Preliminary results in invasive bladder cancer with transurethral resection, neoadjuvant chemotherapy and combined pelvic irradiation plus cisplatin chemotherapy.
Preliminary data are presented of a clinically feasible pilot study to select a significant subgroup of patients among those with muscle-invading bladder tumors for local cure and bladder preservation, while also to offer all patients the possibility of preventing the development of distant metastases. Transurethral debulking surgical resection was combined with neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy plus 2 additional courses of cisplatin and 4,000 cGy. If tumor was found on cystoscopic re-evaluation by biopsy and for cytology after cisplatin and partial irradiation (4,000 cGy.) immediate cystectomy was advised. If tumor was not found consolidation by a radiotherapy boost to a total of 6,480 cGy. plus 1 additional course of cisplatin was given. Of 53 consecutive patients the planned treatment was completed in 42 (79%). With a median followup of 26 months (range 15 to 42 months), 72% of all entered patients were alive, 70% have not required cystectomy and 74% have not had distant metastases. Among the 42 patients who completed the planned protocol chemotherapy dose reductions were required in 39% for stomatitis, bone marrow depression and/or renal dysfunction. There were 2 serious complications but no treatment-related sepsis, deaths or significant renal dysfunction. Eight patients underwent immediate radical cystectomy because of positive biopsy and/or cytology results after 4,000 cGy., while 34 completed full chemotherapy and radiotherapy without any significant bladder or bowel injury. Of 42 patients 22 (52%) have maintained the bladder without any recurrence, and of those selected for full chemotherapy and radiotherapy this number increased to 65%. To date 12 patients have persistent or recurrent bladder tumors: 5 (15%) had invasive tumors treated by cystectomy and 7 (21%) had carcinoma in situ treated by intravesical therapy. The true success of this or other selective bladder-preserving treatments will require 3 to 5 years of followup to be confident that such treatment has sterilized the bladder of cancer. This feasibility study has been clinically practical, modestly well tolerated and encouraging for the significant proportion of patients with a sustained complete response and for the 70% over-all survival rate at 2 years. To evaluate critically the efficacy of methotrexate, cisplatin and vinblastine chemotherapy in the prevention of occult distant micrometastases and in increasing the rate of successful bladder preservation, in May 1988 we began a randomized phase 3 trial with and without neoadjuvant methotrexate, cisplatin and vinblastine chemotherapy.


A Fluorescent Molecular Probe for the Detection of Hydrogen Based on Oxidative Addition Reactions with Crabtree-Type Hydrogenation Catalysts.
A Crabtree-type Ir(I) complex tagged with a fluorescent dye (bodipy) was synthesized. The oxidative addition of H2 converts the weakly fluorescent Ir(I) complex (Φ=0.038) into a highly fluorescent Ir(III) species (Φ=0.51). This fluorogenic reaction can be utilized for the detection of H2 and to probe the oxidative addition step in the catalytic hydrogenation of olefins.


Effects of pantoprazole in experimental acute pancreatitis.
Oxidative stress with free radicals plays a crucial role in acute pancreatitis (AP). Pantoprazole (PPZ), widely used as a proton pump inhibitor, possesses reactivity towards hydroxyl radicals. The aim of the study was to examine the effect of PPZ on the course of experimental AP. Mild AP was induced in rats by caerulein (n=12). Severe AP was induced by infusion of glycodeoxycholic acid (10mM) into the pancreatic duct combined with caerulein (n=12). Both AP models were randomized to PPZ treatment (20mg/kg at baseline and after 12h) or placebo. Control animals received Ringer solution (n=6) without AP induction. After 24h severity of AP was examined by histology, enzyme levels, edema and inflammatory markers (myeloperoxidase, protein profiling). Furthermore, CD62P and CD31 for leukocyte and platelet activation were investigated. Histology showed that PPZ treatment reduced tissue infiltration of inflammatory cells and acinar cell necrosis in severe AP. After PPZ treatment CD62P expression in mild AP and CD31 expression in severe pancreatitis decreased, indicating an inhibition of platelet activation. In mild and severe AP, PPZ significantly decreased amylase, LDH, edema and myeloperoxidase activity. Protein profile of pancreatic juice and serum revealed different spectra and less pancreatic juice proteins in PPZ treated groups indicating less acinar cell leakage. PPZ possesses anti-inflammatory in vivo properties and attenuates the course of AP. This is mediated via a reduced expression of inflammatory and adhesive proteins with a consecutive decrease in platelet and leukocyte activation as key steps in the pathogenesis of AP.


Dasotraline as a selective cytochrome 2B6 inhibitor for reaction phenotyping.
Reaction phenotyping using human liver microsomes or hepatocytes with chemical inhibitors is one of the most commonly applied methods to assess the fraction metabolized (fm ) of drug candidates by enzymes. The fm information is critical to understanding the risk of victim drug-drug interactions in the clinic. Inhibitor selectivity is essential in order to generate reliable data and irreversible inhibitors are often preferred over reversible inhibitors to minimize the impact of inhibitor depletion. Although many selective cytochrome P450 (CYP) inhibitors are available, the identification of selective CYP2B6 inhibitors has been challenging due to cross inhibition to the other enzymes. In this study, dasotraline was evaluated as a selective inactivator of CYP2B6 under reaction phenotyping conditions with human hepatocytes. The results show that dasotraline is a very selective inactivator for CYP2B6 with minimal inhibition to other enzymes. A concentration of 0.1 μM dasotraline is recommended for reaction phenotyping with a hepatocyte cell density of 0.5 million cells/ml or 0.5 μM for 2 million cells/ml, when using a 15 minute preincubation, as well as the protocol of inactivator removal before the addition of substrates.


Characteristics of attenders to community based alcohol treatment centre with special reference to sex difference.
Alcohol misusers attending a London community day treatment centre were interviewed about their drinking habits and the expectations they had of the treatment they were receiving. The results show that the women experienced twice as many alcohol related problems as the men and were significantly more dependent upon alcohol. The men reported that they hoped to improve their health and confidence by coming for treatment.


Private speech use in arithmetical calculation: relationship with phonological memory skills in children with and without mathematical difficulties.
The majority of recent studies conclude that children's private speech development (private speech internalisation) is important for mathematical development and subject to disabling. The main concern of the present study was whether or not the two phonological memory factors evaluated in the study (i.e. the results of children's digit span assessments, both forward and backward) relates to private speech internalisation and whether this relationship changes with children's age, or mathematical achievement levels, or both. We made comparisons between children with acknowledged mathematical difficulties (MD) and children without mathematical difficulties (MN), basing on private speech differences, phonological memory differences and differences in the relationship between private speech internalisation and phonological memory skills. The results not only confirm the impact of private speech internalisation but also emphasise a possible parallel role of phonological memory for subsequent mathematical achievement. In contrast to the MD children, children without MD showed an age-determined shift from a lesser to greater relationship between a high level of private speech internalisation and a high level phonological memory skills. As a whole, the results are consistent with a developmental difference and not with a developmental delay model and suggest that relationships between private speech internalisation and phonological memory may reflect individual differences in children's mathematical achievement. The results are discussed in terms of directions for future research.


Technological delegation: responsibility for the unintended.
This article defends three interconnected premises that together demand for a new way of dealing with moral responsibility in developing and using technological artifacts. The first premise is that humans increasingly make use of dissociated technological delegation. Second, because technologies do not simply fulfill our actions, but rather mediate them, the initial aims alter and outcomes are often different from those intended. Third, since the outcomes are often unforeseen and unintended, we can no longer simply apply the traditional (modernist) models for discussing moral responsibility. We need to reinterpret moral responsibility. A schematic layout of a model on Social Role-Responsibility that incorporates these three premises is presented to allow discussion of a new way of interpreting moral responsibility.


Changes in the faecal bacterial microbiota during hospitalisation of horses with colic and the effect of different causes of colic.
Previous studies have identified alterations in the faecal microbiota of horses with colic; however, further work is needed to interpret these findings. To compare the faecal microbiota of horses presenting for colic at hospital admission, day 1 and day 3/discharge and with different colic duration and lesion locations. Prospective observational clinical study. Faecal samples were collected from 17 colic cases at hospital admission, on day 1 and on day 3 post-admission or at the time of hospital discharge if prior to 72 hours. Faecal samples were extracted for genomic DNA, PCR-amplified, sequenced and analysed using QIIME. Species richness and Shannon diversity (alpha diversity) were estimated. The extent of the relationship between bacterial communities (beta diversity) was quantified using pairwise UniFrac distances, visualised using principal coordinate analysis (PCoA) and statistically analysed using permutational multivariate analysis of variance (PERMANOVA). The relative abundance of bacterial populations at the different time points and in different types of colic was compared using ANCOM. There was a decrease in species richness from admission to day 3/hospital discharge (P < .05), and a lower species richness (P = .005) and Shannon diversity (P = .02) in horses with colic ≥60 h compared to <60 h. Based on PCoA and PERMANOVA, there was a significant difference in bacterial community composition for horses with different colic duration (P = .001) and lesion location (P = .006). Several differences in bacterial phyla and genera were observed at different time points and with different types of colic. Relatively low numbers and a diverse population of horses. The microbiota change from hospital admission to day 3/discharge in horses with colic and horses with colic ≥60 h and large colon lesions have a distinct bacterial population compared to horses with colic <60 h and small intestinal lesions.


Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level resistance to kanamycin, amikacin, and capreomycin in clinical isolates from mainland China.
Mutations correlating phenotypic resistance level with the injectable second-line anti-tuberculosis drugs (SLDs) including kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) remain elusive. A collection of 114 Mycobacterium tuberculosis clinical isolates from mainland China was analyzed. The minimum inhibitory concentration (MIC) of each strain was determined and the sequences of rrs, tlyA, promoter of eis as well as 5' untranslated region (UTR) of whiB7 were amplified and sequenced. No mutation in tlyA, promoter of eis and 5' UTR of whiB7, was found to be associated with resistance among these samples. Sequencing data of 1400 rrs region demonstrated the A1401G mutation in rrs was prevalent, which presented in 84% of the KAN resistant isolates while only in about 50% of the AMK or CAP resistant isolates. Furthermore, most of the resistant isolates with A1401G mutation showed high-level resistance to these injectable SLDs. In conclusion, our results suggest the rrs A1401G mutation was related to high-level resistance to KAN, AMK, and CAP in M. tuberculosis isolates from mainland China.


