Transdermal iontophoretic delivery of vapreotide acetate across porcine skin in vitro.
The purpose of this study was to evaluate the feasibility of delivering vapreotide, a somatostatin analogue, by transdermal iontophoresis. In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying vapreotide transport into and across the skin, the effect of peptide delivery on skin permselectivity was also measured. The influence of (1) current density, (2) pre- and post-treatment of the skin, (3) competitive ions, and (4) inclusion of albumin in the receptor on vapreotide delivery were investigated. Epidermis proved to be a better model than dermatomed skin for vapreotide transport studies. Despite the susceptibility of vapreotide to enzymatic degradation, a flux of 1.7 microg/cm2 per hour was achieved after 7 h of constant current iontophoresis (0.15 mA/cm2). Post-iontophoretic extraction revealed that, depending on the experimental conditions, 80-300 microg of peptide were bound to the skin. Vapreotide was found to interact with the skin and displayed a current-dependent inhibition of electroosmosis. However, neither the pre-treatment strategies to saturate the putative binding sites nor the post-treatment protocols to displace the bound peptide were effective. Based on the observed transport rate of vapreotide across porcine epidermis and its clinical pharmacokinetics, therapeutic concentrations should be achievable using a 15-cm2 patch.


Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.
Midazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet. The objective was to describe intraindividual variability in absolute bioavailability and clearance of midazolam in healthy individuals without obesity. This study included 33 healthy volunteers [28 ± 8 years, 21% males, body mass index (BMI) 23 ± 2.5 kg/m2] subjected to four pharmacokinetic investigations over a 2-month period (weeks 0, 2, 4, and 8). Semi-simultaneous oral (0 h) and intravenous (2 h later) midazolam dosing was used to assess absolute bioavailability and clearance of midazolam. At baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively. The mean coefficient of variation (CV, %) for absolute bioavailability and clearance of midazolam was 26 ± 15% and 20 ± 10%, respectively. Approximately one-third had a CV > 30% for absolute bioavailability, while 13% had a CV > 30% for clearance. On average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals.


Psychological inflexibility and somatization in nonepileptic attack disorder.
There is no clear understanding of what causes and maintains nonepileptic attack (NEA) disorder (NEAD), or which psychological therapies may be helpful. The relationships between variables of psychological inflexibility: experiential avoidance (EA), cognitive fusion (CF), mindfulness, and key outcome variables in NEAD: somatization, impact upon life, and NEA frequency were investigated. Two hundred eighty-five individuals with NEAD completed validated measures online. Linear regression was used to explore which variables predicted somatization and impact upon life. Ordinal regression was used to explore variables of interest in regard to NEA frequency. Mindfulness, EA, CF, somatization, and impact upon life were all significantly correlated. Mindfulness uniquely predicted somatization when considered in a model with EA and CF. Higher levels of somatization increased the odds of experiencing more NEAs. Individuals who perceived NEAD as having a more significant impact upon their lives had more NEAs, more somatic complaints, and more EA. Higher levels of CF and EA appear to be related to lower levels of mindfulness. Lower levels of mindfulness predicted greater levels of somatization, and somatization predicted NEA frequency. Interventions that tackle avoidance and increase mindfulness, such as, acceptance and commitment therapy, may be beneficial for individuals with NEAD. Future directions for research are suggested as the results indicate more research is needed.


Response of terminal Schwann cells following volumetric muscle loss injury.
An often-overlooked component of traumatic skeletal muscle injuries is the impact on the nervous system and resultant innervation of the affected muscles. Recent work in a rodent model of volumetric muscle loss (VML) injury demonstrated a progressive, secondary loss of neuromuscular junction (NMJ) innervation, supporting a role of NMJ dysregulation in chronic functional deficits. Terminal Schwann cells (tSCs) are known to be vital for the maintenance of NMJ structure and function, in addition to guiding repair and regeneration after injury. However, the tSC response to a traumatic muscle injury such as VML is not known. Thus, a study was conducted to investigate the effect of VML on tSC morphological characteristics and neurotrophic signaling proteins in adult male Lewis rats that underwent VML injury to the tibialis anterior muscle using a temporal design with outcome assessments at 3, 7, 14, 21, and 48 days post-injury. The following salient observations were made; first, although there is a loss of innervation over time, the number of tSCs per NMJ increases, significantly so at 48 days post-injury compared to control. The degree of NMJ fragmentation was positively correlated with tSC number after injury. Moreover, neurotrophic factors such as NRG1 and BDNF are elevated after injury through at least 48 days. These results were unanticipated and in contrast to neurodegenerative disease models, in which there is a reduction in tSC number that precedes denervation. However, we found that while there are more tSCs per NMJ after injury, they cover a significantly smaller percent of the post-synaptic endplate area compared to control. These findings support a sustained increase in neurotrophic activity and tSC number after VML, which is a maladaptive response occurring in parallel to other aspects of the VML injury, such as over-accumulation of collagen and aberrant inflammatory signaling.


Patterns of Behavioral Deficits in Rodents Following Brain Injury Across Species, Gender, and Experimental Model.
Behavioral data were collected from several hundred mice and rats using a variety of experimental models of brain injury. The use of consistent protocols allowed compilation of these data, facilitating analyses of animal behaviors across experimental models, species, and gender. Spatial learning and sensorimotor/coordination data are presented, suggesting that, in general, rats performed better than mice both in the water maze and on the rotarod. Compared with females, males performed slightly better in the water maze and slightly worse on the rotarod. However, gender by species interactions accounted for both of these differences. Male rats performed better in the water maze than female rats, male mice, and female mice, which did not differ. Male mice performed worse on the rotarod than female mice, male rats, and female rats, which performed similarly. Furthermore, animals with subcortical injury were impaired in the water maze, but performed better than animals with cortical injuries. However, only animals with cortical injuries were impaired on the rotarod. Additional covariates, such as edema and lesion size, may further clarify these phenotypes. Overall, we provide evidence that abbreviated test batteries can be specifically designed to test deficits, depending on the species, gender, and model.


Interactions between light and carbon signaling pathways in Arabidopsis.
Two major signals perceived by plants are light and the source of carbon. A new report has examined the interactions between the signaling pathways from these two stimuli on a genome-wide scale in the model plant Arabidopsis thaliana.


Refractory symptomatic ventricular tachycardia and ventricular fibrillation in elderly patients.
The problem of refractory life-threatening ventricular tachyarrhythmias in elderly patients has not been previously studied. To determine if clinical, anatomic, or electrophysiologic variables and prognosis are significantly different in elderly subjects, 49 elderly (68 to 84 years) and 44 younger (44 to 53 years) survivors of refractory symptomatic ventricular tachycardia and/or ventricular fibrillation secondary to coronary artery disease were studied. Elderly patients displayed more extensive anatomic coronary artery disease, with 80 percent having three-vessel disease in comparison with 30 percent of the younger patients (p less than 0.001). Prior myocardial infarction, heart failure, and cardiomegaly were more common in the elderly group (p less than 0.01, p less than 0.001, and p less than 0.034, respectively), whereas angina was more common in the younger group (p less than 0.001). In 55 percent of the elderly patients and 58 percent of the younger patients, electrophysiologic testing demonstrated inducible sustained ventricular tachycardia that required treatment with an investigative antiarrhythmic drug and/or cardiac surgery, including implantation of an automatic defibrillator. Elderly patients tolerated aggressive evaluation as well as did younger patients, and despite the difference in clinical and anatomic findings, long-term survival curves were similar, although the probability of survival at 20 months was 62 percent in the elderly and 80 percent in the younger patients. This difference in early survival is explained by eight surgical deaths in the elderly group, compared with two in the younger group.


Vaccination of mice with DNA vaccine induces the immune response and partial protection against T. spiralis infection.
Trichinellosis is a serious parasitic zoonosis which is widely distributed in the world. Pork still is the predominant source of outbreaks of human trichinellosis in many countries. Vaccines are urgently needed to prevent swine from Trichinella infection. The gene (TspE1) encoding a 31 kDa antigen of T. spiralis was cloned to a eukaryotic expression plasmid pcDNA3 as DNA vaccine. The ability of the DNA vaccine to express antigen in mammalian CHO cells was previously confirmed by indirect fluorescencent antibody test (IFAT) and Western blotting. To evaluate its immunogenicity and its host protective potential, BALB/c mice were immunized with the DNA vaccine by intramuscular injection and gene-gun delivery. The serum antibody response was assayed by IFAT, enzyme linked immunosorbant assay (ELISA) and Western blotting. The cellular immune response was investigated by splenocyte proliferation assay. Vaccine administration by either route induced both humoral and cellular immune response against TspE1, which provided the partial protection against challenge infection with T. spiralis, as shown by significant reduction of larval burden in muscles. Thus, DNA immunization may offer an attractive alternative strategy against swine trichinellosis.


Shiga toxin from Shigella dysenteriae 1 inhibits protein synthesis in reticulocyte lysates by inactivation of aminoacyl-tRNA binding.
Inhibition of the peptide elongation cycle of eukaryotic protein synthesis by Shiga toxin from Shigella dysenteriae 1 was examined in toxin-treated reticulocyte lysate mixtures. Peptidyl transferase activity of toxin-treated ribosomes was measured by following the decrease in peptidyl-tRNA concentrations when puromycin was added after incubation with toxin. Concentrations of [3H]leucine-labeled peptidyl-tRNA were measured by extraction with cetyltrimethylammonium bromide. The data suggest that Shiga toxin inhibited aminoacyl-tRNA binding. Toxin-treated ribosomes retained peptidyl transferase activity, and toxin did not block translocation. Furthermore, no inhibition of initiation of protein synthesis could be observed. Finally, Shiga toxin had no detectable nucleolytic effect on polysomal 28S rRNA, nor was hydrolysis of 5.8S or 5S rRNA observed.


