Individual differences in BEV drivers' range stress during first encounter of a critical range situation.
It is commonly held that range anxiety, in the form of experienced range stress, constitutes a usage barrier, particularly during the early period of battery electric vehicle (BEV) usage. To better understand factors that play a role in range stress during this critical period of adaptation to limited-range mobility, we examined individual differences in experienced range stress in the context of a critical range situation. In a field experiment, 74 participants drove a BEV on a 94-km round trip, which was tailored to lead to a critical range situation (i.e., small available range safety buffer). Higher route familiarity, trust in the range estimation system, system knowledge, subjective range competence, and internal control beliefs in dealing with technology were clearly related to lower experienced range stress; emotional stability (i.e., low neuroticism) was partly related to lower range stress. These results can inform strategies aimed at reducing range stress during early BEV usage, as well as contribute to a better understanding of factors that drive user experience in low-resource systems, which is a key topic in the field of green ergonomics.


The submaximal effort tourniquet test: its use in evaluating experimental and chronic pain.
The submaximal effort tourniquet test has been widely used to evaluate experimental and chronic pain; however, there has been great variation in the manner in which the test has been applied. The present study systemitically evaluates how different levels of exercise duration and effort affect subjects' report of pain. The data indicate the following: (1) the manner in which the exercise is performed has an important effect on subjects' rating of pain, and (2) under all conditions studied, the pain ratings do not increase as a linear function of time. Both findings warrant precautions when using the submaximal effort tourniquet test to study experimental and chronic pain.


Conferences confront abortion bans and anti-LGBTQ+ laws.
Survey shows few societies are pulling out of affected U.S. states, but many are implementing safety measures.


Comparison of two probes for testing susceptibilities of pathogenic yeasts to voriconazole, itraconazole, and caspofungin by flow cytometry.
A cytometric approach to determine the susceptibilities of Candida spp. and Cryptococcus neoformans to voriconazole, itraconazole, and caspofungin is described. A total of 63 clinical isolates with different susceptibility patterns were exposed for 1, 2, 4, and 6 h to serial concentrations of each antifungal agent, followed by staining with two fluorescent probes: propidium iodide (PI) and FUN-1. FUN-1 was able to identify the susceptibility patterns of the assayed strains to the three agents after 1 h. PI penetrated a maximum of 50% of the cells treated with PI, at the highest concentration of caspofungin, 16 mug/ml, after 6 h of incubation (this percentage varied with the strain and was drug concentration and time of incubation dependent) and did not stain cells treated with high concentrations of either azole after 6 h. The use of FUN-1 appears to be an excellent fast and reliable alternative to the classical dilution method for determining the susceptibility of Candida spp. and C. neoformans to these three antifungal agents.


Separation of macromolecular RNAs by reversed-phase high-performance liquid chromatography.
The reversed-phase high-performance liquid chromatography of synthetic and natural RNAs was studied. The results show that base composition alone cannot explain the retention characteristics of natural RNAs; secondary structures are probably involved. However, under the conditions described, the separation was independent of the sizes of the molecules. 18S and 28S ribosomal RNAs were eluted after tRNAs but before 9S globin mRNA. Furthermore, globin mRNA was resolved into two species, one containing and the other lacking poly(A). When applied to the separation of HeLa cell poly(A)-containing RNA, an heterogeneous pattern was obtained. Analysis of peptides synthesized by the mRNA showed that the separation is independent of size.


Natural selection: Fair weather cooperators.
An impressive long-term study of Greater Ani birds reveals fluctuating selection for group size. In wet years, with abundant food, larger groups enjoy greater protection from predators. In dry years, however, larger groups suffer greater nestling mortality relative to smaller groups.


Inter- and intra-observer agreement of the AO classification for operatively treated distal radius fractures.
The reproducibility of the AO classification for distal radius fractures remains a topic of debate. Previous studies showed variable reproducibility results. Important treatment decisions depend on correct classification, especially in comminuted, intra-articular fractures. Therefore, reliable reproducibility results need to be undisputedly determined. Hence, the study objective was to assess inter- and intra-observer agreement of the AO classification for operatively treated distal radius fractures. A database of 54 radiographs of all AO types (A, B and C) and groups (A2-3, B1-3, and C1-3) of distal radius fractures was assessed in twofold. Likewise, a subset of 152 radiographs of solely C-type groups (C1-3) was assessed. All fractures were classified by six observers with different experience levels: three consultant trauma surgeons, one sixth-year trauma surgery resident, a consultant trauma radiologist, and an intern with limited experienced. The inter-observer agreement of both main types and groups was moderate (κ = 0.49 resp. κ = 0.48) in combination with a good intra-observer agreement (κ = 0.68 resp. κ = 0.70). The inter-observer agreement of the subset C-type fractures group was fair (κ = 0.27) with moderate intra-observer agreement (κ = 0.43). According to these results, the reproducibility of the AO classification of main types and groups of distal radius fractures based on conventional radiographs is insufficient (κ < 0.50), especially at group level of C-type fractures.


The use of skin sparing mastectomy in the treatment of breast cancer: The Emory experience.
Long-term follow-up of the use of skin sparing mastectomy (SSM) in the treatment of breast cancer is presented to determine the impact of local recurrence (LR) on survival. 565 cases of breast cancer were treated by SSM and IBR from 1/1/1989-12/31/1998. The AJCC pathological staging was Stage 0 175 (31%), Stage I 135 (23.9%), Stage II 173 (30.6%), Stage III 54 (9.6%), Stage IV 8 (1.4%), recurrent 20 (3.5%). Forty-one patients received postoperative adjuvant radiation therapy. Thirty-one patients developed a LR during the follow-up including five who received adjuvant radiation. The distribution of LR stratified by cancer stage was Stage 0 1 (3.2%), Stage I 5 (16.1%), Stage II 17 (54.8%), Stage III 6 (19.4%), and recurrent 2 (6.5%). The overall LR was 5.5%. Isolated LRs were treated with surgical resection and radiation therapy if not previously administered. Twenty-four patients (77.4%) developed a systemic relapse and 7 (22.6%) patients remained free of recurrent disease at a mean follow-up of 78.1 months. The cancer stage of those remaining disease free was Stage 0 1, Stage I 4, and Stage II 2. LR of breast cancer after SSM is not always associated with systemic relapse.


Severe underweight decreases the survival rate in adult lung transplantation.
The body mass index (BMI) before lung transplantation (LT) is a benchmark of the post-LT survival. The aim of the study is to determine the BMI inadequate for the post-LT survival. We examined the survival after LT in patients grouped into the following BMI categories: <18.5 kg/m2 (underweight), 18.5-24.9 kg/m2 (normal weight), 25-29.9 kg/m2 (overweight), and ≥30.0 kg/m2 (obese) according to the World Health Organization (WHO) criteria. A more detailed categorization was made for further evaluation of the underweight group: mild (17.0 ≤ BMI < 18.5 kg/m2) and severely underweight (BMI <17.0 kg/m2). There was no statistically significant difference in the post-LT survival between underweight and normal-weight patients (5-year survival: 78.7 vs. 76.1%). Patients with BMI <17.0 kg/m2 had a worse prognosis than those with 17.0 ≤ BMI < 18.5 kg/m2 (5-year survival: 70.3 vs. 90.0%). Standard BMI categorization per the WHO criteria is inadequate for determining the post-LT survival, especially in underweight patients. For the nutritional evaluation of underweight pre-LT patients, BMI <17.0 kg/m2 should be used instead of BMI <18.5 kg/m2.


Role of redox status on the activation of mitogen-activated protein kinase cascades by NSAIDs.
High concentrations of non steroidal antiinflammatory drugs (NSAIDs) exert preventive effects against carcinogenesis. Their molecular mechanism of action remains to be elucidated. Based on previous reports with salicylate, we have made the hypothesis that various NSAIDs can activate the mitogen-activated protein kinases (MAPK). Moreover, we tested the idea that NSAIDs act by increasing the effects of oxidative stress. We report that in human colorectal carcinoma cells NSAIDs stimulated the three families of MAPK, extracellular regulated kinases, c-Jun N-terminal kinases, p38 MAPK and that this stimulation is prevented by N-acetyl cysteine. In cultured astrocytes, a biological system less sensitive to oxidative stress, we show that a short treatment by NSAIDs strongly activated the three MAP kinases in the presence of H(2)O(2). A 25 microM H(2)O(2), unable to stimulate by itself the MAP kinases, promote an almost complete activation of MAP kinases in the presence of NSAIDs. The activation of MAP kinases by H(2)O(2) and NSAIDs was suppressed by quinone reductase inhibitors, suggesting that "redox cycling" was involved in the activation mechanisms of MAP kinases by H(2)O(2) and NSAIDs. The mobility on SDS-PAGE of the apoptosis signal-regulating kinase, which activates C-Jun N-terminal kinases and p38 MAPK cascades, was reduced by H(2)O(2) and NSAIDs, suggesting, that H(2)O(2) and NSAIDs activated apoptosis signal-regulating kinase by increasing its state of phosphorylation. In conclusion, we demonstrate that various NSAIDs can activate the three families of MAP kinases and that this activation depends on the presence of reactive oxygenated species. These results give a new insight into the mechanism of the action of NSAIDs.


A DS2-specific flavonoid-based probe with a unique dual-emissive response to human serum albumin.
The hydroxyl substituent in flavonoids can cause the binding site to change from DS1 to DS2 and restore the ESIPT process of flavonoids, thereby leading to a unique dual-emissive response towards human serum albumin.


Constraints on bosonic dark matter from ultralow-field nuclear magnetic resonance.
The nature of dark matter, the invisible substance making up over 80% of the matter in the universe, is one of the most fundamental mysteries of modern physics. Ultralight bosons such as axions, axion-like particles, or dark photons could make up most of the dark matter. Couplings between such bosons and nuclear spins may enable their direct detection via nuclear magnetic resonance (NMR) spectroscopy: As nuclear spins move through the galactic dark-matter halo, they couple to dark matter and behave as if they were in an oscillating magnetic field, generating a dark-matter-driven NMR signal. As part of the cosmic axion spin precession experiment (CASPEr), an NMR-based dark-matter search, we use ultralow-field NMR to probe the axion-fermion "wind" coupling and dark-photon couplings to nuclear spins. No dark matter signal was detected above background, establishing new experimental bounds for dark matter bosons with masses ranging from 1.8 × 10-16 to 7.8 × 10-14 eV.


