetic resonance imaging of GMH-IVH in a 24-week fetus. The newborn presented posthemorrhagic ventriculomegaly and was found to be heterozygous for two thrombophilic patterns, factor V Leiden and methylenetetrahydrofolate reductase mutation. The combination of this hypercoagulable state and prenatal GMH-IVH is discussed together with the opportunity of testing these infants for thrombophilia.


CT intracranial localization with a new marker system.
Application of a new CT localization system for intracranial lesions in pre- and intraoperative guidance is described. This system consists of air grooves within an acrylic plate for CT examinations and a duplicate plate with wires in place of air grooves for scout radiography. This new device can also be applied in stereotaxic surgery or in radiotherapy planning.


Laser evoked potentials and prepulse inhibition of the blink reflex in patients with Wallenberg's syndrome.
Spinothalamic tract lesions in patients with Wallenberg's syndrome can be demonstrated by abnormalities in the laser evoked potentials (LEPs) to stimulation of the affected side. However, before reaching the structures generating LEPs, laser stimuli can induce effects at a subcortical level. We examined LEPs and laser-induced prepulse inhibition of the blink reflex in seven patients with Wallenberg's syndrome within a month after the infarct. All patients had abnormally elevated thresholds for temperature and pain sensation, and for pinprick pain induced by laser stimuli, in the affected vs the non-affected side. LEPs to stimulation of the affected side were abnormal because of absent, reduced or delayed responses. However, the same laser stimuli that were unable to induce LEPs generated normal inhibition of the blink reflex response when applied 250ms before a trigeminal nerve electrical stimulus. The percentage inhibition induced in the R2 response of the blink reflex by laser stimulation of the affected side was not different from that induced by stimulation of the non-affected side, or in control subjects. These results are compatible with either a different pathway for prepulse inhibition and evoked potentials or a reduced energy requirement of the sensory input generating prepulse inhibition in comparison to that generating evoked potentials.


Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice.
There is intense interest in the design and use of vaccine strategies against influenza to enhance protective immune responses in the elderly. To address the need for improved influenza vaccines for the aged, two inflammatory adjuvants, Imject(®) alum (a stimulator of the Nod-like receptor, Nalp3) and poly I:C (a toll-like receptor type 3 ligand), were used during vaccination with novel influenza virus-like particles (VLP). Adult (4 month old) or aged (24 month old) mice were vaccinated with VLPs alone or in combination with adjuvant. VLP-vaccinated adult mice were protected from a lethal influenza virus challenge without the use of either adjuvant. In contrast, only aged mice that were vaccinated with VLPs plus adjuvant survived challenge, whereas ∼33% of the mice vaccinated with VLP only survived challenge. Mice vaccinated with adjuvant only did not survive challenge despite similar levels of activation of CD11b(+)/CD11c(+) dendritic cells in the lungs. The protection was not associated with HAI titers or HA specific CD8(+) T cells, since both adjuvants boosted the VLP-induced serum HAI titers and CD8(+) responses in adult mice, but not aged mice. Influenza VLPs used in combination with two different inflammatory adjuvants during vaccination allow for the immune system to overcome the deficiency in the aged immune system to influenza virus infection.


Safety, reactogenicity, and immunogenicity of live attenuated varicella vaccine in children between 1 and 9 years of age with atopic dermatitis.
Infection with varicella-zoster virus (VZV) is known to facilitate secondary bacterial infection, which is cause for particular concern in children with atopic dermatitis. This 2-year study assessed the safety, reactogenicity, and immunogenicity of a live attenuated Oka strain varicella vaccine (Varilrix, GlaxoSmithKline Biologicals) in 160 children aged 1-9 years with atopic dermatitis randomized to vaccination at the start of either the 1st or 2nd study year (VAR-1Y and VAR-2Y, respectively). Mean SCORing Atopic Dermatitis (SCORAD) scores at baseline were 19.3+/-11.1 and 26.0+/-10.4 in the two groups, respectively. Varicella vaccination did not adversely affect the severity of atopic dermatitis, with analysis of variance (ANOVA) confirming equivalence for the change in SCORAD index from baseline to week 8 between vaccinated and unvaccinated subjects. Within-group comparison of post-vaccination changes in SCORAD index from baseline to week 8 and month 12 in the VAR-2Y group showed a greater reduction in mean SCORAD scores following vaccination in year 2 than in year 1 when subjects were unvaccinated. Overall, SCORAD indices fell by approximately 10 points in both study groups over the 2 years of follow-up. Varicella vaccination was well tolerated, with no children withdrawn due to adverse events. Injection site redness was the most frequent solicited adverse event, occurring in 17.1% of subjects. Seroconversion rates were 94.3% at week 8 and 88.9% at month 12. In all, 43.6% of vaccinees reported at least one varicella contact during the course of the study. However, none developed varicella infection after vaccination over the 2 years of follow-up. In summary, vaccination with a live attenuated varicella vaccine appears safe and effective in children with atopic dermatitis.


[Effect of Gardenia jasminoides Ellis (GJE) on the blood flow of internal organs at the early stage of acute necrotizing hemorrhagic pancreatitis in rats].
Effect of GJE on the prevention and treatment of experimental acute pancreatitis was observed by means of testing pancreatic, hepatic, gastric and intestinal blood flow. The results show that the blood flow of internal organs that decreases significantly at the early stage of acute necrotizing hemorrhagic pancreatitis in rats can be picked up by GJE especially pancreatic.


Abdominal wall pain caused by cutaneous nerve entrapment in an adolescent girl taking oral contraceptive pills.
The etiology of chronic abdominal pain can be elusive. The diagnostic workup, therefore, often includes superfluous and expensive tests, as well as invasive procedures which do not contribute to the final diagnosis. Studies have shown that some patients suffer from prolonged pain in the abdominal wall and often are misdiagnosed and treated as having a visceral source for their complaints. The abdominal wall might be considered to be an unlikely source of prolonged abdominal pain, but one study reported that in 15% of patients with prolonged, nonspecific abdominal pain, the abdominal wall was the source of the complaint. Abdominal pain resulting from cutaneous nerve entrapment has not been reported previously in children and adolescents, nor has nerve entrapment been reported as a complication of oral contraceptives. The case of a 15-year-old girl who came to the hospital emergency room with abdominal pain of 3 months duration is reported. A comprehensive workup had not established a specific cause for the pain. On the basis of the clinical findings, the possibility of a cutaneous nerve entrapment was suggested. After the involved cutaneous nerve was selectively blocked by subcutaneous infiltration, the pain disappeared immediately and completely. Recognition of this apparently unusual condition can lead to gratifying results. It is proposed that oral contraceptive therapy may have caused changes in the abdominal wall which led to nerve entrapment and the ensuing severe, prolonged pain.


High serum levels of remnant lipoproteins predict ischemic stroke in patients with metabolic syndrome and mild carotid atherosclerosis.
Metabolic syndrome is prevalently associated with stroke. Triglyceride-rich lipoproteins contribute to atherothrombotic complications in metabolic syndrome. This study examined whether high levels of remnant lipoprotein, atherogenic triglyceride-rich lipoprotein, may be associated with future ischemic stroke in metabolic syndrome. We followed up 292 consecutive patients with metabolic syndrome meeting ATP III criteria and mild carotid plaques for a period of </=24 months until occurrence of an ischemic stroke. Remnant lipoprotein (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method. Twenty-two ischemic stroke events occurred during follow-up. A multivariate Cox proportional hazards models showed that high RLP-C levels were a significant and independent predictor of ischemic stroke events (p<0.01). Echolucent carotid plaques were also a significant predictor of ischemic stroke that was independent of other carotid ultrasound parameters in Cox proportional hazards models (p<0.01). High RLP-C levels were intimately and independently associated with carotid plaque echolucency (p<0.01). High RLP-C levels are an independent risk factor for future ischemic strokes in metabolic syndrome. High RLP-C levels may be related to echolucent carotid plaque, partly accounting for high risk for ischemic stroke in metabolic syndrome.


An ultrasensitive and rapid "sample-to-answer" microsystem for on-site monitoring of SARS-CoV-2 in aerosols using "in situ" tetra-primer recombinase polymerase amplification.
Airborne transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the urgent need for aerosol monitoring of SARS-CoV-2 to prevent sporadic outbreaks of COVID-19. The inadequate sensitivity of conventional methods and the lack of an on-site detection system limited the practical SARS-CoV-2 monitoring of aerosols in public spaces. We have developed a novel SARS-CoV-2-in-aerosol monitoring system (SIAMs) which consists of multiple portable cyclone samplers for collecting aerosols from several venues and a sensitive "sample-to-answer" microsystem employing an integrated cartridge for the analysis of SARS-CoV-2 in aerosols (iCASA) near the sampling site. By seamlessly combining viral RNA extraction based on a chitosan-modified quartz filter and "in situ" tetra-primer recombinase polymerase amplification (tpRPA) into an integrated microfluidic cartridge, iCASA can provide an ultra-high sensitivity of 20 copies/mL, which is nearly one order of magnitude greater than that of the commercial kit, and a short turnaround time of 25 min. By testing various clinical samples of nasopharyngeal swabs, saliva, and exhaled breath condensates obtained from 23 COVID-19 patients, we demonstrate that the positive rate of our system was 3.3 times higher than those of the conventional method. Combining with multiple portable cyclone samplers, we detected 52.2% (12/23) of the aerosol samples, six times higher than that of the commercial kit, collected from the isolation wards of COVID-19 patients, demonstrating the excellent performance of our system for SARS-CoV-2-in-aerosol monitoring. We envision the broad application of our microsystem in aerosol monitoring for fighting the COVID-19 pandemic.


