Changes in sitting posture affect shoulder range of motion.
To assess the effect of slouched sitting on shoulder range of motion (ROM). 30 asymptomatic males aged between 18 and 35 years with no history of shoulder problems within the last 6 months. Shoulder ROMs in flexion and abduction as well as external rotation and internal rotation in 90° of shoulder abduction were measured while the subjects sat in 3 different sitting postures. There were statistically significant mean differences among the 3 sitting postures regarding thoracic kyphosis and shoulder ROMs (p < 0.001). Post hoc analyzes demonstrated significant differences in all comparisons (p < 0.001). Changes in sitting posture affect shoulder ROMs in all directions tested. Greater changes in shoulder ROMs were associated with greater increase in thoracic kyphosis. These findings suggest that even subtle changes in thoracic kyphosis need to be considered during shoulder evaluation.


Conditions favoring retroactive interference between antecedent events (cue competition) and between subsequent events (outcome competition).
Retrieval of a target association (A-B) is often impaired if training of a similar association is interpolated between target training and testing; this is known as retroactive interference. Two experiments, in which rats were used as subjects in a sensory preconditioning preparation, studied the associative nature of retroactive interference between antecedent events (i.e., A and C in the A-B, C-B paradigm) and between subsequent events (i.e., B and C in the A-B, A-C paradigm). With the present preparation, retroactive interference was equally strong between antecedent events and between subsequent events. Moreover, interference occurred only if (1) an association was trained in the interpolated phase and (2) the target and interpolated associations had a common element in a common temporal location.


The Associations Between Children's and Adolescents' Suicidal and Self-Harming Behaviors, and Related Behaviors Within Their Social Networks: A Systematic Review.
Social influences-including the suicidal and self-harming behaviors of others-have been highlighted as a risk factor for suicidal and self-harming behavior in young people, but synthesis of the evidence is lacking. A systematic review of 86 relevant papers was conducted. Considerable published evidence was obtained for positive associations between young people's suicidal and self-harming behavior and that of people they know, with those reporting knowing people who had engaged in suicidal or self-harming behaviors more likely to report engaging in similar behaviors themselves. Findings are discussed in relation to a number of methodological and measurement issues-including the role of normative perceptions-and implications for the prevention of suicidal and self-harming behavior are considered.


Malignancies of the uterine corpus and immunoreactivity score of the DNA "mismatch-repair" enzyme human Mut-S-homologon-2.
We analyzed human Mut-S-Homologon-2 expression in normal endometrial tissue (n = 15) and malignancies of the uterine corpus (n = 40). Human Mut-S-Homologon-2 protein was investigated immunohistochemically on frozen sections, using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). Human Mut-S-Homologon-2 labeling pattern was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. A human Mut-S-Homologon-2 immunoreactivity score (human Mut-S-Homologon-2-IRS: negative 0-1; weak 2-3; moderate 4-6; strong 8-12) for semiquantitative analysis of human Mut-S-Homologon-2 expression is presented. In normal endometrial tissue samples we found weak nuclear immunoreactivity for human Mut-S-Homologon-2 in 67%, whereas the remaining 33% were negative for human Mut-S-Homologon-2 (mean human Mut-S-Homologon-2-IRS 1.25 +/- 1.29). All malignancies of the uterine corpus analyzed revealed moderate to strong nuclear immunoreactivity (mean human Mut-S-Homologon-2-IRS 9.00, +/- 3.16). Human Mut-S-Homologon-2 staining was heterogeneous, with visual differences among individual tumor cells. Expression of human Mut-S-Homologon-2 protein was consistently and strongly upregulated in tumor cells of malignancies of the uterine corpus compared with normal endometrial tissue (human Mut-S-Homologon-2-PP p<0.001; human Mut-S-Homologon-2-IS p<0.001; human Mut-S-Homologon-2-IRS p<0.001). No statistically significant correlation in comparing the labeling patterns for human Mut-S-Homologon-2 with the labeling patterns for Ki-67 (mean percentage of Ki-67-positive tumor cells 22.00% +/- 17.20) was observed in malignancies of the uterine corpus (human Mut-S-Homologon-2-PP p=0.443; human Mut-S-Homologon-2-IS p=0.234; human Mut-S-Homologon-2-IRS p=0.173). Our findings indicate that human Mut-S-Homologon-2 is expressed in normal human endometrial tissue and that expression of human Mut-S-Homologon-2 may be of importance for the genetic stability of malignancies of the uterine corpus in vivo. (J Histochem Cytochem 47:113-118, 1999).


The combined effect of age and body mass index on outcomes in foregut surgery: a regression model analysis of the National Surgical Quality Improvement Program data.
In a parallel demographic phenomenon, the elderly and obese populations will become a larger part of our population and surgical practices. The elderly obese surgical risk profile is not clearly defined, although studies have confirmed their independent negative effect on surgical outcomes. Benign foregut surgery is a relatively common complex procedure performed on this demographic and warrants deeper investigation into outcomes. We investigate the synergistic effect of age and body mass index (BMI) on the outcomes of benign foregut surgery. Data from National Surgical Quality Improvement Program were collected for all patients undergoing foregut surgery from 2005 to 2012. Subjects were over 18 years of age and 16 BMI. Primary and secondary outcomes were 30-day mortality and overall 30-day morbidity, respectfully. Binary logistic regression models were used to assess independent and interactive effects of age and BMI. A total of 19,547 patients had an average age and BMI of 57 and 29.7, respectively. Sample 30-day mortality was 0.32 %. Every 10-year age increase led to a 46 % increased odds of mortality. BMI showed a bimodal distribution with underweight and morbidly obese patients having increased mortality. The effect of BMI only became apparent with increasing age. Both age and BMI are independent predictors of mortality; only older patients experienced the bimodal BMI effect. Therefore, increasing age and BMI have a synergistic effect on outcomes after foregut operations.


Nudges and coercion: conceptual, empirical, and normative considerations.
Given that the concept of coercion remains a central concern for bioethics, Quigley's (Monash Bioethics Rev 32:141-158, 2014) recent article provides a helpful analysis of its frequent misapplication in debates over the use of 'nudges'. In this commentary I present a generally sympathetic response to Quigley's argument while also raising several issues that are important for the larger debates about nudges and coercion. I focus on several closely related topics, including the definition of coercion, the role of empirical research, and the normative concerns at the core of these disputes. I suggest that while a degree of precision is certainly required when deploying the relevant concepts, perhaps informed by empirical data, we need to continue to push these debates towards more pressing normative considerations.


Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.
HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313, and is ongoing. Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47-64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7-49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overdose). No deaths were attributed to adverse events. All deaths in treated patients were due to disease progression. Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability. This treatment is the first US Food and Drug Administration-approved anti-HER2 regimen for metastatic colorectal cancer and is an important new treatment option for chemotherapy-refractory HER2-positive metastatic colorectal cancer. Seagen and Merck & Co.


DEAD-box ATPases as regulators of biomolecular condensates and membrane-less organelles.
RNA-dependent DEAD-box ATPases (DDXs) are emerging as major regulators of RNA-containing membrane-less organelles (MLOs). On the one hand, oligomerizing DDXs can promote condensate formation 'in cis', often using RNA as a scaffold. On the other hand, DDXs can disrupt RNA-RNA and RNA-protein interactions and thereby 'in trans' remodel the multivalent interactions underlying MLO formation. In this review, we discuss the best studied examples of DDXs modulating MLOs in cis and in trans. Further, we illustrate how this contributes to the dynamic assembly and turnover of MLOs which might help cells to modulate RNA sequestration and processing in a temporal and spatial manner.


Assessment of the impact on time to complete medical record using an electronic medical record versus a paper record on emergency department patients: a study.
Electronic medical records are becoming an integral part of healthcare delivery. The goal of this study was to compare paper documentation versus electronic medical record for non-traumatic chest pain to determine differences in time for physicians to complete medical records using paper versus electronic mediums. We also assessed physician satisfaction with the electronic format. We conducted this before-after study in a single large tertiary care academic emergency department. In the 'Before Period', stopwatches determined the time for paper medical recording. In the 'After Period', a template-based electronic medical record was introduced and the time for electronic recording was measured. The time to record in the before and after periods were compared using a two-sided t test. We surveyed physicians to assess satisfaction. We enrolled 100 non-traumatic patients with chest pain in the before period and 73 in the after period. The documentation time was longer using electronic charting, (9.6±5.9 min vs 6.1±2.5 min; p<0.001). 18 of 20 physicians participating in the after period completed surveys. Physicians were not satisfied with the electronic patient recording for non-traumatic chest pain. This is the first study that we are aware of which compared paper versus electronic medical records in the emergency department. Electronic recording took longer than paper records. Physicians were not satisfied using this electronic record. Given the time pressures on emergency physicians, a solution to minimise the charting time using electronic medical records must be found before widespread uptake of electronic charting will be possible.


Biodegradation of Navy N5RL1 carpet dye by Staphylococcus saprophyticus strain BHUSS X3.
Biodegradation of Navy N5RL1, a widely used acidic azo dye in carpet industry, was studied by bacterial strain isolated from the dye-contaminated soil collected from a carpet industry premises located in Bhadohi, Sant Ravidas Nagar and Uttar Pradesh, India. The isolated strain was identified as Staphylococcus saprophyticus BHUSS X3 on the basis of morphological, biochemical and 16S rRNA gene sequencing analysis. The strain BHUSS X3 decolorized 95.7 % of dye (100 mg/l) within 6 h at optimum pH 8, temperature 35 °C, inoculum 4.0 % under static condition during 24 h incubation. The isolated bacterial strain BHUSS X3 can toralate dye concentration upto 1,000 mg/l. The dye degradation metabolites were confirmed by analysis of degraded products using UV-Vis spectrophotometric, HPLC and FTIR technique. The phytotoxicity analysis was also conducted on Phaseolus aureus and enhanced seed germination was recorded.


