Occurrence and ultrastructural localization of duck hepatitis B virus in the liver of ducks after experimental infection.
A sequential study was performed to investigate the occurrence and localization of duck hepatitis B virus in the liver of domestic ducks utilizing the indirect immunoperoxidase method and electron microscopy. Seventeen ducklings were injected intravenously with duck hepatitis B virus-positive serum within 24 hr after hatching and were subsequently sacrificed on the 2nd, 3rd, 4th, 5th, 27th and 44th day after injection. Nine ducklings were not injected and were used as a negative control. Duck hepatitis B virus DNA by spot hybridization using a [3P]-labeled probe occurred in trace amounts on the 2nd day and in large amounts on the 4th day after inoculation. Immunoreactivity for DHBV was seen in the hepatocytes, sporadically on the 2nd day and diffusely on the 4th day, and also in the biliary epithelial cells on the 27th day. Both kinds of cells revealed staining in the cytoplasm but not in the nucleus. Virus particles were recognized by electron microscopy in the hepatocytes beginning on the 4th day. The hepatocytes had many incomplete virus particles, 40 to 61 nm in diameter, and a few complete virus particles, 40 nm in diameter, in the cisternae of the rough and smooth endoplasmic reticula. Such particles and the endoplasmic reticulum showed reaction products for duck hepatitis B virus by immunoelectron microscopy. There were clusters of core particles, 27 nm in diameter, in the hyaloplasm around peroxisomes where an assembly of cores appeared to occur. No conspicuous virus particles were recognized in the biliary epithelial cells. The similarities and differences in virus localization between duck hepatitis B virus and hepatitis B virus are discussed.


Percutaneous microwave ablation of stage I medically inoperable non-small cell lung cancer: clinical evaluation of 47 cases.
To retrospectively evaluate safety and effectiveness of CT-guided percutaneous microwave ablation (MWA) in 47 patients with medically inoperable stage I peripheral non-small cell lung cancer (NSCLC). From February 2008 to October 2012, 47 patients with stage I medically inoperable NSCLC were treated in 47 MWA sessions. The clinical outcomes were evaluated. Complications after MWA were also summarized. At a median follow-up period of 30 months, the median time to the first recurrence was 45.5 months. The local control rates at 1, 3, 5 years after MWA were 96%, 64%, and 48%, respectively. The median cancer-specific and median overall survivals were 47.4 and 33.8 months. The overall survival rates at 1, 2, 3, and 5 years after MWA were 89%, 63%, 43%, and 16%, respectively. Tumors ≤3.5 cm were associated with better survival than were tumors >3.5 cm. The complications after MWA included pneumothorax (63.8%), hemoptysis (31.9%), pleural effusion (34%), pulmonary infection (14.9%), and bronchopleural fistula (2.1%). MWA is safe and effective for the treatment of medically inoperable stage I peripheral NSCLC.


Collision-based spiral acceleration in cardiac media: roles of wavefront curvature and excitable gap.
We have previously shown in experimental cardiac cell monolayers that rapid point pacing can convert basic functional reentry (single spiral) into a stable multiwave spiral that activates the tissue at an accelerated rate. Here, our goal is to further elucidate the biophysical mechanisms of this rate acceleration without the potential confounding effects of microscopic tissue heterogeneities inherent to experimental preparations. We use computer simulations to show that, similar to experimental observations, single spirals can be converted by point stimuli into stable multiwave spirals. In multiwave spirals, individual waves collide, yielding regions with negative wavefront curvature. When a sufficient excitable gap is present and the negative-curvature regions are close to spiral tips, an electrotonic spread of excitatory currents from these regions propels each colliding spiral to rotate faster than the single spiral, causing an overall rate acceleration. As observed experimentally, the degree of rate acceleration increases with the number of colliding spiral waves. Conversely, if collision sites are far from spiral tips, excitatory currents have no effect on spiral rotation and multiple spirals rotate independently, without rate acceleration. Understanding the mechanisms of spiral rate acceleration may yield new strategies for preventing the transition from monomorphic tachycardia to polymorphic tachycardia and fibrillation.


Identifying TNF and IL6 as potential hub genes and targeted drugs associated with scleritis: A bio-informative report.
Scleritis is a serious inflammatory eye disease that can lead to blindness. The etiology and pathogenesis of scleritis remain unclear, and increasing evidence indicates that some specific genes and proteins are involved. This study aimed to identify pivotal genes and drug targets for scleritis, thus providing new directions for the treatment of this disease. We screened candidate genes and proteins associated with scleritis by text-mining the PubMed database using Python, and assessed their functions by using the DAVID database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the functional enrichment of these genes and proteins. Then, the hub genes were identified with CytoHubba and assessed by protein-protein interaction (PPI) network analysis. And the serum from patients with active scleritis and healthy subjects were used for the validation of hub genes. Finally, the DGIdb database was used to predict targeted drugs for the hub genes for treating scleritis. A total of 56 genes and proteins were found to be linked to scleritis, and 65 significantly altered pathways were identified in the KEGG analysis (FDR < 0.05). Most of the top five pathways involved the categories "Rheumatoid arthritis," "Inflammatory bowel disease", "Type I diabetes mellitus," and "Graft-versus-host disease". TNF and IL6 were considered to be the top 2 hub genes through CytoHubba. Based on our serum samples, hub genes are expressed at high levels in active scleritis. Five scleritis-targeting drugs were found among 88 identified drugs. This study provides key genes and drug targets related to scleritis through bioinformatics analysis. TNF and IL6 are considered key mediators and possible drug targets of scleritis. Five drug candidates may play an important role in the diagnosis and treatment of scleritis in the future, which is worthy of the further experimental and clinical study.


Predictors of outcome in children and adolescents with rhabdomyosarcoma of the trunk--the St Jude Children's Research Hospital experience.
The aim of this study was to determine predictors of outcome in childhood truncal rhabdomyosarcoma. Retrospective chart review evaluating the impact of demographic features, disease characteristics, and the extent and timing of surgical intervention on outcome was performed. Thirty-three patients with a median age of 8 years were identified. Most had advanced Intergroup Rhabdomyosarcoma Study group III (n = 13) or group IV (n = 9) disease. Primary site included 20 (61%) chest wall, 6 (21%) paraspinal, 5 (15%) periscapular, and 1 (3%) abdominal wall. Most tumors were embryonal (n = 21), larger than 5 cm (n = 27), and locally invasive (n = 13); 7 had positive nodes. Tumor size, nodal status, and gross total tumor resection (upfront or delayed) were significant predictors of event-free and overall survival. Tumors 5 cm or smaller were amenable to upfront surgical resection (P = .007). In patients with tumors larger than 5 cm, resection at any time was associated with a 10-year overall survival 57% +/- 13% compared with 8% +/- 5% in those who had no surgery (P = .003). Tumor recurrence was local in 44% of cases, and survival after local recurrence was rare (1 of 8). Tumor size, nodal status, and gross total resection at any time are significant predictors of outcome in truncal rhabdomyosarcoma. Gross tumor excision should be the goal of surgical intervention in this disease.


Comprehensive role of thermal combined ultrasonic pre-treatment in sewage sludge disposal.
Thermal/ultrasonic pre-treatment of sludge has been proven to break the hydrolysis barriers of sewage sludge (SS) and improve the performance of anaerobic digestion (AD). In this study, the objective was to investigate whether the combination of two pre-treatment methods can achieve better results on the AD of SS. The results indicated that, compared with the control group and separate pre-treatment groups, the thermal combined ultrasonic pre-treatment presented more obvious solubilization of soluble proteins, polysaccharides, and other organic matters in SS. The combined method promoted the dissolution of protein-like substances more effectively, with biogas production increased by 19% and the volatile solid (VS) removal rate improved to above 50% compared with the control group. The capillary suction time is reduced by about 85%, which greatly improved the dewatering performance of SS. In addition, the combined method has advantages in degrading sulfonamide antibiotics, roxithromycin and tetracycline. Particularly, by analyzing the interaction between the degradation of different antibiotics and the composition of dissolved organic matters (DOMs), it was found that the composition of DOMs could affect the degradability of different antibiotics. Among them, the high content of tyrosine-like and tryptophan-like was conducive to the degradation of sulfamethoxazole, and the high content of fulvic acid-like and humic acid-like was conducive to the degradation of roxithromycin and tetracycline. This work evaluated the comprehensive effect of thermal combined ultrasonic pre-treatment on SS disposal and provided useful information for its engineering.


Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors.
Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted therapies has not been fully appreciated. Performing variant-prioritization analysis on germline DNA of 1,507 C-AYA patients with solid tumors, we show 12% of these patients carrying germline pathogenic and/or likely pathogenic variants (P/LP) in known cancer-predisposing genes (KCPG). An additional 61% have germline pathogenic variants in non-KCPG genes, including PRKN, SMARCAL1, SMAD7, which we refer to as candidate genes. Despite germline variants in a broad gene spectrum, pathway analysis leads to top networks centering around p53. Our drug-target analysis shows 1/3 of patients with germline P/LP variants have at least one druggable alteration, while more than half of them are from our candidate gene group, which would otherwise go unidentified in routine clinical care.


How do grandparents influence child health and development? A systematic review.
Grandparents are often a key source of care provision for their grandchildren, yet they are sidelined in caregiving research and policy decisions. We conducted a global, systematic review of the literature to examine the scope and quality of studies to date (PROSPERO database CRD42019133894). We screened 12,699 abstracts across 7 databases, and identified 206 studies that examined how grandparents influence child health and development. Indicators of grandparent involvement were contact, caregiving behaviors, and financial support. Our review focused on two research questions: how do grandparents influence child health and development outcomes, and what range of child outcomes is reported globally? We examined study design, sample characteristics, key findings, and outcomes pertaining to grandchildren's physical health, socio-emotional and behavioral health, and cognitive and educational development. Our search captured studies featuring grandparent custodial care (n = 35), multigenerational care (n = 154), and both types of care (n = 17). We found substantial heterogeneity in the data provided on co-residence, caregiving roles, resources invested, outcomes, and mechanisms through which "grandparent effects" are manifested. We identified two important issues, related to operationalizing indicators of grandparent involvement and conceptualizing potential mechanisms, leading to gaps in the evidence base. Currently, our understanding of the pathways through which grandparents exert their influence is constrained by limited data on what grandparents actually do and insufficient attention given to interpersonal and structural contexts. We present a conceptual framework to explicitly measure and theorize pathways of care, with a view to inform research design and policy implementation. We underscore the need for more robust data on three indicators of caregiver involvement-contact, behavior, and support-and for careful description of structural and interpersonal contexts in caregiving research.