Patient-Specific Three-Dimensional Printing Guide for Single-Stage Skull Bone Tumor Surgery: Novel Software Workflow with Manufacturing of Prefabricated Jigs for Bone Resection and Reconstruction.
To describe a novel system workflow to design and manufacture patient-specific three-dimensional (3D) printing jigs for single-stage skull bone tumor excision and reconstruction and to present surgical outcomes of 14 patients. A specific computer-aided design/computer-aided manufacturing software and hardware system was set up, including a virtual surgical planning subsystem and a 3D printing-associated manufacturing subsystem. Computed tomography data of the patient's skull were used for 3D rendering of the skull and tumor. The output of patient-specific designing included a 3D printing guide for tumor resection and a 3D printing model of the bone defect after tumor excision. A polymethyl methacrylate implant was fabricated preoperatively and used for repair. The specific 3D printing guide was used to design intraoperative jigs and implants for 14 patients (age range, 1-72 years) with skull bone tumors. In all cases, the cutting jig allowed precise excision of tumor and bone, and implants were exact fits for the defects created. All operative results were successful, without intraoperative or postoperative complications. Postoperative computed tomography scans were obtained for analysis. Postoperative 3D measurement of the skull symmetry index (cranial vault asymmetry index) showed significant improvement of head contour after surgery. The computer-aided design/computer-aided manufacturing system described allows definitive preoperative planning and fabrication for treatment of skull bone tumors. Apparent benefits of the method include more accurate determination of surgical margins and better oncological outcomes.


Sequence specificity of drug-DNA interactions.
Methods for determining sequence specificities of anticancer drugs, carcinogens, and mutagens which interact with natural DNA's are presented. For drugs which nick or covalently bind to DNA and thus leave a permanent record of their residence position on the helix, the sequences important in drug action can be readily determined. For agents which interact with DNA in an equilibrium fashion, "footprinting" analysis, a technique used to investigate protein-DNA binding, has proved to be useful in studying drug-DNA interactions. The sequence specificities of a number of small ligands which interact with natural DNA's are also presented.


Syndecan-1 - A new piece in B-cell puzzle.
Syndecans are transmembrane proteoglycans, with core proteins mainly decorated with heparan sulfate chains. Syndecan-1 is expressed in a tissue-, cell-and differentiation-specific manner. Its extra-cellular domain can bind via HS chains to matrix elements, to growth factors (especially "heparin-binding" proteins) and to certain biological agents. The ectodomain released by proteolysis can also be functionally active. The cytoplasmic domain can take part in signaling processes as well as in modifying cell shape. In hematopoietic cells syndecan-1 is expressed in normal pre-B-cells and plasma cells, as well as in plasmocytoid and lymphoplasmocytoid malignancies. According to our study syndecan-1 is expressed in B-CLL cells both in tissue environment and in circulation.


Children's use of multiple-counting skills: adaptation to task factors.
The purpose of the study was to determine conditions under which young children enumerate by counting in multiples. Thirty-eight kindergartners and first-graders enumerated dot displays and gave verbal reports of their strategies; additionally, they were given an independent assessment of multiple-counting skill. Dot displays varied according to overall numerosity, perceptual arrangement (random, clustered, rectangular), and numerosity of subgroupings. Children were relatively accurate at enumerating small-numerosity and nonrandom displays. They were relatively likely to report counting by multiples, rather than by ones, on small-numerosity and clustered displays. Contingent upon their skill level, children counted by multiple units (twos, threes, and fours) that corresponded to the numerosity of subgroupings (2, 3, and 4). Contrasting effects of different numerosities and perceptual arrangements are discussed in terms of contextual support for the use, and development, of numerical skills among young children.


Degree of bother caused by nocturia in women.
The prevalence of nocturia in women has been studied, but its severity has not been categorized based on degree of bother. The number of nighttime voids that defines clinically significant nocturia has not been established. The objective of this study was to establish how bothersome nocturia is in women and to determine whether number of nighttime voids correlates with the degree of bother. We also sought to determine if this correlation was affected by age or continence status. The charts of 1,214 neurologically healthy women that presented to a female urology office were reviewed. All women completed the American Urological Association Symptom Index (AUASI) and the symptom problem index (SPI). Question no. 7 of the AUASI assesses the number of voids per night and question no. 3 of the SPI assesses the bother of nighttime voiding. The correlation of these two variables was evaluated using a proportional odds model. Mean age was 54.6 years (18-93). 87.3% complained of waking at least one time per night to void. Bother score increased as the number of nightly voids increased, irrespective of age or continence status. The proportional odds model showed that as the number of voids increases 1 value on AUASI, the odds of having an increase in bother increases 2.7 times (P<0.0001). As the number of nighttime voiding episodes increases, the bother increases, independent of age or continent status. Based on the degree of bother, we propose that clinically significant nocturia in women be classified as two or more episodes per night.


ATP and nitric oxide modulate intracellular calcium in isolated pillar cells of the guinea pig cochlea.
Supporting cells in the mammalian cochlea have recently received attention as potential targets of neurotransmitters, neuromodulators, and neurohumoral agents. Calcium homeostasis in Deiters' and Hensen's cells, for example, is regulated by ATP and nitric oxide. We studied the intracellular calcium concentration [Ca2+]i in isolated pillar cells of the guinea pig cochlea in response to extracellular ATP and nitric oxide using the fluorescent indicator fluo-3. [Ca2+]i increased rapidly and significantly throughout the pillar cell in response to a bolus of ATP or 2-methylthio ATP while alpha,beta-methylene ATP was ineffective. The response to ATP was inhibited by suramin and Cibacron Blue but not by pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid. This pharmacological profile is consistent with a [Ca2+]i increase largely mediated by P2Y receptors. In Ca2+-free medium supplemented with EGTA, the response to extracellularATP was reduced by 33%, suggesting a contribution of calcium influx to the overall effect. The ATP-induced increase of [Ca2+] was attenuated by NO donors (sodium nitroprusside or diethylamine NONOate), and this attenuation was reversed by KT5823, an antagonist to protein kinase G. The results indicate the involvement of purinergic mechanisms and the nitric oxide/cyclic GMP/protein kinase G pathway in the regulation of [Ca2+]i in cochlear pillar cells.


[Cognitive and Non-Cognitive, Doctor-Relevant Competencies for the Selection of Prospective Country Doctors in Bavaria: Corona-Compliant Selection Process Across Institutes].
The challenge is to counteract the undersupply of doctors in rural areas in Bavaria. As one possibility, the "Country Doctor Quota" measure provides for the allocation of dedicated medical study places for prospective specialists with general practice activities. A specific selection process for future medical students was established and safely implemented under the safety and hygiene conditions of the corona pandemic. In Bavaria, a two-stage selection process was developed and used in full for the first time in 2021 for the selection of students. Due to the corona pandemic, only the results of stage 1 of the process for the selection of prospective students were taken into account in the previous year. Cognitive and non-cognitive criteria were included in a 2-stage selection process. In the second stage, physician-relevant competencies (e. g. resilience, problem-solving ability, empathy and compassion, communication skills, ethical decision-making, as well as consulting and social skills) were assessed by Bavarian family doctors in four multiple mini interviews and a 10-minute, semi-structured individual interview. A maximum of 100 points could be achieved. A digital, contact-free selection process was established and successfully implemented to ensure protection and hygiene conditions in the context of the interviews. A total of 436 people applied as part of the Bavarian country doctor quota for the 2021/2022 winter semester; 226 applicants were invited to the selection interviews at the second stage, of which 115 applicants received a place at the university. 64% of the participants had already completed medical vocational training, the high school graduation grade average was 2.4. The developed selection process identified applicants as part of the Bavarian country doctor quota and selected using objective criteria. All available medical study places were filled with the 115 finally selected applicants. To what extent the selected applicants (can) counteract the impending shortage of prospective specialists with general practitioner work remains to be seen.


Modified head-neck offset for diagnosing anterior femoro-acetabular impingement.
The head-neck offset described by Eijer et al. (eHNO), which is used to diagnose anterior femoro-acetabular impingement (FAI), can be difficult to measure. The aim of this study was to verify if a modified head-neck offset (mHNO) provides more accurate and reproducible values than those of the eHNO. The eHNO, mHNO, cephalic radius and alpha angle were measured on frog-leg radiographs of a group of patients with FAI and a control group (T); three independent reviewers measured the 50 hips in each group twice. The comparison of the two HNOs focused on reproducibility (intraclass correlation coefficient), validity (correlation with alpha angle), practical utility (difference between means in the FAI and control groups) and accuracy of the diagnostic thresholds. The mHNO had better reproducibility (p < 0.05) within and between observers in all study subjects than that of the eHNO (0.938 and 0.979 vs 0.881 and 0.904). The correlation with the alpha angle was also better (p < 0.05) for the mHNO than that for the eHNO. The diagnostic performances of the mHNO and mAOR thresholds were higher than those of the eHNO, eAOR and alpha angle. The new HNO is easier to measure, more reproducible and more accurate. A modified HNO <5 mm and a modified AOR <0.100 on the frog-leg view argued in favour of a pathological cam-type head-neck junction.


Outcome of esophageal adenocarcinoma detected during endoscopic biopsy surveillance for Barrett's esophagus.
In an attempt to reduce mortality from esophageal adenocarcinoma, it has been recommended to enroll patients with Barrett's esophagus in endoscopic surveillance programs in order to detect malignant degeneration at an early and possibly curable stage. The aim of this study was to assess the impact of endoscopic biopsy surveillance on outcome of Barrett's adenocarcinoma. Between November 1992 and June 2000, 312 patients with histologically proven esophageal adenocarcinoma were referred to our department. Ninety-seven of these patients had Barrett's adenocarcinoma. In 12 (12.2%) patients, cancer was discovered during endoscopic surveillance for Barrett's metaplasia. The prevalence of gastroesophageal reflux disease in the Barrett's group was 38.8% versus 8% (p < 0.01) in non-Barrett's patients. In the surveyed group, there were 9 (75%) early stage tumors (Tis-1/N0) versus 9 (10.6%, p < 0.01) in the nonsurveyed patients. Three of 5 surveyed patients operated on for high-grade dysplasia proved to have invasive carcinoma in the esophagectomy specimen. All surveyed patients were alive at a median follow-up of 48 months; the median survival in the nonsurveyed group was 24 +/- 3 months (p < 0.01). Endoscopic surveillance of Barrett's esophagus provides early detection of malignant degeneration and a better long-term survival than in nonsurveyed patients.