Effect of epicardial fat volume on outcomes after left atrial posterior wall isolation in addition to pulmonary vein isolation in patients with persistent atrial fibrillation.
Greater epicardial adipose tissue (EAT) is related to higher recurrences after atrial fibrillation catheter ablation (AFCA). We investigated the effects of posterior wall box isolation (POBI) in conjunction with circumferential pulmonary vein isolation (CPVI) on rhythm outcomes according to varying EAT volumes among patients with persistent atrial fibrillation (PeAF). We included 1,187 patients with PeAF undergoing a de novo AFCA including those receiving CPVI alone (n = 687) and those receiving additional POBI (n = 500). The rhythm outcomes at 2 years post-AFCA were compared in subgroups stratified by the EAT volume using propensity overlap weighting. A reduced EAT volume was linearly associated with more favorable rhythm outcomes for additional POBI than for CPVI alone (P for interaction = 0.002). Among the patients with smaller EAT volumes (≤116.23 mL, the median value, n = 594), additional POBI was associated with a reduced AF recurrence risk as compared to CPVI only [weighted HR (hazard ratio) 0.74, 95% CI (confidence interval) 0.56-0.99]. In contrast, among the remaining 593 patients with greater EAT volumes (>116.23 mL), No difference was observed in the recurrence risk between the additional POBI and CPVI alone groups (weighted HR 1.13, 95% CI 0.84-1.52). Among 205 patients with repeat ablations, the POBI reconnection rate was more frequent in the large EAT group (77.4%) than in the small EAT group (56.7%, P = 0.034). While PeAF patients with a smaller EAT volume averted AF recurrence by additional POBI after CPVI, no benefit of the POBI was observed in those with a greater EAT volume.


MPTP primate model of Parkinson's disease: a mechanographic and electromyographic study.
Movement parameters and electromyographic (EMG) studies were carried out in two macaque monkeys performing a rapid arm movement before and after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Hypokinesia and rigidity were seen after repeated doses. Disturbances in both movements and EMG activity were similar to those reported in Parkinsonian patients.


Intrauterine infection and preterm labor.
Preterm birth remains the leading cause of perinatal mortality and morbidity. Evidence suggests that intrauterine infection plays an important role in the pathogenesis of preterm labor. This article reviews the clinical data supporting this theory and the cellular and biochemical mechanisms by which intrauterine infection may initiate uterine contractions. The clinical and laboratory methods of diagnosing clinical chorioamnionitis and asymptomatic bacterial invasion of the intraamniotic cavity are also reviewed. Finally, the management of clinical chorioamnionitis and asymptomatic microbial invasion of the amniotic fluid and the use of adjunctive antibiotic therapy in the treatment of preterm labor are presented.


Sexual dysfunction and reproductive concerns in young women with breast cancer: Type, prevalence, and predictors of problems.
A dearth of studies focusing on young women (<40 years) with breast cancer have hampered the understanding of the type, prevalence, and predictors of sexual dysfunction and reproductive concerns in this population. Data were collected from 181 women (response rate = 60%) diagnosed with breast cancer approximately 2 years previously (age 21-39) using the Swedish National Quality Registry for Breast Cancer and a survey including standardized measures of sexual dysfunction, reproductive concerns, body image, and health-related quality of life. Multivariable logistic binary regression analyses were used to identify predictors of sexual dysfunction and reproductive concerns. Sexual dysfunction in at least one domain was reported by 68% of the women, and a high level of reproductive concerns in at least one dimension was reported by 58%. Model results showed that current endocrine treatment was a significant predictor of dysfunction related to lubrication (OR 3.8, 95% CI 1.2-12.1) and vaginal discomfort (OR 8.7, 95% CI 1.5-51.5). Negative body image was related to satisfaction with sex life (OR 1.1, 95% CI 1.0-1.2). A high level of reproductive concerns was predicted by a wish for (additional) children in the future (OR 3.4, 95% CI 1.1-10.2) and by previous chemotherapy (OR 2.5, 95% CI 1.1-5.9). Sexual dysfunction and reproductive concerns are common in young women with breast cancer. Current endocrine treatment, previous chemotherapy, a negative body image, and a wish for children in the future predict higher level of problems.


Mechanisms of cell survival in myocardial hibernation.
Myocardial hibernation represents a condition of regional ventricular dysfunction in patients with chronic coronary artery disease, which reverses gradually after revascularization. The precise mechanism mediating the regional dysfunction is still debated. One hypothesis suggests that chronic hypoperfusion results in a self-protecting downregulation in myocardial function and metabolism to match the decreased oxygen supply. An alternative hypothesis suggests that the myocardium is subject to repetitive episodes of ischemic dysfunction resulting from an imbalance between myocardial metabolic demand and supply that eventually creates a sustained depression of contractility. It is generally agreed that hibernating myocardium is submitted repeatedly to ischemic stress, and therefore one question persists: how do myocytes survive in the setting of chronic ischemia? The hallmark of hibernating myocardium is a maintained viability of the dysfunctional myocardium which relies on an increased uptake of glucose. We propose that, in addition to this metabolic adjustment, there must be molecular switches that confer resistance to ischemia in hibernating myocardium. Such mechanisms include the activation of a genomic program of cell survival as well as autophagy. These protective mechanisms are induced by ischemia and remain activated chronically as long as either sustained or intermittent ischemia persists.


Single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging for radiotherapy planning in patients with lung cancer: a meta-analysis.
Functional imaging modalities enable practitioners to identify functional lung regions. This analysis evaluated the feasibility of nuclear medicine imaging to avoid doses to the functional lung in radiotherapy (RT) planning for patients with lung cancer. This systematic review and meta-analysis was carried out according to PRISMA-P guidelines. A search of EMBASE and PubMed for studies published throughout the last 20 years was performed using the following search criteria: (a) 'lung cancer' or 'lung malignancy' and (b) 'radiotherapy' or 'radiation therapy' or 'RT planning' and (c) 'SPECT' or 'single positron emission computed tomography' or 'functional image.' The analyzed planning parameters were the volumes of the normal lung that have received ≥ 10 Gy and ≥ 20 Gy of radiation (V10 and V20, respectively) and the mean lung dose (MLD). We compared the planning parameters obtained from anatomical RT planning and functional RT planning using perfusion or ventilation imaging ('V10, V20 or MLD' in anatomical plan vs. 'fV10, fV20 or fMLD' in functional plan). A total of 309 patients with 344 RT plan sets from 15 publications (11 perfusion SPECT, 2 ventilation SPECT, and 1 SPECT and 1 PET with both perfusion and ventilation) were included in the meta-analysis. The standard mean differences in planning parameters in functional plans using nuclear imaging were significantly reduced compared to those of anatomical plans (P < 0.01 for all): - 0.42 (95% confidence interval (CI) - 0.78 to - 0.07) for 'V10 vs. fV10', - 0.41 (95% CI - 0.64 to - 0.17) for 'V20 vs. fV20', and - 0.24 (95% CI - 0.45 to - 0.03) for 'MLD vs. fMLD'. In subgroup analysis, the functional plan using perfusion was significantly lower than the anatomical plan in all planning parameters, but there was no significant difference for ventilation. RT planning with nuclear functional lung imaging has potential to reduce radiation-induced lung injury. Perfusion imaging seems to be more promising than ventilation imaging for all planning parameters. There were not enough studies using ventilation imaging to determine what the effect is on the lung plan parameters.


Unilateral pulmonary hypoplasia with abdominal situs inversus.
A case of unilateral pulmonary hypoplasia in association with abdominal situs inversus (Situs Inversus Partialis) is described here in a 2-mo-old baby. The normally related heart (levocardia) is dextroposed due to the hypoplastic right lung and compensatory hyper-inflation of the opposite lung which clinically mimicked a mirror-image situs inversus totalis. Such a combination, to the best of authors' knowledge, has never been reported in the world literature.


Inhibitory effect of antihypertensive drugs on calcineurin in cardiomyocytes.
In recent years, a handful of research investigations have shown that some antihypertensive drugs, i.e., angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB), can inhibit myocardial expression and/or activity of calcineurin. Calcineurin is a Ca(2+)-calmodulin-dependent serine/threonine phosphatase and is a target for some immunosuppressive drugs. It is well known that traditional immunosuppressants, such as cyclosporine A (CsA) and tacrolimus (FK506), are anticalcineurin, and their prohypertensive effects are such that antihypertensive therapy is often required in organ transplant recipients who receive these drugs. Therefore, the idea that ACEI, ARB, and CCBs are both antihypertensive and anticalcineurin seems paradoxical. This invited review tries to summarize these new findings and analyze the scientific and clinical significance of these claims. The review also emphasizes some of the shortcomings in these studies and some questions that need to be addressed in future investigations.


Implementation of pre-clinical methodologies to study fibrosis and test anti-fibrotic therapy.
Diseases where fibrosis plays a major role accounts for enormous morbidity and mortality and yet we have very little in our therapeutic arsenal despite decades of research and clinical trials. Our understanding of fibrosis biology is primarily built on data generated in conventional mono-culture or co-culture systems and in vivo model systems. While these approaches have undoubtedly enhanced our understanding of basic mechanisms, they have repeatedly failed to translate to clinical benefit. Recently, there had been a push to generate more physiologically relevant platforms to study fibrosis and identify new therapeutic targets. Here we review the state-of-the-art regarding the development and application of 3D complex cultures, bio-printing and precision cut slices to study pulmonary, hepatic and renal fibrosis.


Chronic pain management in dermatology: a guide to assessment and nonopioid pharmacotherapy.
Pain is a central component of illness and suffering, yet unfortunately it is frequently undertreated. In dermatology, many acute and chronic conditions are characterized by pain that may require therapeutic intervention in addition to medical treatment aimed at treating the primary disease. To date, however, there are limited recommendations or evidence in the published literature on pain and pain management strategies for patients with skin disease. In an effort to enable providers to more comprehensively and effectively treat chronic pain in the primary and multidisciplinary dermatologic context, these topics will be discussed in this 2-part continuing medical education article. Part I of this series will describe important mechanisms of pain and detail individualized chronic pain assessment and treatment strategies using nonopioid analgesia.