Urology in Undergraduate Medical Education.
Urology is an essential topic in undergraduate medical education (UME). The objective of this article is to review the current state of exposure to urology in medical school, to discuss why it is critical to maintain a urology curriculum, and to review methods in establishing an effective curriculum for all students with limited resources. UME curriculum in urology should be geared toward the widest group of students, namely those entering primary care or internal medicine, where patients with urologic complaints are most likely to first present. Hands-on teaching should focus on skills such as the genitourinary exam and Foley catheter placement, while ancillary modules should be utilized for complex concepts. Medical schools do not sufficiently incorporate didactics in urology as part of their core curriculum. As such, educators in urology must develop curricula that provide fundamental knowledge to all students, especially those pursuing non-urologic specialties who will undoubtedly treat patients with urologic complaints.


Effect of low calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus muscle.
The mechanisms controlling the reorganisation of synaptic inputs to developing skeletal muscle fibres was studied using electrophysiological and histological methods. In the developing rat soleus muscle there is a rapid reduction of polyneuronal innervation between 9 and 12 days. Reducing the local concentration of calcium by applying chelating agents such as EGTA or BAPTA in vivo to 9-day-old rat soleus muscles over a period of 3 days slowed the rate of elimination of polyneuronal innervation. It was established that the reduction of calcium induced by EGTA or BAPTA was not sufficient to produce a detectable reduction in neuromuscular activity. The possibility that a calcium-dependent enzyme such as CANP may play a role in synapse reorganisation was therefore tested. Local application of inhibitors of calcium-activated neutral protease (CANP), leupeptin or E-64, to 9-day-old rat soleus muscles over 3 days had similar effects to those of EGTA or BAPTA, i.e. the elimination of polyneuronal innervation that usually takes place was much slower. Since the inhibition of thiol proteases had similar effects on synapse elimination as a reduction of calcium concentration, it is concluded that CANP is important in the reorganisation of the developing neuromuscular junction.


Oral Misoprostol for Induction of Labour in Term PROM: A Systematic Review.
To assess the efficacy of oral misoprostol for induction of labour (IOL) in the context of term pre-labour rupture of membranes (TPROM), and to assess pregnancy outcomes following the administration of oral misoprostol. A systematic literature search was performed using Ovid Medline, Embase, PubMed, and the Cochrane Database of Systematic Reviews. Eligible studies were quasi-experimental trials or randomized controlled trials involving the use of oral misoprostol in singleton cephalic term pregnancies with confirmed rupture of membranes and no spontaneous labour at the time of membranes rupture, in mothers with no contraindications to vaginal delivery. Studies were excluded if they utilized vaginal misoprostol, excluded primigravid participants, or if the full text of the article was not accessible in English. Data were extracted by two reviewers using a standardized data extraction form. Study quality was assessed using the modified Jadad score. Twelve randomized controlled trials that included 1489 singleton pregnancies were included. Doses of oral misoprostol ranged from 20 to 200 μg. The incidence of vaginal birth ranged from 73.0%-95.0% in the oral misoprostol group compared with 52.4%-94% in the control group. Hyperstimulation was infrequent, ranging from 0% to 13.8% in the oral misoprostol group compared with 0%-24% in the control group. Two trials, involving a total of 144 women that compared 50 μg of oral misoprostol every 4 hours versus expectant management followed by PGE2 gel showed a higher incidence of vaginal birth with misoprostol (pooled risk ratio 1.33, 95% confidence interval 1.10-1.61). Oral misoprostol appears to be a safe and effective for IOL in TPROM. However, the varying administration, dose, and frequency reported in the literature highlights the need to develop a standardized protocol for use in Canadian obstetrical practice.


Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.
Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.


"The Day I Die Is The Day I Will Find My Peace": Narratives of Family, Marriage, and Violence Among Women Living With Serious Mental Illness in India.
In India, there is limited research on the nature of familial relationships and domestic violence that women living with serious mental illness (SMI) experience. Using the self-in-relation theory and through 34 in-depth interviews, I explored narratives related to family, marriage, and violence in familial relationships among women living with SMI at a psychiatric institution in an urban city in India. These narratives are critical because they highlight how the presence of mental illness exacerbates the violence women experience. Informed by participants' narratives, I offer specific recommendations on creating gender-sensitive mental health care that is mindful of women's social realities.


Changes in morphine self-administration and morphine dependence after lesions of the caudate nucleus in rats.
Rats were trained to bar press for intravenous infusions of morphine sulfate during 1-hr daily test sessions. Small, centrally placed bilateral lesions of the caudate nucleus reduced rats of morphine self-administration to approximately one seventh of preoperative levels; postoperative rates were similar to preoperative rates when the postoperative unit infusion dose of morphine was one tenth of the preoperative dose. Caudate lesions also lowered the threshold dose at which morphine's rewarding property could be detected. Physical dependence was studied in other rats receiving a 3-day continuous infusion of morphine sulfate via implanted subcutaneous silicone reservoirs. Caudate lesions ameliorated withdrawal-induced weight loss and naloxone-induced "wet dog shakes". Both the self-administration and dependence data are consistent with the idea that morphine blocks dopaminergic transmission in the striatum.


Postnatal development of methionine-enkephalin modulation of cholinergic transmission in cat ileum.
The age-dependent effects of methionine-enkephalin (Met-enk) on contractions and [3H]-acetylcholine ([3H]-ACh) release evoked by electrical field stimulation (EFS) were studied in vitro on cat terminal ileum of young (2-month old) and adult cats. Radioactivity was measured by liquid scintillation spectrometry and the effect of Met-enk was evaluated by the FrS2/FrS1 ratio. Scopolamine, 1 microM, abolished the EFS-induced contractions. Met-enk dose dependently (0.01-1 microM) decreased the EFS-induced contractions. The inhibitory effect of Met-enk on the evoked contractions was more pronounced in adult cats compared to that in young cats. In adult animals Met-enk, 1 microM, almost completely inhibited the evoked contractions (94.6 +/- 2.6% of inhibition) while in the young cats its inhibitory effect was less pronounced (52.1 +/- 6.8%). Met-enk decreased the EFS-evoked release of [3H]-ACh by 44.6 +/- 4.6% in adult cats and by 21.6 +/- 1.6% in young cats. The data suggest opioid modulation of cholinergic transmission in cat terminal ileum at neuronal level occurring as early as the postnatal period and increasing with the ontogenesis.


Cloning and sequence of the cDNA encoding the beta 4 integrin subunit in rat peripheral nerve.
beta 4 and alpha 6 integrin subunits dimerize to form an adhesion receptor that is necessary to nucleate hemidesmosomes and to anchor epithelial cells to their basal laminae. beta 4 is also expressed in Schwann cell (which do not contain hemidesmosomes) in peripheral nerve, where it may function in the formation or maintenance of myelin. The cDNA for beta 4 integrin has been cloned from epithelia-derived human and mouse tissues. We cloned cDNAs encoding beta 4 integrin from libraries derived from rat peripheral nerve, and determined the complete nucleotide sequence encoding the signal peptide and mature protein. Comparison of the deduced amino acid (aa) sequence revealed 95.1% and 87.5% identity with the mouse and human epithelia-derived sequences, respectively. The amino acid sequence of postulated signal transduction domains in beta 4 was 100% identical among rat, mouse, and human. Our cDNA clones included two of the four postulated alternatively spliced variants previously described in epithelial clones. Despite the potentially diverse functions of beta 4 integrin in Schwann cells and keratinocytes, the cDNAs for nerve-derived beta 4 integrin are highly similar to those cloned from epithelia.


Core-shell nanoparticles as prodrugs: possible cytotoxicological and biomedical impacts of batch-to-batch inconsistencies.
Numerous samples of magnetite@silica and magnetite@silica@silane core-shell nanoparticles, previously used as prodrugs, were prepared by an experienced chemist, using the same identical equipment and the same lots of reagents. Their surface analyses showed batch-to-batch chemical variations: no two batches were found to have the same surface chemistries, showing unexpected Si-O bond scission and amine oxidation. Because the preparations used reactions recognized to be mild, and bond scission and oxidation were never previously reported for similar reactions on larger surfaces, the Fe(3)O(4) nanoparticles that form the nanoparticle core appear to have acted as catalysts for these side reactions. The intended use of these nanoparticles, as drug carriers, is discussed in terms of cytotoxicological and biomedical consequences.


Predicting outcomes in anal cancer patients using multi-centre data and distributed learning - A proof-of-concept study.
Predicting outcomes is challenging in rare cancers. Single-institutional datasets are often small and multi-institutional data sharing is complex. Distributed learning allows machine learning models to use data from multiple institutions without exchanging individual patient-level data. We demonstrate this technique in a proof-of-concept study of anal cancer patients treated with chemoradiotherapy across multiple European countries. atomCAT is a three-centre collaboration between Leeds Cancer Centre (UK), MAASTRO Clinic (The Netherlands) and Oslo University Hospital (Norway). We trained and validated a Cox proportional hazards regression model in a distributed fashion using data from 281 patients treated with radical, conformal chemoradiotherapy for anal cancer in three institutions. Our primary endpoint was overall survival. We selected disease stage, sex, age, primary tumour size, and planned radiotherapy dose (in EQD2) a priori as predictor variables. The Cox regression model trained across all three centres found worse overall survival for high risk disease stage (HR = 2.02), male sex (HR = 3.06), older age (HR = 1.33 per 10 years), larger primary tumour volume (HR = 1.05 per 10 cm3) and lower radiotherapy dose (HR = 1.20 per 5 Gy). A mean concordance index of 0.72 was achieved during validation, with limited variation between centres (Leeds = 0.72, MAASTRO = 0.74, Oslo = 0.70). The global model performed well for risk stratification for two out of three centres. Using distributed learning, we accessed and analysed one of the largest available multi-institutional cohorts of anal cancer patients treated with modern radiotherapy techniques. This demonstrates the value of distributed learning in outcome modelling for rare cancers.