Barriers to the Use of Long-Acting Injectable Antipsychotics in the Management of Schizophrenia.
Schizophrenia and related disorders remain major disabling conditions, mainly due to antipsychotic treatment resistance and to relapses related to antipsychotic nonadherence. Treatment nonadherence rates are consistently high in long-term patients, but also in first-episode patients with schizophrenia. Long-acting injectable antipsychotics (LAIAs) were mainly developed to improve adherence to treatment and to reduce the rate of relapse and rehospitalization in schizophrenia due to treatment discontinuation. There is favorable clinical evidence, in terms of both efficacy and treatment adherence, that could support higher LAIA prescription rates, especially in patients in early phases of psychotic disorders. Several factors could be hindering wider use of LAIAs, mainly associated with perceptions and attitudes of patients, clinicians, and health managers or policy makers. The main aims of this review are (i) to summarize the existing data on the efficacy and tolerability of LAIAs compared with oral formulations in the management of schizophrenia and related disorders, focusing on the novel, second-generation LAIA options; (ii) to analyze the barriers that exist to the more widespread use of these formulations; and (iii) to discuss possible approaches to overcoming these barriers.


Medical management of arrest disorders of labor: a current overview.
In order to evaluate the risks specifically related to arrest disorders of labor, obstetric management and perinatal outcome were studied in 5399 births selected to exclude risks clearly not caused by abnormal labor. Management was primarily medical--among patients with arrest disorders, the cesarean rate was 13% and the midforceps rate was 4%, and among those having cesarean or midforceps delivery, 96% received prior oxytocin stimulation. Perinatal outcome was assessed by the parameters of mortality, low Apgar scores, admission to the nursery intensive care unit, and neurological abnormality. With medical management, arrest disorders were not associated with an increased risk of the adverse perinatal outcome evaluated in this study. It appears possible to reduce operative rates for arrest disorders of labor safely by more extensive use of medical management.


Safety of selamectin in dogs.
Selamectin is a broad-spectrum avermectin endectocide for treatment and control of canine parasites. The objective of these studies was to evaluate the clinical safety of selamectin for topical use in dogs 6 weeks of age and older, including breeding animals, avermectin-sensitive Collies, and heartworm-positive animals. The margin of safety was evaluated in Beagles, which were 6 weeks old at study initiation. Reproductive, heartworm-positive, and oral safety studies were conducted in mature Beagles. Safety in Collies was evaluated in avermectin-sensitive, adult rough-coated Collies. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Endpoints included clinical examinations, clinical pathology, gross and microscopic pathology, and reproductive indices. Selected variables in the margin of safety and reproductive safety studies were subjected to statistical analyses. Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effects on reproduction in adult male and female dogs. There were no adverse effects in avermectin-sensitive Collies or in heartworm-positive dogs. Oral administration of the topical formulation caused no adverse effects. Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg(-1) (6-12mgkg(-1)) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs.


Ammonia metabolism in normal and portacaval-shunted rats.
Ammonia is generated from a large number of metabolically important reactions. Despite its central importance in whole body nitrogen homeostasis excess ammonia is neurotoxic and its concentration must be kept low. Ammonia generated in most extrahepatic tissues is detoxified by incorporation into glutamine (amide). This glutamine may be used in a number of biosynthetic reactions (e.g. in pyrimidine synthesis). Alternatively, as a means of maintaining nitrogen balance, glutamine may be released to the blood. Resting skeletal muscle is particularly important 1) as a "sink" for removal of blood ammonia, and 2) as a major source of circulating glutamine. However, during vigorous exercise skeletal muscle may become a net contributor of ammonia to the blood. A few tissues and cell types (e.g. lymphocytes, macrophages, enterocytes, colonocytes, thymocytes, fibroblasts, bone) and tumors exhibit marked rates of glutamine utilization. In the kidney, glutamine is an important source of urinary ammonia. Ammonia generated from 1) the breakdown of nitrogenous substances in the gut, and 2) from the use of glutamine as a metabolic fuel in the small intestine, is taken up by the liver wherein it is detoxified by conversion to urea and to a lesser extent, glutamine. Some portal vein glutamine acts as a source of urea nitrogen. Ultimately, however, most excess ammonia nitrogen is detoxified indirectly (via glutamine (blood)----glutamine (small intestine)----ammonia (portal vein) or directly in the liver as urea. Portal-systemic shunting of blood, as occurs in chronic cirrhosis of the liver or following the surgical construction of a portacaval shunt results in portal blood bypassing the normal ammonia detoxification machinery of the liver. Under this condition blood ammonia levels rise markedly, increasing the burden on extrahepatic tissues, such as skeletal muscle, brain, and kidney, in maintaining ammonia homeostasis. The most commonly employed animal model of human liver disease is the rat in which an end-to-side portacaval shunt (PCS) has been surgically constructed. Brain glutamine synthetase activity is not increased in PCS rats and in some areas of the brain there may even be a decrease in activity. The brain glutamine synthetase appears to be working at near maximal capacity. Thus, the PCS rats exhibit profound neurological dysfunction when administered ammonium salts in amounts easily tolerated by normal animals. Because of the limited capacity of brain to remove excess ammonia, a rational approach to the treatment of patients with liver disease should include a regimen directed toward lowering the associated hyperammonemia.


Postoperative management and complications after abdominal surgery in children receiving peritoneal dialysis.
Patients on peritoneal dialysis (PD) may develop PD-related complications that necessitate abdominal surgery. However, when to resume PD and how to prescribe PD fluid after surgery in pediatric patients are unknown. Patients on PD who underwent small-incision abdominal surgery between May 2006 and October 2021 were included in this retrospective observational study. The complications after surgery and characteristics of patients with PD fluid leakage were analyzed. Thirty-four patients were included. They underwent 45 surgical procedures, including 23 inguinal hernia repairs, 17 PD catheter repositioning or omentectomy, and 5 others. The median time to resume PD was 1.0 (IQR, 1.0-3.0) days, and the median PD exchange volume at the initiation of PD after surgery was 25 (IQR, 20-30) ml/kg/cycle. PD-related peritonitis occurred in two patients after omentectomy and one after inguinal hernia repair. There was no PD fluid leakage or hernia recurrence among the 22 patients who had a hernia repair. Peritoneal leakage occurred in 3 of the 17 patients who had PD catheter repositioning or an omentectomy and was treated conservatively. No patients who resumed PD 3 days after small-incision abdominal surgery with less than half of PD volume had fluid leakage. Our findings demonstrated that PD could be resumed within 48 h of inguinal hernia repair with no PD fluid leakage or hernia recurrence in pediatric patients. In addition, resuming PD 3 days after a laparoscopic procedure with less than half of the usual dialysate volume might reduce the risk of PD fluid leakage. A higher resolution version of the Graphical abstract is available as Supplementary information.


[Computed tomography characteristics of isolated caecal ischaemia].
The aims of this review are to describe the main characteristics for the CT diagnosis of isolated caecal ischaemia (ICA) and give details of the differential diagnosis with other conditions with a similar clinical picture. A retrospective study was conducted to review the CT findings of 4 patients diagnosed with ICA in our hospital. The parameters recorded to analyse their characteristics in the CT were: maximum thickness of the caecum wall, the appearance of the peri-caecum fat, presence of free fluid, signs of caecal or portal pneumatosis, the appearance of the caecal appendix, and general signs of the presence of vasculopathy. In all cases it was recorded that there was a thickening of the walls of the blind loop with an abrupt transition between the caecal wall and the walls of the ascending colon wall. In all cases the caecal thickening had a characteristic image in the central area. Signs of caecal pneumatosis were observed in two cases. All of them had an appendix with normal characteristics. The combination of caecal wall thickening with oedematous characteristics, with no changes in the appendix, ileum and colon, suggest the diagnosis of caecal ischaemia, particularly with the presence of pneumatosis.


[Patient safety culture in directors and managers of a health service].
To assess patient safety culture in directors/managers. Cross-sectional descriptive study carried out from February to June 2011 among the executive/managing staff of the Aragón Health Service through semi-structured interviews. A total of 12 interviews were carried out. All the respondents admitted that there were many patient safety problems and agreed that patient safety was a priority from a theoretical rather than practical perspective. The excessive changes in executive positions was considered to be an important barrier which made it difficult to establish long-term strategies and achieve medium-term continuity. This study recorded perceptions on patient safety culture in directors, an essential factor to improve patient safety culture in this group and in the organisations they run.


Temperament characteristics, as assessed by the tridimensional personality questionnaire, moderate the response to sertraline in depressed opiate-dependent methadone patients.
During a randomized, double-blind, placebo controlled study of the effects of sertraline in depressed methadone-maintained patients, 82 completed the tridimensional personality questionnaire (TPQ) to assess whether temperament dimensions can affect treatment-related changes in mood and drug use. Mood outcome significantly differed according to scores on the reward dependence scale (RD). Low RD participants displayed a significantly better mood response to sertraline than high RD participants. Participants with high harm avoidance (HA) scores were more likely to be abstinent at the end of the 12 week trial of sertraline than low HA participants. High persistence (P) participants were less likely to be abstinent at the end of the 12-week trial. These results suggest that temperament dimensions may be important for identifying substance dependent patients more likely to benefit from pharmacological interventions for comorbid depressive disorders.


