Ryanodine receptor calcium release channels.
The ryanodine receptors (RyRs) are a family of Ca2+ release channels found on intracellular Ca2+ storage/release organelles. The RyR channels are ubiquitously expressed in many types of cells and participate in a variety of important Ca2+ signaling phenomena (neurotransmission, secretion, etc.). In striated muscle, the RyR channels represent the primary pathway for Ca2+ release during the excitation-contraction coupling process. In general, the signals that activate the RyR channels are known (e.g., sarcolemmal Ca2+ influx or depolarization), but the specific mechanisms involved are still being debated. The signals that modulate and/or turn off the RyR channels remain ambiguous and the mechanisms involved unclear. Over the last decade, studies of RyR-mediated Ca2+ release have taken many forms and have steadily advanced our knowledge. This robust field, however, is not without controversial ideas and contradictory results. Controversies surrounding the complex Ca2+ regulation of single RyR channels receive particular attention here. In addition, a large body of information is synthesized into a focused perspective of single RyR channel function. The present status of the single RyR channel field and its likely future directions are also discussed.


Plafibride treatment and serum lipids in hyperlipoproteinemias.
A study was made of 26 patients suffering from primary hyperlipoproteinemia; 8 belonging to familial hypercholesterolemia (phenotype IIa), 9 to familial combined hyperlipidemia (phenotype IIb, 9 to familial hypertriglyceridemia (phenotype IV). During treatment, which was continued for two years, all patients received a diet consisting of 45% carbohydrates, 33% fats and 22% protein. They were given 400 mg (TID) of Plafibride after breakfast, lunch and dinner. In the three phenotypes studied, significant decreases in cholesterol, triglycerides, glucose, insulin and lecithin were observed, while there was an increase in HDL cholesterol, free fatty acids and lysolecithin. Tolerance to the drug was good, and a study of different serum enzymes revealed no undesirable collateral effects.


Comparison of the Effect of Two Different Doses of Labetalol to Induce Controlled Hypotension on Hemodynamic Changes During Spinal Fusion Surgery.
Spinal fusion surgery is often associated with heavy bleeding. Labetalol is one of the most effective drugs used to control bleeding in surgery. Here, we measured the effect of two therapeutic doses of labetalol on the amount of bleeding. This is a randomized clinical trial that was performed in 2020-2021 in Al-Zahra hospital in Isfahan, Iran, on patients that were candidates for posterior spinal fusion surgery under general anesthesia. A total number of 64 patients were entered and randomized into two groups, one receiving labetalol at the dose of 2 mg/min and another group at 4 mg/min during surgery. The amount of bleeding in patients, heart rate, blood pressure, blood oxygen saturation, hypotension or bradycardia, and the mean length of stay in the recovery room were measured and compared between the groups. Extubation time (14 ± 4) and recovery time (76 ± 17) were significantly lower in patients that received labetalol (2 mg/min) compared to another group (21 ± 7 for intubation time and 116 ± 32 for recovery time (P < 0.001 for both items). Patients that received labetalol (4 mg/min) had significantly lower amounts of hemorrhage compared to other group (P = 0.001), and the surgeon's satisfaction was significantly higher in the second group (P = 0.001). The frequency of hypotension and bradycardia during the surgery were significantly higher among patients that received labetalol at the dose of 4 mg/min (P = 0.002 and P = 0.001, respectively). The patients in the group labetalol at 4 mg/min had also significantly lower systolic and diastolic blood pressure and lower mean arterial pressure (MAP) compared to the other group (P < 0.05). Administration of labetalol at the dose of 4 mg/min had significantly desirable effects on hemodynamics that resulted in reduced bleeding volume and blood pressures compared to labetalol at the dose of 2 mg/min.


The mode of immigrant settlement in the "help the poor" program.
"This paper studies the settlement of the immigrants from the poor areas of China in the aid-the-poor program, which is a government program providing assistance for poor areas of China. The layout and construction of the new immigrant community and the steps necessary for the creation of an immigrant settlement are also discussed in this paper."


Endomyocardial biopsy derived adherent proliferating cells - a potential cell source for cardiac tissue engineering.
Heart diseases are a leading cause of morbidity and mortality. Cardiac stem cells (CSC) are considered as candidates for cardiac-directed cell therapies. However, clinical translation is hampered since their isolation and expansion is complex. We describe a population of human cardiac derived adherent proliferating (CAP) cells that can be reliably and efficiently isolated and expanded from endomyocardial biopsies (0.1 cm(3)). Growth kinetics revealed a mean cell doubling time of 49.9 h and a high number of 2.54 x 10(7) cells in passage 3. Microarray analysis directed at investigating the gene expression profile of human CAP cells demonstrated the absence of the hematopoietic cell markers CD34 and CD45, and of CD90, which is expressed on mesenchymal stem cells (MSC) and fibroblasts. These data were confirmed by flow cytometry analysis. CAP cells could not be differentiated into adipocytes, osteoblasts, chondrocytes, or myoblasts, demonstrating the absence of multilineage potential. Moreover, despite the expression of heart muscle markers like alpha-sarcomeric actin and cardiac myosin, CAP cells cannot be differentiated into cardiomyocytes. Regarding functionality, CAP cells were especially positive for many genes involved in angiogenesis like angiopoietin-1, VEGF, KDR, and neuropilins. Globally, principal component and hierarchical clustering analysis and comparison with microarray data from many undifferentiated and differentiated reference cell types, revealed a unique identity of CAP cells. In conclusion, we have identified a unique cardiac tissue derived cell type that can be isolated and expanded from endomyocardial biopsies and which presents a potential cell source for cardiac repair. Results indicate that these cells rather support angiogenesis than cardiomyocyte differentiation.


The relationship of reported HIV risk and history of HIV testing among emergency department patients.
Among a random sample of emergency department (ED) patients, we sought to determine the extent to which reported risk for human immunodeficiency virus (HIV) is related to ever having been tested for HIV. A random sample of patients (aged 18-64 years) from an adult, urban, northeastern United States, academic ED were surveyed about their history of ever having been tested for HIV and their reported HIV risk behaviors. A reported HIV risk score was calculated from the survey responses and divided into 4 levels, based on quartiles of the risk scores. Pearson's X(2) testing was used to compare HIV testing history and level of reported HIV risk. Logistic regression models were created to investigate the association between level of reported HIV risk and the outcome of ever having been tested for HIV. Of the 557 participants, 62.1% were female. A larger proportion of females than males (71.4% vs 60.6%; P < 0.01) reported they had been tested for HIV. Among the 211 males, 11.4% reported no HIV risk, and among the 346 females, 10.7% reported no HIV risk. The proportion of those who had been tested for HIV was greater among those reporting any risk compared with those reporting no risk for females (75.4% vs 37.8%; P < 0.001), but not for males (59.9% vs 66.7%; P < 0.52). However, certain high-risk behaviors, such as a history of injection-drug use, were associated with prior HIV testing for both genders. In the logistic regression analyses, there was no relationship between increasing level of reported HIV risk and a history of ever having been tested for HIV for males. For females, a history of ever having been tested was related to increasing level of reported risk, but not in a linear fashion. The relationship between reported HIV risk and history of testing among these ED patients was complex and differed by gender. Among these patients, having greater risk did not necessarily mean a higher likelihood of ever having been tested for HIV.


Graduate medical education: what will happen under DRGs?
Changing methods of reimbursement could cause the number of Graduate Medical Education programs to fall, the author says. Here, he explores how this will affect competition in and funding of the programs, and the programs themselves.


Pacing as a treatment modality in migraine and tension-type headache.
To review the pacing literature; describe the use of pacing in a specialty headache clinic; and provide client feedback regarding the effectiveness of pacing in headache self-management. The evidence for this report was derived from a structured literature review, an established pacing intervention program for patients with headache, and patient self-report questionnaire. There are frequent references to pacing in the chronic pain and rheumatic disease literature, but no universal definition and, until recently, few outcome studies. References to pacing in the headache literature are limited. For a small sub-group of clients at a specialty headache clinic (n = 20), pacing principles taught by occupational therapists were reported to prevent increases in headache intensity (70%); decrease headache intensity (65%), and shorten the duration of a headache (40%). Additionally, 70% of respondents used pacing to prevent headache onset. Pacing was seen to contribute to increased quality of life, headache self-efficacy, function, and independence. There were a variety of opinions regarding the most helpful pacing components. The most frequently endorsed were identify and prioritize responsibilities; balance activity and rest; schedule regular rest breaks; and delegate or eliminate tasks. Pacing appears to play an important role in headache self-management. More pacing research is required in both headache and chronic pain populations.


Developmental Relations between Children's Peer Relationship Quality and Prosocial Behavior: The Mediating Role of Trust.
Positive peer relationships are important for children's prosocial development, yet the mechanisms that explain how peers contribute to prosocial outcomes during the preschool and early school years remain understudied. The present study used a prospective longitudinal design to examine whether children's degree of trust in others mediated the association between prior peer relationship quality and later prosocial behavior in a Canadian sample (N = 150; T1 Mage= 4.53 years, 50% female). Primary caregivers (84% mothers) reported on children's peer relationship quality (at age 4), trust in others (ages 4 and 5), and prosocial behavior (ages 4 and 6). Controlling for initial levels of trust and prosocial behavior at age 4, longitudinal path modeling indicated that higher quality peer relationships directly predicted relative increases in trust at age 5. In turn, increased trust at age 5 predicted relative increases in prosocial behavior at age 6. Consistent with longitudinal mediation, the indirect effect of peer relationship quality on later prosocial behavior via trust was also significant. Sensitivity analyses further indicated that these effects held over and above the potential confounding influence of parental warmth and externalizing behavioral problems (assessed at age 6). Programs designed to promote prosocial skills in early childhood may benefit from an increased emphasis on building and maintaining children's interpersonal trust.