Molecular aspects of UVB-induced immunosuppression.
Ultraviolet light can affect the immune system locally as well as systemically leading to an impaired resistance to neoplastic cells and/or infections. Prior to the biological effect, UVB must be absorbed by a chromophore in the skin where it will give a signal that can lead to an altered immune response in the skin or elsewhere. These altered immune responses may be constituted by alteration in among others: cytokine profile, growth factors and costimulatory signals. Several hypotheses about the identity of the photoreceptor have been put forward. One photoreceptor in the skin is urocanic acid (UCA), that can isomerize from the trans- to the cis-isomer. The cis-isomer has immunosuppressive properties. Another photoreceptor is DNA that also efficiently absorbs UV wavelengths. After absorption the structure of the DNA molecule is altered. This alteration might lead to gene activation responsible for the immunotoxic outcome (altered gene expression). It has been demonstrated that the formation of DNA photoproducts by UV light is associated with the activation of many genes. Several studies indicate that UV-induced DNA damage, in the form of cyclobutyl pyrimidine dimers plays a role in UV-induced suppression of the immune system locally as well as systemically. In mice that were injected with liposomes containing the excision repair enzyme T4 endonuclease UVB-induced dimers were removed more efficiently as compared to control mice. In these mice UV-induced immunosuppression was prevented. Pilot studies by Kripke et al. indicated that the release of IL-IO and TNF alpha that are both induced by DNA damage might be involved. In preliminary studies with mice that were deficient with respect to DNA repair lower doses of UV were needed for the induction of immunosuppression as compared to their normal littermates. These studies indicate that altered gene expression plays a pivotal role in UVB-induced immunosuppression. In addition to a role for UCA and DNA in UV-induced immunosuppression it is postulated recently that signal transduction (EGF-receptor mediated upregulation of phospholipase A2) and transcription factors (NF kappa B, p91) are involved in UV-induced immunomodulation.


Lung health in relation to hydrogen sulfide exposure in oil and gas workers in Alberta, Canada.
A study was undertaken to assess pulmonary health effects of hydrogen sulfide (H2S) exposure in a group of workers (n = 175) extracting and processing oil and natural gas in west-central Alberta. Exposure to H2S was assessed by questioning the workers about "exposures strong enough to cause symptoms," and exposures that resulted in loss of consciousness (a "knockdown"). Exposures strong enough to cause symptoms were reported by 34% of the workers. Fourteen workers (8%) reported having had a knockdown. Exposures severe enough to cause symptoms were not associated with lower spirometric values or excess symptoms. Knockdowns were not associated with lower spirometric values but were associated with statistically significant excesses of (1) shortness of breath while hurrying on the level or walking up a slight hill (OR = 3.55; 95%CI = 1.02-12.4); (2) wheeze with chest tightness (OR = 5.15; 95%CI = 1.29-20.6); and (3) attacks of wheeze (OR = 5.08; 95%CI = 1.28-20.2). The pattern of excess respiratory symptoms is consistent with bronchial hyperresponsiveness, which has been documented in studies of high-level exposure to other irritant gases. Additional study is warranted and should include assessment of bronchial reactivity.


A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease.
Both obesity and airways disease can lead to chronic hypercapnic respiratory failure, which can be managed with positive airway pressure (PAP) therapy. The efficacy of PAP has been studied in obesity hypoventilation syndrome as well as in chronic hypercapnic chronic obstructive pulmonary disease patients, but not in patients where both obesity and airway obstruction coexist. This pilot study aims to compare the efficacy of continuous positive airway pressure vs bilevel positive airway pressure spontaneous mode in the treatment of hypoventilation disorder with obesity and obstructive airways disease. We sequentially screened PAP-naïve patients with stable chronic hypercapnic respiratory failure (PaCO2 > 45 mm Hg), obesity (body mass index > 30 kg/m2), and obstructive airways disease. Participants were randomized to continuous positive airway pressure or bilevel positive airway pressure spontaneous mode treatment for 3 months. Participants were blinded to their PAP allocation. Change in awake PaCO2 was the primary endpoint. Secondary endpoints included change in lung function, daytime sleepiness, sleep quality, quality of life, PAP adherence, and neurocognitive function. A total of 32 individuals were randomized (mean ± SD: age 61 ± 11 years, body mass index 43 ± 7 kg/m2, PaCO2 54 ± 7 mm Hg, forced expiratory volume in 1 second 1.4 ± 0.6L, apnea-hypopnea index 59 ± 35 events/h). Sixteen participants in each PAP group were analyzed. Bilevel positive airway pressure yielded a greater improvement in PaCO2 compared to continuous positive airway pressure (9.4 mm Hg, 95% confidence interval, 4.3-15 mm Hg). There were no significant differences in PAP adherence, sleepiness, sleep quality, or neurocognitive function between the two therapies. Although both PAP modalities improved hypercapnic respiratory failure in this group of individuals, bilevel positive airway pressure spontaneous mode showed greater efficacy in reducing PaCO2. Registry: Australian New Zealand Clinical Trials Registry; Name: Nocturnal ventilatory support in obesity hypoventilation syndrome; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12605000096651; Identifier: ACTRN12605000096651. Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP vs bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 2022;18(1):99-107.


High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.
Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.


Adipogenic transcriptional regulation of hepatic stellate cells.
Hepatic stellate cells (HSC) undergo transdifferentiation (activation) from lipid-storing pericytes to myofibroblastic cells to participate in liver fibrogenesis. Our recent work demonstrates that depletion of peroxisome proliferator-activated receptor gamma (PPARgamma) constitutes one of the key molecular events for HSC activation and that ectopic expression of this nuclear receptor achieves the phenotypic reversal of activated HSC to the quiescent cells. The present study extends these findings to test a novel hypothesis that adipogenic transcriptional regulation is required for the maintenance of HSC quiescence. Comparative analysis of quiescent and activated HSC in culture reveals higher expression of putative adipogenic transcription factors such as CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPbeta, C/EBPdelta, PPARgamma, liver X receptor alpha, sterol regulatory element-binding protein 1c and of adipocyte-specific genes in the quiescent cells. Conversely, activated HSC have increased expression of PPARbeta, a transcription factor known to promote fatty acid oxidation. A treatment of activated HSC with the adipocyte differentiation mixture (isobutylmethylxanthine, dexamethasone, and insulin) or ectopic expression of PPARgamma or SREBP-1c in these cells, induces a panel of adipogenic transcription factors, reduces PPARbeta, and causes the phenotypic reversal to quiescent HSC. These results support the importance of adipogenic transcriptional regulation in HSC quiescence and provide a new framework for identifying novel molecular targets for the treatment of liver cirrhosis.


Expression and clinical value of peroxiredoxin-1 in patients with pancreatic cancer.
Peroxiredoxin-1 (Prx-1) is an important protector for redox damage and its abnormal expression is continually reported in various tumors. This study aims to investigate the expression status of Prx-1 and evaluate its clinical value in pancreatic cancer. Immunohistochemistry was used to detect Prx-1 expression in pancreatic cancer tissues and para-cancerous tissues. Enzyme-linked immunosorbent assay (ELISA) method was applied to detect the serum Prx-1 levels. The immunohistochemical results indicated that positive rate of Prx-1 was (p < 0.05) higher in pancreatic cancer tissues (74.4%) than in para-cancerous tissues (37.2%). Prx-1 expression was positively correlated with vascular endothelial growth factor (VEGF) and microvessel density (MVD) in cancer tissues. The ELISA results showed that patients with pancreatic cancer had a higher serum Prx-1 level than healthy subjects (31.2 ± 13.5 vs. 13.2 ± 11.9 ng/ml, p < 0.001). Prx-1 expression was correlated with aggressive clinicopathological parameter. The combination of serum Prx-1 and CA19-9, the area under the curve (AUC) was significantly higher than Prx-1 separate. Positive Prx-1 expression was correlated with disappointing overall survival (OS) (p = 0.002) and disease-free survival (DFS) (p < 0.001). Multivariate analysis showed that Prx-1 staining as an independent biomarker of poor OS (p = 0.035) and DFS (p < 0.001). These findings suggest that the levels of Prx-1 expression are significantly increased in pancreatic cancer. The up-regulated Prx-1 is closely related to tumor angiogenesis and acts as a promising tumor marker for diagnosis and prognosis of pancreatic cancer.


Suppression of HSP70 inhibits the development of acute lymphoblastic leukemia via TAK1/Egr-1.
Acute lymphoblastic leukemia (ALL), usually treated with chemotherapy, has limited therapeutic effects and high toxicity. Upregulation of HSP70 induces tumor development, however, the molecular mechanism of HSP70 in ALL remains unclear. In our research, we aimed to investigate the role of HSP70 in ALL, specifically the molecular mechanisms underlying cell apoptosis and proliferation. We found that HSP70 expression in leukomonocytes from ALL patients was increased compared with the control group. HSP70 expression in NALM-6 and BE-13 was also up-regulated contrast with AHH-1. Inhibition of HSP70 significantly promoted cell apoptosis and suppressed cell proliferation in ALL cell lines. Suppression of HSP70 decreased TAK1 and increased Egr-1 protein expression. Further experiments indicated that overexpression of TAK1 ameliorated the effect of HSP70 inhibition on Egr-1 protein expression, cell apoptosis and proliferation. In order to determine whether the effect of HSP70 inhibition on apoptosis and proliferation of ALL cell lines could be achieved via regulation of Egr-1, we performed a loss-of-function experiment for Egr-1. Egr-1 suppression was found to reverse the effect of HSP70 inhibition on cell apoptosis and proliferation in ALL. Taken together, our results suggest that HSP70 inhibition upregulates Egr-1 via TAK1, inducing apoptosis and restricting proliferation in ALL cells.