Open Endoaneurysmorrhaphy of 9-cm Ruptured Popliteal Aneurysm 7 Years after Initial Repair.
A previously repaired right popliteal artery aneurysm via a medial approach with proximal and distal ligation and interval bypass re-presented 7 years after the initial repair with a ruptured 9 × 25.5 cm right popliteal aneurysm. Surgical repair was complex due to the large size of the aneurysm. Technique and management of popliteal aneurysm repair are discussed, along with a review of the current literature. A 58-year-old male with a 3.5 cm popliteal artery aneurysm was initially treated with end-to-end prosthetic bypass and proximal/distal aneurysm ligation from a medial-approach without complication. Seven years later, he presented with a 9-cm popliteal aneurysm rupture. Posterior approach endoaneurysmorrhaphy repair was far more complicated than expected with massive blood loss. Despite this, he was discharged without complication POD #5, but on POD #19 presented with cellulitis and underwent incision and drainage of retained hematoma with cultures positive for Strep dysgalactiae. With appropriate treatment, he was healed in 3 months. Surgical repair of large popliteal aneurysms can be challenging, but continued aneurysmal degeneration is a potential consequence if the sac continues to be pressurized from patent geniculate arteries. Surgical repair of large popliteal artery aneurysms is complex and requires adjunctive techniques to maximize success. A posterior approach is described and the literature reviewed to support recommendations for primary popliteal artery aneurysm repair and repair of large degenerated popliteal artery aneurysms. We recommend primary popliteal artery aneurysm repair from a posterior approach with endoaneurysmorrhaphy and an interposition bypass. For ruptured large popliteal artery aneurysms, there is a high risk of hemorrhage and wound complications. Therefore, we recommend the use of a tourniquet, surgical drain and to consider the collection of intraoperative cultures to guide potential antibiotic management.


Phospholipid changes in synaptic membranes by lipolytic enzymes and subsequent restoration of opiate binding with phosphatidylserine.
A study has been made of the role of phosphatidylserine in stereospecific opiate binding to neural membranes, utilizing specific lipolytic enzymes to attack the lipid. At very low concentrations phospholipase A2 from bee venom will preferentially hydrolyze C22:6-fatty acid; and even after a few percent of the total phosphatidylserine is hydrolyzed, opiate binding is greatly inhibited. The addition of brain phosphatidylserine will restore opiate binding; however, when the inhibition approaches 50% restoration is only partial. Exposure of membranes to phosphatidylserine decarboxylase will partially inhibit opiate binding; and the binding returns to the control level after the addition of phosphatidylserine. The partial inhibition of opiate binding by low concentrations of Triton X-100, which presumably remove lipids, can be partially reversed by phosphatidylserine. The binding of 3H-naloxone, an opiate antagonist, is similar to agonists in its behavior towards phospholipases and phosphatidylserine; however, binding of naltrexone, also an antagonist, is far less responsive. It is concluded that the phosphatidylserine associated with the opiate receptor is the C18:0, 22:6-diacyl form, which is closely associated with protein.


Transient subcutaneous granulomatosis of the upper extremities in Crohn's disease.
Skin lesions occur fairly commonly in patients with Crohn's disease of the colon (14%). Erythema nodosum and pyoderma gangrenosum are the most frequently recognized. Granulomatosis of the skin, continuous with bowel involvement, has been reported. Involvement of the subcutaneous tissue, discontinuous with intestinal disease, is unusual and we wish to report a case of Crohn's disease of the colon complicated by infraepidermal perivascular granulomas of the forearms. The lesions disappeared spontaneously.


Sequencing of modern Lepus VDJ genes shows that the usage of VHn genes has been retained in both Oryctolagus and Lepus that diverged 12 million years ago.
Among mammals, the European rabbit (Oryctolagus cuniculus) has a unique mechanism of generating the primary antibody repertoire. Despite having over 200 VH genes, the VH1 gene, the most D-proximal VH gene, is used in 80-90 % of VDJ rearrangements, while the remaining 10-20 % is encoded by the VHn genes that map at least 100 Kb upstream of VH1. The maintenance of the VHn genes usage in low frequency in VDJ rearrangements has been suggested to represent a relic of an ancestral immunologic response to pathogens. To address this question, we sequenced VDJ genes for another leporid, genus Lepus, which separated from European rabbit 12 million years ago. Approximately 25 VDJ gene sequences were obtained for each one of three Lepus europaeus individuals. We found that Lepus also uses the VHn genes in 5-10 % of its VDJ rearrangements. Our results show that the VHn genes are a conserved ancestral polymorphism that has been maintained in the leporids genome and is being used for the generation of VDJ rearrangements by both modern Lepus and Oryctolagus.


Differential pulse polarographic determination of 2,3-dimercaptosuccinic acid and tin (II) in radiopharmaceuticals.
A differential pulse polarographic procedure was developed for the assay of dimercaptosuccinic acid and tin(II), components of a commercially available pharmaceutical kit for kidney scintigraphy. The method is quantitative and qualitative for both the chelated and unchelated forms of dimercaptosuccinic acid and tin(II) in a mixture of the two.


Spiking Neural Networks applied to the classification of motor tasks in EEG signals.
Motivated by the recent progress of Spiking Neural Network (SNN) models in pattern recognition, we report on the development and evaluation of brain signal classifiers based on SNNs. The work shows the capabilities of this type of Spiking Neurons in the recognition of motor imagery tasks from EEG signals and compares their performance with other traditional classifiers commonly used in this application. This work includes two stages: the first stage consists of comparing the performance of the SNN models against some traditional neural network models. The second stage, compares the SNN models performance in two input conditions: input features with constant values and input features with temporal information. The EEG signals employed in this work represent five motor imagery tasks: i.e. rest, left hand, right hand, foot and tongue movements. These EEG signals were obtained from a public database provided by the Technological University of Graz (Brunner et al., 2008). The feature extraction stage was performed by applying two algorithms: power spectral density and wavelet decomposition. Likewise, this work uses raw EEG signals for the second stage of the problem solution. All of the models were evaluated in the classification between two motor imagery tasks. This work demonstrates that with a smaller number of Spiking neurons, simple problems can be solved. Better results are obtained by using patterns with temporal information, thereby exploiting the capabilities of the SNNs.


Use of cellular metabolomics and lipidomics to decipher the mechanism of Huachansu injection-based intervention against human hepatocellular carcinoma cells.
Huachansu (HCS) injection has been used for the clinical treatment of hepatocellular carcinoma (HCC) patients in China for more than thirty years. However, the underlying mechanisms of HCS injection in inhibiting HCC remains unclear. In this study, we aimed to evaluate the effects of HCS injection on HCC both in vitro and in vivo and to systematically explore the underlying mechanisms of HCS's actions against HCC using an ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS)-based cellular metabolomics and lipidomics approach. MTT and DAPI staining were performed to evaluate the effects of HCS injection on cell proliferation and apoptosis, respectively, in human HepG2 HCC cells with and without HCS treatment. An H22 hepatoma-bearing mouse model was employed to investigate the anti-HCC action of HCS injection in vivo. A UPLC-HRMS-based cellular metabolomics and lipidomics method was employed to characterize cellular metabolite fingerprinting, to identify potential biomarkers associated with the effect of HCS injection on the inhibition of HCC and to explore the anti-HCC mechanisms of HCS injection from the perspective of cellular metabolism. As a result, HCS injection inhibited the proliferation of HepG2 cells and induced their apoptosis. Body weight loss, sarcoma weights and volumes of H22 hepatoma-bearing mice in the HCS treatment group were significantly attenuated compared to those in the model group. Twenty-five biomarkers responsible for the intervention effect of HCS were screened and annotated using UPLC-HRMS-based cellular metabolomics and lipidomics. Among these biomarkers, two cellular metabolites, uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) and glutathione, were confirmed unambiguously using the reference substances. Metabolic pathway analysis revealed that the anti-HCC effects of HCS injection primarily involved the metabolism of glutathione, cysteine and methionine, sphingolipid, fatty acid biosynthesis, amino sugar and nucleotide sugars. As evidenced by western blotting experiments, the changes in UDP-GlcNAc content in response to HCS injection were linked to the inhibition of UDP-GlcNAc pyrophosphorylase 1 (UAP1) expression in HepG2 cells. In conclusion, HCS injection has a curative anti-HCC effect, and a UPLC-HRMS-based cellular metabolomics and lipidomics approach combined with further confirmatory experiments is a promising means of discovering its underlying mechanisms.


Atomic resolution (1.1 A) structure of the ribosome-inactivating protein PD-L4 from Phytolacca dioica L. leaves.
The ribosome inactivating protein PD-L4 from Phytolacca dioica is a N-beta-glycosidase, probably involved in plant defence. The crystal structures of wild type PD-L4 and of the S211A PD-L4 mutant with significantly decreased catalytic activity were determined at atomic resolution. To determine the structural determinants for the reduced activity of S211A PD-L4, both forms have also been co-crystallized with adenine, the major product of PD-L4 catalytic reaction. In the structure of the S211A mutant, the cavity formed by the lack of the Ser hydroxyl group is filled by a water molecule; the insertion of this non-isosteric group leads to small albeit concerted changes in the tightly packed active site of the enzyme. These changes have been correlated to the different activity of the mutant enzyme. This work highlights the importance of atomic resolution studies for the deep understanding of enzymatic properties.