Acute mastoiditis complicated by cerebral venous sinus thrombosis in children.
Diagnosis and management of complicated mastoiditis in childhood are still controversial. We investigated the clinical manifestations, evaluation and management of children with mastoiditis complicated with cerebral venous sinus thrombosis. Retrospective cohort study that included all children admitted for acute mastoiditis over the last 5 years. Children were divided in two groups based on the presence or not of venous sinus thrombosis. Clinical, laboratory, imaging and management data were retrieved and compared. Overall, 20 children with acute mastoiditis were included, of whom 5 had magnetic resonance imaging-confirmed cerebral venous sinus thrombosis and elevated intracranial pressure (ICP). In all complicated cases, neurological signs rather than mastoiditis signs, prevailed. The more prominent neurologic signs observed were lethargy (60%), nuchal rigidity (60%), abducens nerve palsy (60%) and ataxic gait (20%). Treatment consisted of intravenous antibiotics combined with anticoagulation. Surgery was performed in four children (4/5). Complicated cases had prolonged symptoms prior to admission (p 0.002), presented with neurologic signs and symptoms (p < 0.001), underwent more often lumbar puncture (p < 0.001) and brain imaging (p < 0.001), and were treated with prolonged courses of antibiotics and surgery (<0.001), compared to children with uncomplicated mastoiditis. Neurological signs and symptoms and elevated ICP dominate in children with mastoiditis complicated with thrombosis. Brain imaging is essential for early diagnosis of cerebral venous sinus complications and appropriate management.


Transcutaneous Columellar Strut for Correcting Caudal Nasal Septal Deviation.
Correction of caudal septal deviation is a challenging issue because of its significant role in tip support mechanisms. Some interventions especially aggressive resection of caudal septum to correct deviation, may compromise external nasal valve, tip ptosis and persistence of nasal obstruction. Many surgical techniques have been suggested to correct this type of nasal septal deviation. This study presents a technique to correct caudal septal deviation without weakening of tip support mechanisms. To evaluate the efficacy of insertion of a transcutaneous columellar strut during correction of caudal septal deviation. The study was performed in patients complaining from nasal obstruction with caudal septal deviation. After intranasal incision and elevation of mucoperichondrial flap, Caudal septum released from anterior nasal spine (ANS) and a band of cartilage removed from inferior and caudal part of septum and septum again fixed to ANS. Through a vertical transcutaneous incision, a cartilaginous strut is placed in columella, between medial crurae. Preoperative and postoperative NOSE score determined and photographs were taken. In 14 patients we performed this technique, the postoperative NOSE score showed significant improvement, (p = 0.001). Nasal breathing improved in all patients without any complication or tip ptosis or worsening of nasal appearance. This septoplasty technique along with placement of transcolumellar strut, is an easy, efficient and complication free method for simultaneously correction of caudal deviation of nasal septum, reinforcing external nasal valve and prevents tip ptosis.


Study of anthranilate synthase function by replacement of cysteine 84 using site-directed mutagenesis.
Cysteine 84 was replaced by glycine in Serratia marcescens anthranilate synthase Component II using site-directed mutagenesis of cloned trpG. This replacement abolished the glutamine-dependent anthranilate synthase activity but not the NH3-dependent activity of the enzyme. The mutation provides further evidence for the role of active site cysteine 84 in the glutamine amide transfer function of anthranilate synthase Component II. By the criteria of circular dichroism, proteolytic inactivation, and feedback inhibition the mutant and wild type enzymes were structurally similar. The NH3-dependent anthranilate synthase activity of the mutant enzyme supported tryptophan synthesis in media containing a high concentration of ammonium ion.


Hysteroscopic biopsy compared with endometrial curettage to assess the preoperative rate of atypical hyperplasia underestimating endometrial carcinoma.
To evaluate the rate of atypical hyperplasia (AH) underestimating endometrial cancer (EC) comparing endometrial biopsy (EB) accomplished by hysteroscopic biopsy with dilatation and curettage (D&C). Second, to compare the two techniques to foresee EC grading. This trial was based on the findings of two Gynecological Departments within the same Public Utility, sharing pathological service and database but routinely performing EB under hysteroscopic visualization (group A) or hysteroscopy followed by D&C (group B). We retrieved the clinical data of patients showing EC on hysterectomy throughout a 10-year period. The accuracy of hysteroscopic-view diagnosis and EB pathology were compared, having the pathologic findings of hysterectomy as reference. A total of 161 patients met the inclusion criteria. Among these, 109 and 52 were included in groups A and B, respectively. In group A, 32.1% of patients underwent EB in an out-patient setting. To foresee EC, hysteroscopic view showed a sensitivity of 82.5% and 70.2% in groups A and B, respectively (P = 0.019). An underestimation of EC diagnosed as AH on EB was found in 20 patients (12.4%). Among these, 18 (16.5%) and 2 (3.8%) were included in groups A and B, respectively (P = 0.022). In group A, a fault diagnosis of AH resulted higher when EB was performed as out-patient setting (P = 0.006). EB allowed the grading of EC in 73.3% and 90.3% of patients in groups A and B, respectively. The agreement was 73.7% and 85.1%, leading to moderate (κ = 0.56) and good (κ = 0.77) "κ" coefficient of concordance for groups A and B, respectively. EB performed by D&C lowers the rate of AH underestimating concurrent EC and improves the grading agreement when compared with hysteroscopic sampling.


Monitoring of simulated occlusal tooth wear by objective outcome measures.
This in vitro study explored quantitative outcome measures as clinical indicators of simulated occlusal tooth wear progression. Ten sound, extracted human premolars were selected and submitted to occlusal tooth wear simulation in 0.5-mm steps (0/0.5/1.0/1.5 mm). At each step, enamel thickness on the buccal cusp tips was evaluated using cross-polarization optical coherence tomography (CP-OCT) and micro-computed tomography (μ-CT). The occlusal surface of each premolar was also scanned at each step using a 3D digital intraoral scanner, followed by morphological characterization using standard topography attributes (Slope, Relief, RFI, OPCr). Repeated measures ANOVA assessed differences in simulated wear levels for the μ-CT and CP-OCT data as well as the topography values. Correlations were also calculated between the μ-CT/CP-OCT and topography data. Significant differences were observed for enamel thickness at each simulation wear stage, for both CP-OCT (p < 0.001) and μ-CT (p < 0.001), with good agreement between methods (intraclass correlation: 0.89). For topography analysis, as wear increased, the average Slope, RFI, and Relief values decreased, and average OPCr values increased, with more significant differences shown for Slope. Slope showed significant (p < 0.05) positive correlations with CP-OCT. OPCr showed significant negative correlations with μ-CT, and CP-OCT (p < 0.05). RFI and Relief were not correlated with either μ-CT or CP-OCT (p > 0.05). Our findings suggest the potential of PS-OCT for measuring enamel thickness changes in the cusp tips of the occlusal surface. Similarly, conventional intraoral scanners can serve effectively for monitoring overall tooth wear when combined with dental topographic analyses of resultant point clouds. CP-OCT measures of enamel thickness and dental 3D topographic attributes showed potential as objective outcomes for the clinical monitoring of occlusal tooth wear. Their combination provided a comprehensive understanding of the tooth wear development process.


Psychosocial and Ethical Behaviors and Attitudes of Health Care Professionals in the Clinical Setting of Living Kidney Donors: A Qualitative Study.
There are several psychosocial and ethical issues surrounding the decision making of living kidney transplant donors. This study aimed to determine what health care professionals (HPs) consider in their clinical practice and their attitudes toward donors' decision-making processes. Face-to-face semistructured interviews were conducted with 15 HPs. A thematic analysis was performed to categorize the thematic elements of the transcripts. All procedures were approved by the relevant review board and conducted in accordance with the Declaration of Helsinki. Six main categories-maintaining family relationships, improving donor understanding, supporting voluntary decision making, setting the environment for the examination, having different attitudes toward the donor's intentions, and resisting confirmation of intent-were identified. The HPs provided diverse considerations to respect the donors' autonomy. In clinical practice, there is a lack of practical methods to confirm living donors' levels of understanding and spontaneity, suggesting that these methods need to be established. Factors related to family functioning may reflect the unique culture of Japan, and this may be indicative of the need to consider treatment based on cultural values.


Hyponatremia associated with sertraline and fluoxetine: a case report.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a rare but serious adverse effect of the selective serotonin reuptake inhibitors (SSRIs). Although many case reports describe this association, few report the effect of rechallenge with another SSRI. We present a case of an elderly patient who developed hyponatremia with sertraline and SIADH when rechallenged with fluoxetine.


A Systematic Review and Meta-Analysis of Methods Used to Reduce Infectious Complications Following Transrectal Prostate Biopsy.
We reviewed and analyzed the most effective methods to reduce infectious complications (IC) after transrectal prostate biopsy (TRPB). We included only prospective randomized-controlled trials in the analysis. The analysis neither demonstrated any superiority of fluoroquinolones over other antibiotic classes nor of targeted antibiotics over empiric regimens in men undergoing TRPB. However, longer course antibiotics (3 days or more) compared to single dose or day regimens, combination of fluoroquinolones with aminoglycosides compared to fluoroquinolones alone and povidone-iodine rectal cleansing compared to control significantly reduced IC following TRPB. A combination of addition of aminoglycosides to oral antibiotics for 3 days along with povidone-iodine rectal cleansing may be an optimum strategy to minimize the risk of IC after TRPB.


Spatial patterns for an interaction-diffusion equation in morphogenesis.
A certain interaction-diffusion equation occurring in morphogenesis is considered. This equation is proposed by Gierer and Meinhardt, which is introduced by Child's gradient theory and Turing's idea about diffusion driven instability. It is shown that slightly asymmetric gradients in the tissue produce stable striking patterns depending on its asymmetry, starting from uniform distribution of morphogens. The tool is the perturbed bifurcation theory. Moreover, from a mathematical point of view, the global existence of steady state solutions with respect to some parameters is discussed.