2,4-Bis(2-eth-oxy-phen-yl)-7-methyl-3-aza-bicyclo-[3.3.1]nonan-9-one.
The crystal structure of the title compound, C(25)H(31)NO(3), exists in a twin-chair conformation with an equatorial orientation of the ortho-eth-oxy-phenyl groups. According to Cremer and Pople [Cremer & Pople (1975 ▶), J. Am. Chem. Soc. 97, 1354-1358], both the piperidone and cyclo-hexa-none rings are significantly puckered with total puckering amplitutdes Q(T) of 0.5889 (18) and 0.554 (2) Å, respectively. The ortho-eth-oxy-phenyl groups are located on either side of the secondary amino group and make a dihedral angle of 12.41 (4)° with respect to each other. The methyl group on the cyclo-hexa-none part occupies an exocyclic equatorial disposition. The crystal packing is stabilized by weak van der Waals inter-actions.


Giant aneurysm causing frontal lobe syndrome.
A 67-year-old patient with a completely thrombosed giant aneurysm of the anterior communicating artery is described. The only neurological findings were a disturbance of stance and gait and slight bilateral grasp reflexes. He had had the features of a frontal lobe psychotic syndrome for more than 12 years. Computed tomography demonstrated a primarily hyperdense calcified suprasellar space-occupying lesion. Magnetic resonance imaging proved valuable in establishing the correct diagnosis, which was confirmed post mortem.


Development and validation of a rapid and simple LC-MS/MS method for quantification of vemurafenib in human plasma: application to a human pharmacokinetic study.
Vemurafenib (Zelboraf) is a new tyrosine kinase inhibitor that selectively targets activated BRAF V600E gene and is indicated for the treatment of advanced BRAF mutation-positive melanoma. We developed a simple method for vemurafenib quantification using liquid chromatography-tandem mass spectrometry. A stability study of vemurafenib in human plasma was also performed. (13)C(6)-vemurafenib was used as the internal standard. A single-step protein precipitation was used for plasma sample preparation. Chromatography was performed on an Acquity UPLC system (Waters) with chromatographic separation by the use of an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7-mm particle size; Waters). Quantification was performed using the monitoring of multiple reactions of following transitions: m/z 488.2 → 381.0 for vemurafenib and m/z 494.2 → 387.0 for internal standard. This method was linear over the range from 1.0 to 100.0 mcg/mL. The lower limit of quantification was 0.1 mcg/mL for vemurafenib in plasma. Vemurafenib remained stable for 1 month at all levels tested, when stored indifferently at room temperature (20 °C), at +4 °C, or at -20 °C. This method was used successfully to perform a plasma pharmacokinetic study of vemurafenib in a patient after oral administration at a steady state. This liquid chromatography-tandem mass spectrometry method for vemurafenib quantification in human plasma is simple, rapid, specific, sensitive, accurate, precise, and reliable.


Insights into pectin O-acetylation in the plant cell wall: structure, synthesis, and modification.
O-Acetyl esterification is an important structural and functional feature of pectins present in the cell walls of all land plants. The amount and positions of pectin acetyl substituents varies across plant tissues and stages of development. Plant growth and response to biotic and abiotic stress are known to be significantly influenced by pectin O-acetylation. Gel formation is a key characteristic of pectins, and many studies have shown that gel formation is dependent upon the degree of acetylation. Previous studies have indicated that members of the TRICHOME BIREFRINGENCE-LIKE (TBL) family may play a role in the O-acetylation of pectin, however, biochemical evidence for acceptor specific pectin acetyltransferase activity remains to be confirmed and the exact mechanism(s) for catalysis must be determined. Pectin acetylesterases (PAEs) affect pectin acetylation as they hydrolyze acetylester bonds and have a role in the amount and distribution of O-acetylation. Several mutant studies suggest the critical role of pectin O-acetylation; however, additional research is required to fully understand this. This review aims to discuss the importance, role, and putative mechanism of pectin O-acetylation.


Mechanics of elastin: molecular mechanism of biological elasticity and its relationship to contraction.
Description of the mechanics of elastin requires the understanding of two interlinked but distinct physical processes; the development of entropic elastic force and the occurrence of hydrophobic association. Elementary statistical-mechanical analysis of AFM single-chain force-extension data of elastin model molecules identifies damping of internal chain dynamics on extension as a fundamental source of entropic elastic force and eliminates the requirement of random chain networks. For elastin and its models, this simple analysis is substantiated experimentally by the observation of mechanical resonances in the dielectric relaxation and acoustic absorption spectra, and theoretically by the dependence of entropy on frequency of torsion-angle oscillations, and by classical molecular-mechanics and dynamics calculations of relaxed and extended states of the beta-spiral description of the elastin repeat, (GVGVP)n. The role of hydrophobic hydration in the mechanics of elastin becomes apparent under conditions of isometric contraction. During force development at constant length, increase in entropic elastic force resulting from decrease in elastomer entropy occurs under conditions of increase in solvent entropy. This eliminates the solvent entropy change as the entropy change that gives rise to entropic elastic force and couples association of hydrophobic domains to the process. Therefore, association of hydrophobic domains within the elastomer at fixed length stretches interconnecting dynamic chain segments and causes an increase in the entropic elastic force due to the resulting damping of internal chain dynamics. Fundamental to the mechanics of elastin is the inverse temperature transition of hydrophobic association that occurs with development of mechanical resonances within fibrous elastin and polymers of repeat elastin sequences, which, with design of truly minimal changes in sequence, demonstrate energy conversions extant in biology and demonstrate the special capacity of bound phosphates to raise the free energy of hydrophobic association.


Blood lead and cadmium levels are negatively associated with bone mineral density in young female adults.
The organ toxicities of lead and cadmium have been extensively studied; however, studies of their toxic effects on bone remain limited, especially in young adults. The objective of this study was to examine the associations of blood lead levels (BLL) and blood cadmium levels (BCL) with bone mineral density (BMD) among young adults. We performed a cross-sectional study using the National Health and Nutrition Examination Survey 2011-2018 database. Because of the skewed distribution, BLL and BCL were Ln-transformed for analysis. Weighted multivariate regressions were performed to evaluate the associations between LnBLL and LnBCL and lumbar BMD. Subgroup analyses were further performed. A total of 3234 participants aged 20-35 years were included in this study. No significant association between LnBLL and lumbar BMD was found (β = - 5.6, 95%CI: - 13.5-2.3). However, in the subgroup analysis stratified by sex, this association became negative in women (β = - 18.2, 95%CI: - 29.9- - 6.4). Moreover, this negative association was more prominent in female blacks (β = - 35.5, 95%CI: - 63.4- - 7.6). On the other hand, a negative association between LnBCL and lumbar BMD was found (β = - 7.4, 95%CI: - 14.0- - 0.8). In the subgroup analysis stratified by sex, this negative association only existed in women (β = - 18.7, 95%CI: - 28.0- - 9.5). Moreover, this negative association was more prominent in female whites (β = - 31.1, 95%CI: - 46.2- - 16.1). Our finding showed that both BLL and BCL were independently and negatively associated with lumbar BMD among young females, but not among young males.


Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.
We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.


A fine-tuned azobenzene for enhanced photopharmacology in vivo.
Despite the power of photopharmacology for interrogating signaling proteins, many photopharmacological systems are limited by their efficiency, speed, or spectral properties. Here, we screen a library of azobenzene photoswitches and identify a urea-substituted "azobenzene-400" core that offers bistable switching between cis and trans with improved kinetics, light sensitivity, and a red-shift. We then focus on the metabotropic glutamate receptors (mGluRs), neuromodulatory receptors that are major pharmacological targets. Synthesis of "BGAG12,400," a photoswitchable orthogonal, remotely tethered ligand (PORTL), enables highly efficient, rapid optical agonism following conjugation to SNAP-tagged mGluR2 and permits robust optical control of mGluR1 and mGluR5 signaling. We then produce fluorophore-conjugated branched PORTLs to enable dual imaging and manipulation of mGluRs and highlight their power in ex vivo slice and in vivo behavioral experiments in the mouse prefrontal cortex. Finally, we demonstrate the generalizability of our strategy by developing an improved soluble, photoswitchable pore blocker for potassium channels.


Patellar Tendon Revision Reconstruction With Hamstring Tendon Autografts.
Patellar tendon rupture is an infrequent cause of disability in patients younger than 40 years, with chronic injury and repeat procedures creating difficulty in facilitating healing. Use of hamstring autograft to reinforce the repair has been reported to strengthen the repair construct in patients with previous failure or chronic injury. This technique describes utilization of gracilis and semitendinosus tendon autografts to reconstruct the patellar tendon in a case of primary repair failure.