Role of 5-HT1A and 5-HT2 receptors in the aversion induced by electrical stimulation of inferior colliculus.
In addition to being a relay station for auditory pathways in the brainstem, the inferior colliculus may also be part of a brain system commanding defensive behavior. In the present work, we present evidence for the serotonergic modulation of the neural substrate of aversion in this structure. Rats implanted with an electrode-cannula in the inferior colliculus were placed inside a shuttle-box and submitted to a switch-off paradigm. Microinjections of zimelidine, a 5-HT uptake blocker, caused dose-dependent increases in latency and reductions in the frequency of switch-off responses to the inferior colliculus electrical stimulation. The 8-OH-DPAT, a classical 5-HT1A agonist, and alpha-methyl-5-hydroxytryptamine, a highly selective 5-HT2 agonist, injected directly into th e inferior colliculus also produced clear antiaversive effects in a dose-dependent manner. The antiaversive effect produced by alpha-methyl-5-hydroxytryptamine was attenuated by the systemic administration of ketanserin, a preferential 5-HT2 receptor antagonist. These results suggest that serotonergic mechanisms modulate the neural substrates commanding defensive behavior in the inferior colliculus, probably through a cooperative mechanism with the activation of 5-HT1A and 5-HT2 receptors.


The limiting factors and regulatory processes that control the environmental responses of C3, C3-C4 intermediate, and C4 photosynthesis.
Here, we describe a model of C3, C3-C4 intermediate, and C4 photosynthesis that is designed to facilitate quantitative analysis of physiological measurements. The model relates the factors limiting electron transport and carbon metabolism, the regulatory processes that coordinate these metabolic domains, and the responses to light, carbon dioxide, and temperature. It has three unique features. First, mechanistic expressions describe how the cytochrome b6f complex controls electron transport in mesophyll and bundle sheath chloroplasts. Second, the coupling between the mesophyll and bundle sheath expressions represents how feedback regulation of Cyt b6f coordinates electron transport and carbon metabolism. Third, the temperature sensitivity of Cyt b6f is differentiated from that of the coupling between NADPH, Fd, and ATP production. Using this model, we present simulations demonstrating that the light dependence of the carbon dioxide compensation point in C3-C4 leaves can be explained by co-occurrence of light saturation in the mesophyll and light limitation in the bundle sheath. We also present inversions demonstrating that population-level variation in the carbon dioxide compensation point in a Type I C3-C4 plant, Flaveria chloraefolia, can be explained by variable allocation of photosynthetic capacity to the bundle sheath. These results suggest that Type I C3-C4 intermediate plants adjust pigment and protein distributions to optimize the glycine shuttle under different light and temperature regimes, and that the malate and aspartate shuttles may have originally functioned to smooth out the energy supply and demand associated with the glycine shuttle. This model has a wide range of potential applications to physiological, ecological, and evolutionary questions.


[The situation existing in some vital forms of care of ageing citizens in an urban district of Leipzig (author's transl)].
513 old-age pensioners aged 66 to 70 were asked about various aspects of their life in compliance with the "Guideline for interviewing ageing citizens". Special attention was paid to simple vital domestic work and conclusions were drawn with regard to improving the care of ageing citizens.


Food dependence and energetics of freeliving nematodes : I. Respiration, growth and reproduction of Caenorhabditis briggsae (Nematoda) at different levels of food supply.
Some bioenergetic parameters of Caenorhabditis briggsae, a saprophagous nematode, were analysed under different conditions of food availability. Respiration (R) and production rates (P) of experimental animals grown on media of defined bacterial concentrations were measured throughout the life cycle of the species at 20°C. Energetics are expressed in the form of instantaneous rates and as cumulative budgets. 1. Food dependence: The food threshold of the species is defined as A (assimilation)=R, P=zero. The respiratory level of the species is generally high compared to other nematode species and increases only weakly with food availability. Starvation (food densities below threshold) is expressed in a strong reduction in metabolism within 48 h. The food dependence of biosynthetic processes (body growth and egg production) follows a hyperbolic form, which can be described by the Michaelis-Menten function. The relationship P:R changes drastically with availability of food, e.g. the production efficiency for the period of maximal reproduction is 0% at 2·108 cells ml-1 (threshold) and 86% at 1010 cells ml-1. 2. R and P follow different forms of size dependence in the course of the life cycle. The relationship between R and body weight (W) can be described by an allometric function, e.g. at high food density, R=2.8 W 0.75 (R in nl O2 ind-1 h-1; W in μg fresh weight). Weight-specific production rates vary considerably during the life cycle: ±constant in the early larval phase (exponential growth, "g"=1.44 day-1 at 1010 cells ml-1); decreasing in the latter larval phase; peak values shortly after onset of reproduction as a result of both body growth and egg production. 3. Differences in resource allocation at varying food densities are also manifest in cumulative energy budgets, e.g. higher R cum is necessary to achieve the same body size at lower food densities. Size at maturation and egg size are reduced to a different degree at low food densities, indicating bioenergetical constraint and trade-off between metabolic processes.


CYP gene family variants as potential protective factors in drug addiction in Han Chinese.
There is growing evidence that genetic factors also contribute to drug addiction. The human cytochrome P450 has shown special interest because of pharmacokinetic variation in different individuals and populations, which is largely determined by the relevant genes. The present study aimed to investigate the polymorphism of the CYP/addicts relationship. We genotyped 13 tag single-nucleotide polymorphisms (tSNPs) from three genes, including 692 cases and 700 controls. Sequenom MassARRAY RS1000 (Sequenom, Inc., San Diego, CA, USA) was used for SNP genotyping. Statistical analysis of the association between tSNPs and drug addiction was performed using the chi-squared test and SNP Stats software (http://bioinfo.iconcologia.net). The T/T genotype of rs2242480 in CYP3A4 was associated with decreased risk in the recessive model (p = 0.0002). Allele frequency at rs3743484 in CYP1A2 showed significant differences between addicts and controls (p = 0.046; odds ratio = 0.80; 95% confidence interval = 0.65-1.00). In genetic model analyses, the minor C allele of rs3743484 in CYP1A2 was associated with a reduced risk of drug addiction based on analysis using codominant and additive models (p = 0.027 dominant model; p =0.038 additive model). Our findings show that at allelic and genotypic level polymorphisms in CYP3A4 and CYP1A2 are significantly associated with a reduced risk of drug addiction in X'ian Han Chinese individuals. However, this result needs to be confirmed in additional studies. Copyright © 2016 John Wiley & Sons, Ltd.


Maintenance of species integrity in sympatrically occurring Rhinanthus minor and R. serotinus in The Netherlands.
In certain localities, R. minor and R. serotinus grow sympatrically and the flowering-periods overlap. The species hybridize but can still be recognized as distinct taxonomic entities. In the field s x m crosses can be expected to occur more frequently than the reverse, on the basis of flower morphology and pollinator (bumblebee) efficiency. Observation of pollen germination, pollen tube growth, seed set, and seed germination in artificial, reciprocal crosses permits the conclusion that a single m x s pollination leads to more offspring than a single s x m pollination. The two species are isolated from each other by a series of mechanisms none of which is 100% effective by itself, but their combined action comes close to that figure. The leakages in the ethological barrier against hybridization are closed, partly, by physiological mechanisms.


UV mutagenesis in inhibitor depleted conidia of Aspergillus nidulans.
UV treated conidia of a strain of Aspergillus nidulans (meth Gl. biAl) depleted of germination inhibitory substances have been examined for inactivation and mutation induction at groups of suppressor gene loci defining three classes of methionine revertants. An exponential decline in the colony forming ability and quadratic increase in mutation frequency (for each class of revertant) as the incident dose increased were observed. The induced mutation frequency for each class and the loss of colony forming ability of the conidia are greater in the absence than in the presence of these self-inhibitors of germination. However, the relative frequencies of the individual classes of revertants did not differ whether the inhibitory substances were present or not. Liquid holding effects leading to increases in survival and mutation have been observed, but the relative frequencies of the individual revertant classes remain unchanged.


Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer.
Colon cancer is one of the most common malignancies causing death worldwide. It is well known that the cells of the tumor microenvironment contribute to the progression and prognosis of colon cancer. However, the gene alterations and potential remodeling mechanisms in the tumor microenvironment of colon cancer remain largely unknown. In this study, immune scores from the ESTIMATE algorithm were used to discriminate between patients with high or low immune-cell infiltration. There were 42 immune differentially expressed genes (DEGs) of prognostic value identified in this study. Among them, KCNJ5 is a key factor in promoting M2 macrophage recruitment and tumor immune infiltration in colon cancer. These findings may provide novel insights for decoding the complicated interplay between cancer cells and the tumor microenvironment as well as for developing new avenues for therapeutic intervention in colon cancer.


Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on high-sensitivity C-reactive protein levels.
Cardiovascular disease is the leading cause of death among adults in the United States, in Europe, and in much of Asia. Despite advances in primary prevention of coronary artery disease, including early detection and treatment of dyslipidemia, one half of all myocardial infarctions and strokes occur in patients with normal serum cholesterol levels. Observations like this prompt the search for new risk factors and improved identification of individuals at high risk. One proposed risk factor is an elevated level of C-reactive protein (CRP), a marker of inflammation independent of other risk factors. The CRP assay is desirable in terms of standardization and cost. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are indicated for the treatment of dyslipidemias, but data support their protective role against cardiovascular disease beyond their effects on lipids. Statins directly affect inflammatory markers, and nearly 2 dozen randomized studies have demonstrated statins' effects on CRP. Because information regarding the role of CRP in cardiovascular disease is compelling but sometimes contradictory and because the need to reduce CRP levels is unclear, the American Heart Association and the Centers for Disease Control and Prevention presented a panel statement on the topic. Ongoing trials will assist in determining the need to reduce CRP levels to lower cardiovascular risk. An understanding of these issues is important for improving the prediction of cardiovascular risk and for intervening to reduce this risk.


Electronic nose shows promise for detecting early-stage lung cancer.
A simple, non-invasive screening test for lung cancer? Not yet, but investigators are excited about new evidence that signs of lung cancer can actually be picked up from breath samples. The hope is that a simple, inexpensive breath test may eventually hold the key to detecting lung cancer at an early, highly treatable stage.


