Ocular oncology service during the COVID-19 outbreak in Florence (Italy): Practical considerations for the management of patients.
The Coronavirus disease 2019 (COVID-19) outbreak has imposed the adoption of strategies to limit the risk of contagion for cancer patients without compromising their healthcare. As well as cancers of other sites, the treatment of certain ocular and periocular malignancies is considered non-deferrable and should proceed despite the pandemic. Delays in treatment of these patients may result in negative outcomes. Herein, we provide some practical considerations deriving from our experience at the Ocular Oncology Unit of Careggi University Hospital (Florence, Italy).


Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease.
In this population-based case-control study, we examined the relationship between the fibrinolytic variables tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity, cardiovascular risk factors and peripheral arterial disease. Cases and controls were selected from the Edinburgh Artery Study, a random sample survey of men and women, aged 55-74 years. Mean levels of t-PA antigen and PAI activity were significantly elevated in 121 cases compared to 126 controls. The increased risks of peripheral arterial disease with increasing PAI activity and t-PA antigen levels were partly mediated by interactions with serum triglycerides, high density lipoprotein (HDL) cholesterol and cigarette smoking. For example, adjustment for triglycerides significantly reduced the odds of disease for PAI activity from 1.41 (95% confidence intervals 1.08, 1.86) to 1.24 (0.93, 1.65) and from 1.47 (1.09, 1.98) to 1.34 (0.99, 1.82) for t-PA antigen. We conclude that impaired fibrinolytic potential (raised PAI activity and t-PA antigen) is associated with peripheral atherosclerosis and that this relationship is partly influenced by lipids and cigarette smoking.


The Effects of Music Therapy on Patients With Coronary Artery Disease Before the Invasive Procedure: A Randomized Controlled Study.
This study was designed to investigate the effects of music therapy provided to patients who would undergo Coronary Angiography before the invasive procedure on pain, anxiety, and vital signs to reduce the administration of sedatives and to ask the views of the patients regarding the music to which they listened. This study was a randomized controlled study. The research sample included 62 patients; 31 in the experimental group and 31 in the control group, who were waiting for having femoral angiography in the waiting room of the invasive procedure and diagnostic laboratory of a training and research hospital in Izmir. Data were collected using "Patient Information Form", "Vital Signs Inspection Form", "State-Trait Anxiety Inventory", and "Visual Analog Scale". The experimental group listened to nonverbal and instrumental music in the forms of taqsim, saz semai, and peshrev at the speeds of 60 (Adagio) and 100 (Andante). Nihavend mode is the most used mode in music therapy and is suitable for the Turkish Cultural structure. The scale of nihavend mode has the same structure with the g minor scale of classical western music. For both groups, pain and anxiety levels were simultaneously measured before and after the process; vital signs were measured before, during, and after the process. The findings obtained in this study showed that there was a statistically significant difference between the means of anxiety (P = .000) and pain (P = .001) of the patients in experimental and control groups after the procedure. A significant difference was determined between the means before and after the procedure for diastolic (P = .002) blood pressure and pulse wave velocity (P = .002) in vital signs. A significant difference was not determined between the mean of patients' systolic blood pressures (P = .082) and respiration rates (P = .836) before and after the procedure. The findings suggest that music therapy is effective in reducing blood pressure, respiration rate, anxiety, pain level, and sedative application for the patients. Music therapy within the scope of the nonpharmacological complementary therapies can be administered by the healthcare providers, given that the patients have no adverse effects or additional costs and thanks to ease of implementation.


Serotonin transporter and receptor ligands with antidepressant activity as neuroprotective and proapoptotic agents.
Serotonin exhibits multiple non-neural functions involved in essential hypertension, early embryogenesis, follicle maturation and behaviour. The growth stimulatory effects of the neurotransmitter have been described for a variety of cell types. 5-HT was found to induce migration of the human prostate cancer cell lines - PC-3 and Du145 - and several 5-HT1A antagonists and serotonin reuptake inhibitors were reported to inhibit the growth of different tumour cell lines in vitro. Recent studies suggest that neurogenesis is involved in the action of antidepressants and an involvement of antidepressants in adult hippocampal neurogenesis has been demonstrated. Antidepressants also exhibit neuroprotective activity, which could be connected to their antidepressant activity. However, it has been reported that certain antidepressants may induce apoptosis in some cancer cell lines. In the present paper the neuroprotective and proapoptotic activities of serotonergic antidepressants (SSRIs and TCAs), as well as 5-HT1A receptor ligands are summarized and discussed based on biochemical transduction pathways associated with these activities.


Cystic tumors of the pancreas: ultrasound, computed tomography, and magnetic resonance imaging features.
Cystic tumors of the pancreas are a subset of rare pancreatic tumors that vary from benign to malignant. Many have specific imaging findings that allow them to be differentiated from each other. This article aims to review the histopathologic and imaging findings of the relatively common lesions (serous microcystic adenoma, mucinous cystic tumor, intraductal papillary mucinous tumor, and solid pseudopapillary tumor) and uncommon lesions (cystic endocrine tumors, cystic metastases, cystic teratomas, and lymphangiomas) in this group.


RNAi-induced targeted silencing of developmental control genes during chicken embryogenesis.
The RNA interference technique is a powerful tool to understand gene function. Intriguingly, RNA interference cannot only be used for cells in vitro, but also in living organisms. Here, we have adapted the method for use in the chick embryo. However, this technique is limited by the uncertainty in predicting the RNAi transfection efficiency and site in the embryo. Hence, we elaborated a modified vector system, pEGFP-shRNA, which can coexpress enhanced green fluorescent protein (EGFP) and short hairpin RNA (shRNA) simultaneously to facilitate analysis of gene silencing in chicken embryos. We tested the silencing of two highly conserved genes (cAxin2, cParaxis), which play crucial roles in chicken embryonic developmental processes. For each target gene, four to five small DNA inserts, each of them encoding one shRNA, were selected and cloned individually to the vector downstream of the Pol III promoter (either human H1 or U6 promoter), which shared with highly conserved motifs in human and chicken. The pEGFP-shRNA constructs were electroporated into the neural tube or somites. After subsequent re-incubation of 24 h, the EGFP expression, with green fluorescent signal, indicated the transfected regions in the neural tube or somites. The EGFP expressing embryos were further submitted into the process of in situ hybridization for examination of the silencing effects. The results show that the EGFP signal in transfected areas correlated with the silencing of the target genes (cAxin2, cParaxis). The cAxin2 expression was inhibited by shRNAs of either targeting the RGS domain or the DAX domain coding region. The cParaxis mRNA level in transgenic somites and the related migratory myogenic population was also reduced. The results suggest that our novel dual expression EGFP-shRNA system opens a new possibility to study gene function in a convenient and efficient way.


The incidence of residual neuromuscular blockade associated with single dose of intermediate-acting neuromuscular blocking drugs.
The goal of this study is to investigate the incidence and risk factors of residual paralysis associated with single-dose intermediate-acting muscle relaxants (atracurium, vecuronium, rocuronium) during early postoperative period. Adult patients (ASA I and II) who received a single dose of vecuronium, atracurium or rocuronium during general anesthesia for elective surgical procedure were included in the study. Train-of-four (TOF) ratios under 0.9 were recorded as "postoperative residual neuromuscular block (PRNB)". Age, weight, gender, reversal, anesthesia duration, time for transfer to the recovery room after extubation were studied regarding with PRNB. 84 patients were included in this study. 29 patients were received vecuronium, 28 patients were received atracurium and 27 patients were received rocuronium. Neostigmine was used for reversal in 49 patients (58.3%) at the end of the surgery. PRNB incidence (TOF < 0.9) was 13.1%. Based on the regression analysis, the only risk factor affecting PRNB was found as gender. PRNB risk was increased in women (OR: 7.250, 95%, CI: 1.019-51.593). In patients who have general anesthesia longer than one hour, "gender" may affect residual paralysis incidence associated with single-dose intermediate-acting muscle relaxants use.


An arts-based intervention at a nursing home to improve medical students' attitudes toward persons with dementia.
Emerging data suggest that students' attitudes toward older patients may be positively affected by geriatric experiences that are not clinically based, but no known interventions have used creative arts to integrate humanistic experiences into medical student geriatric education. This 2012 study evaluated whether participating in TimeSlips, a creative group-based storytelling program involving persons with dementia, improved medical students' attitudes toward such patients. The authors administered the Dementia Attitudes Scale (DAS) to 22 fourth-year medical students to evaluate the mean change in their self-reported attitudes toward persons with dementia. The authors used paired t tests or Wilcoxon signed-rank tests to analyze pre- and post-program scores on the individual items of the DAS, on the subdomains of "comfort" and "knowledge," and on the overall scale. They used Cronbach alpha to evaluate the internal consistency and reliability of the "comfort" and "knowledge" subdomains and of the overall scale. Medical students' attitudes, as measured by the significantly higher scores on 12 of the 20 items, on each of the two subdomains, and on the overall scale, showed improvement after the TimeSlips sessions. The DAS showed acceptable to good internal consistency on both subdomains and on the overall scale both pre and post session; however, the internal consistency analysis is preliminary because of small sample size. The authors' findings provide preliminary evidence that participation in a creative storytelling program at a nursing home improves medical students' attitudes toward persons with dementia and adds to evidence supporting the reliability of the DAS.


Correlation Between Superoxide Dismutase Serum Level Alteration with Neck Metastatic Tumor Post Cisplatin-Paclitaxel Chemotherapy Response in Nasopharyngeal Carcinoma Patients.
Nasopharyngeal carcinoma (NPC) is a malignant tumor in the nasopharynx. The patients treated with neoadjuvan combination chemotherapy cisplatin-paclitaxel while waiting a radiotherapy. This combination can produce a very high reactive oxygen species (ROS) level. Our body has a protective mechanism against oxidant through superoxide dismutase (SOD) that can inhibit DNA chain damage from ROS induction produced by chemotherapy in NPC patients. This study aimed to analyze the correlation between SOD level alteration with neck metastatic tumor response after cisplatin-paclitaxel chemotherapy. This was a cohort study. Thirty samples examined for neck metastasis tumor volume (VTM) and serum SOD were examined with ELISA pre- and postchemotherapy. Statistical significance was defined as p < 0.05. Mean SOD serum level pre-chemotherapy and post-chemotherapy were was 179.5 and 209.1, respectively. Mean tumor metastaic volume pre and post chemotherapy were 127.3 and 62.7, respectively. The correlation test with the result (r) 0.180 and p = 0.340. There was no correlation between SOD serum level alteration with VTM volume post cisplatin-paclitaxel chemotherapy in NPC patients.