Activation of Toll-like receptor 4 (TLR4) attenuates adaptive thermogenesis via endoplasmic reticulum stress.
Adaptive thermogenesis is the cellular process transforming chemical energy into heat in response to cold. A decrease in adaptive thermogenesis is a contributing factor to obesity. However, the molecular mechanisms responsible for the compromised adaptive thermogenesis in obese subjects have not yet been elucidated. In this study we hypothesized that Toll-like receptor 4 (TLR4) activation and subsequent inflammatory responses are key regulators to suppress adaptive thermogenesis. To test this hypothesis, C57BL/6 mice were either fed a palmitate-enriched high fat diet or administered with chronic low-dose LPS before cold acclimation. TLR4 stimulation by a high fat diet or LPS were both associated with reduced core body temperature and heat release. Impairment of thermogenic activation was correlated with diminished expression of brown-specific markers and mitochondrial dysfunction in subcutaneous white adipose tissue (sWAT). Defective sWAT browning was concomitant with elevated levels of endoplasmic reticulum (ER) stress and autophagy. Consistently, TLR4 activation by LPS abolished cAMP-induced up-regulation of uncoupling protein 1 (UCP1) in primary human adipocytes, which was reversed by silencing of C/EBP homologous protein (CHOP). Moreover, the inactivation of ER stress by genetic deletion of CHOP or chemical chaperone conferred a resistance to the LPS-induced suppression of adaptive thermogenesis. Collectively, our data indicate the existence of a novel signaling network that links TLR4 activation, ER stress, and mitochondrial dysfunction, thereby antagonizing thermogenic activation of sWAT. Our results also suggest that TLR4/ER stress axis activation may be a responsible mechanism for obesity-mediated defective brown adipose tissue activation.


Epithelioid Hemangioendothelioma of the Lower Limb, Discovered by a Claudication.
Epithelioid hemangioendothelioma (EHE) is a rare case of a tumor with different clinical behaviors and a difficult anatomopathological diagnosis. The diagnosis of EHE is usually confirmed by postoperative histopathologic examination. Actually, it is a challenge to put a correct diagnosis and to propose aggressive treatment. We report a case of an EHE of the left lower limb discovered in a 53-year-old claudicant woman. Surgical resection, arterial, and venous bypass were performed. The histology demonstrated EHE with a low mitotic index, emerging for the femoral vein.


Machine learning in cardiovascular radiology: ESCR position statement on design requirements, quality assessment, current applications, opportunities, and challenges.
Machine learning offers great opportunities to streamline and improve clinical care from the perspective of cardiac imagers, patients, and the industry and is a very active scientific research field. In light of these advances, the European Society of Cardiovascular Radiology (ESCR), a non-profit medical society dedicated to advancing cardiovascular radiology, has assembled a position statement regarding the use of machine learning (ML) in cardiovascular imaging. The purpose of this statement is to provide guidance on requirements for successful development and implementation of ML applications in cardiovascular imaging. In particular, recommendations on how to adequately design ML studies and how to report and interpret their results are provided. Finally, we identify opportunities and challenges ahead. While the focus of this position statement is ML development in cardiovascular imaging, most considerations are relevant to ML in radiology in general. KEY POINTS: • Development and clinical implementation of machine learning in cardiovascular imaging is a multidisciplinary pursuit. • Based on existing study quality standard frameworks such as SPIRIT and STARD, we propose a list of quality criteria for ML studies in radiology. • The cardiovascular imaging research community should strive for the compilation of multicenter datasets for the development, evaluation, and benchmarking of ML algorithms.


Preoperative assessment of chemotherapeutic associated liver injury based on indocyanine green retention test.
The aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI). Patients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered. 166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria. The median number of cycles of preoperative chemotherapy was 6.0 ± 4.87. Chemotherapy was mainly based on oxaliplatin in 123 (74.1%). Bevacizumab was associated in 51(31%) patients. A total of 102 (61.4%) patients had at least 1 CALI. Grade 2-3 steatosis occurred in 56 (33.7%) patients and steatohepatitis in19(11.5%). Sinusoidal obstructive syndrome (SOS) was presented in 93 (56%) patients. 23(13.8%) patients had nodular regeneration hyperplasia. At multivariate analysis the only predictive factor of ICGR≥10% was age≥65 years (p = 0.001). A median split (ICGR15 = 8%) was used to categorized ICGR15 value. Multivariate analysis showed that age≥ 65 [OR 2.530 (CI95% 1.28-4.97) p < 0.001], male sex [OR 2.614 (CI95% 1.31-5.20) p < 0.001], SOS [OR 1.954 (CI95% 1.00-3.81) p = 0.050] and administration of Bevacizumab [OR 2.201 (CI95% 1.07-4.50) p = 0.031] were predictive factors for ICGR≥8%. ICGR15 test can predict the diagnosis of SOS. High ICGR15 value is more common in elderly male patients and after bevacizumab administration.


Imipenem (N-formimidoyl thienamycin): in vitro antimicrobial activity and beta-lactamase stability.
In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers. More extensive comparative studies were also performed with 605 representative isolates, comparing imipenem to six other beta-lactams. Although the newer beta-lactams were often more active against susceptible species, imipenem demonstrated the broadest spectrum of antibacterial activity, with MIC 90s less than or equal to 4.0 micrograms/ml for all species tested except Pseudomonas maltophilia and P. cepacia. Imipenem was very active against all streptococci and staphylococci, in contrast to the third-generation cephalosporins. There was no evidence of cross-resistance between imipenem and the cephalosporins or penicillins. Resistance to hydrolysis by seven beta-lactamase preparations was documented for imipenem, cefotaxime, and moxalactam. Like many other beta-lactams, imipenem inhibited the Type I beta-lactamase produced by Enterobacter cloacae. Other beta-lactamases from gram-negative bacilli were also inhibited by high concentrations of imipenem.


Combining the genetic algorithm and successive projection algorithm for the selection of feature wavelengths to evaluate exudative characteristics in frozen-thawed fish muscle.
The potential use of feature wavelengths for predicting drip loss in grass carp fish, as affected by being frozen at -20°C for 24 h and thawed at 4°C for 1, 2, 4, and 6 days, was investigated. Hyperspectral images of frozen-thawed fish were obtained and their corresponding spectra were extracted. Least-squares support vector machine and multiple linear regression (MLR) models were established using five key wavelengths, selected by combining a genetic algorithm and successive projections algorithm, and this showed satisfactory performance in drip loss prediction. The MLR model with a determination coefficient of prediction (R(2)P) of 0.9258, and lower root mean square error estimated by a prediction (RMSEP) of 1.12%, was applied to transfer each pixel of the image and generate the distribution maps of exudation changes. The results confirmed that it is feasible to identify the feature wavelengths using variable selection methods and chemometric analysis for developing on-line multispectral imaging.


Using Microinjection of Mammalian Cultured Cells to Study Cell Division.
The introduction of macromolecules directly into individual cells by microinjection is an important technique for manipulating mitotic cells. mRNA, purified proteins, or concentrated antibodies can all be injected directly into a single cell, and their effects monitored by live-cell imaging. The equipment necessary is relatively simple, and the technique can be easily mastered. Here we describe our microinjection setup, how to microinject cultured mammalian cells in mitosis, and how to analyze those cells by same-cell live and fixed imaging.


Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma.
This prospective study was designed to examine whether consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES-BCAA) administration group. Liver function testing was performed and Child-Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post-RFA. Compared to the control and M-BCAA groups, the LES-BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post-RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement-induced vomiting. LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance.


Standardized fracture creation in the distal humerus and the olecranon for surgical training and biomechanical testing.
Surgical training and biomechanical testing require models that realistically represent the in vivo injury condition. The aim of this work was to develop and test a method for the generation of distal humerus fractures and olecranon fractures in human specimens, while preserving the soft tissue envelope. Twenty-one cadaveric upper extremity specimens (7 female, 14 male) were used. Two different experimental setups were developed, one to generate distal humerus fractures and one to generate olecranon fractures. Specimens were placed in a material testing machine and fractured with a predefined displacement. The force required for fracturing and the corresponding displacement were recorded and the induced energy was derived of the force-displacement graphs. After fracturing, CT imaging was performed and fractures were classified according to the AO classification. Eleven distal humerus fractures and 10 olecranon fractures with intact soft tissue envelope could be created. Distal humerus fractures were classified as AO type C (n = 9) and as type B (n = 2), all olecranon fractures were classified as AO type B (n = 10). Distal humerus fractures required significantly more load than olecranon fractures (6077 N ± 1583 vs 4136 N ± 2368, p = 0.038) and absorbed more energy until fracture than olecranon fractures (17.8 J ± 9.1 vs 11.7 J ± 7.6, p = 0.11), while the displacement at fracture was similar (5.8 mm ± 1.6 vs 5.9 mm ± 3.1, p = 0.89). The experimental setups are suitable for generating olecranon fractures and distal humerus fractures with intact soft tissue mantle for surgical training and biomechanical testing.