Radioprotective Effects of Combined Melatonin and Famotidine Treatment on Radiation Induced Apoptosis in Peripheral Blood Leukocytes of Breast Cancer Patients and Normal Individuals.
The aim of this study was to evaluate the effects of individual or combined use of two antioxidants, melatonin and famotidine on radiation induced apoptosis in leukocytes from breast cancer (BC) patients. In this experimental study, the DPPH assay was used to determine the appropriate doses of melatonin and famotidine for treatment of BC and control leukocytes. The leukocytes were cultured in complete RPMI1640 medium and treated with either agent for two hours. Cells were exposed to 4 Gy gamma rays generated from a Co-60 source at a dose rate of 0.85 Gy for 48 hours before harvesting. The cells were placed on slides and the neutral comet assay was performed. A total of 500 cells were stained with ethidium bromide and assessed for the amount of apoptosis under a fluorescent microscope x400 magnification. We observed significantly more apoptosis following radiation alone in the leukocytes from BC patients compared with normal individuals (P<0.01). Individual use of famotidine and melatonin induced very low frequencies of apoptosis that was not significantly different from the control (P>0.05). However, when combined with radiation, there was a decreased frequency of apoptosis in leukocytes of both normal and BC patients (P<0.05). The effect of famotidine was more pronounced than melatonin. Melatonin, despite its potent antioxidant property, does not significantly affect radiation induced apoptosis in leukocytes derived from normal individuals; however, it has a moderately significant protective effect on in leukocytes derived from BC patients. Therefore, when used with radiation it might not intervene with the radiotherapy (RT) regimen of BC cancer patients. Famotidine is a good radioprotector for normal tissue. However, the efficacy of RT might be reduced with an accumulation of famotidine in tumour tissues.


Sunitinib-induced severe hypoglycemia in a diabetic patient.
Sunitinib is an oral inhibitor of tyrosine kinase that was used for the treatment of mRCC. The general side effects are fatigue, asthenia, diarrhea, mucositis, nausea, vomiting, skin changes, hypertension, hypothyroidism and hematologic side effects. In addition, sunitinib-induced hypoglycemia has also been reported. There are limited number of case reports related to sunitinib-induced hypoglycemia. In this case report, we have presented a patient with type 2 diabetes mellitus (DM) with emerging severe hypoglycemia after sunitinib treatment. It was shown that blood glucose levels were normalized two weeks after the interruption of sunitinib. Although the underlying mechanism of sunitinib-induced hypoglycemia is not completely understood, sunitinib can be regarded to have an antidiabetic effect. In the literature, there are some reports about sunitinib/other TKI induced hypoglycemia; however, life threatening hypoglycemia is rare. There is no case report of severe hypoglycemia due to imatinib; however, there are two case reports with severe hypoglycemia due to sunitinib treatment. Symptomatic hypoglycemic episodes due to sunitinib may lead to hospital admission. Diabetic patients may develop severe hypoglycaemia and it should be kept in mind that the discontinuation of antihyperglycemic treatment may be required. Therefore, blood glucose levels should be closely monitored in diabetic patients with mRCC during sunitinib therapy.


LPCAT1 enhances castration resistant prostate cancer progression via increased mRNA synthesis and PAF production.
Our previously study shown that Lysophosphatidylcholine Acyltransferase1 (LPCAT1) is overexpressed in castration resistant prostate cancer (CRPC) relative to primary prostate cancer (PCa), and androgen controls its expression via the Wnt signaling pathway. While highly expressed in CRPC, the role of LPCAT1 remains unclear. In vitro cell experiments referred to cell transfection, mutagenesis, proliferation, migration, invasion, cell cycle progression and apoptosis, Western blotting, Pulse-chase RNA labeling. BALB/c nude mice were used for in vivo experiments. We found that LPCAT1 overexpression enhanced the proliferation, migration, and invasion of CRPC cells both in vitro and in vivo. Silencing of LPCAT1 reduced the proliferation and the invasive capabilities of CRPC cells. Providing exogenous PAF to LPCAT1 knockdown cells increased their invasive capabilities; however platelet activating factor acetylhydrolase (PAF-AH) and the PAFR antagonist ABT-491 both reversed this phenotype; proliferation of CRPC cells was not affected in either model. LPCAT1 was found to mediate CRPC growth via nuclear re-localization and Histone H4 palmitoylation in an androgen-dependent fashion, increasing mRNA synthesis rates. We also found that LPCAT1 overexpression led to CRPC cell resistance to treatment with paclitaxel. LPCAT1 overexpression in CRPC cells drives tumor progression via increased mRNA synthesis and PAF production. Our results highlight LPCAT1 as a viable therapeutic target in the context of CRPC.


Changes in intraocular pressure associated with topical dorzolamide and oral methazolamide in glaucomatous dogs.
To compare the reduction in intraocular pressure (IOP) by topical 2% dorzolamide to oral methazolamide (5 mg/kg) in dogs, and determine if the combination of both drugs would reduce IOP more than either drug administered alone. Thirteen glaucomatous beagles. Measurements, including applanation tonometry, pupil size and heart rate, were obtained at 8 am, 12 noon, and 5 pm on days 1, 3 and 5. The 5-day drug studies included placebo (0.5% methylcellulose); 2% dorzolamide administered in one eye twice daily (8 am and 5 pm), and repeated again in one eye three times (8 am, 12 noon and 5 pm) daily; methazolamide (5 mg/kg per os administered at 8 am and 5 pm); 2% dorzolamide instilled twice daily (5 days) combined with oral methazolamide on the last 3 days, and methazolamide (5 days) combined with 2% dorzolamide on the last 3 days and instilled twice daily. Statistical comparisons between drug groups included control (nondrug) eye and treated (placebo/drug) eyes for days 1, day 3 and 5. Topical 2% dorzolamide, administered twice and three times daily, significantly decreased IOP (mean +/- SEM) in glaucomatous dogs on the first day (twice daily 7.6 +/- 2.4 mmHg, and three times daily 16.4 +/- 3.6 mmHg) that was even greater by day 5 (twice daily 10.4 +/- 2.0 mmHg, and three times daily 13.9 +/- 2.7). Oral methazolamide also significantly lowered IOP in both eyes. Oral methazolamide (administered from day 1 through to day 5) combined with 2% topical dorzolamide (instilled in the drug eye for day 3 through to day 5) also significantly lowered IOP of both eyes for all days, and for day 5 the mean +/- SEM IOP was decreased by 7.9 +/- 1.7 mmHg (methazolamide plus dorzolamide) and 7.5 +/- 2.6 mmHg (methazolamide only). Topical dorzolamide (instilled in the drug eye for day 1 through to day 5) combined with oral methazolamide (administered from day 3 through to day 5) significantly lowered IOP in the drug eye on day 1 (5 pm: 9.6 +/- 1.9 mmHg), for day 3 (11 am and 5 pm) and for all of day 5 for both eyes (5 pm: control eye 9.5 +/- 1.8 mmHg; drug eye 9.2 +/- 1.9 mmHg). Topical dorzolamide (2%) instilled three times daily produces similar IOP declines compared to the combination of oral methazolamide and 2% dorzolamide administered twice daily. Dorzolamide (2%) instilled twice or three times daily causes significant decreases in IOP in glaucomatous dogs. Twice daily instillations caused progressive declines in IOP from day 1 to day 5. Dorzolamide (2%) combined with oral methazolamide (5 mg/kg per os twice daily) produces similar but not additional declines in IOP.


Multiple mtDNA deletions with features of MNGIE.
Two sisters developed gastrointestinal malabsorption with pain and unsteady gait due to polyneuropathy at age 15. Both had ophthalmoplegia, neurogenic EMG, and COX-negative muscle fibers. One patient had low muscle complex I-IV activity, multiple mtDNA deletions, and depletion, but no thymidine phosphorylase (TP) or dNT-2 gene mutations. TP activity and brain MRI were normal. The condition resembles mitochondrial neurogastrointestinal encephalomyopathy, except for the absence of leukoencephalopathy, and is likely caused by a nuclear DNA mutation that disrupts intergenomic signaling.


Studies on the relationship between esophageal acid exposure, mucosal lesions and heartburn using an acid exposure sensor.
In vitro studies of a recently developed acid exposure sensor show that the sensor response (SR) to acid <pH 4 is linearly determined by the duration and degree of acidity. The aim was to determine whether SR correlates with the severity of acid-induced esophageal mucosal lesions and acid-induced heartburn. HCl pH 1.5 or saline was infused into the feline esophagus for 5-20 min. Simultaneously, sensor measurements were performed below the infusion port. The histological damage was scored by an independent pathologist. In 15 normal subjects, HCl pH 1 was infused into the esophagus and the severity of the heartburn (0-5) was scored at 5-min intervals. In 10 subjects who experienced heartburn during acid perfusion, initial perfusion with HCl was repeated during heartburn induction time minus 5 min, followed by perfusion with the subject's own gastric juice, titrated to pH 2; heartburn severity was again scored at 5-min intervals. Acid exposure sensors positioned below the infusion port were removed at heartburn scores 1, 2 and 3. A good correlation was found between SR and the histological score for mucosal damage in the cat esophagus (r = 0.64, P < 0.005). There was a good relation between heartburn severity score and acid exposure time (r = 0.84, P < 0.001), and a significant but weaker relation between heartburn severity and SR. In cats, there is a good relation between the severity of acid-induced esophageal mucosal lesions and SR. In men, there is a significant correlation between the severity of acid-induced heartburn and the simultaneously measured SR. Therefore, SR measurement has the potential of yielding clinically relevant information in the investigation of GERD.


A missense mutation in TMEM67 causes Meckel-Gruber syndrome type 3 (MKS3): a family from China.
Meckel-Gruber syndrome (MKS) is a lethal autosomal recessive condition characterized by renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly. Genetic heterogeneity has been demonstrated at eleven loci, MKS1-11. Here, we present the clinical and molecular characteristics of a Chinese MKS3 family with occipital encephalocele and kidney enlargement. DNA sequencing of affected fetuses revealed a homozygous c.1645C>T substitution in exon 16 of TMEM67, leading to a p.R549C substitution in meckelin. The R549 residue is highly conserved across human, rat, mouse, zebrafish, chicken, wolf and platypus genomes. Hha I restriction analysis demonstrated that the c.1645C>T mutation was absent in 200 unrelated control chromosomes of Chinese background, supporting the hypothesis that it represents causative mutation, not rare polymorphism. Our data provide additional molecular and clinical information for establishing a better genotype-phenotype understanding of MKS.