NONSYNDROMIC RETINITIS PIGMENTOSA WITH BILATERAL RETINAL NEOVASCULARIZATION DUE TO HGSNAT MUTATION.
To describe a case of nonsyndromic retinitis pigmentosa caused by presumed compound heterozygous A615T and T522M mutations in HGSNAT, characterized by bilateral cystoid macular edema and retinal neovascularization. Case report. The patient underwent clinical evaluation, multimodal imaging, and next-generation panel sequencing. In silico analysis was performed with PolyPhen-2, SIFT, and MutationTaster. Segregation analysis was not available. A 35-year-old hypertensive man presented with nyctalopia, photopsia, and difficulty reading for six months. He had no family history of visual deficits. The best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. Examination revealed midperipheral bone spicules and macular neovascularization in both eyes. Multimodal imaging demonstrated cystoid macular edema, ellipsoid band loss outside the central macula, and leakage from the neovascularization in both eyes. Sequencing detected four mutations in three genes, including two heterozygous mutations in HGSNAT (c.1843G>A, p.A615T and c.1565C>T, p.T522M). A615T is a pathogenic, hypomorphic mutation. T522M has not been previously phenotypically described. It is predicted damaging by in silico analysis and occurs at a conserved position near the eighth transmembrane domain, adjacent to residues in which missense mutations result in protein misfolding. This is, to the best of our knowledge, the first reported case of retinal neovascularization in a case of nonsyndromic retinitis pigmentosa due to HGSNAT mutation. The T522M variant likely functions as a severe mutation alongside the hypomorphic A615T mutation. These findings expand the genotypic and phenotypic spectrum of nonsyndromic retinitis pigmentosa.


Solid organ transplantation in older adults. Infectious and other age-related considerations.
In the U.S., older adults aged 65 or above comprise nearly one quarter of the solid organ transplant (SOT) waitlists, and the number of transplants performed in this age group continues to increase. There are no specific guidelines for the assessment and follow up of the older SOT candidate or recipient. Older adults are at increased risk of infectious complications after SOT. Despite these complications and even with the use of suboptimal donors, overall outcomes are favorable. We provide an overview to specific consideration as they relate to the older SOT candidate and recipient.


Morphology of rat spinal motoneurons with normal and hormonally altered specificity.
Potential determinants of motoneuronal morphology were examined by using a sexually dimorphic, steroid-sensitive neuromuscular system in the rat spinal cord. In males, the spinal nucleus of the bulbocavernosus (SNB) innervates the perineal muscles bulbocavernosus (BC) and levator ani (LA), and the dorsolateral nucleus (DLN) innervates the ischiocavernosus muscle (IC). Adult females normally lack these motoneurons and the peripheral targets. Prenatal exposure of females to the androgen dihydrotestosterone propionate (DHTP) partially masculinizes this neuromuscular system and alters moto-neuron-to-muscle specificity, resulting in retained SNB target muscles anomalously innervated by motoneurons in the DLN. Because the morphology of SNB and DLN motoneurons normally differs significantly, the influence of spinal cord location and peripheral target on motoneuron morphology can be directly compared. Injection of cholera toxin conjugated to horseradish peroxidase (CTHRP) into the LA of DHTP-treated females labeled motoneurons predominantly in the SNB. These (SNB-LA) motoneurons in DHTP females were identical in all morphological measures to those of normal males. CTHRP injection into the BC of DHTP females labeled motoneurons in both the SNB and the DLN. SNB-BC motoneurons in DHTP females resembled those of normal males in process number and orientation, but were significantly smaller in dendritic length per motoneuron and in soma size. The DLN motoneurons anomalously projecting to the BC in DHTP females differed significantly from SNB-BC motoneurons in soma size and number and orientation of primary processes. However, these motoneurons were identical in all respects to DLN-IC motoneurons in DHTP females; DLN-IC motoneurons were similar to those of normal males in the orientation of their dendritic arbor, but were significantly smaller in dendritic length, soma size, and number of primary processes. These comparisons make it clear that DHTP selectively affects motoneuronal specificity and morphology in specific motoneuron classes. Further, motoneuronal morphology in the SNB/DLN system appears to be influenced more by spinal cord location than by peripheral target.


Extended pyelolithotomy: the use of renal artery clamping and regional hypothermia.
Extended pyelolithotomy is a technique applicable for removal of most staghorn, and large pelvic and caliceal calculi. Nephrotomy incisions can be avoided in many cases. The efficiency of extended pyelolithotomy in difficult cases can be improved by renal artery occlusion combined with regional renal hypothermia. Devascularization of the kidney produces softening of the renal substance, which facilitates stone removal. The operative method is described and 5 cases are presented.


Characterization of Toll-like receptor 3 gene in rainbow trout (Oncorhynchus mykiss).
Antiviral immunity in fish is not well understood. In mammals, Toll-like receptor (TLR) 3 is involved in double-stranded RNA recognition and host immune response activation. Here, we report the first identification of a rainbow trout TLR3 ortholog (rtTLR3), its genomic structure, and mRNA regulation. Six exons and five introns were identified from bacterial artificial chromosome (BAC) and expressed sequence tag (EST) sequencing, and this genomic organization is similar to mammalian and fish TLR3 genes. The putative 913 amino acid protein has a Toll/interleukin (IL)-1R (TIR) domain, a transmembrane domain, and leucine-rich repeats. In healthy trout, rtTLR3 is highly expressed in the liver, pyloric ceca, intestine, spleen, and anterior and trunk kidney tissues. To investigate whether rtTLR3 is involved in antiviral immunity, transcriptional regulation in vivo was examined by quantitative real-time polymerase chain reaction (PCR) after poly inosinic:cytidylic (I:C) and infectious hematopoietic necrosis virus (IHNV) treatments. TLR3 mRNA expression peaked 1 day after poly (I:C) injection of live animals, while the peak of gene expression after live IHNV challenge was observed on day 3. In vitro stimulation of rainbow trout anterior kidney leukocytes with poly (I:C) also enhanced rtTLR3 expression. Up-regulation was specific to viral challenge as there was no significant up-regulation of rtTLR3 mRNA levels in the spleen and a modest down-regulation in the anterior kidney after bath challenge with a gram-negative bacterial trout pathogen, Yersinia ruckeri. The sequence conservation of trout TLR3 and mRNA regulation after poly (I:C) or RNA virus exposures strongly suggest a role for trout TLR3 in antiviral immunity.


Nucleated red blood cells count in pregnancies with idiopathic intra-uterine growth restriction.
Elevated nucleated red blood cell (NRBC) count is introduced as a potential marker of intra-uterine growth restriction (IUGR). To investigate the probable association regardless of any known underlying disease, we aimed to study disturbances in NRBC count in infants experiencing idiopathic IUGR. Twenty three infants regarded IUGR without any known cause were chosen to be compared to 48 normal neonates. Blood samples were collected instantly after birth and the same measurements were done in both groups. NRBC count/100 white blood cells was significantly higher in the IUGR group (P value < 0.001). pH measurements did not reveal any significant difference. Increased NRBC count in cases of idiopathic IUGR in absence of chronic hypoxia could strengthen its predictive value suggested in previous studies. It could help early IUGR detection and beneficial intervention.


Identification of a novel splicing mutation in the SLC25A13 gene from a patient with NICCD: a case report.
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the most common inherent causes of cholestatic jaundice in Asian infants. Mutations in the SLC25A13 gene, which encodes citrin protein expressed in the liver, have been identified as the genetic cause for NICCD. Here, we report a 4-month-old female with clinical features including jaundice, hyperbilirubinemia, hyperlactacidemia, and abnormal liver function. The patient was diagnosed with NICCD by differential diagnosis using genetic analysis. Mutations in 60 jaundice-related genes were tested by using amplicon sequencing, which was performed on an Ion S5XL genetic analyzer. A compound heterozygous mutation in the SLC25A13 gene was identified, consisting of a known deletion SLC25A13:c.852_855delTATG and a novel splicing mutation SLC25A13:c.1841 + 3_1841 + 4delAA. Sanger sequencing for the proband and her parents was performed to validate the result and reveal the source of mutations. A compound heterozygous mutation in the SLC25A13 gene was identified in a 4-month-old female patient with NICCD. Our data suggest that amplicon sequencing is a helpful tool for the differential diagnosis of inherited diseases with similar symptoms. Further studies of the mutation spectrum of neonatal jaundice in China are warranted.


Prevalence of skin test reactivity to aeroallergens in the Pakistani population.
The prevalence of allergies has increased in all parts of the world. The present study was conducted to determine the prevalence of sensitivity to common aeroallergens, pollen, thresher dust and cotton dust, in Pakistan. Retrospective cohort study. Record of 65067 who attended the Allergy Centre, National Institute of Health, Islamabad, Pakistan from January 2007 to August 2008 was retrieved. Subjects that were skin prick test (SPT) negative and those that were SPT positive to aeroallergens were extracted and subcategorized on the basis of the 8 provinces of Pakistan, including, Islamabad Capital Territory, Punjab, Baluchistan, Sindh, Northern Areas, Kashmir, North Western Frontier Province (NWFP) and Federally Administered Tribal Areas (FATA). Monthly analysis of prevalence of allergies was also determined. Of the total, 68.6% were SPT positive. The highest number of affected individuals was from the Punjab region (41%). The highest number of cases of all aeroallergens was reported in the month of August (3532, 13.7%). Significant high correlations were observed between mixed pollen, thresher dust and raw cotton and allergic rhinitis, asthma, uriticaria and allergic conjunctivitis. There was no significant correlation between allergen sensitivity and atopic edema. A high prevalence of sensitivity to aeroallergens is observed in the Punjab Province of Pakistan.


Evolutionary diversification of cytokinin-specific glucosyltransferases in angiosperms and enigma of missing cis-zeatin O-glucosyltransferase gene in Brassicaceae.
In the complex process of homeostasis of phytohormones cytokinins (CKs), O-glucosylation catalyzed by specific O-glucosyltransferases represents one of important mechanisms of their reversible inactivation. The CK O-glucosyltransferases belong to a highly divergent and polyphyletic multigene superfamily of glycosyltransferases, of which subfamily 1 containing UDP-glycosyltransferases (UGTs) is the largest in the plant kingdom. It contains recently discovered O and P subfamilies present in higher plant species but not in Arabidopsis thaliana. The cis-zeatin O-glucosyltransferase (cisZOG) genes belong to the O subfamily encoding a stereo-specific O-glucosylation of cis-zeatin-type CKs. We studied different homologous genes, their domains and motifs, and performed a phylogenetic reconstruction to elucidate the plant evolution of the cisZOG gene. We found that the cisZOG homologs do not form a clear separate clade, indicating that diversification of the cisZOG gene took place after the diversification of the main angiosperm families, probably within genera or closely related groups. We confirmed that the gene(s) from group O is(are) not present in A. thaliana and is(are) also missing in the family Brassicaceae. However, cisZOG or its metabolites are found among Brassicaceae clade, indicating that remaining genes from other groups (UGT73-group D and UGT85-group G) are able, at least in part, to substitute the function of group O lost during evolution. This study is the first detailed evolutionary evaluation of relationships among different plant ZOGs within angiosperms.