Effect of sorbed and desorbed Zn(II) on the growth of a green alga (Chlorella pyrenoidosa).
Toxic effect of Zn(II) on a green alga (Chlorella pyrenoidosa) in the presence of sepiolite and kaolinite was investigated. The Zn-free clays were found to have a negative impact on the growth of C. pyrenoidosa in comparison with control samples (without adding any clay or Zn(II)). When Zn(II) was added, the algae in the presence of clays could be better survived than the control samples, which was actually caused by a decrease in Zn(II) concentration in the solution owing to the adsorption of Zn(II) on the clays. When the solution system was diluted, the growth of algae could be further inhibited as compared to that in a system which had the same initial Zn(II) concentration as in the diluted system. This in fact resulted from desorption of Zn(II) from the zinc-contaminated clays, although the effect varied according to the different desorption capabilities of sepiolite and kaolinite. Therefore the adsorption and desorption processes of Zn(II) played an important part in its toxicity, and adsorption and desorption of pollutants on soils/sediments should be well considered in natural eco-environmental systems before their risk of toxicity to aquatic organisms was assessed objectively.


Inequalities in adherence to the continuum of maternal and child health service utilization in Ethiopia: multilevel analysis.
Despite progress made to improve access to child health services, mothers' consistent utilization of these services has been constrained by several factors. This study is aimed at assessing the inequalities in key child health service utilization and assess the role of antenatal care (ANC) on subsequent service use. The analysis of the present study was based on the Ethiopian Demographic and Health Surveys, a nationally representative sample of 10,641 children. A health service utilization score was constructed from the affirmative responses of six key child health interventions associated with the most recent birth: ANC service, delivery of the last child at health facilities, postnatal care services, vitamin A intake, iron supplementation and intake of deworming pills by the index child. A mixed effect Poisson regression model was used to examine the predictors of health service utilization and three separate mixed effect logistic regression models for assessing the role of ANC for continued use of delivery and postnatal care services. The results of mixed effect Poisson regression indicate that the expected mean score of health service utilization was lower among non-first birth order children, older and high parity women, those living in polygamous families and women living in households with no access to radio. The score was higher for respondents with better education, women who had previous experience of terminated pregnancy, residing in more affluent households, and women with experiences of mild to high intimate partner violence. Further analysis of the three key health services (ANC, delivery, and postnatal care), using three models of mixed effect logistic regression, indicates consistent positive impacts of ANC on the continuum of utilizing delivery and postnatal care services. ANC had the strongest effects on both institutional delivery and postnatal care service utilization. The findings implicated that maternal and child health services appear as continuum actions/behavior where utilization of one affects the likelihood of the next service types. The study indicated that promoting proper ANC services is very beneficial in increasing the likelihood of mothers utilizing subsequent services such as delivery and postnatal care services.


Spectacle: An interactive resource for ocular single-cell RNA sequencing data analysis.
Single-cell RNA sequencing has revolutionized ocular gene expression studies. This technology has enabled researchers to identify expression signatures for rare cell types and characterize how gene expression changes across biological conditions, such as topographic region or disease status. However, sharing single-cell RNA sequencing results remains a major obstacle, particular for individuals without a computational background. To address these limitations, we developed Spectacle, an interactive web-based resource for exploring previously published single-cell RNA sequencing data from ocular studies. Spectacle is powered by a locally developed R package, cellcuratoR, which utilizes the Shiny framework in R to generate interactive visualizations for single-cell expression data. Spectacle contains five pre-processed ocular single-cell RNA sequencing data sets and is accessible via the web at OcularGeneExpression.org/singlecell. With Spectacle, users can interactively identify which cell types express a gene of interest, detect transcriptomic subpopulations within a cell type, and perform highly flexible differential expression analyses. The freely-available Spectacle system reduces the bioinformatic barrier for interacting with rich single-cell RNA sequencing studies from ocular tissues, making it easy to quickly identify cell types that express a gene of interest.


CT scanning of bronchioloalveolar carcinoma: specific appearances.
We reviewed CT scans in 38 cases with pathologically proved bronchioloalveolar carcinoma. CT revealed three CT patterns: solitary, pneumonic and diffuse forms. The solitary pattern (22 patients) had a high percentage of air bronchograms (95%), pleural indentation (77%) and spiculation (68%). The pneumonia-like pattern (16 lesions in 10 patients) had air bronchograms in all cases (100%), low attenuation (88%) and protrusion of interlobar fissures (63%). The diffuse form (six patients) had 2 or 3 mm diffuse small nodules scattered throughout the entire lung. CT of bronchioloalveolar carcinoma revealed many findings and was useful in recognizing the tumor distribution and extent. We conclude that CT is helpful for the diagnosis and evaluation of bronchioloalveolar carcinoma.


Radiation therapy for soft tissue sarcoma.
Sarcomas are relatively uncommon tumors of mesenchymal origin. They may arise anywhere within the musculoskeletal system and are typically classified by clinical behavior into benign, borderline, or malignant. This article focuses primarily on the role of radiation for malignant soft tissue sarcoma and selected borderline tumors.


Five-year survival of patients with disseminated nonseminomatous testicular cancer treated with cisplatin, vinblastine, and bleomycin.
Ninety-one patients with disseminated testicular non-seminomas were treated with 3 to 4 cycles of cisplatin, vinblastine, and bleomycin (PVB) induction chemotherapy followed by cisplatin and vinblastine maintenance therapy for 1 year. The follow-up of these patients ranges from 24 to 66 months. Forty-nine (54%) patients achieved complete remission by chemotherapy alone and 14 (15%) were rendered free of tumor by surgery after chemotherapy, for a total complete remission rate of 69%. Three complete responders relapsed within 13 months, and two died. One additional complete responder died of a noncancer-related cause. One of the surgical complete responders relapsed and died. Overall, 58 (64%) patients remain free of disease. The 5-year survival is 95% for complete responders, 32% for partial responders, and 72% overall. This combination regimen has significantly improved the survival of disseminated testicular cancer patients, equaling that of Stage II patients in older literature.


Spatial distribution, ecological risk assessment, and potential sources of heavy metal(loid)s in surface sediments from the Huai River within the Bengbu section, China.
The Huai River is one of the major drinking water resources in Bengbu City of China's eastern Anhui Province. The study focused on extracting information for spatial distributions of heavy metal(loid)s (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) based on the contents of pollutants in 20 surface sediments. Geoaccumulation index and Hakanson potential ecological index were used to calculate the ecological risk of sediment environment in this paper. The I geo results indicated that the sediments were moderately contaminated by Hg and Pb. The potential ecological risk sequence of the metals was Hg > Cd > Pb > Cu > Ni > Cr > Zn > As. Among the metal(loid)s, Hg was the main source of pollution that contributed ∼76% towards the potential ecological risk, followed by Cd. Finally, multivariate statistical analysis methods were conducted to identify the potential causes of pollution and provide basis for environment treatment in Bengbu Reach. The results depicted that Pb may be mainly derived from the traffic emission and manufacturing industry, while Hg may be originated from agricultural emissions.


Effect of climate change on fluxes of nitrogen from the Tovdal River basin, Norway, to adjoining marine areas.
The mass transport model TEOTIL was used to project nitrate (NO3) fluxes from the Tovdal River basin, southernmost Norway, given four scenarios of climate change. Forests, uplands, and open water currently account for 90% of the NO3 flux. Climate scenarios for 2071-2100 suggest increased temperature by 2-4 degrees C and precipitation by 3-11%. Climate experiments and long-term monitoring were used to estimate future rates of nitrogen (N) leaching. More water will run through the terrestrial catchments during the winter but less will run in the spring. The annual NO3 flux from the Tovdal River to the adjoining Topdalsfjord is projected to remain unchanged, but with more NO3 delivered in the winter and less in the spring. Algal blooms in coastal waters can be expected to occur earlier in the year. Major sources of uncertainty are in the long-term fate of N stored in soil organic matter and the impacts of forest management.


Local control, toxicity, and cosmesis in women >70 years enrolled in the American Society of Breast Surgeons accelerated partial breast irradiation registry trial.
The American Society of Breast Surgeons enrolled women in a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System breast brachytherapy device. The present report examined the outcomes in women aged >70 years enrolled in the trial. A total of 1,449 primary early stage breast cancers were treated in 1,440 women. Of these, 537 occurred in women >70 years old. Fisher's exact test was performed to correlate age (≤ 70 vs. >70 years) with toxicity and with cosmesis. The association of age with local recurrence (LR) failure times was investigated by fitting a parametric model. Older women were less likely to develop telangiectasias than younger women (7.9% vs. 12.4%, p = 0.0083). The incidence of other toxicities was similar. Cosmesis was good or excellent in 92% of the women >70 years old. No significant difference was found in LR as a function of age. The 5-year actuarial LR rate with invasive disease for the older vs. younger population was 2.79% and 2.92%, respectively (p = 0.5780). In women >70 years with hormone-sensitive tumors ≤ 2 cm who received hormonal therapy (n = 195), the 5-year actuarial rate of LR, overall survival, disease-free survival, and cause-specific survival was 2.06%, 89.3%, 87%, and 97.5%, respectively. These outcomes were similar in women who did not receive hormonal therapy. Women with small, estrogen receptor-negative disease had worse LR, overall survival, and disease-free survival compared with receptor-positive patients. Accelerated partial breast irradiation with the MammoSite radiation therapy system resulted in low toxicity and produced similar cosmesis and local control at 5 years in women >70 years compared with younger women. This treatment should be considered as an alternative to omitting adjuvant radiotherapy for older women with small-volume, early-stage breast cancer.