Poplar PtabZIP1-like enhances lateral root formation and biomass growth under drought stress.
Developing drought-resistance varieties is a major goal for bioenergy crops, such as poplar (Populus), which will be grown on marginal lands with little or no water input. Root architecture can affect drought resistance, but few genes that affect root architecture in relation to water availability have been identified. Here, using activation tagging in the prime bioenergy crop poplar, we have identified a mutant that overcomes the block of lateral root (LR) formation under osmotic stress. Positioning of the tag, validation of the activation and recapitulation showed that the phenotype is caused by the poplar PtabZIP1-like (PtabZIP1L) gene with highest homology to bZIP1 from Arabidopsis. PtabZIP1L is predominantly expressed in roots, particularly in zones where lateral root primordia (LRP) initiate and LR differentiate and emerge. Transgenics overexpressing PtabZIP1L showed precocious LRP and LR development, while PtabZIP1L suppression significantly delayed both LRP and LR formation. Transgenic overexpression and suppression of PtabZIP1L also resulted in modulation of key metabolites like proline, asparagine, valine and several flavonoids. Consistently, expression of both of the poplar Proline Dehydrogenase orthologs and two of the Flavonol Synthases genes was also increased and decreased in overexpressed and suppressed transgenics, respectively. These findings suggest that PtabZIP1L mediates LR development and drought resistance through modulation of multiple metabolic pathways.


Interim analyses of survival data in cancer clinical trials.
It is common practice to undertake interim analyses of accumulating survival data in a cancer clinical trial while patient entry and/or follow-up is still in progress. The purpose of making an interim analysis is to stop the trial if a convincing treatment difference can be demonstrated. The main problem with repeated significance tests is that the more often one analyses accumulating data, the greater the probability of eventually obtaining a significant result, p < 0.05 say, even when there is in reality no treatment difference. To allow for repeated testing one must therefore choose a more stringent nominal significance level as a criterion for stopping the trial. Repeated significance tests are normally applied at equally spaced intervals, and the maximum number of tests is decided in advance. This paper presents and compares the properties of two simple and commonly applied strategies for undertaking interim analyses of accumulating survival data.


Remittance or persistence of attention deficit-hyperactivity disorder (ADHD) and its impact on recidivism in risky driving behaviors.
Recent data regarding the persistence or remittance of attention deficit-hyperactivity disorder (ADHD) diagnosis into adulthood raise the question of its possible role in crucial public health issues, including road safety, especially when neurocognitive capacities are challenged. The study included 611 participants with serious traffic violations. The Spanish version of the Mini International Neuropsychiatric Interview (M.I.N.I.) was used to assess psychopathology. They were grouped into 3 diagnostic conditions: non-ADHD, persistent ADHD (ADHD-P), and remittent ADHD (ADHD-R). Several risky driving behaviors were analyzed. Although participants with ADHD have more driving violations relative to non-ADHD, ADHD-R, and ADHD-P drivers have similar profiles. ADHD-R and ADHD-P drivers are more prone to perform risky and recidivistic behaviors relative to non-ADHD counterparts (P = .044 and P = .047, respectively); ADHD-R and ADHD-P participants are statistically comparable in this proneness (P = .772). These results suggest that the underlying core deficits of ADHD-attention and other executive disabilities-persist despite the fact that some people no longer reach the threshold for clinical diagnosis.


How we launched a developmental student-as-teacher (SAT) program for all medical students.
Teaching is a necessary skill for medical trainees and physicians. We designed and launched a developmental Student-as-Teacher program for all students, beginning with the class of 2016. A task force of faculty and students designed the program. The goal is to enable all students to acquire basic principles of teaching and learning at different stages in their four-year medical school career. Upon completion, students will achieve twenty-eight learning objectives grouped within four competency domains: (1) Adult and Practice-Based Learning; (2) Learning Environment; (3) Instructional Design and Performance; and, (4) Learner's Assessment and Evaluation. The program combines online learning modules and a field teaching experience. The entire class of 2016 (N = 200) completed the first online module. Students found the module effective, and 70% reported an increase in their level of knowledge. Although most students are expected to complete their field teaching experience in fourth year, twelve students completed their field experience in first year. Reported strengths of these experiences include reinforcement of their medical knowledge and improvement of their adult teaching skills. The program was successfully launched, and students are already experiencing the benefits of training in basic teaching skills in the first year of the program.


Implementing Online Discussion and Mind Mapping to Investigate a Disease Outbreak.
The recent increase in online learning modalities due to coronavirus disease 2019 (COVID-19) has created a significant gap in real-time discussions on complex issues. This lack of enrichment from student discussions levies the concern of a deficiency in strong learning outcomes. This learning activity focused on mind mapping to facilitate small group discussions on the 2010 cholera outbreak in Haiti. Students learned about the disease triangle and cause-and-effect relationships on a large spatial and temporal scale. In this case, the three points of the triangle represented the pathogen (Vibrio cholerae), the environment (Haiti), and the hosts (Haitians). Each student in each small group was required to read a unique article to present to their group on the day of the activity. Using mind mapping, each group illustrated relationships that may have exacerbated the cholera outbreak. Learning outcomes were assessed through the evaluation of questions relevant to that week's exercise. Students were assessed on their ability to recognize relationships between the pathogen, environment, and hosts, as well as the ability to apply what they learned to the present-day COVID-19 pandemic. The disease triangle activity is readily accessible and can be easily implemented for identifying cause-and-effect relationships in large-scale systems. Importantly, this learning activity retained real-time discussion-based problem-solving for improving students' critical thinking skills and approaches to complex issues.


Neuronavigated surgery of intracranial cavernomas--enthusiasm for high technologies or a gold standard?
The aim of this study was to investigate the effect of neuronavigation on the following parameters: "skin incision", "craniotomy", "intraoperative anatomical orientation", "dissection guiding", "localization of the pathological formation", "assessment of the degree of resection" and "duration of surgical procedure" in resections of intracranial cavernomas and to specify the indications for neuronavigation in their surgical treatment. The present prospective study included 20 patients with intracranial cavernomas who underwent neuronavigated surgery between March 2003 and December 2005 at the Clinic of Neurosurgery of the "St. I. Rilsky" University Hospital, Medical University, Sofia. The female/male ratio in the series was 9/11 (45%-55%). The patients' mean age was 27.96 +/- 11.61 years (age range 1.2 to 44 years). The patients were examined and followed up in a standard manner. Cavernous malformations were totally removed in 19 patients. One patient with thalamic cavernoma underwent navigated endoscopic biopsy. There was no morbidity or mortality associated with the method. Neuronavigation allowed precise localization and individual design of the skin incision and craniotomy. Neuronavigated intraoperative anatomical orientation, dissection guiding, localization of the pathological formation, and assessment of degree of resection were evaluated as markedly useful. They resulted in excellent surgery results and reduced operation time in comparison with the conventional surgery. In intracranial cavernomas frameless stereotaxy provides the surgeon with useful feedback in the preoperative anatomical orientation, the planning and simulation of surgical approach, the intraoperative navigation, in avoiding vital neurovascular structures, in the assessment of the degree of resection and the identification of possible residual parts. That is why cavernous malformations are among the most common indications for cranial neuronavigation.


Distribution of Breast Cancer Subtypes Among Nigerian Women and Correlation to the Risk Factors and Clinicopathological Characteristics.
Breast cancer in African women differs from the Caucasian. Understanding the profile of Nigerian women with breast cancer will help with preventive measures and treatment. This study focused on the clinico-pathological characteristics, with risk factors of breast cancer patients in Nigeria. Newly diagnosed female patients with breast cancer were assessed over 12 months. Patients were reviewed using a predesigned proforma which focused on socio-demographic information, clinical information, risk factors and tumor biology. A total of 251 women were identified; their mean age was 46 years. More than half (62.5%) are premenopausal at presentation, 37.8% with Eastern Cooperative Oncology Group (ECOG) score of 0 and right side (50.2%) as the most common primary site of disease. Less than half of them (43.0%) are estrogen receptor (ER) positive, 27.9% are progesterone receptor (PR) positive, 43.8% and 47.4% are hormone receptor positive and triple negative, respectively. Most patients presented at the latter stage of the disease, stage III (66.9%) and stage IV (18.3%). Only 15.9% are well differentiated and almost all (92.8%) had invasive ductal histological type. Obesity (66.2%) and physical inactivity (41.9%) are the most common risk factors for the disease. A significant relationship was found between immunohistochemistry status and family history of breast cancer, tumor site, previous breast surgery, previous lump and alcohol intake. Findings from this study showed that Nigerian breast cancer patients differ from their counterparts in the high human development index (H-HDI) countries in terms of the patients and disease characteristics. In view of this, prevention and treatment options should consider this uniqueness to ensure better outcome.


lncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis.
Increasing evidence indicated that long noncoding RNAs (lncRNA) play critical roles in the progression of multiple cancers and that dysregulation of lncRNA promotes tumor progression. However, the function and underlying mechanism of lncRNA DLEU2 in biological behaviors of NSCLC cells are still largely unknown. Our studies confirmed that lncRNA DLEU2 was highly expressed in NSCLC tissues and cell lines, which was correlated with shorter overall survival in NSCLC patients. In vitro, knockdown of lncRNA DLEU2 inhibited proliferation, invasion, migration and induced apoptosis of both A549 and LLC cells; In vivo, it suppressed tumor growth and metastasis. lncRNA DLEU2 directly interacted with miR-30c-5p, which further targeted SOX9 and exerted oncogenic functions in NSCLC. Mechanistically, overexpression of lncRNA DLEU2 exhibits tumorigenic effects through downregulating the inhibitory effect of miR-30c-5p on SOX9 expression. In conclusion, Our finding confirmed that lncRNA DLEU2 as a novel oncogenic in NSCLC, which provide a potential novel diagnostic and therapeutic target for NSCLC.


Purification and properties of lipases/esterases from a Bacillus strain for enantioselective resolution of (S)-Ketoprofen.
A Bacillus strain having a certain extent of asymmetric resolution for (S)-ketoprofen was studied for its culture and conversion condition. The distribution and properties of lipases/esterases from its bacterial cell and the change of asymmetric resolution ability were also investigated. After purification by hydrophobic interaction chromatography and gel filtration, the lipase/esterase terase activity of active fraction was 61.7 times higher than the crude enzyme and the purity of 23 kDa protein increased more than 400 times. Hydrolytic activity of lipase/esterase using ketoprofen chloroethyl ester and pNPA as substrate remained essentially constant in the reaction system during the purification procedure. The above result clearly indicated that the application of hydrophobic interaction chromatography-gel filtration was fast, useful and effective when compared to the difficulties in purification of low content crude enzyme prepared directly from bacterial cells. Experimental results also indicated that there are several lipases/esterases in the bacillus cell selective to the optically active ketoprofen and the conversion result was derived from the comprehensive function of all these enzymes. This is a new way to understand the bacterial asymmetric resolution with high conversion rate and low optical purity. The ESI-QUAD-TOF mass spectrum was used to analyze 23 kDa protein. Protein identities were revealed by searching sequence databases (MSDB) with peptide sequence tags. The result showed that 23 kDa protein is a novel protein.