Effect of immunization on the development of latent ganglionic infection in mice challenged intravaginally with herpes simplex virus types 1 and 2.
Immunization of BALB/c mice with virulent and avirulent strains of HSV-1 resulted in high levels of neutralizing antibody and protected against both the lethal effect of the virus and the development of a latent ganglionic infection when animals were challenged by the intravaginal route. In animals immunized with avirulent strain of HSV-2 and challenged with a high virulent strain of HSV-2, substantial protection against death was observed despite low levels of neutralizing antibody. Nineteen per cent of the survivors, however, developed a latent ganglionic infection. Relatively little protection was observed in mice immunized with HSV-1 and challenged with HSV-2.


Neuroinflammatory Biomarkers in Cerebrospinal Fluid From 106 Patients With Recent-Onset Depression Compared With 106 Individually Matched Healthy Control Subjects.
Neuroinflammation has been linked to depression; however, neuroinflammatory biomarkers in the cerebrospinal fluid (CSF) have not previously been thoroughly investigated in a large group of patients with recent-onset depression compared with healthy control subjects. We conducted an individually matched case-control study comparing patients with recent-onset depression (ICD-10: F32) to control subjects. Primary outcomes were CSF white cell count (WCC), CSF-to-serum albumin ratio, CSF total protein, and immunoglobulin G (IgG) index. Secondary outcomes were CSF WCC differential count and CSF neutrophil-to-lymphocyte, CSF-to-serum IgG, and CSF-to-plasma glucose ratios. Linear models adjusting for sex and age were applied. We included 106 patients with recent-onset depression (84.0% outpatients) and 106 healthy control subjects. Patients had 18% higher CSF WCC relative to control subjects (relative mean difference [MD]: 1.18; 95% CI: 1.02-1.40; p = .025). CSF WCC differed with depression symptomatology (p = .034), and patients with severe depression (n = 29) had 43% higher CSF WCC relative to control subjects (MD: 1.43; 95% CI: 1.13-1.80, p = .003). Two (1.9%) patients and no controls (0.0%) had CSF WCC above the normal range (>5 × 106/L). No significant differences between groups were observed regarding CSF-to-serum albumin ratio (MD: 1.07; 95% CI: 0.97-1.18; p = .191), CSF total protein (MD: 1.01; 95% CI: 0.94-1.09; p = .775), or IgG index (MD: 1.05; 95% CI: 0.97-1.15; p = .235). Regarding secondary outcomes, the proportion of CSF neutrophils was lower among patients (MD: 0.22; 95% CI: 0.08-0.59; p = .003) relative to control subjects, whereas the remaining outcomes were not significantly different (all p > .06). Patients had higher CSF WCC relative to control subjects, indicating increased neuroimmunologic activation, particularly for severe depression.


Real world efficacy of dolutegravir plus lamivudine in people living with HIV with undetectable viral load after previous failures.
Dolutegravir (DTG) +lamivudine (3TC) combination has been found to be as effective as triple therapies, and has been extensively prescribed in clinical practice as a maintenance therapy. We aimed to investigate the effect of previous virological failures (VFs) on virological efficacy. The analysis included data of people living with HIV (PLWH) with HIV-RNA ≤50 copies/mL enrolled in an Italian retrospective multicohort study who were switching to DTG+3TC. Primary endpoint was viral rebound (VR; confirmed HIV-RNA ≥50 copies/mL or single HIV-RNA ≥50 copies/mL followed by change of antiretroviral therapies [ART]). Kaplan-Meier curves were used to estimate probabilities of VR based upon histories of previous VFs (single HIV-RNA ≥1000 copies/mL or confirmed HIV-RNA ≥50 copies/mL). A weighted Cox regression model was fitted to estimate the causal hazard ratio (HR) of history of failure on the risk of VR. A total of 966 PLWH were included; 20.1% had a history of previous VF. VR was detected in 23 PLWH. The one-year probability was 1.2% (95% confidence interval [CI], 0.2%-2.2%) in PLWH without previous VF and 3.3% (95% CI, 0.4%-6.2%) in those with ≥1 VF (log-rank P = 0.042). By multivariate analysis adjusted for CD4+ cell count at nadir, duration of virological suppression, and mode of HIV transmission, PLWH with ≥1 previous VF had a higher risk of virological rebound than those without previous VF (adjusted hazard ratio 3.06 [95% CI, 1.00-9.44], P = 0.051). Despite the low absolute one-year risk in both groups, real-world data confirmed that PLWH with a previous failure have an increased risk of viral rebound.


Characterization of breakpoints in the GABRG3 and TSPY genes in a family with a t(Y;15)(p11.2;q12).
We report the clinical, cytogenetic, and molecular findings in a family in which a t(Y;15)(p11.2;q12) is segregating. The Y chromosome breakpoint disrupts the DYZ5 sequence containing the TSPY genes that are exclusively expressed in the testes while the chromosome 15 breakpoint is within the GABRG3 gene. The father and his son who both carried the balanced form of the translocation are clinically normal. A daughter who carried the der Y had the clinical features of Prader-Willi syndrome while a son who carries the der 15 has mild developmental delay and hypogonadism. The relationship of the translocation to the clinical phenotypes is discussed.


Spatial distribution of perfluoroalkyl acids in the Pearl River of southern China.
An intensive campaign was conducted in September 2012 to collect surface water samples along the tributaries of the Pearl River in southern China. Thirteen perfluoroalkyl acids (PFAAs), including perfluorocarboxylates (PFCAs, C4-C11) and perfluorosulfonates (PFSAs, C4, C6-C8, and C10), were determined using high-performance liquid chromatography/negative electrospray ionization-tandem mass spectrometry (HPLC/(-)ESI-MS/MS). The concentrations of total PFAAs (ΣPFAAs) ranged from 3.0 to 52 ng L(-1), with an average of 19±12 ng L(-1). The highest concentrations of ΣPFAAs were detected in the surface water of the Dong Jiang tributary (17-52 ng L(-1)), followed by the main stream (13-26 ng L(-1)) and the Sha Wan stream (3.0-4.5 ng L(-1)). Perfluorooctanoate (PFOA), perfluorobutane sulfonate (PFBS), and perfluorooctane sulfonate (PFOS) were the three most abundant PFAAs and on average accounted for 20%, 24%, and 19% of ΣPFAAs, respectively. PFBS was the most abundant PFAA in the Dong Jiang tributary, and PFOA was the highest PFAA in the samples from the main stream of the Pearl River. A correlation was found between PFBS and PFOA, which suggests that both of these PFAAs originate from common source(s) in the region. Nevertheless, the slope of PFBS/PFOA was different in the different tributaries sampled, which indicates a spatial difference in the source profiles of the PFAAs.


L-carnitine in inborn errors of metabolism: what is the evidence?
A questionnaire was posted on the electronic mailing-list Metab-1 to determine current practice as regards the use of oral L-carnitine in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, propionic acidaemia (PA) and methylmalonic acidaemia (MMA). Thirty-one centres replied: L-carnitine was used routinely by 94% of respondents in PA and MMA but by only 36% in MCAD deficiency. A search was made for published papers on the use of L-carnitine in organic acidaemias and in MCAD deficiency. The quality of evidence to support the use of L-carnitine was graded according to the scale published by the Scottish Intercollegiate Guideline Network. No high-quality evidence was identified.


Returning human factors to an engineering discipline: expanding the science base through a new generation of quantitative methods--preface to the special section.
Newell and Card (1985) warned the human factors community that the way to deal with scientists, engineers, and designers was not through the use of platitudes or by advocating the empirical testing of an infinity of design alternatives but, rather, through the use of predictive and reliable quantitative techniques. As the scope and scale of the issues that the human factors community was asked to consider expanded, the tool chest of quantitative methods seemed to diminish. That situation appears to be changing. As the papers in this special section show, the science base and techniques available for applying that science through use of quantitative formalisms have progressed. The pendulum is swinging back, and human factors engineers are in the ascendance. Engineering quantitative formal models of human performance is the wave of the present and represents an important part of the future of our profession.


Effect of first-dimension column film thickness on comprehensive two-dimensional gas chromatographic separation.
In comprehensive two-dimensional gas chromatography (GC x GC), samples experience two-dimensional separation implemented by a modulator which helps preserve the first-dimension separation and facilitates the second-dimension separation by periodically collecting, focusing and launching the material from the primary column onto the secondary column with a different stationary phase. Column overloading in GC x GC is a considerable problem, aggravated by the fact that two columns are involved. Broad first-dimension peaks of an analyte help produce smaller fractions of the analyte in the second-dimension, reducing the chance of secondary column overloading. One of the means to generate broad peaks in the first-dimension is to use thick film primary columns. A series of primary columns of various film thickness were tested in the study, and the results indicate that when other conditions are kept constant, 1 microm film columns often provide better resolution in both first and second-dimension but at the expense of a much longer separation time; 0.1 microm is clearly inadequate for GC x GC separation; 0.5 and 0.25 microm film columns seem to be the best compromises.


Evaluation of bone mineral density in patients with hemoglobin H disease.
This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) of patients with hemoglobin H (HbH) disease. BMD and BMC were measured by dual energy X-ray absorptiometry of the lumbar spines and femur neck in 21 patients with Hb H disease over the age of 10 years. An association of BMD with sex, age, hemoglobin, calcium, phosphorus, and serum ferritin level was also evaluated. Prevalence of BMD below the expected range for age in the lumbar spine and femur neck region in patients with HbH disease were 33.3 and 14.3 %, respectively. Lumbar BMD was significantly lower in the patients compared to healthy individuals (median (min-max) 0.725 (0.595-0.924) vs. 1.061 (0.645-1.238), P < 0.001)). There was no significant relationship between BMD in the lumbar and femur neck with any of the evaluated variables (P value >0.05). Data regarding bone density in HbH disease is limited; osteoporosis as a common complication of β-thalassemia intermedia syndrome should be considered even in HbH which shows its prevalence is less than β-thalassemia intermedia.