Pulsatile low-flow perfusion for enhanced cerebral protection.
We examined the oxygen tension, carbon dioxide tension, and pH in canine brains under profound hypothermia to evaluate the effects of perfusion (circulatory arrest for 1 hour; 25 and 50 mL.kg-1 x min-1 for 2 hours) with and without pulsatile assistance. The effects of pulsatile flow on cerebral blood flow and metabolism were also evaluated in dogs supported by low-flow perfusion (25 mL.kg-1 x min-1) for 2 hours. Profound hypoxia occurred in the brain after 20 to 60 minutes of circulatory arrest. Brain tissue acidosis with hypercapnia was moderated by perfusion at a rate of flow of 50 mL.kg-1 x min-1. Pulsatile low-flow perfusion (25 mL.kg-1 x min-1) moderated cerebral hypercapnia and made the cerebral metabolism aerobic without affecting the total cerebral blood flow and consumption of oxygen.


Skills centre: why we did it, how we did it.
A review of current nurse education research in the UK, and relevant research from the USA has indicated that nursing students are experiencing difficulties in acquiring psychomotor skills. The reasons are possibly quite complex, but student and clinical staff evaluations point to short clinical placements and lack of college preparation as the cause. As a result of this review and a pilot survey, a skills centre has been built at Avon and Gloucestershire College of Health (Avon Site). This paper examines in detail the literature that led to the commissioning of the skills centre and provides practical guidelines on how a skills learning facility can be developed together with information on using a structured, but not confining, approach to teaching psychomotor skills. Further study will demonstrate how the skills centre can be evaluated using qualitative and quantitative research strategies.


Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study.
Ischemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D. This study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014-2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone. From the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61-0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64-0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66-1.22; p = 0.492). In T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.


High pressure magnetic resonance imaging with metallic vessels.
High pressure measurements in most scientific fields rely on metal vessels given the superior tensile strength of metals. We introduce high pressure magnetic resonance imaging (MRI) measurements with metallic vessels. The developed MRI compatible metallic pressure vessel concept is very general in application. Macroscopic physical systems are now amenable to spatially resolved nuclear magnetic resonance (NMR) study at variable pressure and temperature. Metallic pressure vessels not only provide inherently high tensile strengths and efficient temperature control, they also permit optimization of the MRI RF probe sensitivity. An MRI compatible pressure vessel is demonstrated with a rock core holder fabricated using non-magnetic stainless steel. Water flooding through a porous rock under pressure is shown as an example of its applications. High pressure NMR spectroscopy plays an indispensable role in several science fields. This work will open new vistas of study for high pressure material science MRI and MR.


Metabolic tumor volume and total lesion glycolysis as prognostic factors in head and neck cancer: Systematic review and meta-analysis.
The role of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in head and neck cancer (HNC) prognosis is not well established. We conducted a systematic review focusing on MTV and TLG measured by 18 F-FDG positron-emission tomography in HNC. Meta-analyses were developed, estimating hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Eighteen studies were found with a total of 1512 patients. MTV-adjusted analysis had an HR of 4.65 (95% CI = 2.04-10.6) for DFS and 3.89 (95% CI = 1.47-10.30) for OS. TLG-unadjusted analysis had an HR of 3.19 (95% CI = 2.33-4.37) for DFS and 2.48 (95% CI = 1.82-3.39) for OS. TLG-adjusted analysis for DFS obtained an HR of 2.05 (95% CI = 0.96-4.39). MTV and TLG are good prognostic factors in HNC, as high values predict a worse OS and DFS. Given the important information they provide, these parameters may be considered in clinical practice, as they are easily obtainable with current technology.


Providing adult and pediatric care in the same unit: multiple considerations.
As always in acute and critical care, preparation is fundamental to positive patient and family outcomes. Although integration of diverse age populations may occur rarely in a unit, strategic planning should be in place for such occurrences,with relevant competencies considered, addressed, and evaluated on a continuing basis.


Interaction between a photoisomerizable azobenzene compound and alpha-lactalbumin: Spectroscopic and computational simulation studies.
The combination of light and photoresponsive compounds provides a peculiar way of regulating biological systems. Azobenzene is a classical organic compound with photoisomerization properties. Exploring the interactions between azobenzene and proteins can deepen the biochemical applications of the azobenzene compounds. In this paper, the interaction of 4-[(2,6-dimethylphenyl)diazenyl]-3,5-dimethylphenol with alpha-lactalbumin was investigated by UV-Vis absorption spectra, multiple fluorescence spectra, computer simulations, and circular dichroism spectra. Most critically, the interaction differences between proteins and the trans- and cis-isomer of ligands have been analyzed and compared. Results showed that both isomers of ligands were bound to alpha-lactalbumin to form ground state complexes and statically quenched the steady-state fluorescence of alpha-lactalbumin. The van der Waals forces and hydrogen bonding dominated the binding; the difference is that the binding of the cis-isomer to alpha-lactalbumin is more rapidly stabilized, and the binding strength is greater than the trans-isomer. These binding differences were modeled and analyzed by molecular docking and kinetic simulations, and we found that both isomers bind through the hydrophobic aromatic cluster 2 of alpha-lactalbumin. However, the bent structure of the cis-isomer is more closely aligned with the construction of the aromatic cluster and may have contributed to the above differences.


Human microvessel endothelial cell isolation and vascular graft sodding in the operating room.
We have evaluated multiple factors inherent to an operating room-compatible endothelial cell procurement and sodding procedure. Microvessel endothelial cell isolations have been performed on fat tissue obtained from over 140 patients with a 100% success rate. Liposuction-derived fat was optimal with respect to cell yield, and isolation time. The devices and equipment used were acceptable to the operating room and the complete cell procurement procedure was successful even in the hands of personnel with minimal training. Fat digestion was achieved using crude clostridial collagenase, with an average cell yield of 1 x 10(6) microvessel endothelial cells/gm of fat. Evaluation of this procedure with canine fat using an operating room acceptable procedure resulted in a 100% procurement success rate requiring 1.5 hours (+/- .5 hrs) for completion of the fat isolation, and cell isolation procedure. Microvessel EC could subsequently be used in graft seeding or sodding techniques to establish endothelial cell monolayers on vascular grafts. Our results indicate that one person with minimal cell isolation background can reproducibly isolate large quantities of sterile autologous endothelial cells in the operating room for immediate use in endothelial cell seeding/sodding procedures.


Recombination of integral and peripheral protein fractions from human red cell membrane with homologous lipids.
Integral and peripheral protein fractions from human red cells membranes were recombined with a total red cell lipid extract and with homologous lipids in varying mixtures, by dialysis from 2-chlorethanol solutions. The 2 protein fractions were compared for lipid binding capacity and for selectivity towards individual lipids.


Development of a Clinical Risk Score Prediction Tool for 5-, 9-, and 13-Year Risk of Dementia.
Although researchers have devoted substantial efforts, money, and time to studying the causes of dementia and the means to prevent it, no effective treatment exists yet. Identifying preclinical risk factors of dementia could help prevent or delay its progression. To develop a point risk score prediction model of dementia. This study used a large UK population-based prospective cohort study conducted between March 13, 2006, and October 1, 2010. Data analysis was performed from June 7 to September 15, 2021. Individual analyses of time end points were concluded at the first dementia diagnosis during the follow-up period. The data were split into training and testing data sets to separately establish and validate a prediction model. Outcomes of interest included 5-, 9-, and 13-year dementia risk. Least absolute shrinkage and selection operator and multivariate Cox proportional hazards regression models were used to identify available and practical dementia predictors. A point risk score model was developed for the individual prediction of 5-, 9-, and 13-year dementia risk. A total of 502 505 participants were selected; the population after exclusions for missing data and dementia diagnosis at baseline was 444 695 (205 187 men; mean [SD] age, 56.74 [8.18] years; 239 508 women; mean [SD] age, 56.20 [8.01] years). Dementia occurrence during the 13 years of follow-up was 0.7% for men and 0.5% for women. The C statistic of the final multivariate Cox proportional hazards regression model was 0.86 for men and 0.85 for women in the training data set, and 0.85 for men and 0.87 for women in the testing data set. Men and women shared some modifiable risk and protective factors, but they also presented independent risk factors that accounted for 31.7% of men developing dementia and 53.35% of women developing dementia according to the weighted population-attributable fraction. The total point score of the risk score model ranged from -18 to 30 in men and -17 to 30 in women. The risk score model yielded nearly 100% prediction accuracy of 13-year dementia risk both in men and women. In this diagnostic study, a practical risk score tool was developed for individual prediction of dementia risk, which may help individuals identify their potential risk profile and provide guidance on precise and timely actions to promote dementia delay or prevention.


Periparturient stocking density affects lying and ruminating behavior and one-week-calf performance of Holstein cows.
This study aimed to investigate the effect of stocking density on the behavior, productivity, and metabolism of periparturient Holstein cows as well as calf performance. A total of 48 periparturient cows were randomly assigned into three groups at 28 days (±3 days) before their expected calving date. The stocking densities of the groups, relative to the standard cubicle and feed bunk number, were i) 80% (13 cows), ii) 100% (16 cows), and iii) 120% (19 cows). Lying and rumination behavior was recorded using electronic data loggers and HR-Tags from d -21 ("d-" means days before calving) until the calving date, d 0. Lying time was assessed to determine the diurnal total hours spent lying per day. Rumination time was averaged in 2 hours interval periods over 24 hours during the experimental period. Cows in the 80% group spent more time lying and ruminating between d -21 and d -7 and tended to ruminate more between d -14 and d 0. Calcium levels tended to be higher for cows in the 80% group, no other observable differences were found in monitored blood parameters. Moreover, 3.5% fat corrected milk and energy corrected milk yields were higher in 80% group in the first month of lactation. No other observable differences were found in the yield and composition of colostrum and milk in the first 10 months of lactation. The growth and performance of calves in the first week of life was not affected by stocking density of the dams. We concluded that lower stocking density may increase lying and ruminating behavior of prepartum Holstein cows. However, this did not translate into improved productivity and metabolism.