Study on high temperature solidification behavior and crack sensitivity of Fe-Mn-C-Al TWIP steel.
Fe-Mn-C-Al alloy is a new steel grade of TWIP steel developed in recent years. It has an excellent combination of elongation and tensile strength, as well as good anti-delayed fracture property. However, the crack sensitivity of this new TWIP steel has not been reported yet. In this study, differential thermal analysis (DTA) method was used, combined with professional thermodynamic software ThermoCalc to analyze the solidification behavior for Fe-Mn-C-Al alloys with different chemical compositions. Based on this, the crack sensitivity of TWIP steel is further determined. Through this study, it was found that Fe-Mn-C-Al TWIP steel may have a solidification sequence with high crack sensitivity, belonging to hypo-peritectic steel. Moreover, it was found that the carbon content has a large influence on the solidification behavior, and the manganese content also affects the solidification sequence. It can make the phase transition sequence of the solidification process change significantly, which may avoid the solidification behavior of hypo-peritectic reaction. The analysis results by thermodynamic software ThermoCalc are in good agreement with the experimental results. It displays thermoCalc can be a cost-effective way to develop Fe-Mn-C-Al TWIP steel. It is of great significance for shortening the development period of new Fe-Mn-C-Al steel grades.


Droplet etching of deep nanoholes for filling with self-aligned complex quantum structures.
Strain-free epitaxial quantum dots (QDs) are fabricated by a combination of Al local droplet etching (LDE) of nanoholes in AlGaAs surfaces and subsequent hole filling with GaAs. The whole process is performed in a conventional molecular beam epitaxy (MBE) chamber. Autocorrelation measurements establish single-photon emission from LDE QDs with a very small correlation function g ((2))(0)≃ 0.01 of the exciton emission. Here, we focus on the influence of the initial hole depth on the QD optical properties with the goal to create deep holes suited for filling with more complex nanostructures like quantum dot molecules (QDM). The depth of droplet etched nanoholes is controlled by the droplet material coverage and the process temperature, where a higher coverage or temperature yields deeper holes. The requirements of high quantum dot uniformity and narrow luminescence linewidth, which are often found in applications, set limits to the process temperature. At high temperatures, the hole depths become inhomogeneous and the linewidth rapidly increases beyond 640 °C. With the present process technique, we identify an upper limit of 40-nm hole depth if the linewidth has to remain below 100 μeV. Furthermore, we study the exciton fine-structure splitting which is increased from 4.6 μeV in 15-nm-deep to 7.9 μeV in 35-nm-deep holes. As an example for the functionalization of deep nanoholes, self-aligned vertically stacked GaAs QD pairs are fabricated by filling of holes with 35 nm depth. Exciton peaks from stacked dots show linewidths below 100 μeV which is close to that from single QDs.


Development of hypothyroidism over 13 years of follow-up of patients with hyperthyroidism after radioiodine therapy.
To analyze the incidence and associated factors of hypothyroidism after radioiodine treatment for hyperthyroidism during a 13-year follow-up period. This was a retrospective study of consecutive patients with hyperthyroidism who were treated using a single dose of radioactive iodine (RAI) with a calculated dose regimen from 07/2005 to 12/2012. Univariate and multivariate Cox regression models were used to examine the factors that are associated with the occurrence of hypothyroidism after RAI therapy. Kaplan-Meier analysis was used for confirming associations between these models. A total of 182 patients were included during a 7.5-year median follow-up (range: 6-13 years). They were 36.4±11.1 years. The mean radioactive iodine dosage was 308.2±104.3 (range: 129.5-740.0) MBq. The rates of euthyroidism, early hypothyroidism, improvement, and ineffective treatment at 6 months were 48.4%, 37.9%, 8.8%, and 4.9%, respectively. The cumulative incidence of hypothyroidism in all patients with hyperthyroidism was 45.6% at 1 year, 48.9% at 5 years, and 52.3% at 10 years. Thyroid weight >46g (HR=0.643, 95%CI: 0.422-0.981, P=0.040) and a course of disease of 0.5-3 years (HR=0.592, 95%CI: 0.358-0.981, P=0.042) were identified as independent factors associated with an increased risk of hypothyroidism after radioactive iodine therapy. Radioactive iodine treatment with a calculated dose has a high cure rate for hyperthyroidism and has a low annual increase of hypothyroidism. Hypothyroidism after radioactive iodine treatment is more likely to occur in patients with small thyroid and a short disease course.


The bug stops with me: Prevention of COVID-19 nosocomial transmission during radiographic procedures.
Nosocomial transmission of Coronavirus Disease 2019 (COVID-19) is a preventable risk to the patient population and radiographer workforce. This article aims to describe the prevention of COVID-19 nosocomial transmission during radiographic procedures by the utilization of stringent infection prevention measures at a leading tertiary hospital in Singapore. The implemented measures are the appropriate use of personal protective equipment, staff education, infection controls measures such as equipment disinfection, physical distancing and segregation of staff and patients. Despite the handling of 1637 COVID-19 cases as of July 25, 2020, there has not been a single case of known nosocomial transmission of the disease in the institution. The absence of nosocomial transmission suggests that the implemented measures are adequate. These measures will need to be sustainable for the long term in order to ensure continued success. Radiographers are a crucial part of the team in the fight against COVID-19 and are at risk of contracting COVID-19. Strict adherence to appropriate infection control measures is essential for the safety of Radiology staff and their patients, and the successful control of this pandemic.


Hierarchical multi-label classification based on LSTM network and Bayesian decision theory for LncRNA function prediction.
Growing evidence shows that long noncoding RNAs (lncRNAs) play an important role in cellular biological processes at multiple levels, such as gene imprinting, immune response, and genetic regulation, and are closely related to diseases because of their complex and precise control. However, most functions of lncRNAs remain undiscovered. Current computational methods for exploring lncRNA functions can avoid high-throughput experiments, but they usually focus on the construction of similarity networks and ignore the certain directed acyclic graph (DAG) formed by gene ontology annotations. In this paper, we view the function annotation work as a hierarchical multilabel classification problem and design a method HLSTMBD for classification with DAG-structured labels. With the help of a mathematical model based on Bayesian decision theory, the HLSTMBD algorithm is implemented with the long-short term memory network and a hierarchical constraint method DAGLabel. Compared with other state-of-the-art algorithms, the results on GOA-lncRNA datasets show that the proposed method can efficiently and accurately complete the label prediction work.


Rederivation by Cryopreservation of a Paternal Line of Rabbits Suggests Exhaustion of Selection for Post-Weaning Daily Weight Gain after 37 Generations.
Rabbit selection programmes have mainly been evaluated using unselected or divergently selected populations, or populations rederived from cryopreserved embryos after a reduced number of generations. Nevertheless, unselected and divergent populations do not avoid genetic drift, while rederived animals seem to influence phenotypic traits such as birth and adult weights or prolificacy. The study aimed to evaluate the effect of a long-term selection for post-weaning average daily weight gain (ADG) over 37 generations with two rederived populations. Specifically, two coetaneous populations were derived from vitrified embryos with 18 generational intervals (R19 and R37), reducing or avoiding genetic drift and environmental and cryopreservation effects. After two generations of both rederived populations (R21 vs. R39 generations), all evaluated traits showed some progress as a result of the selection, the response being 0.113 g/day by generation. This response does not seem to affect the estimated Gompertz growth curve parameters in terms of the day, the weight at the inflexion point or the adult weight. Moreover, a sexual dimorphism favouring females was observed in this paternal line. Results demonstrated that the selection programme had improved ADG without variations in adult body weight but, after 37 generations of selection, this trait seems exhausted. Given the reduction in the cumulative reproductive performance and as a consequence in the selection pressure, or possibly/perhaps due to an unexpected effect, rederivation could be the cause of this weak selection response observed from generation 18 onwards.


Racial Differences in the Presentation and Progression of Huntington's Disease.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that predominantly impacts a Caucasian population, but few efforts have explored racial differences in presentation and progression. The aim was to assess the presentation and progression of HD across race groups using the Enroll-HD longitudinal observational study. We applied propensity score matching for cytosine-adenine-guanine age product score, and age, to identify White, Hispanic, Asian, and Black participants from the Enroll-HD database. We compared clinical presentations at baseline, and progression over time, using White participants as a control cohort. Black participants were more severe at baseline across all clinical measures. No significant differences in progression were observed between race groups. We consider the factors driving clinical differences at baseline for Black participants. Our data emphasize the necessary improvement in underrepresented minority recruitment for studies of rare diseases. © 2023 International Parkinson and Movement Disorder Society.


Alu Sx repeat-induced homozygous deletion of the StAR gene causes lipoid congenital adrenal hyperplasia.
Lipoid congenital adrenal hyperplasia (Lipoid CAH) is the most severe form of the autosomal recessive disorder CAH. A general loss of the steroid biosynthetic activity caused by defects in the StAR gene manifests as life-threatening primary adrenal insufficiency. We report a case of Lipoid CAH caused by a so far not described homozygous deletion of the complete StAR gene and provide diagnostic results based on a GC-MS steroid metabolomics and molecular genetic analysis. The patient presented with postnatal hypoglycemia, vomiting, adynamia, increasing pigmentation and hyponatremia. The constellation of urinary steroid metabolites suggested Lipoid CAH and ruled out all other forms of CAH or defects of aldosterone biosynthesis. After treatment with sodium supplementation, hydrocortisone and fludrocortisone the child fully recovered. Molecular genetic analysis demonstrated a homozygous 12.1 kb deletion in the StAR gene locus. The breakpoints of the deletion are embedded into two typical genomic repetitive Alu Sx elements upstream and downstream of the gene leading to the loss of all exons and regulatory elements. We established deletion-specific and intact allele-specific PCR methods and determined the StAR gene status of all available family members over three generations. This analysis revealed that one of the siblings, who died a few weeks after birth, carried the same genetic defect. Since several Alu repeats at the StAR gene locus increase the probability of deletions, patients with typical symptoms of lipoid CAH lacking evidence for the presence of both StAR alleles should be analyzed carefully for this kind of disorder.


Observation of microsphere movement driven by optical pulse: comment.
We show that fiber-delivered, pulsed laser propulsion of glass microspheres, as observed in a recent Letter [Opt. Lett. 36, 1996 (2011).], due to only radiation pressure cannot explain the measured maximum velocity of microspheres. Our considerations, based on the reported results, indicate that the main momentum transfer mechanism is due to mass recoil that very likely follows a dielectric breakdown near or on the surface of the microsphere.