Liver stem cell-derived beta-cell surrogates for treatment of type 1 diabetes.
Consistent with the common embryonic origin of liver and pancreas as well the similar glucose-sensing systems in hepatocytes and pancreatic beta-cells, it should not be surprising that liver stem cells/hepatocytes can transdifferentiate into insulin-producing cells under high-glucose culture conditions or by genetic reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic beta-cell precursors. In vitro culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia are required for further differentiation and maturation of liver-derived pancreatic beta-cell precursor into functional insulin-producing pancreatic beta-like cells. Under appropriate conditions, multiple pancreatic transcription factors can work in concert to reprogram liver stem/adult liver cells into functional insulin-producing cells. If such autologous liver-derived insulin-producing cells can be made to escape the type 1 diabetes-associated autoimmunity, they may serve as a valuable cell source for future cell replacement therapy without the need for life-long immunosuppression.


[Paget's disease of bone: MR characteristics at 1.5 T].
Thirteen patients with confirmed Paget's disease were examined using a 1.5 T MR tomograph. Five patients had polyostotic and eight patients monostotic forms of the disease. The results of these MR examinations were compared with the results of MR examinations performed on patients with osseous changes of different origin (metastases of breast cancer and prostate cancer, osteomyelitis, bone marrow infiltration due to acute lymphatic leukaemia and plasmocytoma). MR tomography permits evaluation of bone marrow space, osseous changes, and the surrounding soft tissue. Areas of sclerotic bone, thickened corticalis and bands of connective tissue in the marrow space were recognised as structures with no signal in T1- and T2-weighted images. The red and yellow marrows showed normal signal intensity patterns, although they were often reduced in size.


'Racist abuse ruined my life'.
Rosie Purves, a black nurse who was prevented from looking after a white baby, won a racial discrimination claim against her employer in May this year. Ms Purves was awarded pounds sterling 20,000--the highest payout possible for her type of claim--after an employment tribunal ruled that Southampton University Hospitals NHS Trust was 'effectively silent and complicit' in the racist demands made by a woman who did not want her baby treated by black staff. Here Ms Purves tells Nursing Times her harrowing story of how for seven years she suffered this abuse in silence.


Spontaneous growth hormone secretion and IGF1:IGFBP3 molar ratios in children born small for gestational age (SGA).
To analyze spontaneous nocturnal GH profiles, IGF1 and IGFBP3 serum levels, as well as IGF1:IGFBP3 molar ratios in SGA children without postnatal catch-up growth. Short statured prepubertal SGA children (n = 24) were matched retrospectively for sex, age and BMI to short statured children born appropriate for gestational age (AGA), who underwent the same diagnostic program. GH deficiency was excluded in all children by a normal increase of GH in 2 stimulation tests (>8 microg/L). For assessment of spontaneous nocturnal GH secretion, GH serum levels were measured every 20 min for 10 h. Pulsatility was analyzed with Pulsar. None of the Pulsar derived descriptive parameters showed a significant difference between SGA and AGA children. Overall, median IGF1 levels were approximately one SDS below zero SDS (p < 0.001), whereas IGFBP3 levels were normal in both groups. Thus, the IGF1:IGFBP3 molar ratios were significantly lower from zero (p < 0.01) in SGA as well as in AGA children. However, IGF1- and IGFBP3-SDS levels related either to chronological or to bone age did not differ significantly between SGA and AGA children. Building matched pairs of short statured children born either SGA or AGA for sex, age and BMI we did not find any significant differences in spontaneous nocturnal GH secretion, IGF1, IGFBP3, and IGF1:IGFBP3 molar ratios.


In vitro macrophage activity: biphasic effect of prolactin and indirect evidence of dopaminergic modulation.
Prolactin (PRL), a peptide hormone produced by the pituitary gland, is involved in the interaction between the neuroendocrine and immune system. Since dopamine receptor antagonists increase serum levels of PRL, both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing means of communication between the nervous and immune systems. This study evaluated the effects of PRL and the dopamine antagonist domperidone (DOMP) on macrophage activity of female rats. Oxidative burst and phagocytosis of peritoneal macrophages were evaluated by flow cytometry. Samples of peritoneal liquid from female rats were first incubated with PRL (10 and 100 nM) for different periods. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 nM). In vitro incubation of macrophages with 10 nM DOMP decreased oxidative burst, after 30 min, whereas the PMA-induced burst was decreased by DOMP 10 nM after 2 and 4 h. Treatment with PRL (10 and 100 nM) for 30 min decreased oxidative burst and rate of phagocytosis (10 nM). After 2 h of incubation, 10 nM PRL decreased oxidative burst and phagocytosis intensity, but increased the rate of phagocytosis. On the other hand, after 4 h, PRL 10 and 100 nM increased oxidative burst and the rate of phagocytosis, but decreased intensity of phagocytosis. These observations suggest that macrophage functions are regulated by an endogenous dopaminergic tone. Our data also suggest that both PRL and dopamine exert their action by acting directly on the peritoneal macrophage.


Pt-catalyzed tandem 1,2-acyloxy migration/intramolecular [3 + 2] cycloaddition of enynyl esters.
A platinum-catalyzed tandem reaction involving enynyl ester isomerization and subsequent intramolecular [3 + 2] cyclization has been developed. This strategy provides an efficient approach to five-, six-, or seven-membered cyclic polyfunctional compounds.


Discriminative strain and temperature measurement using Brillouin scattering and fluorescence in erbium-doped optical fiber.
We develop a novel discriminative sensing technique of strain and temperature using Brillouin scattering and fluorescence in an erbium-doped fiber (EDF). First, we show that the fluorescence intensity ratio (FIR), the ratio of the fluorescence intensities at two different wavelengths (1530 nm and 1565 nm in this experiment), is linearly dependent on temperature (with a coefficient of 5.6 × 10⁻⁴ /°C) but almost independent of strain. Then, by combined use of the FIR and the Brillouin frequency shift in an EDF, we experimentally demonstrate discriminative measurements of strain and temperature with four different sets of strain and temperature changes.


Impact of full range of amylose contents on the architecture of starch granules.
The effects of amylose deposition on crystalline regions of barley starch granules were studied in granules containing zero to 99.1% amylose using "waxy" (WBS, 0% amylose), normal (NBS, 18% amylose) and amylose-only barley lines (AOS, 99.1% amylose). The effects were probed after hydrolysis of amorphous regions of starch granules in dilute HCl generating lintners, which typically represent the crystalline lamella of starch granules. Compared to NBS and WBS, AOS granules exhibited an irregular, multilobular morphology with a rough surface texture. AOS displayed lower rates of acid hydrolysis than WBS, and AOS reached a plateau at ∼45wt% acid hydrolysis. High-performance anion-exchange chromatography of lintners at equivalent levels of hydrolysis (45wt%) revealed the average degree of polymerization (DP) of AOS lintners was 21, substantially smaller than that of NBS and WBS (DP 42). AOS lintners contained the lowest number of chains (NC) per molecule (1.1) compared to NBS (2.8) and WBS (3.3) and the average chain length of AOS, NBS and WBS lintners was 19, 15 and 13, respectively. Hence, both NC and the average chain length correlated with amylose content. The size distribution profile of AOS lintners revealed a repeat motif in the molecules corresponding to 5-6 glucose residues.


Papulo Necrotic Tuberculid on Glans Penis.
A case of papulo-necrotic tuberculids affecting only glans penis is described. A positive Mantoux test, characteristic histology and response to anti tuberculous drugs confirmed the diagnosis.


Manipulation of oxygenation and flow-induced shear stress can increase the in vitro yield of platelets from cord blood.
A method to produce clinically useful platelets in vitro would help overcome the frequent shortages, donor deferrals, disease transmission, and alloimmunization with volunteer donor-derived platelets. Using CD34 positively selected cord blood cells, we investigated ways to increase platelet quality and yield in a three-dimensional modular perfusion bioreactor system. We found a two- to threefold increase in platelet numbers produced only when the early phases of the culture process were carried out at 5% oxygen, versus when 20% oxygen was used throughout the culture period (p<0.05), and much more than when 5% oxygen was used throughout. When the medium was routed through the cell-scaffold construct, versus when it flowed under and over the construct, or just intermittent feeding was used, the number of platelets increased two- to threefold (p<0.05), and enhanced collagen-induced aggregation. The 5% oxygen early in the culture process mimics the marrow adjacent to the bone where early progenitors proliferate. Flow through the cell-scaffold construct creates shear forces that mimic the flow in central venous sinuses of the marrow and enhances platelet production from proplatelets. The use of altered oxygen levels and cross flow enhanced platelet numbers and quality, and will contribute to eventual in vitro platelet production for clinical use.


Characteristics of brain metastases from esophageal carcinoma.
Esophageal carcinoma (EC) is a major malignancy with a poor prognosis. Although esophageal cancers rarely metastasize to the brain, the number of patients diagnosed with brain metastases (BM) from EC is steadily increasing. Therefore, the risk factors for BM from EC should be known. Here we reviewed our experiences and the previous literature regarding BM from EC. Between 2000 and 2013, we retrospectively reviewed the clinical features and neurological findings of 19 patients diagnosed with and treated for BM from EC to determine the clinical risk factors and features. In all patients, the lesions were partially or completed located in the thoracic esophagus, and the average size of the EC lesion at diagnosis was 5.8 ± 2.9 cm, which was smaller than the previously reported size of EC lesions accompanied by BM. Patients without lung metastases were more common than those with lung metastases. The lesions in the 13 patients included squamous cell carcinoma (SqCC) in 9 (69.2%) and small cell carcinoma (SmCC) in 3 (23.0%). Six patients were not examined. Although there was no trend toward a higher incidence of BM in patients with adenocarcinoma and SqCC, this trend was observed in patients with SmCC. Excluding a single patient with SmCC, all patients had beyond stage III disease at EC diagnosis. Our study suggests that BM can occur in patients with EC lesions smaller than those previously reported; moreover, SmCC may be a risk factor for BM from EC.


