Patterns of aggression in the personality structure of depressed patients.
The personality characteristics of 208 depressed patients of both sexes were studied by means of a Swedish personality inventory--the KSP--when the patients had recovered from the depressive syndrome. The patients in the study were divided into unipolars, bipolars, neurotic-reactive and "unspecified", i.e. those patients who did not meet the criteria for inclusion in any of the aforementioned groups. Female patients scored higher on variables of anxiety and psychasthenia and male patients scored higher on variables indicating distance preference and hostility. Several traits, in particular those reflecting aggression-out and hostility-out, appeared to be negatively correlated with age, whereas inhibition of aggression appeared to be positively related with age. Bipolar patients scored slightly differently from unipolars in many variables but none of the differences was significant. Neurotic-reactive patients distinguished themselves from the other in variables of aggression-out. Several interrelations between different personality characteristics and aspects of aggression have been investigated. Significant correlation could be shown between aspects of aggression and socialization, impulsiveness and aspects of anxiety. A positive correlation was shown between inhibition of aggression and social desirability, and both variables were shown to correlate with age. It is concluded that the difference in inhibition of aggression between "endogenous" and "non-endogenous" patients found in earlier studies might be due to a difference in age, and to the influence of social desirability.


Comparative defense-associated responses in salmon skin elicited by the ectoparasite Lepeophtheirus salmonis.
Susceptibility among salmonids to the ectoparasite Lepeophtheirus salmonis is related to inflammatory reactions at the site of parasite attachment. Salmon from two susceptible (Salmo salar, Oncorhynchus keta) and one resistant (Oncorhynchus gorbuscha) species were exposed to adult L. salmonis. After 24 and 48h, skin samples directly below the attachment site and at non-attachment sites were assessed for transcriptomic profiles of select innate defense genes. Abrasion of the skin permitted comparisons between abrasion-associated injury and louse-associated injury. Infection responses were consistently higher than those caused by abrasion. Temporal patterns of expression were evident in all species for the transcription factor CCAAT/enhancer-binding protein β (C/EBP-β), the cytokine interleukin-6 (IL-6) and the enzyme prostaglandin D synthase (PGDS) at attachment sites. O. gorbuscha was the highest responder in a number of genes while there was an absence of C-reactive protein (CRP) gene expression in S. salar and O. keta, indicating an altered acute-phase response. Moreover, O. keta displayed distinct interleukin-8 (IL-8) and serum amyloid P (SAP) responses. Impaired genetic expression or over-expression in these pathways may be evidence for species-specific pathways of susceptibility to the parasite. At L. salmonis attachment sites, reduced expression compared to non-attachment sites was observed for C/EBP-β (S. salar), CRP (S. salar), SAP (S. salar, O. gorbuscha, O. keta), PGDS (S. salar, O. gorbuscha, O. keta), and major histocompatibility class II (MH class II, S. salar), suggesting local immunodepression.


Postoperative delirium after hip surgery is a potential risk factor for incident dementia: A systematic review and meta-analysis of prospective studies.
Although a few trials have explored the relationship between postoperative delirium (POD) and incident dementia in patients with hip surgery, the numbers of participants in each study are relatively small. Thus, we performed a meta-analysis to examine whether POD after hip surgery is a risk factor for incident dementia. Six prospective cohort studies investigating the development of incident dementia in patients with POD after hip surgery were retrieved from PubMed, Embase, and the Cochrane Library. We performed a pairwise meta-analysis using fixed- and random- effect models. POD significantly increased the risk of incident dementia and cognitive decline (overall odds ratio [ORs] = 8.957; 95 % confidence interval [CI], 5.444-14.737; P < 0.001 in fixed-effects model; overall ORs = 8.962; 95 % CI, 5.344-15.029; P < 0.001 in random-effects model). A publication bias was not evident in this study. Our meta-analysis revealed that POD after hip surgery is a risk factor for incident dementia. Early identification of cognitive function should be needed after surgery and appropriate prevention and treatment for dementia will be required, especially in cases with POD.


Clinical characteristics and results of noninvasive tests in 60 diabetic patients after acute myocardial infarction.
Diabetic patients who survive myocardial infarction have more similarities than differences when compared with nondiabetic patients. Silent myocardial infarctions were not more common in the diabetic population. The higher percentage of women among diabetic patients with infarction has been well recognized. Of the primary risk factors, hypertension was more common in diabetic patients. Clearly, a history of ischemic heart disease was more common in diabetic patients. The course in the coronary care unit was similar for both the diabetic and nondiabetic patient groups. Likewise, there were no striking differences in left ventricular ejection fractions or results of 24-hour Holter monitoring between the groups. The fact that a higher percentage of diabetic patients were excluded from taking the limited activity treadmill test, primarily because of angina after infarction, may account for the observation that the percent of patients with an ischemic response to exercise and the percent with exercise-induced ventricular ectopy did not differ between diabetic and nondiabetic groups.


Medical student changes in self-regulated learning during the transition to the clinical environment.
Self-regulated learning (SRL), which is learners' ability to proactively select and use different strategies to reach learning goals, is associated with academic and clinical success and life-long learning. SRL does not develop automatically in the clinical environment and its development during the preclinical to clinical learning transition has not been quantitatively studied. Our study aims to fill this gap by measuring SRL in medical students during the transitional period and examining its contributing factors. Medical students were invited to complete a questionnaire at the commencement of their first clinical year (T0), and 10 weeks later (T1). The questionnaire included the Motivated Strategies for Learning Questionnaire (MSLQ) and asked about previous clinical experience. Information about the student's background, demographic characteristics and first clinical rotation were also gathered. Of 118 students invited to participate, complete paired responses were obtained from 72 medical students (response rate 61%). At T1, extrinsic goal orientation increased and was associated with gender (males were more likely to increase extrinsic goal orientation) and type of first attachment (critical care and community based attachments, compared to hospital ward based attachments). Metacognitive self-regulation decreased at T1 and was negatively associated with previous clinical experience. Measurable changes in self-regulated learning occur during the transition from preclinical learning to clinical immersion, particularly in the domains of extrinsic goal orientation and metacognitive self-regulation. Self-determination theory offers possible explanations for this finding which have practical implications and point the way to future research. In addition, interventions to promote metacognition before the clinical immersion may assist in preserving SRL during the transition and thus promote life-long learning skills in preparation for real-world practice.


Global coronary arteries spasm in a young patient.
Coronary artery spasm is a transient narrowing of coronary arteries that slows or stops blood flow through the artery. We present a 42-year-smoker man without any medical problem who developed syncope. Coronary angiography revealed diffuse significant narrowing of proximal left anterior descending artery (LAD), 90% osteal stenosis of large obtuse marginal (OM), 90% diffuse narrowing of proximal right coronary artery (RCA), which was relieved by intracoronary administration of nitrate. He was discharged on calcium channel blockers and nitrates but one month later developed syncope again and died. Multivessel coronary artery spasm should be considered in young smoker patients without any other coronary risk factors who present with syncope.


Stability of clinical outcome measures in rheumatoid arthritis patients with stable disease defined on the basis of the EULAR response criteria.
Natural variation also known as measurement error is assessed in individuals in "steady state." The study aimed to examine inter-visit variations in clinical outcome measures in rheumatoid arthritis (RA) patients with stable disease defined on the basis of the EULAR response criteria. Two hundred thirty-three RA patients with stable disease defined as a change in Disease Activity Score (DAS28-CRP) ≤0.6 between two consecutive visits were identified in the Danish rheumatology registry for biological treatment (DANBIO). Clinical data from a single set of such two visits were extracted for each patient. Using the Bland-Altman method, lower and upper 95 % limits of agreement (LLoA; ULoA) between the consecutive assessments and the bias were calculated for each measure. Associations were characterized by Pearson's r-values and standard errors of estimation (SEE). The mean change in DAS28-CRP was 0.0 ± 0.3. Agreements between the assessments were close on the group level but poor on the individual level. For example, LLoA; ULoA [bias] for patient global assessment (0-100) was -28.3; 29.7 [0.7], for fatigue (0-100) -38.1; 36.3 [-0.9] and for 28 swollen joint count -3.3; 3.3 [0.0]. Inter-visit differences were poorly explained by the baseline values (r [SEE] ranging from 0.15 [12.6] for fatigue to 0.58 [1.4] for 28 tender joint count) and by changes in other outcome variables. In conclusion, outcome measures fluctuated substantially and unpredictably in individual RA patients considered in steady state. The observed between-visit differences may be interpreted to reflect natural variation or measurement error that should be taken into account when monitoring patients in the daily clinic.


Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints.
One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent. www.ClinicalTrials.gov, identifiers NCT05307549 and NCT05307575.


Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats.
The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.


Motor delay - An early and more common "red flag" in girls rather than boys with autism spectrum disorder.
Autism and intellectual disability may coincide and be preceded by global developmental delay or by motor delay. Motor delay in the context of global developmental delay is an initial "red flag" for ASD, with added risk in girls. To assess early developmental milestones in girls with ASD as compared to diagnosed boys, considering prematurity risk. Developmental milestones in a cohort of 467 children with ASD - diagnosed at mean age of 3.4 years (SD = 2.2) - were analyzed according to gender and prematurity risk. 111 girls (24 %), 356 boys (76 %), presented with motor milestones acquisition grossly within the normal range. However, there was a shift towards acquisition of walking being at the later end of the norm range, with this shift being more prominent in girls. 60 % of girls and 47 % of boys with ASD had motor delay and 49 % of girls and 36 % of boys had global developmental delay. The extent of the delays was greater in the prematurity subgroup. Global delay of early milestones occurred in half of children with ASD and in 60 % of girls with ASD. Delayed acquisition of independent walking is relatively more common in girls subsequently diagnosed with ASD.