The status and stigma consequences of mental illness labels, deviant behavior, and fear.
Despite the breadth of research on mental illness, there remains some ambivalence about the distinct and combined effects of mental illness labels and deviant behavior for stigma and status. To examine the effects of mental illness labels and deviant behavior on stigma and status, we use experimental methods. Because fear is tightly linked with understandings of mental illness, we also consider the role of fear in these processes. We find that absent behavioral descriptions, mental illness labels do not affect status; however, deviant behavior that is and is not labeled as a mental illness decreases status. Neither deviant behavior nor mental illness labels independently affect stigma; however, compared to unlabeled deviant behavior, deviant behavior that is labeled as a mental illness either increases or decreases stigma for fear-inducing and fear-neutral behavior, respectively. In summary, the effects of mental illness labels appear to depend on behavioral connotations, including fear.


Association of TSC1/hamartin, 14-3-3sigma, and p27 expression with tumor outcomes in patients with pTa/pT1 urothelial bladder carcinoma.
TSC1/hamartin is a tumor suppressor gene involved in the development of various malignancies, including bladder cancer. In vitro studies showed that hamartin controls cell proliferation partly by up-regulating p27 and 14-3-3sigma. This study was designed to explore the value of these biomarkers in predicting outcome in pTa/pT1 tumors and validate the regulation of p27 and 14-3-3sigma by hamartin in vivo using human bladder cancer tissue. A tissue microarray of 134 pTa and pT1 tumors was constructed, and sections were stained with hamartin, 14-3-3sigma, and p27 antibodies. In multiple Cox regression analysis, pTa/pT1 tumors with reduced or low expression of hamartin tended to have higher risk of progression (P = .030). High-grade tumors tended to be at higher risk of progression in comparison with low-grade tumors (P < .001). The combination of expression of these 3 biomarkers did not add predictive value regarding disease outcomes. Low hamartin expression and high tumor grade are independent factors in predicting faster pTa/pT1 tumor progression. In a subset of pTa/pT1 tumors, hamartin has a role in bladder carcinogenesis by positively regulating 14-3-3sigma and p27.


Feedback loops shape cellular signals in space and time.
Positive and negative feedback loops are common regulatory elements in biological signaling systems. We discuss core feedback motifs that have distinct roles in shaping signaling responses in space and time. We also discuss approaches to experimentally investigate feedback loops in signaling systems.


Synergistic effects of HIV coat protein and NMDA receptor-mediated neurotoxicity.
Exposure of rat retinal cultures to HIV-1 coat protein gp120 for several minutes increases [Ca2+]i in approximately half of the ganglion cells; this effect is associated with delayed-onset neuronal injury, similar to that previously reported in NMDA receptor-mediated neurotoxicity. Here we show that NMDA antagonists can prevent both the rise in [Ca2+]i and subsequent neuronal damage engendered by 20 pM gp120. However, whole-cell patch-clamp recordings demonstrate that gp120 does not directly evoke an NMDA-like response or enhance glutamate/NMDA-activated currents. Moreover, complete protection from gp120-induced [Ca2+]i increases and neurotoxicity is afforded by incubation with glutamate-pyruvate transaminase, which breaks down endogenous glutamate as verified by HPLC. Since, under standard conditions in these cultures, neither glutamate nor a low picomolar concentration of gp120 is deleterious on its own, our results suggest that their neurotoxicity is synergistic.


Autophagy Induction Ameliorates Inflammatory Responses in Intestinal Ischemia-Reperfusion Through Inhibiting NLRP3 Inflammasome Activation.
Intestinal ischemia/reperfusion (I/R)-induced systemic inflammation leads to multiple organ dysfunction syndrome. Previous studies have indicated that the NOD-like receptor protein (NLRP)3 inflammasome modulates intestinal inflammation; however, the pathophysiological mechanisms remain unclear. Autophagy is a critical metabolic mechanism that promotes cellular survival following ischemic injury. Recently, basal autophagy has been implicated in the alleviation of extensive inflammation. However, the role of autophagy in NLRP3 inflammasome activation in intestinal I/R-induced inflammatory injury remains undefined. In the present study, we examined whether NLRP3 inflammasome activation is induced in mice subjected to intestinal I/R injury, which is measured as increased apoptosis-associated speck-like protein containing a CARD levels, caspase-1 activity, and interleukin-1β (IL-1β) secretion. Importantly, the in-vitro results showed that NLRP3 knockdown decreases proinflammatory cytokine production and increases resistance to hypoxia/reoxygenation (H/R)-triggered inflammation. Subsequently, we demonstrated a critical role for autophagy in suppressing intestinal I/R-induced NLRP3 inflammasome activation in vivo. Furthermore, we showed that the loss of autophagy activates inflammasome-mediated IL-1β secretion, which aggravates H/R injury, and NLRP3 knockdown reverses these effects. Collectively, these results directly implicated the homeostatic process of autophagy and NLRP3 inflammasome in ischemic bowel disease and identified a novel pathway for therapeutic intervention in intestinal I/R.


Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.
Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.


Viral load and clinical features in children infected with seasonal influenza B in 2006/2007.
In influenza B infection, viral load is believed to be related to the severity of clinical illness. The correlation between viral load and symptoms is not known. We conducted a study to assess the relationship between virus load and clinical features in children infected with influenza B, in the hope that clinical features could be used as surrogate markers of viral load to guide treatment. Between December 2006 and February 2007, 228 patients with fever and respiratory symptoms were prospectively enrolled in our tertiary hospital-based study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine viral load. Real-time RT-PCR was positive for influenza B in 76 patients. Using virus culture as the gold standard, the sensitivity and specificity were 95% and 87%, respectively. Influenza culture positive rate significantly correlated with viral load (p = 0.03). The median copy number of influenza B virus in the 76 RT-PCR positive patients was 9735 copies/ml (range 4.8×10¹-2.0×10⁶ copies/ml). Samples obtained later in the clinical course tended to have lower viral load (p = 0.7), while patient age (p = 0.72) and fever duration (p = 0.96) positively related to viral load. In patients >3 years of age, myalgia was related to statistically lower viral loads (14300 vs. 1180; p = 0.025). Patients with chills tended to have higher viral loads (72450 vs. 7640; p = 0.1). Patients with abdominal pain tended to have lower viral loads (1998 vs. 12550; p = 0.06). Culture rate positively correlated with viral load. Patients with myalgia had a lower viral load.


The Global Burden of Esophageal Cancer: A Disability-Adjusted Life-Year Approach.
Esophageal cancer is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths. As a significant cause of morbidity and mortality, its burden on society has yet to be fully characterized. The aim of this study is to examine its global burden through estimation of the disability-adjusted life years (DALYs) attributable to it. Global incidence and mortality estimates for esophageal cancer were obtained from the International Agency for Research on Cancer GLOBOCAN 2008 database. DALYs were calculated, using methodology established by the World Health Organization. In 2008, 3,955,919 DALYs were attributed to esophageal cancer, at a global rate of 0.58 DALYs per 1000 people annually. Years of life lost (YLL) accounted for 96.8 % of DALYs, while years lived with disability (YLD) accounted for 3.2 %. 83.8 % of the global DALYs occurred in less-developed countries, with most accrued in Eastern Asia, comprising 50.9 % of the total. The highest rate of DALY accrual was in Southern Africa, at 1.62 DALYs per 1000 people annually. A substantial number of years of life were lost or affected by esophageal cancer worldwide in 2008, with the burden resting disproportionately on less-developed countries. Geographically, the greatest burden is in Eastern Asia. The vast majority of DALYs were due to YLL, rather than YLD, indicating the need to focus resources on disease prevention and early detection. Our findings provide an additional basis upon which to formulate global priorities for interventions that affect DALY reduction in esophageal cancer.


Contrasting diel hysteresis between soil autotrophic and heterotrophic respiration in a desert ecosystem under different rainfall scenarios.
Diel hysteresis occurs often between soil CO2 efflux (R(S)) and temperature, yet, little is known if diel hysteresis occurs in the two components of R(S), i.e., autotrophic respiration (R(A)) and heterotrophic respiration (R(H)), and how diel hysteresis will respond to future rainfall change. We conducted a field experiment in a desert ecosystem in northern China simulating five different scenarios of future rain regimes. Diel variations of soil CO2 efflux and soil temperature were measured on Day 6 and Day 16 following the rain addition treatments each month during the growing season. We found contrasting responses in the diel hysteresis of R(A) and R(H) to soil temperature, with a clockwise hysteresis loop for R(H) but a counter-clockwise hysteresis loop for R(A). Rain addition significantly increased the magnitude of diel hysteresis for both R(H) and R(A) on Day 6, but had no influence on either on Day 16 when soil moisture was much lower. These findings underline the different roles of biological (i.e. plant and microbial activities) and physical-chemical (e.g. heat transport and inorganic CO2 exchange) processes in regulating the diel hysteresis of R(A) and R(H), which should be considered when estimating soil CO2 efflux in desert regions under future rainfall regime.


Effect of gonadectomy on pituitary levels of mRNA encoding gonadotropin subunits and secretion of luteinizing hormone.
Using cell-free translation of pituitary mRNAs we have investigated how, following gonadectomy in rats, the translational capacity of the specific messages encoding precursors to gonadotropin subunits alpha, LH-beta and FSH-beta increases with time. In parallel, serum LH was assayed in order to compare release and synthesis patterns. We observed a rapid rise in the rate of synthesis of all three precursors, with a significant increase already detectable 4 days after gonadectomy, and a plateau reached after 21 days. The kinetics were similar in both males and females, but maximal translational values for alpha-subunit were slightly higher in males. During the same time period, serum LH rapidly increased in the males, while in the females the rise of circulating LH was somewhat delayed. Although no direct correlation seems to exist between synthesis and release processes of gonadotropins, it is evident from our previous findings and the present data that both phenomena are dependent on gonadal steroids. In this respect, estradiol has been shown to regulate negatively, via different routes, the synthesis as well as the secretion of pituitary gonadotropins.