Circulating palmitoleic acid is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals: a longitudinal analysis.
Experimental studies suggest that the fatty acid palmitoleate may act as an adipocyte-derived lipid hormone (or 'lipokine') to regulate systemic metabolism. We investigated the relationship of circulating palmitoleate with insulin sensitivity, beta cell function and glucose tolerance in humans. Plasma NEFA concentration and composition were determined in non-diabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study cohort at baseline (n = 1234) and after a 3 year follow-up (n = 924). Glucose tolerance, insulin secretion and beta cell function were assessed during an OGTT. Whole-body insulin sensitivity was measured by a hyperinsulinaemic-euglycaemic clamp (M/I) and OGTT (oral glucose insulin sensitivity index [OGIS]). The liver insulin resistance index was calculated using clinical and biochemical data. Body composition including fat mass was determined by bioelectrical impedance. Circulating palmitoleate was proportional to fat mass (r = 0.21, p < 0.0001) and total NEFA levels (r = 0.19, p < 0.0001). It correlated with whole-body insulin sensitivity (M/I: standardised regression coefficient [std. β] = 0.16, p < 0.0001), liver insulin resistance (std. β = -0.14, p < 0.0001), beta cell function (potentiation: std. β = 0.08, p = 0.045) and glucose tolerance (2 h glucose: std. β = -0.24, p < 0.0001) after adjustment for age, sex, BMI, adiposity and other NEFA. High palmitoleate concentrations prevented the decrease in insulin sensitivity associated with excess palmitate (p = 0.0001). In a longitudinal analysis, a positive independent relationship was observed between changes in palmitoleate and insulin sensitivity over time (std. β = 0.07, p = 0.04). We demonstrated that plasma palmitoleate is an independent determinant of insulin sensitivity, beta cell function and glucose tolerance in non-diabetic individuals. These results support the role of palmitoleate as a beneficial lipokine released by adipose tissue to prevent the negative effects of adiposity and excess NEFA on systemic glucose metabolism.


Stage 2 Registered Report: Epigenetic Intergenerational Transmission: Mothers' Adverse Childhood Experiences and DNA Methylation.
Individual differences in risk for mental disorders over the lifespan are shaped by forces acting before the individual is born-in utero, but likely even earlier, during the mother's own childhood. The environmental epigenetics hypothesis proposes that sustained effects of environmental conditions on gene expression are mediated by epigenetic mechanisms. Recent human studies have shown that adversities in childhood are correlated with DNA methylation (DNAm) in adulthood. In the current study, we tested the following pre-registered hypotheses: Mothers' adverse childhood experiences (ACEs) are correlated with DNAm in peripheral blood during pregnancy (hypothesis 1) and in cord blood samples from newborn infants (hypothesis 2), and women's depression and anxiety symptoms during pregnancy mediate the association between mothers' ACE exposure and prenatal/neonatal DNA methylation (hypothesis 3). Data were from the Avon Longitudinal Study of Parents and Children Accessible Resource for Integrated Epigenomic Studies substudy. Women provided retrospective self-reports during pregnancy of ACE exposure. We conducted an epigenome-wide association study testing whether mothers' ACE exposure, cumulative score (0-10), was associated with DNAm in maternal antenatal blood and infant cord blood in more than 450,000 CpG (point on DNA sequence where cytosine and guanine base pairs are linked by a phosphate, where methylation usually occurs) sites on the Illumina 450K BeadChip. Analyses for cord blood were separated by infant sex, a pre-registered analysis. Hypothesis 1: In 896 mother-infant pairs with available methylation and ACE exposure data, there were no significant associations between mothers' ACE score and DNAm from antenatal peripheral blood, after controlling for covariates. Hypothesis 2: In infant cord blood, there were 5 CpG sites significantly differentially methylated in relation to mothers' ACEs (false discovery rate [FDR] < .05), but only in male offspring. Effect sizes were medium, with partial eta squared values ranging from 0.060 to 0.078. CpG sites were in genes related to mitochondrial function and neuronal development in the cerebellum. Hypothesis 3: There was no mediation by maternal anxiety/depression symptoms found between mothers' ACEs score and DNAm in the significant CpG sites in male cord blood. Mediation was not tested in antenatal peripheral blood, because no direct association between mothers' ACE score and antenatal peripheral blood was found. Our results show that mothers' ACE exposure is associated with DNAm in male offspring, supporting the notion that DNAm could be a marker of intergenerational biological embedding of mothers' childhood adversity. Epigenetic Intergenerational Transmission: Mothers' Adverse Childhood Experiences and DNA Methylation; https://doi.org/10.1016/j.jaac.2020.03.008.


Phylogeny, gene structures, and expression patterns of the auxin response factor (GhARF2) in upland cotton (Gossypium hirsutum L.).
Auxin response factors (ARFs) are a class of transcription factors that regulate the expression of auxin-responsive genes and play important functions in plant growth and development. To understand the biological functions of the auxin response factor GhARF2 gene in upland cotton, the coding sequence (CDS) of GhARF2 gene was cloned, and its protein sequence, evolutionary relationship, subcellular localization and expression pattern were analysed. The CDS sequence of GhARF2 gene was cloned from upland cotton variety Baimian No.1, and its protein sequence was analyzed by bioinformatics method. The subcellular localization of GhARF2 protein was detected by tobacco epidermal transient transformation system, and the tissue expression and stress expression pattern of GhARF2 were analyzed by quantitative Real‑Time PCR (qRT-PCR). The full-length CDS of GhARF2 gene was 2583 bp, encoded 860 amino acids, and had a molecular weight and an isoelectric point of 95.46 KDa and 6.02, respectively. The GhARF2 protein had multiple phosphorylation sites, no transmembrane domain, and secondary structures dominated by random coils and alpha helix. The GhARF2 protein had 3 conserved typical domains of ARF gene family members, including the B3 DNA binding domain, the Auxin_resp domain, and the Aux/IAA domain. Phylogenetic analysis revealed that ARF2 proteins in different species were clustered in the Group A subgroup, in which GhARF2 was closely related to TcARF2 of Theobroma cacao L. (Malvaceae). The subcellular localization results showed that the GhARF2 protein was localized in the nucleus. Analysis of tissue expression pattern showed that the GhARF2 gene was expressed in all tested tissues, with the highest expression levels in sepal, followed by leaf, and the lowest expression levels in fiber. Further stress expression analysis showed that the GhARF2 gene was induced by drought, high-temperature, low-temperature and salt stress, and had different expression patterns under different stress conditions. These results established a foundation for understanding the functions of GhARF2 and breeding varieties with high-stress tolerance in cotton.


Effect of soil compaction on organic carbon amounts and distribution, South-Central Iowa.
Soils on the Mormon Trail have been compacted for over 150 years. Bulk density, carbon, and nitrogen samples were taken in 5-cm increments to 20 cm. Bulk density was determined using rings of known volume; total carbon and nitrogen with a LECO CHN-600. Total above ground biomass (AGB) samples were collected by clipping vegetation within a 0.25 m2 frame and were analyzed for carbon. Statistical comparisons were made using a t-test (alpha = 0.05). Bulk density was higher in the on-trail soils from 5 to 20 cm; soil carbon and C/N ratios were higher in the off-trail soils from 10 to 20 cm. AGB and AGB carbon is significantly less on the trail. Results indicate the compacted layer on the trail alters the soil carbon pool by limiting additions of fresh organic matter to the soil, limiting vegetative production, and by "pooling" carbon additions in the upper 10 cm of the soil.


Comparison of multi-criteria analysis methodologies for the prioritization of arsenic-contaminated sites in the southwest of China.
The issue of contaminated sites has been highlighted as an immediate priority in the 13th Five-Year Plan of China. Identification and prioritization of contaminated sites are of key importance for proposing effective strategies for the regional management of contaminated sites. In this study, three advanced multi-attribute methodologies, the risk-based priority methodology, the regional risk assessment methodology, and the dominance-based rough set approach (DRSA), were comparatively employed to screen contaminated sites in, Guangxi, Southwest of China. The results of the three prioritizations show that the highest ranking site identified by the three methods had great agreement. In regard to the screening attributers, while the risk-based prioritization methodology and regional risk assessment methodology allowed a high discrimination in the screening of contaminated sites associated with different attributes, such as farmland, residential areas, contaminant level, number of people, area, storage quality, site service life, and surrounding communities, the DRSA allowed the identification of contamination strength (CS) and contamination potential (CP).


Validity of some prediction equations to assess resting energy expenditure (REE) in 29 elderly obese subjects (>60 years).
Recent estimates in US have shown that more than a third of 65 years old subjects are obese. The objective of this study was to test the accuracy of six prediction equations to estimate resting energy expenditure (REE) in elderly obese subjects (age >60 years). Twenty-nine obese Caucasian male (n=8) and female (n=21) subjects (age range: 60-77 years) attended the Outpatient Clinic of the Neuroscience Department of Naples "Federico II" University Medical School (Italy), Section of Aging and Nutrition from January 2005 to January 2006. Weight, height, BMI and body composition (bioimpedance) were measured. REE was measured using a ventilated-hood indirect calorimetry and compared to six prediction equations (Harris-Benedict, Fredrix, Mifflin, Owen, WHO, Livingston). Mean age and body mass index (BMI) were 65.9+/-4.8 years and 36.8+/-5.3 kg/m2, respectively. The measured REE was 1658+/-289 kcal/day. The Harris-Benedict', Owen' and Livingston's equations performed less well than the other equations and they showed a tendency towards underestimation. The equation with the best REE prediction was the Fredrix's one (DeltaREE=-19.4kcal/day) with 66% of REE predictions lying within 10% of measured REE. These data support the utilization of the Fredrix's equation to calculate REE in obese elderly subjects.


Surveillance and rescue of pancreas grafts.
Technical failure rates are higher for pancreas allografts (PA) compared with other solid organs. Posttransplant surveillance and prompt availability of rescue teams with multidisciplinary expertise both contribute to improve this result. We herein report a single institution's experience with posttransplant surveillance and rescue of PA. A retrospective survey was performed of a consecutive series of 177 whole organ pancreas transplants in 173 patients. Antithrombotic prophylaxis was used in all recipients and tailored on anticipated individual risk of thrombosis. During the first posttransplant week, all PA were monitored with daily Doppler ultrasonography. Surgical complications were defined as all adverse events requiring relaparotomy during the initial hospital stay or the first 3 posttransplant months. A total of 26 relaparotomies were performed in 25 patients (14.7%). One recipient needed two relaparotomies (0.6%). Graft rescue was attempted in patients without permanent parenchymal damage at repeat surgery and in 12 recipients diagnosed with nonocclusive vascular thrombosis. Overall 25 grafts (96.3%) were rescued and one was lost. One-year recipient and graft survivals in patients with versus without complications potentially leading to allograft loss were 92.6% and 63.0% versus 94.4% and 94.3%, respectively. Excluding complications for which graft rescue was not possible, 1-year graft survival rate increased to 78.7%. Close posttransplant surveillance can allow rescue of a relevant proportion of PA developing nonocclusive venous thrombosis or other surgical complications. Further improvement awaits better understanding of biological reasons for posttransplant complications jeopardizing PA survival and the development of more effective preventive measures.