A manoeuvre to cover exposed metal using a de-epithelialised "turn-over" fasciocutaneous flap.
This paper describes a technical manoeuvre to accommodate an exposed metal implant used in the treatment of a fracture of the tibia within a "turn-over" de-epithelialised fasciocutaneous flap. The need for such a procedure in this particular case is commented upon. A discussion is also included on the nature of the blood supply to the integument based on available information.


Transient appearance of circulating tumor DNA associated with de novo treatment.
The limitation of circulating tumor DNA (ctDNA) is its inability to detect cancer cell subpopulations with few or no dying cells. Lung cancer patients subjected to the EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment were prospectively collected, and ctDNA levels represented by the activating and T790M mutations were measured. The first data set (21 patients) consisting of samples collected in the period from before initiation of EGFR-TKI to at least 2 weeks after initiation: the ctDNA dynamics generally exhibited a rapid decrease and/or a transient increase. In 4 patients, we detected a transient increase of ctDNA bearing activating mutations not identified in biopsy samples. ctDNA with the same genotypical pattern was identified in 7 out of the 39 patients of the second data set intended to include samples until the onset of disease progression. In 6 of the 7 patients, this unique ctDNA appeared in the early period after treatment initiation, and did not reappear even after disease progression or chemotherapy. In another patient, similar ctDNA appeared upon radiation therapy. The identification of ctDNA with a unique genotype indicates the presence of cancer cell subpopulations that normally contain few or no dying cells, but generate dead cells because of the treatment.


Anatomical bases of the surgical dissection of the interatrial septum: a morphological and histological study.
The interatrial septum (IAS) can be dissected to resect pulmonary tumors invading the left atrium. The aim of this study was to describe the dissected structures, and to expose the benefits, the limits, and the embryologic reasons of such dissection. We dissected the IAS of 11 fresh, non-embalmed human hearts. The dissected structures were described and the length and depth of the dissection were measured. A histological study was performed in four other fresh hearts to identify and differentiate between dissectible and non-dissectible structures. The dissection was performed through a fatty tissue located between two muscular walls. The depth limit of the IAS dissection was identified as the limbus of the fossa ovalis and the muscular roof of the atria. The section of the latter doubles the depth of the dissection at the level of the upper pulmonary veins. Mean length of the dissected IAS was 77 mm (55-90). Mean depths of the IAS were 41 mm (35-50) at the level of the left upper pulmonary vein, 27 mm (12-35) between the upper and lower pulmonary veins, and 14 mm (8-20) at the level of the left inferior pulmonary vein The surgical dissection of the IAS is performed through the septum secundum that appears as an infold of the atrial wall. The length of the resectable left atrial cuff reaches a mean of 40 mm at the level of the upper pulmonary vein.


Changes in nucleic acid content in aging Drosophila bipectinata.
DNA content decreases during first 20 and 25 days of survival in male and female flies of Drosophila bipectinata respectively. RNA as well as RNA/DNA content show a similar trend in males while in females both rise significantly during the first 5 to 10 days of survival followed by a steady decline till day 25. The study suggests that decreasing nucleic acid content of aging D. bipectinata is accompanied by the decline in protein synthesizing capacity.


Augmentation of uridine diphosphate glucuronyltransferase activity in rat liver by adenosine 3',5'-monophosphate.
The role of cyclic adenosine 3',5'-monophosphate (cAMP) in the regulation of rat liver bilirubin uridine diphosphate glucuronyltransferase (UDP-GT) was studied. Augmentation of UDP-GT activity was obtained by cAMP, but not by 3'-AMP. A single administration of glucagon initiated a rapid but limited increase in enzyme activity, which reached a maximum after 2 hr. Similar augmentation of the hepatic enzyme was produced by injection of N6,O2-dibutyryl cAMP. The nucleotide is the mediator for UDP-GT augmentation by glucagon. The injection of glucagon led within 20 min to a 40-fold increase in the concentration of cAMP. The augmentation of UDP-GT activity by glucagon or dibutyryl cAMP was fully inhibited by actinomycin D. A second stimulation of liver by glucagon or dibutyryl cAMP 4 hr after the first injection, produced a new increase of UDP-GT activity.


Highly cooperative ion-pair recognition of potassium cyanide using a heteroditopic ferrocene-based crown ether-trifluoroacetylcarboxanilide receptor.
A heteroditopic receptor having crown ether and trifluoroacetylcarboxanilide groups selectively recognizes both potassium and cyanide ions in acetonitrile with an association constant of as high as Ka = 1.9 x 10(7) M(-1) through a highly cooperative ion-pair interaction, resulting in two orders of magnitude enhancement in the binding affinity.


Ultrafast Ultrasound Imaging in Pediatric and Adult Cardiology: Techniques, Applications, and Perspectives.
Ultrasound techniques currently used in echocardiography are limited by conventional frame rates. Ultrafast ultrasound imaging is able to capture images at frame rates up to 100 times faster compared with conventional imaging. Specific applications of this technology have been developed and tested for clinical use in pediatric and adult cardiac imaging. These include ultrafast Doppler or vector flow imaging, shear wave imaging, electromechanical wave imaging, and backscatter tensor imaging. The principles of these applications are explained in this manuscript with illustrations on how these methods could be applied in clinical practice. Ultrafast ultrasound has great clinical potential in the assessment of cardiac function, in noninvasive hemodynamic analysis, while providing novel techniques for imaging coronary perfusion and evaluating rhythm disorders.


The advantage of attending ants and gall aggregation for the gall wasp Andricus symbioticus (Hymenoptera: Cynipidae).
Gall clusters of Andricus symbioticus secrete a sweet and sticky food attractive to ants. An ant exclusion experiment demonstrated the selective advantage of attending ants and gall aggregation for A. symbioticus. This gall wasp interacts with the gall-attending ants only through the host plant. Evolution of this symbiotic relationship seems to be associated with gall aggregation.


Correction of restricted extraocular muscle motility in surgical management of strabismus in graves' ophthalmopathy.
To compare the success rates for strabismus surgery designed to correct limitation of duction with surgery designed to correct deviation in patients with Graves' ophthalmopathy. Retrospective nonrandomized comparative trial. One hundred thirty-seven patients with Graves' ophthalmopathy who had undergone at least one extraocular muscle surgery were divided into two groups: those whose first surgery occurred before June 1997 (control group) and those whose first surgery occurred in June 1997 or thereafter (case group). Extraocular muscle surgery primarily directed at either correcting deviation (control group) or correcting limitation of ductions (case group). Postoperative deviations in the primary position were measured in prism diopters 30 to 180 days after surgery. A postoperative deviation of less than 5 diopters was considered a successful surgical outcome. Patients undergoing strabismus surgery specifically designed to correct limitation of duction achieved a 74% success rate compared with a 44% success rate in the control group (P < 0.01). Furthermore, the rate of reoperation in this group was only 27% compared with 44% in the control group (P < 0.04). Compared with surgery aimed primarily at the correction of deviation, extraocular muscle surgery tailored to address restriction of ductions in patients with Graves' ophthalmopathy is associated with improved surgical success of initial realignment and with a lower rate of reoperation


Antigen-specific augmentation of delayed-type hypersensitivity by a humoral factor in the culture supernatant of immune spleen cells.
Supernatants were harvested from a 24-hr culture of immune mouse spleen cells and erythrocyte antigens. Delayed footpad reactions to such heterologous erythrocytes were augmented antigen specifically when the supernatants were transferred a few hours before immunization of recipients. The augmentation factor(s) contained in the supernatants may exert its effect on the induction phase of delayed-type hypersensitivity.


Near-infrared light device can improve intravenous cannulation in critically ill children.
Vascular access in critically ill children can be a real challenge for medical staff. To evaluate the effectiveness of a near-infrared light vein-viewing device for critically ill children, 60 pediatric inpatients were enrolled in a randomized prospective observation trial for intravenous cannulation. The patients' demographic data, mean time required to find the first available vessel, first-attempt success rate, mean number of attempts per patient, and the total time taken on the attempts per patient were compared. Less time was required to find the first available vessel in the near-infrared light device group compared with the control group (126.37 vs. 383.61 seconds; p = 0.027). In addition, the near-infrared light device group had a fewer number of attempts compared with the control group (median 1 vs. 2; p = 0.004), and also a shorter total time of attempts per patient compared with the control group (186.16 vs. 497.23 seconds; p = 0.014). The use of a near-infrared light vein-viewing device for vascular access in critically ill children can decrease the total medical time and cost.


Mesothelioma after crocidolite exposure during gas mask manufacture.
Of 199 persons employed in the manufacture and handling of Canadian military gas mask canisters containing pure crocidolite, 1939 to 1942, by the end of 1975, 56 had died, 120 were still alive, and 23 could not be traced. Nine (16%) of the deaths were probably due to malignant mesothelioma, six involving the peritoneum. The risk of mesothelioma after crocidolite exposure appears to be many times greater than that after chrysotile.


Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers.
Alpha-synuclein aggregation is thought to be a key event in the pathogenesis of synucleinopathies. Although different alpha-synuclein alterations and modifications have been proposed to be responsible for early aggregation steps, the mechanisms underlying these events remain unclarified. Alpha-synuclein is a small protein localized to synaptic terminals and its intrinsic structure has been claimed to be an important factor for self-oligomerization and self-aggregation. Alpha-synuclein expression studies in cell cultures have demonstrated that posttranslational modifications, such as phosphorylation, oxidation, and sumoylation, are primarily involved in alpha-synuclein aggregation. Furthermore, in the last few years accumulating evidence has pointed to alternative splicing as a crucial mechanism in the development of neurodegenerative disorders. At least three different alpha-synuclein isoforms have been described as products of alternative splicing. Two of these isoforms (alpha-synuclein 112 and alpha-synuclein 126) are shorter proteins with probably altered functions and aggregation propensity. The present review attempts to summarize the data so far available on alpha-synuclein structure, posttranslational modifications, and alternative splicing as possible enhancers of aggregation.