The results of anterior cervical fusion in cervical spondylosis. Review of 125 cases.
A retrospective study of 125 patients with cervical spondylosis with, in the main, myelographic features, and treated by the anterior cervical route (Cloward's operation) is presented. Patients were selected for this type of surgery as opposed to the posterior approach, on clinical and radiological grounds which are described. Results of this treatment have generally been good and this is particularly so in very elderly patients with a single lesion at C 3/4. There is a group of patients in whom the disease process seems to progress despite surgery.


Breaking bad news in the era of artificial intelligence and algorithmic medicine: an exploration of disclosure and its ethical justification using the hedonic calculus.
An appropriate ethical framework around the use of Artificial Intelligence (AI) in healthcare has become a key desirable with the increasingly widespread deployment of this technology. Advances in AI hold the promise of improving the precision of outcome prediction at the level of the individual. However, the addition of these technologies to patient-clinician interactions, as with any complex human interaction, has potential pitfalls. While physicians have always had to carefully consider the ethical background and implications of their actions, detailed deliberations around fast-moving technological progress may not have kept up. We use a common but key challenge in healthcare interactions, the disclosure of bad news (likely imminent death), to illustrate how the philosophical framework of the 'Felicific Calculus' developed in the eighteenth century by Jeremy Bentham, may have a timely quasi-quantitative application in the age of AI. We show how this ethical algorithm can be used to assess, across seven mutually exclusive and exhaustive domains, whether an AI-supported action can be morally justified.


Childhood leukemia in Belarus before and after the Chernobyl accident: continued follow-up.
Earlier assessments led to the conclusion that due to the added radiation after the Chernobyl accident, childhood leukemia in Belarus was not recognisably increased in the years 1987-1994 compared to the years 1982-1986, i.e. the period before the accident. The present paper gives the data of the continued follow-up (1995-1998) which was conducted by the Institute of Haematology and Blood Transfusion, Minsk. In line with the earlier observations no increase has been identified. The incidence rates have been compared to the data of the newly established Belarussian Childhood Cancer Registry and a tentative explanation is given for apparent differences between the rates from our follow-up and the data reported earlier by the Belarussian Childhood Cancer Registry.


Evaluation of the American Hospital Association Annual Survey for health services research in emergency medicine.
Emergency department (ED) data are often used to address questions about access to and quality of emergency care. Our objective was to compare one of the most commonly used data sources for national ED information, the American Hospital Association (AHA) Annual Survey, with a criterion database: the National Emergency Department Inventory (NEDI)-USA data set. We compared the 2015 and 2016 AHA surveys to the following 3 criterion standards: (1) the 2015 and 2016 NEDI-USA databases, which have information about all US EDs, including merged data from (2) Council of Teaching Hospitals (COTH) and (3) the Critical Access Hospital (CAH) program. We present descriptive results about the number of EDs in each data set; total and median visit volumes; locations in rural areas; and COTH, CAH, and freestanding ED (FSED) status. The AHA survey identified 3893 US EDs in 2015. These EDs had a total annual visit volume of 129,197,493 visits, with a median of 22,772 visits (interquartile range, 8311-47,938). Compared with the NEDI-USA, the AHA included 1433 fewer EDs (-27%; 95% confidence interval [CI], -28% to -26%) and 23,615,163 (-15%) fewer visits. Specifically, AHA was missing 245 (-22%; 95% CI, -24% to -19%) of those located in rural areas, 268 (-20%; 95% CI, -22% to -18%) in a CAH, and 240 (-47%; 95% CI, -51% to -42%) FSEDs. We saw similar results using 2016 data. Although several aggregated results were similar between the compared data sources, the AHA data set excluded many US EDs, including many rural EDs and FSEDs. Consequently, the AHA underreported total ED visits by 15%. We encourage data users to be cautious when interpreting results from any 1 ED data source, including the AHA.


Comment on "Computational study of H[Formula: see text]S adsorption on the pristine and transitional metal-doped phosphorene".
In a recent paper, Molaei et al. (J Mol Model 27:181-188, 2021) studied the H[Formula: see text]S gas adsorption on transition metal (TM) doped phosphorene monolayer using the density functional theory. They claimed that Ti-, V-, Fe- and Sc-doped phosphorene systems are more favorable than the other doped systems. Their electronic calculations showed that they did not consider spin-polarized calculations for TM doped structures. Here, we present all spin-polarized electronic calculations based on generalized gradient approximation (GGA) and GGA plus Hubbard correction (GGA+U). Our results reveal that doped systems are magnetic and thus spin-polarized effect must be considered in these structures.


Sustained depression of brainstem auditory electrophysiology during the first months in term infants after perinatal asphyxia.
To gain further insights into the pathophysiological processes of neuronal impairment in neonatal brainstem after perinatal asphyxia. Maximum-length sequence brainstem auditory-evoked response (MLS BAER) was recorded with clicks at 91, 227, 455 and 910/s on days 1, 3, 5, 7, 10, 15 and 30 after birth in 108 term infants who suffered perinatal asphyxia. Wave amplitude variables in the MLS BAER were analysed in detail at 40 dB above BAER threshold in 86 infants who had no peripheral hearing impairment. On day 1 the amplitudes of MLS BAER waves I, III and V were all reduced significantly at all click rates, especially at higher ones (91-910/s, ANOVA P<0.05-0.001). On day 3 these amplitudes were reduced further. On days 5 and 7, the amplitude reduction persisted and did not show any significant further changes. On days 10 and 15 the reduced amplitudes were increased slightly. On day 30 all amplitudes were still reduced significantly (P<0.05-0.0001). During the first month, the reduction of wave amplitudes was more significant for the later MLS BAER components than for the earlier ones, and occurred most significantly at 455 and 910/s clicks. By comparison, the amplitude reduction in conventional BAER was much less significant. During the first month after perinatal asphyxia the amplitudes of MLS BAER waves were reduced significantly and persistently, which was more significant at higher rates of clicks than at lower rates. The reduction is much more persistent than the increase in wave latencies and intervals we previously reported. There is sustained depression of brainstem auditory electrophysiology, indicating neuronal damage of the auditory brainstem, in infants after perinatal asphyxia. This may have important clinical implications.


Transcriptome alterations of radish shoots exposed to cadmium can be interpreted in the context of leaf senescence.
Till now few transcriptome studies have described shoot responses of heavy metal (HM)-sensitive plants to excess Cd and still a unifying model of Cd action is lacking. Using RNA-seq technique, the transcriptome responses of radish (Raphanus sativus L.) leaves to Cd stress were investigated in plants raised hydroponically under control and 5.0 mg L-1 Cd. The element was mainly accumulated in roots and led to declined biomass and photosynthetic pigments, increased H2O2 and lipid peroxidation, and the accumulation of sugars, protein thiols, and phytochelatins. Out of 524 differentially expressed genes (DEGs), 244 and 280 upregulated and downregulated ones were assigned to 82 and 115 GO terms, respectively. The upregulated DEGs were involved in osmotic regulation, protein metabolism, chelators, and carbohydrate metabolisms, whereas downregulated DEGs were related to photosynthesis, response to oxidative stress, glucosinolate, and secondary metabolite biosynthesis. Our transcriptome data suggest that Cd triggers ROS production and photosynthesis decline associated with increased proteolysis through ubiquitin-proteasome system (UPS)- and chloroplast-proteases and in this way brings about re-mobilization of N and C stores into amino acids and sugars. Meanwhile, declined glucosinolate metabolism in favor of chelator synthesis and upregulation of dehydrins as inferred from transcriptome analysis confers shoots some tolerance to the HM-derived ionic/osmotic imbalances. Thus, the induction of leaf senescence might be a major long-term response of HM-sensitive plants to Cd toxicity.


The eating experience after treatment for head and neck cancer: A review of the literature.
Research has identified significant challenges that patients experience following treatment for head and neck cancer (HNC). These include the physical and emotional impacts of the diagnosis and treatment, which compound weight loss and negatively impact eating ability. There is limited research about the lived experience and the changed meaning of food, eating and the eating experience after treatment for patients with HNC. The purpose of this review was to explore available research pertinent to the lived experiences of patients in regards to the changed meaning of food, eating and the eating experience after treatment for HNC. The review identified a limited number of studies that focused on the eating experience and/or the changed meaning of food after a HNC diagnosis. However, the findings do highlight that there are physical, psychological/emotional and social losses associated with the changed meaning of food and eating within the HNC population. The eating experience is impacted after treatment for HNC. Physical, emotional and social losses in regards to the eating experience have been identified. Acknowledging the significance of eating challenges and the changed meaning of food is necessary to ensure patients receive the appropriate management and support to best manage these challenges in a timely manner.


Net reclassification index in comparison of prognostic value of disseminated intravascular coagulation diagnostic criteria by Japanese Society on Thrombosis and Hemostasis and International Society on Thrombosis and Haemostasis: a multicenter prospective cohort study.
We compared the prognostic value of the Japanese Society on Thrombosis and Hemostasis (JSTH) disseminated intravascular coagulation (DIC) diagnostic criteria with that of the International Society on Thrombosis and Haemostasis (ISTH) DIC diagnostic criteria for 28-day in-hospital mortality. We conducted a multicenter prospective cohort study involving two hematology departments, four emergency departments, and one general medicine department in Japan between August 2017 and July 2021. We assessed three ISTH DIC diagnostic criteria categories using low cutoff levels of D-dimer (low D-dimer), high cutoff levels of D-dimer (high D-dimer), and fibrinogen/fibrin degradation products (FDP) as fibrin-related markers. The main outcome was diagnosis-based category additive net reclassification index (NRI). A total of 222 patients were included: 82 with hematopoietic disorders, 86 with infections, and 54 with other diseases. The 28-day in-hospital mortality rate was 14% (n = 31). The DIC rates diagnosed by the JSTH, ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were 52.7%, 47.3%, 42.8%, and 27.0%, respectively. The overall category additive NRI by JSTH DIC diagnosis vs. ISTH-low D-dimer, high D-dimer, and FDP DIC diagnosis were - 10 (95% confidence interval [CI]: -28 to 8, p = 0.282), - 7.8 (95% CI: -26 to 10, p = 0.401), and - 11 (95% CI: -26 to 3, p = 0.131), respectively. JSTH criterion showed the highest sensitivity for DIC diagnosis that did not improve but reflected the same prognostic value for mortality evaluated using ISTH DIC diagnosis criteria. This finding may help clinicians to use JSTH DIC criterion as an early intervention strategy in patients with coagulopathy.


Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis.
Tyro3, Axl, and Mertk (abbreviated TAMs) comprise a family of homologous type 1 receptor tyrosine kinases (RTKs) that have been implicated as inhibitory receptors that dampen inflammation, but their roles in the pathogenesis of rheumatoid arthritis remains understudied. Here, to investigate TAMs in an inflammatory arthritis model, antibody-induced arthritis in single TAM-deficient mice (Tyro3- KO, Axl-KO, Mertk-KO) was induced by K/BxN serum injection. Subsequently, joint inflammation and cytokine levels, as well as the expression of Fcγ Rs and complement receptors were assessed in WT and TAM-deficient mice. Compared with littermate control mice, Axl-/- and Mertk-/- mice developed more severe antibody-induced arthritis, while in contrast, Tyro3-/- mice showed diminished joint inflammation. Concomitantly, the levels of cytokines in joints of Axl-/- and Mertk-/- mice were also significantly increased, while cytokines in the Tyro3-/- joint tissues were decreased. At the molecular and cellular level, TAMs showed distinct expression patterns, whereby monocytes expressed Axl and Mertk, but no Tyro3, while neutrophils expressed Axl and Tyro3 but little Mertk. Moreover, expression of Fcγ receptors and C5aR showed different patterns with TAMs expression, whereby FcγRIV was higher in monocytes of Axl-/- and Mertk-/- mice compared to wild-type mice, while Tyro3-/- neutrophils showed lower expression levels of FcγRI, FcγRIII and FcγRIV. Finally, expression of C5aR was increased in Mertk-/- monocytes, and was decreased in Tyro3-/- neutrophils. These data indicate that Axl, Mertk and Tyro3 have distinct functions in antibody-induced arthritis, due in part to the differential regulation of cytokines production, as well as expression of FcγRs and C5aR. Video Abstract.


Cost/health effectiveness of home uterine activity monitoring in a Medicaid population.
It has been shown that an intensive system of preterm birth prevention using home uterine activity monitoring can decrease the number of early births. Such a system was employed in 130 public assistance (Medicaid) patients who were at high risk for preterm birth. A retrospective review of the pregnancy outcome in these subjects was conducted and their data exposed to a model for projected patient care cost. The incidence of preterm labor in the at-risk group was 46%, with an average prolongation of pregnancy of 4.9 weeks. The occurrence of preterm delivery for failed tocolysis or advanced cervical dilatation was less than 10%. Based on a cost-analysis model that considered newborn charges and monitoring expenses, nearly [corrected] $3 million (an average of $21,813 [corrected] per patient) was saved using this system.


Uncertainty and agency in COVID-19 hotel quarantine in Australia.
Mandatory 14-day hotel COVID-19 quarantine was introduced for international arrivals into Australia in late March 2020, with no precedent and little time to prepare. This public health initiative was a key factor in Australia's relatively low COVID-19 burden in the first 18 months of the pandemic. We conducted an empirical bioethics study exploring the experience of people who had quarantined in hotels in Australia. We used in depth interviews to develop an understanding of context and normative analysis to consider whether the way the program is conducted is ethically justifiable. 58 people participated; they had been in hotel quarantine in different parts of Australia in the period March 2020-January 2021. Participants faced considerable uncertainty while in quarantine and many experienced this as burdensome. Some uncertainty resulted from not being given information about key aspects of quarantine, some from rules that changed frequently or were otherwise inconsistent, some from being physically isolated. Lack of information and uncertainty contributed to diminished agency. Communication efforts made by individual hotels was well received. Earlier ethics literature about quarantine does not take into account the context our participants described, where the hotel and supervision arrangements were central to the experience. We argue that more suitable arrangements must be made if quarantine is to be an ongoing proposition.


Thermoperiodism and the thermal environment of the pitcher-plant mosquito, Wyeomyia smithii.
Wyeomyia smithii Coq. (Diptera: Culicidae) completes its pre-adult development only within leaves of the purple pitcher-plant, Sarracenia purpurea. Between early June and mid-October in northern New York State, the daily temperature cycle in leaves lagged the photic cycle by 0-6 h and exhibited a mean daily amplitude of 14.5°C.Thermoperiod acts as a potent zeitgeber. At constant temperatures, W. smithii respond to the shorter dark period of a symmetric skeleton photoperiod as "day". However, a superimposed thermoperiod having the thermophase coincident with the longer dark period overrides this tendancy. Thermoperiods may also perturb the photoperiodic clock but W. smithii compensate for the range of phase relationships between the photic and thermal cycles observed in nature.Compared with constant temperatures, W. smithii develop more slowly but exhibit a 7-fold increase in fecundity when reared under fluctuating temperatures. The net result is a 50% greater capacity for increase in the latter regimen. These results suggest that maximum fitness in W. smithii is achieved through the action of, and not despite, thermal heterogeneity.


Transfusions via hand-held syringes and small-gauge needles as risk factors for hyperkalemia.
Pediatric emergency RBC transfusions are often infused rapidly through 22-gauge (ga) or smaller needles or catheters using hand-held syringes. Data relating needle size, unit age, and infusion rate are needed to assess the risk of hemolysis and hyperkalemia in this setting. Multiple simulated transfusions were performed during storage of RBC units. Aliquots from five units were rapidly passed through needles (18, 20, 22-25 ga) using a hand-held syringe. Resulting plasma Hb and K+ concentrations were measured. Free Hb levels were used as a measure of needle-associated hemolysis (NAH). Passage through 18-ga and 20-ga needles caused no hemolysis, but rapid passage through 23-ga, 24-ga, and 25-ga did. RBCs stored less than 7 days showed significant K+ release with 23- to 25-ga needles. The greatest needle-associated K+ release was 10 mEq per L, on Day 5. Due to high K+ concentrations resulting from spontaneous efflux, K+ release from NAH was not detectable after 2 or more weeks of storage. Rapidly transfusing RBCs using hand-held syringes through 23-ga or smaller needles can cause hemolysis. In RBCs stored 2 weeks or more, NAH does not measurably increase K+ concentrations above that present from storage-related efflux. During rapid transfusions, RBC storage time is the primary risk factor for transfusion-associated hyperkalemia.


Exploiting comparative mapping among Brassica species to accelerate the physical delimitation of a genic male-sterile locus (BnRf) in Brassica napus.
The recessive genic male sterility (RGMS) line 9012AB has been used as an important pollination control system for rapeseed hybrid production in China. Here, we report our study on physical mapping of one male-sterile locus (BnRf) in 9012AB by exploiting the comparative genomics among Brassica species. The genetic maps around BnRf from previous reports were integrated and enriched with markers from the Brassica A7 chromosome. Subsequent collinearity analysis of these markers contributed to the identification of a novel ancestral karyotype block F that possibly encompasses BnRf. Fourteen insertion/deletion markers were further developed from this conserved block and genotyped in three large backcross populations, leading to the construction of high-resolution local genetic maps where the BnRf locus was restricted to a less than 0.1-cM region. Moreover, it was observed that the target region in Brassica napus shares a high collinearity relationship with a region from the Brassica rapa A7 chromosome. A BnRf-cosegregated marker (AT3G23870) was then used to screen a B. napus bacterial artificial chromosome (BAC) library. From the resulting 16 positive BAC clones, one (JBnB089D05) was identified to most possibly contain the BnRf (c) allele. With the assistance of the genome sequence from the Brassica rapa homolog, the 13.8-kb DNA fragment covering both closest flanking markers from the BAC clone was isolated. Gene annotation based on the comparison of microcollinear regions among Brassica napus, B. rapa and Arabidopsis showed that five potential open reading frames reside in this fragment. These results provide a foundation for the characterization of the BnRf locus and allow a better understanding of the chromosome evolution around BnRf.


Stable transformation of mouse L cells for human membrane T-cell differentiation antigens, HLA and beta 2-microglobulin: selection by fluorescence-activated cell sorting.
We isolated stable transformants of mouse L cells expressing human cell surface differentiation antigens by using immunofluorescence with monoclonal antibodies and selection with a fluorescence-activated cell sorter (FACS). Mouse L cells (TK-) were cotransformed with human cellular DNA and the herpes simplex virus thymidine kinase (TK) gene. TK+ transformants were first selected. The TK+ populations were stained with various fluorescent antibodies to membrane antigens, and positive cells were sorted and cloned by using a FACS. Transformants for HLA class I antigens, for beta 2-microglobulin, and for the T-cell differentiation antigens Leu-1 and Leu-2 were isolated. The frequency of antigen transformants among the TK+ transformants was about 0.5 X 10(-3). The sizes of the HLA, Leu-1, and Leu-2 molecules expressed by the transformants were the same as those of the proteins present on DNA-donor cells.


A Fluorescent Sensor for Dual-Channel Discrimination between Phosgene and a Nerve-Gas Mimic.
The ability to analyze highly toxic chemical warfare agents (CWAs) and related chemicals in a rapid and precise manner is essential in order to alleviate serious threats to humankind and public security caused by unexpected terrorist attacks and industrial accidents. In this investigation, we designed a o-phenylenediamine-pyronin linked dye that is capable of both fluorogenic and colorimetric discrimination between phosgene and the prototypical nerve-agent mimic, diethyl chlorophosphate (DCP) in the solution or gas phase. Moreover, this dye has been used to construct a portable kit that can be employed for real-time monitoring of DCP and phosgene in the field, both in a discriminatory manner, and in a simple and safe way.