Topical Chinese herbal medicine in treating atopic dermatitis (eczema): A systematic review and meta-analysis with core herbs exploration.
Topical Chinese herbal medicine (CHM) is commonly used to relieve atopic dermatitis (AD); however, the up-to-date evidence concerning the effectiveness of topical CHM on treating AD is lacking. Moreover, the CHM prescriptions are often too complicated to realize the overall mechanisms of CHM, especially when compared to western medicines (WM). To evaluate the effectiveness of topical CHM for treating AD by conducting a meta-analysis on randomized clinical trials (RCTs). Twenty RCTs comparing topical CHM to active control/placebo were included in the final analysis. The primary outcome was the symptom scores changed from baseline and the effectiveness rate was the secondary outcome. Subgroup analysis on different initial symptom severity and the different interventions in control groups was performed. System pharmacology analysis was performed to explore core CHM and possible pharmacological mechanisms of CHM for AD. Compared with active/blank placebo, topical CHM seemed more effective (SMD: -0.35, 95 %CI: -0.59 to -0.10, p-value = 0.005, I2 = 60%). The effectiveness rate was higher (RR: 1.29, 95 %CI 1.15-1.44, p-value <0.00001, I2 = 71%). In subgroup analysis, mild and moderate AD patients with topical CHM were more effective than placebo (SMD: -0.28, 95 %CI -0.56 to -0.01, p-value = 0.04, I2 = 5%; -0.34, 95%CI -0.64 to -0.03, p-value = 0.03, I2 = 0%, separately). Topical CHM has 1.25 times more effective than the topical glucocorticoid (95 %CI 1.09-1.43, p-value = 0.001, I2 = 64%). Core CHMs, such as Phellodendron chinense C.K. Schneid., Sophora flavescens Ait., Cnidium monnieri (L.) Cusson, and Dictamnus dasycarpus Turcz., had effects on the pathways on immune and metabolism systems different from WM. Our results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.


A Rare Case of Pott's Disease (Spinal Tuberculosis) Mimicking Metastatic Disease in the Southern Region of Denmark.
Pott's disease (PD) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (TB) cases. The incidence of PD has recently increased in Europe and the United States, mainly due to immigration; however, it is still a rare diagnosis in Scandinavian countries, and if overlooked it might lead to significant neurologic complications. A 78-year-old woman, originally from Eastern Europe, presented to the emergency department with a complaint of nausea, vomiting, weight loss, and severe back pain. On admission she was febrile and had leukocytosis and increased C-reactive protein. Initial spinal x-ray was performed and revealed osteolytic changes in the vertebral body of T11 and T12. Magnetic resonance imaging (MRI) of the spine illustrated spondylitis of T10, T11, and T12, with multiple paravertebral and epidural abscesses, which was suggestive of PD. Polymerase chain reaction (PCR) of the patient's gastric fluid was positive for Mycobacterium tuberculosis (MT). Based on MRI and PCR findings, standard treatment for TB was initiated. Results of the spine biopsy and culture showed colonies of MT and confirmed the diagnosis afterwards. Due to the instability of the spine and severe and continuous pain, spine-stabilizing surgery was performed. Her TB was cured after nine months of treatment. PD is an important differential diagnosis of malignancy that should be diagnosed instantly. History of exposure to TB and classic radiologic finding can help make the diagnosis.


Signs and symptoms that trigger nurses' concerns about deteriorating conditions in hospitalized pediatric patients: a scoping review protocol.
The objective of this scoping review is to identify and map the signs and symptoms that trigger nurses' concerns about the deteriorating conditions of hospitalized pediatric patients. Standardized observations and risk assessments of hospitalized pediatric patients are important in modern health systems. The Pediatric Early Warning Score (PEWS) is based on objective criteria, such as vital parameters, but does not include subjective criteria, such as nurses' worry. A Dutch study has shown that adding indicators for "worry" or "concern" to an early warning system based on vital signs improves the prediction of unplanned adult admissions to intensive care units. However, this has not been studied in a pediatric population. Clarifying the signs and symptoms that trigger nurses' concerns about pediatric patients' conditions could possibly help them take actions based on their intuitive feelings and obtain medical support for pediatric patients in the early stages of deterioration. This review will consider studies that include nurses working in hospital settings who care for pediatric patients (up to 18 years of age). Specifically, this scoping review will explore the signs and symptoms that underlie nurses' concerns about a pediatric patient's condition when the patient's vital signs are not a cause of worry. This scoping review will be conducted in accordance with the JBI methodology for scoping reviews. The review will search MEDLINE (via PubMed), CINAHL, Embase, Scopus and Swemed databases. The review will also search for unpublished PhD dissertations using the ProQuest Dissertations and Theses.


Presenile dementia--the use of the flash and pattern VEP in diagnosis.
Flash, pattern reversal and pattern onset-offset VEPs were recorded in 17 patients with a clinical diagnosis of presenile dementia. The results were compared with those from two control groups--17 normal volunteers of equivalent ages and 17 patients from the same psychiatric hospital with affective disorders but no clinical evidence of dementia. The flash P2 component was found to be significantly delayed in the group of patients with dementia, but the latency of the P1 component and pattern VEP components were all within normal limits. This unusual finding presents a useful index for the diagnosis of presenile dementia.


Detection of high-risk human papillomavirus by two molecular techniques: hybrid capture and linear array.
A number of human papillomaviruses (HPV) are the etiological agents of cervical cancer. The present study compared the performance of the hybrid capture method with that of linear array for the detection of high-risk HPV in 218 cervical samples. For the linear array technique, the DNA was extracted using two different procedures, one manual and the other automated. There was no difference in high-risk HPV (HR-HPV) detectability between the two extraction procedures but the automated procedure had the advantages of simplicity, time and efficiency. There was agreement in 199 (91.3%) of the results. The K value for the two assays was 0.81 indicative of "near perfect" agreement. Both methods, hybrid capture and linear array, are sensitive options for detection of HPV in cervical samples. Linear array enables the identification of the genotype present in the sample and the presence of multiple infections.


Binding and release of cholesterol in the Osh4 protein of yeast.
Sterols have been shown experimentally to bind to the Osh4 protein (a homolog of the oxysterol binding proteins) of Saccharomyces cerevisiae within a binding tunnel, which consists of antiparallel beta-sheets that resemble a beta-barrel and three alpha-helices of the N-terminus. This and other Osh proteins are essential for intracellular transport of sterols and ultimately cell life. Molecular dynamics (MD) simulations are used to study the binding of cholesterol to Osh4 at the atomic level. The structure of the protein is stable during the course of all MD simulations and has little deviation from the experimental crystal structure. The conformational stability of cholesterol within the binding tunnel is aided in part by direct or water-mediated interactions between the 3-hydroxyl (3-OH) group of cholesterol and Trp(46), Gln(96), Tyr(97), Asn(165), and/or Gln(181) as well as dispersive interactions with Phe(42), Leu(24), Leu(39), Ile(167), and Ile(203). These residues along with other nonpolar residues in the binding tunnel and lid contribute nearly 75% to the total binding energy. The strongest and most populated interaction is between Gln(96) and 3-OH with a cholesterol/Gln(96) interaction energy of -4.5 +/- 1.0 kcal/mol. Phe(42) has a similar level of attraction to cholesterol with -4.1 +/- 0.3 kcal/mol. A MD simulation without the N-terminus lid that covers the binding tunnel resulted in similar binding conformations and binding energies when compared with simulations with the full-length protein. Steered MD was used to determine details of the mechanism used by Osh4 to release cholesterol to the cytoplasm. Phe(42), Gln(96), Asn(165), Gln(181), Pro(211), and Ile(206) are found to direct the cholesterol as it exits the binding tunnel as well as Lys(109). The mechanism of sterol release is conceptualized as a molecular ladder with the rungs being amino acids or water-mediated amino acids that interact with 3-OH.


In vitro antibacterial activity of ceftazidime/avibactam in combination against planktonic and biofilm carbapenemase-producing Klebsiella pneumoniae isolated from blood.
The aim of this study was to report on in vitro tests of antibacterial activity of ceftazidime/avibactam in combination against planktonic or biofilm KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), the rate of KPC-Kp blood isolates in University of Perugia Hospital over a 5-year period, and their antimicrobial susceptibility patterns. The antibacterial activity of ceftazidime/avibactam in combination with other antimicrobials was assessed against planktonic and biofilm bacteria by Etest and checkerboard assay. A retrospective review of laboratory data was performed to evaluate the rate of KPC-Kp from blood samples and their antimicrobial susceptibility patterns. Between 2014 and 2019, 130/4241 (3.1%) KPC-Kp were identified from blood cultures. Their rate increased from 2.3% in 2014-2015 to 4.5% over the last 3 years. Overall, 4.6% (6/130) of KPC-Kp isolates were susceptible to meropenem, 65.4% (85/130) to colistin, 65.1% (84/129) to tigecycline, 34.6% (45/130) to amikacin, 36.2% (42/116) to gentamicin, 40.2% (39/97) to fosfomycin and 91.5% (65/71) to ceftazidime/avibactam. Five of six ceftazidime/avibactam-resistant KPC-Kp were isolated from patients not treated with ceftazidime/avibactam. Synergism was detected both by Etest and checkerboard assay for the combination of ceftazidime/avibactam plus meropenem against planktonic isolates, whilst lower bactericidal activity was observed in biofilm KPC-Kp isolates. Our in vitro data suggest that the combination of ceftazidime/avibactam plus meropenem has a synergistic antibacterial activity against planktonic bacteria, whilst a lower activity was detected against biofilm, suggesting worse clinical outcomes whenever biofilm infections are present. Further analyses are required to confirm these results before extending them to clinical practice.


Prenatal Care for Women Veterans Who Use Department of Veterans Affairs Health Care.
The number of women Veterans of childbearing age enrolling in Department of Veterans Affairs (VA) health care is increasing. Our objective was to describe characteristics of women veterans and resumption of VA care after delivery by use of VA prenatal benefits. We used data from the National Survey of Women Veterans, a population-based survey. VA-eligible women veterans with at least one live birth who had ever used VA and were younger than 45 years when VA prenatal benefits became available were categorized based on self-reported receipt of VA prenatal benefits. Characteristics of by use of VA prenatal benefits were compared using χ2 tests with Rao-Scott adjustment. All analyses used sampling weights. In our analytic sample, of those who potentially had the opportunity to use VA prenatal benefits, 25% used these benefits and 75% did not. Compared with women veterans not using VA prenatal benefits, those who did were more likely to be 18 to 24 years old (39.9% vs. 3.7%; p=.03), and more likely to have self-reported diagnosed depression (62.5% vs. 24.5%; p=.02) and current depression or posttraumatic stress disorder (PTSD) symptoms (depression, 46.1% vs. 8% [p=.02]; PTSD, 52.5% vs. 14.8% [p=.02]). Compared with women veterans not using VA prenatal benefits, those who did were more likely to resume VA use after delivery (p<.001). Pregnant women veterans who use VA prenatal benefits are a high-risk group. Among those who opt not to use these benefits, pregnancy is an important point of attrition from VA health care, raising concerns regarding retention of women veterans within VA and continuity of care.