Terminal deletion of chromosome 6q.
Terminal deletions of chromosome 6q are rare. Clinical features associated with 6q terminal deletion syndrome include psychomotor retardation, seizures, hypotonia, short neck, and facial abnormalities, as well as various case-specific anomalies. Here, we describe a girl with 6q terminal deletion syndrome and unusually short stature. Features of previously described patients are also summarized.


New matrix metalloproteinase inhibitors based on γ-fluorinated α-aminocarboxylic and α-aminohydroxamic acids.
Matrix metalloproteinases (MMPs) are involved in a number of physiological as well as pathological processes such as atherosclerosis and tumorigenesis, where an up-regulation of MMPs is predominant. Fluorinated analogues of the hydroxamate-based non-peptidic broad-spectrum MMP inhibitor (MMPI) CGS 27023A were synthesized and inhibition potencies for MMP-2 and MMP-9 in the nanomolar range were measured using fluorimetric in vitro assays. The inhibition potencies of the herein reported fluorinated MMPIs were comparable or even superior in some cases to their non-fluorinated analogues. In contrast to the lead structure, both enantiomers of fluorinated MMPs were almost equally potent. Modelling studies suggest that the core α-amino hydroxamic acid residues appear to influence the relative potencies via specific inhibitor-peptidase interactions, including short fluorine-hydrogen contacts, within the enzyme's pockets. The binding of the essential hydroxamate group to the zinc ion is rather unaffected by the rest of the molecule. In contrast, the corresponding α-aminocarboxylic acid derivatives are 10(3) times less potent or were even inactive.


RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.
To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.


Saving time and money in biomedical publishing: the case for free-format submissions with minimal requirements.
Manuscript preparation and the (re)submission of articles can create a significant workload in academic jobs. In this exploratory analysis, we estimate the time and costs needed to meet the diverse formatting requirements for manuscript submissions in biomedical publishing. We reviewed 302 leading biomedical journals' submission guidelines and extracted information on the components that tend to vary the most among submission guidelines (the length of the title, the running title, the abstract, and the manuscript; the structure of the abstract and the manuscript, number of items and references allowed, whether the journal has a template). We estimated annual research funding lost due to manuscript formatting by calculating hourly academic salaries, the time lost to reformatting articles, and quantifying the total number of resubmissions per year. We interviewed several researchers and senior journal editors and editors-in-chief to contextualize our findings and develop guidelines that could help both biomedical journals and researchers work more efficiently. Among the analyzed journals, we found a huge diversity in submission requirements. By calculating average researcher salaries in the European Union and the USA, and the time spent on reformatting articles, we estimated that ~ 230 million USD were lost in 2021 alone due to reformatting articles. Should the current practice remain unchanged within this decade, we estimate ~ 2.5 billion USD could be lost between 2022 and 2030-solely due to reformatting articles after a first editorial desk rejection. In our interviews, we found alignment between researchers and editors; researchers would like the submission process alignment between researchers and editors; researchers would like the submission process to be as straightforward and simple as possible, and editors want to easily identify strong, suitable articles and not waste researchers' time. Based on the findings from our quantitative analysis and contextualized by the qualitative interviews, we conclude that free-format submission guidelines would benefit both researchers and editors. However, a minimum set of requirements is necessary to avoid manuscript submissions that lack structure. We developed our guidelines to improve the status quo, and we urge the publishers and the editorial-advisory boards of biomedical journals to adopt them. This may also require support from publishers and major international organizations that govern the work of editors.


Small-cell lung cancer presenting as diabetes insipidus and Cushing's syndrome.
Small-cell lung cancer presenting with a combination of cranial diabetes insipidus and Cushing's syndrome secondary to ectopic adrenocorticotropin (ACTH) secretion is very rare and has only been described previously in one case report Our patient was a 49 year old man, in whom the initial presenting features of small-cell lung cancer were cranial diabetes insipidus secondary to pituitary metastases and severe hypokalaemia resulting from ectopic ACTH hormone secretion. This case is a remarkable example of the complex metabolic endocrine manifestations of small-cell lung cancer.


Post-therapeutic needle biopsy in patients with hepatocellular carcinoma is a useful tool to evaluate response to proton irradiation.
Proton beam therapy is safe and more effective than conventional radiation therapy for the local control of nodular hepatocellular carcinoma (HCC). However, evaluating therapeutic response by imaging is not accurate during the early post-irradiation period. Therefore, we examined whether the histopathological study of biopsy specimens obtained at 3 weeks after irradiation can be used to more accurately assess therapeutic response. Fifteen HCC lesions from 13 patients were treated with proton beam irradiation. Tissue biopsy samples were obtained using abdominal ultrasound-guided percutaneous fine-needle aspiration from the center of the tumor before, 3 weeks after and 1 year post-proton therapy. The specimens were examined after staining with hematoxylin-eosin (HE) and a MIB-1 antibody. MIB-1 labeling indices (LI) before treatment were 13.0 ± 8.5% (mean ± SD; range, 0.6-27.0), whereas those 3 weeks after proton therapy were significantly reduced to 3.2 ± 2.4% (range, 0.6-8.9) (P < 0.05). Although the tumor size was reduced, we did not observe a reduction in tumor blood flow by dynamic computed tomography or degenerative changes by HE. All lesions that displayed reduced MIB-1 LI at 3 weeks post-proton treatment were ultimately diagnosed as complete response at 1 year after treatment. In contrast, one case with increased MIB-1 LI at 3 weeks had significant tumor size progression at 1 year post-treatment. The percutaneous fine-needle aspiration biopsy of HCC is a safe and useful tool that can be used to evaluate the response to proton irradiation. In particular, MIB-1 LI may provide additional information to assess the therapeutic response of HCC during the early post-irradiated period.


The cognitive P40, N60 and P100 components of somatosensory evoked potentials and the earliest electrical signs of sensory processing in man.
Selective attention tasks involving random sequences of electrical stimulation of fingers were designed to compare cerebral potentials to identical stimuli (for example to the left thumb) when they are 'infrequent target' signals or 'frequent-neglected' signals in the series. The experiments were carried out in normal adult subjects. The early SEP components were analyzed for the earliest cortical electrical sign of information processing stages. Two new components, P40 (with onset at 26 msec) and N60, precede the processing positivity P100 which may be more significant in somatosensory processing than the negativities recorded in auditory or visual tasks.


Production of recombinant proteins using multiple-copy gene integration in high-cell-density fermentations of Ralstonia eutropha.
We have previously reported the development of a novel protein expression system based on Ralstonia eutropha. In this study we report on the influence of gene copynumber on recombinant protein expression in R. eutropha. We compare recombinant gene stability and expression levels of chromosomal integration with a plasmid-based expression system. Single, double, and triple copies of a gene encoding organophosphohydrolase (OPH), an enzyme prone to inclusion-body formation in E. coli, were integrated into the R. eutropha chromosome. A linear increase between the concentration of soluble, active OPH and gene copynumber was found. Using a triple-copy integrant, we were able to produce approximately 4.3 g/L of OPH in a high-cell-density fermentation. This represents the highest titer reported to date for this enzyme, and is approximately 30 times greater than expression levels reported in E. coli.


Adrenergic response of splanchnic arteries from cirrhotic patients: role of nitric oxide, prostanoids, and reactive oxygen species.
Peripheral and splanchnic vasodilatation in cirrhotic patients has been related to hyporesponsiveness to vasoconstrictors, but studies to examine the vascular adrenergic response provide contradictory results. Hepatic arteries from cirrhotic patients undergoing liver transplantation and mesenteric arteries from liver donors were obtained. Segments 3 mm long from these arteries were mounted in organ baths for testing isometric adrenergic response. The concentration-dependent contraction to noradrenaline (10(-8) to 10(-4) M) was similar in hepatic and mesenteric arteries, and prazosin (alpha 1-adrenergic antagonist, 10(-6) M), but not yohimbine (alpha 2-adrenergic antagonist, 10(-6) M), produced a rightward parallel displacement of this contraction in both types of arteries. Phenylephrine (alpha 1-adrenergic agonist, 10(-8) to 10(-4) M) and clonidine (alpha 2-adrenergic agonist, 10(-8) to 10(-4) M) also produced concentration-dependent contractions that were comparable in hepatic and mesenteric arteries. The inhibitor of cyclooxygenase meclofenamate (10(-5) M), but not the inhibitor of nitric oxide synthesis N(w)-nitro-l-arginine methyl ester (l-NAME, 10(-4) M), potentiated the response to noradrenaline in hepatic arteries; neither inhibitor affected the response to noradrenaline in mesenteric arteries. Diphenyleneiodonium (DPI; 5 x 10(-6) M), but neither catalase (1000 U/ml) nor tiron (10(-4) M), decreased the maximal contraction for noradrenaline similarly in hepatic and mesenteric arteries. Therefore, it is suggested that, in splanchnic arteries from cirrhotic patients, the adrenergic response and the relative contribution of alpha 1- and alpha 2-adrenoceptors in this response is preserved, and prostanoids, but not nitric oxide, may blunt that response. Products dependent on NAD(P)H oxidase might contribute to the adrenergic response in splanchnic arteries from control and cirrhotic patients.