X-linked dystonia ("Lubag") presenting predominantly with parkinsonism: a more benign phenotype?
"Lubag," or Filipino X-linked dystonia, typically presents with either pure dystonia (that inexorably becomes generalized) or combined dystonia-parkinsonism. We report on three cases of Lubag presenting with isolated parkinsonism without dystonia or late-onset dystonia and a slower course.


New chlorine-containing phenoloid from Curculigo capitulata.
A new chlorine-containing phenoloid, named capitulatin A, has been isolated from the rhizomes of Curculigo capitulata. Its structure was established as 2,4-dichloro-3-methyl-5-hydroxy-6-methoxylphenol-beta-D-xylopyranosyl (1 --> 6)-beta-D-glucopyranoside (1) on the basis of the spectral data and chemical evidence.


MR imaging of the thoracic inlet.
The thoracic inlet serves as the junction between the neck and the chest. As such, it is sometimes considered a sort of "no-man's-land" between the well-defined and comfortable territories of the thoracic radiologist and that of the head and neck radiologist. Crucial digestive, respiratory, vascular, lymphatic, and neural structures traverse the thoracic inlet. Endocrine structures also are in close proximity to, and sometimes extend into, the thoracic inlet. Familiarity with the normal anatomy of the thoracic inlet on routine chest or neck imaging, and on dedicated high-resolution examinations of such areas as the brachial plexus, is critical for detection and characterization of pathologic conditions.


Four new species of the genus Thoracophorus Motschulsky, 1857 for the Neotropical region (Coleoptera: Staphylinidae: Osoriinae).
Four new species of the genus Thoracophorus Motschulsky, 1857 of the Neotropical region are described: T. verhaaghi n. sp., T. zicsii n. sp., T. struyvei n. sp., and T. perplexus n. sp. The new species originate from French Guiana, Peru, and Ecuador. Similar species T. filum Sharp, 1887, T. proximus Irmler, 1985, T. exilis (Erichson, 1840) and T. aequalis Sharp, 1887 are compared to discuss differences between them and the newly described species and their known distribution.


Sex attractant of sugar beet wireworm: identification and biological activity.
The sex attractant produced by adult females of the sugar beet wire-worm, Limonius californicus (Mannerheim) has been isolated and identified as valeric acid. In the laboratory, male wireworm beetles are repelled by the pure attractant but are drawn with intense sexual excitement to its dilute solutions; in the field, male beetles are lured from a distance of 12 meters. The pheromone occurs in unusually large amounts in the female's body.


Effectiveness and Long-Acting of the Hyaluronic Acid Injected into the Nasolabial Fold Measured Through Magnetic Resonance Imaging.
MRI analyzed quantitatively the HA injected into the NLF subcutaneous fat to correlate the gel diffusion and degradation with the morphological changes of the NLF appearance for twelve months. Measurements of the gel diffusion and degradation were taken by MRI as parameters to assess the clinical efficacy and long-acting of the HA in NLF rejuvenation. HA was applied into the superficial compartment of the subcutaneous fat of twenty NLFs. Each NLF received three injection points, from the nasal ala toward the oral commissure, 1.0-1.5 cm distant from each other, according to the NLF length. A bolus injection technique without retrograde backflow applied per injection point 0.15-0.20 ml of HA for moderate. NLF and 0.20-0.25 ml for severe NLF. Patients were evaluated through MRI and clinically twenty-four hours, one month and twelve months after the HA application. MRI, in T2-weighted, displayed the gel as a dense, spindle-shaped nodule as pattern of the gel diffusion, measuring its largest longitudinal and transverse axes. Twenty-four hours after HA application the longitudinal axis measured 1.79 cm, after one month 2.33 cm and at month twelve 0.91 cm. The transverse axis measured 0.92 cm at 24 hours, 1.13 cm after one month and 0.47 cm at month twelve. Despite reduction in size and denseness of the spindle-shaped nodule, the small amount of gel presenting into the subcutaneous fat after twelve months of the application evidenced the HA efficacy and long-acting in NLF rejuvenation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .


Changes in cerebral blood oxygenation induced by active standing test in children with POTS and NMS.
Orthostatic dysregulation (OD) has been classified into subtypes by heart rate and blood pressure; however, the hemodynamics of brains have not yet been revealed. Therefore, we investigated changes in cerebral blood flow and oxygenation during an active standing test to clarify the pathophysiology of two subtypes: postural tachycardia syndrome (POTS) and neurally mediated syncope (NMS). We studied 31 children (15 boys, 16 girls; mean age, 14.0 ± 1.7 years) who presented with OD at the Department of Pediatrics and Child Health, Nihon University School of Medicine between 2009 and 2011. OD was diagnosed using the Japanese clinical guidelines for juvenile orthostatic dysregulation. After a 10-min resting period in the supine position, patients were asked to quickly stand up and keep upright for 10 min. Cerebral blood flow and cerebral oxygenation were measured using transcranial Doppler sonography and near-infrared spectroscopy. POTS showed a significant decrease of oxy-Hb and resistance index (RI), suggesting transient ischemia with maintainable cerebral autoregulation. NMS showed a decrease of oxy-Hb and an increase of RI, suggesting ischemia and impairment of autoregulation.


A potential misdiagnosis in the COVID-19 pandemic era: a case report of superimposed thrombosis or tumor recurrence.
The clinical manifestations of coronavirus disease 2019 (COVID-19) overlap with those of other disorders, especially cardiovascular disease. We herein describe a 58-year-old woman who presented with syncopal episodes and dyspnea on exertion with a left atrial (LA) mass, scheduled for surgical removal and mitral valve replacement. Nearly 3 months later, the patient developed dyspnea, fever, and a sore throat, resulting in hospital admission with suspected COVID-19. During the diagnostic evaluation, a larger LA mass was detected. The mass seemed to be a COVID-19-induced organized thrombus with prosthetic mitral valve malfunction. Resection was, therefore, planned. An immunohistochemistry study revealed a liposarcoma. The unusual early recurrence of liposarcomas and the misdiagnosis with COVID-19-induced thrombosis are the hallmark of the present case.


Procedural Time and Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention.
Chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) can be lengthy procedures. We sought to investigate the effect of procedural time on CTO PCI outcomes. We examined the procedural time required for the various steps of CTO PCI in 6,442 CTO PCIs at 40 US and non-US centers between 2012 and 2022. The mean and median procedure times were 129 ± 76 and 112 minutes, respectively, with no significant change over time. The median times from access to wire insertion, guidewire manipulation time, and post crossing were 20, 32, and 53 minutes, respectively. Lesions crossed in <30 minutes were less complex, as reflected by lower Japanese CTO score (1.89 ± 1.19, p <0.001) than lesions that were not successfully crossed (2.88 ± 1.22) and lesions that were crossed in ≥30 minutes (2.85 ± 1.13). The likelihood of successful crossing if crossing was not achieved after 30, 90, and 180 minutes were a 76.7%, 60.7%, and 42.7%, respectively. The parameters independently associated with ≥30 minutes guidewire manipulation time in patients with a primary antegrade approach included left anterior descending target vessel, proximal cap ambiguity, blunt/no stump, occlusion length, previous failed attempt, medium/severe calcification, and medium/severe tortuosity. The mean duration of CTO PCI is approximately 2 hours (∼20% of time for access to wire insertion, ∼30% wire manipulation time, and ∼50% postwiring time). Guidewire crossing time was shorter in less complex lesions and in cases without complications.


Exploring bioactive peptides as potential therapeutic and biotechnology treasures: A contemporary perspective.
In preceding years, bioactive peptides (BAPs) have piqued escalating attention owing to their multitudinous biological features. To date, many potential BAPs exhibiting anti-cancer activities have been documented; yet, obstacles such as their safety profiles and consumer acceptance continue to exist. Moreover, BAPs have been discovered to facilitate the suppression of Coronavirus Disease 2019 (CoVID-19) and maybe ideal for treating the CoVID-19 infection, as stated by published experimental findings, but their widespread knowledge is scarce. Likewise, there is a cornucopia of BAPs possessing neuroprotective effects that mend neurodegenerative diseases (NDs) by regulating gut microbiota, but they remain a subject of research interest. Additionally, a plethora of researchers have attempted next-generation approaches based on BAPs, but they need scientific attention. The text format of this critical review is organized around an overview of BAPs' versatility and diverse bio functionalities with emphasis on recent developments and novelties. The review is alienated into independent sections, which are related to either BAPs based disease management strategies or next-generation BAPs based approaches. BAPs based anti-cancer, anti-CoVID-19, and neuroprotective strategies have been explored, which may offer insights that could help the researchers and industries to find an alternate regimen against the three aforementioned fatal diseases. To the best of our knowledge, this is the first review that has systematically discussed the next-generation approaches in BAP research. Furthermore, it can be concluded that the BAPs may be optimal for the management of cancer, CoVID-19, and NDs; nevertheless, experimental and preclinical studies are crucial to validate their therapeutic benefits.


Nasal or oral oil application on infants: a possible risk factor for adult bronchiectasis.
Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into the nose or throat as part of an old custom. We performed a case-control study to test the hypothesis, that this ancient tradition may be a predisposing factor to bronchiectasis. A case group of 59 patients with bronchiectasis and three control groups -46 patients with COPD, 32 asthmatics, and 71 healthy Saudis-were questioned about possible risk factors of bronchiectasis including nasal or oral application of oil/butter at infancy. The risk of witnessed exposure to this old folk remedy was significantly higher among the cases than the controls (OR = 3.9 (1.7-8.8), (95% confidence interval) p < 0.001). Application of oil or butter into the nasal or oral cavity of infants may be a risk factor for bronchiectasis.


Imaging the dopamine uptake site with ex vivo [18F]GBR 13119 binding autoradiography in rat brain.
We studied the binding of [18F]GBR 13119 (1-[[(4-[18F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine) to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum greater than nucleus accumbens = olfactory tubercle greater than substantia nigra = ventral tegmental area greater than other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site. Unilateral 6-hydroxy-dopamine lesions of dopamine neurons caused a marked decrease in striatal and nigral binding on the side of the lesion. We conclude that intravenous injection of [18F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.