Analysis of m6A methylation patterns and tumor microenvironment in endometrial cancer.
The N6-methyladenosine (m6A) modification is the most common epigenetic modification in eukaryotic mRNA. In recent years, lots of studies have shown that the tumor microenvironment (TME) plays a critical role in tumor growth and development. However, there are few studies on the interaction between m6A methylation and the TME in uterine corpus endometrial carcinoma (UCEC). Three distinct m6A modification patterns were based on 21 m6A regulators of UCEC patients and tumor-free individuals. We investigated the relationship between m6A modification patterns and associated features of the TME. Differentially expressed genes were selected and the m6A score was established to evaluate the prognosis and immunotherapeutic efficacy of UCEC patients. We identified three different m6A modification patterns. The TME infiltrating characteristics were highly consistent with tumors with three distinct immune phenotypes. Besides, our analysis showed that the m6A score was shown to be useful in predicting clinical outcomes. Patients with the low m6A score seemed to have a better prognosis, a stronger immunotherapeutic response, and a higher tumor mutation burden. Our study explored the influence of m6A modification and TME on the prognosis of cancer patients, which will contribute to the discovery of immunotherapy strategies to improve their prognosis.


Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour Doppler ultrasonography.
To investigate, using transrectal colour Doppler ultrasonography, (TRCDUS) whether perfusion of the bladder and prostate is reduced in elderly patients with lower urinary tract symptoms (LUTS), common in later life, as experimental data suggest that chronic ischaemia has a key role in the development of LUTS. In 32 elderly patients with LUTS (12 women, mean age 82.3 years, group 1; and 20 men, 79.4 years, group 2) perfusion of the bladder neck (in women) and of the bladder neck and prostate (in men) was measured using TRCDUS and the resistive index (RI) and colour pixel density (CPD) determined, assessed by a TRUS unit and special software. To assess the age-related effect two control groups of 10 young healthy women (mean age 42.3 years, group 3) and 10 age-matched healthy men (mean age 41.5 years, group 4) were also enrolled. Irrespective of gender, there was markedly lower bladder perfusion in elderly patients with LUTS than in the younger subjects. The mean (SD) RI of the bladder neck in group 1, of 0.88 (0.06), and group 2, of 0.80 (0.08), was higher than in control groups 3, of 0.62 (0.05), and group 4, of 0.64 (0.09). The results were similar for the CPD measurements. The frequency of daily and nightly micturition showed a strong negative correlation with perfusion in the urinary bladder. In elderly patients with LUTS there was decreased perfusion of the bladder neck and prostate when assessed using TRCDUS. Therefore, decreased perfusion in the urinary bladder might be responsible for the development of LUTS with advancing age.


Effects of Parkia biglobosa aqueous seed extract on some biochemical, haematological and histopathological parameters in streptozotocin induced diabetic rats.
Parkia biglobosa seeds are used to treat diabetes and complications hence this study. This study investigated the effects of Parkia biglobosa aqueous seed extract on some biochemical, haematological and histopathological indices in streptozotocin-induced diabetic rats. Wistar rats of either sex (180-300 g) were fasted overnight and diabetes mellitus induced using streptozotocin 40 mg/kg IP. Diabetes mellitus (fasting blood glucose ≥ 200 mg/dl) was confirmed 48 h later. The rats were randomly grouped into six groups (n = 5): Group 1 (diabetic untreated control), group 2 (Parkia biglobosa 200 mg/kg), group 3 (Parkia biglobosa 400 mg/kg). group 4 (Parkia biglobosa 800 mg/kg), group 5 (glibenclamide 5 mg/kg as standard drug control) and group 6 (normoglycaemic control). They were treated daily. Acute toxicity study and phytochemical screening were also performed. Fourteen days later, they were sacrificed under chloroform anaesthesia. Vital organs (kidneys, liver and pancreas) and blood samples were obtained for histopathological, biochemical and haematological analysis. Parkia biglobosa aqueous seed extract at the various doses caused significant (P < 0.05) elevations in red blood cell parameters in comparison to the diabetic control. The mean cell volume did not differ significantly from the diabetic control while 200 mg/kg and 400 mg/kg doses of the extract did not significantly modify the HCT levels. Treatment with Parkia biglobosa significantly (P < 0.05) lowered white blood cell and platelet counts in comparison to the diabetic control. Liver enzymes and total bilirubin levels were significantly (P < 0.05) reduced while total protein increased in the treated diabetic rats in comparison to controls. Treatment with Parkia biglobosa extract significantly (P < 0.05) increased bicarbonate and sodium ion levels while decreasing potassium ion levels. Chloride levels were not significantly different from the diabetic control. These data suggest that Parkia biglobosa ameliorates biochemical, haematological and histopathological changes associated with diabetes mellitus.


Prescribing for inpatients with schizophrenia: an international multi-center comparative study.
This study compares prescription practices for acute inpatients with schizophrenia among six academic departments located in China, Japan, Hungary, and the U.S. Prescription data for a sample of 429 inpatients from six academic departments were collected on a randomly chosen census day. All patients met criteria for schizophrenia according to DSM-IV and had a length of illness of at least two years. While patients at the different centers varied in their demographic and clinical characteristics, i. e., age, sex, and length of illness, a great variation in prescription patterns for antipsychotic and other psychotropic drugs among centers was observed even within the same country for all the variables studied (i. e., number and dose antipsychotics, atypical and depot antipsychotics, other psychotropic drugs, multiple antipsychotics, and daily dose) except antidepressant use. In most cases these differences persisted even after adjusting for demographic and clinical characteristics (age, sex, and length of illness) of the subjects. Antipsychotics were usually prescribed in divided daily doses in combination with one or more other psychotropic drugs, including anticholinergics, anticonvulsants, benzodiazepines, and non-benzodiazepine hypnotics. Anticholinergic use was more common with typical antipsychotics. Rates of atypical antipsychotic drug use were lowest in the Japanese center. The Japanese center had by far the highest mean daily dose of antipsychotics. The results indicate that prescription patterns in different centers do not follow any specific guidelines for the treatment of schizophrenia. The results also confirm previous findings that prescribing practices for schizophrenia vary greatly among centers and countries. A common prescribing pattern found was the use of atypical antipsychotic drugs in combination with psychotropic drugs, such as anticholinergics, hypnotics, anticonvulsants, and benzodiazepines, administered in multiple daily doses.


Key causes and long-term trends related to emergency department and inpatient hospital admissions of homeless persons in England.
It is estimated that approximately 300,000 people are experiencing homelessness in England. The aim of this study was to evaluate key causes and long-term trends of emergency departments (EDs) and in hospital inpatient admissions of persons experiencing homelessness in England. ED and hospital inpatient admissions data were obtained from Hospital Episode Statistics (HES) covering all National Health Service (NHS) England hospitals. Anyone identified or declared to be experiencing homelessness during the service usage are recorded in HES datasets. Data were extracted for the 10-year study period and compared to the general population, which includes all patients attending the ED or admitted to inpatient care in England. Drug- and alcohol-related causes contribute to the most frequent reasons for attendance and admissions of persons experiencing homelessness in the ED and inpatient respectively. A total of 30,406 ED attendances were recorded for persons experiencing homelessness in the year 2018/2019 (+ 44.9% rise vs 2009/10) of which injuries and poisoning respectively represented 21.8% and 17.9% of all persons experiencing homelessness presentations to the ED. Poisoning (including drug overdose) represented only 1.9% of all attendances by the general population during the same study year (rate ratio vs general populations 9.2 95% CI 9.0-9.4). High mortality rates were observed in relation to presentations attributed to drug- and alcohol-related causes. A total of 14,858 persons experiencing homelessness inpatient admissions were recorded in 2018/2019 (+ 68.6% vs 2009/2010). Psychoactive substance use constituted 12.7% of all admissions in 2018/2019 compared to 0.4% of in the general populations (rate ratio: 33.3, 95% CI: 31.9-34.7). There was a 44.3% rise in the number of admissions related to poisoning in the study period amongst persons experiencing homelessness in England (vs 14.2% in general population). Marked disparities around primary causes of ED and inpatient admissions were identified between persons experiencing homelessness and the general population. There is a continued need for prevention measures to reduce the prevalence of drug and alcohol, injury and poisoning-related admissions to the ED, enhanced service provision at the community level, and multisector collaborations. These initiatives should maximise opportunities for early interventions and improve outcomes for persons experiencing homelessness, including increased accessibility of healthcare and mental health services, particularly in areas that demonstrate increasing ED and inpatient attendance rates over time.


Effects of low dietary intake of methionine, choline or proteins on the biotransformation of arsenite in the rabbit.
The effects of 6 weeks feeding with diets low in methionine, choline, or proteins on the biotransformation and retention of 76As-labelled arsenite (0.4 mg As/kg bw) in rabbits have been studied. All test diets caused a significant decrease in the urinary excretion of dimethyl[76As]-arsinic acid, the main metabolite of inorganic arsenic. This gave rise to an increased retention of arsenic in the tissues, especially liver and lung. The test diets also caused a specific increase of the arsenic concentration in liver microsomes. The results indicate that subjects with a poor nutritional status have a lower capacity of methylating and thereby detoxifying inorganic arsenic.