Has joint involvement lessened in Kawasaki disease?
Kawasaki disease (KD) is an acute systemic vasculitis affecting medium-sized arteries, particularly the coronary arteries. Classic diagnosis is based in prolonged fever and different clinical features, including acute arthritis. Our objective is to determine the prevalence of arthritis at the moment of the diagnosis, the response to intravenous immunoglobulin infusion and the relation with cardiac findings. Retrospective study through review of medical records of 42 patients with KD from 1988 to 2013. Demographic, clinical, laboratory variables and treatment were reviewed. Male sex was predominant (57%). Fever (100%), exanthema (92,9%), conjunctivitis (78,6%), oropharingeal changes (76,2%), cervical lymphadenopathy (71,4%), edema (52,4%) and peripheral desquamation (46,3%) were reported. Eight patients presented ecocardiography alterations (ectasia and aneurism). Acute articular involvement was reported in 7 (16%) patients, including oligoarticular (57%), monoarticular (29%) and polyarticular (14%) patterns. All patients had elevation of acute phase reactants with neutrophilia (57%) and hypoalbuminemia (71,5%), but showed a good therapeutic response to intravenous immunoglobulin, without sequelaes. Sixteen patients had incomplete KD nine males, with 100% of fever exanthema (75%), conjunctivitis (56%) and 50% of cervical lymphadenopathy. Whereas oropharingeal changes and edemas was described in 44% and 25% of them. Four patients with incomplete KD had coronary artery abnormalities. Acute arthritis was an uncommon finding (16%) and resulted in no sequelae. Maybe the treatment with intravenous immunoglobulin and aspirin prevents the development of articular abnormalities and then leading to a decrease in its follow-up requierement by reumathologist. The cardiovascular sequelae, mainly incomplete KD, remains determining its prognosis. The presence of articular involvement seems not to have influence over cardiac involvement.


Preterm birth and risk of epilepsy in Swedish adults.
To determine whether preterm birth is associated with epilepsy in a national cohort of adults aged 25-37 years. We conducted a national cohort study of 630,090 infants born in Sweden from 1973 through 1979, including 27,953 born preterm (<37 weeks), followed from 2005 to 2009 for 1) hospitalization for epilepsy and 2) outpatient and inpatient prescription of antiepileptic drugs. Epilepsy diagnoses and medication data were obtained from all hospitals and pharmacies throughout Sweden. We found a strong association between preterm birth and epilepsy that increased by earlier gestational age. After adjusting for fetal growth and potential confounders, odds ratios for hospitalization for epilepsy were 4.98 (95%confidence interval [CI] 2.87-8.62) for those born at 23-31 weeks, 1.98 (95% CI 1.26-3.13) for those born at 32-34 weeks, and 1.76 (95% CI 1.30-2.38) for those born at 35-36 weeks, relative to those born full-term (37-42 weeks). A similar but slightly weaker trend was observed for the association between preterm birth and antiepileptic drug prescription. These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors. These findings suggest that preterm birth, including late preterm birth, is strongly associated with epilepsy in Swedish adults aged 25-37 years. This association was independent of fetal growth and was not mediated by cerebral palsy or other comorbidities.


Geographical Text Analysis: A new approach to understanding nineteenth-century mortality.
This paper uses a combination of Geographic Information Systems (GIS) and corpus linguistic analysis to extract and analyse disease related keywords from the Registrar-General's Decennial Supplements. Combined with known mortality figures, this provides, for the first time, a spatial picture of the relationship between the Registrar-General's discussion of disease and deaths in England and Wales in the nineteenth and early twentieth centuries. Techniques such as collocation, density analysis, the Hierarchical Regional Settlement matrix and regression analysis are employed to extract and analyse the data resulting in new insight into the relationship between the Registrar-General's published texts and the changing mortality patterns during this time.


A new concept for ferredoxin-NADP(H) oxidoreductase binding to plant thylakoids.
During the evolution of photosynthesis, regulatory circuits were established that allow the precise coupling of light-driven electron transfer chains with downstream processes such as carbon fixation. The ferredoxin (Fd):ferredoxin-NADP(+) oxidoreductase (FNR) couple is an important mediator for these processes because it provides the transition from exclusively membrane-bound light reactions to the mostly stromal metabolic pathways. Recent progress has allowed us to revisit how FNR is bound to thylakoids and to revaluate the current view that only membrane-bound FNR is active in photosynthetic reactions. We argue that the vast majority of thylakoid-bound FNR of higher plants is not necessary for photosynthesis. We furthermore propose that the correct distribution of FNR between stroma and thylakoids is used to efficiently regulate Fd-dependent electron partitioning in the chloroplast.


Organoamine-induced isomerism of calixarene-based complexes: from 1D to 2D.
Two isomers of the calixarene-based cobalt complex [Co4Cl(TC4A)(BCPT)2]- (H4TC4A = p-tert-butylthiacalix[4]arene; H2BCPT = 3,5-bis (4'-carboxy-phenyl)-1,2,4-triazole) were obtained under the solvothermal conditions with tetramethylammonium/tetraethylammonium hydroxide (CIAC-236) and triethylamine (CIAC-237). Single crystal X-ray diffraction reveals that CIAC-236 has a 1D zigzag aggregate constructed by bridging the shuttlecock-like Co4-TC4A secondary building units (SBUs) with two pairs of opposite V-shaped BCPT ligands while CIAC-237 possesses a 2D layer assembly with each Co4-TC4A SBU bonded by four BCPT ligands in a same direction (clockwise or counterclockwise), which indicates that different shapes of the organoamines lead to different assembly of the BCPT ligands and the formation of different extended aggregates. For comparison, only the 1D structure ([Fe4Cl(TC4A)](BCPT)2]-, CIAC-238) was obtained for the iron complexes with all these three organoamines, which would be attributed to different property and coordination of iron element. Magnetic properties of all these three compounds were studied.


Rare FBXO18 variations and risk of schizophrenia: Whole-exome sequencing in two parent-affected offspring trios followed by resequencing and case-control studies.
Rare variations are suggested to play a role in the genetic etiology of schizophrenia; to further investigate their role, we performed a three-stage study in a Japanese population. In the first stage, we performed whole-exome sequencing (WES) of two parent-affected offspring trios. In the second stage, we resequenced the FBXO18 coding region in 96 patients. In the third stage, we tested rare non-synonymous FBXO18 variations for association with schizophrenia in two independent populations comprising a total of 1376 patients and 1496 controls. A rare frameshift variation (L116fsX) in the FBXO18 gene was recurrently identified by WES in both trios. Resequencing FBXO18 coding regions, we detected three rare non-synonymous variations (V15L, L116fsX, and V1006I). However, there were no significant associations between these rare FBXO18 variations and schizophrenia in the case-control study. Our present study does not provide evidence for the contribution of rare non-synonymous FBXO18 variations to the genetic etiology of schizophrenia in the Japanese population. However, to draw a definitive conclusion, further studies should be performed using sufficiently large sample sizes.


Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation.
Recently it has become clear that more potent methods for DNA vaccine delivery need to be developed to enhance the efficacy of DNA vaccines. In vivo electroporation has emerged as a potent method for DNA vaccine delivery. In a mouse model, we evaluated the CD8(+) T lymphocyte response to a prostate cancer DNA vaccine encoding prostate-specific antigen (PSA) after intradermal electroporation. A significantly increased gene expression (100- to 1000-fold) and higher levels of PSA-specific T cells, compared to DNA delivery without electroporation, was demonstrated. Interestingly, investigation of a panel of different electroporation conditions showed that only some conditions that induce high levels of gene expression additionally induced cellular immunity. This suggests that electroporation parameters should be carefully optimized, not only to enhance transfection efficiency, but also to enhance the immune response to the vaccine. This study demonstrates the applicability of intradermal electroporation as a delivery method for genetic cancer vaccines and other DNA vaccines relying on antigen-specific T cell induction.


Predictive factors for the outcome of a multidisciplinary pain rehabilitation programme on sick-leave and life satisfaction in patients with whiplash trauma and other myofascial pain: a follow-up study.
To evaluate the effects of a multidisciplinary rehabilitation programme on sick-leave, coping resources and life satisfaction in whiplash patients and other pain patients. Forty patients suffering from symptoms after whiplash trauma and 33 patients with musculoskeletal pain in the neck or back were recruited for this study. Ninety-seven consecutive patients admitted to the Department of Neurosurgery with cervical pain, cervical disc herniation or symptomatic spondylosis served as a control group. Decreased coping resources and poorer life satisfaction were observed for whiplash subjects at the beginning of the rehabilitation programme compared to the control group from the Department of Neurosurgery. After the rehabilitation period 49% of the patients had improved their coping resources totalling to 63% after 2 years. At that follow-up 46% of patients had increased their life satisfaction. Furthermore, the group with whiplash injury showed a significant increase in sick absenteeism whereas the group without whiplash trauma had decreased their sick-leave. Eighty-eight per cent of the subjects could be correctly classified according to their vocational outcome by means of discriminant function. The elapse of time since working, low life satisfaction, lack of increase in coping resources during the rehabilitation programme, ethnic origin of the patient and living in the countryside predicted poor vocational outcome. Our results suggest variables from the social environment and coping resources as useful predictors for treatment outcome.