Installation of an aryl boronic acid function into the external section of N-aryl-oxazolidinones: Synthesis and antimicrobial evaluation.
N-aryl-oxazolidinones is a prominent family of antimicrobials used for treating infections caused by clinically prevalent Gram-positive bacteria. Recently, boron-containing compounds have displayed intriguing potential in the antibiotic discovery setting. Herein, we report the unprecedented introduction of a boron-containing moiety such as an aryl boronic acid in the external region of the oxazolidinone structure via a chemoselective acyl coupling reaction. As a result, we accessed a series of analogues with a distal aryl boronic pharmacophore on the oxazolidinone scaffold. We identified that a peripheric linear conformation coupled with freedom of rotation and no further substitution on the external aryl boronic ring, an amido linkage with hydrogen bonding character, in addition to a para-relative disposition between boronic group and linker, are the optimal combination of structural features in this series for antimicrobial activity. In comparison to linezolid, the analogue comprising all those features, compound 20b, displayed levels of antimicrobial activity augmented by an eight-fold to a thirty-two-fold against a panel of Gram-positive strains, and a near one hundred-fold against Escherichia coli JW5503, a Gram-negative mutant strain with a defective efflux capability.


Synthesis, toxicological, and pharmacological assessment of derivatives of 2-aryl-4-(3-arylpropyl)morpholines.
The synthesis of nine original morpholine derivatives, i.e. 2-aryl-4-(3-arylpropyl)morpholines, is described. The structure of all synthesised derivatives was proved by IR and 1H-NMR, and some of them by 13C-NMR. Acute toxicity studies of the compounds were performed on mice. A comparative pharmacological study of the in vivo effects on the central nervous system was undertaken using the screening tests: hexobarbital induced sleeping time: locomotor activity; and behaviour despair (for antidepressive activity). The most active compound 4-(2-benzoylethyl)-2-phenyl-3-methyl) morpholine 4e was studied for MAO-A and MAO-B inhibition in vitro in rat brain mitochondria preparations.


Intra-operative monitoring in scoliosis surgery with multi-pulse cortical stimuli and desflurane anesthesia.
Prospective, observational study. Country General Hospital, Singapore. Intraoperative monitoring (IOM) with motor-evoked potentials (MEPs) assesses the integrity of cortical spinal tracts during scoliosis surgery. MEPs are sensitive to the effects of inhalational anesthetic agents. We evaluate the use of desflurane in combination with multipulse cortical stimulation in this study. In all, 10 consecutive neurologically normal subjects underwent scoliosis surgery with desflurane anesthesia (0.5 maximum alveolar concentration) and five pulse cortical stimulation (250 Hz) from two stimulators in parallel configuration, delivering a maximum intensity of 160 mA. Consistent MEPs were obtained from the abductor hallucis and tibialis anterior in nine of ten and five of five of subjects, respectively. Baseline coefficients of variations were below 16% for both muscles. This combination of anesthetic and stimulation protocols is efficacious for IOM during spinal cord surgery. Our findings support the use of desflurane for successful acquisition of MEPs during scoliois surgery as an alternative anesthetic regime.


Outcomes of granulocyte colony-stimulating factor use in pediatric kidney transplant recipients: A Pediatric Nephrology Research Consortium study.
Neutropenia is common in the first year after pediatric kidney transplant and is associated with an increased risk of infection, allograft loss, and death. Granulocyte colony-stimulating factor (G-CSF) increases neutrophil production, but its use in pediatric solid organ transplant recipients remains largely undescribed. We performed a multicenter retrospective cohort study of children with neutropenia within the first 180 days after kidney transplant. Multivariable linear regression and Poisson regression were used to assess duration of neutropenia and incidence of hospitalization, infection, and rejection. Of 341 neutropenic patients, 83 received G-CSF during their first episode of neutropenia. Median dose of G-CSF was 5 mcg/kg for 3 (IQR 2-7) doses. G-CSF use was associated with transplant center, induction immunosuppression, steroid-free maintenance immunosuppression, hospitalization, and decreases in mycophenolate mofetil, valganciclovir, and trimethoprim-sulfamethoxazole dosing. Absolute neutrophil count nadir was also significantly lower among those treated with G-CSF. G-CSF use was not associated with a shorter duration of neutropenia (p = .313) and was associated with a higher rate of neutropenia relapse (p = .002) in adjusted analysis. G-CSF use was associated with a decreased risk of hospitalization (aIRR 0.25 (95%CI 0.12-0.53) p < .001) but there was no association with incidence of bacterial infection or rejection within 90 days of neutropenic episode. G-CSF use for neutropenia in pediatric kidney transplant recipients did not shorten the overall duration of neutropenia but was associated with lower risk of hospitalization. Prospective studies are needed to determine which patients may benefit from G-CSF treatment.


Kindling in the deep prepyriform cortex of the rat.
Rats were electrically kindled in deep prepyriform cortex (DPC) and in immediately surrounding areas, pyriform cortex, and the basolateral amygdala in an effort to identify an area of the basal forebrain crucially involved in epileptogenesis and the kindling of seizures. Picomolar quantities of carbachol were also microinjected into DPC. All of these areas kindled at equivalent rates. Injection of picomolar quantities of carbachol failed to evoke epileptiform spiking, but injection of nanomolar quantities of carbachol usually evoked epileptiform spiking. Bilateral radiofrequency lesions of the DPC did not affect the rate of electrical kindling of the basolateral amygdala. We conclude that the DPC kindles readily at a rate that is similar to that of surrounding basal forebrain tissue and that the integrity of the DPC is not necessary for basolateral amygdaloid kindling.


Postoperative oxygenation assessed by SpO2/FiO2 ratio and respiratory complications after reversal of neuromuscular block with Sugammadex or neostigmine: A retrospective cohort study.
Residual neuromuscular block may lead to postoperative muscle weakness, inadequate oxygenation, and other pulmonary complications. Sugammadex may provide more rapid and effective restoration of neuromuscular function than neostigmine. We therefore tested the primary hypothesis that noncardiac surgical patients given sugammadex oxygenate better during initial recovery than those given neostigmine. Secondarily, we tested the hypothesis that patients given sugammadex have fewer pulmonary complications during hospitalization. Retrospective cohort analysis. Postoperative recovery area of a tertiary care hospital. Adults who had non-cardiothoracic surgery and were given either neostigmine or sugammadex. None. The primary outcome was the lowest SpO2/FiO2 ratio in the post-anesthesia care unit. The secondary outcome was a composite of pulmonary complications. Among 71,457 cases, 10,708 (15%) were given sugammadex and 60,749 (85%) received neostigmine. After propensity weighting, the mean minimum SpO2/FiO2 ratio was 301 ± 77 (SD) in patients given sugammadex and 303 ± 71 in those given neostigmine, yielding an estimated difference in means of -3.5 (95% confidence interval: -5.3, -1.7; P = 0.0002). 4.4% of patients given sugammadex and 3.6% of patients given neostigmine had postoperative pulmonary complications (P = 0.0005, number-needed-to-be-exposed =136; 95% CI: 83, 330), with the main contributing components being new bronchospasm or exacerbation of obstructive pulmonary disease. Postoperative minimum SpO2/FiO2 ratio during PACU admission was similar after reversal of neuromuscular block by sugammadex and neostigmine. Reversal with sugammadex was associated with more pulmonary complications, but most were minor and of little consequence.


Connect, Engage: Televisits for Children With Asthma During COVID-19 and After.
Despite the many barriers to receiving care, children with asthma must have access to regular care and frequent follow-up visits. The usual barriers to the provision of asthma care have been made even more complicated by the current coronavirus disease 2019 pandemic. To minimize the disruption of care due to the necessary constraints dictated by coronavirus disease 2019, the televisit provides a practical solution that can assess the child's current level of symptom control, reinforce asthma education, and determine treatment options. This article provides the tools and guidelines to facilitate the implementation of successful televisits to provide uninterrupted care for children with asthma.


Economic burden of drug dependency. Social costs incurred by drug users at intake to the National Treatment Outcome Research Study.
The use of illegal drugs is seen as a major social problem. The social costs can be high. Self-report data from interviews at intake to the National Treatment Outcome Research Study (NTORS) for 1075 drug users and cost data from various sources were used to estimate criminal behaviour and health and addiction service costs for a 12-month period. Multivariate statistical analysis was used to analyse cost variations. Total costs for one year for the drug users amounted to over 12 million Pounds, the majority attributable to self-reported criminal behaviour. Social costs were positively related to a variety of factors including instability in living circumstances, amount of heroin used and whether or not drugs were taken intravenously. The study clearly demonstrates the economic and social burden associated with heavy drug users and highlights the need for further investigations into the costs and benefits of policies that can reduce these social costs.


The turgor sensor KdpD of Escherichia coli is a homodimer.
Escherichia coli responds to K+-limitation or high osmolarity by induction of the kdpFABC operon coding for the high affinity K+-translocating KdpFABC complex. Expression of the corresponding operon is controlled by the membrane-bound sensor kinase KdpD and the cytoplasmic response regulator KdpE. Here, we examine the oligomeric state of KdpD. KdpD-His673-->Gln and KdpD-Asn788-->Asp are kinase inactive. When the corresponding genes are coexpressed, the resulting KdpD protein regains kinase activity in vitro, suggesting that the functional state of KdpD is at least a dimer and that the kinase reaction is a result of a trans-phosphorylation between two monomers. Furthermore, coexpression of kdpD-6His and kdpD-(Delta128-391) leads to stable heterooligomers that can bind to Ni-NTA agarose and that are coeluted. Purified and solubilized KdpD-6His has been electrophoresed in blue native polyacrylamide gels (BN-PAGE), and unphosphorylated and phosphorylated KdpD resulted in the same band pattern suggesting that the oligomeric state of KdpD does not change upon phosphorylation. In addition, determination of the molecular masses of KdpD-6His and KdpD-6His approximately 32P by gel filtration reveals a value of 245 kDa for both forms of the protein. The Stokes radius is determined to be 5.4 nm. Sucrose gradient sedimentation analysis of KdpD-6His results in a molecular mass of 289 kDa. The calculated molecular mass of a KdpD-6His monomer is 99.6 kDa. Considering the detergent bound to KdpD the obtained data reveal that KdpD is a homodimer and there is no change in the oligomeric state upon activation. Crosslinking experiments with single Cys KdpD molecules indicate that there is a close contact between the monomers in the transmitter as well as in transmembrane domain 1. BN-PAGE of solubilized and purified KdpD-6His devoid of Cys residues demonstrates that Cys residues do not contribute to the stabilization of the dimer.