Proteolytic yeasts isolated from raw, ripe tomatoes and metabiotic association of Geotrichum candidum with Salmonella.
Metabiotic associations between food-borne fungi and bacteria capable of causing human diseases are a public health concern. A survey of decayed and damaged, uncooked, ripe tomatoes was done to determine the presence and prevalence of yeasts capable of increasing the pH pulp tissue, thus creating a more favorable environment for survival and growth of enteric pathogens. Sixty-two of the 371 (16.7%) fungi isolated from 215 decayed or damaged tomatoes; 12 of the 62 (19.4%) yeasts showed proteolytic activity on gelatin agar (GA) and/or standard methods caseinate (SMC) agar. The pH of tomato pericarp (pulp) tissue from which 9 of the 12 yeasts were isolated ranged from 4.3 to 7.5 (mean=5.3) compared to 4.2-5.1 (mean=4.8) for sound pulp tissue in the same tomatoes. The 12 proteolytic yeasts consisted of four strains of Cryptococcus albidus, two strains each of Debaryomyces hansenii and Trichosporon pullulans, and one strain each of Cryptococcus humicolus, Cryptococcus laurentii, Geotrichum candidum, and Sporidiobolus pararoseus. Survival and growth characteristics of a five-serotype mixture of Salmonella co-inoculated with G. candidum into sound (not chill injured) and chill-injured tomatoes were studied. Storage of sound tomatoes at 15 degrees C for 10 days resulted in an increase in population of 7.6 log(10) cfu of Salmonella/g of a 2-g sample of co-infected pulp tissue. Increases were less in tissue inoculated with Salmonella only, Salmonella on day 0 followed by G. candidum on day 3, or G. candidum on day 0 followed by Salmonella on day 3. Trends were similar in sound inoculated tomatoes stored at 25 degrees C. Growth of Salmonella was enhanced in chill-injured tomatoes compared to sound tomatoes; a population of 10 log(10) cfu/g of chill-injured pulp tissue was reached within 10 days at 25 degrees C. Results clearly show that growth of a proteolytic, alkalinizing yeast such as G. candidum in raw tomatoes enhances conditions for growth of Salmonella. The removal of tomatoes infected with proteolytic yeasts and other fungi from lots intended for minimally processed tomato products is an essential step in reducing the risk of human diseases caused by pathogenic bacteria favored by increased pH of decayed pulp tissue.


Videofluoroscopic Evaluation of the Influence of a Gradually Reducing Femoral Radius on Joint Kinematics During Daily Activities in Total Knee Arthroplasty.
Paradoxical anterior translation in midflexion is reduced in total knee arthroplasties (TKAs) with a gradually reducing femoral radius, when compared to a 2-radii design. This reduction has been shown in finite element model simulations, in vitro tests, intraoperatively, and recently also in vivo during a lunge and unloaded flexion-extension. However, TKA kinematics are task dependent and this reduction has not been tested for gait activities. Thirty good outcome subjects (≥1 year postoperatively) with a unilateral cruciate-retaining TKA with a gradually reducing (n = 15) or dual (n = 15) femoral radius design were assessed during 5 complete cycles of level walking, stair descent (0.18-m steps), deep knee bend, and sitting down onto and standing up from a chair, using a moving fluoroscope (25 Hz, 1 ms shutter time). Kinematic data were extracted by 2D/3D image registration. Tibiofemoral ranges of motion for flexion-extension, abduction-adduction, internal-external rotation, and anteroposterior (AP) translation were similar for both groups, whereas the pattern of AP translation-flexion-coupling differed. The subjects with the dual-radii design showed a sudden change in direction of AP translation around 30° of flexion, which was not present in the subjects with the gradually reducing femoral radius design. Through the unique ability of moving fluoroscopy, the present study confirmed that the gradually reducing femoral radii eliminated the paradoxical sudden anterior translation at 30° present in the dual-radii design in vivo during daily activities, including gait and stair descent.


Adsorption and removal of organophosphorus pesticides from Chinese cabbages and green onions by using metal organic frameworks based on the mussel-inspired adhesive interface.
Based on the mussel-inspired adhesive interface (Fe3O4-g-C3N4@PDA), a novel bionic metal-organic framework (Fe3O4-g-C3N4-PDA@MIL-101) was successfully prepared. The composite featured a high specific surface area and a multi-microchannel structure, as well as strong thermochemical stability. The structural property of Fe3O4-g-C3N4-PDA@MIL-101(Fe) was characterized, and the results indicated that Fe3O4, PDA, and MIL-101(Fe) were uniformly coated on the g-C3N4 surface. The adsorption and desorption of organophosphorus pesticides with Fe3O4-g-C3N4-PDA@MIL-101(Fe) were evaluated by batch experiments. This composite showed high adsorption efficiency and selective removal of coralox, phosalone, and chlorpyrifos. Under the optimal conditions, three organophosphorus pesticides were adsorbed from Chinese cabbage and green onion samples with Fe3O4-g-C3N4-PDA@MIL-101(Fe). The analytical method exhibited high sensitivity (LOD, 0.19-2.34 μg/L; LOQ, 0.65-7.82 μg/L), excellent practicality, and good stability, suggesting that Fe3O4-g-C3N4-PDA@MIL-101 was an ideal candidate magnetic adsorbent for the removal of organophosphorus pesticides in Chinese cabbage and green onion samples.


Proliferating trichilemmal cyst: an ultrastructural study.
A 73-year-old woman had a walnut-sized tumor in the occipital region for 10 years. The growth consisted of multiple small and large cystic epithelial masses. The cyst wall exhibited trichilemmal keratinization. Numerous squamous eddies as well as many glycogen-rich cells were present in the cyst wall. Some small round keratohyalin granules were observed in the cells below the horny layer. The desmosomes and masses of lipid droplets were seen in the horny layer. The findings described above are similar to those observed in the follicular isthmus and the follicular infundibulum. Other interesting findings include the presence of intranuclear inclusions of tonofilament-like material and/or keratohyalin-like granules within the cells near the mid-layer of the cyst wall.


Variant Philadelphia translocation in an immunologically and clinically typical case of chronic myeloid leukaemia.
Cytogenetic analysis of bone marrow from a chronic myeloid leukemia patient in chronic phase revealed a classical Philadelphia chromosome from a complex translocation t(2;9;22). The break points on 9 and 22 were, apparently, the same as for the standard translocation (9;22). However, whereas the terminal band of 9 (9q34) was translocated in the usual site, that is on 22q-, the tract deleted from 22 was present on band p13 of chromosome 2. The finding of this rare 22 translocation in classical CML would seem to support the hypothesis that the crucial event in the pathogenesis of CML is the translocation of band 9q34, that contains the c-abl oncogene, onto the Ph' chromosome, rather than the translocation of the tract deleted from 22 to some other chromosome site.


Cigarette smoking has no pro-cognitive effect in subjects with obsessive-compulsive disorder: A preliminary study.
The prevalence of cigarette smoking in patients with different psychiatric disorders is higher than that in the general population, which is partly explained by the pro-cognitive effect of smoking on cognitive functions. In subjects with obsessive-compulsive disorder (OCD), the prevalence of smokers is lower than that in other psychiatric disorders. We hypothesized that cigarette smoking does not provide benefits and even worsen cognitive performance in OCD. We compared different executive function subdomains in 20 smoking and 20 non-smoking inpatients with OCD. At the beginning of hospitalization, we assessed visuo-spatial working memory, planning and set-shifting abilities (Cambridge Neuropsychological Test Automated Battery), smoking habits (standardized personal interviews), and the severity of obsessive-compulsive symptoms (Dimensional Yale-Brown Obsessive-Compulsive Scale). The performance of smokers and non-smokers did not differ significantly in any cognitive subdomain. The smoking duration was significantly associated with poorer visuo-spatial working memory performance (P=0.001). Our results showed that cigarette smoking did not provide cognitive enhancement across various executive function subdomains in subjects with OCD. The lack of beneficial cognitive effects of smoking may make these subjects less prone to smoking and may partially explain the lower rate of smokers in OCD compared with other psychiatric conditions.


Two-dimensional high-performance liquid chromatographic method for assaying S-adenosyl-L-methionine and its related metabolites in tissues.
S-Adenosyl-L-methionine (SAM) is a methyl-donor compound which is actively involved in a variety of biochemical reactions. An assay has been developed permitting the quantitative measurement of SAM and its related metabolites (S-adenosylhomocysteine, decarboxylated SAM, methylthioadenosine, adenosine and adenine) in liver and cell cultures. As gradient reversed-phase chromatographic or cation-exchange chromatographic methods often resulted in overlapping peaks, a two-dimensional high-performance liquid chromatographic (HPLC) procedure was developed involving gradient reversed-phase chromatographic separation followed by ion-exchange chromatography. After precipitating large molecules in the sample by perchloric acid, gel permeation was carried out on a Sephadex G 25 column to separate small water-soluble metabolites from proteins and membrane fragments. The freeze-dried sample was injected onto an ODS column and a 0-10% acetonitrile gradient in 10 mM ammonium formate buffer (pH 2.9) (20 min, linear) was applied. The relevant fractions were collected and injected onto a cation-exchange column (Partisil SCX, 10 microns, 250 mm x 4.6 mm I.D.). Elution and quantification were carried out using ammonium formate buffers of various concentration (15-400 mM), pH 2.9. The detector response (254 nm) as a function of concentration was linear over the concentration range 30-500 pmol. The detection limits of the compounds after the two-dimensional chromatographic procedure ranged from 10 to 60 pmol and the recovery was higher than 70%. The reproducibility of the results obtained from given samples was within 9-22% for rat liver and 6-24% for mast cells.


Enhancing slow wave sleep with sodium oxybate reduces the behavioral and physiological impact of sleep loss.
To investigate whether enhancement of slow wave sleep (SWS) with sodium oxybate reduces the impact of sleep deprivation. Double-blind, parallel group, placebo-controlled design Sleep research laboratory Fifty-eight healthy adults (28 placebo, 30 sodium oxybate), ages 18-50 years. A 5-day protocol included 2 screening/baseline nights and days, 2 sleep deprivation nights, each followed by a 3-h daytime (08:00-11:00) sleep opportunity and a recovery night. Sodium oxybate or placebo was administered prior to each daytime sleep period. Multiple sleep latency test (MSLT), psychomotor vigilance test (PVT), Karolinska Sleepiness Scale (KSS), and Profile of Mood States were administered during waking hours. During daytime sleep, the sodium oxybate group had more SWS, more EEG spectral power in the 1-9 Hz range, and less REM. Mean MSLT latency was longer for the sodium oxybate group on the night following the first daytime sleep period and on the day following the second day sleep period. Median PVT reaction time was faster in the sodium oxybate group following the second day sleep period. The change from baseline in SWS was positively correlated with the change in MSLT and KSS. During recovery sleep the sodium oxybate group had less TST, SWS, REM, and slow wave activity (SWA) than the placebo group. Pharmacological enhancement of SWS with sodium oxybate resulted in a reduced response to sleep loss on measures of alertness and attention. In addition, SWS enhancement during sleep restriction appears to result in a reduced homeostatic response to sleep loss.