Synthesis of noraristeromycin analogues possessing SAH hydrolase inhibitory activity for the development of antimalaria agents.
Noraristeromycin analogues such as 3',4'-anhydronoraristeromycins, 2-amino-3',4'-anhydronoraristeromycin and N6-cyclopropylnoraristeromycin were synthesized and their inhibitory activity against human and Plasmodium falciparum (P. falciparum) recombinant SAH hydrolase was investigated. Among them, 3',4'-anhydronoraristeromycin showed inhibitory activity against human recombinant S-adenosyl-L-homocysteine hydrolase (Ki = 12.4 microM, Kinact = 0.55 min-1).


Regulation of palmitoyl-CoA chain elongation and linoleoyl-CoA chain elongation in rat liver microsomes and the differential effects of peroxisome proliferators, insulin and thyroid hormone.
Treatment of rats with p-chlorophenoxyisobutyric acid (clofibric acid), 2,2'-(decamethylenedithio)diethanol, di(2-ethylhexyl)phthalate or acetylsalicylic acid caused an increase in activity of palmitoyl-CoA chain elongation in hepatic microsomes. The activity of palmitoyl-CoA chain elongation decreased in both hypothyroid-state and diabetic-state rats, increased in hyperthyroid-state rats and did not change in adrenalectomized rats. The administration of clofibric acid to these rats in an altered hormonal state caused an increase in the activity of palmitoyl-CoA chain elongation, but no additional increase in the activity was observed with treatment of hyperthyroid rats with clofibric acid. The activity of linoleoyl-CoA chain elongation did not respond to the changes in either the nutritional conditions or the hormonal state of insulin so sensitively as the activity of palmitoyl-CoA chain elongation. The treatment of rats with triiodothyronine caused a marked increase in the activity of linoleoyl-CoA chain elongation; nevertheless, the activity of linoleoyl-CoA chain elongation was not changed by the treatment of rats with clofibric acid. The results suggest that rat liver microsomes contain at least two fatty acid chain elongation systems and that these chain elongation systems are regulated differently by hormones and drugs.


Increased production of cellulases and xylanases by Penicillium echinulatum S1M29 in batch and fed-batch culture.
The development of more productive strains of microorganisms and processes that increase enzyme levels can contribute to the economically efficient production of second generation ethanol. To this end, cellulases and xylanases were produced with the S1M29 mutant strain of Penicillium echinulatum, using different concentrations of cellulose (20, 40, and 60 g L(-1)) in batch and fed-batch processes. The highest activities of FPase (8.3 U mL(-1)), endoglucanases (37.3 U mL(-1)), and xylanases (177 U mL(-1)) were obtained in fed-batch cultivation with 40 g L(-1) of cellulose. The P. echinulatum enzymatic broth and the commercial enzyme Cellic CTec2 were tested for hydrolysis of pretreated sugar cane bagasse. Maximum concentrations of glucose and xylose were achieved after 72 h of hydrolysis. Glucose yields of 28.0% and 27.0% were obtained using the P. echinulatum enzymatic extract and Cellic CTec2, respectively.


Disc formation in cholesterol-free liposomes during phase transition.
Cryogenic transmission electron microscopy (cryo-TEM) images of lysolipid-containing thermosensitive liposomes (LTSL) revealed that open liposomes and bilayer discs appeared when liposomes were cycled through the gel (Lbeta') to liquid-crystalline (Lalpha) phase transition. The amount of bilayer discs generated was dependent on the combined presence of PEG-lipid and lysolipid in the membrane. We hypothesize that micelle-forming membrane components stabilize the rim of bilayer openings and membrane discs that form when liposomes are cycled through TC.


Sequence and structural features associated with translational initiator regions in yeast--a review.
We have compared the translational initiator regions of 131 yeast genes. 95% utilize the first AUG from the 5' end of the message as the start codon for translation. Yeast leader regions in general are rich in adenine nucleotides (nt), have an average length of 52 nt, and are void of significant secondary structure. Sequences immediately adjacent to AUG start codons are preferred, however, the bias in nucleotide distribution (5'-A-YAA-UAAUGUCU-3') does not reflect a higher eukaryotic consensus (5'-CACCAUGG-3') with the exception of an adenine nucleotide preference at the -3 position. A minority of yeast mRNAs that contain AUG codons in the leader region that do not serve as the start codon for the primary gene product differ from the majority of mRNAs by one or more of these general properties. This analysis appears to indicate that basic features associated with yeast leader regions are consistent with a general mechanism of initiation of protein synthesis in eukaryotes, as proposed by the ribosomal 'scanning' model, but perhaps only basic features associated with ribosomal recognition of an AUG start codon are intact.


[Primary cutaneous osteosarcoma].
Osteosarcoma is a malignant tumor of mesenchymatous origin that chiefly affects the metaphysis of long bones. The extraskeletal form of the disease is rare, and even rarer is a cutaneous site, whether metastatic or primary. Herein, we report a new case of primary cutaneous osteosarcoma. A 54-year-old woman presented a hard subcutaneous nodular tumor on her left arm noted 1 year earlier. The diagnosis of cutaneous osteosarcoma was made on the basis of histological analysis of the lesion, which showed a sarcomatous dermal-hypodermal proliferation secreting osteoid. Clinical and radiological staging ruled out any extra-cutaneous spread, particularly to bone, thus confirming the primary cutaneous nature of the osteosarcoma. Primary cutaneous osteosarcoma is a rare tumor, diagnosis of which is normally based on histopathological features.


Solitary Fibrous Tumor of the Dorsal Tongue Area.
Solitary fibrous tumor (SFT) is a rare tumor occurring in pleura or extrapleural areas. The tongue is infrequently affected, in less than 25 published cases. A female patient, 35 years of age, noticed an oval mass in the posterior dorsal part of the tongue. The operated mass was nodule, 10 mm in size, sharply circumscribed, rather firm. The histology shows uniform CD34 positive spindle tumor cells. The diagnosis of benign SFT of the tongue was made.


Thematic Analysis of the Health Records of a National Sample of US Veterans With Advanced Kidney Disease Evaluated for Transplant.
To be considered for a kidney transplant, patients with advanced kidney disease must participate in a formal evaluation and selection process. Little is known about how this process proceeds in real-world clinical settings. To characterize the transplant evaluation process among a representative national sample of US veterans with advanced kidney disease who were referred to a kidney transplant center. This qualitative study was a thematic analysis of clinician notes in the electronic health records of US veterans referred for kidney transplant evaluation. In a random sample of 4000 patients with advanced kidney disease between January 1, 2004, and December 31, 2014, cared for in the US Department of Veterans Affairs (VA) health care system, there were 211 patients who were referred to a transplant center during the follow-up period. This group was included in the qualitative analysis and was followed up until their date of death or the end of the follow-up period on October 8, 2019. Dominant themes pertaining to the kidney transplant evaluation and selection process identified through thematic analysis. Among 211 study patients, the mean (SD) age was 57.9 (9.5) years, and 202 patients (95.7%) were male. The following 4 dominant themes regarding the transplant evaluation process emerged: (1) far-reaching and inflexible medical evaluation, in which patients were expected to complete an extensive evaluation that could have substantial physical and emotional consequences, made little accommodation for their personal values and needs, and impacted other aspects of their care; (2) psychosocial valuation, in which the psychosocial component of the transplant assessment could be subjective and intrusive and could place substantial demands on patients' family members; (3) surveillance over compliance, in which the patients' ability and willingness to follow medical recommendations was an important criterion for transplant candidacy and their adherence to a wide range of recommendations and treatments was closely monitored; and (4) disempowerment and lack of transparency, in which patients and their local clinicians were often unsure about what to expect during the evaluation process or about the rationale for selection decisions. For the evaluation process to proceed, local clinicians had to follow transplant center requirements even when they believed the requirements did not align with best practices or the patients' needs. In this qualitative study of US veterans with advanced kidney disease evaluated for transplant, clinician documentation in the medical record indicated that, to be considered for a kidney transplant, patients were required to participate in a rigid, demanding, and opaque evaluation and selection process over which they and their local clinicians had little control. These findings highlight the need for a more evidence-based, individualized, and collaborative approach to kidney transplant evaluation.


Desmoplastic fibroma of bone: an immunohistochemical study including beta-catenin expression and mutational analysis for beta-catenin.
Desmoplastic fibroma of bone is a very rare primary bone tumor morphologically resembling desmoid-type fibromatosis, its much more common counterpart of soft tissue. The aim of this study is to investigate the immunohistochemical profile and the involvement of the beta-catenin pathway in desmoplastic fibroma as it is known in desmoid-type fibromatosis. Immunohistochemistry was performed on 13 cases of desmoplastic fibroma for muscle-specific markers, estrogen and progesterone receptors, CD117, beta-catenin, and the potential downstream target of beta-catenin, namely, cyclin D1. In all 13 cases, DNA sequencing was performed for the detection of activating beta-catenin gene mutations. There was no immunoreactivity of CD117, estrogen, and progesterone receptors. Seven cases were immunoreactive for one or more muscle-specific markers. In 6 cases, there was overexpression of beta-catenin in the cytoplasm; in one of these cases, there was also accumulation of beta-catenin in the nucleus. In 6 cases in which DNA sequencing was successful, no beta-catenin mutations were detected. Search in a national database showed that not a single case over a frame of 23 years was associated with occurrence of colon cancer in the same patient. The epidemiological, histological, and immunohistochemical findings in desmoplastic fibroma are suggestive of desmoplastic fibroma being the bony counterpart of the more common desmoid-type fibromatosis of soft tissue. However, the beta-catenin pathway does not seem to have the same essential role in the tumorigenesis of desmoplastic fibroma, as it has in desmoid-type fibromatosis.