Placenta previa: effect of age, gravidity, parity and previous caesarean section.
To study the effect of maternal age, gravidity, parity, previous abortion and previous caesarean section on placenta previa. We reviewed records of 95 women with placenta previa and compared with 190 women delivered during the same period, all delivering between 16 April 1994 and 15 May 1997. We compared maternal age, parity, gravidity, previous abortion, and previous caesarean section. Placenta previa is higher among women gravida > 4 (p < 0.002), para > 3 (p < 0.01) and previous caesarean section (p < 0.02). There is no increase in the incidence of placenta previa with increasing maternal age and previous abortion. The risk of placenta previa is increased with higher gravidity, higher parity, previous lower segment caesarean section, while increasing maternal age and previous abortion had no significant effect.


Coupled molecular and isotopic evidence for denitrifier controls over terrestrial nitrogen availability.
Denitrification removes ecologically available nitrogen (N) from the biosphere and influences both the pace and magnitude of global climate change. Disagreements exist over the degree to which this microbial process influences N-availability patterns across Earth's ecosystems. We combine natural stable isotope methods with qPCR to investigate how denitrifier gene abundance is related to variations in nitrate (NO3-) pool sizes across diverse terrestrial biomes and conditions. We analyze NO3- isotope composition (15N/14N, 18O/16O) and denitrifier gene nirS in 52 soil samples from different California ecosystems, spanning desert, chaparral, oak-woodland/savanna and forest. δ15N-NO3- correlates positively with δ18O-NO3- (P⩽0.03) and nirS abundance (P=0.00002) across sites, revealing the widespread importance of isotopic discrimination by soil denitrifiers. Furthermore, NO3- concentrations correlate negatively to nirS (P=0.002) and δ15N-NO3- (P=0.003) across sites. We also observe these spatial relationships in short-term (7-day), in situ soil-incubation experiments; NO3--depletion strongly corresponds with increased nirS, nirS/16 rRNA, and enrichment of heavy NO3- isotopes over time. Overall, these findings suggest that microbial denitrification can consume plant-available NO3- to low levels at multiple time scales, contributing to N-limitation patterns across sites, particularly in moist, carbon-rich soils. Furthermore, our study provides a new approach for understanding the relationships between microbial gene abundance and terrestrial ecosystem functioning.


Effect of continuing nursing education on nurses' attitude toward and accuracy of nursing diagnosis.
To test the effectiveness of a 12-hr educational course on nursing diagnosis, critical thinking, and clinical reasoning. This two-group, quasi-experimental study was conducted with 100 practicing nurses, 50 in each group. Attitude was measured by the Positions on Nursing Diagnosis scale. Accuracy of nursing diagnosis was measured with three valid and reliable case studies, and the Lunney scoring method. After completion, there was a significant difference in the mean attitude between control and experimental groups, and in the accuracy of nursing diagnosis. Continuing education can improve clinical reasoning, as shown by improved attitudes toward and accuracy of nursing diagnosis. Nurse educators should create educational strategies for practicing nurses to improve clinical reasoning skills.


Hepatic insulin-degrading enzyme regulates glucose and insulin homeostasis in diet-induced obese mice.
The insulin-degrading enzyme (IDE) is a metalloendopeptidase with a high affinity for insulin. Human genetic polymorphisms in Ide have been linked to increased risk for T2DM. In mice, hepatic Ide ablation causes glucose intolerance and insulin resistance when mice are fed a regular diet. These studies were undertaken to further investigate its regulatory role in glucose homeostasis and insulin sensitivity in diet-induced obesity. To this end, we have compared the metabolic effects of loss versus gain of IDE function in mice fed a high-fat diet (HFD). We demonstrate that loss of IDE function in liver (L-IDE-KO mouse) exacerbates hyperinsulinemia and insulin resistance without changes in insulin clearance but in parallel to an increase in pancreatic β-cell function. Insulin resistance was associated with increased FoxO1 activation and a ~2-fold increase of GLUT2 protein levels in the liver of HFD-fed mice in response to an intraperitoneal injection of insulin. Conversely, gain of IDE function (adenoviral delivery) improves glucose tolerance and insulin sensitivity, in parallel to a reciprocal ~2-fold reduction in hepatic GLUT2 protein levels. Furthermore, in response to insulin, IDE co-immunoprecipitates with the insulin receptor in liver lysates of mice with adenoviral-mediated liver overexpression of IDE. We conclude that IDE regulates hepatic insulin action and whole-body glucose metabolism in diet-induced obesity via insulin receptor levels.


Heart failure induced by the restrictive left ventricle due to hiatus hernia.
A 76-year-old woman presented with shortness of breath and dyspnea after the intake of meals. Chest X-ray showed pulmonary congestion and pleural effusion. Computed tomography disclosed a hiatus hernia. Echocardiography demonstrated that the motion of the posterior wall in the left ventricle (LV) was paradoxically by the hiatus hernia, although LV ejection fraction was preserved. The restriction of LV by hiatus hernia could cause heart failure and open surgical repair of the hiatus hernia was performed. Dyspnea after the intake of meals disappeared and no recurrence of heart failure was observed in the subsequent period of several years.


A model for the study of the physical behaviour of the lung-surfactant film in vitro.
A model of the alveolar air-fluid boundary was developed for a future study of the influence of several gases and gas mixtures on the surfactant film of the lung. Since the surface behaviour of the film material changed after denaturation, we had to use it in its native state. It was collected as foam during lung lavage and applied upon a hypophase of concentrated lavage fluid. This combination showed a constant physical behaviour during repeated compression and expansion of its surface. After the excess of applied material had left the surface there was hardly any change of gammamin and gammamax or of the shape of the area versus surface-tension curve (A-gamma curve) during several hours. Mean values of gammamin and gammamax were 5.5 +/- 2.0 and 55.0 +/- 2.0 dyne/cm respectively. The mean value of the hysteresis area was 847 +/- 82 dyne cm. Its shape was similar in all experiments. The stability of this model makes it useful for the intended investigations, but also seems to offer useful data for calculations in relation to the actual behaviour of lung alveolar surfactant in vivo.


Hypothalamic prostaglandin E2 receptors coupled to an adenylyl cyclase.
We show that the effect of prostaglandin (PG) E2 on luteinizing hormone-releasing hormone (LHRH) release involves a receptor-mediated process coupled to an adenylyl cyclase system. The adenylyl cyclase activity in rat hypothalamus synaptic membrane preparations was stimulated by PGE2 and this stimulation was directly related to the presence of guanine nucleotide (GTP). PGE2 specifically bound to P2 membranes from rat and porcine hypothalami with similar characteristics. Computer-fitted saturation curves provided evidence for two binding components which may be two states of the same receptor (RH and RL). Experiments with Gpp(NH)p, a non-metabolizable analogue of GTP, suggested the interconversion of RH and RL. These results may reflect different states of the ternary complex (hormone-receptor-guanine binding protein). Magnesium (Mg2+) can modify the RH and RL binding parameters, but seems to act directly on the PGE2 receptor site.


Extraterritorial hunting expeditions to intense fire scars by feral cats.
Feral cats are normally territorial in Australia's tropical savannahs, and hunt intensively with home-ranges only two to three kilometres across. Here we report that they also undertake expeditions of up to 12.5 km from their home ranges to hunt for short periods over recently burned areas. Cats are especially likely to travel to areas burned at high intensity, probably in response to vulnerability of prey soon after such fires. The movements of journeying cats are highly directed to specific destinations. We argue that the effect of this behaviour is to increase the aggregate impact of cats on vulnerable prey. This has profound implications for conservation, considering the ubiquity of feral cats and global trends of intensified fire regimes.


Comprehensive risk assessments and anesthetic management for children with osteogenesis imperfecta: A retrospective review of 252 orthopedic procedures over 5 years.
Major anesthetic risks arise in orthopedic surgeries for children with osteogenesis imperfecta, a rare genetically inherited condition presenting diverse skeletal issues. We aimed to investigate anesthetic risks, including difficult airway, hypo- and hyperthermia, blood loss, and pain, in connection with patient, anesthetic, and surgical factors. Both descriptive and inferential statistics were employed to study the anesthetic risks and their predictors. Data of 252 surgeries for 132 Chinese osteogenesis imperfecta patients aged 18 or below were retrieved from the authors' hospital between 2015 and 2019. Two thirds of the cohort were Sillence type IV patients, with types I, III, and V accounting for 7.6%, 14.4%, and 11.4%, respectively. Video and direct laryngoscopy were used. No case of difficult airway was identified. Due to a careful management strategy, intraoperative temperature varied on average between -0.38°C and +0.89°C from the initial temperature. Fifty-two and 18 cases of hyper- and hypothermia were encountered, respectively. The use of sevoflurane for maintenance resulted in a mean increase of +0.24°C [95% CI 0.05 ~ 0.42] in the maximum temperature. Massive blood losses (>20% of estimated total blood volume) were observed in 18.3% of the cases. Neither intraoperative temperature changes nor blood loss was found to be related to Sillence classification. Regional anesthesia techniques were applied to 72.6% of the cases. Ultrasound guidance was used per the judgment of anesthesiologists or when in case of difficult landmarks. The incidence of difficult regional anesthesia was low (4 out of 252). For postoperative analgesia, 154 neuraxial blocks (including 77 caudal and 77 lumbar epidural) and 29 peripheral nerve blocks were performed. Anesthesia for children with osteogenesis imperfecta undergoing complex orthopedic procedures was challenging. Proper anesthesia planning was essential for both intraoperative management and postoperative analgesia. Age, surgical duration, and use of sevoflurane for maintenance impacted the intraoperative temperature most, and massive blood loss was not uncommon. The risks for airway or regional anesthesia difficulties were low. Pain scores could be controlled to be ≤3 via multiple techniques.