Juvenile-onset systemic lupus erythematosus: Update on clinical presentation, pathophysiology and treatment options.
Juvenile-onset systemic lupus erythematosus (jSLE) accounts for up to 20% of all SLE patients. Key differences between juvenile- and adult-onset (aSLE) disease include higher disease activity, earlier development of damage, and increased use of immunosuppressive treatment in jSLE suggesting (at least partial) infectivity secondary to variable pathomechanisms. While the exact pathophysiology of jSLE remains unclear, genetic factors, immune complex deposition, complement activation, hormonal factors and immune cell dysregulation are involved to variable extents, promising future patient stratification based on immune phenotypes. Though less effective and potentially toxic, jSLE patients are treated based upon evidence from studies in aSLE cohorts. Here, age-specific clinical features of jSLE, underlying pathomechanisms, treatment options and disease outcomes will be addressed. Future directions to improve the care of jSLE patients, including implementation of the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, biomarkers, treat to target and personalized medicine approaches are discussed.


Context dependent substitution biases vary within the human genome.
Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored. To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes. We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome.


Initial clinical and radiological features of patients with multiple sclerosis in Oman.
Multiple sclerosis (MS) is a lifelong demyelinating disorder with a varying disease course, resulting in different degrees of physical disability for affected patients. This study aimed to present the initial clinicoradiological features of Omani MS patients presenting to a tertiary care center in Oman. In this retrospective study, all Omani patients diagnosed with MS from January 2006 to December 2020, whose treatment and followup were conducted in our center, were included. Data was retrieved from the patients' medical records. Disability status was assessed according to the Expanded Disability Status Scale. A total of N = 155 Omani patients were diagnosed with MS of whom 68.4% were female. The mean age at diagnosis was 28.6 ± 8 years. The mean duration from symptoms to diagnosis was 1.9 years. Relapsing-remitting MS was diagnosed in 97.4% patients. Most common presenting symptoms were unifocal (84.5%), supratentorial (34.2%) and optic pathway (33.5%). At first assessment, 94.8% patients had no to mild disabilities and 3.2% had severe disabilities. During the mean follow up period of 61.2 months, the frequency of severe disabilities increased to 12.9%. Out of 155 patients, 98 (63.2%) had their initial brain magnetic resonance (MRI) report available for review, 62/98 (63%) of whom showed ≥ 20 T2-weighted (T2W) lesions. Of these lesions, 75/98 (76.5%) were periventricular, 66 (67.3%) juxtacortical, and 56 (57.1%) infratentorial. The most common initially prescribed disease modifying therapies (DMT) were interferons (104/155; 67%), followed by fingolimod (16; 10.3%), natalizumab (14; 9%) and dimethyl fumarate (4; 2.6%). The results of this study indicate that the demographic and clinicoradiological features of MS patients in Oman are similar to those reported elsewhere in the Arabian Gulf region.


Data of de novo assembly and functional annotation of the leaf transcriptome of Impatiens balsamina.
Impatiens balsamina is both an ornamental and pharmacologically important plant widely distributed in many Asian countries. The leaf of the plant contains many secondary metabolites possessing anti-microbial, anti-tumour and anti-cancer properties. Though there are many phytochemical studies done on the different natural extracts for this plant, not much of genetic information is currently available. This is the first transcriptome of I. balsamina leaf using paired-end Illumina HiSeq sequencing which generated 10.79 GB of raw data. Information of pre-processing (reads filtering), de novo assembly and functional annotation are presented. This data is accessible via NCBI BioProject (PRJNA505711).


Response to IL-6 stimulation of human hepatoblastoma cells: production of pancreatic secretory trypsin inhibitor.
LPS-stimulated macrophage conditioned medium and IL-6 markedly stimulated the secretion of PSTI by cultured hepatoblastoma cells. The mechanism underlying the cellular response of IL-6-induced secretion of PSTI was investigated. Among the agents affecting the signal transduction pathways, forskolin significantly induced PSTI secretion whereas PMA or A23187 did not, suggesting that IL-6 induced PSTI secretion is mediated by cAMP dependent protein kinase A.


Potential cardiovascular consequences of switching from atorvastatin to generic simvastatin in the Netherlands.
The statin authorisation form implemented in the Netherlands in January 2009 has led to significant switching of patients from atorvastatin to generic simvastatin, but often to less than equipotent doses. We sought to assess the potential consequences of this. A modelling analysis was undertaken using data from a pharmacy database covering the majority of drug prescriptions in the Netherlands. Recent meta-analyses provided data on the dose-specific, lipid-modifying potencies of atorvastatin and simvastatin, and the relationship between reduction in low-density lipoprotein cholesterol (LDL-C) achieved by statin therapy and relative reduction in risk of cardiovascular disease (CVD). In the first quarter of 2009, 33.7%, 47.2% and 19.1% of Dutch patients initially on atorvastatin were switched to less potent, equipotent and more potent doses of simvastatin, respectively. The net effect was estimated to be a 6.8% increase in LDL-C. Assuming a pre-switch LDL-C of 2 mmol/L, the predicted relative increases (95%CI) in the risks of all-cause mortality and major cardiovascular events were 1.7% (0.9%-2.6%) and 2.8% (1.6%-4.1%), respectively. In the Netherlands, policy-driven switching from atorvastatin to generic simvastatin led overall to less potent doses being used, with possible significant clinical implications.


Suppression of Plasmodium MIF-CD74 signaling protects against severe malaria.
The deadliest complication of infection by Plasmodium parasites, cerebral malaria, accounts for the majority of malarial fatalities. Although our understanding of the cellular and molecular mechanisms underlying the pathology remains incomplete, recent studies support the contribution of systemic and neuroinflammation as the cause of cerebral edema and blood-brain barrier (BBB) dysfunction. All Plasmodium species encode an orthologue of the innate cytokine, Macrophage Migration Inhibitory Factor (MIF), which functions in mammalian biology to regulate innate responses. Plasmodium MIF (PMIF) similarly signals through the host MIF receptor CD74, leading to an enhanced inflammatory response. We investigated the PMIF-CD74 interaction in the onset of experimental cerebral malaria (ECM) and liver stage Plasmodium development by using a combination of CD74 deficient (Cd74-/- ) hosts and PMIF deficient parasites. Cd74-/- mice were found to be protected from ECM and the protection was associated with the inability of brain microvessels to present parasite antigen to sequestered and pathogenic Plasmodium-specific CD8+ T cells. Infection of WT hosts with PMIF-deficient sporozoites or infection of Cd74-/- hosts with WT sporozoites impacted the survival of infected hepatocytes and subsequently reduced blood-stage associated inflammation, contributing to protection from ECM. We recapitulated these finding with a novel pharmacologic PMIF-selective antagonist that reduced PMIF/CD74 signaling and fully protected mice from ECM. These findings reveal a conserved mechanism for Plasmodium usurpation of host CD74 signaling and suggest a tractable approach for new pharmacologic intervention.


The P-domain or trefoil motif: a role in renewal and pathology of mucous epithelia?
By analogy with epidermal growth factor and EGF-like repeats, the P-domain, or trefoil motif, is a characteristic shuffled module containing six invariant cysteine residues that forms the basic unit for a family of mucin-associated peptides. These P-domain peptides are potential modulators of cell growth and they are also expressed under certain pathological conditions. Furthermore, P-domains have been found as components of extracellular mosaic proteins including certain mucins, where they are thought to play a role either in protein-protein or in lectin-like interactions.


Memory characteristics of silicon nanowire transistors generated by weak impact ionization.
In this study, we demonstrate the static random access memory (SRAM) characteristics generated by weak impact ionization in bendable field-effect transistors (FETs) with n+-p-n+ silicon nanowire (SiNW) channels. Our bendable SiNW FETs show not only superior switching characteristics such as an on/off current ratio of ~105 and steep subthreshold swing (~5 mV/dec) but also reliable SRAM characteristics. The SRAM characteristics originate from the positive feedback loops in the SiNW FETs generated by weak impact ionization. This paper describes in detail the operating mechanism of our device and demonstrates the potential of bendable SiNW FETs for future SRAM applications.


[Recurrence of cutaneous sarcoidosis during immune reconstitution syndrome in an HIV-infected patient].
Association of sarcoidosis and HIV can occur in the context of immune reconstitution syndrome (IRS) after initiation of antiretroviral therapy (ART). Herein we report a case of cutaneous sarcoidosis in remission in an HIV-infected patient but relapsing during IRS associated with initiation of ART. A 33-year-old female HIV-infected patient from Cameroon was treated with triple therapy with good efficacy. The patient previously had a small nodular lesion on her left cheek which disappeared spontaneously 2 months before the diagnosis of HIV infection. Three months after initiation of triple ART, the patient consulted again for recurrence of the lesion, which had gradually increased in size. Clinical examination revealed a purplish-red nodular plaque of lupoid appearance under vitropression, located between the inner corner of the eye, the nasal wing and the left cheek. A skin biopsy revealed giant-cell epithelioid dermal granulomas without caseous necrosis. Blood angiotensin-converting enzyme levels were elevated and intradermal reaction to tuberculin was negative. A diagnosis was made of cutaneous sarcoidosis. The patient was treated with chloroquine 200mg/day for 3 months, resulting in total subsidence of the lesions. No recurrence was observed at 1 year. Introduction of ART has changed the dermatological aspect of HIV infection. In addition to specific dermatological signs specific to HIV and to immunosuppression, there are the cutaneous adverse effects of antiretroviral drugs and skin disorders indicating reconstituted immunity during IRS. Schematically, three forms of IRS may be distinguished: the paradoxical form, the infectious form, and the inflammatory form. The latter corresponds to the onset or exacerbation of inflammatory conditions or autoimmune diseases after the start of ART. Thirty cases of association between sarcoidosis and HIV have been described, of which two-thirds occurred during IRS. The central role of CD4 in sarcoidosis explains its occurrence in HIV patients during reconstitution of the CD4 count. In HIV-infected patients treated with anti-retroviral treatment, certain skin diseases such as sarcoidosis may be related to IRS.