Factors affecting the clinical development of cytochrome p450 3A substrates.
The objective of this review is to evaluate the risks associated with the discovery and development of cytochrome p450 (CYP) 3A substrates. CYP3A is the most abundant p450 enzyme in human liver and is highly expressed in the intestinal tract. The enzyme contributes substantially to metabolism of approximately 50% of currently marketed drugs that undergo oxidative metabolism. As a result, drug-drug interactions involving inhibitors of CYP3A-mediated metabolism can be of great clinical consequence. It is the position of the authors that, because of the factors responsible for the broad substrate specificity of CYP3A, discovery and development of compounds across a large and broad portfolio that are completely devoid of CYP3A metabolism is not feasible. Thus, it is important that scientifically valid approaches to the discovery and development of compounds metabolised by CYP3A be realised. The clinical relevance of CYP3A metabolism is dependent on a multitude of factors that include the degree of intestinal and hepatic CYP3A-mediated first-pass extraction, the therapeutic index of the compound and the adverse event associated with inhibition of CYP3A metabolism. Thus, a better understanding of the disposition of a CYP3A-metabolised compound relative to the projected or observed therapeutic index (or safety margin) can provide ample evidence to support the continued development of a CYP3A substrate. This document will highlight current practices as well as the benefits and risks associated with those practices.


Properties of rat liver nuclear protein kinases.
Two cyclic nucleotide-independent protein kinases (ATP:protein phosphotransferase, EC 22.214.171.124) have been purified to homogeneity from rat liver nuclei. While these enzymes have many similar catalytic properties (preference for acid rather than basic proteins), they differ in molecular weight and subunit composition. Protein kinase NII will utilize ATP and GTP as phosphate donors while protein kinase NI will only effectively use ATP. Both enzymes reveal an unusual activation by Fe2+.


Dopamine D4 receptor subtype activation reduces the rat cardiac parasympathetic discharge.
The dopaminergic system influences the heart rhythm by inhibiting the rat cardiac sympathetic and parasympathetic neurotransmissions through activation of D2-like receptors (encompassing the D2, D3, and D4 subtypes). Whereas D2 receptor subtype activation results in cardiac sympatho-inhibition, the dopamine receptor subtypes involved in rat cardiac vago-inhibition remain unknown. Hence, this study investigated the specific functional role of the D2-like receptor subtypes (D2, D3, and/or D4) inhibiting the rat heart cholinergic drive. For this purpose, male Wistar rats were pithed and prepared for cardiac vagal stimulation. Bradycardic responses were obtained by electrical stimulation of vagal fibres (3, 6, 9 Hz; n = 100) or i.v. acetylcholine (ACh; 1, 5, 10 μg/kg; n = 15). Expression of D2, D3, and D4 receptors was studied in left and right atrium samples by PCR (n = 4). Intravenous injections of quinpirole (D2-like agonist; 1-30 μg/kg), but not of SFK-38393 (D1-like agonist; 1-30 μg/kg), dose-dependently inhibited the vagally induced bradycardia. The vago-inhibition induced by quinpirole (which failed to affect the bradycardia to i.v. ACh) was unchanged after i.v. injections of the antagonists L-741,626 (D2; 100 μg/kg) or SB-277011-A (D3; 100 μg/kg), but it was abolished by L-745,870 (D4; 100 μg/kg). mRNA levels of D2, D3, and D4 receptor subtype were detected in the left and right rat atria. Our results suggest that the quinpirole-induced vagolytic effect involves prejunctional D4 receptor subtypes, located in the left and right atria. This provides new evidence on the relevance of D4 receptor modulating the heart parasympathetic control.


Neutrophil transepithelial migration in response to the chemoattractant fMLP but not C5a is phospholipase D-dependent and related to the use of CD11b/CD18.
In Crohn's disease and ulcerative colitis patients, the numbers of neutrophils recovered from stool directly correlates with the severity of disease, implying that neutrophils in the lumen contribute to the tissue destruction; therefore, it is important to understand the mechanisms behind transintestinal epithelial migration. Neutrophil transintestinal epithelial migration to fMLP is appreciated to be CD11b/CD18 integrin (Mac-1)-dependent, while we recently reported that migration to C5a is Mac-1-independent. Here, we investigated whether phospholipase D (PLD), a signaling molecule linked to chemoattractant activation of neutrophils, is necessary for both Mac-1-dependent and Mac-1-independent migration. Both fMLP and C5a increased neutrophil expression of the Mac-1 activation epitope, indicating PLD was activated. This up-regulation was dose-dependently prevented by incubation of neutrophils in 1-butanol, an inhibitor of PLD activity. Despite this effect on Mac-1, 1-butanol did not prevent neutrophil migration across acellular filters. Incubation in 1-butanol did inhibit fMLP but not C5a-mediated migration across intestinal epithelial cell monolayers, showing that transepithelial migration to fMLP but not C5a is dependent on PLD. The addition of phosphatidic acid, a reaction product of PLD, partially restored fMLP-mediated transepithelial migration in the presence of 1-butanol but not the migration of Mac-1-deficient neutrophil-differentiated HL-60 cells. Thus PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. Moreover, as PLD controls other neutrophil functions, such as the oxidative response, degranulation, and protease release, we could exclude these functions as being important in neutrophil transepithelial migration to C5a.


Cholesterol synthesis in patients with glutathione deficiency.
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate-limiting step in cholesterol synthesis. Glutathione (GSH) has been postulated to be an important activator of HMG-CoA reductase in vivo. HMG-CoA reductase activity was assayed in cultured fibroblasts from healthy children. Solubilized enzyme preparations were prepared by ultracentrifugation after freezing and thawing of fibroblasts. Such treatment increased the relative enzyme activity markedly. Enzymological assay conditions were established. Addition of GSH stimulated the reaction, whereas there was inhibition after addition of glutathione disulphide (GSSG). The inhibitory effect of GSSG could be reversed by the addition of excess GSH. Fibroblast preparations, deficient in GSH, were obtained from children with glutathione synthetase deficiency or from normal subjects after the growth of fibroblasts in the presence of buthionine sulphoximine. Solubilized enzyme preparations from GSH-deficient fibroblasts had HMG-CoA reductase activities lower than or comparable with those of control preparations. The results indicate only some reduction in the capacity for cholesterol synthesis in subjects with glutathione deficiency. The existence of additional activation mechanisms in vivo, alternative to GSH, for thiol-dependent modulation of HMG-CoA reductase activity seems likely.


Prevalence of Traditional Risk Factors in First-Degree Relatives of Patients With Established Cardiovascular Disease.
World Health Organization (WHO)/International Society of Hypertension (ISH) risk prediction charts are useful for predicting 10-year combined myocardial infarction and stroke risk (fatal and non-fatal). Hence the current study was conducted to assess the 10-year risk of cardiovascular disease among adults in Ahmedabad, India. The primary aim of the study was to assess the cardiovascular risk among first-degree relatives of patients attending the outpatient clinic. Also, to create awareness regarding assessment of cardiovascular risk among the studied group. A cross-sectional study was carried out among 372 first-degree relatives of patients at an out-patient cardiology clinic present in Vadaj, Ahmedabad. The WHO/ISH risk prediction chart for South-East Asia Region D (SEAR D) was used for calculating the 10-year cardiovascular risk. A maximum (80.10%) of the study participants were in the low-risk (<10%) category followed by 8.33% for moderate-risk (10-20%), 7.25% for moderately high-risk (20-30%), 2.42% for high-risk (30-40%) and 1.88% for very high-risk (>40%). WHO/ISH risk prediction charts provide a quick and effective way to assess and categorize the population in a low-resource setting which in turn helps in delivering focused intervention to the high-risk groups.


Renal transplantation in the rat--a new simple, non-suture technique.
Renal transplantation in the rat can be performed by a simple technique utilising cuff anastomosis. This method is quick and reliable, and the results compare well with those achieved by standard microsurgical techniques.


[Is every case of muscle damage during hypolipemic therapy the side effect of this therapy? A case report].
Hypolipemic agents, both statins and fibrates, may cause a spectrum of side-effects, including the transient increase in creatine phosphokinase (CPK) activity. Muscle injury may present as common myalgia, non-specific myositis with normal CPK levels, myopathy and in the most serious cases, as rhabdomyolysis. Muscle damage is much more probably in patients with concomittant kidney and liver diseases, hypothyroidism, and serious infections or after some injuries or a heavy physical effort. On the other hand, one of the most common causes of secondary hypercholesterolemia and myopathy is hypothyroidism. This condition, which may enhance the risk of muscle damage in the course of hypolipemic treatment, may sometimes present with an atypical clinical presentation, making its diagnosis challenging. In this article, we present the case of a 50-year-old male physical worker presented with marked dyslipidemia, in whom myopathy was diagnosed during therapy with hypolipemic agents. Cessation of the treatment resulted in the only moderate reduction of CPK activity. Only just the introduction of thyroid hormone supplementation led to regression of symptoms and normalization of abnormalities found in laboratory examinations including remarkable improvement in lipid profile. After several months of observation we consider that hypolipemic treatment probably revealed previously occult autoimmune thyroid disease in this patient.


Bid, a critical mediator for apoptosis induced by the activation of Fas/TNF-R1 death receptors in hepatocytes.
The Bcl-2 family proteins consist of both antiapoptosis and pro-apoptosis members that regulate apoptosis typically at the mitochondrial level, mainly by controlling the release of cytochrome c and other mitochondrial apoptotic events. However, death signals mediated by Fas/TNF-R1 receptors can usually activate caspases directly, bypassing the need for mitochondria and escaping the regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family protein that is activated by Caspase 8 in response to Fas/TNF-R1 death receptor activation. Activated Bid is translocated to mitochondria and induces cytochrome c release, which in turn activates the downstream caspases. This Bid-mediated pathway is critical in hepatocyte apoptosis induced by Fas/TNF-R1 engagement, where direct activation of cytosolic caspase cascade seems inefficient. The dependence on Bid, and thus on the mitochondrial cytochrome c release, of hepatocyte apoptosis induced by the death receptors also renders it sensitive to the inhibitory regulation by the anti-apoptosis members of the Bcl-2 family proteins, such as Bcl-2 and Bcl-xL. Moreover, the revealing of this death pathway in hepatocytes is important to the understanding of the pathogenesis of a number of hepatic diseases such as hepatitis or endotoxemia-related hepatic failure.