High-performance liquid chromatography of N-terminal tryptophan-containing peptides with precolumn fluorescence derivatization with glyoxal.
A precolumn fluorescence derivatization method combined with high-performance liquid chromatography is described for the sensitive and selective determination of N-terminal tryptophan-containing peptides. The peptides and tryptophan were converted into fluorescent derivatives with glyoxal in a moderately acidic medium (pH 4.5). The derivatives were separated on a reversed-phase column with isocratic elution with an aqueous mobile phase composed of acetonitrile, methanol and phosphate buffer (pH 6.0), and subsequently detected by fluorimetry. The derivatization technique provided the respective N-terminal tryptophan-containing oligopeptides with single fluorescent peaks in chromatography. The detection limits for the peptides were 55-382 fmol per 100-microliters injection volume at a signal-to-noise ratio of 3. The method also allowed the facile detection of an N-terminal tryptophyl fragment in the enzyme reaction mixture of dynorphin A with trypsin.


β1-Integrin blockade prevents podocyte injury in experimental models of minimal change disease.
Activation of the focal adhesion kinase (FAK) in podocytes is involved in the pathogenesis of minimal change disease (MCD), but the pathway leading to its activation in this disease is unknown. Here, we tested whether podocyte β1 integrin is the upstream modulator of FAK activation and podocyte injury in experimental models of MCD-like injury. We used lipopolysaccharide (LPS) and MCD sera to induce MCD-like changes in vivo and in cultured human podocytes, respectively. We performed functional studies using specific β1 integrin inhibitors in vivo and in vitro, and integrated histological analysis, western blotting, and immunofluorescence to assess for morphological and molecular changes in podocytes. By ELISA, we measured serum LPS levels in 35 children with MCD or presumed MCD (idiopathic nephrotic syndrome [INS]) and in 18 healthy controls. LPS-injected mice showed morphological (foot process effacement, and normal appearing glomeruli on light microscopy) and molecular features (synaptopodin loss, nephrin mislocalization, FAK phosphorylation) characteristic of human MCD. Administration of a β1 integrin inhibitor to mice abrogated FAK phosphorylation, and ameliorated proteinuria and podocyte injury following LPS. Children with MCD/INS in relapse had higher serum LPS levels than controls. In cultured human podocytes, β1 integrin blockade prevented cytoskeletal rearrangements following exposure to MCD sera in relapse. Podocyte β1 integrin activation is an upstream mediator of FAK phosphorylation and podocyte injury in models of MCD-like injury.


Genome-wide association study reveals structural chromosome variations with phenotypic effects in wheat (Triticum aestivum L.).
Structural chromosome variations (SCVs) are large-scale genomic variations that can be detected by fluorescence in situ hybridization (FISH). SCVs have played important roles in the genome evolution of wheat (Triticum aestivum L.), but little is known about their genetic effects. In this study, a total of 543 wheat accessions from the Chinese wheat mini-core collection and the Shanxi Province wheat collection were used for chromosome analysis using oligonucleotide probe multiplex FISH. A total of 139 SCVs including translocations, pericentric inversions, presence/absence variations (PAVs), and copy number variations (CNVs) in heterochromatin were identified at 230 loci. The distribution frequency of SCVs varied between ecological regions and between landraces and modern cultivars. Structural analysis using SCVs as markers clearly divided the landraces and modern cultivars into different groups. There are very clear instances illustrating alien introgression and wide application of foreign germplasms improved the chromosome diversity of Chinese modern wheat cultivars. A genome-wide association study (GWAS) identified 29 SCVs associated with 12 phenotypic traits, and five (RT4AS•4AL-1DS/1DL•1DS-4AL, Mg2A-3, Mr3B-10, Mr7B-13, and Mr4A-7) of them were further validated using a doubled haploid population and advanced sib-lines, implying the potential value of these SCVs. Importantly, the number of favored SCVs that were associated with agronomic trait improvement was significantly higher in modern cultivars compared to landraces, indicating positive selection in wheat breeding. This study demonstrates the significant effects of SCVs during wheat breeding and provides an efficient method of mining favored SCVs in wheat and other crops.


Studies on the 'linear pattern' in renal glomeruli demonstrated with immunofluorescence.
We have experimentally induced the 'linear pattern' in immunofluorescence: the linear deposition of endogenous immunoglobulin (Ig) along the glomerular basement membrane (GBM) in rats injected with both protamine and nephrotoxic serum. This Ig was demonstrated to have no specific antibody activity against GBM or rabbit serum. Our findings could be of value in the analysis of the mechanism and pathological meaning of the 'linear pattern' of endogenous Ig in immunofluorescence.


Newly defined fracture pattern specific to Mason III radial head fractures: fracture description, management and outcomes using screw fixation.
Radial head fractures are the most common type of elbow fracture and are universally classified under the Mason classification system. Mason type III fractures are comminuted and are the most difficult to treat, generally requiring plating if possible, or more commonly arthroplasty or excision, which gives a variable outcome. We hypothesized that a new and specific fracture pattern of the radial head (Mason III) can be treated successfully with screw fixation. Six patients presented to the senior surgeon's clinic with this unusual Mason III fracture pattern. In these patients, the fracture was acute, requiring an open reduction and internal fixation with the use of three headless compression screws. Average follow-up time was 21 months. Using serial X-rays and the Broberg-Morrey elbow score, the six acute fractures were evaluated radiologically and functionally. All six patients had good to excellent results using the Broberg-Morrey scoring system. All patients showed radiological and clinical union within 3 months of injury. No patient required revision surgery or excision at a later date. We have recognized a specific type of comminuted and displaced Mason III radial head fracture that has not previously been described in the literature. This type of fracture is amenable to open reduction internal fixation with buried compression screws giving a good to excellent outcome, while avoiding the common consequences seen with a radial head excision, arthroplasty or plate fixation.


Electrophysiological effects of disopyramide phosphate during experimental myocardial ischemia.
In order to correlate the antiarrhythmic and electrophysiological effects of disopyramide phosphate during acute myocardial ischemia, we performed experiments in 17 mongrel dogs. Refractory periods obtained by the extrastimulus method and conduction times recorded from local electrograms were determined in potentially ischemic and nonischemic areas prior to, after left anterior descending coronary occlusion, and following intravenous administration of disopyramide phosphate 3 mg./Kg. Control refractory periods were similar in both nonischemic and ischemic areas. Following coronary ligation, a disparity of refractoriness of 28 msec. was induced between these two areas. After disopyramide administration, this disparity was reduced from 28 msec. to 5 msec. (p less than 0.001) after 5 to 15 minutes, and to 15 msec. (p less than 0.01) after 15 to 30 minutes. Coronary ligation prolonged conduction times by 8 msec. (p less than 0.005) in ischemic areas and disopyramide further prolonged conduction in these areas by an additional 9 msec. (p less than 0.001). A minimal and transient prolongation of conduction was present in nonischemic areas. We conclude that the differential effects exerted by disopyramide phosphate in ischemic areas may explain its suppressant action of arrhythmias of ventricular origin.


The role of lipoxygenases in epidermis.
Lipoxygenases (LOX) are key enzymes in the biosynthesis of a variety of highly active oxylipins which act as signaling molecules involved in the regulation of many biological processes. LOX are also able to oxidize complex lipids and modify membrane structures leading to structural changes that play a role in the maturation and terminal differentiation of various cell types. The mammalian skin represents a tissue with highly abundant and diverse LOX metabolism. Individual LOX isozymes are thought to play a role in the modulation of epithelial proliferation and/or differentiation as well as in inflammation, wound healing, inflammatory skin diseases and cancer. Emerging evidence indicates a structural function of a particular LOX pathway in the maintenance of skin permeability barrier. Loss-of-function mutations in the LOX genes ALOX12B and ALOXE3 have been found to represent the second most common cause of autosomal recessive congenital ichthyosis and targeted disruption of the corresponding LOX genes in mice resulted in neonatal death due to a severely impaired permeability barrier function. Recent data indicate that LOX action in barrier function can be traced back to the oxygenation of linoleate-containing ceramides which constitutes an important step in the formation of the corneocyte lipid envelope. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.


"Behavior" of the Hormonal Ensemble through the Prism of Cluster Analysis.
The serum hormone concentrations were studied in a group of male F1 (C57BL/6×DBA/2) mice in different states of food activity (satiety, 24-h food deprivation, and cognitive load against the background of food deprivation). The hormonal response depended on food activity: the content of leptin, triiodothyronine, and testosterone decreased in hungry animals, while during cognitive load (learning), we observed a decrease in the concentrations of ghrelin, leptin, thyroxine, and testosterone. The exceptions were neuropeptide Y (its concentration increased in hungry animals) and corticosterone (its level remained unchanged). The use of hierarchical cluster analysis allowed identifying functional organization of the relationships within the hormonal ensemble that underwent plastic changes depending on the state of the organism. It was shown that the hormonal ensemble was system-organized in the form of a "core" that determines stability of the system and the "field", within which functional interactions of the hormones are preserved.


Long-term effectiveness of total arch replacement for type A aortic dissection.
With recent improvements in cerebral protection during aortic arch repair, total aortic arch replacement has become an accepted surgical method for acute type A aortic dissection involving the aortic arch. Our surgical strategy is to perform total arch replacement with a branched graft using antegrade selective cerebral perfusion for the patients with type A aortic dissection involving the aortic arch. The objective of this study is to evaluate the effectiveness of this strategy on late outcome. From October 1988 to April 2003, 46 patients underwent total arch replacement for acute type A dissection involving the aortic arch. Operations were performed with hypothermic cardiopulmonary bypass, antegrade selective cerebral perfusion during the arch repair, and open distal anastomosis. Hospital mortality was 6.5% (3 patients), and permanent neurologic dysfunction was observed in 1 patient. During the follow-up period (mean, 5.4 years; range, 13 months to 15.6 years), 2 patients died, but the causes were not related to the aorta or aortic valve. Survival rates at 5 and 10 years postoperatively were 89.6% +/- 5.2% and 82.7% +/- 8.2%, respectively. Of the 41 survivors, 3 patients underwent successful reoperation for the distal thoracic aorta. Freedom from reoperation was 93.6% +/- 4.6% and 88.7% +/- 6.5% at 5 and 10 years, respectively. The residual false lumen in the thoracic aorta was frequently thrombosed (76.2%). Total arch replacement for acute type A dissection may decrease the risk of late complications related to the false lumen and lead to excellent long-term survival.