Eyelashes on an extruding porous polyethylene orbital implant.
This photo essay describes a patient with eyelashes perpendicular to the extruding part of a porous polyethylene orbital implant. The upright position of these eyelashes created the impression of growth on the extruding implant, but they are lost eyelashes that became entrapped in the pores of the implant.


The Erysichthon syndrome. Progression of coronary atherosclerosis and dietary hyperlipidemia.
One hundred nineteen patients with coronary artery disease confirmed by coronary arteriograms were studied. Cine coronary arteriography confirmed progression of atherosclerosis in 106 (89%) patients (mean age 50.9 yr) and nonprogression in 13 (11%) patients (mean age 50.3 yr). Progression was defined as follows: any increase to 50% stenosis, 50% to 75% narrowing, 75% to 90%, 90% to 99%, 99% to total occlusion. Only one patient of the 106 who progressed (less than 1%) had ideal values for both cholesterol and triglyceride. Three of 13 patients (23%) who did not progress had ideal lipid values (P less than 0.005). Fifty four of 106 patients who progressed had cholesterol levels greater than or equal to 250 mg%; none of 13 patients who did not progress had such levels (P less than 0.005). Thirty-nine of 98 (40%) patients who progressed had hypertension; only one (8%) who did not progress had hypertension (P less than 0.025). Seventy-four of 96 patients who progressed were smokers (77%); two of 13 nonprogression patients smoked (15%) (P less than 0.005).


Dynamic diversification history with rate upshifts in Holarctic bell-flowers (Campanula and allies).
Campanula s.l. is one of the most speciose flowering plant lineages of the Holarctic (ca. 600 species). In the present study we sequenced three regions of the plastid genome (petD, rpl16 and trnK/matK) across a broad sample of Campanula s.l., which markedly improved phylogenetic resolution and statistical support compared to previous studies. Based on this robust phylogenetic hypothesis we estimated divergence times using BEAST, diversification rate shifts using Bayesian Analysis of Macroevolutionary Mixture (BAMM) and TreePar, and ancestral ranges using Biogeography with Bayesian (and likelihood) Evolutionary Analyses in R. Campanula s.l. is estimated to have originated during the Early Eocene but the major diversification events occurred between the Late Oligocene and Middle Miocene. Two upward diversification rate shifts were revealed by BAMM, specific to the crown nodes of two Campanula clades: CAM17, a mostly South European-SW Asian lineage originating during the Middle Miocene and containing nearly half of all known Campanula species; and CAM15B, a SW Asian-Sino-Himalayan lineage of nine species originating in the early Pleistocene. The dynamic diversification history of Campanula and the inferred rate shifts are discussed in a geo-historical context.


The secretion and maturation of prosaposin and procathepsin D are blocked in embryonic neural progenitor cells.
The notion that prosaposin (Prosap) is likely involved in brain development and regeneration led us to explore its expression in stem/progenitor neural cells and its fate after cell differentiation. The expression of procathepsin-cathepsin D (proCath-Cath D), an endoprotease that plays an important role in the processing and sorting of Prosap, has been concomitantly examined. Our data evidenced that in embryonic human neural progenitor cells (eHNPCs) intact and high molecular weight intermediate forms of Prosap and intermediate forms of Cath D accumulated inside the cells, while the formation of saposins and mature Cath D was impaired. Furthermore, neither Prosap nor proCath D were secreted from eHNPCs. The block of the processing and secretion shared by Prosap and proCath D was overcome during the course of differentiation of eHNPCs into a mixed population of astrocytes and neuronal cells. Upon differentiation, large amounts of Prosap and proCath D were secreted from the cells, while saposins and mature Cath D were produced inside the cells. The dramatic accumulation of Prosap (an antiapoptotic factor) and reduction of mature Cath D (a proapoptotic factor) in the undifferentiated eHNPCs most likely play a role in the molecular mechanisms regulating the resistance to apoptotic signals of these cells and might represent a critically important issue in HNPCs biology.


Detection of bile acids in small volume human bile samples via an amino metal-organic framework composite based solid-phase microextraction probe.
In recent years, bile acids (BAs), the important component of bile, were found closely related to the occurrence and development of diseases, therefore, determination of BAs in bile samples is of great significance. However, biological matrix complexity and low concentrations of BAs were still challenging for BA detection in small amount of bile samples. In this work, a core-shell NH2-MIL101@mSiO2 was designed to improve the capture ability of BAs in biological samples, as well as possess good biocompatibility. Subsequently, solid-phase microextraction (SPME) probe of the NH2-MIL101@mSiO2 was coupled with HPLC-MS/MS to establish the analysis method for detecting eight BAs in bile samples. The established method received extraction efficiencies of (30-2143)-fold higher than those of the commercial probes and low limit of detection (LOD ≤ 0.21 ng mL-1). The miniaturization of SPME sampling devices, as well as the low LOD of this work, endowed this method advantage of low consumption of bile samples (30 μL). Based on the proposed method, eight BAs in bile samples of pancreatic cancer patients and cholelithiasis patients were detected successfully. A distinct difference was found in the concentrations of four targeted BAs in bile samples from pancreatic cancer patients and cholelithiasis patients. This work provided a method for quantification of eight BAs in small volume human bile samples, and it could open up a perspective regarding the relationship between BA metabolism and the occurrence of diseases.


Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates.
Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional organs. Here we show that conjugation of 2'-O-hexadecyl (C16) to siRNAs enables safe, potent and durable silencing in the central nervous system (CNS), eye and lung in rodents and non-human primates with broad cell type specificity. We show that intrathecally or intracerebroventricularly delivered C16-siRNAs were active across CNS regions and cell types, with sustained RNA interference (RNAi) activity for at least 3 months. Similarly, intravitreal administration to the eye or intranasal administration to the lung resulted in a potent and durable knockdown. The preclinical efficacy of an siRNA targeting the amyloid precursor protein was evaluated through intracerebroventricular dosing in a mouse model of Alzheimer's disease, resulting in amelioration of physiological and behavioral deficits. Altogether, C16 conjugation of siRNAs has the potential for safe therapeutic silencing of target genes outside the liver with infrequent dosing.


Effects of Ebola Virus Disease Outbreak on Bush Meat Enterprise and Environmental Health Risk Behavior Among Households in South-East Nigeria.
The 2014 disease outbreak in West Africa of the Ebola virus was the longest, largest, deadliest, and most complex epidemic of its kind in history. It was believed to have originated from bushmeat consumption and exhibited sustained human-to-human transmission. We assessed the effects of the virus outbreak in West Africa on bushmeat enterprise and environmental health risk behaviors among households in Nigeria. We adopted a multistage sampling technique to select 100 respondents. We structured two sets of questionnaires for both bushmeat sellers and consumers. The questionnaire contained information about the respondent's socioeconomic characteristics; perceived causes of the Ebola outbreak; risk behaviors; level of sales; and consumption before, during, and after the Ebola outbreak. We found a significant decrease in the levels of sales and consumption of bushmeat during the outbreak. Consumers perceived touching an infected person, but not eating bushmeat, as a significant mode of Ebola transmission. Although respondents knew about some practices that help to prevent Ebola, they did not practice these to a reasonable extent. We also found that females were 25% more likely than males to consume bushmeat during the outbreak. Given these findings, we recommend that the government should sensitize people and educate them on risk prevention behaviors they should adopt to prevent the transmission of the Ebola disease.


Psychiatric aspects of organ transplantation in critical care.
Intensive care unit teams are a critical part of the solid organ transplant process. The psychosocial issues involved during critical periods of transplantation are important for intensive care physicians and clinicians to understand to provide comprehensive care to transplant patients. This article provides a brief overview of transplant epidemiology, followed by a review of the psychosocial issues relevant to the phases of the transplant process. Considered are the pretransplant evaluation phase, psychiatric disorders in transplant patients, and cognitive impairments and delirium with additional issues specific to particular organs. Also covered are the side effects of immunosuppressive medications and special issues arising with living donors.


Intersex in teleost fish: are we distinguishing endocrine disruption from natural phenomena?
Intersex is defined as the simultaneous presence of male and female gonadal tissue in a gonochoristic (fixed-sex) species. The intersex condition has been documented in both wild and laboratory animals, including fish, amphibians, and reptiles. In aquatic animals, intersex is often viewed as a signature effect of exposure to endocrine disrupting compounds. At least 37 fish species from 17 families have been identified with intersex gonads in 54 field survey studies. However, reports of the occurrence of intersex at reference sites have led to speculation that a baseline level of intersex is "normal". The objective of this critical review was to assess factors potentially associated with baseline levels of intersex in fish and to examine the mechanisms involved in the intersex condition in order to identify priority research areas. Based on current literature, the relationship between intersex and physiological parameters such as plasma sex steroids and vitellogenin is not well characterized or conclusive. Moreover, the literature is not definitive on whether field studies are distinguishing between natural intersex and intersex due to stressors. High throughput transcriptomics will improve understanding of how intersex condition manifests after exposure to aquatic pollution and it is recommended that studies consider both males with and without intersex that inhabit the same polluted site in order to differentiate pathways associated with xenobiotic responses versus molecular pathways associated with intersex. Other experimental design considerations for field studies examining intersex include data collection on life history (e.g. migratory patterns) and improved reference site characterization.


Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.
Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis. One hundred and twenty-three patients with HCC who underwent radical resection were divided into two groups according to a cut-off value of 5.0 ng/ml for serum CEA: high (n=24) and normal (n=99) groups. We compared the clinicopathological factors with serum CEA levels and its correlations with CEACAM1 expression, EMT-related factors and microvessel density (MVD) of tumor tissues by immunohistochemistry. In the high CEA group, the disease-free survival (DFS) rate was significantly worse than in the normal CEA group. Multivariate analysis revealed that a high CEA level was an independent factor predictive of recurrence. Furthermore, increased serum CEA levels were positively correlated with CEACAM1 expression. Moreover, CEACAM1 expression was positively correlated with expression of EMT-related factors and MVD of tumor tissues. Increased serum CEA level reflected CEACAM1 expression and was an independent factor predictive of recurrence in HCC through EMT and tumor angiogenesis.