Phakic and pseudophakic eyes in patients during hyperbaric oxygen therapy.
To examine the optical components of phakic and pseudophakic eyes during hyperbaric oxygen (HBO) therapy, and to quantify their relative impact on ocular refractive changes. HBO therapy was given to 16 phakic and six pseudophakic patients for 90 min daily at a pressure of 240 kPa, 5 d a week for 20 days. An eye examination was performed on the first day of HBO therapy and repeated when the patients had completed 19 days of the treatment. Refractive error, best-corrected visual acuity, corneal power, radius, thickness and volume, anterior chamber depth, axial length, lens opacity, and intraocular pressure were measured in all patients. Serum glucose, glycosylated hemoglobin, serum electrolytes, and protein were measured in the phakic patients. In the phakic group, a significant myopic shift (≥ -0.50 D) occurred in 26 (81%) single eyes during the treatment. The median myopic shift was -0.63 D (min -0.25 D/max -1.88 D) in the OD, and -0.69 D (min -0.38 D/max -2.25 D) in the OS. No myopic shift appeared in the pseudophakic patients; the median refractive changes were +0.06 D (min -0.13 D/max +0.25 D) in the OD and +0.13 D (min 0.00 D/max +0.25 D) in the OS. Intraocular pressure, serum electrolytes, glucose, and glycosylated hemoglobin remained unchanged. Myopic shifts occurred in phakic but not in pseudophakic eyes during HBO therapy. The myopic shifts must be attributed to changes in the crystalline lens.


EDTA-polyvinylpyrrolidone as a preservation medium for immunohistochemistry.
In a solution on 7% EDTA and 5% polyvinylpyrrolidone in 0.1 mol/l. Tris buffer, pH = 6.95, tissues samples can be stored at room temperature for 1 week without detectable loss of structural integrity or antigenicity (as demonstrated in immunohistochemistry with monoclonal antibodies to intermediate filament proteins).


Predictors of mortality in outborns with neonatal sepsis: A prospective observational study.
Neonatal sepsis-related mortalities are the outcome of a complex interaction of maternal-foetal colonisation, transplacental immunity and physical and cellular defence mechanisms of neonates. The objective of this study was to evaluate the risk factors of mortality in outborn neonatal sepsis. A 1-year prospective observational study was undertaken at a tertiary care centre. All referred neonates with maternal and neonatal risk factors of sepsis were enrolled. Blood culture, sepsis screen and other relevant investigations were performed. The mortality rate of neonatal sepsis among outborns was 38.24%. The common presentations of these neonates were respiratory distress, lethargy and hypothermia. On univariate analysis, significant risk factors for mortality included male sex (P = 0.05), weight on admission <1500 g (P < 0.001), hypothermia (P = 0.003), respiratory distress (P = 0.04), cyanosis (P = 0.001), convulsions (P = 0.02), prolonged capillary refill time (P < 0.001), thrombocytopenia (P < 0.001), abnormal radiological finding (P = 0.01), cerebrospinal fluid cellularity (P = 0.002) and positive C-reactive protein (P < 0.001). Maternal factors such as hypertension in pregnancy (P = 0.001) and antepartum haemorrhage (P = 0.03) were associated with statistically significant mortality. Gestational age (odds ratio [OR]: 0.49, confidence interval [CI]: 0.26-0.90, P = 0.02), weight on admission (OR: 1.57, CI: 1.08-2.27, P = 0.01), age at admission (OR: 0.89, CI: 0.78-0.99, P = 0.04), distance travelled with neonate (OR: 1.01, CI: 1.00-1.01, P = 0.003), duration of hospital stay (OR: 0.69, CI: 0.63-0.74, P < 0.001), hypothermia (OR: 1.87, CI: 1.01-3.42, P = 0.04), convulsion (OR: 2.88, CI: 1.33-6.20, P = 0.007), cyanosis (OR: 2.39, CI: 1.07-5.35, P = 0.03) and prolonged capillary refill time (OR: 3.34, CI: 1.78-6.24, P < 0.001) were the independent predictors of mortality in neonatal sepsis. Gestational age; birth weight; long distance travelled with neonate and presentation with hypothermia, cyanosis, convulsions and prolonged capillary refill time were the independent risk factors for mortality in neonatal sepsis among outborns.


The influence of hypothalamically administered reserpine on the sexual behavior of the female cat.
Ovariectomized cats with intracerebral implants of reserpine, a monoamine depletor, were tested for sexual behavior by introducing them to sexually vigorous males and by artificial stimulation. Approximately a third of the animals mated in response to reserpine and another third exhibited some components of sexual behavior. The behavior exhibited by these animals had none of the frenzy of normal estrous behavior. Some components of the normal pattern were missing while all others were curtailed in duration and vigor. These animals responded with normal sexual behavior to intracerebrally and systemically administered estrogen. It is suggested that the unusual sexual behavior in response to reserpine was due to the release of these behavioral patterns from a monoamine system, inhibitory to sexual behavior.


Contribution of lipid environment to NADPH oxidase activity: influence of sterol.
The NADPH-oxidase complex, which plays beneficial or detrimental role in the inflammatory and degenerative diseases, is a membrane multi-subunit complex tightly regulated in order to produce superoxide anions, precursor of oxygen reactive species (ROS), in cells. The flavocytochrome b(558) (Cytb(558)) is the catalytic core of the NADPH oxidase which consists of two membrane proteins gp91(phox) (highly glycosylated) and p22(phox). In this work we took advantage of heterologous yeast cells engineered to express wild-type bovine Cytb(558) to analyze the properties of the NADPH oxidase activity during the biosynthesis processing steps of gp91(phox) and p22(phox) within endoplasmic reticulum (ER) and plasma membrane (Pmb). Our data showed that, in yeast, the heterodimerization at the endoplasmic reticulum membranes was concomitant with high level glycosylation of gp91(phox) and the heme acquisition. This study also demonstrated that the phagocyte NADPH oxidase was active at ER membranes and that this activity was surprisingly higher at the ER compared to the Pmb membranes. We have correlated these findings with the presence of sterols in the plasma membranes and their absence in ER membranes. This correlation was confirmed by decreased superoxide anion production rates in proteoliposomes supplemented with ergosterol or cholesterol. Our data support the idea that membrane environment might be determinant for ROS regulation and that sterols could directly interact with the membrane proteins of the NADPH oxidase constraining its capacity to produce superoxide anions.


Use of hands-free technique among operating room nurses in the Republic of Korea.
The recently introduced concept of hands-free technique (HFT) currently has no recommendations or formal educational program for use in the Republic of Korea. This study evaluated the level of HFT use and investigated factors related to HFT use among Korean operating room nurses. Data were obtained through a self-administered questionnaire from 158 operating room nurses in 7 general hospitals in Busan, Republic of Korea, in April and May 2006. The questionnaire elicited information on demographics, exposure to education on HFT, attitude toward the need for HFT, concerns about exposure to bloodborne pathogens, and experience with HTF use. Multilevel multiple logistic regression analysis with generalized estimating equations was used, and adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. We found that 56% of the participants had used HFT, and 50% had received education on HFT. The use of HFT had a significant association with both education on HFT (OR = 12.02; 95% CI = 7.50 to 19.25) and attitude toward the need for HFT (OR = 4.22; 95% CI = 2.43 to 7.35). Increasing education about HFT could be the most important approach to increasing the use of HFT among Korean operating room nurses. Thus, routine teaching about HFT should be provided to these nurses.


Exercise therapy for low back pain: a small-scale exploratory survey of current physiotherapy practice in the Republic of Ireland acute hospital setting.
A small-scale exploratory cross-sectional survey investigated the current use of a range of exercise therapy approaches for low back pain (LBP) by outpatient physiotherapists in the acute hospital setting in the Republic of Ireland, where the majority of publicly funded treatment is delivered. Of the 120 postal questionnaires distributed to 24 physiotherapy departments, 87 were returned (72.5% response rate). The results showed specific spinal stabilization exercises were the most popular exercise therapy for acute (39%; n = 35) and chronic (51%; n = 48) LBP, followed by the McKenzie approach (acute LBP (ALBP) 35.6%; n = 32: chronic LBP (CLBP) 17%; n = 16), and abdominal exercise (ALBP 11.1%; n = 10: CLBP 9.6%; n = 9). The most popular forms of exercise therapy used by outpatient physiotherapists in acute hospital settings in Ireland lack support from evidence-based clinical guidelines, and further large-scale high quality randomized controlled trials of these approaches are warranted. Further research should also establish the use of exercise therapy and attitudes to clinical guidelines of physiotherapists in other countries and healthcare settings.


Mechanical analysis of prosthetic bars and dental implants in 3 and 4 implant-supported overdenture protocols using finite element analysis.
In some clinical situations, the installation of four or more dental implants may be infeasible. Therefore, the installation of protocol-type prostheses with only three implants may be necessary. The mechanical failures can hinder the success of the rehabilitation treatment. To evaluate and compare the mechanical stress of the metallic prosthetic bar when installed over protocol-type prostheses of three and four implants, and to evaluate the stress on the dental implants. Two three-dimensional human jaw models were created. In one model, four dental implants (P4) were designed and in the other model three dental implants (P3) were designed. In both models, according to the arrangement of the dental implants, prosthetic bars were designed. In a finite element analysis software, compressive forces were applied to the ends of both prosthetic bars, simulating the force application during mastication. Tension and stress dissipation were analyzed on the prosthetic bar and dental implants. Both P4 and P3 protocol-type prostheses supported the force efficiently without breaking the bar or the implants. Force dissipation along the bar was more homogeneous in the P3 prosthetic bar than in P4. In addition, P3 implants received a higher concentration of stress in relation to P4 implants. Prosthetic bars and dental implants withstand the stress of load application in both four and three implant protocol-type prostheses. Three-implants protocol showed more satisfactory force dissipation than the four-implant protocol.