Two polycyclic aromatic hydrocarbon o-quinone reductases from a pyrene-degrading Mycobacterium.
Polycyclic aromatic hydrocarbon (PAH) o-quinone reductase (PQR) plays a crucial role in the detoxification of PAH o-quinones by reducing them to catechols. Two constitutive PQRs were found in cell extracts of a pyrene-degrading Mycobacterium sp. strain PYR100. The enzymes had an activity towards 9,10-phenanthrenequinone (PQ) and/or 4,5-pyrenequinone (PyQ), and the relative amounts varied with the pH of the culture media. PQR1, containing an FAD cofactor, was a monomer (20.1 kDa), and PQR2, with no flavin cofactor, was a homodimer (26.5 kDa subunits). There was no homology between the N-terminal sequences of PQR1 and PQR2. Dicumarol and quercetin inhibited PQR2 more strongly than PQR1. PQR1 had much lower specificity constants (k(cat)/K(m), 10(5)M(-1)s(-1)) for menadione (0.80) and PQ (5.19) than PQR2 (13.9 for menadione and 176 for PQ). Additionally, PQR2 exhibited a broad substrate specificity with high specificity constants for 1,4-naphthalenequinone, 1,2-naphthalenequinone, and PyQ.


A 53,000-Da esterase in Strongylocentrotus purpuratus semen is derived from phagocytic cells, not sperm.
Semen from the sea urchin Strongylocentrotus purpuratus contains sperm and a small volume (1%) of phagocytes, which often contain degraded sperm. A 53,000-Da esterase in the semen is inhibited by diisopropyl fluorophosphate, but not by soybean trypsin inhibitor (STI). Differential centrifugation experiments now reveal that 70% of the esterase activity (formerly described as a sperm protease precursor; Levine and Walsh, 1980) is associated with the phagocytes, which sediment more rapidly than the sperm. The 53K esterase is also present in spawned ovaries and testes. However, as previously reported, the sperm do contain an STI-inhibitable protease as shown by the digestion of [14C]lysozyme. Intact sperm exhibit STI-inhibitable hydrolytic activity toward N-alpha-[3H]benzoyl-L-arginine ethyl ester [3H]BAEE), but crude homogenates do not until they are extracted at pH 2.5 and fractionated by ion exchange chromatography. Although not obtained in pure form, the protease activity appears to migrate with a molecular weight of 20,000 (gel filtration). The protease and the esterase differ markedly in acid stability. After preincubation at pH 2.5 the protease still hydrolyzes [3H]BAEE, while the esterase is irreversibly inactivated. This last observation may explain an earlier interpretation (A. E. Levine and K. A. Walsh, 1980, J. Biol. Chem. 255, 4814-4820) that the 53K enzyme dissociated at pH 2.5 into two unequal subunits, one of which was the active protease. Since it has been shown that the contaminating phagocytes contribute most of the esterase activity of the semen, the occurrence of even a small number of nonsperm cells cannot be ignored in future investigations of sperm enzymes.


Enhanced fear acquisition in individuals with evening chronotype. A virtual reality fear conditioning/extinction study.
Circadian rhythms have received increasing attention within the context of mental disorders. Evening chronotype has been associated with enhanced risk to develop anxiety and post-traumatic stress disorder (PTSD). The classical fear conditioning paradigm is a powerful tool to reveal key mechanisms of anxiety and PTSD. We used this paradigm to study the neurocognitive basis of the association between chronotype and fear responses in healthy humans. 20 participants with evening chronotype and 20 controls (i.e., intermediate chronotype) completed a 2-day Pavlovian fear learning and extinction virtual reality task. Participants received fear conditioning, and extinction learning on day 1. Extinction memory recall was tested on day 2. To address interactions between chronotype and time of day of the fear conditioning, and extinction performance, half of the participants were tested in the morning, and the other half in the evening. Skin conductance response (SCR) and subjective fear ratings were measured as primary outcomes. Chronotype was established via the morningness-eveningness questionnaire (MEQ). We found an overall higher SCR for fear acquisition in participants with the evening chronotype profile, compared to controls. Moreover, the higher the MEQ scores -indicative of less eveningness - the lower the SCR was. No effects of chronotype were found for extinction and extinction recall. The higher vulnerability of the evening chronotype for anxiety and related disorders may thus be explained by enhanced fear acquisition of this group.


Preliminary effectiveness of online opioid overdose and naloxone administration training and impact of naloxone possession on opioid use.
Despite the demonstrated value of opioid overdose education and naloxone distribution (OEND) programs, uptake and utilization remains low. Accessibility to OEND is limited and traditional programs may not reach many high-risk individuals. This study evaluated the effectiveness of online opioid overdose and naloxone administration education and the impact of naloxone possession. Individuals with self-reported illicit use of opioids were recruited via Craigslist advertisements and completed all assessments and education online via REDCap. Participants watched a 20-minute video outlining signs of opioid overdose and how to administer naloxone. They were then randomized to either receive a naloxone kit or be given instructions on where to obtain a kit. Effectiveness of training was measured with pre- and post-training knowledge questionnaires. Naloxone kit possession, overdoses, opioid use frequency, and treatment interest were self-reported on monthly follow-up assessments. Mean knowledge scores significantly increased from 6.82/9.00 to 8.22 after training (t(194)=6.85, p <0.001, 95% CI[1.00, 1.81], Cohen's d=0.85). Difference in naloxone possession between randomized groups was significant with a large effect size (p <0.001, diff=0.60, 95% CI[0.47, 0.73]). A bidirectional relationship was found between naloxone possession and frequency of opioid use. Overdoses and treatment interest were similar across possession status. Overdose education is effective in online video format. Disparity in naloxone possession across groups indicates barriers to obtaining naloxone from pharmacies. Naloxone possession did not influence risky opioid use or treatment interest and its impact on frequency of use warrants further investigation. Clinitaltrials.gov-NCT04303000.


The role of dorsal premotor area in reaction task: comparing the "virtual lesion" effect of paired pulse or theta burst transcranial magnetic stimulation.
We compared the effect on reaction times of transient interference with function of the dorsal premotor cortex (PMd) using a pair (25-ms interval) of transcranial magnetic stimulation (TMS) pulses with long-term interference produced by a new repetitive TMS paradigm known as "theta burst stimulation" (TBS). Pairs of TMS pulses over left PMd increased choice but not simple reaction times of the right hand if given at the onset of the reaction interval. There was no effect of stimulation over right PMd or at a midline parietal control site (Pz). In contrast, TBS over either left or right PMd increased choice RTs of both hands for at least 5-10 min after the end of TBS. Pairs of TMS pulses over left PMd also increased error rates whereas TBS had no effect on error rates despite the effect on RTs. We suggest that TBS leads to widespread changes in activity and more complex effects on behaviour than expected from the paired pulse TMS and conclude that transient and long-term forms of interference with function may influence behavioural tasks in subtly different ways.


Left main coronary artery stenosis following mediastinal irradiation.
The association of mediastinal radiation therapy and coronary artery disease has been documented over the past three decades. This report describes a case of left main coronary artery stenosis eight years after radiation therapy in a 27-year-old woman. The patient was a young woman with no risk factors for coronary artery disease who had development of new-onset angina at rest. At coronary arteriography, the patient was found to have a tight ostial left main stenosis. The association of mediastinal radiation therapy with fixed and vasospastic coronary artery disease is reviewed. With many patients treated by radiation therapy now surviving their thoracic malignancies, an enlarging young population may be susceptible to the early development of ischemic heart disease.


Systemic extrapancreatic lesions associated with autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) is often associated with systemic extrapancreatic lesions. We studied 31 cases of AIP to clarify the diversity of associated systemic extrapancreatic lesions and the differences between AIP with and without systemic extrapancreatic lesions. The clinical features and courses were compared by age, sex, and blood chemistry between those with and without systemic extrapancreatic lesions. In addition, we reviewed the available literature on systemic extrapancreatic lesions with AIP. Seven of the 31 cases of AIP had associated systemic extrapancreatic lesions, which were diagnosed simultaneously with AIP; however, 1 case presenting with various extrapancreatic lesions was diagnosed independently of the AIP lesion. Patients with systemic extrapancreatic lesions needed maintenance steroid therapy for AIP in 4 cases and systemic extrapancreatic lesions in 2 cases; the ratio of cases requiring maintenance steroid therapy was significantly higher among those with systemic extrapancreatic lesions (6/8) than those without (7/23). There were no significant differences between groups with regard to age, sex, extent of narrowing of the main pancreatic duct, and enlargement of the pancreas. gamma-globulin, IgG, and IgG4 levels were significantly higher in patients with AIP with systemic extrapancreatic lesions than those without. The systemic extrapancreatic lesions associated with AIP found in the literature were Sjögren syndrome, ulcerative colitis, retroperitoneal fibrosis, sialadenitis, thyroiditis, and idiopathic thrombocytopenic purpura. The results of this study suggest that, when encountering a case of AIP with elevated levels of gamma-globulins, IgG, and IgG4, an effort should be made to detect other systemic extrapancreatic abnormalities and initiate steroid administration.