Chemical characteristics of rainwater in the tropical rainforest region in northwestern Borneo.
A comprehensive study of the chemical composition of rainwater was carried out from October 2016 to September 2017 in the equatorial tropical rainforest region of northwestern Borneo. Monthly cumulative rainwater samples were collected from different locations in the Limbang River Basin (LRB) and were later categorized into seasonal samples representing northeast monsoon (NEM), southwest monsoon (SWM), and inter-monsoon (IM) periods. Physical parameters (pH, EC, TDS, DO, and turbidity), major ions (HCO3-, Cl-, Ca2+, Mg2+, Na+, and K+) and trace metals (Co, Ni, Cd, Fe, Mn, Pb, Zn, and Cu) were analyzed from collected rainwater samples. Rainwater is slightly alkaline with mean pH higher than 5.8. Chloride and bicarbonate are the most abundant ions, and the concentration of major ions in seasonal rainwater has shown slight variation which follows a descending order of HCO3-> Cl-> Na+ > Ca2+ > Mg2+ > K+ in NEM and Cl- > HCO3- > Na+ > Ca2+ > K+ > Mg2+ in SWM and Cl- > HCO3- > Na+ > Ca2+ > Mg2+ > K+ in IM period. Trace metals such as Fe and Ni have shown dominance in seasonal rainwater samples, and all the metals have shown variation in concentration in different seasons. Variation in chemical characteristic of seasonal rainwater samples identified through piper diagram indicates dominance of Ca2+-Mg2+-HCO3- and mixed Ca2+-Mg2+-Cl- facies during NEM, SWM, and IM periods. Statistical analysis of the results through two-way ANOVA and Pearson's correlation also indicates significant variation in physico-chemical characteristics. This suggests a variation in contributing sources during the monsoon seasons. Factor analysis confirmed the source variation by explaining the total variance of 79.80%, 90.72%, and 90.52% with three factor components in NEM, SWM, and IM rainwater samples with different loading of parameters. Enrichment factor analysis revealed a combined contribution of marine and crustal sources except K+ which was solely from crustal sources. Sample analysis of backward air mass trajectory supports all these findings by explaining seasonal variation in the source of pollutants reaching the study area. Overall, the results show that the chemical composition of seasonal rainwater samples in LRB was significantly influenced by natural as well as anthropogenic processes. These include (long-range and local) industrial activities, fossil fuel combustion, forest burning, transportation activities including road transport and shipping activities, and land-derived soil dust along with chemical constituents carried by seasonal wind.


Declining tree growth rates despite increasing water-use efficiency under elevated CO2 reveals a possible global overestimation of CO2 fertilization effect.
Though rising atmospheric CO2 concentrations (Ca) harm the environment and society, they may also raise photosynthetic rates and enhance intrinsic water-use efficiency (iWUE). Numerous short-term studies have investigated tree growth under elevated CO2 (eCO2) conditions, but no long-duration study has investigated eCO2 impacts on tree growth and iWUE under natural conditions. Utilizing a new dendrochronological experimental design in a heavily-touristed nature preserve in Southwest China (Jiuzhaigou National Nature Reserve), we compared tree growth (e.g., basal area increment) and iWUE in two biophysically and environmentally similar valleys with contrasting anthropogenic activities. Trees in the control valley with ambient CO2 benefited from increasing Ca, possibly due to the CO2 fertilization effect and optimal environmental conditions. However, trees in the treatment valley with intensive tourism experienced comparatively higher localized eCO2 and growth rate declines. While iWUE increased (1959-2017) in the control (25.3%) and treatment sites (47.8%), declining tree growth rates in the treatment site was likely because comparatively extreme CO2 exposure levels encouraged stomatal closures. As the first long-term study investigating eCO2 impacts on tree growth and iWUE under natural conditions, we demonstrate that increased forest iWUE is unlikely to overcome negative drought stress and rising temperature impacts. Thus, forest potential for mitigating eCO2 and global climate change is likely overestimated, particularly under dry temperate conditions.


Interstitial high-dose-rate brachytherapy in the treatment of keloids: Moving toward a volumetric approach.
Brachytherapy (BT) after surgical resection of keloids reduces the risk of local recurrence, but standardization of dose/technique is lacking. Typical keloid BT treatment utilizes a single-channel source prescribed to 5-mm depth. We investigated the dosimetry of a volume-based target definition for interstitial high-dose-rate BT treatment of keloids. We retrospectively identified consecutive 14 patients who had a total of 20 keloids treated with interstitial high-dose-rate BT for keloids at our institution between 2004 and 2014. Keloids were treated with a single 8 Gy fraction prescribed to 5 mm beneath the scar within 36 h of surgery. Retrospectively, a 3-mm skin high-risk clinical target volume (HR-CTV) was contoured under the scar for volume-based dose calculations. Mean (SD) HR-CTV was 3.91 cm3 (3.1) and mean (SD) HR-CTV dose was 11.3 Gy (3.6). Mean D90 (SD) was 62.9% (25.8) and mean V100 (SD) was 56.5% (26.4). The mean V150 (SD), V200 (SD), and V300 (SD) were as follows: 37.6% (19.9), 25.1% (14.4), and 11.3% (6.5), respectively. No local failures were reported at 9 months median followup. There were no Grade 2 or higher late toxicities. Using a volume-based target definition, a wide range of target coverage was observed. This is likely a consequence of the curvature of the skin and the challenges of keeping the catheter equidistant from the skin across the target. Additional data are needed to define the potential clinical impact on outcomes/toxicities of dosimetric correlates with single-catheter BT keloid treatment.


RACK1 is evolutionary conserved in satellite stem cell activation and adult skeletal muscle regeneration.
Skeletal muscle growth and regeneration involves the activity of resident adult stem cells, namely satellite cells (SC). Despite numerous mechanisms have been described, different signals are emerging as relevant in SC homeostasis. Here we demonstrated that the Receptor for Activated C-Kinase 1 (RACK1) is important in SC function. RACK1 was expressed transiently in the skeletal muscle of post-natal mice, being abundant in the early phase of muscle growth and almost disappearing in adult mature fibers. The presence of RACK1 in interstitial SC was also detected. After acute injury in muscle of both mouse and the fruit fly Drosophila melanogaster (used as alternative in vivo model) we found that RACK1 accumulated in regenerating fibers while it declined with the progression of repair process. To note, RACK1 also localized in the active SC that populate recovering tissue. The dynamics of RACK1 levels in isolated adult SC of mice, i.e., progressively high during differentiation and low compared to proliferating conditions, and RACK1 silencing indicated that RACK1 promotes both the formation of myotubes and the accretion of nascent myotubes. In Drosophila with depleted RACK1 in all muscle cells or, specifically, in SC lineage we observed a delayed recovery of skeletal muscle after physical damage as well as the low presence of active SC in the wound area. Our results also suggest the coupling of RACK1 to muscle unfolded protein response during SC activation. Collectively, we provided the first evidence that transient levels of the evolutionarily conserved factor RACK1 are critical for adult SC activation and proper skeletal muscle regeneration, favoring the efficient progression of SC from a committed to a fully differentiated state.


[Assessment of movements of the different anatomic portions of the bladder, implications for image-guided radiation therapy for bladder cancer].
To assess interfraction and intrafraction bladder wall movements in the different anatomic portions of the bladder. Six patients were treated for prostate cancer with conformal irradiation. Daily online cone beam computed tomography was performed for repositioning and an additional one was performed following irradiation once weekly. Four craniocaudal levels were defined to calculate movements amplitudes compared to the scanner tracking: level 1 at the bladder neck, level 2 at mid-height of the bladder, level 3 at mid-height of the dome, level 4 at the apex in a distended bladder. Bladder height was also measured. On 198 daily cone beam computed tomographies, radial bladder right/left/anterior/posterior wall displacements at level 2 were 0.08 ± 0.24, 0.11 ± 0.33, 0.16 ± 0.45 and 0.14 ± 0.50 cm and at level 3 0.07 ± 0.78, 0.18 ± 0.98, 0.43 ± 0.94 and 0.04 ± 1.02 cm. Dome and neck displacements were 0.08 ± 1.41 cm and 0.08 ± 0.64 cm. Seventeen cone beam computed tomographies were done following irradiation. Radial bladder right/left/anterior/halfway up the trine wall displacements at level 2 before and after irradiation were 0.02±0.18, 0.01±0.30, 0.09 ± 0.32 and 0.22 ± 0.42 cm and at level 3 0.27 ± 0.60, 0.37 ± 1.15, 0.18 ± 0.87 and 0.54 ± 1.68 cm. Significant bladder wall displacements were observed on the anterior wall and upper portion of the bladder. Isotropic margins may not be sufficient to account for inter- and intrafraction bladder wall displacements at the latter levels. Tailored bladder anatomy-based anisotropic margins may be necessary to optimally spare the small intestine and to guaranty proper tumour coverage in case of bladder cancer. For upper bladder tumours, margins of over 2 cm would be necessary, which make them less adequate for external beam irradiation.


Staphylococcus aureus in veterinary medicine.
Staphylococcus aureus is a major opportunistic pathogen in humans and one of the most important pathogenic Staphylococcus species in veterinary medicine. S. aureus is dangerous because of its deleterious effects on animal health and its potential for transmission from animals to humans and vice-versa. It thus has a huge impact on animal health and welfare and causes major economic losses in livestock production. Increasing attention is therefore being paid to both livestock and companion animals in terms of this pathogen. In this review, we summarise the current knowledge on the animal host adaptation of S. aureus. Different types of S. aureus infections in animals are also presented, with particular emphasis on mastitis in dairy herds, which is probably the costliest and therefore the best documented S. aureus infection seen in animals.


Quantitative determination of coccidian oocysts in beef calves from the coastal plain area of Georgia (U.S.A.).
For two consecutive years, determinations were made of the prevalence and abundance of coccidian oocysts from crossbred beef calves raised on Bahia grass pastures in the coastal plain area of Georgia. Of the 534 fecal samples collected during the survey, 461 (86.3%) contained one or more species of coccidian oocysts. The total mean oocysts per gram of feces (OPG) was significantly different (P less than 0.10) between the two years. Thirteen species of Eimeria were found during both years of the survey. Eimeria bovis was the most prevalent species found in the survey; E. ellipsoidalis, however, had the greatest number of OPG. Eimeria bukidnonensis, E. pellita, and E. brasiliensis were the least prevalent species and also had the lowest numbers of OPG. Only one clinical case of coccidiosis was seen. A nine-month-old calf had E. zuernii coccidiosis; it excreted E. zuernii oocysts in several fecal samples before the clinical disease appeared.


Pediatric allergic contact dermatitis. Part 2: Patch testing series, procedure, and unique scenarios.
Patch testing is the criterion standard for diagnosing allergic contact dermatitis. Causative allergens differ between children and adults, necessitating the development of pediatric-specific patch test series. The Pediatric Baseline Series was developed in 2018 through expert consensus and includes relevant pediatric allergens that dermatologists can use in practice. Obstacles in patch testing, such as the need for multiple office visits, length of patch application, and avoidance of sweat and water on the testing area, are particularly challenging for the pediatric population, and several strategies are proposed. Aside from formal patch testing, alternatives like the repeat open application test and empiric allergen avoidance can be helpful in children. The key to management of allergic contact dermatitis is allergen avoidance, with emphasis on the need to properly identify causative allergens. Continued data collection through registries allows for a better understanding of the diagnosis and management of pediatric allergic contact dermatitis.


Lost in (Clinical) Translation: Recent Advances in Heparin Neutralization and Monitoring.
The heparin family, which includes unfractionated heparin, low-molecular heparin, and fondaparinux, is a class of drugs clinically used as intravenous blood thinners. To date, issues related to both the reversal of anticoagulation and the blood level determination of the anticoagulant at the point-of-care remain: while the only U.S. Food and Drug Administration (FDA) approved antidote for heparin displays serious efficacy and safety drawbacks, the current assays for heparin monitoring are indirect measurements subject to their own limitations and variations. Herein, we provide an update on the numerous recent chemical approaches to tackle these issues, from which it is clear that some new antidotes and sensors for heparin certainly have the potential to exceed current clinical standards. This review aims to review a field that requires close collaborations between physicians, biologists, and chemists in order to foster advances toward clinical translation.


Paeoniflorin protects against ANIT-induced cholestasis by ameliorating oxidative stress in rats.
Paeoniflorin, one of the primary bioactive components in Chi shao, are widely used in traditional Chinese medicine. A lot of evidences suggest that Paeoniflorin has potential anti-oxidant effects. However, whether Paeoniflorin plays roles in cholestasis is unclear. In this study, we examined the protective effect of Paeoniforin against alpha-naphthylisothicaynate (ANIT)-induced cholestasis in rats. Our data demonstrated that the high (0.2 g/kg body weight) and medium (0.1 g/kg body weight) doses of Paeoniflorin significantly prevented ANIT-induced changes in bile flow and the serum levels of total bilirubin, direct bilirubin, total bile acid, γ-glutamyltranspeptidase, glutamate-pyruvate transaminase, glutamate-oxaloacetic transaminase and alkaline phosphatase. Moreover, we also found that Paeoniflorin significantly inhibited nitric oxide and malondialdehyde production, and restored glutathione decrease induced by ANIT. EPR data further indicated that Paeoniflorin inhibited ANIT-mediated reactive oxygen species (ROS) production. The overexpression of NADPH oxidase 4 induced by ANIT were significantly reversed when treated with Paeoniflorin, suggesting that Paeoniflorin could scavenge ROS via inhibiting NADPH oxidase 4 expression. Paeoniflorin treatment could also relieve ANIT-induced liver pathological injuries as indicated by histological assay. These findings indicate that Paeoniflorin exerts a dose-dependent protective effect on ANIT-induced cholestatic liver injury in rats, and the mechanism of this activity is related to its attenuation of oxidative stress in liver tissue.


Protection by ethyl pyruvate against gamma radiation induced damage in bovine serum albumin.
Environmental factors like ionizing radiation induced generation of reactive oxygen species (ROS) cause macromolecular damage under physiological conditions. Proteins are the potential targets of ROS induced oxidative damage because of their abundance and their critical functions in the biological systems. The present study investigates the protective potential of ethyl pyruvate (EP) against ionizing radiation induced oxidative damage of bovine serum albumin (BSA) using spectroscopic, biochemical and SDS-PAGE techniques. Spectroscopic data shows that EP prevents the build up of protein damage markers like bityrosine formation and oxidation of tryptophan. Protein melting studies shows that the melting temperature (Tm) of the irradiated protein does not change significantly in the presence of EP. Biochemical assays indicate that ionizing radiation causes the generation of carbonyls and malondialdehyde and the loss of thiol content in proteins that is prevented by EP. The SDS-PAGE profile of gamma irradiated BSA shows the radioprotective effect of EP. These results indicate the radiation induced oxidative and molecular changes in the protein and that the EP protected the BSA from these modifications. Therefore, these results imply that EP has a good antiradical property and hence it can be proposed as a good radioprotective agent.


Supramolecular design of coordination bonding architecture on zein nanoparticles for pH-responsive anticancer drug delivery.
A pH-responsive system by constructing a designable coordination bonding-based metal-tannic acid (TA) architecture on zein nanoparticles (NPs) has been investigated. Film formation was initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. The prepared metal-TA coated zein NPs (zein-TA/metal NPs) demonstrated good stability to maintain particle size in cell culture medium at 37 °C. The microstructure of the NPs was revealed by transmission electron microscopy (TEM). To confirm the surface chemical information of the NPs, XPS analysis was performed. Furthermore, in vitro viability studies revealed that the zein-TA/metal NPs showed no significant cytotoxicity against HepG2 cells for 24h. Because of the pH-responsive coordination bonding between TA and metal ions, the functional property of the metal-TA films was tailored for drug delivery. Biocompatible AuNPs were produced using zein-TA/metal NPs as reducing and stabilizing agents which were promising in the photothermal therapy of cancers and other diseases.


Outsourcing loses its 'MO'. Our annual survey points to a plateau for most contract services.
Outsourcing remains popular with health care executives hungry to control costs. But our annual survey shows that its momentum is stalling. Most respondents don't expect their contracting of business, support, and clinical services to change much over the next two years.


Routine Postoperative Radiographs Do Not Affect Decision Making Following Carpometacarpal Arthroplasty.
Arthritis of the first carpometacarpal (CMC) joint affects up to 15% of the population aged over 30 years and 40% of the population aged over 50 years. Arthroplasty of the first CMC joint is a widely accepted treatment option for these patients, with most patients doing well long term despite radiographic evidence of subsidence. Postoperative treatment protocols vary with no defined gold standard, and the need for routine postoperative radiographs has not been defined. The purpose of this study was to evaluate the use of routine postoperative radiographs following CMC arthroplasty. A retrospective review of patients who underwent CMC arthroplasty from 2014 to 2019 at our institution was performed. Patients receiving a concomitant trapezoid resection or metacarpophalangeal capsulodesis/arthrodesis were excluded. Demographic data, as well as the frequency and timing of postoperative radiographs, were collected. Radiographs were included if taken up to 6 months from the date of surgery. The primary outcome was a repeated operative intervention. Descriptive statistics were used for the analysis. A total of 155 CMC joints from 129 patients were included in the study. Sixty-one (39.4%) patients had no postoperative radiographs, 76 (49.0%) patients had one postoperative radiographic series, 18 (11.6%) had two, 8 (5.2%) had three, and 1 (0.6%) patient had four postoperative series of radiographs. A radiographic series is defined as multiple views taken at a single time point. Four of 155 (2.6%) patients underwent additional operative intervention. There were no patients who underwent revision CMC arthroplasty. Two had wound infections that underwent irrigation and debridement. Two developed metacarpophalangeal arthritis and underwent arthrodesis. There were no cases where repeat operative intervention was driven by postoperative radiographic findings. Routine postoperative radiographs following CMC arthroplasty do not lead to changes in patient management, specifically further surgery. These data may support forgoing routine radiographs in the postoperative period following CMC arthroplasty. Therapeutic IV.


Effects of estrogen on intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors and on acetylcholinesterase activity in rat hippocampus.
The aim of the present study was to investigate the effects of estrogen lack and estrogen replacement on the production of total [3H]inositol phosphate ([3H]IP) induced by the activation of muscarinic acetylcholine receptors (mAChRs) and on the mechanisms for inactivation of acetylcholine. Hippocampi were obtained from rats in proestrus (PE), ovariectomized for 15 days (C15), ovariectomized for 15 days and then treated with 17beta-estradiol for 7 days (E7) and ovariectomized and immediately treated with 17beta-estradiol for 21 days (E21). Ovariectomy did not change the basal level of total [3H]IP in the hippocampus. 17beta-Estradiol replacement (E7 and E21) reduced the basal level of total [3H]IP. In all experimental groups, carbachol (CCh) caused a concentration-dependent rise in total [3H]IP. The maximum effect was reached with 10(-4) M CCh. The response to 10(-4) M CCh in the hippocampi from C15 and E7 rats was twofold higher than in hippocampi from PE and E21 animals and was blocked by pirenzepine, but not by methoctramine. Ovariectomy or 17beta-estradiol treatment for 7 days did not change neither the total acetylcholinesterase (AChE) activity nor the relative amount of mono- and dimeric G1/G2 and tetrameric G4 globular forms. Conversely, hormonal treatment for 21 days induced an increase in AChE activity of G1/G2 and G4 forms, indicating that 17beta-estradiol stimulates both synthesis and assembly of AChE molecular forms. The present results suggest that the duration and/or a critical period with regard to the initiation of estrogen therapy are important to regulate the function of mAChRs and AChE activity in female rat hippocampus.


[Cytokines and T cell differentiation in systemic sclerosis].
The physiopathology of systemic sclerosis remains unclear within a complex interaction between vasculopathy, perivascular inflammatory infiltrate, extensive tissue fibrosis and auto-immune manifestations. Chronology between vascular disease and adjacent inflammatory cell infiltration is still not yet clarified. There is growing evidence that T cell activation and its cytokine expression play a key role in vascular impairment occurrence and collagen dysregulation. Nevertheless, cytokine descriptions are mainly limited to blood and tissue measurement and the T cells differentiation analysis restricted to the Th1/Th2 balance. The purpose of this review is to establish an exhaustive cartography of cytokines involved in T cell differentiation, regarding the recent advance in T lymphocyte differentiation, including Th9, Th17, Th22 and regulatory T cells (Treg) pathways. This review will focus on Th17, Th22 and Treg differentiation, corresponding to the equilibrium between inflammation and tolerance. Finally, regarding published results in systemic sclerosis, T cells participation appears to be more a Th1/Th2 co-expression than an exclusive Th1 or Th2 polarization. Also, a possible Th22/Treg imbalance is suggested, leading to a Th22 overexpression and likely to tissue inflammation genesis.