Identification of Factors in Moderate-Severe TBI Related to a Functional Decline in Cognition Decades After Injury.
To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury. Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI. TBI Model Systems Centers. Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732). Not applicable. FIM Cognitive Scale. Injury characteristics such as timing and features pertaining to severity and health-related factors (eg, alcohol use, socioeconomic status) were examined to discriminate stable from declining participants on the FIM Cognitive Scale using logistic regression. At 20 years post-injury, there was a low base rate of FIM Cognitive decline (11%, n=78), with most being stable or having meaningful improvement (89%, n=654). Older age at injury, longer duration of post-traumatic amnesia, and presence of repetitive seizures were significant predictors of FIM Cognitive decline in the final model (area under the curve=0.75), while multiple health-related factors that can represent independent co-morbidities or possible consequences of injury were not. The strongest contributors to reported functional decline in cognitive activities later-in-life were related to acute characteristics of m-sTBI and experiencing post-traumatic seizures. Future studies are needed integrating functional with performance-based cognitive assessments to affirm conclusions and identify the timeline and trajectory of cognitive decline.


Fibrinous material in a pericardial effusion mimicking intraatrial thrombus.
A 74-year-old woman presented with an acute cerebrovascular infarct involving multiple vascular territories, suggestive of an embolic event. The initial transesophageal images create the impression of an echogenic mass in the left atrial appendage. A small pericardial effusion was also seen surrounding the left atrial appendage. After further views were obtained, the echogenic mass appeared to be in this fluid-filled space rather than in the appendage itself. To confirm this finding, echo contrast (Definity) was administered. After contrast injection, the left atrial appendage was opacified, while the effusion around the appendage and the echodensity within this space were not opacified. Our case highlights the utility of contrast-enhanced echocardiography in clearly delineating the boundaries of the endocardium in cases, when a pericardial effusion surrounds the left atrial appendage.


Uniportal Video-Assisted Thoracoscopic Surgery Segmentectomy.
This article addresses technical details of uniportal VATS segmentectomy by lung segments, suggesting available techniques for lesion localization and identification of the intersegmental plane. Long-term results and superiority have not yet been characterized in standard VATS for lung malignancy. Indications include almost all thoracic procedures currently performed by conventional multiport VATS. We review our experience and published literature on the feasibility of uniportal VATS segmentectomy.


The measurement of indirect costs in the health economics evaluation literature. A review.
In this paper we develop a framework to categorize the concepts used to estimate indirect costs in economic evaluation. We apply this framework in a literature review of economic evaluation studies. We searched all English language literature from 1994-96. Following the application of a search algorithm, which yielded 25 articles, we abstracted information from these articles to determine the methods used to identify the relative contribution of indirect costs of the cost-effectiveness ratio, the time horizon selected by the authors, the identification of those activities that were foregone, the time given up by these activities, and the valuation placed on this time. These methods were then assessed. Indirect costs, as they have been measured, significantly influence efficiency ratios. A wide variation exists among studies in how they incorporate each of the components of indirect costs. All of the four components that were identified will affect the measurement of indirect cost. Future guidelines in this area should address the entire measurement process.


Review of the clinical pharmacology of the monobactam antibiotic aztreonam.
Serum and urine levels of aztreonam after 0.5, 1, and 2 g doses are potentially therapeutic for susceptible gram-negative organisms. Aztreonam is widely distributed in body fluids and tissues, and concentrations exceeding the minimal inhibitory concentrations of important gram-negative pathogens are attained in those compartments in which infections are most common. Aztreonam is eliminated primarily in the urine in unchanged form, although it is also secreted into the bile and is metabolized to a minor extent. Renal insufficiency may significantly impair the elimination of aztreonam, thus requiring modification of the dosage regimen. The monobactam can be cleared by hemodialysis but is only minimally cleared by peritoneal dialysis. Parenterally and orally administered aztreonam can selectively reduce the population of aerobic gram-negative bacteria in the gut without notably altering the number of anaerobic organisms.


Maternal aggression towards different sized male opponents: effect of chlordiazepoxide treatment of the mothers and d-amphetamine treatment of the intruders.
Lactating female rats vigorously attack equally sized conspecific males introduced into their home cage. Under conditions of such high aggression, the previously reported pro-aggressive action of a low (5 mg/kg) dosage of chlordiazepoxide (CDP) is hardly detectable. When opponents are large, the intensity of the aggression is less than what is seen with small ones. In this situation treatment of the females with CDP increases aggression levels substantially. The importance of intruders evoking aggression was further investigated by treating different sized opponents with d-amphetamine. d-Amphetamine treatment did not lead to major changes in the defensive capacities of either types of intruder. The data demonstrate that drug effects, such as pro-aggressive actions, may be observed using larger sized opponents that are not so easily defeated and show more adequate defense than small ones. The subtleness of the dyadic interactions in maternal aggression indicates that drug effects should be considered carefully before extrapolation to other conditions.


Restriction endonuclease gene mapping studies of an Indian (A gamma delta beta)zero-thalassaemia, previously identified as G gamma-HPFH.
Restriction endonuclease mapping data are presented for the DNA of a young Indian homozygous patient (and his heterozygous parents) who were identified 10 years ago as having a G gamma-hereditary persistence of fetal haemoglobin (Sukumaran et al, 1972). However, the present results indicate a genetic lesion in these persons which is similar to that observed in another Indian with (A gamma delta beta)0-thalassaemia homozygosity (Amin et al, 1979) and is characterized by two relatively short deletions and an inversion involving the A gamma, delta and beta globin genes (Jones et al, 1981a). Some additional blot hybridization studies have provided further data confirming the deletion-inversion hypothesis.


Generation of homozygous PRKN, PINK1 and double PINK1/PRKN knockout cell lines from healthy induced pluripotent stem cells using CRISPR/Cas9 editing.
Autosomal recessive mutations in either PRKN or PINK1 are associated with early-onset Parkinson's disease. The corresponding proteins, PRKN, an E3 ubiquitin ligase, and the mitochondrial serine/threonine-protein kinase PINK1 play a role in mitochondrial quality control. Using CRISPR/CAS9 technology we generated three human iPSC lines from the well characterized AIW002-02 control line. These isogenic iPSCs contain homozygous knockouts of PRKN (PRKN-KO, CBIGi001-A-1), PINK1 (PINK1-KO, CBIGi001-A-2) or both PINK1 and PRKN (PINK1-KO/PRKN-KO, CBIGi001-A-3). The knockout lines display normal karyotypes, express pluripotency markers and upon differentiation into relevant brain cells or midbrain organoids may be valuable tools to model Parkinson's disease.


Post-traumatic venous and systemic air embolism associated with spinal epidural emphysema: multi-slice computed tomography diagnosis.
A 30-year-old man was admitted with chest trauma after a road traffic accident. The patient was paraplegic and suffered from transient monoparesia of the left arm. The chest X-ray revealed a severe right tension pneumothorax and thoracic spine fractures. Emergency right thoracic drainage was carried out followed by angiography. Unfortunately the patient died and an autopsy was not permitted. Consequently post-mortem multi-slice computed tomography (MSCT) was performed, revealing presence of air inside the right cerebral arteries, bilateral pneumothorax accompanied by a severe right tension pneumothorax, bilateral haematic pleural effusion, pneumomediastinum and bilateral lung contusions. Air was also observed within the right coronary artery, ascending aorta and right ventricle. Thoracic and cervical spinal epidural emphysema were diagnosed. Venous air embolism followed by arterial air embolism producing paradoxical embolism was diagnosed. To the best of our knowledge, this is the first case illustrating by post-mortem MSCT such simultaneous complications after chest trauma as spinal epidural emphysema and cerebral and coronary air embolism.


Subtotal splenectomy for the treatment of chronic lymphocytic leukemia.
Although splenectomy is helpful in the management of selected patients with chronic lymphocytic leukemia (CLL), in most cases this procedure is accompanied by a greater morbidity and mortality, mainly due to sepsis. Thus, it may be proposed that a conservative procedure that reduces the spleen size may have an effect similar to that of total spleen ablation for the treatment of CLL. The present paper describes our experience with an 81-year-old patient submitted to subtotal splenectomy for treatment of CLL. Indications for surgery were uncontrolled leukemic activity and intense abdominal discomfort due to the huge spleen. The good results obtained with subtotal splenectomy in the present case indicate that this procedure may be a new alternative for the treatment of CLL when removal of the spleen is indicated.


Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration.
To determine the baseline predictors of visual acuity (VA) outcomes 1 year after treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). Cohort study within the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). A total of 1105 participants with neovascular AMD, baseline VA 20/25 to 20/320, and VA measured at 1 year. Participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as-needed schedule. Masked readers evaluated fundus morphology and features on optical coherence tomography (OCT). Visual acuity was measured using electronic VA testing. Independent predictors were identified using regression techniques. The VA score, VA score change from baseline, and ≥3-line gain at 1 year. At 1 year, the mean VA score was 68 letters, mean improvement from baseline was 7 letters, and 28% of participants gained ≥3 lines. Older age, larger area of choroidal neovascularization (CNV), and elevation of retinal pigment epithelium (RPE) were associated with worse VA (all P<0.005), less gain in VA (all P<0.02), and a lower proportion gaining ≥3 lines (all P<0.04). Better baseline VA was associated with better VA at 1 year, less gain in VA, and a lower proportion gaining ≥3 lines (all P<0.0001). Predominantly or minimally classic lesions were associated with worse VA than occult lesions (66 vs. 69 letters; P=0.0003). Retinal angiomatous proliferans (RAP) lesions were associated with more gain in VA (10 vs. 7 letters; P=0.03) and a higher proportion gaining ≥3 lines (odds ratio, 1.9; 95% confidence interval, 1.2-3.1). Geographic atrophy (GA) was associated with worse VA (64 vs. 68 letters; P=0.02). Eyes with total foveal thickness in the second quartile (325-425 μm) had the best VA (P=0.01) and were most likely to gain ≥3 lines (P=0.004). Predictors did not vary by treatment group. For all treatment groups, older age, better baseline VA, larger CNV area, predominantly or minimally classic lesion, absence of RAP lesion, presence of GA, greater total fovea thickness, and RPE elevation on optical coherence tomography were independently associated with less improvement in VA at 1 year. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


A (18)F-labeled glucose analog: synthesis using a click labeling method and in vitro evaluation.
A (18)F-labeled glucose analog, 4-[(2-[(18)F]fluoroethyl)-1-(beta-D: -glucopyranosyl)]-1H-1,2,3-triazole ([(18)F]1), was synthesized using a click labeling method and evaluated in vitro for its cellular transportation via glucose transporter (Glut-1) and its potential as a hexokinase substrate. The click labeling method was superior to conventional labeling method, due to a higher decay-corrected radiochemical yield (30% vs. 21%), higher specific activity (59.9 GBq/mumol vs. 23.5 GBq/mumol), and shorter synthesis time (75-80 min vs. 95-100 min). In vitro evaluation demonstrated that [(18)F]1 does not act as a hexokinase substrate and has low and non-specific uptake by SNU-C5 cells. These results suggest that click chemistry offers a rapid and efficient radiolabeling method which does not require the protection of functional groups, although a triazole moiety at C1 of [(18)F]1 is incompatible for hexokinase phosphorylation and facilitative diffusion via Glut-1.


Identification of moaA3 gene in patient isolates of Mycobacterium tuberculosis in Kerala, which is absent in M. tuberculosis H37Rv and H37Ra.
Tuberculosis is endemic to developing countries like India. Though the whole genome sequences of the type strain M. tuberculosis H37Rv and the clinical strain M. tuberculosis CDC1551 are available, the clinical isolates from India have not been studied extensively at the genome level. This study was carried out in order to have a better understanding of isolates from Kerala, a state in southern India. A PCR based strategy was followed making use of the deletion region primers to understand the genome level differences between the type strain H37Rv and the clinical isolates of M. tuberculosis from Kerala. PCR analysis of patient isolates using RD1 region primers revealed the amplification of a 386 bp region, in addition to the expected 652 bp amplicon. Southern hybridization of genomic DNA with the 386 bp amplicon confirmed the presence of this new region in a majority of the patient isolates from Kerala. Sequence comparison of this amplicon showed close homology with the moaA3 gene of M. bovis. In M. bovis this gene is present in the RvD5 region, an IS6110 mediated deletion that is absent in M. tuberculosis H37Rv. This study demonstrates the presence of moaA3 gene, that is absent in M. tuberculosis H37Rv and H37Ra, in a large number of local isolates. Whether the moaA3 gene provides any specific advantage to the field isolates of the pathogen is unclear. Field strains from Kerala have fewer IS6110 sequences and therefore are likely to have fewer IS6110 dependent rearrangements. But as deletions and insertions account for much of the genomic diversity of M. tuberculosis, the mechanisms of formation of sequence polymorphisms in the local isolates should be further examined. These results suggest that studies should focus on strains from endemic areas to understand the complexities of this pathogen.


A change in the stability of globin mRNA during the induction of murine erythroleukemia cells.
The stability of globin mRNA in murine erythroleukemia cells (Friend cells) before and during DMSO-induced differentiation was investigated. Cells were exposed to 3H-uridine for 2 hr and then transferred to medium without the radioactive precursor. The loss of radioactivity in total RNA, poly(A)-containing RNA and globin mRNA was followed. The globin mRNA was isolated using a highly specific globin cDNA column. In uninduced cells and cells early in differentiation, the globin mRNA decays with a half-life of less than 50 hr. After 4 days of induction, the globin mRNA decays with a half-life of 17 hr, demonstrating a change in stability during the induction process. Although the stability of globin mRNA changes during induction, this is not true for total poly(A)-containing RNA. At all times of induction, the poly(A)-containing RNA decays as two populations, one with a half-life of 6 hr and the other with a half-life of 36 hr. The half-life of the rRNA also remains unchanged during differentiation.


4-Amino-6-(piperidin-1-yl)pyrimidine-5-carbo-nitrile.
In the title compound, C10H13N5, the piperidine ring adopts a chair conformation with the exocyclic N-C bond in an axial orientation, and the dihedral angle between the mean planes of piperidine and pyrimidine rings is 49.57 (11)°. A short intra-molecular C-H⋯N contact generates an S(7) ring. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into (100) sheets and a weak aromatic π-π stacking inter-action is observed [centroid-centroid separation = 3.5559 (11) Å] between inversion-related pyrimidine rings.


Quantitative image analysis of the density and pattern of adrenergic innervation of blood vessels of rat spinal cord.
The density and pattern of the noradrenergic innervation of the main extramedullary blood vessels of the rat spinal cord was studied using combined glyoxylic acid histofluorescence and quantitative image analysis techniques. The anterior spinal artery has a perivascular plexus of fine noradrenergic nerves rich in varicosities; the central artery has nerve fibers of various sizes; and the posterior spinal vein has a limited plexus of noradrenergic nerve fibers. The possible significance of the noradrenergic innervation of extramedullary spinal cord blood vessels is discussed.


Properties of Longitudinal Electromagnetic Oscillations in Metals and Their Excitation at Planar and Spherical Surfaces.
The common definition of the spatially dispersive permittivity is revised. The response of the degenerate electron gas on an electric field satisfying the vector Helmholtz equation is found with a solution to the Boltzmann equation. The calculated longitudinal dielectric function coincides with that obtained by Klimontovich and Silin in 1952 and Lindhard in 1954. However, it depends on the square of the wavenumber, a parameter of the vector Helmholtz equation, but not the wave vector of a plane electromagnetic wave. This new concept simplifies simulation of the nonlocal effects, for example, with a generalized Lorents-Mie theory, since no Fourier transforms should be made. The Fresnel coefficients are generalized allowing for excitation of the longitudinal electromagnetic waves. To verify the theory, the extinction spectra for silver and gold nanometer-sized spheres are calculated. For these particles, the generalized Lorents-Mie theory gives the blue shift and broadening of the plasmon resonance which are in excellent agreement with experimental data. In addition, the nonlocal theory explains vanishing of the plasmon resonance observed for gold spheres with diameters less than or equal to 2 nm. The calculations using the Klimontovich-Silin-Lindhard and hydrodynamic dielectric functions for silver are found to give close results at photon energies from 3 to 4 eV. We show that the absolute values of the wavenumbers of the longitudinal waves in solids are much higher than those of the transverse waves.


The prospective association of perceived criticism with dyspnea in chronic lung disease.
Perceived criticism from family members influences mental health. The link between perceived criticism and physical health has not been thoroughly investigated. The objective of this study was to examine the association of perceived criticism with dyspnea in chronic obstructive pulmonary disease (COPD). 401 individuals with alpha-1 antitrypsin deficiency-associated COPD completed questionnaires at baseline, 1- and 2-year follow-up. Perceived criticism at baseline was examined as a predictor of dyspnea at all three time points using a linear mixed model that adjusted for demographic and health characteristics. There was an interaction between perceived criticism and psychological distress (p=0.038). Perceived criticism was associated with dyspnea only among individuals with elevated psychological distress (b=0.32, SE=0.13, p=0.018). Further research is needed to replicate these findings and determine the extent to which they apply to other common subjective physical symptoms such as pain.


Going with the (patient) flow. JCAHO's 'watered down' ER patient-management standard relieves hospital executives, disappoints docs.
It started as a proposed JCAHO standard to address emergency room overcrowding. But after a lobbying blitz from hospitals, its focus was transformed to managing patient flow throughout a facility. ER doctors charge the standard was watered down. JCAHO officials disagree, saying the initial document focused too much attention on the ER.


The effect of phosphoramidon on inflammation-mediated preterm delivery in a mouse model.
Several metallopeptidases have been implicated in both term and preterm parturition. We hypothesize that endotoxin-induced preterm delivery can be prevented by the administration of a metallopeptidase inhibitor. We used an animal model of endotoxin-induced preterm delivery in timed pregnancy C57Bl/6 mice. Test animals received lipopolysaccharide followed by phosphoramidon, either every 1.5 or every 3 hours. Control mice received lipopolysaccharide followed by buffer injections at the same intervals. The primary outcome was a preterm delivery rate. The rate of preterm delivery for the control animals was 88.0% compared with the treatment groups of 45.5% for the mice that received phosphoramidon every 3 hours and 30.8% for the group that received it every 1.5 hours (P<.01). The administration of a metallopeptidase inhibitor resulted in a decreased rate of preterm delivery in this animal model.


Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats.
Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the faecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct microbiome species and their respective gene programs in obese individuals. Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n = 10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four investigatory or approved anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. Only sibutramine treatment induced consistent weight loss and improved glycaemic control in the obese rats. Weight loss was associated with reduced food intake and changes to the faecal microbiome in multiple microbial taxa, genes, and pathways. These include increased β-diversity, increased relative abundance of multiple Bacteroides species, increased Bacteroides/Firmicutes ratio and changes to abundance of genes and species associated with obesity-induced inflammation, particularly those encoding components of the flagellum and its assembly. Sibutramine-induced weight loss in obese rats is associated with improved metabolic health, and changes to the faecal microbiome consistent with a reduction in obesity-induced bacterially-driven inflammation.