Blinking suppresses the neural response to unchanging retinal stimulation.
Blinks profoundly interrupt visual input but are rarely noticed, perhaps because of blink suppression, a visual-sensitivity loss that begins immediately prior to blink onset. Blink suppression is thought to result from an extra-retinal signal that is associated with the blink motor command and may act to attenuate the sensory consequences of the motor action. However, the neural mechanisms underlying this phenomenon remain unclear. They are challenging to study because any brain-activity changes resulting from an extra-retinal signal associated with the blink motor command are potentially masked by profound neural-activity changes caused by the retinal-illumination reduction that results from occlusion of the pupil by the eyelid. Here, we distinguished direct top-down effects of blink-associated motor signals on cortical activity from purely mechanical or optical effects of blinking on visual input by combining pupil-independent retinal stimulation with functional MRI (fMRI) in humans. Even though retinal illumination was kept constant during blinks, we found that blinking nevertheless suppressed activity in visual cortex and in areas of parietal and prefrontal cortex previously associated with awareness of environmental change. Our findings demonstrate active top-down modulation of visual processing during blinking, suggesting a possible mechanism by which blinks go unnoticed.


Effects of finite carbon nanotube length on sidewall addition of fluorine atom and methylene.
Density functional computations (PBE and B3LYP) in conjunction with 3-21G and 6-31G basis sets are used to determine the energy of fluorine atom and CH(2) addition to the sidewall of (5,5) C(30+10)(n)()H(20) (n = 0, 1, 2.18) carbon nanotube slabs. A pronounced oscillation of the addition energy is found for fluorine atom addition, while oscillations are significantly damped for carbene addition due to the insertion into CC bonds. [structure: see text]


The Sublaterodorsal Tegmental Nucleus Functions to Couple Brain State and Motor Activity during REM Sleep and Wakefulness.
Appropriate levels of muscle tone are needed to support waking behaviors such as sitting or standing. However, it is unclear how the brain functions to couple muscle tone with waking behaviors. Cataplexy is a unique experiment of nature in which muscle paralysis involuntarily intrudes into otherwise normal periods of wakefulness. Cataplexy therefore provides the opportunity to identify the circuit mechanisms that couple muscle tone and waking behaviors. Here, we tested the long-standing hypothesis that muscle paralysis during cataplexy is caused by recruitment of the brainstem circuit that induces muscle paralysis during REM sleep. Using behavioral, electrophysiological, and chemogenetic strategies, we found that muscle tone and arousal state can be decoupled by manipulation of the REM sleep circuit (the sublaterodorsal tegmental nucleus [SLD]). First, we show that silencing SLD neurons prevents motor suppression during REM sleep. Second, we show that activating these same neurons promotes cataplexy in narcoleptic (orexin-/-) mice, whereas silencing these neurons prevents cataplexy. Most importantly, we show that SLD neurons can decouple motor activity and arousal state in healthy mice. We show that SLD activation triggers cataplexy-like attacks in wild-type mice that are behaviorally and electrophysiologically indistinguishable from cataplexy in orexin-/- mice. We conclude that the SLD functions to engage arousal-motor synchrony during both wakefulness and REM sleep, and we propose that pathological recruitment of SLD neurons could underlie cataplexy in narcolepsy.


A preliminary test of Pearson's formula for estimation of height of Sri Lankans.
The validity of Pearson's formula for estimation of height from the length of bones, has not been tested for Sri Lankan populations. Such a validation was attempted on 27 male cadavers using the recumbent heel to vertex height, and the physiological femoral length. The standard Pearson's formula was found to contain an error in the tested population. Based on these findings, a new formula was therefore evolved where S = 27.48 + 3.08F (as opposed to S = 81.306 + 1.88F in the standard formula). The new formula will be tested further on a larger sample, with a view to making further indicated adjustments.


[Surgical tactics in drainage of the thoracic duct].
A method of finding the thoracic lymphatic duct, paracentetic method of its opening, method of the fixation of the catheter, ensuring a longlasting withdrawal of the lymph, are described.


Detection mechanism and the outlook of metal-organic frameworks for the detection of hazardous substances in milk.
Milk has a high nutritional value. However, milk is easily contaminated in the production, processing, and storage processes, which harms consumers' health. Therefore, the harmful substances' detection in milk is important. Metal-organic frameworks (MOFs) have proven high potential in food safety detection due to their unique porous structure, large effective surface area, large porosity, and structural tunability. This article systematically describes the detection mechanism of fluorescence, electrochemical, colorimetric, and enzyme-linked immunosorbent assay based on MOFs. The progress of the application of MOFs in the detection of antibiotics, harmful microorganisms and their toxins, harmful ions, and other harmful substances in milk in recent years is reviewed. The structural tunability of MOFs enables them to be functionalized, giving the ability to be applied to different detection methods or substances. Therefore, MOFs can be used as an advantageous sensing material for detecting harmful substances in the complex environment of milk.


Visualization of UV and ECD spectra of E&Z isomers of N-(4'-Hydroxy-cinnamoyl)- 5- hydroxyanthranilic acid.
Avenanthramides are secondary metabolites most prominently found in oat (Avena sativa.L). These are amides of cinnamoyl-anthranilic acids derivatives. Due to their fascinating biological potential, these compounds have attracted the curiosity of chemists. Herein, the theoretical background of the electronic transition in UV-Vis and ECD spectra of the (E&Z) isomers of N-(4'-Hydroxy-cinnamoyl)- 5- hydroxyanthranilic acid was studied. The physical mechanism of the electron transfer process during light excitation is more intuitively described with two-dimensional and three-dimensional visualization methods. The characteristics of the UV-Vis spectrum were extended to the electron-hole conceptualization and the charge transfer process was described with charge difference density (CDD) and transition density matrix (TDM). The interaction mechanism between light and molecule in ECD is quantitatively revealed by the transition electric dipole moment, transition magnetic dipole moment, and their tensor product. A well-defined UV -Vis spectrum was obtained for the E isomer whereas the ECD spectrum for the Z isomer.


Analysis of academic publishing output among 1634 successful applicants in the 2011-2018 neurosurgery residency match.
Research productivity is a key criterion for applicant selection reported by residency program directors. Research volume reported on neurosurgery residency applications has risen steadily over the past decade. Perform retrospective bibliographic searches of successful applicants who matched into U.S. neurosurgery residency programs from 2011 to 2018, and assess the relationship between academic publishing and residency placement. Gender, MD/PhD status, U.S. News research ranking of medical school, and international medical graduate status (IMG) were determined for 1634 successful applicants from 2011 to 2018. Indexed publications before and after the start of residency were tabulated by Scopus®. Publication counts were stratified by first author, basic/clinical science, case reports, reviews, or other research. We then compared publishing trends across demographic variables and match cohorts. Average pre-residency publications increased from 2.6 [1.7, 3.4] in 2011 to 6.5 [5.1, 7.9] in 2018. Men, PhD-holders, Top 20 and Top 40 U.S. medical school graduates, and IMGs had higher pre-residency publication counts overall. After stratifying by match cohort, however, there was no significant effect of gender on pre-residency publications. Applicants matching into residency programs with highly ranked affiliated hospitals had significantly higher pre-residency publications. Publishing volume of successful neurosurgery applicants in the U.S. has risen recently and is associated with the stature of matched residency programs. Given the gap between verifiable and claimed research on residency applications, attention is needed to objectively evaluate research credentials in the selection process. The impending phase out of USMLE step 1 scores may increase emphasis on academic productivity.


Centenary of Christfried Jakob's discovery of the visceral brain: an unheeded precedence in affective neuroscience.
The benchmark discovery of the cingulate gyrus as a brain structure receiving stimuli from muscles and viscera (proprioception and interoception) is traced to a 1907/1908 article by neuropathologist Christfried Jakob. Further, the involvement of the mamillary bodies, anterior thalamic nucleus, cingulate cortex and hippocampus in the circuitry of the emotive brain (i.e. all elements of the 1937 'circuit of Papez') was published by Jakob in his 1911 and 1913 monographs on human and comparative neuroanatomy. In those works, Jakob also described the thalamocingulate projection, commonly attributed to a 1933 study by Le Gros Clark and Boggon, and introduced the term 'visceral brain', commonly attributed to a 1949 paper by MacLean. The present article includes the first English translations of Jakob's relevant passages, which incontrovertibly document his chronological priority in discovering the visceral brain and some of its key constituent elements.


Potentiation of antibody responses by specific IgM: specificity and thymus dependency.
Modulation of antibody responses induced by IgM directed against the immunogen was investigated. When IgM directed against ox erythrocytes (ORBC) was given together with trinitrophenyl (TNP)-ORBC, the subsequent antibody response to the carrier, ORBC, as well as the response to the hapten, TNP, was potentiated. In contrast, IgG with carrier specificity inhibited both responses. The hapten-specific potentiation was found in both direct and indirect plaques, and was antigen-dose dependent, i.e., no potentiation was found with the lowest antigen doses. The response to 2,4-dinitrophenyl (DNP)-labeled proteins was potentiated by a monoclonal IgM with specificity for the hapten. The effects were observed both in primary and secondary responses. One strict requirement for IgM potentiation to occur was observed. The determinant against which potentiation was achieved had to be physically linked to the determinant against which the IgM was directed, be it hapten or carrier determinants. Thus, irrelevant IgM-antigen complexes were incapable of potentiating the responses. Similar specificity requirements were found for IgG induced suppression of antibody responses. Experiments with nude mice and their euthymic littermates showed that IgM potentiation of antibody production is T-cell dependent. Furthermore, passive transfer of carrier-primed spleen cells together with antigen challenge suggests that IgM potentiation of secondary antibody responses is dependent on specific carrier-primed immune T cells.