Transfer from table to wheelchair in men and women with spinal cord injury: coordination of body movement and arm forces.
A complex set-up was used to investigate kinematics and ground reaction forces. Motor Control and Physical Therapy Research Laboratory, Neurotec Department, Karolinska Institutet, Huddinge, Sweden. To investigate how men and women with spinal cord injury (SCI) perform transfers from table to wheelchair with regard to timing and magnitude of force generation beneath the hands and associated body movements. A total of 13 subjects (seven men, six women) with thoracic SCI. Kinematics of body movement were recorded (Elite 2000 system) simultaneously with the signals from three force plates (AMTI) placed beneath the buttocks and hands. Temporal and spatial parameters regarding head, trunk and trailing arm displacement, loading amplitudes and loading torque directions of both hands were analyzed for each trial and subject and compared between genders. Men and women used similar amplitudes of head bending and forward displacement of the trailing shoulder, while female subjects had significantly larger trunk rotation. Both genders applied significantly more weight on the trailing hand. Differences between genders were seen in direction and timing of peak torque beneath the hands. The forces beneath the trailing hand were larger than those in the leading, if there is weakness or pain in one arm, this arm should be selected as the leading. To avoid excessive load on the arms, technical aids and environmental factors should be very well adapted. This project was funded by the Swedish Research Council and the Health Care Science Committee of Karolinska Institutet.


A Brain Machine Interface for command based control of a wheelchair using conditioning of oscillatory brain activity.
In this research a new method of wheelchair control using a Brain Computer Interface (BCI) is proposed, in an attempt to bridge the gap between in-lab and real life applications, we believe it would provide a high level control over the BCI instead of the normal low level commands. It is anticipated to emphasis on mu rhythm to provide the control signals. The wheelchair is equipped with a mapping system, which scans the area and provides a map containing information about the user's current location and next possible destinations, then provides an optimized list of possible trajectories to reach the destination. The paradigm allows users to control the interface using motor imagery and issue commands to switch between possible trajectories and then confirm the choice. Commands trigger the motion of the wheelchair to the intended destination using a user selected path with speed up to 0.5 m/s. The interface also allows the user to interact with different robots through a common robotic system. Evaluation results indicate that this paradigm is indeed usable and could lead to promising outcomes.


Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing.
Secreted signalling molecules provide cells with positional information that organizes long-range pattern during the development of multicellular animals. Evidence is presented that localized expression of Decapentaplegic instructs cells about their position along the anterior-posterior axis of the Drosophila wing in two distinct ways. One mechanism is based on the local concentration of the secreted protein; the other is based on the ability of the cells to retain an instruction received at an earlier time when their progenitors were in close proximity to the signal. Both mechanisms are involved in axis formation.


Influenza A Viruses: Understanding Human Host Determinants.
Previous influenza A virus (IAV) pandemics have invariably been caused by the introduction of an emergent IAV strain from an animal host into a human population with no or only little pre-existing immunity to the novel strain. Although zoonotic spillover of IAVs into humans can be associated with severe disease and a high fatality rate, these strains are typically poorly adapted to humans and are unable to establish sustained transmission between humans. Given the presumably very high degree of exposure to animal populations with endemic IAV, the number of pandemics remains surprisingly low. In this review, we provide an updated perspective on the molecular mechanisms underlying the adaptation of zoonotic IAV to human hosts, and discuss the implications for future pandemics.


Mutation spectra of TA*, the major photoproduct of thymidylyl-(3'5')-deoxyadenosine, in Escherichia coli under SOS conditions.
The biological activity of TA*, the major photoproduct of thymidylyl-(3',5')-deoxyadenosine, has remained speculative since it was identified a decade ago. To determine the mutagenicity of TA* in Escherichia coli, we constructed the replicative form of an M13mp18-derived phage containing TA* in the (-)-strand by polymerase-catalyzed elongation of a TA*-containing 49mer opposite a uracil-containing (+)-strand of the phage. The in vitro synthesis mixture was transfected into an ung+, phr- E.coli host and the progeny were screened with a hybridization probe unique for the (-)-strand. TA* was found to block DNA replication substantially in the absence of SOS, but under SOS, TA* was bypassed more efficiently and was highly mutagenic. Among 56 analyzed (-)-strand progeny from two transfections, 46 (82%) were mutants, including six (11%) tandem mutants. The most abundant mutation was a 3'A-->T substitution (31/46, 56%). The possible biological consequences of TA* formation in the highly conserved TATA box consensus sequence on gene expression are discussed in light of the mutagenicity of TA*.


Undifferentiated pleomorphic sarcoma of the mandible.
Undifferentiated pleomorphic sarcoma (UPS) is a high-grade neoplasm that is usually located in the extremities and retroperitoneum. In the past, UPS was considered the most common soft tissue sarcoma in adults; due to improvements in diagnostic techniques, most cases have been reclassified as other lineage-specific tumors. Gnathic bones are rarely affected, and the clinicopathological characteristics of this neoplasm when diagnosed in the jaw remain to be better described. In this report, we present a rare case of mandibular UPS affecting an 88-year-old female who demonstrated a painful swelling on the right side of the mandible that was accompanied by a pathological fracture. Microscopic examination revealed a pleomorphic spindlecell neoplasm with mitotic figures and necrosis. The patient underwent surgery and adjuvant radiotherapy but experienced metastasis after 12 months of follow-up and died. Diagnosis of UPS is challenging, and oral pathologists must be aware of this entity when dealing with aggressive undifferentiated neoplasms.


Bulk muscles, loose cables.
The accessibility and usage of body building supplements is on the rise with stronger internet marketing strategies by the industry. The dangers posed by the ingredients in them are underestimated. A healthy young man came to the emergency room with palpitations and feeling unwell. Initial history and clinical examination were non-contributory to find the cause. ECG showed atrial fibrillation. A detailed history for any over the counter or herbal medicine use confirmed that he was taking supplements to bulk muscle. One of the components in these supplements is yohimbine; the onset of symptoms coincided with the ingestion of this product and the patient is symptom free after stopping it. This report highlights the dangers to the public of consuming over the counter products with unknown ingredients and the consequential detrimental impact on health.


Spontaneous blinking behaviour in persistent vegetative and minimally conscious states: relationships with evolution and outcome.
There is evidence that spontaneous blinking correlates with cognitive functions. This arises from the observation that blinking rate (BR) is modulated by arousal levels, basic cognitive processes (e.g., attention, information processing, memory, etc.) and more complex cognitive functions (e.g., reading, speaking, etc.). The aim of this work was to test the role of BR evaluation in the assessment of cognitive network functioning in awake patients with consciousness deficits. Thirteen patients were recruited for the study, and were assessed by the Glasgow coma scale (GCS) and Glasgow outcome scale (GOS) on admittance and discharge, respectively. A level of cognitive functioning scale (LCFS) score was assigned at every change in awareness or at least every 2 weeks. At the same time as the clinical tests, the BR was observed for a 5-min period. Ten healthy subjects, observed throughout three non-consecutive days, formed the control group. The BR underwent a different temporal behaviour in the two diagnostic categories. In the persistent vegetative state (PVS) group it remained stable throughout time and linked with the clinical conditions of the patients; whereas in the non-persistent vegetative state (NPVS) group it decreased over time as the cognitive conditions improved. Moreover, a strong inverse correlation was found between overall BR values and LCFS scores. We have concluded that the blinking behaviour changes manifested in PVS and NPVS patients reflect different evolution phases of a cholinergic-dopaminergic imbalance, and that a reduced BR characterizes the early stages of consciousness recovery.


[Fertility sparing management of endometrial adenocarcinoma and atypical hyperplasia: a literature review].
In endometrial carcinoma (EC) and atypical hyperplasia (AH) diagnosed in childbearing years, the principle of uterine sparing consists in prescription of antigonadotropic treatment to obtain the remission of the endometrial lesion and allow pregnancy, always with a close follow-up looking for progression or persistence of the tumour. Studies evaluating this strategy have suggested the safety of such an approach, but numerous questions remain unanswered, like those concerning the type and the duration of treatment, and the systematic use of Assisted Reproductive Technologies… We performed a critical literature review in order to analyse patients and tumoral characteristics, treatment management and the results of fertility sparing strategy. This review shows that fertility sparing management of AH and intramucous EC permits to obtain pregnancy in one third of candidates. Few disease-related deaths have been reported after this management. One-third of patients experienced progression lesion beyond the endometrium, but generally limited to the myometrium. Progestins have been widely evaluated in this indication and provide an overall remission rate of 80% with a recurrence risk of 25%.


Effects of Abscisic Acid and High Osmoticum on Storage Protein Gene Expression in Microspore Embryos of Brassica napus.
Storage protein gene expression, characteristic of mid- to late embryogenesis, was investigated in microspore embryos of rapeseed (Brassica napus). These embryos, derived from the immature male gametophyte, accumulate little or no detectable napin or cruciferin mRNA when cultured on hormone-free medium containing 13% sucrose. The addition of abscisic acid (ABA) to the medium results in an increase in detectable transcripts encoding both these polypeptides. Storage protein mRNA is induced at 1 micromolar ABA with maximum stimulation occurring between 5 and 50 micromolar. This hormone induction results in a level of storage protein mRNA that is comparable to that observed in zygotic embryos of an equivalent morphological stage. Effects similar to that of ABA are noted when 12.5% sorbitol is added to the microspore embryo medium (osmotic potential = 25.5 bars). Time course experiments, to study the induction of napin and cruciferin gene expression demonstrated that the ABA effect occurred much more rapidly than the high osmoticum effect, although after 48 hours, the levels of napin or cruciferin mRNA detected were similar in both treatments. This difference in the rates of induction is consistent with the idea that the osmotic effect may be mediated by ABA which is synthesized in response to the reduced water potential. Measurements of ABA (by gas chromatography-mass spectrometry using [(2)H(6)]ABA as an internal standard) present in microspore embryos during sorbitol treatment and in embryos treated with 10 micromolar ABA were performed to investigate this possibility. Within 2 hours of culture on high osmoticum the level of ABA increased substantially and significantly above control and reached a maximum concentration within 24 hours. This elevated concentration was maintained for 48 hours after culturing and represents a sixfold increase over control embryos. The ABA-treated embryos accumulated the hormone very quickly, but ABA concentrations returned to basal levels within 72 hours after treatment. The possibility that embryo-synthesized ABA may be a mediator of effects of osmotic stress on gene expression in Brassica embryos is discussed.