Inducing Tumor Cell Apoptosis: Mediated Survivin miRNA by Ultrasound and Cationic Lipid Contrast Agent.
Non-viral delivery systems is a promising method for gene or drug delivery. Polyethyleneimine (PEI) is a double-edged sword. It internalizes itself into the cell through endocytosis and promotes gene transfer efficiency. However, the strong positive charge also makes PEI highly toxic to cells. Ultrasound-targeted microbubble destruction (UTMD) is a promising non-viral method for gene and drug delivery, but its efficiency still needs to be improved. The aim of this study was to explore a system that combines ultrasound with non-viral gene delivery for the treatment of cervical cancer HeLa cells. In this study, we synthesized a kind of cationic ultrasound contrast agent(CUCA) that the physical and chemical properties, gene carrying capacity and cytotoxicity were verified. On the basis of previous studies, we further optimized the following transfusion parameters including ultrasound parameters, microbubble concentration, plasmid concentration, cell density and other parameters. The experiment was designed to compare the following six groups: (1) Plasmid group (P group), plasmid 15 μg; (2) PEI + plasmid group (PEI + P group),1 μl of PEI containing 10 nmol nitrogen and 1 μg of DNA containing 3 nmol phosphate for a PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection; (3) Ultrasound + plasmid group (US + P), plasmid 15 μg; (4) Ultrasound + cationic liposomal ultrasound contrast agent + plasmid group (UTMD + P group), plasmid 15 μg and cationic liposomal ultrasound contrast agent 5%; (5) Ultrasound + cationic liposomal ultrasound contrast agent + PEI + plasmid group (UTMD + PEI + P group), PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection and cationic liposomal ultrasound contrast agent 5%; and (6) Blank group, no treatment), The influence on Hela cells was observed under microscope, the efficiency of apoptosis was measured by flow cytometry, and cell viability was tested in CCK 8. The optimized transfection parameters can improve the transfection efficiency of ultrasound combined with C-UCA to a certain extent, but its transfection efficiency is still lower than that of branched polyethyleneimine (bPEI) 25 kDa. By investigating the effect of HeLa cells apoptosis induced by UTMD in combination with PEI mediated survivin miRNA, we found that both PEI alone and ultrasound in combination with CUCA were able to transfect cells with survivin miRNA to effectively induce HeLa cell apoptosis. However, the synergistic effect between the two methods was not significant. In contrast, the combined use of ultrasound, C-UCA and PEI may significantly reduce the transfection efficiency of UTMD and PEI, and the specific mechanism remains to be further studied.


Optimization of dose of collagen hydrolysate to prevent UVB-irradiated skin damage.
Collagen hydrolysate (CH) was orally administered to UVB-irradiated hairless mice at doses of 20, 200-2000 mg/kg BW/day. The low dose of CH increased the skin hydration and reduced the transepidermal water loss on damaged skin. These results suggested the optimal dose of collagen to improve the UV-damaged skin condition.


Peak exercise oxygen uptake and changes in renal function in patients after acute myocardial infarction.
The impact of exercise tolerance on renal function change after acute myocardial infarction (AMI) is not clear. The present study aimed to elucidate the effect of peak exercise oxygen uptake (VO2) levels on longitudinal changes in renal function up to 1 year after onset of AMI. This retrospective longitudinal study enrolled 198 AMI patients. Symptom-limited cardiopulmonary exercise testing was performed at completion of early Phase II cardiac rehabilitation, and peak VO2 levels were defined as the primary exposure factor. The estimated glomerular filtration rates (eGFRs) at baseline, 3 months, 6 months and 1 year were collected. Generalized estimating equation (GEE) models were used to test the longitudinal effect of peak VO2 levels on within-patient changes in eGFR. Patients were stratified into tertile groups (Low group, 12.3 ± 1.3 mL/kg/min; Mid group, 15.3 ± 0.7 mL/kg/min; and High group, 19.1 ± 2.3 mL/kg/min) according to peak VO2 levels. The slopes of eGFR over 1 year in the Low (p = 0.024) and Mid groups (p = 0.037) were lower compared to the High group. The Low group had a significantly higher odds ratio of experiencing rapid renal function decline than the High group (odds ratio, 2.87; p = 0.012). There was a significant effect of lower peak VO2 on rapid decline in renal function after AMI. Our findings suggest that the coexistence of exercise intolerance may be a novel risk factor for rapid decline in renal function after AMI.


[Choroidal neovascularisation in type II membranoproliferative glomerulonephritis, photodynamic therapy as a treatment option--a case report].
Photodynamic therapy (PDT) is an established treatment in predominantly classic choroidal neovascularisation (CNV) in exudative age-related macular degeneration (AMD). Membranoproliferative glomerulonephritis (MPGN) type II leads to AMD-similar changes ("pseudo-AMD") of the fundus with CNV as a late complication. We report on a patient suffering from MPGN II and a classic CNV who was treated with PDT. A 31-year old male patient suffering from MPGN II from the age of 8 presented with visual deterioration and metamorphopsies on his left eye (VA OD 1.0, OS 0.25). Funduscopy revealed a "Pseudo"-AMD on both eyes and the left eye showed a 100 % classic CNV in fluorescein angiography (FLA). The left eye has treated with PDT. Visual acuity after PDT remained stable with 0.25 OS and metamorphopsies were reduced. 3 months later FLA showed a small residual leakage, therefore a second PDT was performed. 4 months after the 2 nd PDT the patient suffered again from metamorphopsies with a stable VA of 0.25 OS following a 3 rd PDT. Visual acuity of the left eye remained stable at 0.25 and metamorphopsies reduced due to the treatment of 3 PDT's. Even in "pseudo-AMD" in MPGN II the PDT is able to reduce leakage and stops progression consistent to the results in exudative AMD. In MPGN II associated "pseudo"-AMD with classic CNV the PDT was also successful. The origin of the CNV does not appear to play a role for the success of the PDT.


Long-term (up to 20 years) effects of 50-Hz magnetic field exposure on blood chemistry parameters in healthy men.
The potential effects of a chronic exposure to magnetic fields on blood chemistry in humanswere tested. We examined the nocturnal profiles and levels of the following blood parameters: electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphorus), nonprotein nitrogenous compounds (uric acid, urea, creatinine), and glucose, in 15 men (38.0 ± 0.9 years) exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 μT. The results are compared to those obtained in our control group: 15 unexposed men of similar age (39.4 ± 1.2 years), with the same synchronization and physical activity that served as controls (individual exposures ranged from 0.004 to 0.092 μT). Blood samples were taken hourly from 20:00 h to 08:00 h. This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced significant changes in serum sodium, chloride, phosphorus and glucose where an effect for field-hour interaction was noted for exposures greater than 0.3 μT. Our data suggest that long-term exposure to 50-Hzmagnetic fields (exposure>0.3 μT) in healthy men could induce some biological modifications of certain blood parameters, though their clinical relevance needs further investigation.


Practical Contrast Enhanced Liver Ultrasound.
Contrast-enhanced ultrasound (CEUS) is increasingly performed for focal liver lesion evaluation because of its high safety profile and ability to yield a definitive diagnosis in many patients, obviating multiphase CT or MRI. CEUS uses specific ultrasound contrast agents (UCAs) that are exceedingly safe, without the risk of renal or liver toxicity. UCAs are cleared rapidly from the body, allowing for multiple injections during a single examination, with no potential for deposition in the patient. This review highlights the performance of CEUS for liver lesion evaluation and illustrates the imaging appearance of common liver lesions in children and adults.


Incomplete hypospadiac urethral duplication with posterior urethral valves.
Urethral duplication (UD) is an uncommon malformation. Obstruction rarely occurs in hypospadiac UD. We describe two children with incomplete hypospadiac UD in association with posterior urethral valves, a combination not previously recognised. The embryonic significance of this anomaly is discussed. Keywords Urethral duplication. Hypospadias. Posterior urethral valve. Megalourethra


Bovine adenoviruses--IV. Two mixed antigens for routine serodiagnosis by complement fixation reaction.
The frequency of bovine adenovirus infections occurring in cattle has been grossly underestimated up to the present day. Primary isolation of serotypes belonging to bovine subgroup II is cumbersome. Hardly any laboratory has used all 8 officially-recognised bovine serotypes in seroneutralisation-tests, which should be done when this type-specific method is used for serodiagnosis. The complement fixation test, known as group-reactive from human adenovirus serology, has failed to disclose the true incidence of bovine infections, as until recently the importance of a novel additional group-reactive bovine adenovirus antigen has been undisclosed. Here we describe production, composition and performance of two mixed antigens for complement fixation reactions, which take into account recent findings by our team on peculiarities of bovine adenovirus antigens. Mixed antigen 1 contains bovine serotypes 1, 2 and 3 and detects group-specific antibodies of the classical mastadenoviruses. Mixed antigen 2 contains bovine serotypes 4, 5, 6, 7 and 8 and determines group-specific antibodies against the novel paramastadenoviruses. In addition, each antigen is capable of demonstrating complement-fixing type-specific antibodies in sera against the respective types included in each mixed antigen, with a net enhancing effect produced by mixing. Use of the 2 mixed antigens promptly shows whether bovine adenoviruses, presently recognised as well as unclassified, are involved in a given outbreak of respiratory or enteric disease of cattle. If needed, the responsible type may be determined in a second step of serological investigation.