[Supratentorial cavernous malformations in an Argentinian institution: experience with surgical treatment].
Cavernous malformations are vascular malformations of the central nervous system formed by a group of capillaries not covered by pia mater and communicated to the vascular system at very low pressure with very slow flow. Surgery or radiosurgery are the treatment modalities. To analyze our results after surgical treatment of supratentorial cavernous malformations, reviewing clinical presentation, surgical indications and postoperative complications. Analytical retrospective study of medical records and images of patients who underwent resection of supratentorial cavernomas at FLENI from January 1996 until December 2013. We evaluated 51 patients, mean age 34 years, followed for an average of 30 months. In 1.96% of patients diagnosis was incidental, the rest all presented symptoms. Bleeding at diagnosis was observed in 23.52%. Total excision of supratentorial cavernous malformations was possible in all cases. The only postoperative complication was one case of meningitis. The bleeding rate of supratentorial cavernous malformations in our series was 1.38% per patient per year. Surgical treatment effectively eliminated, or at least reduced symptoms, prevented rebleeding, and decreased need for antiepileptic drug therapy. Surgery have a low complication rate and good outcome.


wrmXpress: A modular package for high-throughput image analysis of parasitic and free-living worms.
Advances in high-throughput and high-content imaging technologies require concomitant development of analytical software capable of handling large datasets and generating relevant phenotypic measurements. Several tools have been developed to analyze drug response phenotypes in parasitic and free-living worms, but these are siloed and often limited to specific instrumentation, worm species, and single phenotypes. No unified tool exists to analyze diverse high-content phenotypic imaging data of worms and provide a platform for future extensibility. We have developed wrmXpress, a unified framework for analyzing a variety of phenotypes matched to high-content experimental assays of free-living and parasitic nematodes and flatworms. We demonstrate its utility for analyzing a suite of phenotypes, including motility, development/size, fecundity, and feeding, and establish the package as a platform upon which to build future custom phenotypic modules. We show that wrmXpress can serve as an analytical workhorse for anthelmintic screening efforts across schistosomes, filarial nematodes, and free-living model nematodes and holds promise for enabling collaboration among investigators with diverse interests.


Enhanced production of 3-hydroxypropionic acid from glucose via malonyl-CoA pathway by engineered Escherichia coli.
In this study, production of 3-HP via malonyl-CoA was investigated by using metabolically engineered Escherichia coli carrying heterogeneous acetyl-CoA carboxylase (Acc) from Corynebacterium glutamicum and codon-optimized malonyl-CoA reductase (MCR) from Chloroflexus aurantiacus. Three engineered E. coli strains with different host-vector systems were constructed and investigated. The results indicated that the combination of E. coli BL21(DE3) and pET28a was the most efficient host-vector system for 3-HP production, and the highest concentration of 3-HP attained in shake flask cultivation reached 1.80g/L by the strain BE-MDA with induction at 0.25mM IPTG and 25°C, and supplementation of NaHCO3 and biotin. In fed-batch fermentation performed in a 5-L reactor, the concentration of 3-HP achieved 10.08g/L in 36h.


Receptive amusia: temporal auditory processing deficit in a professional musician following a left temporo-parietal lesion.
This study examined the musical processing in a professional musician who suffered from amusia after a left temporo-parietal stroke. The patient showed preserved metric judgement and normal performance in all aspects of melodic processing. By contrast, he lost the ability to discriminate or reproduce rhythms. Arrhythmia was only observed in the auditory modality: discrimination of auditorily presented rhythms was severely impaired, whereas performance was normal in the visual modality. Moreover, a length effect was observed in discrimination of rhythm, while this was not the case for melody discrimination. The arrhythmia could not be explained by low-level auditory processing impairments such as interval and length discrimination and the impairment was limited to auditory input, since the patient produced correct rhythmic patterns from a musical score. Since rhythm processing was selectively disturbed in the auditory modality, the arrhythmia cannot be attributed to a impairment of supra-modal temporal processing. Rather, our findings suggest modality-specific encoding of musical temporal information. Besides, it is proposed that the processing of auditory rhythmic sequences involves a specific left hemispheric temporal buffer.


Evidence for induced microsomal bilirubin degradation by cytochrome P450 2A5.
Oxidative metabolism of bilirubin (BR) -- a breakdown product of haem with cytoprotective and toxic properties -- is an important route of detoxification in addition to glucuronidation. The major enzyme(s) involved in this oxidative degradation are not known. In this paper, we present evidence for a major role of the hepatic cytochrome P450 2A5 (Cyp2a5) in BR degradation during cadmium intoxication, where the BR levels are elevated following induction of haem oxygenase-1 (HO-1). Treatment of DBA/2J mice with CdCl(2) induced both the Cyp2a5 and HO-1, and increased the microsomal BR degradation activity. By contrast, the total cytochrome P450 (CYP) content and the expression of Cyp1a2 were down-regulated by the treatment. The induction of the HO-1 and Cyp2a5 was substantial at the mRNA, protein and enzyme activity levels. In each case, the up-regulation of HO-1 preceded that of Cyp2a5 with a 5-10h interval. BR totally inhibited the microsomal Cyp2a5-dependent coumarin hydroxylase activity, with an IC(50) approximately equal to the substrate concentration. The 7-methoxyresorufin 7-O-demethylase (MROD) activity, catalyzed mainly by the Cyp1a2, was inhibited up to 36% by BR. The microsomal BR degradation was inhibited by coumarin and a monoclonal antibody against the Cyp2a5 by about 90%. Furthermore, 7-methoxyresorufin, a substrate for the Cyp1a2, inhibited BR degradation activity by approximately 20%. In sum, the results strongly suggest a major role for Cyp2a5 in the oxidative degradation of BR. Secondly, the coordinated up-regulation of the HO-1 and Cyp2a5 during Cd-mediated injury implicates a network of enzyme systems in the maintenance of balancing BR production and elimination.


Whole hemisphere autoradiography of the postmortem human brain.
Whole hemisphere autoradiography (WHA) with selective high-affinity radioligands is a new tool in studying the distribution of receptors and of other neuronal components postmortem in brains from controls vs. subjects with psychiatric and neurologic diseases. WHA can be performed with several different isotopes (e.g., 3H, 125I, and 11C), and is in addition to characterization studies also used as a tool in early radioligand development. Moreover, using this technique, high-resolution images are obtained that are complementary to those obtained in vivo with e.g., PET and SPECT. Results on dopamine and serotonin receptor subtypes as well as of their transporters show that WHA is a very suitable technique for the detailed characterization of the distribution in the whole human brain.


Immunoregulation of lysozyme-specific suppression. II. Hen egg-white lysozyme-specific monoclonal suppressor T cell factor suppresses the afferent phase of delayed-type hypersensitivity and induces second-order suppressor T cells.
Culture supernatant from a monoclonal T cell lymphoma line (LH8-105) obtained by radiation leukemia virus-induced transformation of hen egg-white lysozyme (HEL)-specific suppressor T lymphocytes is able, when injected into mice, to specifically suppress the delayed-type hypersensitivity (DTH) reaction induced by HEL. The suppressor T cell factor (TsF) exhibits fine antigenic specificity since it suppresses the DTH response induced by HEL without affecting the DTH response induced by ring-necked pheasant egg-white lysozyme (REL), a lysozyme closely related to HEL. Conversely, LH8-105 TsF is able to suppress the DTH response induced by human lysozyme, distantly related to HEL but sharing a common epitope critical for induction of suppressive activity. The fine antigenic specificity of LH8-105 TsF for a restricted epitope on the HEL molecule is confirmed by binding to HEL but not to REL immunosorbents. This TsF also bears I-J determinants, as demonstrated by binding to monoclonal anti-I-J immunosorbents, and it suppresses the afferent but not the efferent phase of the DTH response to HEL. The afferent suppression is controlled by genes apparently mapping in the I-J subregion of the H-2 complex since I-J-incompatible mice are not suppressed by LH8-105 TsF injection. This inducer-type TsF induces second-order effector suppressor T cells only in HEL-primed mice indicating the primary role of antigen, in association with H-2 (I-J) products, in the afferent portion of this suppressive circuit.


Corticotropin-releasing factor, but not arginine vasopressin, stimulates concentration-dependent increases in ACTH secretion from a single corticotrope. Implications for intracellular signals in stimulus-secretion coupling.
The two fundamental parameters of corticotropin (ACTH) secretion are the number of secreting corticotropes and the amount of ACTH secreted by each cell. We have measured these parameters in rat corticotropes in response to increasing concentrations of corticotropin-releasing factor (CRF) or arginine vasopressin (AVP). Increasing concentrations of AVP stimulated more corticotropes to secrete, while the amount of ACTH each cell secreted remained relatively fixed (nongraded secretory response). Conversely, increasing concentrations of CRF stimulated more ACTH secretion per cell (graded secretory response), while the number of secretory cells remained relatively constant. When viewed from the perspective of a single corticotrope, it was clear that CRF and AVP induced completely distinct specific responses. We have previously shown, and provide further evidence here, that secretory responses to CRF or AVP occur in the same cell. It is therefore apparent that a single corticotrope is able to generate either a graded, or a nongraded secretory response. We have also considered the potential intracellular changes that must direct graded or nongraded secretion. It is generally accepted that CRF stimulates activation of adenylate cyclase, whereas AVP activates phosphoinositidase in pituitary corticotropes. Our findings, and others surveyed here, suggest that the activation of adenylate cyclase results in graded secretion, while the activation of phosphoinositidase induces the nongraded secretion. Graded or nongraded secretion may therefore be linked to specific second messengers. It is hypothesized that the inositol 1,4,5-trisphosphate-mediated release of an intracellular Ca2+ store constitutes a mechanism whereby phosphoinositidase-coupled hormones set in motion the nongraded secretory response. These findings suggest novel functions for individual second messengers.