Oral fixed drug eruptions to mefenamic acid - adverse drug reaction to over the counter medication taken for menstrual pain.
The reports on adverse drug reactions(ADR) to self-medication or over-the-counter medication are common across medical literature. However, the occurrence of oral fixed drug eruptions (FDE) to mefenamic acid is unique. We report a case of FDE to a drug obtained over the counter for menstrual pain. The essential findings from history, oral/dental examination, diagnostic approach, and treatment are briefly discussed along with a note on time and dosing for the oral drug provocation tests. The occurrence of ADR may be avoided by spreading awareness against OTC medication and labeling the specific drug for patients with established ADR.


Recognition of linear stress fibers based on Hough transform.
To present an algorithm based on Hough transform for recognition and extraction of linear stress fibers formed on exposure to lysophosphatidic acid (LPA). A ridge set of head points with lower shoulders is calculated, followed by a thinning process shrinking long, narrow regions to regions of single pixel thickness, then converted into a rectangular map whose value is the number of regional points in the path of a straight line at the angle and intercept determined by two coordinates. The location of the maximum in the map is sought, and the corresponding line with an unlimited length is constructed from the paired coordinates. We removed the line before repeating the process for the next longest straight line, continuing until all lines with reasonable lengths are extracted. Application of the algorithm to the stress fiber images of DOV13 cells stained with Texas red-phalloidin on LPA and AG1478 demonstrates close matches between stress fibers in the original images and linear lines. An algorithm for recognition of linear stress fibers formed on exposure to LPA is described and applications to stress fiber images using DOV13 cells with Texas red-phalloidin staining are demonstrated.


The square kilometre array and the transient universe.
The square kilometre array (SKA) is a next generation radio telescope that will be built in southern Africa and Australasia. It will be built in two phases and will use a range of detectors, from aperture arrays to dishes, to span the frequency range from a few tens of megahertz to a few gigahertz. The combination of great sensitivity, wide field of view and unprecedented computing power mean that the SKA will be an excellent instrument for studying the transient radio universe. Transient radio emission is generated in extremes of: gravitational and magnetic fields, velocity, temperature, pressure and density. While we know about plenty of source classes for this type of short duration radio emission, there is still a large range of transient parameter space that has not yet been sampled owing to the limitations of current generation radio telescopes.


43K protein and acetylcholine receptors colocalize during the initial stages of neuromuscular synapse formation in vivo.
The 43K protein is a cytoplasmic peripheral membrane protein concentrated subsynaptically in skeletal muscle. Recombinant 43K has been shown to cause clustering of acetylcholine receptors (AChRs) in cultured cells. However, the role of 43K in vivo is disputed, because in some cases it appears only after AChRs have clustered. We therefore examined the expression and distribution of 43K and AChRs during synapse formation in embryonic mouse muscles. Messenger RNA for 43K was detected on Embryonic Day (E) 12, a day prior to the first AChR clusters. Immunofluorescence showed that both AChRs and 43K were colocalized in patches by E13, the stage at which intramuscular nerves were first detected. The AChR/43K patches were nerve associated, and more than 98% of AChR patches were accompanied by 43K. The precise colocalization of 43K and AChRs persisted through development. These results are consistent with 43K being involved in the nerve-induced clustering of AChRs during synapse formation.


Heme oxygenase-1 as a protective gene.
Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in the formation of carbon monoxide, iron and biliverdin that is subsequently reduced to bilirubin by biliverdin reductase. The products of this enzymatic reaction have important biological effects, including antioxidant, anti-inflammatory and cytoprotective functions. Three isoforms of heme oxygenase (HO) have been described: two constitutively expressed isoforms, HO-2 and HO-3, and an inducible isoform, HO-1 that is increased as an adaptive response to several injurious stimuli including heme, hyperoxia, hypoxia, endotoxin and heavy metals. Induction of HO-1 has been implicated in numerous clinically relevant disease states including transplant rejection, hypertension, atherosclerosis, lung injury, endotoxic shock and others. This review will focus on the protective functions of HO-1.


Cell permeabilization and inhibition of voltage-gated Ca(2+) and Na(+) channel currents by nanosecond pulsed electric field.
Previous studies have found that nanosecond pulsed electric field (nsPEF) exposure causes long-term permeabilization of the cell plasma membrane. In this study, we utilized the whole-cell patch-clamp method to study the nsPEF effect on currents of voltage-gated (VG) Ca(2+) and Na(+) channels (I(Ca) and I(Na)) in cultured GH3 and NG108 cells. We found that a single 300 or 600 ns pulse at or above 1.5-2 kV/cm caused prolonged inhibition of I(Ca) and I(Na). Concurrently, nsPEF increased a non-inactivating "leak" current (I(leak)), presumably due to the formation of nanoelectropores or larger pores in the plasma membrane. The nsPEF effects were similar in cells that were exposed intact and subsequently brought into the whole-cell recording configuration, and in cells that were first brought into the whole-cell configuration and then exposed. Although both I(leak) and the inhibition of VG currents were enhanced at higher E-field levels, these two nsPEF effects showed relatively weak correlation with each other. In some cells, I(leak) increased 10-fold or more while VG currents remained unchanged. At longer time intervals after exposure (5-15 min), I(Ca) and I(Na) could remain inhibited although I(leak) had largely recovered. The causal relation of nsPEF inhibitory effects on VG currents and permeabilization of the plasma membrane is discussed.


Nogo-66 receptor prevents raphespinal and rubrospinal axon regeneration and limits functional recovery from spinal cord injury.
Axon regeneration after injury to the adult mammalian CNS is limited in part by three inhibitory proteins in CNS myelin: Nogo-A, MAG, and OMgp. All three of these proteins bind to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth in vitro. To explore the necessity of NgR for responses to myelin inhibitors and for restriction of axonal growth in the adult CNS, we generated ngr(-/-) mice. Mice lacking NgR are viable but display hypoactivity and motor impairment. DRG neurons lacking NgR do not bind Nogo-66, and their growth cones are not collapsed by Nogo-66. Recovery of motor function after dorsal hemisection or complete transection of the spinal cord is improved in the ngr(-/-) mice. While corticospinal fibers do not regenerate in mice lacking NgR, regeneration of some raphespinal and rubrospinal fibers does occur. Thus, NgR is partially responsible for limiting the regeneration of certain fiber systems in the adult CNS.


Functional interplay between BRCA2/FancD1 and FancC in DNA repair.
A rare hereditary disorder, Fanconi anemia (FA), is caused by mutations in an array of genes, which interact in a common FA pathway/network. These genes encode components of the FA "core" complex, a key factor FancD2, the familial breast cancer suppressor BRCA2/FancD1, and Brip1/FancJ helicase. Although BRCA2 is known to play a pivotal role in homologous recombination repair by regulating Rad51 recombinase, the precise functional relationship between BRCA2 and the other FA genes is unclear. Here we show that BRCA2-dependent chromatin loading of Rad51 after mitomycin C treatment was not compromised by disruption of FANCC or FANCD2. Rad51 and FancD2 form colocalizing subnuclear foci independently of each other. Furthermore, we created a conditional BRCA2 truncating mutation lacking the C-terminal conserved domain (CTD) (brca2DeltaCTD), and disrupted the FANCC gene in this background. The fancc/brca2DeltaCTD double mutant revealed an epistatic relationship between FANCC and BRCA2 CTD in terms of x-ray sensitivity. In contrast, levels of cisplatin sensitivity and mitomycin C-induced chromosomal aberrations were increased in fancc/brca2DeltaCTD cells relative to either single mutant. Taken together, these results indicate that FA proteins work together with BRCA2/Rad51-mediated homologous recombination in double strand break repair, whereas the FA pathway plays a role that is independent of the CTD of BRCA2 in interstrand cross-link repair. These results provide insights into the functional interplay between the classical FA pathway and BRCA2.


McComedy: A user-friendly tool for next-generation individual-based modeling of microbial consumer-resource systems.
Individual-based modeling is widely applied to investigate the ecological mechanisms driving microbial community dynamics. In such models, the population or community dynamics emerge from the behavior and interplay of individual entities, which are simulated according to a predefined set of rules. If the rules that govern the behavior of individuals are based on generic and mechanistically sound principles, the models are referred to as next-generation individual-based models. These models perform particularly well in recapitulating actual ecological dynamics. However, implementation of such models is time-consuming and requires proficiency in programming or in using specific software, which likely hinders a broader application of this powerful method. Here we present McComedy, a modeling tool designed to facilitate the development of next-generation individual-based models of microbial consumer-resource systems. This tool allows flexibly combining pre-implemented building blocks that represent physical and biological processes. The ability of McComedy to capture the essential dynamics of microbial consumer-resource systems is demonstrated by reproducing and furthermore adding to the results of two distinct studies from the literature. With this article, we provide a versatile tool for developing next-generation individual-based models that can foster understanding of microbial ecology in both research and education.


TRPA1 as a therapeutic target for nociceptive pain.
Chronic pain affects approximatively 30-50% of the population globally. Pathologies such as migraine, diabetic neuropathy, nerve injury and treatment with chemotherapeutic agents, can induce chronic pain. Members of the transient receptor potential (TRP) channels, including the TRP ankyrin 1 (TRPA1), have a major role in pain. We focus on TRPA1 as a therapeutic target for pain relief. The structure, localization, and activation of the channel and its implication in different pathways to signal pain are described. This paper underlines the role of pharmacological interventions on TRPA1 to reduce pain in numerous pain conditions. We conducted a literature search in PubMed up to and including July 2020. Our understanding of the molecular mechanisms underlying the sensitization of central and peripheral nociceptive pathways is limited. Preclinical evidence indicates that, in murine models of pain diseases, numerous mechanisms converge on the pathway that encompasses oxidative stress and Schwann cell TRPA1 to sustain chronic pain. Programs to identify and develop treatments to attenuate TRPA1-mediated chronic pain have emerged from this knowledge. Antagonists explored as a novel class of analgesics have a new and promising target in the TRPA1 expressed by peripheral glial cells.