(S)-Alanine ethyl ester tetra-cyanidoborate, (C5H12NO)[B(CN)4].
The title mol-ecular salt, C5H12NO+·C4BN4 - or (C5H12NO)[B(CN)4], was obtained as single crystals by slow evaporation of a solution of the compound in aceto-nitrile over several weeks. The asymmetric unit contains two (S)-alanine ethyl ester cations and two tetra-cyanidoborate anions, which are linked by N-H⋯N hydrogen bonds. The compound exhibits a relatively low melting point of 110°C and shows a solid-solid phase transition near room temperature (T s-s = 29°C) on the basis of DSC measurements.


TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells.
Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity.


Resource limitation of tephritid flies on lesser burdock, Arctium minus (Hill) Bernh. (Compositae).
The intensity of resource exploitation by phytophagous insects is usually considered to reflect population size. For populations of two flowerhead-attacking tephritid flies, however, the resources utilised were not related to the numbers of searching adults. Tephritis bardanae Schrank attacked 11-13% of the total flowerheads each year, and Cerajocera tussilaginis (Fab) 17-65%, despite much wider and uncorrelated variation in adult numbers. Analysis of field data showed that the proportion of flowerheads used was not limited by poor flowerhead quality, but was restricted by (1) the synchronisation of adult activity with the appearance of flowerheads at the correct age for oviposition, and (2) by factors which influenced the ability of female flies to locate available heads. These restrictions were more severe in T. bardanae and explained its relatively low rate of infestation. Both tephritids tended to avoid flowerheads in open areas. The processes governing resource exploitation in each tephritid operated independently of the other, and a partial separation of the two species between flowerhead types and habitats arose simply because of their different timing of attack.


Development and validation of a sensitive and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of quetiapine and its active metabolite norquetiapine in human plasma.
Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia, acute mania, and acute bipolar depression. The antidepressive response is considered to be mediated by the metabolite norquetiapine (N-desalkylquetiapine), and the aim of this study was to develop an LC-MS/MS method to measure concentrations of these compounds in human plasma. Following one step liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a Sunfire C18 column (50mm×2.1mm, 5μm). The retention times were 2.12, 2.24, 2.12 and 2.19min for quetiapine, norquetiapine and their respective stable labeled internal standards, respectively. Cycle time was 4min. Selected reaction monitoring (SRM) in positive ion mode was used for quantitation. The present method exhibited a linear dynamic range of 0.5-500ng/ml for quetiapine and 0.6-600ng/ml for norquetiapine. The applicable range was extended by dilution up to 5-fold with blank matrix. The accuracy and precision for quetiapine were <103.0% and 8.8%, for norquetiapine were <108.8% and 11.1%, respectively. A rapid, sensitive, and robust LC-MS/MS method for quantifying quetiapine and its metabolite norquetiapine levels in human plasma was validated and successfully applied to samples from schizophrenic patients in clinical pharmacokinetics studies.


Biogenesis of secretory immunoglobulin M requires intermediate non-native disulfide bonds and engagement of the protein disulfide isomerase ERp44.
Antibodies of the immunoglobulin M (IgM) class represent the frontline of humoral immune responses. They are secreted as planar polymers in which flanking µ2 L2 "monomeric" subunits are linked by two disulfide bonds, one formed by the penultimate cysteine (C575) in the tailpiece of secretory µ chains (µs tp) and the second by C414 in the Cµ3. The latter bond is not present in membrane IgM. Here, we show that C575 forms a non-native, intra-subunit disulfide bond as a key step in the biogenesis of secretory IgM. The abundance of this unexpected intermediate correlates with the onset and extent of polymerization. The rearrangement of the C-terminal tails into a native quaternary structure is guaranteed by the engagement of protein disulfide isomerase ERp44, which attacks the non-native C575 bonds. The resulting conformational changes promote polymerization and formation of C414 disulfide linkages. This unusual assembly pathway allows secretory polymers to form without the risk of disturbing the role of membrane IgM as part of the B cell antigen receptor.


The bovine pericardial xenograft: I. Effect of fixation in aldehydes without constraint on the tensile viscoelastic properties of bovine pericardium.
Tensile testing of tissue strips has been used to examine the effect of simple fixation in glutaraldehyde and formaldehyde on the viscoelastic properties of bovine pericardium. To assess tissue anisotropy, tissue strips were cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees relative to the base-to-apex direction. Fresh anterior pericardium was modestly anisotropic, being least extensible in the base-to-apex direction; however, fixation removed this anisotropy. Fixation also produced a marked change in the response of the material to initial cyclic loading during preconditioning. Overall extensibility of the fixed material was significantly greater than that for the fresh tissue, consistent with a 10.7% shrinkage in aldehydes calculated from strain at fracture data. Reductions in stress relaxation and creep after fixation were noted as well, consistent with intrafibrillar crosslinking. Cyclic hysteresis and ultimate tensile strength were unaffected. Since the observed changes in the stress-strain response were largely attributable to shrinkage, control of shrinkage by physical means would allow for engineering modification of bovine pericardial mechanics for controlled anisotropy.


Autonomic dysfunction: Diagnosis and management.
The autonomic nervous system is designed to maintain physiologic homeostasis. Its widespread connections make it vulnerable to disruption by many disease processes including primary etiologies such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, and pure autonomic failure and secondary etiologies such as diabetes mellitus, amyloidosis, and immune-mediated illnesses. The result is numerous symptoms involving the cardiovascular, gastrointestinal, and urogenital systems. Patients with autonomic dysfunction (AUD) often have peripheral and/or cardiac denervation leading to impairment of the baroreflex, which is known to play a major role in determining hemodynamic outcome during orthostatic stress and low cardiac output states. Heart rate and plasma norepinephrine responses to orthostatic stress are helpful in diagnosing impairment of the baroreflex in patients with orthostatic hypotension (OH) and suspected AUD. Similarly, cardiac sympathetic denervation diagnosed with MIBG scintigraphy or 18F-DA PET scanning has also been shown to be helpful in distinguishing preganglionic from postganglionic involvement and in diagnosing early stages of neurodegenerative diseases. In this chapter, we review the causes of AUD, the pathophysiology and resulting cardiovascular manifestations with emphasis on the diagnosis and treatment of OH.


Quantitative brain lesion distribution may distinguish MOG-ab and AQP4-ab neuromyelitis optica spectrum disorders.
Antibodies to myelin oligodendrocyte glycoprotein (MOG-ab) and antibodies to aquaporin-4 (AQP4-ab) have been suggested to play roles in commonly separated subsets of patients with neuromyelitis optica spectrum disorder (NMOSD) phenotypes. The aim of this study is to quantitatively delineate and compare the brain lesion distributions of AQP4-ab-positive and MOG-ab-positive patients. Fifty-seven and twenty-eight clinical MRI scans were collected from fifty-two AQP4-ab-positive and twenty-four MOG-ab-positive patients, respectively. T2 lesions were segmented manually on each axial FLAIR image. Probabilistic lesion distribution maps were created for each group after spatial normalization. Lobe-wise and voxel-wise quantitative comparisons of the two distributions were performed. A classification model based on the lesion distribution features was constructed to differentiate the two patient groups. Infratentorial and supratentorial brain lesions were found in both AQP4-ab-positive and MOG-ab-positive patients, with large inter-group overlap mainly in deep white matter (WM). In comparison with those in the AQP4 group, the brain lesions of the MOG-ab-positive patients had a larger size, dispersed distribution, and higher probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in temporal, sublobar, frontal, and parietal lobes. The area under the receiver operating characteristic curve of the lesion-distribution-based classification model was 0.951. MOG-ab-positive and AQP4-ab-positive groups showed similar but quantitatively different brain lesion distributions. These results may help clinicians in considering MOG versus AQP4 in initial diagnosis, and add rationale for sending corresponding serologic testing. • Brain lesion distributions of AQP-ab-positive and MOG-ab-positive NMOSD patients • Larger size, dispersed distribution, higher lesion probabilities in the cerebellum, pons, midbrain, and GM and juxtacortical WM in the MOG group • The lesion-distribution-based classification model differentiates the two groups with AUC = 0.951.


An assessment of the behavior of sexually abused and nonsexually abused children with anatomically correct dolls.
The behaviors of two groups of children were observed and recorded in their play with anatomically correct dolls. One group had been determined to have been sexually abused and the other group had not been determined to have been sexually abused. The findings show that significantly more children who had been sexually abused demonstrated sexual behavior(s) with the anatomically correct dolls than did the group of children who had not been sexually abused. These findings suggest that anatomically correct dolls are a useful instrument in sexual abuse investigations.


A comparative trial of haematinic supplements in pregnancy.
Four haematinic supplements--Slow-Fe, FGF, Ferro-Gradumet and Ferro-Grad tfolic--were prospectively studied in 103 healthy pregnant patients. Significant differences in the mean cell counts, haematocrit values, haemoglobin levels, iron-binding capacities and serum folate levels were noted. The changes paralleled the elemental iron present in the compount. In this series, side effects principally vomiting and constipation, were more frequent in the lower dose iron group. Form both the haematological status aspect and the lack of side effects, Ferro-Grad Folic and Ferro-Gradumet were superior to both FGF and Slow-Fe (old formulation).


Binding of immunoglobulins to the major progesterone-induced proteins secreted by the sheep uterus.
We examined the binding of immunoglobulins to the uterine milk proteins, the major progesterone-induced proteins secreted by uterine endometrium of pregnant ewes. Binding was ascertained by measuring binding of 125 I-immunoglobulin to uterine milk proteins that were Western or dot-blotted to nitrocellulose or were coupled to Sepharose. The magnitude of binding was greatest for sheep IgM, intermediate for sheep secretory IgA, low for human secretory and serum IgA, and barely detectable for sheep IgG. Binding of IgA and IgM to uterine milk proteins was time and concentration dependent, saturable, inhibited by high ionic strength buffers, and lost due to enzymatic destruction of the Fc portion of the immunoglobulin molecule. In conclusion, the uterine milk proteins preferentially bind IgA and IgM in a species-dependent manner. Such binding may be related to the role of these proteins in the uterus and may make the uterine milk proteins a useful tool for studying or purifying sheep immunoglobulins.