Diet plays a central role in parental self-treatment of children with Hirschsprung's disease-a qualitative study.
Hirschsprung's disease is a congenital disorder requiring surgery. Most children operated on for Hirschsprung's disease experience postoperative bowel dysmotility. Although various food is known to influence bowel motility, evidence of diet's role and dietary guidelines in treatment of bowel dysfunction in Hirschsprung's disease is lacking. The aim was to explore parental experiences of dietary effects on bowel function in children with Hirschsprung's disease. A qualitative study including three focus groups with ten parents of children with Hirschsprung's disease at a national Hirschsprung's disease centre. Data were analysed through content analysis. Parents emphasised diet as a strong influencer on their child's bowel function in Hirschsprung's disease. They expressed great concerns about their responsibility and strived hard to explore and adjust dietary habits to control the child's bowel function. Families' daily and social lives were influenced by the child's diet and bowel function. The parents desired dietary support and guidelines to improve their confidence in self-treatment of Hirschsprung's disease. Dietary habits play a key role in parental self-treatment of bowel function in their children with Hirschsprung's disease. Dietary guidelines for patients with Hirschsprung's disease are anticipated.


Unusual pressure dependence of the lateral motion of pyrene-labeled phosphatidylcholine in bipolar lipid vesicles.
The lateral mobility of a pyrene-labeled phosphatidylcholine probe in liposomes containing archaebacterial bipolar lipids has been studied isothermally as a function of pressure. The pressure-dependence of the probe mobility, R, is found to be slightly positive or zero in the temperature range of 17 - 48 degrees C. At temperatures > 48 degrees C, R becomes negative and decreases with temperature. The data indicate that lateral mobility only becomes appreciable at high temperatures. In addition, the R values obtained with other lipid membranes are much lower than that obtained with bipolar liposomes, implying that the membranes of archaebacterial liposomes are laterally immobile, as compared to other lipid membranes.


Enhanced wastewater nutrients removal in vertical subsurface flow constructed wetland: Effect of biochar addition and tidal flow operation.
Dissolved oxygen (DO) and carbon stock in substrate medium play a vital role in the nutrient removal mechanism in a constructed wetland (CW). This study compiles the results of dynamics of DO, ammonium N (NH4+-N), nitrate (NO3-N), sulfate (SO4-2), phosphate (PO4-3), chemical oxygen demand (COD), in three setups of vertical-flow constructed wetlands (TFCWs) (SB: substrate + biochar; SBP: substrate + biochar + Colocasia esculenta plantation; SP: substrate + Colocasia esculenta (SP), operated with tidal flow cycles. Experimental analyses illustrated the continuous high DO level (2.743-5.66 mg L-1) in SB and SBP after the I and II cycle of tidal flow (72 h flooding and 24 h dry phase). COD reduction efficiencies increased from 15.75 - 61.86% to 48.55-96.80% after tidal operation among operating TFCWs. N (NH4+-N) and N (NO3-N) removal were found to be 88.16%, and 76.02%; 49.32, and 57.85%; and 40.23%, and 48.94 % in SBP, SP and SB, respectively. The theory of improved nitrification and adsorption through biochar amended substratum was proposed for TFCW systems. PO4-3 and SO4-2 removal improved from 22.63 to 80.50%, and 19.69 to 75.20%, respectively after first tidal operation in all TFCWs. The microbial inhabitation on porous biochar could promote the transformation of available P into microbial biomass and also helped by the plant uptake process while SO4-2 reduction in TFCWs could be mainly due to sulfate-reducing bacterial activity and nitrate reduction process, mainly facilitated by high DO and biochar addition in such setups. The study suggests that effluent re-circulation through tidal operation and biochar supplementation in the substratum could be an effective mechanism for the improvement of the working efficiencies of CWs operated with low energy input systems.


Establishing a sensitive and specific assay for determination of glucocorticoid bioactivity.
Glucocorticoids are hormones that play a major role in energy homeostasis and stress response of the body. As drugs they are most frequently used for immunosuppressive and anti-inflammatory purposes. Glucocorticoids are exploited successfully in the treatment of a wide variety of diseases; however, some patients develop side-effects, while others fail to respond to this form of therapy. Alterations in pharmacodynamic and pharmacokinetic actions might contribute to individual differences in glucocorticoid sensitivity. Antibody-based methods such as RIA (Radioimmunoassay) and ELISA (Enzyme-linked immunosorbent assay) are routinely used to determine glucocorticoid serum levels. However, as these techniques measure the total amount of a specific glucocorticoid and do not discriminate between protein-bound and freely available (i.e. biologically active) glucocorticoids, the results do not necessarily reflect the active levels of glucocorticoid, i.e. the "glucocorticoid milieu" in a patient. Being able to determine glucocorticoid bioactivity in serum or other body fluids could help identifying glucocorticoid-sensitive or -resistant patients and help finding explanations for different responses in individual patients. For this reason, we established a glucocorticoid bioactivity assay that is based on the measurement of glucocorticoid-dependent reporter gene activity. Making use of a human T-cell leukemia line, equipped with the glucocorticoid receptor and the fluorescence protein Venus as the assay's reporter (Jurkat(GR)-MMTV-VNP), glucocorticoid bioactivity can be determined from small amounts of serum or other biologic fluids. The developed glucocorticoid bioassay is both sensitive and reproducible, without any relevant cross-reactivity with steroid hormones other than glucocorticoids and can be practically applied in daily laboratory routine.


Ultrasonographic prevalence of ulnar nerve displacement at the elbow in young baseball players.
Overhead-throwing athletes are at risk of elbow injury because of valgus stress, leading to unstable ulnar nerves and neuropathy. Studies regarding ulnar nerve damage/displacement have been performed primarily in adults. To determine the prevalence and related factors associated with ulnar nerve displacement at the elbow in young baseball players. Cross-sectional study. Youth baseball players ages 10-12 years were eligible to participate. Exclusion criteria were history of neuropathic pain, trauma, or prior surgery of the upper limb. Fifty-seven participants were eligible for inclusion in the study. Demographic data and ultrasonography findings of ulnar nerve dynamics at the cubital tunnel were analyzed in a total of 114 elbows. Elbows were grouped into nondislocation and displacement (subluxation or dislocation) groups according to ultrasound findings. Logistic generalized estimating equations were used to identify factors associated with ulnar nerve displacement. Thirty-six (31.6%) elbows demonstrated sonographic findings of ulnar nerve displacement, with 13 (11.4%) subluxations and 23 (20.2%) dislocations. Fourteen (24.6%) participants experienced nerve displacement in the dominant elbow only, whereas nerve displacement in both elbows occurred in 11 (19.3%) participants. Nerve displacement in the nondominant elbow only was not observed. Hand dominance and tenderness of the arcade of Struthers' were factors associated with ulnar nerve displacement (odds ratio, 2.81, and 9.73; 95% confidence interval, 1.34-5.91 and 2.45-38.68; p = .006 and .001, respectively). One-third of the young baseball players evaluated had ultrasonographic findings compatible with ulnar nerve displacement at the elbow. Hand dominance and tenderness of Struthers arcade were the only factors associated with ulnar nerve displacement. Ultrasound may help identify patients with ulnar nerve displacement and contribute to the understanding of its pathophysiology in young baseball players.


Do chronic stressors lead to physiological dysregulation? Testing the theory of allostatic load.
To explore three questions: 1) Do chronic stressors predict physiological dysregulation? 2) Is that relationship moderated by characteristics of the individual and his or her social environment? and 3) Do perceived levels of stress mediate the relationship between stressors and dysregulation? Data come from a nationally representative, longitudinal study of older Taiwanese (n = 916). Regression models are used to examine the relationship between the number of life challenges (i.e., stressors) during 1996 to 2000 and physiological dysregulation (in 2000) based on 16 biomarkers that reflect neuroendocrine function, immune system, cardiovascular function, and metabolic pathways. We include interaction terms to test whether psychosocial vulnerability moderates the impact of stressors. Additional models evaluate the mediating effects of perceived stress. We find a positive association between the number of stressors and physiological dysregulation. The results indicate that this relationship is stronger for persons with greater psychosocial vulnerability, but even so, the magnitude of the effect remains modest. We find some evidence that the level of perceived stress mediates the relationship between chronic stressors and physiological dysregulation. Our results provide some support for the theory of allostatic load, although the relationship between life challenges and physiological dysregulation is weak. The evidence also supports the stress-buffering hypothesis: the combination of low social position, weak social networks, and poor coping ability is associated with greater physiological consequences of life challenges.


Comparing the effectiveness of negative-pressure barrier devices in providing air clearance to prevent aerosol transmission.
To investigate the effectiveness of aerosol clearance using an aerosol box, aerosol bag, wall suction, and a high-efficiency particulate air (HEPA) filter evacuator to prevent aerosol transmission. The flow field was visualized using three protective device settings (an aerosol box, and an aerosol bag with and without sealed working channels) and four suction settings (no suction, wall suction, and a HEPA filter evacuator at flow rates of 415 liters per minute [LPM] and 530 LPM). All 12 subgroups were compared with a no intervention group. The primary outcome, aerosol concentration, was measured at the head, trunk, and foot of a mannequin. The mean aerosol concentration was reduced at the head (p < 0.001) but increased at the feet (p = 0.005) with an aerosol box compared with no intervention. Non-sealed aerosol bags increased exposure at the head and trunk (both, p < 0.001). Sealed aerosol bags reduced aerosol concentration at the head, trunk, and foot of the mannequin (p < 0.001). A sealed aerosol bag alone, with wall suction, or with a HEPA filter evacuator reduced the aerosol concentration at the head by 7.15%, 36.61%, and 84.70%, respectively (99.9% confidence interval [CI]: -4.51-18.81, 27.48-45.73, and 78.99-90.40); trunk by 70.95%, 73.99%, and 91.59%, respectively (99.9% CI: 59.83-82.07, 52.64-95.33, and 87.51-95.66); and feet by 69.16%, 75.57%, and 92.30%, respectively (99.9% CI: 63.18-75.15, 69.76-81.37, and 88.18-96.42), compared with an aerosol box alone. As aerosols spread, an airtight container with sealed working channels is effective when combined with suction devices.