Differential regulation of seizure activity in the hippocampus of male and female rats.
The aim of the current study was to directly examine and compare the susceptibility to N-methyl-D-aspartate-induced seizures in male versus female rats. We also sought to compare the anticonvulsant effects of magnesium sulfate in these two groups. Eighteen female and 10 male rats were stereotaxically implanted with a chronic bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 1 week rats randomly received an intravenous injection of 90 mg/kg magnesium sulfate or saline solution control. Fifteen minutes after the infusion rats were given the convulsant N-methyl-D-aspartate at a dose of 5 micrograms/microliters by direct intraventricular injection. Electrical seizure activity was thereafter assessed for 20 minutes. All data were analyzed by the Mann-Whitney U test and Student t test. In saline solution-treated rats receiving the convulsant N-methyl-D-aspartate, females had significantly lower total duration (p < 0.01) and total number of seizures (p < 0.05) compared with the male rats. The initial seizure was not affected by gender. In the female animals magnesium sulfate significantly reduced first seizure duration (p < 0.01) compared with saline solution controls. In males magnesium sulfate reduced both total duration (p < 0.05) and total seizure number (p < 0.05) compared with saline solution-treated animals. N-methyl-D-aspartate-induced seizure activity is more severe in males versus female rats. Magnesium sulfate's effect on N-methyl-D-aspartate-induced seizures is also dependent on gender. We speculate that seizure regulation may be hormonally influenced.


Sleep physiological network analysis in children.
Physiological networks have recently been employed as an alternative to analyze the interaction of the human body. Within this option, different systems are analyzed as nodes inside a communication network as well how information fows. Several studies have been proposed to study sleep subjects with the help of the Granger causality computation over electroencephalographic and heart rate variability signals. However, following this methodology, novel approximations for children subjects are presented here, where comparison between adult and children sleep is followed through the obtained connectivities. Data from ten adults and children were retrospectively extracted from polysomnography records. Database was extracted from people suspected of having sleep disorders who participated in a previous study. Connectivity was computed based on Granger causality, according to preprocessing of similar studies in this feld. A comparison for adults and children groups with a chi-square test was followed, employing the results of the Granger causality measures. Results show that differences were mainly established for nodes inside the brain network connectivity. Additionally, for interactions between brain and heart networks, it was brought to light that children physiology sends more information from heart to brain nodes compared to the adults group. This study represents a frst sight to children sleep analysis, employing the Granger causality computation. It contributes to understand sleep in children employing measurements from physiological signals. Preliminary fndings suggest more interactions inside the brain network for children group compared to adults group.


Cloning, structural characterization and functional expression of a zebrafish bradykinin B2-related receptor.
The actions of bradykinin (BK) in mammals are mediated through the activation of the B1 and B2 BK receptors. The only BK receptor that has been cloned from a non-mammalian species is a B2-like receptor from the chicken (termed the ornithokinin receptor). Pharmacological studies have demonstrated the presence of BK receptors in tissues of teleost fishes, such as trout and cod, but the ligand-binding properties of these receptors differ appreciably from those of the mammalian and chicken receptors. We report here the cloning of a B2-like receptor in zebrafish that shares 35% identity with human B2 and 30% identity with human B1. Phylogenetic analyses confirm a closer relationship with B2 than B1. The receptor gene was mapped to linkage group 17, which is syntenic to the human B2-B1 gene region. After functional expression of the zebrafish B2 receptor in mammalian cells, nanomolar concentrations of trout BK ([Arg0,Trp5,Leu8]-BK) and the derivative [des-Arg0,Trp5,Leu8]-BK (where 'des' indicates a missing amino acid) induced a significant transient rise in intracellular free Ca2+. The B1-selective analogue [Arg0,Trp5,Leu8,des-Arg9]-BK was inactive at nanomolar concentrations. Taken together, these results strongly support the gene's identity as a piscine orthologue of the mammalian B2 receptor.


Mechanotransduction of flow-induced shear stress by endothelial glycocalyx fibers is torque determined.
To test the hypothesis that the mechanotransduction of flow-induced shear stress on endothelial cells (ECs) might be triggered by the total torque transmitted from the glycocalyx fibers to the ECs rather than by the total shear force acting directly on the membrane of ECs, we formulated the arterial wall as a five-layer model and numerically investigated the effect of two types of damages to the endothelial glycocalyx layer (EGL) on the flow in the EGL and on the drag force and bending moment acting on the glycocalyx fibers. One type of damage was to alter the thickness of the EGL, and the other was to damage its integrity. The results revealed that almost all amount of the shear stress acting on ECs was transmitted to the cells by the EGL and that the flow-induced shear stress acting directly on the cell membrane was negligibly small. In addition, the total force transmitted from the glycocalyx fibers to the cell membrane in the forms of drag force was hardly affected by the damages to the EGL. However, such damages could significantly influence the total torque at the roots of the EGL fibers. In conclusion, the mechanotransduction of shear stress by the EGL might be torque determined rather than force determined.


Addition of lemon before boiling chlorinated tap water: A strategy to control halogenated disinfection byproducts.
Chlorine disinfection is required to inactivate pathogens in drinking water, but it inevitably generates potentially toxic halogenated disinfection byproducts (halo-DBPs). A previous study has reported that the addition of ascorbate to tap water before boiling could significantly decrease the concentration of overall halo-DBPs in the boiled water. Since the fruit lemon is rich in vitamin C (i.e., ascorbic acid), adding it to tap water followed by heating and boiling in an effort to decrease levels of halo-DBPs was investigated in this study. We examined three approaches that produce lemon water: (i) adding lemon to tap water at room temperature, termed "Lemon"; (ii) adding lemon to boiled tap water (at 100 °C) and then cooling to room temperature, termed "Boiling + Lemon"; and (iii) adding lemon to tap water then boiling and cooling to room temperature, termed "Lemon + Boiling". The concentrations of total and individual halo-DBPs in the resultant water samples were quantified with high-performance liquid chromatography-tandem mass spectrometry and the cytotoxicity of DBP mixtures extracted from the water samples was evaluated using human epithelial colorectal adenocarcinoma Caco-2 cells and hepatoma HepG2 cells. Our results show that the "Lemon + Boiling" approach substantially decreased the concentrations of halo-DBPs and the cytotoxicity of tap water. This strategy could be applied to control halo-DBPs, as well as to lower the adverse health effects of halo-DBPs on humans through tap water ingestion.


Validation of the Hemo_Control instrument for determination of B-haemoglobin concentration in primary health care.
The aim of this study was to evaluate the analytical performance of a new portable haemoglobinometer, Hemo_Control (EKF-diagnostic, GmbH, Germany), which measures haemoglobin concentration in venous and capillary samples. The within series and between series imprecision of the Hemo_Control instrument were calculated after measuring the concentration of venous samples under standardized conditions; by experienced laboratory technicians in a hospital laboratory, and venous and capillary samples under conditions similar to where the instrument is intended for use; by personnel at two primary health care centres. The bias of the Hemo_Control instrument was calculated as the difference between its results and results obtained with a Coulter LH 750 instrument traceable to the ICSH reference method. The uncertainty of the Hemo_Control instrument for venous samples was lower than the quality goal of +/- 5% considered acceptable for patient care. High within series imprecision (5.5%) was observed for measurements of capillary blood samples in one of the primary care centres, whereas adequate analytical performance was obtained at the other centre. The Hemo_Control instrument showed negligible bias of +0.8 g/L for both venous and capillary samples in primary health care. The observed uncertainty indicates that Hemo_Control is appropriate for near patient testing using venous samples. Capillary samples may be used if sampling skills are adequate.


Road map to a revolution: highlights from the 1993 APNA conference.
1. However it may happen, change is certain to occur; mental health care will be reformed in the near future. 2. The Coalition of Psychiatric Nursing Organizations developed an 85-page position paper on essential services. One topic dealt with is "barriers to care," which include public attitudes, fragmented systems, poverty and race, private insurance, and public funding. 3. As a result of increasingly sophisticated and assertive lobbying efforts, nurses have been more involved in the political scene. Ira Magaziner, project director for the Health Care Reform Task Force, addressed 100 nurses recently. 4. For psychosocial nurses, "the future is now." There is a window of opportunity at this time, and nurses must agree on what is wanted and work together to take advantage of that window.


Exome-driven characterization of the cancer cell lines at the proteome level: the NCI-60 case study.
Cancer genome deviates significantly from the reference human genome, and thus a search against standard genome databases in cancer cell proteomics fails to identify cancer-specific protein variants. The goal of this Article is to combine high-throughput exome data [Abaan et al. Cancer Res. 2013] and shotgun proteomics analysis [Modhaddas Gholami et al. Cell Rep. 2013] for cancer cell lines from NCI-60 panel to demonstrate further that the cell lines can be effectively recognized using identified variant peptides. To achieve this goal, we generated a database containing mutant protein sequences of NCI-60 panel of cell lines. The proteome data were searched using Mascot and X!Tandem search engines against databases of both reference and mutant protein sequences. The identification quality was further controlled by calculating a fraction of variant peptides encoded by the own exome sequence for each cell line. We found that up to 92.2% peptides identified by both search engines are encoded by the own exome. Further, we used the identified variant peptides for cell line recognition. The results of the study demonstrate that proteome data supported by exome sequence information can be effectively used for distinguishing between different types of cancer cell lines.


[Influence of interferon on the toxic effect and antitumor activity of vinblastine in the combined therapy of metastatic Lewis carcinoma].
Antitumour and antimetastatic effects of the combination of vinblastine (VLB) and L-cell interferon were examined. It is shown that mice with 3LL carcinoma are more sensitive to common toxic effect of VLB than intact animals. Interferon (IF) decreases the toxic effect of VLB in tumour-bearing mice, and thus provides a possibility to increase the total therapeutic dose of the cytostatic. The combination of VLB and IF showed a synergistic inhibitory effect on the development of carcinoma metastases and significantly increases the survival rate of the tumour-bearing mice. Neither synergistic nor additive antitumour effects of the combined therapy were observed on the primary tumour. IF suppresses the primary tumour growth more significantly when given by intratumoural injection. At the same time the inhibition of metastase development was more efficient with intraperitoneal injection of IF.