Genistein protection against acetaminophen-induced liver injury via its potential impact on the activation of UDP-glucuronosyltransferase and antioxidant enzymes.
The purpose of this study was to investigate genistein's influence on the relationship between the activation of uridine diphosphate glucuronosyltransferase (UGTs) and the protection against acetaminophen-induced liver toxicity. Animal experimental results revealed that genistein (50, 100 or 200mg/BWkg) significantly ameliorated the biomarkers alanine aminotransferase, alanine aminotransferase, lactate dehydrogenase and malondialdehyde, as indicators of acute liver damage caused by APAP (200mg/BWkg). The level of GSH declined sharply after treatment with APAP within 1h in both the liver and blood with and without genistein. However, after 16h, the levels approached or returned to the original level. Genistein may accelerate and promote APAP glucuronidation as the results showed that APAP-glucuronide increased by 18.44%, 46.79%, and 66.49% for 4h of treatment with genistein dosages of 50, 100 or 200mg/BWkg, respectively, compared with the APAP-only treatment. The activation of UGTs and glutathione peroxidase and the inhibition of CYP2E1 by genistein were observed, and UGTs mRNA expression level with genistein was measured. These findings suggest that genistein can prevent and protect against APAP-induced liver toxicity due to the inhibition of APAP biotransformation and the resistance to oxidative stress via the modulation of the activities of metabolism and the antioxidant enzyme.


Meta-analysis of published studies or meta-analysis of individual data? Caesarean section in HIV-positive women as a study case.
Very few comparative evaluations of meta-analysis of published data and meta-analysis using individual patient data have appeared in the medical literature. The association between type of delivery and HIV perinatal transmission appears to be an excellent study case, given the recent publication of the meta-analysis of individual patient data by the International Perinatal HIV Group. In this paper, we report the results of a meta-analysis of the published studies, which show a statistically significant reduction of perinatal HIV transmission rate with Caesarean section. The results are surprisingly similar to those of the recently published meta-analysis of individual patient data, indicating that, in the absence of significant confounding, the two meta-analytic methods are likely to give consistent results. In this era of constrained resources for biomedical research, caution should be taken in abandoning meta-analysis of published data for studying epidemiological associations of public health interest.


The role of the serotonergic system in motor control.
The serotonergic system in the vertebrate brain is implicated in various behaviors and diseases. Its involvement in motor control has been studied for over half a century, but efforts to build a unified model of its functions have been hampered due to the complexity of serotonergic neuromodulation. This review summarizes the anatomical structure of the serotonergic system, its afferent and efferent connections to other brain regions, and recent insights into the sensorimotor computations in the serotonergic system, and considers future research directions into the roles of serotonergic system in motor control.


Incorporation of [3H]fucose in rat hippocampal structures after conditioning by perforant path stimulation and after LTP-producing tetanization.
The contribution of glycoprotein synthesis to functional synaptic changes and to the formation of memory traces was investigated by autoradiographic determination of the incorporation of [3H]fucose into the hippocampal structures of rats. In the first experiment, the fucose incorporation was measured after induction of post-tetanic long-term potentiation (LTP) in granular cell synapses by repeated tetanization (200 cps) of the perforant path, and after stimulation of this hippocampal input by the same number of impulses with very low frequency (0.2 cps) not producing LTP. In the second experiment, the incorporation of fucose was determined after an active avoidance training using the stimulation of the perforant path by impulse trains of 15 cps as conditioning stimuli, and after a session of corresponding unpaired stimulations of the perforant path. Unstimulated animals were used in both experiments to measure the basal glycosylation. LTP-producing tetanization resulted only in a slight increase of incorporation into the ipsilateral hippocampal structures without significant differences to similar changes after the corresponding control stimulation with single impulses. After a session of unpaired stimulation of the perforant path with impulse trains of 15 cps only slight and inconsistent changes of incorporation occurred in the hippocampus too. However, after conditioning by the corresponding perforant path stimulation as conditioned stimulus, considerable increases of incorporation were observed in all structures of the ipsilateral hippocampus, when compared to the unpaired control stimulation. An enhanced labeling occurred also in some structures of the contralateral hippocampus mainly receiving commissural inputs. The results suggest again, that the activation of one single hippocampal afferent, even if producing LTP, would not be sufficient to induce an increased glycosylation of neuronal proteins. The increase of glycoprotein formation seems to require the convergence of several inputs, which can be assumed to occur during learning. Therefore, LTP of a single synaptic population seems not to represent the complete long-lasting memory trace, but only one of its components, or a preceding transient storage mechanism.


Tissue response to subperiosteal implantation of dense hydroxyapatite: case report.
Hydroxyapatite is becoming a popular implant material, yet reports on the tissue response it evokes in humans have been few in number and are based on relatively short periods of implantation. In the present case, implant material became available when it proved necessary to modify an alveolar ridge augmentation procedure carried out 18 month previously. Histology showed that whilst some parts of the implanted material were embedded only in fibrous tissue, others had become fully integrated within partly remodelled bony trabeculae. These findings confirm the status of hydroxyapatite as a biocompatible implant material and provide further evidence of its bone-bonding and osteoconductive capacities.


Staff Duress Alarms for Workplace Violence in the Emergency Department: A Mixed-Methods Evaluation.
Complex personal duress alarms may be implemented as part of a multicomponent approach to preventing and mitigating workplace violence in emergency departments. Evaluation of duress alarms after implementation has been identified as a gap in the literature. The purpose of this quality improvement project was to examine the impact of a duress alarm system on workplace violence and user experience in an urban emergency department. A comprehensive system evaluation was performed using a mixed-methods approach, which included retrospective data review, key informant interviews, observations, and a survey. Forty clinical staff at an emergency department in North Carolina were interviewed and provided feedback on the duress system. Findings indicated that the duress system was not associated with a decrease in workplace violence, and that the majority of clinical staff did not even wear the duress alarm. Staff indicated that the primary barriers to use of the alarm were the bulky design of the alarm badge, inadequate education about the alarm device and process, and the lack of a reliable and timely response from security. Ongoing engagement of clinical staff is critical to the success of health care technology implementations. Staff feedback, periodic re-education, and recurring process evaluations are vital to ensuring the continued relevance of systems, especially when staff safety is the intended purpose.


Protection of mice against the lethal effects of sodium metavanadate: a quantitative comparison of a number of chelating agents.
10 Chelating agents were administered to mice by intraperitoneal (i.p.) injection in order to compare their relative effectiveness in preventing death after a single i.p. injection of NaVO3. Ascorbic acid, Tiron (4,5-dihydroxy-1,3-benzene-disulfonic acid) and deferoxamine were the most effective antidotes for acute NaVO3-toxicity. The therapeutic index of ascorbic acid against 0.61 mmol/kg NaVO3 was found to be 95.2. This was 4.6 and 12.2 times greater than those of Tiron and Deferoxamine respectively. L-Cysteine greater than Na2CaEDTA greater than Na3CaDTPA reduced the acute mortality of mice following i.p. injection of NaVO3. Sodium salicylate, D,L-penicillamine, DMSA and DDC were not effective as antidotes for acute NaVO3-toxicity.


Identification of Dirofilaria immitis miRNA using illumina deep sequencing.
The heartworm Dirofilaria immitis is the causative agent of cardiopulmonary dirofilariosis in dogs and cats, which also infects a wide range of wild mammals and humans. The complex life cycle of D. immitis with several developmental stages in its invertebrate mosquito vectors and its vertebrate hosts indicates the importance of miRNA in growth and development, and their ability to regulate infection of mammalian hosts. This study identified the miRNA profiles of D. immitis of zoonotic significance by deep sequencing. A total of 1063 conserved miRNA candidates, including 68 anti-sense miRNA (miRNA*) sequences, were predicted by computational methods and could be grouped into 808 miRNA families. A significant bias towards family members, family abundance and sequence nucleotides was observed. Thirteen novel miRNA candidates were predicted by alignment with the Brugia malayi genome. Eleven out of 13 predicted miRNA candidates were verified by using a PCR-based method. Target genes of the novel miRNA candidates were predicted by using the heartworm transcriptome dataset. To our knowledge, this is the first report of miRNA profiles in D. immitis, which will contribute to a better understanding of the complex biology of this zoonotic filarial nematode and the molecular regulation roles of miRNA involved. Our findings may also become a useful resource for small RNA studies in other filarial parasitic nematodes.


The effect of lesions of the epithalamus on plasma aldosterone and corticosterone levels in Japanese quail.
The peripheral plasma aldosterone and corticosterone concentrations were measured by CPBA and RIA method in Japanese quails in which the subcommissural organ (SCO) or the habenula had been destroyed. Lesion of the SCO reduced the plasma aldosterone level by 50%. The lesion of n. habenularis medialis and lateralis on the other hand did not affect the plasma corticosteroid level. It is suggested that in birds the SCO takes part in a multifactorial regulation of aldosterone secretion.


Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function.
Despite radiation forming the curative backbone of over 50% of malignancies, there are no genomically-driven radiosensitizers for clinical use. Herein we perform in vivo shRNA screening to identify targets generally associated with radiation response as well as those exhibiting a genomic dependency. This identifies the histone acetyltransferases CREBBP/EP300 as a target for radiosensitization in combination with radiation in cognate mutant tumors. Further in vitro and in vivo studies confirm this phenomenon to be due to repression of homologous recombination following DNA damage and reproducible using chemical inhibition of histone acetyltransferase (HAT), but not bromodomain function. Selected mutations in CREBBP lead to a hyperacetylated state that increases CBP and BRCA1 acetylation, representing a gain of function targeted by HAT inhibition. Additionally, mutations in CREBBP/EP300 are associated with recurrence following radiation in squamous cell carcinoma cohorts. These findings provide both a mechanism of resistance and the potential for genomically-driven treatment.


A new cognitive behavior therapy for adolescents with avoidant/restrictive food intake disorder in a day treatment setting: A clinical case series.
Avoidant/restrictive food intake disorder (ARFID) is a new diagnosis in the DSM-5 Feeding and Eating Disorders section, for which very limited treatment research has been carried out, yet. A new, 4-week exposure based cognitive behavioral therapy (CBT) day treatment, which integrated the inhibitory learning principles, was developed for adolescents with ARFID, and tested in the current study. A nonconcurrent multiple baseline design was used in a clinical case series of eleven 10- to 18-year-old patients. After baseline, the 4-week CBT followed. Measurements of DSM-5 ARFID diagnosis, food neophobia and related measures such as body weight and length, were taken at baseline (t1), at the end of the 4-week intensive day treatment (t2) and 3 months after treatment (follow-up, t3). A food selectivity test, a 1-week food diary, and behavioral measures on food intake were also taken at baseline and at 3-month follow-up. Furthermore, continuous measurements of believability of dysfunctional cognitions, anxiety, and food acceptance were taken throughout the 4-weeks day treatment. At follow-up, 10 out of 11 patients were in remission and had a healthy body weight and an average, age-adequate nutritional intake. For most patients, food neophobia scores decreased to a nonclinical range. The belief in dysfunctional cognitions and anxiety levels decreased during treatment. This new exposure-based CBT for adolescents with ARFID seems promising. These results may be very useful for clinical practice and stimulate further development of effective CBT interventions in the area of ARFID.


Membrane filter staining method: bacterial plate counts in 24 H.
We describe a technique to stain bacterial colonies on membrane filters. The procedure yielded reliable and reproducible bacterial plate counts in 24 h. The procedure can be applied to treated and untreated water samples requiring prompt analysis.


MR imaging of the sternoclavicular joint following trauma.
The purpose of this study is to describe the magnetic resonance imaging (MRI) findings of the sternoclavicular (SC) joint seen in patients who presented to our department with joint pain related to trauma. Clinical history and MRI findings on 41 patients were reviewed retrospectively to establish types and frequencies of soft tissue injuries and subluxations. Because both SC joints were imaged, the asymptomatic joints were used as a control group. Articular disk injuries were seen in 80% of patients. Injuries of the anterior, posterior, interclavicular and costoclavicular ligaments were seen in 73%, 39%, 29% and 14% of patients, respectively. Most clavicular subluxations were in the superior and posterior directions. Posterior impingement of mediastinal structures was seen in cases of posterior clavicular subluxation as well as in cases of retrosternal inflammatory or fibrotic tissue without clavicular subluxation. Biomechanical models of the SC joint are discussed to explain how different ligamentous injuries typically result in different types of subluxations.


Fibrous dysplasia complicated by aneurysmal bone cyst formation affecting multiple cervical vertebrae.
Fibrous dysplasia is a well-known benign dysplastic process of bone. However, fibrous dysplasia is very uncommon in the spine. Further, to our knowledge, coexistence of fibrous dysplasia and aneurysmal bone cyst in the spine has not been reported. This manuscript presents a patient who had both processes involving the cervical spine.


Probing polyproline structure and dynamics by photoinduced electron transfer provides evidence for deviations from a regular polyproline type II helix.
Polyprolines are well known for adopting a regular polyproline type II helix in aqueous solution, rendering them a popular standard as molecular ruler in structural molecular biology. However, single-molecule spectroscopy studies based on Förster resonance energy transfer (FRET) have revealed deviations of experimentally observed end-to-end distances of polyprolines from theoretical predictions, and it was proposed that the discrepancy resulted from dynamic flexibility of the polyproline helix. Here, we probe end-to-end distances and conformational dynamics of poly-l-prolines with 1-10 residues using fluorescence quenching by photoinduced-electron transfer (PET). A single fluorophore and a tryptophan residue, introduced at the termini of polyproline peptides, serve as sensitive probes for distance changes on the subnanometer length scale. Using a combination of ensemble fluorescence and fluorescence correlation spectroscopy, we demonstrate that polyproline samples exhibit static structural heterogeneity with subpopulations of distinct end-to-end distances that do not interconvert on time scales from nano- to milliseconds. By observing prolyl isomerization through changes in PET quenching interactions, we provide experimental evidence that the observed heterogeneity can be explained by interspersed cis isomers. Computer simulations elucidate the influence of trans/cis isomerization on polyproline structures in terms of end-to-end distance and provide a structural justification for the experimentally observed effects. Our results demonstrate that structural heterogeneity inherent in polyprolines, which to date are commonly applied as a molecular ruler, disqualifies them as appropriate tool for an accurate determination of absolute distances at a molecular scale.


Gaining insight into the impact of electronic property and interface electrostatic field on ORR kinetics in alloy engineering via theoretical prognostication and experimental validation.
Alloy engineering has been utilized as a potent strategy to modulate the oxygen reduction reaction (ORR) activity. However, the regulatory mechanism underpinning the ORR kinetics by means of alloy engineering is still shrouded in ambiguity. This work places emphasis on the kinetics of the ORR concerning Pt3M (M = Cr, Co, Cu, Pd, Sn, and Ir) catalysts, and integrates theoretical prognostication and experimental validation to illuminate the fundamental principles of alloy engineering. The ORR kinetic activity, as prognosticated by theory, shows significant agreement with experimental results, provided that the rate-determining step (RDS) accounts for a dominant role in the potential-independent kinetic mechanism. In essence, alloy engineering manipulates electronic properties through electron transfer to modulate intermediate adsorption and adjusts the interface electric field (Efield) to regulate hydrogen atom transport, ultimately influencing kinetics. The Efield holds greater significance in ORR kinetics compared to the intermediate adsorption (EadsO), the corresponding degrees of correlation with free energy barriers (Ea) of RDS are -0.89, and 0.75, respectively. This work highlights the nature of alloy engineering for ORR kinetics modulation and assists in the design of efficient catalysts.


The Life Cycle of the Nephron Progenitor.
Although we know that mesenchymal progenitors give rise to nephrons in the kidney, how they balance self-renewal versus differentiation is still unclear. In this issue of Developmental Cell, Chen et al. (2015) show that nephron progenitors age, but not necessarily irreversibly: old progenitors can be "rejuvenated" by a young crowd.


Reflective writing: Implementation and learning perception from students and teachers of French nursing schools.
To support reflective skills development, French nursing students write analyses of professional situations (Situation Analysis) experienced during their practice. Sixteen nursing schools in Paris have developed a common framework to support and evaluate students on these skills. The aims of the study were to assess and understand the implementation of the Situation Analysis in French nursing schools as well as their effects on students' learning. A quantitative approach was based on two questionnaires: students (n = 1525, 27.6% of participation) and teachers (n = 131, 49.2%). The results showed that there were variations in teaching of situation analysis. There were correlations between the perception of learning and the modalities of implementation. Not always easy to choose, the situations described were authentic for 97.8% of students, concerned mainly their own practice and relationship with patients. Emotional situations were less frequent. Feedback was generally present and encouraging, but not enough on the students' self-evaluation skills. Slightly more than half of students and teachers were satisfied of the situation analysis. Both of them made positive and negative comments. The study highlights what can be improved in teaching to increase student's learning through situation analysis, for example teamdefined objectives.


Retrieval practice and judgements of learning enhance transfer of physiology information.
It is well-documented that retrieval practice enhances the recall of simple and complex information (Karpicke and Aue in Educ Psychol Rev 27(2):317-326, 2015). Evidence is also accumulating that retrieval practice can enhance other cognitive processes such as the ability to critically evaluate research articles (Dobson et al. in Med Educ 52(5):513-525, 2018) and transfer of learning (Butler in J Exp Psychol Learn Mem Cogn 36(5):1118, 2010). One aim of this investigation was to explore the effects of retrieval practice on transfer of learning with physiology information. A second aim was to compare recall and transfer of physiology information following retrieval practice versus a judgment of learning task (JOL) that is potentially less time consuming for students to use. Participants were randomly assigned to learn three physiology texts using each of the following strategies: (1) studying a text four times (S-S-S-S), (2) studying and then retrieving a text two times (S-R-S-R), and (3) studying a text four times while completing multiple JOL during the second and fourth repetitions (S-S/J-S-S/J). Recall and accuracy on transfer questions were assessed 1 week after the learning phase, and the results were analyzed using repeated measures ANOVAs. The S-R-S-R strategy (21.35 ± 1.08%) produced significantly greater recall than the S-S-S-S strategy (17.35 ± 0.86%), and both the S-R-S-R (44.60 ± 2.55%) and S-S/J-S-S/J (41.79 ± 2.63%) strategies lead to significantly greater transfer than the S-S-S-S strategy (36.07 ± 2.40%). These results provide evidence that retrieval practice enhances recall and transfer of physiology information and that a JOL task can also prove to be beneficial but to a lesser degree.