Transcriptional effects of polyethylene microplastics ingestion in developing zebrafish (Danio rerio).
Over the last few decades, plastic waste has become an increasing environmental concern as it accumulates in every environment on our planet. Though traditionally seen as a macroscopic problem (i.e., large plastic debris), plastic pollution is also evident at smaller scales. Indeed, the intentional industrial production of small plastic particles and the physical degradation of larger plastic debris have overtime resulted in an increased environmental prevalence of smaller plastic particles, including microplastics. While the effects of these small polymers on marine biota have been an important research focus, recent global surveys indicate that our freshwater lakes and rivers are also plagued by microplastics. However, despite these discoveries we currently have a limited understanding of the impact these particles may have on freshwater animals, particularly on vertebrate species. Thus, the aim of the present study was to assess the impact of high concentrations of microplastics (5 and 20 mg.L-1) on the early life stages in zebrafish, a model freshwater vertebrate model. To do this, we exposed embryonic and larval zebrafish to fluorescently labelled polyethylene microspheres for up to 14 days and assessed their microplastic content, growth, hatching and oxygen consumption rates. We then explored the molecular underpinnings of the microplastic response by RNA sequencing. Over the course of the exposure, we observed a consistent accumulation of microplastics in the gastrointestinal tract of the fish in a concentration dependent manner, but could not detect any detrimental effects of these particles on larval development, growth or metabolism. However, whole animal transcriptomics revealed that microplastics induced a transient and extensive change in larval gene expression within 48 h exposure, which largely disappeared by 14 days. However, as these transcriptional changes occurred during a critical period of larval development, we suggest that an evaluation of the potential long-term impact of these particles is warranted.


Development and testing of a synthetic oligonucleotide probe for the detection of pathogenic Yersinia strains.
A 24-base oligonucleotide probe specific for a region of the Yersinia enterocolitica virulence plasmid (pYV) associated with HEp-2 cell cytotoxicity and the Sereny reaction was constructed by using sequences flanking critical TnphoA insertions in a subcloned fragment of pYV. This probe, highly specific and sensitive for virulent yersiniae, detected pathogenic Y. enterocolitica isolates in artificially inoculated foods.


Twisted memories: Addiction-related engrams are strengthened by desire thinking.
Associative learning plays a central role in addiction by reinforcing associations between environmental cues and addiction-related information. Unsupervised learning models posit that memories are adjusted based on how strongly these representations are coactivated during the retrieval process. From a different perspective, clinical models of addiction posit that the escalation and persistence of craving may depend on desire thinking, a thinking style orienting to prefigure information about positive addiction-related experiences. In the present work, we tested the main hypothesis that desire thinking is a key factor in the strengthening of addiction-related associations. A group of adult smoking volunteers (N = 26) engaged in a period of desire thinking before performing an associative learning task in which neutral words (cues) were shown along with images (smoking-related vs. neutral context) at different frequencies. Two retrieval tests were administered, one immediately after encoding and the other after 24 h, to test how the recall of associations changed as a function of retention interval. Two control groups, smokers (N = 21) and non-smokers (N = 22), performed a similar procedure, with a neutral imagination task replacing desire thinking. Participants who engaged in desire thinking increased their performance from the first to the second retrieval test only for the most frequent smoking-related associations. Crucially, this selective effect was not observed in the two control groups. These results provide behavioral evidence in support of the idea that desire thinking plays a role in strengthening addiction-related associations. Thus, this thinking process may be considered a target for reconsolidation-based conceptualizations of, and treatments for, addiction.


Localization of immunoreactive gastrin-like cells in the alimentary tract of the ascidian Styela plicata.
The occurrence of a gastrin-like immunoreactivity in the alimentary tract of the ascidian Styela plicata has been investigated using immunocytochemical methods. Gastrin-like cells are present only in the gastric epithelium among the cell types responsible for digestion and absorption of food. The physiological role played by the ascidian gastrin-like peptides is discussed together with the evolutionary history of peptides of the gastrin/cholecystokinin family.


Hepatitis B virus infections in families in which the mothers are negative but the fathers are positive for HBsAg.
We studied a total of 37 families, in which HBsAg was positive in either or both of father and mother, to assess intra-familial transmission of hepatitis B virus (HBV). The HBsAg positive rate for children with HBsAg-negative mothers was significantly lower than that with positive mothers (4 of 31, 12.9% versus 18 of 32, 56.3%, p<0.01) of course. However, there were three families in which the infection source for children was thought to be fathers, not mothers, i.e., of eight children in these three families with HBsAg +/- father/mother pairs, 4 (50%) were positive for both HBsAg and HBV DNA of genotypes identical to those of their fathers, and another child was positive for HBcAb despite being negative for HBsAg. Interestingly, moreover, all the mothers in these three families were HBcAb-positive even though HBsAg-negative, suggesting that not only father-to-child but also inter-spouse HBV transmission might have occurred. With these findings we would suggest that all the family members with HBsAg-positive fathers should receive HBV vaccine, let alone for those with HBsAg-positive mothers.


Antibacterial and antiplaque efficacy of a lactoperoxidase-thiocyanate-hydrogen-peroxide-system-containing lozenge.
Antimicrobial agents are considered valuable adjuncts to mechanical methods of plaque control. However, their long-term use can be limited because of side effects. Therefore, using physiological substances is promising due to no risk of development, for example, of microbial resistances, allergies or DNA damaging. The lactoperoxidase-thiocyanate-hydrogen peroxide system (LPO-system) is a highly effective antimicrobial system. This study aimed to evaluate in a randomized study with a four-replicate cross-over design the effectiveness of two oral hygiene lozenges containing LPO-system in oral hygiene. After using the mouth rinse as positive control (A) and allocated test lozenges (B) (0.083% H2O2) & (C) (0.04% H2O2) for 4 days instead of the normal oral hygiene procedures (tooth brushing etc.), Listerine rinse (A) was statistically significantly more effective than the LPO-system-lozenge with 0.083% H2O2, the LPO-system-lozenge with 0.04% H2O2, and the placebo lozenge (D) in inhibiting plaque. Lozenges B and C were statistically significantly more effective than the placebo lozenge, but no statistically significant differences could be observed between them. The LPO-system-lozenge (B) reduced statistically significantly more S. mutans than the LPO-system-lozenge with (C) and the placebo lozenge (D). The LPO-system-lozenge (C) reduced statistically significantly more Lactobacilli than Listerine (A), the LPO-system-lozenge (B) and the placebo lozenge (D). There were no statistically significant differences in the total CFUs between Listerine rinse, the LPO-system-lozenge with 0.083% H2O2 (B), the LPO-system-lozenge with 0.04% H2O2 (C), and the placebo lozenge (D). On day 5 there were no differences of the OSCN--values between all A, B, C, and D. However, the SCN--values increased over the days in both LPO-system-lozenges (B/C). The statistically significant differences between B/C and A/D on day 5 were as followed: A to B p = 0.0268; A to C p = 0.0035; B to D p = 0.0051; C to D p = 0.0007. Only in the group of Listerine (A) increased the NO3-/NO2--quotient over the test time, which indicates a reduction of nitrate-reducing bacteria. On Day 5 the statistically significant difference between A and B was p = 0.0123. The results indicate that lozenges containing a complete LPO-system, inhibiting plaque regrowth and reducing cariogenic bacteria, may be used in the daily oral hygiene.


Molecular and Crystal Structure, Spectroscopy, and Photochemistry of a Dispiro Compound Bearing the Tetraoxane Pharmacophore.
The molecular structure and photochemistry of dispiro[cyclohexane-1,3'-[1,2,4,5]tetraoxane-6',2''-tricyclo[188.8.131.52,7 ]decan]-4-one (TX), an antiparasitic 1,2,4,5-tetraoxane was investigated using matrix isolation IR and EPR spectroscopies, together with quantum chemical calculations undertaken at the DFT(B3LYP)/6-311++G(3df,3pd) level of theory, with and without Grimme's dispersion correction. Photolysis of the matrix-isolated TX, induced by in situ broadband (λ>235 nm) or narrowband (λ in the range 220-263 nm) irradiation, led to new bands in the infrared spectrum that could be ascribed to two distinct photoproducts, oxepane-2,5-dione, and 4-oxohomoadamantan-5-one. Our studies show that these photoproducts result from initial photoinduced cleavage of an O-O bond, with the formation of an oxygen-centered diradical that regioselectivity rearranges to a more stable (secondary carbon-centered)/(oxygen-centered) diradical, yielding the final products. Formation of the diradical species was confirmed by EPR measurements, upon photolysis of the compound at λ=266 nm, in acetonitrile ice (T=10-80 K). Single-crystal X-ray diffraction (XRD) studies demonstrated that the TX molecule adopts nearly the same conformation in the crystal and matrix-isolation conditions, revealing that the intermolecular interactions in the TX crystal are weak. This result is in keeping with observed similarities between the infrared spectrum of the crystalline material and that of matrix-isolated TX. The detailed structural, vibrational, and photochemical data reported here appear relevant to the practical uses of TX in medicinal chemistry, considering its efficient and broad parasiticidal properties.


Environmental exposure to cadmium and renal function of elderly women living in cadmium-polluted areas of the Federal Republic of Germany.
An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium-polluted areas of the Federal Republic of Germany is associated with an increased prevalence of biological signs of kidney dysfunction in population groups non-occupationally exposed to heavy metals. The study was run in two industrial areas known to be highly contaminated by cadmium, lead and other heavy metals, viz. Stolberg and Duisburg. Düsseldorf was selected as a reference area. As a study population we selected 65- and 66-year-old women (n = 286) who had spent the major part of their lives in one of these areas. The average cadmium levels in blood (CdB) and urine (CdU) revealed significant differences in exposure to cadmium in the order Stolberg greater than Duisburg greater than Düsseldorf. Serum creatinine levels were, on average, significantly higher in the Stolberg group than in the Duisburg and Düsseldorf groups. However, with respect to the urinary excretion of low molecular weight proteins (beta 2-microglobulin, retinol-binding protein), albuminuria, total proteinuria, aminoaciduria, phosphaturia and some other biological findings, no significant differences between the study populations were noted. Similarly, the prevalence of clinically-confirmed hypertension as well as the relative frequency of hypertensive subjects (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mm Hg) did not differ significantly among the three study groups. There was no exposure-response relationship between CdU and tubular proteinuria in the range of the CdU-levels found (0.1 to 5.2 micrograms/g creatinine). However, albuminuria tended to be increased at CdU levels greater than 2 micrograms/g creatinine.


Loss of Taste and Smell as Distinguishing Symptoms of Coronavirus Disease 2019.
In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 [62%]) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive predictive value (83% [95% confidence interval [CI], 55%-95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.