[Is ureteral dilatation necessary in ureterorenoscopy?].
A retrospective analysis of 136 patients, who were submitted rigid ureteroscopy for stone removal, was performed. Patients were divided into two groups. First group consisted of 63 patients with routine balloon dilation of intramural part of ureter before ureteroscopy. 73 patients of the second group were submitted ureteroscopy without previous ureter dilation. The total success rate was achieved in the first and second group of the patients in 90.5% and 91.8%. The success rate achieved in removing of the stone of upper, middle and lower part of the ureter was in the first group 81.8%, 88.9% and 94.1% and in the second group 78.6%, 95%, 94.9%, respectively. None of the patients have demonstrated vesico-renal reflux. With respect to our similar success rate in both of the groups they don't consider routine dilation of ureter as necessary before ureteroscopy.


Investigating the Neurotoxic Impacts of Arsenic and the Neuroprotective Effects of Dictyophora Polysaccharide Using SWATH-MS-Based Proteomics.
Arsenic (As) is one of the most important toxic elements in the natural environment. Currently, although the assessment of the potential health risks of chronic arsenic poisoning has received great attention, the research on the effects of arsenic on the brain is still limited. It has been reported that dictyophora polysaccharide (DIP), a common bioactive natural compound found in dietary plants, could reduce arsenic toxicity. Following behavioral research, comparative proteomics was performed to explore the molecular mechanism of arsenic toxicity to the hippocampi of SD (Sprague Dawley) rats and the protective effect of DIP. The results showed that exposure to arsenic impaired the spatial learning and memory ability of SD rats, while DIP treatment improved both the arsenic-exposed rats. Proteomic analysis showed that arsenic exposure dysregulated the expression of energy metabolism, apoptosis, synapse, neuron, and mitochondria related proteins in the hippocampi of arsenic-exposed rats. However, DIP treatment reversed or restored the expression levels of these proteins, thereby improving the spatial learning and memory ability of arsenic-exposed rats. This study is the first to use high-throughput proteomics to reveal the mechanism of arsenic neurotoxicity in rats as well as the protective mechanism of DIP against arsenic neurotoxicity.


Is the Effect of Behavioral Synchrony on Cooperative Behavior Mediated by Pain Threshold?
Synchronized behavior results in a variety of prosocial behaviors. Research has also implicated that interpersonal synchrony affects pain thresholds, inferred as indicative of endorphin levels. The current study was designed to see if these pain threshold effects mediated the effect of synchrony on interpersonal cooperation. Twenty six individuals were randomly assigned to complete a 30 minute run on a treadmill in either a synchronized or nonsynchronized condition. Pain threshold was measured both before and after exercise as an indicator of endorphin activity. A postrun social investment game measured interpersonal cooperation. Analyses showed that there was a significant direct relationship between condition and cooperation but that this effect was not mediated by pain threshold.


A comparison of the effects of intravenous propranolol and nadolol on the renal response to hypertonic saline infusion.
Intravenous loading with 500 ml of 2.7% saline increased the clearance of PAH and inulin and urine sodium excretion in 14 healthy subjects. Intravenous propranolol (0.075 and 0.15 mg/kg) did not alter PAH or inulin clearance at rest but abolished the increase expected during saline infusion. There was no consistent effect on urinary sodium excretion. Intravenous nadolol (0.05 and 0.75 mg/kg) reduced resting PAH and inulin clearances by up to 25%. Both clearances fell significantly during saline infusion but natriuresis was not significantly reduced in spite of the changes in renal function. There was no evidence from these studies in normal volunteers that nadolol confers any advantages over propranolol in its effects on renal function.


[Treatment of intracranial saccular aneurysms by detachable balloon].
Eight cases of intracranial saccular aneurysm treated with detachable balloon were reported in this article. The aneurysms were located at ophthalmic artery (2 cases) anterior and posterior communicating artery (2 cases respectively), and basilar artery (2 cases). The detachable balloon was successfully put into the aneurysmal sac in 6 cases and obliterated the parent artery in another 2 cases. The material used to fill the balloon is made by our own hospital. All the cases were cured with the exception of 1 patient who had a contralateral hemiparesis. The indication of using detachable balloon and its technique were discussed in detail.


Cerebellar cortical stimulation increases spinal visceral nociceptive responses.
The role of the cerebellum in modulating nociceptive phenomena is unclear. In this study, we focus on the effects of cerebellar cortical stimulation on the responses of midline neurons of the lumbosacral spinal cord to graded nonnoxious and noxious visceral (colorectal distension) as well as somatic (brush, pressure, pinch) stimuli. Extracellular recording was used for the isolation and recording of spinal nociceptive neurons, while electrical current pulses and chemical injection of D, L-homocysteic acid were used to stimulate the cortex of the posterior cerebellar vermis. Cerebellar cortical stimulation increased the responses of all isolated cells to colorectal distension, whereas the effect on the responses to somatic stimuli was variable. These findings indicate that the posterior cerebellar vermis may exert a pro-nociceptive effect on spinal visceroceptive neurons.


Endocrine correlates of parental care in an Antarctic winter breeding seabird, the emperor penguin, Aptenodytes forsteri.
Plasma levels of luteinizing hormone (LH) and prolactin associated with parental behavior were measured in the Antarctic winter breeding emperor penguin, Aptenodytes forsteri. Males exclusively incubate the egg while females exclusively brood the nonhomeothermic young; both sexes alternate in rearing the homeothermic young. Birds were sampled on arrival from the sea through egg laying, incubation, and brooding. All parent birds lost their chicks at the end of the brooding period due to harsh weather but sampling continued. In females, LH titers dropped after egg laying but levels were restored when the birds returned from the sea to brood the chicks and were not depressed by high prolactin levels. Plasma prolactin remained low in males captured on arrival and kept until the free-living males finished incubation. In breeders, prolactin secretion increased during the prelaying period when day length decreased. Prolactin levels stayed elevated in males during incubation and in brooding females returning after a 2-month absence at sea. Prolactin values were higher in brooding females than in males ending incubation or returning in late brooding. These levels did not drop after chick loss, and the sexual difference in prolactin values was maintained after breeding failure. In emperor penguins, increased prolactin secretion appears to be triggered around the time of egg laying and continues, driven by an endogenous mechanism, through incubation and brooding until rearing is completed. Prolactin secretion independent of external stimuli may have evolved in pelagic seabirds to maintain parental care despite long absences at sea from the breeding colony.


Probing the interaction of superparamagnetic iron oxide nanoparticles with lipase and their interacting consequences at the molecular level.
Although superparamagnetic iron oxide nanoparticles (SPIONs) are used as carriers for candida rugosa lipase (CRL) in biomedical fields, their interactions and the influences on CRL are still unknown. Consequently, SPIONs were synthesized, characterized, and incubated with CRL to explore their molecular interactions and interacting consequences in this study. The toxic effects of SPIONs on CRL and their molecular interactions were explored through transmission electron microscope, isothermal titration calorimetry, zeta potential measurements, multi-spectroscopic techniques, and biological enzyme activity tests. Results revealed the adsorption of SPIONs to CRL and the reduction of CRL aggregation. The unfolding and loosening of CRL structure as well as the change of secondary structure with the decrease of α-helix were found under SPIONs exposure. Moreover, higher SPIONs concentrations contributed to larger conformational changes and less aggregation of CRL. Meanwhile, it showed that hydrophobic forces were the dominant driving forces in the binding process, with the participation of electrostatic forces. CRL binds to SPIONs with the stoichiometry of 20.7 and the binding constant of 9.9 × 106 M-1. No obvious changes were found in CRL activity due to no interference to Ser-209, Glu-341, and His-449 residues. This study examined the biological compatibility of SPIONs at the molecular level and provided important information about the structure and function of CRL upon binding to SPIONs. Our work might contribute to comprehend the molecular toxicity of SPIONs and the risks of engineered nanoparticles to human health.


Gossypol as an inducer or inhibitor in Spodoptera littoralis larvae.
Gossypol occurs naturally in the pigment glands in cotton. It has a role in protecting cotton plants from insect pests such as bollworms, yet it was not toxic to the cotton leafworm larvae Spodoptera littoralis up to 2-5% concentration in artificial diet or at 125 micrograms/ larva by topical application. The compound inhibited protease and lipid peroxidase activities in larvae with in vitro I50 values of 1.5 X 10(-3)M, and 4.4 X 10(-4)M respectively. When gossypol was fed to Spodoptera larvae, it stimulated the microsomal N-demethylase in vitro. This inductive effect was time-dependent similar to that of phenobarbital. Gossypol stimulates ATPase at lower concentrations and inhibited it at higher concentrations. The I50 for mitochondrial ATPase was 1.7 X 10(-4)M, while the corresponding values for DDT and fenvalerate were 1.1 X 10(-4)M and 7.0 X 10(-4)M respectively. Gossypol at 1.5% concentration in the diet reduced the larval weight to 50% of the control within two days, and increased the duration of each larval stage. The number of eggs and their hatchability was seriously decreased in larvae treated for three consecutive generations. Such an effect can be attributed to the ability of gossypol to interfere with protein bio-synthesis.


Phospholipase A2 and its molecular mechanism after spinal cord injury.
Phospholipases A(2) (PLA(2)s) are a diverse family of lipolytic enzymes which hydrolyze the acyl bond at the sn-2 position of glycerophospholipids to produce free fatty acids and lysophospholipids. These products are precursors of bioactive eicosanoids and platelet-activating factor which have been implicated in pathological states of numerous acute and chronic neurological disorders. To date, more than 27 isoforms of PLA(2) have been found in the mammalian system which can be classified into four major categories: secretory PLA(2), cytosolic PLA(2), Ca(2+)-independent PLA(2), and platelet-activating factor acetylhydrolases. Multiple isoforms of PLA(2) are found in the mammalian spinal cord. Under physiological conditions, PLA(2)s are involved in diverse cellular responses, including phospholipid digestion and metabolism, host defense, and signal transduction. However, under pathological situations, increased PLA(2) activity, excessive production of free fatty acids and their metabolites may lead to the loss of membrane integrity, inflammation, oxidative stress, and subsequent neuronal injury. There is emerging evidence that PLA(2) plays a key role in the secondary injury process after traumatic spinal cord injury. This review outlines the current knowledge of the PLA(2) in the spinal cord with an emphasis being placed on the possible roles of PLA(2) in mediating the secondary SCI.