Non-canonical NF-κB contributes to endothelial pyroptosis and atherogenesis dependent on IRF-1.
Cell inflammation and death are closely linked processes contributing to endothelial dysfunction, which plays a critical role in atherogenesis. Activation of the NLRP3 inflammasome causes pyroptosis, the Gasdermin D (GSDMD)-mediated inflammatory cell death. The non-canonical NF-κB pathway has been implicated in inflammation; however, its role in NLRP3 inflammasome-mediated endothelial dysfunction has not been investigated. This study investigated a role for the non-canonical NF-κB pathway in regulating endothelial pyroptosis as it relates to atherogenesis. Immunohistochemistry indicated inflammasome activation in the endothelial cells (EC) of human atherosclerotic arteries. Flow cytometry and Western blot analysis revealed that oxidized low-density lipoprotein (oxLDL) activated the NLRP3 inflammasome, concomitant with the activation of non-canonical NF-κB in primary human aortic EC. Interference of NF-κB inducing kinase (NIK), the key regulator of the non-canonical pathway, significantly attenuated oxLDL- or LPS/ATP-induced NLRP3 inflammasome activation, pyroptosis, IL-1β, and IL-18 secretion. In contrast, overexpression of NIK exacerbated these responses. Chromatin immunoprecipitation revealed that activation of the non-canonical NF-κB pathway upregulated the transcription factor IRF-1 through RelB/p52 binding to its promoter region at -782/-770. In addition to the known target CASP1, RNA sequencing further identified GSDMD as a target gene of IRF-1. IRF-1 but not RelB/p52 interacted with the GSDMD promoter at -526/-515 and the CASP1 promoter at -11/10 to promote the expression and CASP1-mediated activation of GSDMD. Consistent with the observations in cultured endothelium, endothelial-specific deficiency of NIK or IRF-1 attenuated atherosclerosis in high-fat diet-fed Apoe-null mice. These data demonstrate that the non-canonical NF-κB pathway contributes to NLRP3 inflammasome-mediated endothelial pyroptosis and the development of atherosclerosis through GSDMD activation in a manner dependent on IRF-1. Further investigation may facilitate the identification of specific therapeutic targets for atherosclerotic heart diseases.


Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients. Bezafibrate Infarction Prevention (BIP) Study Group.
Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality.


Perceptions of pelvic floor dysfunction and rehabilitation care amongst women in southeast China after radical hysterectomy: a qualitative study.
To investigate the perceptions of pelvic floor dysfunction (PFD) and rehabilitation care amongst women after radical hysterectomy and to explore ways to improve quality of care. Thirty-six women who underwent radical hysterectomy at a hospital in southeast China were enrolled via purposive sampling. Semi-structured in-depth interviews were conducted. The texts were analysed via qualitative content analysis. Four themes were obtained: serious lack of knowledge, heavy psychological burden, different coping strategies and great eagerness to receive multiparty support on PFD rehabilitation care. The society and professional staff should strengthen health education on PFD. Professionals should offer education before and after surgery and actively provide rehabilitation consultation to promote the availability of rehabilitation to support women with PFD rehabilitation care. In addition, family-centred care is an important way to support women to return to normal life, and women's need for family support should be more actively expressed. Moreover, knowledge of medical insurance should be popularised, especially in rural areas in China.


Rapid-eye-movement sleep in jittery infants.
The pathogenesis of neonatal jitteriness (JT) remains unknown. Neonatal JT could be one of the symptoms associated with drug withdrawal syndrome due to maternal medication. To study the influence of chemicals and environment on brain development in the fetal period, Swaab and Mirmiran proposed "behavioral teratology". JT could be one of the targets for this concept. Swaab and Mirmiran postulated that rapid-eye-movement sleep (REM sleep) is useful for studying behavioral teratology. We aimed to determine the neurophysiological alterations in infants with JT by investigating REM sleep. Sleep records were obtained three times for each of six jittery infants. The mothers of three infants had been on medication (either alpha-methyl dopa, reserpine or haloperidol) during pregnancy, whereas the mothers of the other three infants took no medication during pregnancy. REM sleep parameters (the amount of REM sleep against the total sleep time, newly designated indices-tonic inhibition index (TII) and phasic inhibition index--, and the incidences of gross movements, phasic chin muscle activity (PCMA), and bursts of rapid eye movements) in the six jittery infants were compared with those in age-matched controls. Regardless of maternal medication, TIIs, which represent the shortening of PCMA during REM sleep, were higher in the jittery infants than in the controls. No other REM sleep parameters showed constant differences between the patients and controls. Release of the blockade of dopamine D2 receptors in the fetal brain is considered to be critical for the occurrence of neonatal JT with elevation of TII. Since the abnormal elevation of TII continued after 6 months of age when our patients did not show JT anymore, we have to keep monitoring jittery infants from the standpoint of "behavioral teratology".


Suitability of time estimates for survival analysis of endodontic treatment.
This study aimed to determine the most suitable estimates of the event date for Kaplan-Meier (K-M) survival analysis for the assessment of endodontic treatment outcomes. Survival probability computed using the Weibull accelerated failure time (WAFT) models based on interval-censored data was used for comparison. A sample of root canal-treated teeth was included for survival analysis using the K-M and WAFT models. Treatment outcomes were categorized for the presence or absence of periapical healing and tooth survival. For the K-M analysis, the following time estimates between a visit when failure was diagnosed and the preceding visit were tested: the one-quarter point (T1), the half-way point (T2), the three-quarter point (T3), the date of diagnosis (T4), and the geometric mean (T5). The survival curve plotted from T2 consistently showed the least discrepancies in trend when compared against the WAFT curve. Those curves generated from T1 to T5 were significantly different from each other for periapical healing but not for tooth survival. T2 is the most reliable date for K-M analysis for measuring endodontic outcomes, especially when periapical healing is concerned. T4 would be a reasonable estimate for assessing tooth survival. Further research aiming at appropriate statistical exercise with simulations followed by proper goodness of fit tests should be considered.


A comparison between atria from control and streptozotocin-diabetic rats: the effects of dietary myoinositol.
1. Atria, isolated from control rats, six-week streptozotocin-diabetic rats and from similarly diabetic rats treated with myo-inositol (MI) were compared. The MI treatment was shown to reverse the depressed sciatic nerve MI which was observed in the untreated diabetic group. 2. Spontaneously beating atria from the untreated diabetic animals beat more slowly, and with greater force than tissues from the control group. When electrically driven at 4 Hz they were found to be less sensitive to the negative inotropic effect of acetylcholine. No differences between the two groups were observed in responses to isoprenaline. 3. Intramural nerve stimulation in the presence of 10(-6)M propranolol (vagal stimulation) had a greater negative inotropic effect in the untreated diabetic rat atria than in the controls. Positive inotropic responses to nerve stimulation in the presence of 10(-6) M atropine (sympathetic stimulation) were not significantly different between the two groups. 4. Atria from the MI-treated diabetic animals were found to have a lower spontaneous contractile force and greater sensitivity to acetylcholine than tissues from the untreated diabetic animals. The values obtained in both cases were similar to those from the controls. No significant effect of MI treatment on spontaneous contractile rate or on responses to nerve stimulation was demonstrated. 5. Atrial (mainly myocardial) MI was measured in additional control, six-week diabetic and six-week MI-treated diabetic animals. A significantly higher concentration was observed in the MI supplemented group compared to the untreated diabetic group. The mean MI content in the latter group was lower than that obtained from control tissues but not significantly so. 6. The results implicate MI depletion either in the neurones or in the myocardium in at least some of the changes observed. Possible mechanisms involved are discussed.


Retrobulbar block using pentothal as a sedative for ambulatory cataract surgery.
Cataract surgery comprises 80% to 85% of the surgical procedures performed at our ambulatory surgical center. We have developed a safe and effective method of sedation and amnesia for performing a retrobulbar block. We use sodium thiopental, administered intravenously, just prior to the block. We encourage the anesthesia departments of other facilities to consider this relatively simple blocking procedure for the comfort and safety of the patient.


Second malignancies after ewing tumor treatment in 690 patients from a cooperative German/Austrian/Dutch study.
Ewing tumor treatment involves high cumulative doses of alkylating agents and topoisomerase inhibitors, drugs capable of inducing second cancers. We analyzed the second cancer risk in a large cohort of consistently treated patients. Six hundred ninety Ewing tumor patients were treated between 1992 and 1999 with local therapy and vincristine. doxorubicin, ifosfamide and/or cyclophosphamide, and antinomycin D, with or without etoposide as a randomized question. Second cancer incidences were estimated by competing risk analyses; standardized incidence ratios (SIR) in comparison to registry data were compiled. After a median observation time of 56 months (32 months for survivors), 6 of 690 patients had developed second cancers: MDS/AML, two, ALL/NHL, two, squamous cell carcinoma, one, liposarcoma, one. SIR were increased 20-30 fold in comparison to the general population. The cumulative second cancer risk five years after diagnosis of the Ewing tumor was 0.0093 for the total group, zero for patients without etoposide, and 0.0118 with etoposide. Additional phase II high-dose therapy increased the risk to 0.0398 after five years. The second cancder risk observed was in the range to be expected in cancer survivors. High-dose therapy, and less markedly, etoposide, may contribute to the overall second cancer risk.