The impact of humor therapy on people suffering from depression or anxiety: An integrative literature review.
To identify and synthesize existing research on the effectiveness and feasibility of multiform humor therapy on people suffering from depression or anxiety, with the hope of benefiting future research. An integrative literature review of quantitative, qualitative, and mixed studies was performed. The PubMed, Cochrane Library, Web of Science, Embase, and CINAHL databases were searched up to March 2022. Two independent reviewers conducted each stage of the review process, by assessing eligibility using preferred reporting items for systematic review and meta-analyses (PRISMA) and quality appraisal using the Mixed Methods Appraisal Tool, and data extraction. In this integrative review, 29 papers were included, containing 2964 participants across a diverse range of studies, including quantitative, qualitative, and mixed methods. The articles were from the United States, Australia, Italy, Turkey, South Korea, Iran, Israel, China, and Germany. The findings indicated that most of the subjects thought humor therapy was effective in improving depression and anxiety while a few participants considered the effect insignificant. However, more high-quality studies will be needed to confirm these conclusions. This review collated and summarized findings from studies examining the impact of humor therapy (medical clowns, laughter therapy/yoga) on people with depression or anxiety, including children undergoing surgery or anesthesia, older people in nursing homes, patients with Parkinson's disease, cancer, mental illness, and undergoing dialysis, retired women, and college students. The results from this review may help inform future research, policy, and practice in humor therapy to improve people's symptoms of depression and anxiety. This systematic review objectively evaluated the effect of humor therapy on depression and anxiety. As a simple and feasible complementary alternative therapy, humor therapy may provide a favorable alternative for clinicians, nurses, and patients in the future.


[Transvestibular closure with an autologous bone graft as surgical repair of a nasoseptal defect due to Le Fort-I osteotomy].
Defects of the nasal septum are a common complication after nasal surgery. Affected patients frequently suffer from bleeding, crusting and impaired nasal air flow. The surgical closure of septal defects remains a distinctive challenge. Though many different techniques have been described, the failure rate of this procedure remains high. In the case presented here, a large basal septum defect occurred after a prosthetic Le Fort-I osteotomy. The attempt to cover the distance between the bony nasal floor and the nasal septum with pedicled mucosal flaps failed due to extensive scar formation of the nasal mucosa. Therefore a nasal floor elevation by insertion of an autologous bone graft from the iliac crest was conducted. The bone graft was connected with the hard palate via two titanium screws. Other than with an autologous cartilage graft, no major resorption of the bone graft is to be expected. This indirect method for the closure of a basal nasal septum defect is new.


Additional to caudal bupivacaine preemptive oral ibuprofen does not improve postoperative pain, nausea or vomiting, and resumption of normal activities in children after ambulatory pediatric urologic surgery.
To investigate the possible advantage of administration of preemptive oral ibuprofen in children after ambulatory pediatric urologic surgery such as penile surgery (circumcision and hypospadias repair) and inguinal surgery (communicating hydrocele and orchidopexy), a study was performed on the experience of postoperative pain, nausea or vomiting, and resumption of normal activities such as normal sleep and play activity. In addition, this study has validated a method of measurement of pain and resumption of normal activities in children. In a prospective, randomized, double-blind study, 66 prepubertal boys (0-12 years) underwent an ambulatory pediatric urological intervention. One hour prior to surgery, the experimental group received 10 mg/kg oral ibuprofen along with their usual premedication (<8 years midazolam 0.5 mg/kg PO or rectal; >8 years or >30 kg alprazolam 0.5 mg, 0.25-0.5 mg PO), whereas the children of the control group received only the usual premedication. Anesthesia was achieved with Sevorane (Sevoflurane) inhalation induction (Sevoflurane 8% in 50% N(2)O/50% O(2)) and a locoregional caudal block (0.5-1.0 ml/kg levobupivacaine 0.25% with a maximum of 30 ml). Immediate postoperative pain was assessed by the child, the parents and a single observer using the Faces Pain Scale and the CHEOPS behavioral scale (Children's Hospital of Eastern Ontario Pain Scale). Vomiting and nausea were also assessed. On the first and second postoperative day the same variables were evaluated by the child and the parents, as well as quality of sleep and play, and need for pain medication. No difference in the experience of pain was found at any point after the operation between the experimental and control groups; moreover, the consumption of pain medication postoperatively did not differ between the two groups. There was also no difference in the incidence of vomiting and nausea in the hospital or at home (p>0.05). The method for measuring pain and normal activities was validated as the assessments of the parents, children and the investigators were concordant throughout the study. Children who received preoperative oral ibuprofen (10 mg/kg) did not experience less pain or less nausea and vomiting, and did not show a better pattern of sleep and play up to 2 days after ambulatory pediatric urologic surgery than children who did not receive this medication.


Assessing financial performance through green bond markets and energy reliance in Asian economies.
This article's overarching goal is to learn more about the effects of financial performance on the reliance upon or migration to energy efficiency sources in Asian countries using data envelopment analysis (DEA) and system GMM from 2017 to 2022. The results demonstrated the importance of relying on renewable energy sources when expanding the electricity sector effectively in an Asian environment. This same influence of green bond financing on energy investment during an eco-friendly improving economy is in addition to the proportion of renewable energy demands, power usage to gross domestic product, power manufacturing stretchability, electricity usage stretchability, or the overall impact of renewable energy transformation. The analysis revealed that the organizational climate has implicit implications that advance wage activity and that Asian financial systems drove a 30% point transition in the period studied from traditional power generation manufacturing and use methods toward sustainable energy. With this, we see a dramatic increase in the use of green power. This is largely attributable to the widespread use of green financing in constructing hydroelectric facilities throughout Asia. The theoretical underpinnings and empirical setting of the research are both original. Moreover, the association between green bond issuance and green, sustainable growth in industry and agriculture supports the response theory. Major governmental aspects include modernizing and expanding the finance system, updating national efficiency metrics, and creating a technological long-term infrastructure market. While previous studies have looked into the connections between green finance and economic growth, technological advancements in the energy sector, environmental responsibility, and renewable energy sources, this study is the first to focus on how green finance facilitates the shift to renewable energy in Asia's economies. The study's findings suggest how to manage renewable energy in Asia in a way that could work.


Effective oral ganciclovir prophylaxis against cytomegalovirus disease in heart transplant recipients.
The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.


Cycles of silence: First Nations women overcoming social and historical barriers in supportive cancer care.
First Nations people with cancer in Canada confront several critical inequities in physical and psychosocial domains. First Nations women are at a particular disadvantage as they are disproportionately affected by social determinants of health, but how they navigate these challenges within their communities is poorly understood. Our study explores survivorship experiences of First Nations women with cancer and their caregivers. Drawing from a larger data set on survivorship, we identify several major barriers to cancer communication and support in First Nations communities. Our team conducted a participatory, arts-based study using several data collection methods (interviews, sharing sessions, photovoice, and other creative activities) with 43 participants (24 cancer survivors and 19 caregivers) from four First Nations communities in Canada. Two major themes have emerged out of our data analyses: (1) suffering without support leads to cycles of silence and (2) community-based supports can disrupt these cycles. We identified several social, historical, and institutional barriers to speaking about cancer and finding/providing support; however, communities met the challenge of silence through voluntary and unsolicited provision of support. Widespread silence around cancer reflects both the limited access First Nations people have to formal, supportive programs and services, as well as the creative ways they provide emotional, social, and financial support within their informal networks. Beyond the support of their communities, they also required institutional provision of care that is culturally safe, addressing the colonial impacts on cancer communication and the disproportionate burdens of disease in First Nations communities.


Improved detection of bovine coronavirus N gene in faeces of calves infected naturally by a semi-nested PCR assay and an internal control.
Bovine coronavirus (BCoV), a positive sense single-stranded RNA virus, is an important causative agent of neonatal diarrhoea in calves from beef and dairy cattle worldwide. The routine detection and diagnosis of BCoV have been mainly dependent on assays with low sensitivity. The aim of the present study was to develop and evaluate a semi-nested PCR (SN-PCR) to amplify a 251bp fragment of BCoV N gene from fresh (n=25) and frozen (n=25) diarrhoeic faecal samples of naturally infected calves. To improve detection of BCoV in faecal samples by the SN-PCR an internal control was developed, and the results were compared with a conventional RT-PCR assay. The rates of positive samples by SN-PCR and RT-PCR were 24% (12/50) and 8% (4/50), respectively (K=0.43). Only fresh samples were positive in RT-PCR while the SN-PCR detected BCoV in both fresh and frozen faecal samples. The sensitivity of SN-PCR was determined by 10-fold serial dilutions of the BCoV Kakegawa strain (HA titre: 256) that was detected until 10(-7) dilution. The specificity of the amplicons was assessed by restriction fragment length polymorphism and sequence analysis. The inclusion of an internal control provides a way to detect assay inhibition in faecal samples and failure of nucleic acid extraction that allow reduction of the number of false-negative results.


Heterologous expression and purification of biologically active domains 3 and 4 of human polymeric immunoglobulin receptor and its interaction with choline binding protein A of Streptococcus pneumoniae.
Streptococcus pneumoniae, one of the common causes of pneumonia, colonises the epithelium via the interaction between a choline binding protein of S. pneumoniae and the human polymeric immunoglobulin receptor (pIgR). One of the functions of pIgR is to mediate the transcytosis of polymeric immunoglobulins from the basolateral to the apical surface of epithelial cells. S. pneumoniae invades human epithelial cells by exploiting the transcytosis machinery. Due to an increase in the prevalence of antibiotic resistant strains of S. pneumoniae, and the limitations and expense of the vaccines available, extensive research may provide insights into the potential of new therapeutic regimes. This study investigated the potential of pIgR domains as an alternative non-antibiotic immune therapy for treating pneumonia. The aim was to determine the binding affinity of recombinant D3D4 protein, the domains of pIgR responsible for binding S. pneumoniae, to recombinant R1R2 repeat domains of choline binding protein A of S. pneumoniae. Biologically active recombinant D3D4 was produced in Escherichia coli using a gel filtration chromatography refolding method, a novel approach for the refolding of pIgR domains, after the purification of inclusion bodies using nickel affinity chromatography. Surface Plasmon resonance (SPR) spectroscopy showed that purified recombinant D3D4 binds recombinant R1R2 with an equilibrium dissociation constant (KD) of 3.36×10(-7)M.