Lumbar erector spinae plane block: an anatomical and dye distribution evaluation of two ultrasound-guided approaches in canine cadavers.
To examine the anatomy of the lumbar epaxial region and to describe two different ultrasound-guided approaches for the lumbar erector spinae plane (ESP) block in dogs. An anatomical and experimental cadaver study. A group of 19 canine cadavers. The anatomy was described following dissection of two cadavers. Bilateral ultrasound-guided ESP injections with 0.4 mL kg-1 of contrast dye were performed in 17 adult Beagle cadavers using either transversal (TVS) or parasagittal (PST) approaches. Computed tomography was performed to measure the total length of the contrast dye column and the epidural, intravascular, hypaxial and intra-abdominal migration. Dissections were performed to assess the spread of the contrast dye and to determine the degree of staining of the dorsal branches of the spinal nerves (DBSN). Mann-Whitney U and chi-square tests were used to compare data between groups. Using both techniques, the contrast dye was observed within the ESP compartment. There was no difference in the total length of the contrast dye column between TVS and PST approaches (p = 0.056). Using the TVS approach, multisegmental staining of the DBSN was visible with 100% (17/17) of injections, while complete staining of the DBSN was achieved at 94% of the injection sites. Using the PST approach, these values were 29% (5/17) and 23% (4/17), respectively. The TVS approach stained more DBSN than the PST approach (p = 0.001), with a median (range) of 2 (2-3) versus 0 (0-3) DBSN, respectively. Using the TVS approach, epidural and intravascular migration were present in 2/17 (p = 0.485) and 3/17 (p = 0.227) injections, respectively. Both ultrasound-guided approaches resulted in a spread of the contrast dye within the ESP compartment. Although there were no differences in the total length of the contrast dye column, the TVS approach was superior to the PST approach in staining DBSN.


From the past, a long way to future challenges for a greater control of tuberculosis.
Tuberculosis (TB) and humans have coexisted for more than 40,000 years; however TB remains a global threat to human kind. The international community has developed new tools for early detection, but TB strains evolved acquiring resistance to first-line therapeutic drugs with increasing treatment challenges. Furthermore, TB has formed also an alliance with human immunodeficiency virus; in this way the poorest populations are most affected. The current vaccine planning activity includes 14 new vaccines against TB (11 of those in the phaseII/III) developed with different techniques. Now, more than ever, new anti-TB drugs and new anti-TB regimens are urgently required as well as universal health care and social protection in order to tackle down both hard to treat TB and the social determinants of TB. Coordinated actions and sharing of information are needed to aspire everywhere to the best clinical practices and improve quality of life of patients and their families.


Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of Locusta migratoria (Orthoptera: Acrididae) as a novel food source.
The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.


Culture in the spotlight-cultural adaptation and content validity of the integrated palliative care outcome scale for dementia: A cognitive interview study.
Dementia is a life-limiting disease with high symptom burden. The Integrated Palliative Care Outcome Scale for Dementia (IPOS-Dem) is the first comprehensive person-centered measure to identify and measure palliative care needs of people with dementia. However, such a measure is missing in the German health care system. To develop a culturally adapted German version of the IPOS-Dem and determine its content validity as a foundation for comprehensive psychometric testing. Cognitive interview study with intermittent analysis and questionnaire adaptation. Interview guide and coding frame followed thematic analysis according to Willis complemented by Tourangeau's model of cognitive aspects of survey methodology: comprehension, retrieval, judgment, response. Purposive sample with professionals (n = 29) and family carers (n = 6) of people with advanced dementia in seven nursing homes and person's own home care in four interview rounds (n = 11; 10; 7; 7). IPOS-Dem was regarded as comprehensive and accessible. Cultural adaption pertained to issues of comprehension and judgment. Comprehension challenges referred to the person-centered concept of "being affected by" used in the POS-measures. Judgment problems related to persons with limited communication causing challenges in assessment. Most issues of cultural adaptation could be addressed by questionnaire modifications. However, interviews unveiled fundamental challenges for using proxy reported person-centered assessments. Continuous training on how to use the instrument is imperative to integrate the person-centered approach of palliative care into nursing homes as a key provider of generalist palliative care for people with dementia. The refined version is ready for psychometric testing.


Acute spinal cord compression: CQI framework increases resource efficiency while promoting delivery of high-quality care.
Literature reports indicate that advanced imaging is overutilized, especially in the emergency setting. At our institution, stat spinal MRI for suspected acute spinal cord compression (ASCC) was perceived to be excessively utilized. A continuous quality improvement process was employed to investigate this trend and improve the efficiency of this diagnosis. Spine imaging in patients with suspected ASCC was retrospectively evaluated for appropriateness of indications and quality of imaging. Based on the results, a new institutional policy for ordering MR for suspected ASCC was implemented, concurrent with development of a new screening spine MRI protocol. Subsequently, indications, efficacy, and imaging utilization of the new strategy were analyzed for improved operational effectiveness. The initial retrospective study demonstrated only a 1.4% positive rate of ASCC as well as image-quality degradation due to patient motion resulting from prolonged scan times. Based on these results, a new institutional policy for ordering stat ASCC spine MRI was instituted with an updated screening MRI protocol. This policy resulted in a positive rate of ASCC of 4.4%, and decreased scan time by 50%-70%, while preserving diagnostic image quality and decreasing resource utilization. As suspected, stat spinal MRI for ASCC was excessively utilized at our institution. The study demonstrated that systemic improvements regarding this issue can be achieved by using a multidisciplinary approach and following a continuous quality improvement methodology. A new MRI protocol for identification of ASCC was found to preserve image quality and diagnostic confidence, while simultaneously decreasing scan time and use of valuable health care resources.


In silico identification, structural characterization, and phylogenetic analysis of MdesDEF-2: a novel defensin from the Hessian fly, Mayetiola destructor.
The CSαβ defensins are one of the most ancient antimicrobial peptide classes and are distributed in plants, invertebrates, and fungi. In the insect immunity, the defensins play a crucial role in protection against pathogens. The discovery of novel insect defensins could be a vital tool in developing novel antimicrobial agents, which are urgently needed because of growing resistance in pathogenic bacteria and the resulting reduction in the effectiveness of conventional antibiotics over the years. In this context, novel insect defensins could be identified from the potential resource of model insects. Here, a novel defensin, MdesDEF-2, was identified from the model insect Mayetiola destructor, the most destructive insect pest of wheat worldwide. The in silico identification of MdesDEF-2 was done through searching by regular expression in M. destructor's protein sequences available at NCBI. MdesDEF-2 has 36 amino acid residues and its model was composed of two β-strands and one α-helix showing three disulfide bridges. According to the classification of CSαβ defensins, MdesDEF-2 belongs to the group of ancient insect-type defensins. The molecular dynamics simulation revealed that MdesDEF-2 has a very flexible N-terminal loop. Moreover, phylogenetic analysis together with functional predictions indicated that MdesDEF-2 could have antibacterial activity without causing membrane disruption. However, while the actual activity of MdesDEF-2 is still unclear, it is evident that its role in the biology of M. destructor is similar to that of its paralogue, MdesDEF-1, protecting the insect against microbial invasion.


Planifilum caeni sp. nov., a novel member of thermoactinomycete isolated from sludge compost.
A Gram positive, thermophilic, and filamentous bacterium, designated strain GIESS004(T), was isolated from a sludge compost from Guangzhou, China. Growth occurred at 45-55 °C (optimum 50-53 °C) and pH 6.0-10.0 (optimum pH 7.0-7.5). The organism formed cream-yellow colonies with radial wrinkles. Aerial mycelium was not produced in any of the growth media tested. Single spores were produced along the substrate hyphae. Strain GIESS004(T) contained MK-7 as the predominant menaquinone and iso-C(16:0), iso-C(15:0) and iso-C(17:0) as the major cellular fatty acids. The cell wall contained meso-diaminopimelic acid. The DNA G+C content was 60.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain GIESS004(T) was associated with the genus Planifilum and formed a cluster with its closest relative of Planifilum composti P8(T) (99.5 % similarity). However, the DNA-DNA pairing study showed that the isolate displayed reassociation value of only 57.6 ± 2.3 % with P. composti P8(T). On the basis of the polyphasic taxonomic results, strain GIESS004(T) (= CCTCC AB2013107(T) = MCCC 1K00414(T)) is designated as the type strain of a novel species of the genus Planifilum, for which the name Planifilum caeni sp. nov. is proposed.


Population Structure of Nation-Wide Rice in Thailand.
Thailand is a country with large diversity in rice varieties due to its rich and diverse ecology. In this paper, 300 rice accessions from all across Thailand were sequenced to identify SNP variants allowing for the population structure to be explored. The result of inferred population structure from admixture and clustering analysis illustrated strong evidence of substructure in each geographical region. The results of phylogenetic tree, PCA analysis, and machine learning on population identifying SNPs also supported the inferred population structure. The population structure inferred in this study contains five subpopulations that tend to group individuals based on location. So, each subpopulation has unique genetic patterns, agronomic traits, as well as different environmental conditions. This study can serve as a reference point of the nation-wide population structure for supporting breeders and researchers who are interested in Thai rice.