Influence of periodic milk or cream treatment on the anti-erosive potential of the acquired enamel pellicle.
The purpose of the present study was to assess the anti-erosive potential of the acquired enamel pellicle formed in situ under the influence of periodic milk or cream treatment. The pellicle was formed on bovine enamel specimens in the oral cavity at buccal and palatal sites of upper molars in 6 subjects, using removable acrylic splints. During 6-h of intraoral exposure, splints were removed from the oral cavity every 25 min, treated with milk or cream for 5 min, and subsequently re-inserted into the oral cavity. After 6 h, pellicle covered specimens were immersed in citric acid (0.1 or 1.0 %) for 1 min, and processed for measurement of surface microhardness, determination of calcium release by atomic absorption spectroscopy, scanning and transmission electron microscopy. Statistical analysis was performed with SAS. Statistical analysis did not indicate major differences between erosive surface alterations on enamel specimens covered by pellicles treated with cream or milk, and those covered by control pellicles. In addition, TEM analysis did not reveal any differences concerning the ultrastructure of the different pellicle treatments during acid exposure. All pellicles were dissolved in part after exposure to 0.1 % citric acid and were nearly completely removed after treatment with 1.0% citric acid. It is concluded that periodic treatment with milk or cream during pellicle formation in situ does not improve the protective potential of the acquired enamel pellicle against erosion. Modification of the pellicle by consumption of milk or cream prior to an acidic challenge cannot sufficiently protect enamel from erosion.


Cell-Membrane-Localizing, Two-Photon Probe for Ratiometric Imaging of γ-Glutamyl Transpeptidase in Cancerous Cells and Tissues.
γ-Glutamyl transpeptidase (GGT), a cell surface-bound protease, is associated with various diseases including cancer. The detection of the enzyme activity is an important subject, leading to about 40 activatable fluorescent probes so far. All of them, however, lack the membrane-localizing ability, raising a reliability issue in the quantitative analysis. Disclosed is the first fluorescent probe that senses the cell surface-bound enzyme, which, furthermore, is capable of ratiometric as well as two-photon imaging with desirable features. Ratiometric imaging of cancer cell lines reveals a 6.4-8.4-fold higher GGT levels than those in normal cell lines. A comparison of the enzyme activity in organ tissues of normal and tumor xenograft mice reveals notably different levels of enzyme activity depending on the kind of tissue. Normal tissues exhibited comparable levels of enzyme activity, except the kidney that has significantly higher GGT activity (2.7-4.0-fold) than the other organs. Compared with the normal tissues, considerably higher enzyme activity was observed in the tumor tissues of the thigh (4.0-fold), colon (2.5-fold), lung (3.6-fold), and liver (2.1-fold), but essentially no enhanced activity in the tumor tissues of the spleen, stomach, and pancreas and a comparable level in both the tumor and normal kidney tissues were observed. The probe offers practical means for studying GGT-associated biology in cells and tissues by one- as well as two-photon ratiometric imaging.


"It is the future. Clinical pharmaceutical care simply has to be a matter of course." - Community pharmacy clinical service providers' and service developers' views on complex implementation factors.
While there is a lot of documented evidence about the clinical and cost effectiveness of pharmacists' role extensions there is an inherent gap between service development and implementation. This study aims to better understand the complex factors that influence the implementation of clinical pharmacy services from both the perspective of the community pharmacy service providers and service developers. A prospective qualitative interview study using purposive sampling of twelve service developers and twelve community pharmacy service providers from across all nine Federal States of Austria. The validated and piloted interview guide contained questions and prompts on role perceptions, attitudes, experience, implementation barriers, training needs and measures identified to strengthen clinical pharmacy provision in community pharmacy. Verbatim quotes were independently mapped to the Framework for the Implementation of Services in Pharmacy (FISpH) by two researchers. 24 Interviews were carried out. Data saturation was achieved. There is a great deal of enthusiasm to develop the remit of clinical pharmacy services. It is seen as important to ensure the future survival of the profession. Service developers are more positive and confident in the implementation success and pharmacists' skills than providers. Clear mandates for politics, academia and individual pharmacists have been discussed to affect change. Austrian pharmacists are facing the same well documented challenges as many other healthcare systems only with more urgency. The development of a clinical pharmacy service framework; education accreditation standard and a well-supported continuous professional development system are considered key to bring about the necessary culture shift.


[Potentiometric methods for determining boron, hydrogen cyanide and hydrogen chloride compounds and their use in controlling the quality of manufacturing and natural environments].
The authors present basic science for, elaborate and set as methodic recommendations some potentiometric methods using ion-selective electrodes. Efficiency of those methods was proved in experiments with such substances as boron compounds, hydrogen cyanide, hydrogen chloride. High sensitivity, selectivity, accuracy and rapidity of the methods with handy technique make the facilities available for analysis of air at workplace, ambient atmosphere, water and biologic materials, detecting wide range of concentrations. Practical application of the methods enabled to specify measures to preserve health of workers and general population, helped in hygienic evaluation of work conditions in composition materials production, high-temperature soldering, optic glass industry.


Increasing diversity in developmental cognitive neuroscience: A roadmap for increasing representation in pediatric neuroimaging research.
Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.


Time-dependent effects of ovarian steroids on tyrosine hydroxylase activity in the limbic forebrain of female rats.
In this work, we have studied the time-course of the effects of pharmacological administration of ovarian steroids on tyrosine hydroxylase (TH) activity in the limbic forebrain of ovariectomized rats. Administration of estradiol produced a late decrease in TH activity. This effect was found 24 hours after the last steroid injection, disappearing at 32 hours. It was antagonized by progesterone, since a single injection of this steroid to estradiol-pretreated rats reversed to control values the estradiol-induced decrease. Nevertheless, the administration of progesterone after estradiol treatment caused a short-time decrease in the limbic activity of TH, which was observed 4 hours after the last steroid injection, disappearing subsequently. On the other hand, the administration of progesterone alone produced a biphasic effect, with a reduction at 24 hours, followed by an increase at 32 hours. These effects were only observed in the animals non-treated with estradiol, disappearing with a previous treatment with estrogens. Hence, it can be concluded that both ovarian steroids may affect the limbic TH activity. Thus, estradiol produced a late inhibitory effect on the activity of this enzyme, which was antagonized by progesterone. Administration of the last one to estradiol-treated rats produced a short-time inhibitory effect, whereas its administration to non-treated rats produced a late biphasic effect (inhibition followed by stimulation), which was not observed in estradiol-treated rats.


Advances in TEER measurements of biological barriers in microphysiological systems.
Biological barriers are multicellular structures that precisely regulate the transport of ions, biomolecules, drugs, cells, and other organisms. Transendothelial/epithelial electrical resistance (TEER) is a label-free method for predicting the properties of biological barriers. Understanding the mechanisms that control TEER significantly enhances our knowledge of the physiopathology of different diseases and aids in the development of new drugs. Measuring TEER values within microphysiological systems called organ-on-a-chip devices that simulate the microenvironment, architecture, and physiology of biological barriers in the body provides valuable insight into the behavior of barriers in response to different drugs and pathogens. These integrated systems should increase the accuracy, reproducibility, sensitivity, resolution, high throughput, speed, cost-effectiveness, and reliable predictability of TEER measurements. Implementing advanced micro and nanoscale manufacturing techniques, surface modification methods, biomaterials, biosensors, electronics, and stem cell biology is necessary for integrating TEER measuring systems with organ-on-chip technology. This review focuses on the applications, advantages, and future perspectives of integrating organ-on-a-chip technology with TEER measurement methods for studying biological barriers. After briefly reviewing the role of TEER in the physiology and pathology of barriers, standard techniques for measuring TEER, including Ohm's law and impedance spectroscopy, and commercially available devices are described. Furthermore, advances in TEER measurement are discussed in multiple barrier-on-a-chip system models representing different organs. Finally, we outline future trends in implementing advanced technologies to design and fabricate nanostructured electrodes, complicated microfluidic chips, and membranes for more advanced and accurate TEER measurements.


Endovascular repair of abdominal aortic aneurysm does not improve early survival versus open repair in patients younger than 60 years.
Multiple randomised trials have demonstrated lower perioperative mortality after endovascular aneurysm repair (EVAR) compared to open surgical repair for infrarenal abdominal aortic aneurysms (AAAs). However, in these trials the mortality advantage for EVAR is being lost within 2 years of repair and the patients evaluated are relatively older with no study specifically comparing EVAR and open repair for patients younger than 60 years of age. A retrospective analysis of prospectively collected data. Patients younger than 60 years of age who underwent EVAR and open surgical repair for elective infrarenal AAA were identified from the 2007-09 National Surgical Quality Improvement Program (NSQIP) - a prospective database maintained at 237 centres across the United States. Univariate and multivariate analyses were performed. Of the 651 patients, 369 (56.7%) underwent EVAR and 282 (43.3%) underwent open repair. Thirty-day mortality for EVAR and open repair were 1.1% and 0.4%, respectively. This was not significantly different on univariate (P = 0.22) as well as multivariate (P = 0.69) analysis after controlling for other co-morbidities. On multivariate analysis, body mass index, history of stroke and bleeding disorder prior to surgery were associated with a higher 30-day mortality after AAA repair (combined open and EVAR). These contemporary results demonstrate that the 30-day mortality rate after open repair is similar to that after EVAR in patients younger than 60 years with infrarenal AAA.


The Burgeoning World of Immunometabolites: Th17 Cells Take Center Stage.
Dysregulation of the Th17/Treg balance is a key driver of autoimmunity. A new study by Xu et al. (2017) has revealed that small-molecule inhibition of 2-hydroxyglutarate synthesis skews Th17 differentiation to the Treg lineage, which is protective against autoimmune inflammation.