Characterization of the mouse Tcra-V22 gene subfamily.
T-cell receptors (Tcrs) of higher organisms play a key role in the specific recognition of self and non-self molecules in the immune system. The large number of Tcr variable (V) genes have been organized into V gene subfamilies according to their sequence similarity at the nucleotide and amino acid level. We cloned and characterized four new members of the Tcra-V22 gene subfamily at the genomic level using a simple and sensitive technique that can rapidly clone members of any multi-member gene family. Sequence analysis reveals that the four Tcra-V22 gene subfamily members have more than 98% sequence similarity in their coding regions, at the nucleotide and amino acid levels. However, the intron between the leader and the coding region varies up to 7% between members of the Tcra-V22 gene subfamily. Comparison of the multi-member Tcra-V22 gene subfamily with other multi-member Tcra-V gene subfamilies (V2, V8, and V11), shows that Tcra-V22 is unique in that it has multiple members with nearly identical amino acid sequence and which are not inherently pseudogenes. Sequence similarity analysis of the Tcra-V22 subfamily with the prototypes of all other Tcra-V subfamilies revealed that the Tcra-V22 subfamily has the closest sequence similarity to that of Tcra-V18 (77% at the nucleotide level and 71% at the amino acid level).


Ontogeny and environment as determinants of the secondary chemistry of three species of white birch.
This study investigates variation in the secondary chemistry of the bark of three closely related, winter-dormant species of white birch (Betula resinifera, B. pendula, and B. platyphylla) at different ontogenetic stages by using different plant parts (top and base). The experimental birches were grown for 4 years in two growing conditions (pot and field) at different nutrient levels. There was considerable species-specific quantitative and qualitative variation in the secondary chemicals in bark, but this was also affected by fertilization and the age of the plant. In general, there was greater chemical diversity in saplings than in seedlings. The study revealed three new components, secoisolariciresinol 9-O-beta-glucopyranoside and two of its derivatives, that have not been reported previously for the bark of white birches. Principal component analysis showed that the species studied had a similar chemical composition at the juvenile stage, but as the plants grew, they became more clearly differentiated, which indicates that the species of older plants can be identified by chemotaxonomy. Evidently, the secondary chemistry of birches is under genetic control, but it is affected by properties of growing conditions and ontogeny.


Chloride dependence of growth in bacteria.
Chloride is an abundant anion on earth but studies analyzing a possible function of chloride in prokaryotes are scarce. To address the question, we have tested 44 different Gram-negative and Gram-positive bacteria for a chloride dependence or chloride stimulation of growth. None required chloride for growth at their optimal growth (salt) conditions. However, in hyperosmotic media containing high concentrations of Na+, 11 bacteria (Aeromonas hydrophila, Bacillus megaterium, Bacillus subtilis, Corynebacterium glutamicum, Escherichia coli, Paracoccus denitrificans, Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus, Thermus thermophilus, and Vibrio fischeri) had a strict chloride dependence for growth or were significantly stimulated by chloride. These data show that chloride is essential for growth at high salt (Na+) concentrations in various species of the domain Bacteria.


Biochar-supported nZVI for the removal of Cr(VI) from soil and water: Advances in experimental research and engineering applications.
Over the past decade, biochar-supported nZVI composites (nZVI/biochar) have been developed and applied to treat various pollutants due to their excellent physical and chemical properties, especially in the field of chromium (VI) removal. This paper reviewed the factors influencing the preparation and experiments of nZVI/biochar composites, optimization methods, column experimental studies and the mechanism of Cr(VI) removal. The results showed that the difference in raw materials and preparation temperature led to the difference in functional groups and electron transfer capabilities of nZVI/biochar materials. In the experimental process, pH and test temperature can affect the surface chemical properties of materials and involve the electron transfer efficiency. Elemental doping and microbial coupling can effectively improve the performance of nZVI/biochar composites. In conclusion, biochar can stabilize nZVI and enhance electron transfer in nZVI/biochar materials, enabling the composite materials to remove Cr(VI) efficiently. The study of column experiments provides a theoretical basis for applying nZVI/biochar composites in engineering. Finally, the future work prospects of nZVI/biochar composites for heavy metal removal are introduced, and the main challenges and further research directions are proposed.


The response of the anophthalmic socket to prosthetic eye wear.
The aim of this study was to investigate the inflammatory response of the anophthalmic socket to prosthetic eye wear. One hundred and two prosthetic eye wearers were recruited for this observational study. Photographic grading scales were used to measure the severity of conjunctival inflammation and the extent and intensity of stained deposits on the prosthetic eyes. Tear volume was measured with the phenol red thread test. For mucoid discharge, visual analogue scales were used to assess frequency of occurrence, colour, volume and viscosity. For the prostheses, assessments were made of weight, shape, wearing time and frequency of cleaning. Anophthalmic sockets had more severe conjunctival inflammation than their companion eyes (p = 0.0001). The difference in inflammation between the companion eye and the anophthalmic socket was associated with discharge volume (p = 0.01) and discharge viscosity (p = 0.007) with greater difference in inflammation being associated with higher levels of discharge volume and viscosity. A greater difference in inflammation was also associated with less surface deposition (p = 0.009). No evidence of associations was found between difference in conjunctival inflammation and the other variables. Recently developed grading scales for measuring inflammation in anophthalmic sockets and deposits on prosthetic eyes were used for the first time in this study. It is recommended that in clinical practice, inflammation grades for both socket and companion eye conjunctivae be compared, when determining if prosthesis-induced inflammation is present. The finding that more discharge was associated with more conjunctival inflammation is logical but the finding that less inflammation was associated with more deposits is counter-intuitive to those familiar with the contact lens literature. The apparently benign nature of at least some deposits on the prostheses raises questions about the maintenance of prosthetic eyes. We conclude that the simple presence of deposits is unlikely to be linked with inflammation of the conjunctiva in wearers of prostheses, who like those in this study, cleaned their prostheses regularly but not frequently.


Membrane potential induced by external electric field pulses can be followed with a potentiometric dye.
A potential-sensitive dye was recently used to measure the spatial variation in the membrane potential induced by an externally applied electric field. In this work, we demonstrate that the time course of these induced potentials can also be followed. Two experimental systems were explored. Dye fluorescence from HeLa cells could be modulated by a train of field pulses; the relative fluorescence change measured with a lock-in amplifier was linear with the field and similar to the fluorescence responses obtained in the static measurements. A model membrane system consisting of a hemispherical bilayer allowed convenient measurement of the dye absorbance change as a function of the bathing solution conductivity. The charging time of the membrane was inversely related to the aqueous conductance as predicted by the theoretical solution to Laplace's equation.


A meta-analysis of perioperative beta blockade: what is the actual risk reduction?
The use of beta blockers in surgical patients has been suggested to decrease perioperative cardiac events. However, the overall risk reduction, on the basis of solely aggregate data from randomized studies, is unknown. The objective is to evaluate the effect of perioperative beta blockade in noncardiac surgery for protection against mortality or cardiac events. We performed a formal meta-analysis. The Medline database was searched for articles published from 1966-2004 by using the terms perioperative, beta blocker, surgery, and noncardiac. Inclusion criteria were randomized controlled trials evaluating perioperative beta blockade in noncardiac surgery. Studies were evaluated independently by 2 researchers. Cochrane Collaboration Software (Review Manager 4.2) was used to calculate relative risk (RR), risk difference (RD), and 95% confidence interval (CI). Six distinct postoperative adverse events were analyzed. Eligible studies included 6 randomized controlled trials evaluating perioperative beta blockade in patients undergoing noncardiac surgery. These studies evaluated a total of 632 patients: 354 received perioperative beta blockade and 278 did not. Results for the 6 postoperative outcomes are shown. [table: see text] The 2 largest effects were a decrease in long-term cardiac mortality from 12% to 2% and a decrease in myocardial ischemia from 33% to 15%. All outcomes except perioperative overall mortality had improvements (P < .02), which favor the use of perioperative beta blockade. This report highlights for the first time the aggregated risk reduction from all published randomized controlled trials, and shows the protection of perioperative beta blockade against both short-term complications and mortality.


Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease.
To investigate whether changes in the frequency of peripheral natural killer T (NKT) cells were correlated with liver disease in patients who had metabolic predispositions to nonalcoholic fatty liver disease (NAFLD). Peripheral blood samples were obtained from 60 Chinese NAFLD patients and 60 age and gender matched healthy controls. The frequency of peripheral NKT cells was detected by flow cytometry. Clinical and laboratory data were collected for further analysis. NAFLD patients had a lower frequency of peripheral NKT cells than healthy controls (1.21% +/- 0.06% vs 1.62% +/- 0.07%, P < 0.001). Further analysis revealed that the frequency of peripheral NKT cells was negatively correlated with body mass index, waist circumference and serum levels of alanine aminotransferase. Logistic regression analysis revealed that elevated body mass index [hazard ratio (HR): 2.991], aspartate aminotransferase levels (HR: 1.148) and fasting blood sugar (HR: 3.133) increased the risk of NAFLD, whereas an elevated frequency of peripheral NKT cells (HR: 0.107) decreased the risk. Changes in the frequency of peripheral NKT cells were correlated with NAFLD and a decreased frequency of peripheral NKT cells was a risk factor for NAFLD.


Choosing the right policy: Factors influencing the preferences of consumption-side personal carbon reduction policies.
With the development of the social economy and the improvement of personal income, the government must consider formulating personal carbon reduction policies to reduce carbon emissions from the consumption side. Therefore, it is valuable to understand the public's preferences for different policies and the factors influencing the willingness of policy support, which can help policy selection and promotion. Using data collected from 2801 college students and a multinomial logit model, this study explores the influence of personal and social factors on preferences for three different personal carbon reduction policies (personal carbon trading, carbon tax, and carbon generalized system of preferences). The results show that individuals with higher levels of affluence, social trust, and social norms prefer personal carbon trading; individuals with higher levels of affluence, self-motivation, and social norms prefer carbon tax; individuals with higher levels of low-carbon behavioral attitudes and social trust prefer carbon generalized system of preferences; and low-carbon responsibility, access to low-carbon information, and social equity are beneficial to all three policies. In addition, this study examined the heterogeneity of individuals with different levels of affluence and low-carbon behavioral attitudes. This study compares the differences in influencing factors of policy preferences, clarifies the effects of various personal and social factors, which can help the government to design consumption-side personal carbon reduction policies in the future, and provide a reference for the promotion of corresponding policies.