Implementing a new method of group toilet training in daycare centres: a cluster randomised controlled trial.
Despite the existing methods, a trend towards a later initiation and completion of toilet training has been seen in Western society. This study is the first to investigate prospectively the efficacy of intensive group toilet training in daycare centres. The primary outcome of interest is the duration until the child is toilet trained. A cluster randomised controlled trial was established in daycare centres; clusters of participants were randomly allocated to an intervention or control group. Intervention group was subjected to an intensive toilet training session. Innovative aspects of this toilet training method were a 2-h training on two consecutive days, carried out in small groups in daycare centres. Parents of children in the control group were encouraged to start TT in their own manner. Children were monitored until they were considered to be fully toilet trained during the day. Median toilet training duration in the intervention group was 2 weeks compared to 5 weeks in controls (p value log rank test = 0.007). The hazard of being clean during the follow-up of 6 weeks was twice as high in the intervention compared to controls (p = 0.018).Conclusion: The intervention had a significant influence on the duration of toilet training in healthy children, with a median duration of 2 weeks. Our findings are clinically relevant for daycare educators, having a considerable responsibility in the development of children.Trial Registration Number: ClinicalTrials.gov NCT04221776. What is Known: • Despite different existing methods, a later initiation of toilet training has been seen in Western society and coherent to this an increasing age of acquiring full bladder control. • Child daycare centres have a growing role in the toilet training process. What is New: • This is the first prospective report describing the results of a new method of toilet training healthy children in small groups in daycare centres. • The intervention had a significant influence on the duration of toilet training, with a median duration of 2 weeks.


Remote testing: Sensory test during Covid-19 pandemic and beyond.
Restrictions adopted by many countries in 2020 due to Covid-19 pandemic had severe consequences on the management of sensory and consumer testing that strengthened the tendency to move data collection out of the laboratory. Remote sensory testing, organized at the assessor's home or workplace and carried out under the live online supervision of the panel leader, represents a trade-off between adequate control and the convenience of conducting testing out of the lab. The Italian Sensory Science Society developed the "Remote sensory testing" research project aimed at testing the effectiveness and validity of the sensory tests conducted remotely through a comparison with evaluations in a classical laboratory setting. Guidelines were developed to assist panel leaders in setting up and controlling the evaluation sessions in remote testing conditions. Different methods were considered: triangle and tetrad tests, Descriptive Analysis and Temporal Dominance of Sensations tests, all of which involved trained panels, and Check-All-That-Apply and hedonic tests with consumers. Remote sensory testing provided similar results to the lab testing in all the cases, with the exception of the tetrad test run at work. Findings suggest that remote sensory testing, if conducted in strict compliance with specifically developed sensory protocols, is a promising alternative to laboratory tests that can be applied with both trained assessors and consumers even beyond the global pandemic.


Evaluation of the carcinogenicity of different preparations of areca nut in mice.
Areca nut has been used as a masticatory since antiquity and it is estimated that more than 10% of the world population chews it in a variety of forms. We have evaluated the carcinogenicity of different preparations of areca nut: ripe-unprocessed-sundried nut (R-UP-SD), ripe-processed-sundried nut (R-P-SD), unripe-processed-sundried nut (UR-P-SD), ripe-unprocessed-sundried-water-soaked nut (R-UP-SD-WS) and ripe-unprocessed-undried-water-soaked nut (R-UP-UD-WS) in mice following diet-feeding or oral feeding for 12 months. Only unprocessed areca nuts (R-UP-SD, R-UP-SD-WS and R-UP-UD-WS), at high doses, displayed a very weak carcinogenicity.


Impact of trauma in childhood and adulthood on eating-disorder symptoms.
Exposure to a traumatic event is concurrently and prospectively associated with disordered-eating behaviors such as binge eating, restricting, and purging. Specifically, purging has been found to be elevated in individuals with trauma histories, suggesting that purging may be a method for coping with trauma-related distress. However, there has been limited research investigating whether the time at which trauma occurs during development is differentially associated with disordered-eating behaviors and internalizing psychopathology. The purpose of this study was to examine the effect of trauma that occurred in childhood, adulthood, or childhood and adulthood on eating disorder (ED) and internalizing psychopathology. Participants were community-recruited adults with a current DSM-5 ED (N = 225) and were subsequently grouped into categories based on the time at which trauma occurred. Groups included: no trauma exposure ED controls (n = 54), child trauma group (n = 53), adult trauma group (n = 53), and child+adult trauma group (n = 65). We compared groups on their level of disordered-eating symptoms. Participants were administered the Structured Clinical Interview for DSM-IV, the Eating Pathology Symptoms Inventory (EPSI), and the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). Univariate analyses revealed significantly higher levels of purging symptomatology in the child+adult trauma group compared to the no trauma, child trauma, and adult trauma groups. The current study highlights the importance of assessing the timing of trauma among individuals with EDs. In particular, our study indicates a need for further investigation to explain why individuals with ED and trauma histories engage in greater purging.


Extremely low placental lactogen hormone (hPL) values in an otherwise uneventful pregnancy preceding delivery of a normal baby.
A case of a normal pregnancy and delivery with extremely low placental lactogen hormone (hPL) values in maternal blood is presented. The low hPL-values were due to the fact that the placenta only produced about 1/25 of the normal estimated output, calculated on the basis of the hPL-concentration in the intervillous spaces. The concentrations of progesterone, the placenta-specific beta-glycoprotein (SP1) and total estriol in serum were normal, while prolactin and chorionic gonadotropin (hCG) were considerably elevated. Glucose levels were normal. At the ultrastructural level the actual placenta under study did not differ from a normal term placenta. In spite of the very low concentrations of hPL there was a good milk secretion, and the mother was still breast-feeding her baby 11 months after the delivery. Basal level of prolactin was at this time normal.


To and Fro Between Eros and Thanatos: What Where and the Death Drive.
This paper tries to read What Where as Beckett's realistic and pessimistic presentation of the ontological conditions of the human history, which the play defines as investigation, exploitation and quest for the ultimate truth. Its analysis finds that this presentation has important threads in common with the criticism of civilization in the later Freud's metapsychology, which formulated "an all-embracing, grand theory of the psyche" in terms of the development of the individual as well as the evolution of the entire species on the basis of the maxim that "ontogeny recapitulates phylogeny" What Where enacts this Freudian vision in theatrical terms as its theater version foregrounds the phylogenetic scale with the physical subjections happening among the characters and its television version the interior depth of the mind with the maneuvering of the television images. Another important commonality is that the character Bam is presented as a figure pertaining to Freud's concept of the death drive. The resulting theatrical picture is a sobering and realistic testimony to the individual and collective human existence that has always survived on questionings about, exploitation of and quest for a different object. This strikes a chord with how Beckett's characters embody his poetics of 'senility,' and leads to the political implications of freedom without hope or meaning, which is the infinite task of Beckett's senile characters.


Immunological analysis of rat pancreatic prokallikrein activation.
The present study shows that tissue kallikrein is present in rat pancreas as a proenzyme that can be converted by autolysis to a 38 000 Da active enzyme. The activation of pancreatic prokallikrein was examined by direct radioimmunoassay, enzymatic assays, active-site labeling with immunoprecipitation, and Western blot analyses. A monoclonal antibody (V1C3), which binds only active kallikrein, was used in a direct radioimmunoassay to monitor the appearance of the active enzyme. During a 22-h autolysis of pancreatic extract, a time-dependent increase in active kallikrein concentration paralleled the increase of kallikrein activities measured by both TosArgOMe esterase and kininogenase assays. The activation process was further analyzed by labeling the pancreatic extract with [14C]diisopropylphosphorofluoridate [( 14C]DFP) followed by immunoprecipitation with sheep anti-kallikrein antiserum. Pancreatic prokallikrein was not labeled by [14C]DFP; however, upon autolysis, a 38 000 Da active kallikrein can be labeled with [14C]DFP and increase in quantity with time. Western blot analysis, using a monoclonal antibody (V4D11) which recognizes both latent and active tissue kallikreins, identified a 39 000 Da pancreatic prokallikrein prior to autolysis and a 38 000 Da active kallikrein after 7 h of autolysis. The results indicate that the pancreatic prokallikrein exists as a 39 000 Da protein which may be converted to a 38 000 Da active kallikrein, indistinguishable from purified urinary, brain, spleen or submandibular gland kallikrein.


Transmittance constraints in serial decompositions of depolarizing Mueller matrices: the arrow form of a Mueller matrix.
The passivity of the linear components in the main approaches for serial decompositions of depolarizing Mueller matrices [J. Opt. Soc. Am. A13, 1106 (1996); J. Opt. Soc. Am. A26, 1109 (2009)] is dealt with, and it is found that it is not always possible to perform such decompositions in terms of passive components. A compact form of Mueller matrix ("arrow matrix") associated with any given Mueller matrix, which retains, in a condensed manner, the physical properties relative to transmittance, diattenuation, polarizance, and depolarization, is presented.


A polyclonal allelic expression assay for detecting regulatory effects of transcript variants.
We present an assay to experimentally test the regulatory effects of genetic variants within transcripts using CRISPR/Cas9 followed by targeted sequencing. We applied the assay to 32 premature stop-gained variants across the genome and in two Mendelian disease genes, 33 putative causal variants of eQTLs, and 62 control variants in HEK293T cells, replicating a subset of variants in HeLa cells. We detected significant effects in the expected direction (in 60% of variants), demonstrating the ability of the assay to capture regulatory effects of eQTL variants and nonsense-mediated decay triggered by premature stop-gained variants. The results suggest a utility for validating transcript-level effects of genetic variants.


CaRF: a neuronal transcription factor that CaREs.
In this issue of Neuron, report the discovery of a new transcription factor, CaRF, that contributes to calcium stimulation of the BDNF gene through CaRE1, one of several calcium response elements found in the promoter of the BDNF gene. The CaRF/CaRE1 transcriptional pathway may control the expression of genes critical for activity-dependent, long-term changes in the central nervous system (CNS).


Measurements of higher order flow harmonics in Au+Au collisions at √s(NN)=200 GeV.
Flow coefficients ν(n) for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at √s(NN)=200 GeV, are measured relative to event planes Ψ(n), determined at large rapidity. We report ν(n) as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The ν(n) are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.


Wide local excision and split-thickness skin graft for circumferential Paget's disease of the anus.
Our aim was to evaluate the results of wide local excision followed by split-thickness skin graft for circumferential perianal Paget's disease. Between 1995 and 1999, 5 patients with perianal Paget's disease underwent wide local excision of the disease. The circumferential involvement was documented by preoperative mapping. Standard orthograde bowel cleansing and oral antibiotics were given the day prior to surgery. The wound was allowed to granulate and confirmation of negative margins was obtained on permanent sections taken from the excised specimens. On postoperative day 4, split-thickness skin grafts harvested from the lateral thigh were applied (surface using area ranging from 100 cm(2) to 240 cm(2)). The grafts were secured in place with a 3-0 Vicryl suture and covered with a pressure dressing. After 4 days of bedrest, the dressing was taken down under anesthesia (day 8). Graft survival was 100% in 3 patients, 80% in 1 patient, and 70% in another. Postoperatively, clinical follow-up was conducted at 3-month intervals. In 2 patients, anal stenosis developed after the operation and resolved by gentle self-dilation. At a mean follow-up of 42 months (range 21 to 78), adequate cosmetic and functional results were obtained. Recurrence of Paget's disease has occurred in 1 patient (at 21 months) and an invasive anal gland carcinoma was found in 1 patient (at 48 months). Wide local excision and circumferential split-thickness skin grafting achieves adequate cosmetic and functional results without the need for diverting colostomy. However, there is a considerable recurrence rate after surgery, which warrants very close follow-up to rule out recurrent disease or underlying adenocarcinoma.


Highly efficient removal of aluminum, iron, and manganese ions using Linde type-A zeolite obtained from hazardous waste.
Coal acid mine drainage (AMD) contaminates natural water to form mine-impacted water (MIW), which is characterized by high levels of acidity, sulfate, and metallic ions. This study investigates the use of a Linde Type-A (LTA) zeolite obtained from a hazardous industrial waste for Al3+, Fe2+, and Mn2+ removal from synthetic aqueous solutions. The aim of this study is to stablish a basis for the subsequent treatment of MIW in order to obtain reuse water. In a central composite rotatable design (CCRD) study, 8.25 g L-1 zeolite and 147 rpm were the optimal conditions for treating the multicomponent solution, yielding 99.9, 99.9 and 99.3% removal for Al3+, Fe2+, and Mn2+, respectively. Isothermal studies showed that the affinity of the ions by the zeolite were ranked as Al3+>Mn2+>Fe2+. The best fitting isothermal models for monocomponent solutions were Tóth, Freundlich, and Sips for Al3+, Fe2+, and Mn2+, respectively. In the multicomponent solution, Sips and Freundlich were the better fitting models for Al3+ and Mn2+, respectively, indicating a weakness of the sorbate-sorbent interactions. Kinetic studies revealed that the quantitative removal of Al3+ was achieved in 5 min. The multicomponent solution was transformed into water that was suitable for non-potable use after an optimal time of 60 min. The results demonstrate that LTA zeolite synthetized from hazardous waste has a high potential for remediating contaminated water by metallic ions at low dosages and short times. Using LTA zeolite for remediating contaminated water could make a positive contribution to the circular economy and environmental sustainability.


[Synthesis of capsular polysaccharide of Streptococcus pneumoniae type 14. 4. Polycondensation of the monomer and characteristics of the polysaccharide].
Synthesis of a regular branched polysaccharide [6(Gal beta 1-4)GlcNAc beta 1-3Gal beta 1-4Glc beta 1]n whose structure corresponds to that of the capsular polysaccharide of Streptococcus pneumoniae type 14, is described, involving a stereospecific polycondensation of the tetrasaccharide monomer, deacylation, and N-acetylation.


Co-localization of hippocampal cholinergic neurostimulating peptide precursor with collapsin response mediator protein-2 at presynaptic terminals in hippocampus.
Hippocampal cholinergic neurostimulating peptide (HCNP) induces the synthesis of acetylcholine in medial septal nucleus in vitro and in vivo. HCNP precursor protein (HCNP-pp) is a multifunctional protein that participates in a number of signaling pathways, including MAPK/extracellular signal and G-protein-coupled receptor kinase 2. We recently demonstrated that the amount of collapsin response mediator protein-2 (CRMP-2) is increased in hippocampus of HCNP-pp transgenic mice. To clarify the interaction between HCNP/HCNP-pp and CRMP-2 and its role in synaptic function, we investigated whether HCNP-pp is localized to the synapse and if it affects protein expression. Here, we demonstrate that HCNP-pp co-localizes with CRMP-2 at presynaptic terminals. Furthermore, HCNP-pp overexpression increases synaptophysin levels. These findings suggest that HCNP-pp, in association with CRMP-2, plays an important role in presynaptic function in the hippocampus.


Post-Mortem Studies of Neurturin Gene Therapy for Parkinson's Disease: Two Subjects with 10 Years CERE120 Delivery.
Neurturin is a member of the glial cell line-derived neurotrophic factor family of neurotrophic factors and has the potential to protectdegenerating dopaminergic neurons. Here, we performed post-mortem studies on two patients with advanced Parkinson's disease that survived 10 years following AAV-neurturin gene (Cere120) delivery to verify long-term effects of trophic factor neurturin. Cere120 was delivered to the putamen bilaterally in one case and to the putamen plus substantia nigra bilaterally in the second. Immunohistochemistry was used to examine neurturin, Rearranged during transfection(RET), phosphor-S6, and tyrosine hydroxylase expressions, inflammatory reactions, and α-synuclein accumulation. In both patients there was persistent, albeit limited, neurturin expression in the putamen covering 1.31% to 5.92% of the putamen. Dense staining of tyrosine hydroxylase-positive fibers was observed in areas that contained detectable neurturin expression. In substantia nigra, neurturin expression was detected in 11% of remaining melanin-containing neurons in the patient with combined putamenal and nigral gene delivery, but not in the patient with putamenal gene delivery alone. Tyrosine hydroxylase positive neurons were 66% to 84% of remaining neuromelanin neurons in substantia nigra with Cere120 delivery and 23% to 24% in substantia nigra without gene delivery. More RET and phosphor-S6 positive neurons were observed in substantia nigra following nigral Cere120. Inflammatory and Lewy pathologies were similar in substantia nigra with or without Cere120 delivery. This study provides evidence of long-term persistent transgene expression and bioactivity following gene delivery to the nigrostriatal system. Therefore, future efforts using gene therapy for neurodegenerative diseases should consider means to enhance remaining dopamine neuron function and stop pathological propagation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Polymorphism detection and sequence analysis of human T-cell receptor V alpha-chain-encoding gene segments.
The T-cell receptor (Tcr) provides specificity for antigen recognition by its variable domain, primarily consisting of two germline encoded variable (V) region gene segments. Thus it has been suggested that inherited polymorphisms in the TCRV gene segments could contribute to differential immune responsiveness (e.g., autoimmunity) in human populations. In the present study, we have sought potentially functional polymorphisms in the germline TCRAV gene segments. Using denaturing gradient gel electrophoresis on polymerase chain reaction (PCR)-amplified products from the pooled DNA of many individuals, we identified polymorphisms in the TCRAV2S1, AV4S1, AV7S1, and AV8S1 gene segments. A complete DNA sequence analysis of these PCR products identified polymorphisms that affected amino acids in the predicted antigen-binding regions of the Tcr alpha chain, as well as polymorphisms in the introns. Genotype analysis of all nine DNA point mutations showed a 5%-50% range (averaging 35%) of minor allele frequencies, often resulting in individuals homozygous for the alternate allele forms. All possible haplotype combinations of the amino acid-affecting polymorphisms were found, indicating that in human populations there are a large number of different germline haplotypes encoding V gene segment alleles. These TCRAV coding region polymorphisms provide the rationale for, and allow the direct testing of, hypotheses concerning inherited polymorphisms within the T-cell receptor genes that may contribute to autoimmune susceptibility.


Degradation of the E. coli antitoxin MqsA by the proteolytic complex ClpXP is regulated by zinc occupancy and oxidation.
It is well established that the antitoxins of toxin-antitoxin (TA) systems are selectively degraded by bacterial proteases in response to stress. However, how distinct stressors result in the selective degradation of specific antitoxins remain unanswered. MqsRA is a TA system activated by various stresses, including oxidation. Here, we reconstituted the Escherichia coli ClpXP proteolytic machinery in vitro to monitor degradation of MqsRA TA components. We show that the MqsA antitoxin is a ClpXP proteolysis substrate, and that its degradation is regulated by both zinc occupancy in MqsA and MqsR toxin binding. Using NMR chemical shift perturbation mapping, we show that MqsA is targeted directly to ClpXP via the ClpX substrate targeting N-domain, and ClpX mutations that disrupt N-domain binding inhibit ClpXP-mediated degradation in vitro. Finally, we discovered that MqsA contains a cryptic N-domain recognition sequence that is accessible only in the absence of zinc and MqsR toxin, both of which stabilize the MqsA fold. This recognition sequence is transplantable and sufficient to target a fusion protein for degradation in vitro and in vivo. Based on these results, we propose a model in which stress selectively targets nascent and zinc-free MqsA, resulting in exposure of the ClpX recognition motif for ClpXP-mediated degradation.


Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin.
(1) Unlike other nonsteroidal anti-inflammatory drugs that inhibit formation of cyclooxygenase (COX)-dependent eicosanoids, acetylation of COX-2 by aspirin switches eicosanoid biosynthesis from prostaglandin E(2) (PGE(2)) to 15-epi-lipoxin A(4) (15-epi-LXA(4) or aspirin-triggered lipoxin, ATL). ATL formation by activated leukocytes (PMN) requires the intervention of 5-lipoxygenase (5-LOX), an enzyme that is involved in leukotriene B(4) (LTB(4)) formation. (2) In the present study, we have examined the role of acetylated COX-2 and 5-LOX in modulating antiadhesive effects of aspirin on adhesion of PMN to endotoxin (LPS)-primed human umbilical endothelial cells (HUVEC). (3) Treating PMN/HUVEC cocultures with aspirin resulted in a concentration-dependent inhibition of cell-to-cell adhesion induced by LPS. Treating HUVEC with selective COX-2 inhibitors, celecoxib and rofecoxib, caused an approximately 70% reversion of antiadhesive effect of aspirin. In contrast, inhibition of neutrophil's 5-LOX pathway with 1 micro M ZD2138, a selective 5-LOX inhibitor, 1 micro M BAY-X-1005, a FLAP inhibitor, or 100 micro M licofelone, a dual COX/5-LOX inhibitor, did not affect antiadhesive properties of aspirin. (4) Exposure to celecoxib (100 micro M) or rofecoxib (10 micro M) completely suppressed ATL formation caused by aspirin without affecting LTB(4) levels. ZD2138, licofelone and BAY-X-1005 inhibited ATL formation as well as LTB(4) generation. (5) Treatment with LXA(4) reduced PMN adhesion to HUVEC and counteracted the proadhesive effect of celecoxib. In contrast, exposure to Boc-1, an LXA(4) antagonist, counteracts the antiadhesive activities of aspirin. Exposure to U75302, an LTB(4) receptor antagonist, enhances the antiadesive effect of aspirin. (6) Reversal of antiadhesive activities of aspirin by celecoxib was associated with increased expression of LFA-1 on PMN and E-selectin on HUVEC. Addition of LXA(4), ZD2138 and U75302 inhibited these changes. (7) The present results support the notion that inhibition of ATL formation is mechanistically linked to the reversal of the antiadhesive activity of aspirin caused by selective COX-1 inhibitors and suggests that the LTB(4)/ATL balance modulates pro- and antiadhesive activity of nonsteroidal anti-inflammatory drugs at the leukocyte-endothelial cell interface.


Habituation of distraction to a tone in the absence of neocortex in rats.
Normal rats and rats with in excess of 95% of neocortex surgically removed (decorticated) were trained to push a food tray door on a Fixed Ratio schedule. Once the behaviour was established a 3720 Hz, 70 dB tone was presented 4 times per session and the duration of distraction from the operant baseline was recorded. Both groups of rats habituated to the presence of the tone within a single session and the effects were retained over a 24 h interval. The decorticates, but not the normal animals, showed a partial spontaneous recovery of the habituated response between sessions. It was concluded that neocortex is not required for either short-term or long-term habituation in this situation though long-term habituation is more complete when neocortex is present.


Sympathetic and immune interactions during dynamic exercise. Mediation via a beta 2-adrenergic-dependent mechanism.
The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.


Stability of reconstituted methohexital sodium.
The purpose of this study was to determine the stability of reconstituted solutions of methohexital sodium over a 6-week period. Stability of methohexital was examined using reversed-phase high-performance liquid chromatography. The results indicate that reconstituted methohexital is extremely stable for up to 6 weeks when stored at 4 degrees C. When stored at room temperature, reconstituted solutions of methohexital contained increasing levels of degradation products and showed a corresponding decrease in methohexital over a 6-week period. However, the rate of degradation of the drug was slow, with less than 10% of the methohexital undergoing breakdown. In addition, tests for microbial contamination of the solutions stored at room temperature and under refrigeration were negative for up to 6 weeks. This study demonstrates that methohexital, when stored under refrigeration for up to 6 weeks, is virtually chemically identical to a freshly reconstituted solution of the drug. When stored at room temperature, there is some degradation of the drug, but it is not known whether the small amount of degradation is clinically significant. This study emphasizes the importance of obtaining scientific data to support changes in guidelines related to handling and storage of drugs.


Expression of a Drosophila GABA receptor in a baculovirus insect cell system. Functional expression of insecticide susceptible and resistant GABA receptors from the cyclodiene resistance gene Rdl.
Recombinant baculoviruses containing two alternative splice forms of the Drosophila Rdl GABA receptor gene were constructed. Spodoptera frugiperda (Sf21) cells infected with either splice form expressed a transcript of expected size (2.5 kb). Western blotting of cell membrane extracts and immunoprecipitation experiments with an anti-Rdl antiserum recognized a protein of the expected size of approximately 65 kDa. Whole cell patch clamp analysis of cells infected with either splice form revealed functional expression of GABA gated chloride ion channels which were blocked by application of 1 microM picrotoxinin. Following replacement of alanine 302 with a serine, a mutation associated with resistance to picrotoxinin and cyclodiene insecticides, mutant channels showed similar levels of insensitivity to picrotoxinin (approximately 100-fold) as those observed in recordings from cultured Drosophila neurons. The significance of the expression of an insect GABA receptor in an insect cell line and the similarity of the results from these functional expression studies to recordings from cultured neurons is discussed.


Local Therapies in Advanced Colorectal Cancer.
Curative intent surgical resection of colorectal metastases to the liver and lungs in eligible patients results in improved disease control and prolonged overall survival with the potential for cure in a subset of patients. Additional ablative and local therapies for use in the liver, lungs, and other body sites have been developed with emerging data on the utility and toxicity of these treatments. Future studies should focus on identification of appropriate candidates for treatment and determining the optimal modality and timing of treatment accounting for both patient and disease factors.


Knockout of vascular early response gene worsens chronic stroke outcomes in neonatal mice.
Vascular early response gene (Verge) is a novel immediate early gene that is highly expressed during developmental angiogenesis and after ischemic insults in adult brain. However, the role of Verge after neonatal injury is not known. In the present study, we investigated the hypothesis that Verge contributes to vascular remodeling and tissue repair after neonatal ischemic injury. The Rice-Vanucci model (RVM) was employed to induce neonatal stroke in both Verge knockout (KO) and wild-type (WT) postnatal day 10 (P10) mice. Histological and behavioral outcomes at acute (24h), subacute (7 days) and chronic (30 days) phases were evaluated. Angiogenesis, neurogenesis, and glial scar formation were also examined in the ischemic brain. No significant differences in outcomes were found between WT and Verge mice at 24h or 7 days after stroke. However genetic deletion of Verge led to pronounced cystic cavitation, decreased angiogenensis and glial scar formation in the ischemic hemisphere compared to WT mice at 30 days. Verge KO mice also had significantly worse functional outcomes at 30 days which was accompanied by decreased neurogenesis and angiogenesis in the ischemic hemisphere. Our study suggests that Verge plays an important role in the induction of neurogenesis and angiogenesis after ischemia, contributes to improved tissue repair, and enhances chronic functional recovery.


Association between haplotypes of manganese superoxide dismutase (SOD2), smoking, and lung cancer risk.
Tobacco smoke contains high concentrations of reactive oxygen species (ROS) that can damage DNA, proteins, and lipids. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals into hydrogen peroxide and protects against oxidative stress in lung tissues. Three tagSNPs were identified in one block of high linkage disequilibrium that spans the entire SOD2 gene and 5-kb promoter region. These tagSNPs, representing four haplotypes (TAA, TCA, TCG, CCG), were genotyped in 372 lung cancer cases and 605 controls. There was no association between the haplotype frequencies and the overall lung cancer risk. The TCG haplotype (6% in controls) was significantly associated with a lower risk of lung cancer in light smokers (<median pack-years; P value=0.02) but not in heavy smokers. In histologic-specific analysis, the TCG haplotype was significantly associated with a reduced risk of lung adenocarcinoma (odds ratio=0.39, 95% CI 0.17-0.88), but an inverse association with squamous cell carcinoma was not significant. The association with adenocarcinoma was most apparent in light smokers (haplotype-specific P value=0.005); none of the 61 case subjects with adenocarcinoma had the TCG allele. This study suggests that subjects with the SOD2 TCG haplotype may be at decreased risk for lung adenocarcinoma and that this association may depend on smoking amount.


Development of a thermo-stable and recyclable magnetic nanobiocatalyst for bioprocessing of fruit processing residues and D-allulose synthesis.
The aim of the study was to covalently immobilize Smt3-D-psicose 3-epimerase onto functionalized iron oxide magnetic nanoparticles. After immobilization, Km of the immobilized enzyme increased, however, Vmax was nearly the same as that of its free form, indicating that immobilization has no detrimental effects on its catalytic output. The covalent immobilization caused a reduction in the deactivation rate constant (kd) values leading to 4-5 fold enhancement in its half-life at 50-65°C, indicating significant thermal stability of the iron-enzyme nanobioconjugate. The immobilized enzyme showed excellent storage stability by losing only 20% activity even after 60days of storage at 4°C. The immobilized enzyme retained up to 90% of its initial activity even after 10 consecutive cycles of catalyzing D-fructose epimerization reactions. Thus, after immobilization the enzyme exhibited remarkable improvements in thermal tolerance, storage stability and recycling efficiency, useful for development of industrially exploitable process for D-allulose production.


Correlated-photon imaging at 10 volumetric images per second.
The correlation properties of light provide an outstanding tool to overcome the limitations of traditional imaging techniques. A relevant case is represented by correlation plenoptic imaging (CPI), a quantum-inspired volumetric imaging protocol employing spatio-temporally correlated photons from either entangled or chaotic sources to address the main limitations of conventional light-field imaging, namely, the poor spatial resolution and the reduced change of perspective for 3D imaging. However, the application potential of high-resolution imaging modalities relying on photon correlations is limited, in practice, by the need to collect a large number of frames. This creates a gap, unacceptable for many relevant tasks, between the time performance of correlated-light imaging and that of traditional imaging methods. In this article, we address this issue by exploiting the photon number correlations intrinsic in chaotic light, combined with a cutting-edge ultrafast sensor made of a large array of single-photon avalanche diodes (SPADs). This combination of source and sensor is embedded within a novel single-lens CPI scheme enabling to acquire 10 volumetric images per second. Our results place correlated-photon imaging at a competitive edge and prove its potential in practical applications.