Quality of care and maternal mortality in a tertiary-level hospital in Mozambique: a retrospective study of clinicopathological discrepancies.
Although an increasing number of pregnant women in resource-limited areas deliver in health-care facilities, maternal mortality remains high in these settings. Inadequate diagnosis and management of common life-threatening conditions is an important determinant of maternal mortality. We analysed the clinicopathological discrepancies in a series of maternal deaths from Mozambique and assessed changes over 10 years in the diagnostic process. We aimed to provide data on clinical diagnostic accuracy to be used for improving quality of care and reducing maternal mortality. We did a retrospective analysis of clinicopathological discrepancies in 91 maternal deaths occurring from Nov 1, 2013, to March 31, 2015 (17 month-long period), at a tertiary-level hospital in Mozambique, using complete diagnostic autopsies as the gold standard to ascertain cause of death. We estimated the performance of the clinical diagnosis and classified clinicopathological discrepancies as major and minor errors. We compared the findings of this analysis with those of a similar study done in the same setting 10 years earlier. We identified a clinicopathological discrepancy in 35 (38%) of 91 women. All diagnostic errors observed were classified as major discrepancies. The sensitivity of the clinical diagnosis for puerperal infections was 17% and the positive predictive value was 50%. The sensitivity for non-obstetric infections was 48%. The sensitivity for eclampsia was 100% but the positive predictive value was 33%. Over the 10-year period, the performance of clinical diagnosis did not improve, and worsened for some diagnoses, such as puerperal infection. Decreasing maternal mortality requires improvement of the pre-mortem diagnostic process and avoidance of clinical errors by refining clinical skills and increasing the availability and quality of diagnostic tests. Comparison of post-mortem information with clinical diagnosis will help monitor the reduction of clinical errors and thus improve the quality of care. Bill & Melinda Gates Foundation and Instituto de Salud Carlos III.


DNA replication studies with coliphage 186. II. Depression of host replication by a 186 gene.
Using pre-labelling rather than pulse-labelling studies to determine rates of replication, we have shown that coliphage 186 infection is accompanied by a depression in host DNA replication. We have isolated mutants of the phage gene involved and mapped them in the early region of the phage genome. Sequencing the mutants ultimately led us to the identification of the gene that we have named the dhr gene.


Erratum to "Extracting Information From Previous Full-Dose CT Scan for Knowledge-Based Bayesian Reconstruction of Current Low-Dose CT Images".
Advertisement, IEEE.


Factors Related to the Intention to Get Vaccinated Against COVID-19 in the Province of New Brunswick, Canada.
Vaccine refusal by even a small subset of the population can undermine the success of the vaccination campaigns which are currently underway worldwide. The goal of this study was to identify determinants of intention to receive COVID-19 vaccine. More precisely, it aimed at examining whether socioeconomic factors, levels of mistrust toward authorities, perceived scientific consensus, and perceived severity of COVID-19 can predict vaccination intentions against COVID-19. Vaccination intentions included being ready to get vaccinated, contemplating vaccination, and not considering vaccination. A sample of 399 individuals from New Brunswick, Canada, completed an online survey in March and April 2021. Results revealed that participants who declared they would probably get vaccinated were more likely to report lower levels of mistrust toward authorities, as well as higher perceived scientific consensus and perceived severity of COVID-19, compared to those who did not intend to get vaccinated or remained unsure. Strategies to guide healthcare professionals in assisting their patients in making the best healthcare decision for their family and themselves are discussed.


Postnatal Neurogenesis Beyond Rodents: the Groundbreaking Research of Joseph Altman and Gopal Das.
An integral component of neural ontogeny and plasticity is the ongoing generation of new neurons from precursor cells throughout the lifespan in virtually all animals with a nervous system. In mammals, postnatal neurogenesis has been documented in the cerebellum, olfactory bulb, hippocampus, striatum, substantia nigra, hypothalamus, and amygdala. Germinal centers of new neuron production in the adult brain have been identified in the neuroepithelium of the subventricular zone and the dentate gyrus. One of the earliest lines of evidence gathered came from studies on the production of cerebellar microneurons in the external germinal layer of rodents and carnivores in the 1960s and 1970s. The undeniable pioneer of that research was the insightful developmental neurobiologist Joseph Altman (1925-2016). This Cerebellar Classic is devoted to the groundbreaking work of Altman and his graduate student and, subsequently, fellow faculty member, Gopal Das (1933-1991), on postnatal neurogenesis using tritiated thymidine autoradiography to tag newly formed neurons in the cerebellum of cats. Perseverant to their ideas and patiently working in West Lafayette (Indiana), they were the founders of two fields that brought about paradigm shifts and led to an explosive growth in brain research: adult neurogenesis and neural tissue transplantation.


Study on the mechanism of Huangqin Decoction on rats with ulcerative colitis of damp-heat type base on mtDNA, TLR4, p-PI3K, p-Akt protein expression and microbiota.
Huangqin decoction (HQD), composed of Scutellaria(Huangqin), Peony(Shaoyao), Liquorice(Gancao) and Jujube(Dazao), is a traditional Chinese medicine prescription, originated from treatise on Febrile Diseases, has the functions of clearing heat, stopping benefits and relieving pain. It is the original prescription for treating heat and relieving dysentery, and is commonly used in clinic for diarrhea and other diseases. In ulcerative colitis, damp-heat syndrome is the most common. However, its mechanism of action is not completely clear. The purpose of the research is to investigate the protective effect of HQD on ulcerative colitis rats and the regulation effect of mitochondrial DNA, TLR4, p-Akt, p-PI3K protein and microbiota. The effects of HQD anti-UC were investigated by fluorescence quantitative PCR, cytokine level and histopathological analysis in DSS-induced ulcerative colitis (UC) rats. The content of mtDNA in colon epithelial cells of rats in each group was detected by fluorescence quantitative PCR, p-PI3K, p-Akt and TLR4 protein expressions in colon tissues of rats in each group were detected by Western blotting. IL-6, IL-17 and IL-23 inflammatory factors were detected by ELISA. The effect of HQD on intestinal microbiota of rats with ulcerative colitis was studied by high-throughput sequencing technology, and the correlation between mtDNA level and inflammatory factors as well as protein expression in colonic epithelium of rats with ulcerative colitis was analyzed by SPSS23.0. HQD significantly alleviated UC symptoms by improving the mucosal intestinal epithelial cell structure, mental state, hair gloss, fecal occult blood, lamina propria intestinal glands and inflammatory cell infiltration. And HQD reduced the pro-inflammatory cytokines in the colonic epithelium of UC rats Production of IL-6, IL-17 and IL-23. The HE stained section of colon tissue showed a complete intestinal epithelial mucosal layer structure. The structure of epithelial cells was more normal and abundant. There were more goblet cells in lamina propria adenoma, which improved the infiltration of inflammatory cells. HQD significantly inhibited the mtDNA content in rat colonic epithelial tissue, and significantly inhibited the expression of TLR4, p-PI3K and p-Akt inflammatory signaling pathways. The results of the microbiota experiment showed that the abundance of HQD in the phylum Firmicutes increased, and the number of Bacteroides phylum decreased (p < 0.05). At the genus level, HQD significantly increased Lactobacillus and Firmicutes Bacteroides, while Treponema and Bacteroides were significantly reduced (p < 0.05). HQD has a certain protective effect on rats with damp heat ulcerative colitis. Its mechanism may be related to regulating the expression of p-PI3K, p-Akt and TLR4 proteins, mitochondrial DNA as well as microbiota.


Effects of YM529, a novel minodronic acid, on adjuvant arthritis in rats.
The effects of a new third-generation bisphosphonate, YM529, on both the development and treatment of adjuvant arthritis were investigated in rats. Five-week-old Lewis rats with adjuvant arthritis were prophylactically and therapeutically treated with 0.001, 0.01 and 0.05 mg/kg/day of YM529 and the arthritis scores were measured. Soft X-ray and histological finding were compared to those of the control group. Body weights were also measured. YM529 suppressed the severity of adjuvant arthritis in a dose-dependent manner when used as either a prophylactic or therapeutic drug. Administration of the drug had little effect on body weight. YM529 may act on arthritic joints locally to prevent inflammation. However, further experiments are necessary to elucidate the underlying mechanisms.


When the Locus Coeruleus Speaks Up in Sleep: Recent Insights, Emerging Perspectives.
For decades, numerous seminal studies have built our understanding of the locus coeruleus (LC), the vertebrate brain's principal noradrenergic system. Containing a numerically small but broadly efferent cell population, the LC provides brain-wide noradrenergic modulation that optimizes network function in the context of attentive and flexible interaction with the sensory environment. This review turns attention to the LC's roles during sleep. We show that these roles go beyond down-scaled versions of the ones in wakefulness. Novel dynamic assessments of noradrenaline signaling and LC activity uncover a rich diversity of activity patterns that establish the LC as an integral portion of sleep regulation and function. The LC could be involved in beneficial functions for the sleeping brain, and even minute alterations in its functionality may prove quintessential in sleep disorders.


The role of WRKY transcription factors in plant abiotic stresses.
The WRKY gene family has been suggested to play important roles in the regulation of transcriptional reprogramming associated with plant stress responses. Modification of the expression patterns of WRKY genes and/or changes in their activity contribute to the elaboration of various signaling pathways and regulatory networks. Furthermore, a single WRKY gene often responds to several stress factors, and then their proteins may participate in the regulation of several seemingly disparate processes as negative or positive regulators. WRKY proteins also function via protein-protein interaction and autoregulation or cross-regulation is extensively recorded among WRKY genes, which help us understand the complex mechanisms of signaling and transcriptional reprogramming controlled by WRKY proteins. Here, we review recent progress made in starting to reveal the role of WRKY transcription factors in plant abiotic stresses. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress.