Gene expressions and activities of protein phosphatases PP1 and PP2A in rat liver regeneration after partial hepatectomy.
We have examined the levels of gene expressions and activities of protein phosphatases, PP1 and PP2A, in rat regenerating livers. PP1 alpha mRNA started to increase from 6 h after partial hepatectomy (PH) and showed two peaks at 12 and 48 h. PP2A mRNA level showed two peaks at 6 and 10-12 h. Protein phosphatase activities were determined both in non-nuclear fraction and in nuclei. While spontaneous PP1 activity in non-nuclear fraction was nearly constant, potential PP1 activity revealed by Co(2+)-trypsin treatment showed a small peak between 7 and 12 h. In nuclei, both spontaneous and potential PP1 activity began to increase from 4-7 h after PH, reached a maximum (about 2.5-fold over control levels) at 12 h, the time which corresponds to the G1 to S transition in the cell cycle, and then declined back to control levels by 7 days. PP2A activity in non-nuclear fraction was nearly constant in both spontaneous and potential forms. PP2A activity in both forms in nuclei was very low throughout. These results suggest the possibility that PP1 in nuclei plays some role in the G1 to S transition in the cell cycle of hepatocyte proliferation.


Laparoscopic single site adrenalectomy using a conventional laparoscope and instrumentation.
We present a case of Laparoendoscopic Single Site Surgery (LESS) left adrenalectomy performed with a conventional laparoscope and instruments. A 45-year-old male was diagnosed with hyperaldosteronism. Computed tomography detected a left adrenal nodule. Bilateral adrenal vein sampling was consistent with a left-sided source for hyperaldosteronism. Total operative time for LESS left adrenalectomy was 120 minutes. The surgery was performed with conventional instruments, a standard 5-mm laparoscope, and a SILS port, with no additional incisions or trocars needed. No complications occurred, and the patient reported an uneventful recovery. LESS adrenalectomy is a feasible procedure. Although articulating instruments and laparoscopes may offer advantages, LESS adrenalectomy can be done without these.


Stereotypes violate the postmodern construction of personal autonomy.
Individual autonomy, as constructed in the postmodern era, is violated by stereotypes, which makes stereotype accuracy morally unpalatable. Yet people are clustered and homogenized by social forces, entailing some accuracy in stereotypes. This tension can be ameliorated by unveiling the constructed nature of autonomous selfhood, and explaining why social clustering has occurred and been adaptive.


Effect of 1,25-dihydroxyvitamin D3 on cytokine-induced thymocyte proliferation.
To clarify the mechanism of the inhibitory effect of 1,25(OH)2D3 on lymphocyte proliferation, the effect of 1,25(OH)2D3 on murine thymocyte proliferation induced by interleukin 1 (IL-1), or 2 (IL-2) was examined. Physiological concentrations of 1,25(OH)2D3 inhibited thymocyte proliferation induced by IL-1 and IL-2 in similar fashion suggesting an inhibition of the response to IL-2 by this hormone. In addition, cortisone-resistant thymocytes (including a majority of medullary thymocytes), which proliferate more vigorously in response to IL-1 than do untreated thymocytes, were more sensitive to 1,25(OH)2D3 inhibition. Therefore, the inhibition of IL-2 production of the mature medullary thymocyte by this hormone was also suggested.


Treatment of men with major depression: a comparison of sequential cohorts treated with either cognitive-behavioral therapy or newer generation antidepressants.
This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.


Chemokine mediated control of dendritic cell migration and function.
Dendritic cells (DC) have historically been viewed as a group of functionally homogeneous cell types that act to stimulate Ag-specific immune responses after migrating to secondary lymphoid organs. DC patterns of chemokine responsiveness have generally been viewed as similar among DC subtypes. Here we discuss recent studies that challenge this view by demonstrating that DC subtypes differ in their response to specific chemokines, their migration patterns, and their capacity to stimulate or inhibit immune response. Thus, individual chemokines may act to regulate the character, strength, and duration of Ag-specific immune responses in a manner that has not previously been appreciated.


Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity to implantation.
In IVF programmes, transvaginal ultrasonography is used as a non-invasive method to evaluate uterine receptivity. The aim of this study was to determine when to perform this investigation in order to optimize prediction of the likelihood of pregnancy. Over 9 months, 124 patients undergoing IVF or intracytoplasmic sperm injection were studied. The ultrasonographic evaluation included endometrial thickness, endometrial pattern, uterine artery pulsatility index, protodiastolic notch, end-diastolic blood flow, and endometrial-subendometrial blood flow distribution pattern. All patients underwent ultrasonographic investigation on the days of human chorionic gonadotrophin (HCG) administration, oocyte retrieval, and embryo transfer. Statistical analysis was done using recursive-partitioning analysis. The pregnancy and implantation rates per transfer were 33 and 19.8% respectively. In terms of single parameters, women with an end-diastolic blood flow, an endometrial-subendometrial blood flow and a multilayered endometrium were more likely to be pregnant than women without one or more of these signs. The most effective combination for evaluation of uterine receptivity was end-diastolic blood flow, endometrial pattern and endometrial thickness. Sensitivity and specificity of this combination were around 81%, positive predictive value was 68.2%, and negative predictive value 89.7%. The best sensitivity and specificity were obtained on the day of HCG administration: respectively 81.1 and 81.3%.


Chemical composition of lipopolysaccharide from Moraxella bovis.
Lipopolysaccharide from Moraxella bovis was isolated and its components characterized by paper and gas-liquid chromatography and mass spectrometry. The endotoxin showed a small amount of protein and contained 2-keto-3-deoxyoctonic acid glucose, mannose, glucosamine, heptose and phosphate. Six fatty acids (palmitic, palmitoleic, margaric, stearic, oleic and arachidic acids) were also identified. Margaric acid was the most prevalent fatty acid present in the lipid fraction.


Expression of a constitutively active Cdc42 homologue promotes development of sclerotic bodies but represses hyphal growth in the zoopathogenic fungus Wangiella (Exophiala) dermatitidis.
In contrast to the CDC42 homologues of Saccharomyces cerevisiae and Schizosaccharomyces pombe, the WdCDC42 gene in the human pathogenic fungus Wangiella (Exophiala) dermatitidis was found to be nonessential for cell viability. Expression of the constitutively active allele wdcdc42(G14V) at 37 degrees C induced nonpolarized growth that led to cell enlargement and multiple nucleation. The swollen cells subsequently converted into planate divided bicellular forms or multiply septated sclerotic bodies in post-log phase, when the G14V-altered protein was diminished. The wdcdc42(G14V) mutation also strongly repressed filamentous growth both in the wild-type strain and in the temperature-sensitive hyphal-form mutant Hf1. In contrast, overexpression of the dominant negative alleles wdcdc42(T19N) and wdcdc42(D120A) had no obvious effect on fungal-cell polarization. These results suggested that WdCdc42p plays a unique regulatory role in cellular morphogenesis in W. dermatitidis. Activation of this protein in response to extracellular or intracellular signals seems to commit its yeast-like cells to a phenotype transition that produces sclerotic bodies while repressing hyphal development.


Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors.
A number of cyclic and linear peptides containing various combinations of amino acids were evaluated for their Src kinase inhibitory potency. Among all the peptides, cyclic decapeptide C[RW]5 containing alternative arginine (R) and tryptophan (W) residues was found to be the most potent Src kinase inhibitor. C[RW]5 showed higher inhibitory activity (IC50=2.8 μM) than C[KW]5, L(KW)5, C[RW]4, and C[RW]3 with IC50 values of 46.9, 69.1, 21.5, and 25.0 μM, respectively, as determined in a fluorescence intensity-based assay. Thus, the cyclic nature, the presence of arginine, ring size, and the number of amino acids in the structure of the peptide were found to be critical in Src kinase inhibitory potency. The IC50 value of C[RW]5 was found to be 0.8 μM in a radioactive assay using [γ-(32)P]-ATP and polyE4Y as the substrate. C[RW]5 was a noncompetitive Src kinase inhibitor, showing approximately fourfold more selectivity towards Src than Abl.


Abietane diterpenoids from suspension cultured cells of Torreya nucifera var. radicans.
Three abietane diterpenoids were isolated from the suspension cultured cells of Torreya nucifera var. radicans along with four known abietane diterpenoids. Based on spectroscopic evidence, the structures of the three were elucidated as (3S,5R,10S)-7-oxo-12-methoxyabieta-8,11,13-triene-3,11-diol, (3S,5R,10S)-7-oxo-12-methoxyabieta-8,11,13-triene-3,11,14-triol and (5R,10S)-3-oxo-7R,12-dimethoxyabieta-8,11,13-trien-11-ol, respectively.


First-line antihypertensive treatment for severe hypertension in pregnancy: A systematic review and network meta-analysis.
Hydralazine, labetalol, and nifedipine are the recommended first-line treatments for severe hypertension in pregnancy. While all three are effective, there is a lack of sufficient evidence regarding their comparative safety and efficacy. To determine the comparative safety and efficacy of the first-line treatment options for severe hypertension in pregnancy. A systematic search of Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 31, 2018 was conducted. RCTs in pregnancy comparing a first-line antihypertensive agent to another first-line agent for the treatment of severe hypertension in pregnancy. Screening, data abstraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a Bayesian network meta-analysis with vague priors was conducted. Of the 1330 publications identified, 17 RCTs comprised of a total of 1591 women met our selection criteria. For successful treatment of severe hypertension, nifedipine was found to be superior to hydralazine (OR 4.13 [95% CrI 1.01-20.75]) but not labetalol (OR 3.43 [95% CrI 0.94-19.95]). This was not associated with an increased risk for caesarean delivery or maternal side effects. There was no significant difference between labetalol and hydralazine. Given the results of this systematic review and network meta-analysis, maternity care providers should feel comfortable initiating management of severe hypertension in pregnancy using oral nifedipine.


Modeling Causal Relationships in Quality Improvement.
Taking the time to plan a quality improvement project before starting the project improves the likelihood of success. Understanding the tools that can be utilized for identification of a problem, the causes behind it, and the development of the theoretical framework of the planned improvement are crucial. Fishbone diagrams or cause and effect diagrams are often utilized to identify the root causes leading to an identified problem. Keydriver diagrams can provide the structure for a quality improvement project, establishing the aim and identifying the drivers and interventions that lead to change. This paper reviews these two quality improvement tools. When beginning a quality improvement project, several tools can be used to begin identifying where to target efforts. Utilizing process maps and failure modes and effects analysis (FMEA) can help define a process, identify failures, and develop interventions to be considered. Process maps identify potential gaps or excess steps and reveal sequential relationships. FMEAs aid in the development of causal relationships between a failure mode and its effects, priming the quality improver to create interventions. An additional way to model causal relationships is with fishbone diagrams and key driver diagrams. The fishbone diagram enables teams to consider why a problem has occurred and search for the root causes. The key driver diagram provides the ultimate aim of the project, identifies the drivers which will affect accomplishing the aim, and the interventions that affect the identified drivers. This paper will carefully examine both fishbone diagrams and key driver diagrams.


Alterations in glutamate but not GABAA receptor subunit expression as a consequence of epileptiform activity in vitro.
The consequences of epileptiform discharge on the expression of glutamate and GABA receptors were examined by in situ hybridization histochemistry after treatment of rat hippocampal slice cultures with convulsants. Application of 500 microM picrotoxin for two days led to decreases in the messenger RNA levels for the N-methyl-D-aspartate receptor subunits, NR2A and NR2B, and for the non-N-methyl-D-aspartate receptor subunits, glutamate receptors 1 and glutamate receptors 2, to about 50% of the levels seen in control cultures. Messenger RNA levels for the N-methyl-D-aspartate receptor subunit, NR1; the non-N-methyl-D-aspartate receptor subunits, glutamate receptors 3 and 4; the high-affinity kainate receptor subunits 1 and 2; and the GABAA receptor subunits, alpha 2, beta 2, gamma 2 were unchanged. Decreased levels of expression were no longer seen five days after removal of convulsant. The down-regulation could be prevented by co-application of both the non-N-methyl-D-aspartate and N-methyl-D-aspartate receptor antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine maleate, but not by applying each alone. Application of CNQX or dizocilpine maleate in the absence of picrotoxin also resulted in changes in glutamate receptor expression. We suggest that the convulsant-induced reduction in glutamate receptor expression leads to a decreased excitability in these cultures, and that this down-regulation represents a compensatory reaction of hippocampal pyramidal cells to enhanced excitatory input.


A community-based telephone survey of social anxiety disorder in Hong Kong.
Research on the prevalence and characteristics of social anxiety disorder (SAD) is lacking in Chinese communities. A random telephone survey of 3006 individuals aged 15-45 years in Hong Kong was conducted using a questionnaire that generated DSM-IV diagnosis and other clinical characteristics of SAD. 3.2% of the participants surveyed met criteria for SAD in the previous year. Their demographic and clinical characteristics are typical. Only 8.7% of sufferers sought medical treatment. No clinical reappraisal was conducted. Severity and comorbidity of SAD were not examined. SAD is a cross-culturally real illness. The prevalence, chronicity, and under-treatment of SAD in Chinese people calls for further research and efforts to reduce its treatment gap.


Reply to Comment on Shen H, et al. "Co-signaling receptors regulate T-cell plasticity and immune tolerance". Frontiers in Bioscience-Landmark. 2019; 24: 96-132.
No abstract present.


Using the Brink score to predict postpartum anal incontinence.
To evaluate whether antepartum pelvic floor muscle strength, as measured by the Brink scale, predicts postpartum anal incontinence. This prospective cohort study of primigravid women used validated questionnaires and standardized pelvic examinations to evaluate subjects during the third trimester and at 2 postpartum time points. Of the initial 129 subjects, 102 and 81 completed 2 week and 6 month postpartum visits. 35% had cesarean deliveries. The antepartum prevalence of fecal incontinence (14%) did not differ significantly from the postpartum (17% at 2 weeks, 11% at 6 months). However, the prevalence of flatal incontinence fell from antepartum (65%) to postpartum (47% at 2 weeks, P = .001; 49% at 6 months, P = .012). Mean Brink score decreased postpartum; no correlations were found between Brink score and questionnaire scores. Anal incontinence symptoms are common in the third trimester of a first pregnancy and may regress or resolve after delivery. Brink score did not predict postpartum anal incontinence.


Genetic control of susceptibility to Candida albicans in susceptible A/J and resistant C57BL/6J mice.
The importance of host factors in determining susceptibility to systemic Candida albicans infections is evident in both humans and mice. We have used a mouse model to study the genetic basis of susceptibility, using the inbred strains A/J and C57BL/6J, which are susceptible and resistant, respectively, based on different parameters of the response to infection. To identify genes responsible for this differential host response, brain and kidney fungal load were measured in 128 [A/J x C57BL/6J] F(2) mice 48 h after infection with 5 x 10(4) C. albicans blastospores. Segregation analysis in this informative population identified complement component 5 (C5/Hc) as the major gene responsible for this differential susceptibility (LOD of 22.7 for kidney, 19.0 for brain), with a naturally occurring mutation that causes C5 deficiency leading to enhanced susceptibility. C5 was also found to control heart fungal load, survival time, and serum TNF-alpha levels during infection. Investigation of the response to C. albicans challenge in a series of AcB/BcA recombinant congenic strains validated the importance of C5 in determining the host response. However, the strains BcA67 and BcA72 showed discordant phenotypes with respect to their C5 status, suggesting additional complexity in the genetic control of the inter-strain difference in susceptibility observed in A/J and C57BL/6J following systemic infection with C. albicans.


Heparin-neutralizing activity in the plasma of women with gynecologic malignancy: the effect of tumor stage on heparin concentration and fibrin generation after low-dose heparin.
The relationship between tumor stage and the concentration of circulating heparin achieved after subcutaneous administration and its effect on fibrin generation were studied in 24 women with gynecologic malignancy. A single subcutaneous injection of 5000, 7500, and 10,000/U of sodium heparin was given in random order on different days. Plasma specimens for antithrombin III, fibrinopeptide A, and heparin were obtained serially over an 11-hour interval. Women with a Stage III or IV malignancy had significantly lower circulating heparin after the 5000 and 10,000/U doses. There was a significant decline in fibrinopeptide A as the concentration of circulating heparin increased. Thirty-three percent of women with a Stage III or IV malignancy had no detectable circulating heparin at any point examined over the 11 hours after 5000/U of heparin. Likewise, 16.7% and 8.4% had no detectable circulating heparin after 7500 and 10,000/U, respectively. A similar percentage was noted in a smaller group of women with Stage II malignancy. Next, a known quantity of heparin was added to the plasma from these patients and the concentration of heparin was determined. A significant amount of heparin-neutralizing activity was documented. We conclude that a large percentage of women with an advanced gynecologic malignancy are able to neutralize heparin administered for the prevention of thromboembolic disease. This heparin-neutralizing activity may account for the failure of low-dose heparin to prevent thromboembolic complications in this patient population.


[Ways of optimization of air-medical evacuation of wounded and ill patients during the armed conflict].
The article is devoted to the experience of airmedical evacuation struck during operations in territory of the Chechen Republic of 1999-2002. We consider, that optimal medical-evacuation system in local wars, local fight actions and battles consists only two stages, then victim after first physician aid is evacuated to specialized medical unit. Own experience of preflight preparation and support is generalized and analysed at carrying out of airmedical evacuation of 928 critically wounded patients and the struck on tactical, operative and strategic levels during a confrontation in territory of the Chechen Republic (1999-2002).


Stability of tympanoplasty in children.
The results of tympanoplasty performed for noncholesteatomatous chronic otitis in children aged 2 to 14 years are described. The authors report that the stability of hearing was excellent; they found hearing to be equally good in young children and in older children. Tympanic membrane perforation can be closed at any age. There is no age limit below which perforation should not be closed.


Surface sensing triggers a broad-spectrum antimicrobial response in Pseudomonas aeruginosa.
Interspecies bacterial competition may occur via cell-associated or secreted determinants and is key to successful niche colonization. We previously evolved Pseudomonas aeruginosa in the presence of Staphylococcus aureus and identified mutations in the Wsp surface-sensing signalling system. Surprisingly, a ΔwspF mutant, characterized by increased c-di-GMP levels and biofilm formation capacity, showed potent killing activity towards S. aureus in its culture supernatant. Here, we used an unbiased metabolomic analysis of culture supernatants to identify rhamnolipids, alkyl quinoline N-oxides and two siderophores as members of four chemical clusters, which were more abundant in the ΔwspF mutant supernatants. Killing activities were quorum-sensing controlled but independent of c-di-GMP levels. Based on the metabolomic analysis, we formulated a synthetic cocktail of four compounds, showing broad-spectrum anti-bacterial killing, including both Gram-positive and Gram-negative bacteria. The combination of quorum-sensing-controlled killing and Wsp-system mediated biofilm formation endows P. aeruginosa with capacities essential for niche establishment and host colonization.


Bromodomain-containing protein 9 promotes the growth and metastasis of human hepatocellular carcinoma by activating the TUFT1/AKT pathway.
Bromodomain-containing protein 9 (BRD9) has a critical role in human squamous cell lung cancer, acute myeloid leukemia, and malignant rhabdoid tumors. However, the expression and biological role of BRD9 in hepatocellular carcinoma (HCC) is poorly understood. In this study, BRD9 expression was found to be elevated in HCC through data mining of public databases. Next, we confirmed that the expression of BRD9 was increased in HCC tissues compared with that in adjacent non-tumor tissues. The upregulated level of BRD9 was also observed in HCC cells in comparison to LO2 cells. The increased BRD9 expression was correlated with unfavorable clinicopathological features. A high level of BRD9 predicted a poorer overall survival and disease-free survival of HCC patients. Functionally, BRD9 overexpression facilitated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of Hep3B cells. Conversely, either BRD9 depletion or pharmacological inhibition of BRD9 resulted in the reduced proliferation and invasiveness of HCCLM3 cells. In addition, the BRD9 knockdown restrained the growth and metastasis of HCCLM3 cells in vivo. Mechanistically, BRD9 positively regulated TUFT1 expression and AKT activation in HCC cells. ChIP-qPCR analysis indicated that BRD9 promoted the binding of P300 acetyltransferase to the TUFT1 promoter and epigenetically regulated TUFT1 expression by increasing H3K27Ac in the promoter. Notably, either TUFT1 knockdown or AKT inhibitor (MK2206) abrogated the promoting effects of BRD9 on the proliferation, migration, invasion, and EMT of Hep3B cells. The forced expression of TUFT1 abolished the effects of BRD9 knockdown on the growth and metastasis of HCCLM3 cells. Altogether, these data indicate that BRD9 promotes the growth and metastasis of HCC cells by activating the TUFT1/AKT pathway and may serve as a promising biomarker and therapeutic target for HCC.


Quantitative analysis of catechol and 4-methylcatechol in human urine.
A method was developed for the quantitative analysis of catechol and 4-methylcatechol in human urine. [U-14C]Catechol was used as in internal standard. Urine was treated with beta-glucuronidase and sulphatase, acidified and extracted with ether. The ether extract was silylated and analysed by glass capillary gas chromatography. Catechol and 4-methylcatechol occurred in urine primarily as conjugates. Levels of catechol and 4-methylcatechol in the urine of nonsmokers on unrestricted diets were 10 +/- 7.3 (mean +/- 1 SD) and 3.4 +/- 2.3 mg/24 hr, respectively. Nonsmokers on uniform restricted diets, in which the intake of plant-derived products was limited, excreted 4.4 +/- 1.2 mg catechol and 8.1 +/- 1.7 mg 4-methylcatechol/24 hr. Smokers on the same restricted diet excreted 6.8 +/- 3.0 mg catechol and 6.1 +/- 2.6 mg 4-methylcatechol/24 hr. These results indicate that diet is a major factor in determining urinary catechol levels and that the contribution of smoking is comparatively small. Catechol and 4-methylcatechol appear to have different dietary precursors.


Pediatric Acute-on-Chronic Liver Failure.
Acute-on-chronic liver failure (ACLF) is characterized by an acute hepatic insult happening in a patient with underlying cirrhosis with compromised hepatic reserve leading to development of systemic inflammation, sepsis, and organ failure resulting in poor outcome in majority. While Asia Pacific Association for Study of Liver Diseases (APASL) emphasizes on early diagnosis before development of organ failure, European Association for Study of Liver Diseases (EASL) mandates the presence of organ failures to define ACLF. There is a lack of consensus definition of pediatric ACLF although recent APASL guidelines have tried to address the issue. While Wilson disease (WD) and autoimmune hepatitis (AIH) are the most common cause of underlying cirrhosis in children, acute viral hepatitis and flares of WD and AIH are the commonest acute precipitating events. Poor outcomes [death and liver transplantation (LT)] ranging from 19 to 59% have been reported. Prognosis in pediatric ACLF is usually better than that in adults due to greater proportion of treatable etiologies, lesser organ failures, comorbidities and better hepatic reserves. APASL ACLF Research Consortium (AARC) score more than or equal to 11 is predictive of poor 28-90 d mortality. Treatment of pediatric ACLF relies mainly on prompt diagnosis and medical management of a potentially treatable etiology of underlying cirrhosis. Bridging therapies, especially high volume plasma exchange can be initiated early as a bridge to LT or native liver recovery. Those with no improvement in 4-7 d should undergo LT before development of sepsis or multi-organ failure.


[Amniotic band syndrome: description of 2 clinical cases and discussion on etiopathogenesis].
The paper reports two cases in which infants were born with alterations described as the Amniotic Band Syndrome. The first one shows inferior limbs in bizarre positions, and the superior mutilated; also a cleft lip was present. The second case corresponds to a newborn with a facionucal band that almost separates the mouth from the rest of the face. Pathogenic theories are reexamined in face of the cases presented.


Electrochemical sensing platform based on the biomass-derived microporous carbons for simultaneous determination of ascorbic acid, dopamine, and uric acid.
A novel and highly selective electrochemical sensing platform (ZnCl2-CF/GCE) based on combination of kiwi skin and zinc chloride nanoparticles was developed for the simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The constructed electrode shows a high surface area and micro-mesoporous structure. And the electrochemical behaviors of the electrode were further explored by cyclic voltammetry (CV), impedance analysis (EIS), and differential pulse voltammetry (DPV). Under the optimal conditions, the ZnCl2-CF provides a high sensitivity and selective signaling in the co-existence system of AA, DA, and UA with linear response ranges of 0.05-200 μM, 2-2000 μM, and 1-2500 μM, respectively. The detection limits (S/N = 3) were calculated to be 0.02 μM, 0.16 μM, and 0.11 μM, respectively. In addition, the method has been successfully applied to determine AA, DA, and UA in real samples, which provides potential applications in further sensing study.


A Cartilaginous Construct with Bone Collar Exerts Bone-Regenerative Property Via Rapid Endochondral Ossification.
Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be implanted into tissue defects with no artificial scaffolds. In addition, the cellular properties and characteristics of the ECM in C-MSCs can be regulated in vitro. Most bone formation in the developmental and healing process is due to endochondral ossification, which occurs after bone collar formation surrounding cartilage derived from MSCs. Thus, to develop a rapid and reliable bone-regenerative cell therapy, the present study aimed to generate cartilaginous tissue covered with a mineralized bone collar-like structure from human C-MSCs by combining chondrogenic and osteogenic induction. Human bone marrow-derived MSCs were cultured in xeno-free/serum-free (XF) growth medium. Confluent cells that formed cellular sheets were detached from the culture plate using a micropipette tip. The floating cellular sheet contracted to round clumps of cells (C-MSCs). C-MSCs were maintained in XF-chondro-inductive medium (CIM) and XF-osteo-inductive medium (OIM). The biological and bone-regenerative properties of the generated cellular constructs were assessed in vitro and in vivo. C-MSCs cultured in CIM/OIM formed cartilaginous tissue covered with a mineralized matrix layer, whereas CIM treatment alone induced cartilage with no mineralization. Transplantation of the cartilaginous tissue covered with a mineralized matrix induced more rapid bone reconstruction via endochondral ossification in the severe combined immunodeficiency mouse calvarial defect model than that of cartilage generated using only CIM. These results highlight the potential of C-MSC culture in combination with CIM/OIM to generate cartilage covered with a bone collar-like structure, which can be applied for novel bone-regenerative cell therapy.


Insect homolog of oxytocin/vasopressin associated with parenting of males but not females in a subsocial beetle.
Parental care is thought to evolve through modification of behavioral precursors, which predicts that mechanistic changes occur in the genes underlying those traits. The duplicated gene system of oxytocin/vasopressin has been broadly co-opted across vertebrates to influence parenting, from a preduplication ancestral role in water balance. It remains unclear whether co-option of these genes for parenting is limited to vertebrates. Here, we experimentally tested for associations between inotocin gene expression and water balance, parental acceptance of offspring, and active parenting in the subsocial beetle Nicrophorus orbicollis, to test whether this single-copy homolog of the oxytocin/vasopressin system has similarly been co-opted for parental care in a species with elaborate parenting. As expected, inotocin was associated with water balance in both sexes. Inotocin expression increased around sexual maturation in both males and females, although more clearly in males. Finally, inotocin expression was not associated with acceptance of larvae, but was associated with a transition to male but not female parenting. Moreover, level of offspring provisioning behavior and gene expression were positively correlated in males but uncorrelated in females. Our results suggest a broad co-option of this system for parenting that may have existed prior to gene duplication.


Detecting alcohol abuse: traditional blood alcohol markers compared to ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) measurement in hair.
Alcohol abuse is a common problem in society; however, the technical capabilities of evaluating individual alcohol consumption using objective biomarkers are rather limited at present. In recent years research has focused on alcohol markers using hair analysis but data on performance and reliable cut-off values are still lacking. In this study 169 candidates were tested to compare traditional biomarkers, such as carbohydrate-deficient-transferrin (CDT), gamma glutamyl transferase (GGT), aspartate amino transferase, alanine amino transferase and the mean corpuscular volume of the erythrocytes, with alcohol markers detectable in hair such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). This study revealed that EtG, GGT and CDT showed the best results, demonstrating areas under the curve calculated from receiver operating characteristics of 0.941, 0.943 and 0.899 respectively. The lowest false-negative and false-positive rates were obtained by using a combined interpretation system for hair EtG and FAEEs. All markers demonstrated only low to moderate correlations. Optimum cut-off values for differentiation between social and chronic excessive drinking calculated for hair EtG and FAEEs were 28 pg/mg and 0.675 ng/mg, respectively. The critical values published in the "Consensus on Alcohol Markers 2012" by the Society of Hair Testing were confirmed.


Faculty development: the educator's portfolio: its preparation, uses, and value in academic medicine.
The educator's portfolio is of value for both university and community-based academic faculty. It can be used to document scholarly activity and teaching and to prepare for periodic evaluations. Many faculty members use it to assist them in managing their careers and to reflect on activities and teaching efforts to ensure continued growth in competency as teachers. Promotion and tenure committees of many institutions now use this document to aid them in making promotion decisions.


Lipoxin A4 analog attenuates morphine antinociceptive tolerance, withdrawal-induced hyperalgesia, and glial reaction and cytokine expression in the spinal cord of rat.
Spinal neuroinflammation has been shown to play an important role in the development of morphine tolerance and morphine withdrawal-induced hyperalgesia. Lipoxins are endogenous lipoxygenase-derived eicosanoids that can function as "braking signals" in inflammation. The present study investigated the effect of 5 (S), 6 (R)-lipoxin A4 methyl ester (LXA4ME), a stable synthetic analog of lipoxin A4, on the expression of antinociceptive tolerance and withdrawal-induced hyperalgesia in chronic morphine-treated rats. Chronic morphine administration through repeated subcutaneous injection induced the development of hyperalgesia and the expression of spinal antinociceptive tolerance to morphine. However, LXA4ME treatment significantly attenuated the development of hyperalgesia and the expression of spinal antinociceptive tolerance to intrathecal morphine in both mechanical and thermal test. Moreover, the administration of LXA4ME during the induction of morphine tolerance inhibited the activation of microglia and astrocytes; reduced the expression of proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α); upregulated the expression of anti-inflammatory cytokines IL-10 and transforming growth factor-β1 (TGF-β1); and inhibited nuclear factor-kappa B (NF-κB) activation at the L5 lumbar spinal cord. These results suggest that treatment of LXA(4)ME provides a potential preventative or therapeutic approach for morphine tolerance and associated abnormal pain sensitivity.


Toxicity of methylparaben to green microalgae species and derivation of a predicted no effect concentration (PNEC) in freshwater ecosystems.
Methylparaben (MeP) is one of the most used preservatives in the industry; however, the toxic effects on aquatic ecosystems are still poorly understood. Therefore, this study was conducted (1) to identify and compare the toxic effects of MeP on physiological parameters of different green microalgae species, using suitable mathematical models; and (2) to estimate a PNEC value for MeP in freshwater ecosystems, adopting either the deterministic or the probabilistic approaches. Toxicity tests were carried out with three green microalgae (Pseudopediastrum boryanum, Desmodesmus communis, Raphidocelis subcapitata), in which different endpoints such as growth rate, chlorophyll-a, and cell viability were measured and compared through the effective concentration which caused a response in x% of test organisms (ECx). ECx were obtained by adjusting different non-linear regression models for each microalgae dataset. Chlorophyll-a endpoint resulted in the lowest EC50 values, respectively 125, 81.2, 18.3 mg L-1 for D. communis, P. boryanum and R. subcapitata, showing R. subicapitata as the most sensitive, and D. communis as the most tolerant species to MeP (P < 0.05). PNEC was estimated from the present study and previous reports resulting in 5.7 and 65 μg L-1, respectively for the deterministic (PNECd) and the probabilistic (PNECp) approach. The development of chronic assays using test organisms from different ecological groups is encouraged to provide robust PNECp. In this meantime, we recommend the use of the estimated PNECd to support MeP risk assessments and policy formulation.


[Use of UV-irradiated autologous bone marrow in the treatment of bone defects in children].
On the basis of experimental researches has been revealed dose-dependent influence of integral UV-irradiation on osteogenic potential of stromal cells--precursors of bone marrow and determined osteogenesis--stimulating dose (300 J/m2). The technique of photomodified bone marrow application for treatment of osseous defects in children has been worked out. Clinical approval (36 observations) has demonstrated high efficiency of the proposed version of osteoplasty: acceleration of reparative processes, reduction of normal osseous structure restoration terms.


Toxic effects of tributyltin and its metabolites on harbour seal (Phoca vitulina) immune cells in vitro.
The widespread environmental contamination, bioaccumulation and endocrine disruptor effects of butyltins (BTs) to wildlife are well documented. Although suspected, potential effects of BTs exposure on the immune system of marine mammals have been little investigated. In this study, we assessed the effects of tributyltin (TBT) and its dealkylated metabolites dibutyltin (DBT) and monobutyltin (MBT) on the immune responses of harbour seals. Peripheral blood mononuclear cells isolated from pup and adult harbour seals were exposed in vitro to varying concentrations of BTs. DBT resulted in a significant decrease at 100 and 200 nM of phagocytotic activity and reduced significantly phagocytic efficiency at 200 nM in adult seals. There was no effect in phagocytosis with TBT and MBT. In pups, the highest concentration (200 nM) of DBT inhibited phagocytic efficiency. A reduction of tumor-killing capacity of adult natural killer (NK) cells occurred when leukocytes were incubated in vitro with 50 nM DBT and 200 nM TBT for 24h. In adult seals, T-lymphocyte proliferation was significantly suppressed when the cells were exposed to 200 nM TBT and 100 nM DBT. In pups, the proliferative response increased after an exposure to 100 nM TBT and 50 nM DBT, but decreased with 200 nM TBT and 100 nM DBT. The immune functions were more affected by BTs exposure in adults than in pups, suggesting that other unsuspected mechanisms could trigger immune parameters in pups. The toxic potential of BTs followed the order of DBT>TBT>MBT. BT concentrations of harbour seal pups from the St. Lawrence Estuary (Bic National Park) ranged between 0.1-0.4 ng Sn/g wet weight (ww) and 1.2-13.4 ng Sn/g ww in blood and blubber, respectively. For these animals, DBT concentrations were consistently below the quantification limit of 0.04 ng Sn/g ww in blood and 0.2 ng Sn/g ww in blubber. Results suggest that concentrations measured in pups are considered too low to induce toxic effects to their immune system during first days of life. However, based on our in vitro results, we hypothesize that BTs, and DBT in particular, could pose a serious threat to the immune functions in free-ranging harbour seal adults.


A possible mechanism for cholesteryl ester formation during demyelination: lecithin:cholesterol acyltransferase (LCAT) activity in rat brain.
Lecithin:cholesterol acyltransferase (LCAT) activity has been examined in the rat by using a brain homogenate preparation as the phospholipid substrate and blood plasma as the enzyme source. LCAT activity was detected on using 60 mul of serum onwards. Successive experiments have also shown that LCAT activity is present in the edematous rat brain tissue homogenate when incubated with inactivated rat plasma as substrate. The results are discussed in relation to cholesteryl ester accumulation in brain during demyelinating diseases.


mHealth intervention for carers of individuals with a history of stroke: Heuristic evaluation and user perspectives.
Caregiving in stroke is complex, with most carers having little to no preparation to care for individuals with a history of stroke, leading to emotional impact. Technologies such as Mobile Health can provide the carer with real-time support and prepare the carer to assume their new roles and responsibilities. To perform a heuristic evaluation of mHealth interventions designed to support carers of individuals with a history of stroke and determine the user preferences in stroke caregiving technology to inform future researchers and developers regarding the best practices to support these individuals. Twenty adults (i.e. 10 usability experts and 10 carers) participated in an iterative user-centred design study that focused on developing and modifying the mHealth intervention (StrokeCaregiver (SeCr)) created to support stroke caregiving. The intervention was repeated in four cycles, including two cycles with five usability experts each and five carers each. SeCr was iteratively improved to develop a highly usable product in multiple cycles. Participants demonstrated critical needs in personalized information support, communication with their healthcare needs, and the trust of the user, content, and developer. These critical needs are required to be met to promote long-term acceptance and adherence. While SeCr was developed to address the needs of carers of individuals with a history of stroke, several considerations must be made to ensure it can be used in a real-world setting. Researchers and developers can use co-design or living lab approaches to further meet the needs and expectations of the carer and enable these individuals to be better prepared for stroke caregiving.


Non-small cell lung carcinoma cell motility, rac activation and metastatic dissemination are mediated by protein kinase C epsilon.
Protein kinase C (PKC) ε, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCε in lung cancer metastasis has not yet been established. Here we show that RNAi-mediated knockdown of PKCε in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCε depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCε with εV1-2, a specific PKCε inhibitor. PKCε was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCε-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Our results implicate PKCε as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target.


Improving existing analysis pipeline to identify and analyze cancer driver genes using multi-omics data.
The cumulative of genes carrying mutations is vital for the establishment and development of cancer. However, this driver gene exploring research line has selected and used types of tools and models of analysis unsystematically and discretely. Also, the previous studies may have neglected low-frequency drivers and seldom predicted subgroup specificities of identified driver genes. In this study, we presented an improved driver gene identification and analysis pipeline that comprises the four most widely focused analyses for driver genes: enrichment analysis, clinical feature association with expression profiles of identified driver genes as well as with their functional modules, and patient stratification by existing advanced computational tools integrating multi-omics data. The improved pipeline's general usability was demonstrated straightforwardly for breast cancer, validated by some independent databases. Accordingly, 31 validated driver genes, including four novel ones, were discovered. Subsequently, we detected cancer-related significantly enriched gene ontology terms and pathways, probable drug targets, two co-expressed modules associated significantly with several clinical features, such as number of positive lymph nodes, Nottingham prognostic index, and tumor stage, and two biologically distinct groups of BRCA patients. Data and source code of the case study can be downloaded at https://github.com/hauldhut/drivergene .


Evaluating slow-transit constipation in patients using laxatives: a better approach or do we need improved patient selection?
Slow-transit constipation is a relatively frequent subtype of constipation, often refractory to medical treatment. Clinical information is usually obtained in patients during laxative withdrawal; thus, data on the effect of laxatives on their daily symptoms are lacking. The evaluated article reports on the effects of laxatives on symptoms (stool frequency, stool form, straining at stool, pain and bloating) and on laxative use by means of a daily stool questionnaire. Most patients used laxatives on an intermittent basis, and a minority also used associated enemas. Use of laxatives yielded an almost average normal daily number of evacuations in this group, with only a minority having less than three bowel movements per week. The days in which patients used laxatives yielded significantly more frequent and loose stools compared with those without laxatives. Thus, the use of laxatives seems to influence the clinical aspects of patients with slow-transit constipation, and this should be considered when evaluating these participants.


Pleiotropic drug resistance in cystic fibrosis fibroblasts: increased resistance to cyclic AMP.
In previous studies, cystic fibrosis (CF) fibroblasts were demonstrated to be resistant to the cytotoxic effects of ouabain, dexamethasone, and the sex hormones, dihydrotestosterone, 17beta-estradiol, and progesterone. We now show that CF fibroblasts also exhibit greatly increased resistance to the cytotoxic effects of exogenous dibutyryl cyclic AMP (cAMP), as well as to isoproterenol and theophylline, drugs which are known to increase endogenous levels of cAMP. CF cells were also shown to have normal amounts of (3H)cAMP binding to protein kinase as well as normal amounts of cAMP-stimulated protein kinase activity. Phosphodiesterase in CF cells was also found to be stimulated by cAMP to the same degree as in normal cells. These findings suggest that there is no detectable protein kinase deficiency in CF cells. cf cells thus appear to be unlike some cAMP-resistant mutants described by others which are defective in protein kinase activity and cAMP regulation of phosphodiesterase levels. The cross-resistance of CF fibroblasts to ouabain, steroid hormones, and cAMP may provide a unique opportunity to study the biochemical events involved in the metabolism of these drugs as well as the basic biochemical defect in a common human genetic disease.


Biflavonoid-rich fraction from Daphne pseudomezereum var. koreana Hamaya exerts anti-inflammatory effect in an experimental animal model of allergic asthma.
Daphne pseudomezereum var. koreana Hamaya is distributed in the Gangwon-do of South Korea and is traditionally used to treat chronic inflammatory diseases, including rheumatoid arthritis. We investigated the anti-inflammatory effect of biflavonoid-rich fraction (BF) obtained from an extract of D. pseudomezereum leaves on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and mouse model of ovalbumin (OVA)-induced allergic asthma. Neochamaejasmin B (NB) and chamaejasmin D (CD) were spectroscopically characterized as major components of BF obtained from the leaves of D. pseudomezereum. RAW264.7 cells pretreated with NB, CD and BF and activated by LPS (500 ng/ml) were used to assess the anti-inflammatory effects of these materials in vitro. To evaluate the protective effect of BF on allergic asthma, female BALB/c mice were sensitized to OVA by intraperitoneal (i.p.) injection and treated with BF by oral administration (15 or 30 mg/kg). Pretreatment with BF inhibited LPS-stimulated nitric oxide (NO), TNF-α and IL-6, and led to upregulation of heme oxygenase-1 (HO-1) in RAW264.7 macrophages. Orally administered BF significantly inhibited the recruitment of eosinophils and the production of IL-5, IL-6, IL-13 and MCP-1 as judged by the analysis of BALF from OVA-induced asthma animal model. BF also decreased the levels of IgE in the serum of asthmatic mice. BF suppressed the influx of inflammatory cells into nearby airways and the hypersecretion of mucus by the airway epithelium of asthmatic mice. In addition, the increase in Penh in asthmatic mice was reduced by BF administration. Furthermore, BF led to Nrf2 activation and HO-1 induction in the lungs of mice. These data have shown the anti-asthmatic effects of BF, and therefore we expect that BF may be a potential candidate as a natural drug/nutraceutical for the prevention and treatment of allergic asthma.


Health workforce governance and professions: a re-analysis of New Zealand's primary care workforce policy actors.
This article contributes to the health workforce planning literature by exploring the dynamics of health professions in New Zealand's Primary Care sector and deriving broad lessons for an international audience. Professions tend influence health policy and governance decisions and practices to retain their place, status and influence. Therefore, understanding their power dynamics and the positions that they have on workforce policies and issues assists workforce governance or health system reform plans. Using the infrequently reported health workforce policy tool, actor analysis, a reanalysis of previously collected data is undertaken using an actor-based framework for the study of professionalism. Two models were developed, (1) the framework's original four-actor model and (2) a five-actor model for the comparison of the Medical and Nurse professions. Existing workforce actor data were reclassified, formatted, and entered into actor analysis software to reveal the professions' relative power, inter-relationships and strategic workforce issue positions. In the four-actor model, the Organised user actor is found to be most influential, while the others are found to be dependent. In the five-actor model, the Medical and Nurse professions are individually more influential than their combined position in the four-actor model. Practicing professionals and Organised user actors have strong converging inter-relationships over workforce issues in both models, though in the five-actor model, the Nurse profession has weaker coherency than the Medical profession. The Medical and Nurse professions are found to be in opposition over the workforce issues labelled divisive. These results reflect the professions' potential to influence New Zealand's Primary Care sector, indicating their power and influence over a range of policy and reform measures. As such, the four lessons that are derived from the case indicate to policy makers that they should be aware of situational contexts and actor power, take care when encountering divisive issues and try to achieve broad-based support for proposed policies.


Proteinuria in the dog: a pathomorphological study of 51 proteinuric dogs.
Renal cortical biopsies of 51 dogs with spontaneous proteinuria were examined by histology, electron microscopy and immunofluorescence. Glomerular lesions were classified in four groups: mesangioproliferative, membranoproliferative and membranous glomerulonephritis and amyloidosis. The glomerular and the tubulointerstitial lesions were graded, using a semiquantitative system. The results were used for the calculation of correlation coefficients between several parameters. A positive correlation was found between the severity of glomerular and tubulointerstitial lesions. Fibrin detection by immunofluorescence and histochemical methods appeared not to be correlated. The presence of electron dense deposits correlated only with the fluorescence for IgG and C3. Fluorescence for IgA and IgM was frequently observed in cases with or without dense deposits.


Editorial Commentary: Successful Hip Arthroscopy for Patients With Hypermobility Requires a Patient-centric Approach, Meticulous Capsular Management, and Preservation of the Fibrous Capsular Ligaments.
Successful arthroscopic hip surgery for patients with generalized ligamentous laxity requires dedicated attention to preoperative patient counseling, including consideration of each patient's functional status and goals, careful evaluation of patient symptomatology, and meticulous capsular management. Maximal preservation of the fibrous capsular ligaments that stabilize the hip is of particular importance. It is incorrect to assume all hip patients with an elevated Beighton score should be categorically treated a certain way. There is a complex interplay of morphologic features, such as acetabular version, femoral orientation, capsular volume, and subspine morphology, that play a role in the symptomatology for every hip patient, hypermobility notwithstanding. Moreover, consideration must be given to the variable degree of phenotypic expression of the hypermobility syndromes.


Methylphenidate remediates error-preceding activation of the default mode brain regions in cocaine-addicted individuals.
Many previous studies suggest the potential of psychostimulants in improving cognitive functioning. Our earlier pharmacological brain imaging study showed that intravenous methylphenidate (MPH) improves inhibitory control by altering cortico-striato-thalamic activations in cocaine-dependent (CD) individuals. Here we provide additional evidence for the effects of MPH in restoring cerebral activations during cognitive performance. Ten CD individuals performed a stop signal task (SST) during functional magnetic resonance imaging (fMRI) in two sessions, in which either MPH (0.5mg/kg body weight) or saline was administered intravenously. In the SST, a frequent go signal instructs participants to make a speeded response and a less frequent stop signal instructs them to withhold the response. Our previous work described increased activation of the precuneus/posterior cingulate cortex and ventromedial prefrontal cortex-regions of the default mode network (DMN)-before participants committed a stop error in healthy control but not CD individuals (Bednarski et al., 2011). The current results showed that, compared to saline, MPH restored error-preceding activations of DMN regions in CD individuals. The extent of the changes in precuneus activity was correlated with MPH-elicited increase in systolic blood pressure. These findings suggest that the influence of MPH on cerebral activations may extend beyond cognitive control and provide additional evidence warranting future studies to investigate the neural mechanisms and physiological markers of the efficacy of agonist therapy in cocaine dependence.


Threshold effect of urinary chromium on kidney function biomarkers: Evidence from a repeated-measures study.
Chronic kidney disease (CKD) is a public health concern worldwide, and chromium exposure may be a risk factor due to its potential nephrotoxicity. However, research on the association between chromium exposure and kidney function especially the potential threshold effect of chromium exposure is limited. A repeated-measures study involving 183 adults (641 observations) was conducted from 2017 to 2021 in Jinzhou, China. Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured as kidney function biomarkers. Generalized mixed models and two-piecewise linear spline mixed models were used to assess the dose-response relationship and potential threshold effect of chromium on kidney function, respectively. Temporal analysis was conducted by the latent process mixed model to depict the longitudinal change of kidney function over age. Urinary chromium was associated with CKD (odds ratio [OR] = 1.29; 95 % confidence interval [CI], 6.41, 14.06) and UACR (Percent change = 10.16 %; 95 % CI, 6.41 %, 14.06 %), and we did not find significant association between urinary chromium and eGFR (Percent change = 0.06 %; 95 % CI, -0.80 %, 0.95 %). The threshold analyses suggested the existence of threshold effects of urinary chromium, with inflection points at 2.74 μg/L for UACR and 3.95 μg/L for eGFR. Furthermore, we found that chromium exposure exhibited stronger kidney damage over age. Our study provided evidence for the threshold effects of chromium exposure on kidney function biomarkers and the heightened nephrotoxicity of chromium in older adults. More attention should be paid to the supervision of chromium exposure concentrations for preventing kidney damage, especially in older adults.


A novel ranacyclin-like peptide with anti-platelet activity identified from skin secretions of the frog Amolops loloensis.
Albeit many bioactive peptides have been reported from amphibian skins, no anti-platelet peptide has been identified till to date. Here, an anti-platelet peptide, namely Zongdian platelet inhibitor (ZDPI), with the molecular weight of 1798.6 Da, was purified and characterized from skin secretions of the frog, Amolops loloensis. The amino acid sequence of ZDPI was determined as FRGCWLKNYSPRGCL-NH2 by combination methods of Edman degradation, mass spectrometry analysis and carboxypeptidase Y treatment revealing that it is composed of 15 amino acid residues with two cysteines formed an intra-molecular disulfide bridge and C-terminal amidation. cDNA encoding ZDPI precursor was cloned from skin cDNA library of A. loloensis. The precursor is composed of 63 amino acid (aa) residues including the predicted signal peptide (22 aa), an acidic spacer peptide (19 aa), and mature ZDPI. BLAST search indicates that ZDPI belongs to antimicrobial peptide family of ranacyclin, peptide leucine arginine or odorranain. It was found to inhibit ADP-induced platelet aggregation in a dose-dependent manner. At the concentration of 32 μg/ml, ZDPI completely inhibited platelet aggregation induced by ADP. To the best of our knowledge, this is the first report about an anti-platelet peptide from amphibian skin secretions. Considering its strong inhibitory ability on platelets and simple structure, ZDPI might be an excellent candidate or template to develop anti-thrombosis agent. In addition, the discovery of anti-platelet peptide in the frog skin increases biological function spectrum of amphibian skin peptides.


Studies on the differentiation pathway and growth characteristics of epithelial culture cells of the human prostate.
We established explant primary cultures in order to study the growth and hormone responsiveness, and the differentiation process of prostatic epithelial cells. Cell outgrowth was achieved from explant tissue by using a new DU145-cell-conditioned medium and special plastic coverslips. To define the present model, proliferation assays were tested by [3H]thymidine assay and planimetric analysis. Cells were analyzed using immunocytochemistry, light, phase contrast and electron microscopy, polymerase chain reaction, telomerase ELISA and immunoassay (PSA). Morphology and electron microscopy revealed typical epithelial differentiation. Immunocytochemistry showed the content of basal and secretory epithelial cells, endocrine paracrine cells and a high level of proliferation. With increasing culture time, mature epithelial differentiation (PSA) increases and the initial increase of alpha-smooth muscle actin (alpha-SMA) decreases again. After further passaging, alpha-SMA expression is no longer detected and PSA expression decreases. Furthermore, epithelial cells showed both androgen responsiveness and androgen receptor expression. These findings show the presence of epithelial cells in a process of differentiation with endocrine paracrine cells and a high level of proliferation. This model may maintain the cellular and functional properties more closely related to the human prostate and may provide a valuable tool for studying stem cells and differentiation characteristics.


Electrocatalytic detection of noxious antioxidant diphenylamine in fruit samples with support of Cu@nanoporous carbon modified sensor.
Herein, the facile synthesis of copper(II) and benzene-1,3,5-tricarboxylate (Cu-BTC) and copper nanoporous carbon (Cu@NPC) for the electrochemical detection of diphenylamine (DPA) was systematically investigated. The Cu-BTC and Cu@NPC materials structural, morphological, and thermal stability were evaluated and confirmed using FE-SEM, HR-TEM, XRD, FT-IR, and TGA. The electrocatalytic behavior of sensor materials was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). It is presumed that the structural stability and synergic effect exhibited in Cu@NPC are favorable for enhanced sensitivity and selectivity towards the detection of DPA. The Cu@NPC exhibited a wide linear range (0.09-396.82 μM) and the lowest limit of detection (5 nM). Furthermore, the real sample analysis of the sensor for the detection of DPA in apples and pears confirms its potential capability in practical application.


Predictors of the development of surgical complications among hematopoietic stem cell transplantation recipients.
This study was designed to determine possible risk factors for the development of surgical complications after hematopoietic stem cell transplantation (HSCT). HSCT carries the possibility for the development of surgical morbidities and mortalities; certain populations of patients are at higher risk for developing complications. Defining those risk factors will help surgeons to anticipate and manage these complications. The records of 165 patients at King Hussein Cancer Center (KHCC) were reviewed from January 2007 to December 2008. Patients' characteristics, including age, source and type of transplant, behavior of disease, total body irradiation (TBI), immunity status, and intensity of conditioning were studied. According to our data, abdominal complications were more common among patients who received TBI versus patients who did not, and in patients who received peripheral blood versus bone marrow and cord blood as the source of stem cells. Ear, nose, and throat (ENT) complications were found more in patients who underwent nonmyeloablation conditioning. Catheter-related complications were found more significantly in immune-compromised patients during the post-engraftment period. We also found that ENT complications were more frequent in patients with cord blood as the source of stem cells, although the results are inconclusive due to the small sample size. Pretransplantation factors can be used as predictors for the development of surgical complications in HSCT recipients. Abdominal complications were significantly more common in patients who received total body irradiation as part of their conditioning regimen and when the peripheral blood was a source for stem cell transplantation.


Can we dissociate hypervigilance to social threats from altered perceptual decision-making processes in lonely individuals? An exploration with Drift Diffusion Modeling and event-related potentials.
It has been hypothesized that lonely individuals demonstrate hypervigilance toward social threats. However, recent studies have raised doubts about the reliability of tasks commonly used to measure attentional biases toward threats. Two alternative approaches have been suggested to overcome the limitations of traditional analysis of attentional bias. First, the neurophysiological indicators of orienting to threats were shown to have superior psychometric characteristics compared to overt measures of behavioral performance. The second approach involves utilizing computational modeling to isolate latent components corresponding to specific cognitive mechanisms from observable data. To test the usefulness of these approaches in loneliness research, we analyzed behavioral and electroencephalographic (EEG) data from 26 lonely and 26 non-lonely participants who performed a dot-probe task using a computational modeling approach. We applied the Drift Diffusion Model (DDM) and extracted N2pc-an event-related potential that serves as an indicator of spatial attention. No evidence for social threat hypervigilance has been found in DDM parameters nor in N2pc characteristics in the current study. However, we did observe decreased drift rate and increased variability in drift rate between trials within the lonely group, indicating reduced efficiency in perceptual decision-making among lonely individuals. These effects were not detected using standard behavioral measures used in the dot-probe paradigm. Given that DDM indicators were sensitive to differences in perceptual discrimination between the two groups, even when no overt differences were found in standard behavioral measures, it may be postulated that computational approaches offer a more comprehensive understanding of cognitive processes.


Exploring the Onset and Progression of Prostate Cancer through a Multicellular Agent-based Model.
Over 10% of men will be diagnosed with prostate cancer during their lifetime. Arising from luminal cells of the prostatic acinus, prostate cancer is influenced by multiple cells in its microenvironment. To expand our knowledge and explore means to prevent and treat the disease, it is important to understand what drives the onset and early stages of prostate cancer. In this study, we developed an agent-based model of a prostatic acinus including its microenvironment, to allow for in silico studying of prostate cancer development. The model was based on prior reports and in-house data of tumor cells cocultured with cancer-associated fibroblasts (CAF) and protumor and/or antitumor macrophages. Growth patterns depicted by the model were pathologically validated on hematoxylin and eosin slide images of human prostate cancer specimens. We identified that stochasticity of interactions between macrophages and tumor cells at early stages strongly affect tumor development. In addition, we discovered that more systematic deviations in tumor development result from a combinatorial effect of the probability of acquiring mutations and the tumor-promoting abilities of CAFs and macrophages. In silico modeled tumors were then compared with 494 patients with cancer with matching characteristics, showing strong association between predicted tumor load and patients' clinical outcome. Our findings suggest that the likelihood of tumor formation depends on a combination of stochastic events and systematic characteristics. While stochasticity cannot be controlled, information on systematic effects may aid the development of prevention strategies tailored to the molecular characteristics of an individual patient. We developed a computational model to study which factors of the tumor microenvironment drive prostate cancer development, with potential to aid the development of new prevention strategies.


Revisiting the use of the provocative acetylcholine test in patients with chest pain and nonobstructive coronary arteries: A five-year follow-up of the AChPOL registry, with special focus on patients with MINOCA.
This study aimed to assess the angiographic characteristics, feasibility and safety of the provocative test with acetylcholine (AChT), and the influence on further treatment and prognosis of Middle European patients in 5-year follow-up, especially focusing on those with a history of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA). The AChPOL Registry was an ongoing prospective single-center registry that included patients undergoing AChT from December 2010 to March 2013 for further diagnostic evaluation of a suspicious variant angina or coronary microvascular spasm, based on the COVADIS criteria. AChT was injected in incremental doses of 25, 50, and 75µg into the right coronary artery and 25, 50, and 100 µg into the left coronary artery, and the patients were followed up for 5 years. We enrolled 211 patients in the AChPOL Registry. Their mean age was 60.5 ± 7.8 years, with women accounting for 67.8%. The median follow-up was 56 months. AChT revealed variant angina in 99 patients (46.9%) and coronary microvascular spasm in the remaining 72 patients (34.1%). In patients with variant angina, spasm was most frequently observed in the left anterior descending artery (89.9%) and was most frequently diffuse (61.6%). In the microvascular spasm subgroup, there was a significantly higher rate of recurrent chest pain requiring hospitalization in the follow-up than in AChT negative patients. Interestingly, patients with a history of MINOCA had higher rates of MI and recurrent chest pain requiring hospitalization in the follow-up. We showed that AChT was safe in Middle European patients. In the follow-up patients with microvascular spasm and a history of MINOCA had the highest risk of MI and recurrent chest pain requiring hospitalization.


Agrypnia Excitata: a generalized overactivity syndrome and a useful concept in the neurophysiopathology of sleep.
To analyse the clinicophysiological features of delirium tremens (DT), Morvan's fibrillary chorea (MC) and fatal familial insomnia (FFI) as representative of the new concept of Agrypnia Excitata (AE). DT, MC and FFI were compared for their clinical and polysomnographic features and, for MC and FFI, post-mortem verification. DT, MC and FFI all display profound loss of slow-wave sleep (SWS) and abnormal rapid eye movement (REM) sleep with lack of muscular atonia and enacted dreams. Sleep spindles and K complexes are severely reduced. Motor overactivity is associated with increased sympathergic functions. Neuropathology discloses severe loss of neurons in the thalami and cingular areas in FFI, and leakage of antibodies in the thalamus in MC. Based on the similarities in DT, MC and FFI, we propose the new concept of AE as a clinical condition characterized by loss of SWS and abnormal REM sleep, associated with motor and autonomic sympathergic activation. AE is due to dysfunction of the thalamo-limbic system. Moreover, the preservation of light sleep in the face of severe loss of deep sleep in AE argues that 3 rather than the usually considered two (non REM and REM) independent states of sleep exist.


Mortality in Cushing's syndrome: a systematic review and meta-analysis.
Data on mortality associated with Cushing's disease (CD) and Cushing's syndrome (CS) are scarce. To perform a systematic review and meta-analysis of mortality studies in patients with CD and CS secondary to a benign adrenal adenoma. A search was performed in seven electronic databases. Sixty-six articles were retrieved for analysis and 7 included in the final study. The main outcome measure was standardized mortality ratio (SMR). Studies reporting SMR for patients diagnosed with CD and/or CS. Outcomes were stratified by subtype of Cushing's syndrome. Studies were appraised by two authors and were synthesized using a weighted estimate based on the standard error of the SMR. The weighted mean of SMR for patients with CD was 1.84 (95% confidence interval (CI): 1.28-2.65). CD patients with persistent disease after initial surgery had a SMR of 3.73 (95% CI: 2.31-6.01), whereas mortality of CD patients with initial remission did not differ significantly from the general population (SMR: 1.23 (95% CI: 0.51-2.97)). SMR for patients with a benign adrenal adenoma was 1.90 (95% CI: 0.93-3.91). Age, sex and observation time did not significantly impact mortality. CD as opposed to CS due to a benign adrenal adenoma is associated with an excess mortality, which is attributed to patients in whom initial surgical cure is not obtained. This underlines the importance of a rigorous and early follow-up of newly operated patients with CD.


Nitrogen uptake : Apparent pattern during old field succession in Southeastern U.S.
Nitrogen uptake from applied nutrient solutions was evaluated in two old fields, in a pine plantation, and in a hardwood stand, to test the idea that plant communities become more efficient trappers and retainers of plant nutrients during succession. Uptake was estimated as the difference between nutrient concentrations in water collected from beneath soil profiles with and without roots by lysimeters within each successional stage. Results suggest that nitrate uptake decreased while ammonia uptake increased with succession. This apparent shift from a nitrate to an ammonia nitrogen economy during succession has been reported by other workers and is evolutionarily significant as an energy, nitrogen, and cation saving mechanism.


Timing of bimanual movements and deafferentation: implications for the role of sensory movement effects.
In a repetitive tapping task, the within-hand variability of intertap intervals is reduced when participants tap with both hands instead of single-handedly. This bimanual advantage has been attributed to timer as opposed to motor variance (according to the Wing-Kristofferson model; Helmuth and Ivry 1996) and related to the additional sensory consequences of the movement of the extra hand in the bimanual case (Drewing et al. 2002). In the present study the effect of sensory feedback of the movement on this advantage was investigated by comparing the results of a person (IW) deafferented below the neck with those of age-matched controls. IW showed an even more pronounced bimanual advantage than controls, suggesting that the bimanual advantage is not due to actual sensory feedback. These results support another hypothesis, namely that bimanual timing profits from the averaging of different central control signals that relate to each effector's movements.


Photodynamic therapy inhibits experimental allograft rejection. A novel approach for the development of vascular bioprostheses.
Biological vascular allografts have proved unsatisfactory because of thrombosis, occlusion, and aneurysmal degeneration during chronic rejection. Photodynamic therapy (PDT), a technique that leads to the production of cytotoxic free radicals, was investigated as a novel method to prepare arterial allografts. Shortly after impregnation with the photosensitizer drug chloroaluminum sulfonated phthalocyanine, infrarenal aortas of ACI rats were PDT-treated and orthotopically grafted in Lewis rats (PDT). The transplanted grafts were sequentially analyzed at 2, 4, and 8 weeks by morphometry, immunohistochemistry, and scanning electron microscopy. Of 25 untreated allografts, 4 (16%) developed aneurysms compared with 0 of 33 in PDT or untreated isografts (ISO, P < .001). PDT treatment of allografts significantly inhibited intimal hyperplasia (P < .001) and resulted in intimal areas comparable to those in ISO. However, medial thickness in both control allografts and PDT grafts was markedly decreased compared with ISO. External graft diameters of control allografts at 8 weeks were significantly enlarged (P < .02) compared with PDT or ISO. At all time points, T lymphocytes were found in a substantially larger number in untreated control grafts than in PDT or ISO. Scanning electron microscopy at 4 weeks confirmed complete repopulation with endothelial cells in PDT, which was not seen in the control allografts. Our findings suggest that local PDT treatment of arterial allografts inhibits inflammatory infiltration, aneurysmal dilatation, and development of intimal hyperplasia and may be used to develop vascular bioprostheses for use in humans.


Juvenile psammomatoid ossifying fibroma of the maxilla and mandible: A systematic review of published case reports.
The aim of this study is to evaluate recent evidence-based data that summarize the clinicopathological findings and treatment along with follow-up measures taken in terms of published cases of Juvenile psammomatoid ossifying fibroma (JPOF) of the maxilla and mandible by a systematic review. MATERIALS AND METHODS: The databases searched were PubMed, MEDLINE, Scopus, Google scholar, and Cross references. Only those case reports of JPOFs published in the English language from 2000 to 2022 were considered. All cases included confirmed JPOF lesions histopathologically. The SR-included details like clinical and radiographic data, follow-up details such as recurrence, and the presence of any adverse outcome. The database search produced 595 articles from 2000 to 2022, among which 22 case reports were included in the systematic review. The mean age of JPOF occurrence in patients was 18 ± 16 years. A male predilection was noted among patients younger than 14 years of age, whereas a female predilection was noted in patients older than 14 years of age. Frequent involvement of the mandible (56%) compared to the maxilla (44%) was reported. The posterior mandible was the most commonly affected site involving numerous adjacent structures. The expansile nature of the JPOF displayed 57% buccolingual expansion, 50% downward displacement or erosion of the lower border of the mandible and 81% of involvement of the maxillary antrum/pterygoid plate/orbital floor. Among the 20 cases reported, the treatment provided included surgical excision in 45% of the patients, jaw resection in 35% of the patients, and enucleation and curettage in 18% of the patients. Follow-up details were provided in 80% of the reports that showed recurrence. The diagnosis of JPOF requires correlation of the clinical and radiographic features with key histopathological features. Although long-term follow-up of the case reports has been reported, the data lack information about the long-term outcomes of JPOF.


N6-methyladenosine regulates ATM expression and downstream signaling.
N6-methyladenosine (m6A) is the most abundant modification in eukaryotic mRNAs, which plays an important role in regulating multiple biological processes. ATM is a major protein kinase that regulates the DNA damage response. Here, we identified that ATM is a m6A-modificated gene. METTL3 (a m6A "writer") and FTO (a m6A "eraser") oppositely regulated ATM expression and its downstream signaling. Mechanically, m6A "readers" YTHDFs and eIF3A suppressed ATM expression in the post-transcriptional levels. We also revealed the oncogenic potential of METTL3 and YTHDF1 related to ATM modulation. This is the first report that ATM, a master in the DNA damage response, is modified by m6A epigenetic modification, and METTL3 disrupts the ATM stability via m6A modification, thereby affecting the DNA-damage response.


Combined Dup(7)(q22.1q32.2), Inv(7)(q31.31q31.33), and Ins(7;19)(q22.1;p13.2p13.2) in a 12-year-old boy with developmental delay and various dysmorphism.
De novo combined duplications/inversions are very rare chromosomal rearrangements. For chromosome 7 just some dozen cases of duplications of various parts of the long arm have been published. We report on a 12-year-old boy with muscular hypotonia, global developmental delay, short stature, and various facial dysmorphism including frontal bossing, temporal narrowing, slightly down-slanting palpebral fissures, a broad nasal root, a long philtrum, a thin and tented upper lip, a drooping lower lip, micrognathia, prominent ears, a short neck, and a low posterior hairline. Karyotype analysis and molecular investigations revealed a complex de novo chromosomal rearrangement on 7q. FISH analysis with locus specific YACs and BACs and SNP array with the Illumina(®) HumanOmni1-Quad v1.0 BeadChip disclosed a direct duplication in the long arm of chromosome 7 (q22.1→q32.2) and an inversion located at the breakpoint between the two copies of the duplication (q31.31→q31.33). In addition, breakpoint characterization at the molecular level revealed a 386 bp insertion carrying two Alu elements of chromosome 19p13.2 between the two copies of the duplication. By a comparison of the SNP haplotypes of the derivative chromosome of the patient and both parents a two-step formation during spermatogenesis was suggested as the most likely mechanism of formation.


Prevalence of poor and rapid metabolizers of drugs metabolized by CYP2B6 in North Indian population residing in Indian national capital territory.
Identification of poor and rapid metabolizers for the category of drugs metabolized by cytochrome P450 2B6 (CYP2B6) is important for understanding the differences in clinical responses of drugs metabolized by this enzyme. This study reports the prevalence of poor and rapid metabolizers in North Indian population residing in the National Capital Territory. The prevalence of poor and rapid metabolizers was determined in the target population for the category of drugs metabolized by CYP2B6 by measuring plasma bupropion, a drug metabolized by CYP2B6, and its metabolite. Bupropion (75 mg) was administered to 107 volunteers, and the drug (bupropion) and its metabolite (hydroxybupropion) were determined simultaneously by LCMS/MS in the plasma. CYP2B6 activity was measured as hydroxybupropion/bupropion ratio, and volunteers were categorized as rapid or poor metabolizers on the basis of cutoff value of log (hydroxybupropion/bupropion). Significant differences were observed between the mean metabolite/drug ratio of rapid metabolizers (Mean = 0.59) and poor metabolizers (Mean = 0.26) with p<0.0001. Results indicate that 20.56% individuals in the target population were poor metabolizers for the category of drugs metabolized by CYP2B6. Cutoff value defined in this study can be used as a tool for evaluating the status of CYP2B6 using bupropion as a probe drug. The baseline information would be clinically useful before administering the drugs metabolized by this isoform.


Voltage-controlled quantum light from an atomically thin semiconductor.
Although semiconductor defects can often be detrimental to device performance, they are also responsible for the breadth of functionality exhibited by modern optoelectronic devices. Artificially engineered defects (so-called quantum dots) or naturally occurring defects in solids are currently being investigated for applications ranging from quantum information science and optoelectronics to high-resolution metrology. In parallel, the quantum confinement exhibited by atomically thin materials (semi-metals, semiconductors and insulators) has ushered in an era of flatland optoelectronics whose full potential is still being articulated. In this Letter we demonstrate the possibility of leveraging the atomically thin semiconductor tungsten diselenide (WSe2) as a host for quantum dot-like defects. We report that this previously unexplored solid-state quantum emitter in WSe2 generates single photons with emission properties that can be controlled via the application of external d.c. electric and magnetic fields. These new optically active quantum dots exhibit excited-state lifetimes on the order of 1 ns and remarkably large excitonic g-factors of 10. It is anticipated that WSe2 quantum dots will provide a novel platform for integrated solid-state quantum photonics and quantum information processing, as well as a rich condensed-matter physics playground with which to explore the coupling of quantum dots and atomically thin semiconductors.


Erratum - A Novel Model for Studying Voltage-Gated Ion Channel Gene Expression during Reversible Ischemic Stroke.
[This corrects the article DOI: 10.7150/ijms.27442.].


Behavioral and histological neuroprotection by tamoxifen after reversible focal cerebral ischemia.
We have previously shown that tamoxifen can reduce infarct sizes measured by 2,3,5,-triphenyltetrazolium chloride (TTC) staining at 72 h after 2 h of reversible middle cerebral artery occlusion (rMCAo) in rats. In this study, we tested whether improvement is found in both behavioral measures of protection and by histological measures of infarcted tissue at 7 and 14 days after 2 h rMCAo. Tamoxifen (10 mg/kg) was given once by intravenous injection 1 h after reperfusion, i.e. 3 h after initiation of rMCAo. Neurobehavioral deficits were evaluated daily for 1 week or 2 weeks followed by infarct volumes measurements by hematoxylin-eosin (HE) staining. Tamoxifen-treated rats had significantly improved neurobehavioral deficit scores when evaluated daily throughout the 1 week or 2 week periods and showed significantly reduced median infarct volumes measured after 1 week and 2 weeks. Median infarct values were 149 mm3 (interquartile range, IQR: 92 to 258) and 124 mm3 (IQR: 69 to 174) for the 1 and 2 week vehicle groups, respectively, compared with 5 mm3 (IQR: 3 to 16) and 4 mm3 (IQR: 0 to 48) for the comparable treated groups (both P < 0.05, Mann-Whitney test), giving a reduction of more than 90% in both cases. Thus, a single administration of tamoxifen given 3 h after initiation of rMCAo is extremely effective in producing long-term neuroprotection as assessed by neurobehavioral measures and histopathology in experimental stroke in rats. If these results are extrapolatable to human stroke, these data indicate that tamoxifen may be a useful neuroprotectant.


Semiquantitative assessment of regional cerebral perfusion using 99mTc HM-PAO and emission tomography.
A method for the relative quantification of 99mTc-HM-PAO distribution in brain SPECT is described. The method, applied in 12 normal volunteers and 150 patients suffering from different cerebral diseases, uses circumferential profiles to quantify the relative radionuclide distribution in the brain tomograms as an angular function with the origin at the center of the brain slice. Abnormal 99mTc-HM-PAO distribution is evaluated by comparing the count content of symmetrical selected parts of the profile curve and comparing each patient's profile with the corresponding limits of normal ones, determined from the pooled profiles of 12 normal subjects. This computerized method allows an accurate, reproducible and objective assessment of the relative HM-PAO distribution in the brain.


Juvenile manic depressive psychosis - report of 3 cases.
Three patients, one female and two males, with bipolar affective psychosis beginning at the ages of twelve, nine and fourteen years, are described. The symptomatology in all the three patients was similar to that of the adult manic depressive psychosis and the response to lithium was good.


Behavioural patterns of conflict resolution strategies in preschool boys with language impairment in comparison with boys with typical language development.
Children with language impairment (LI) experience social difficulties, including conflict management. This paper is therefore motivated to examine behavioural processes guiding preschool peer conflict progression, which ultimately contributes to overall development. To describe behavioural sequences in conflicts between children with typically developing language (TL) and between children with LI. Attention is particularly focused on the conflict resolution strategy reconciliation, i.e. friendly contact between former opponents shortly following conflict termination. It is hypothesized that children with LI, with weaker language skills, experience difficulties attaining effective reconciliation. Unstructured play of 11 boys with LI (4-7-years-old), at a specialized language preschool, and 20 TL boys (4-6-years-old), at mainstream preschools, were video filmed. Conflicts were identified and recorded according to a validated coding system. Recorded conflict details included behavioural sequences constituting conflict cause (conflict period) and in the post-conflict period, reconciliatory behaviours that were classified into six 'categories' (Invitation to play, Body contact, Object offer, Verbal apology, Self-ridicule, Cognition, i.e. offering privileges/negotiating) and the verbal character of accepted behaviours were determined. The mean proportion of individual target children's conflicts in which specific behavioural sequences had occurred were calculated and thereafter compared between and within the groups. Boys with LI reconcile fewer conflicts than TL boys (LI: 47.3 +/- 4.5%; TL: 63.6 +/- 2.0%). Contributory factors include the occurrence of conflicts caused by aberrance, i.e. conflicts initiated by inappropriate behavioural play intensities (i.e. 'a pillow fight' where one partner swings so intensively the other partner cannot participate as a player in the game) and protests that are no longer directed to the opponent within reciprocal exchanges, but escalate to screaming/physical ranting. Aberrant caused conflicts were rarely observed as the conflict cause for TL boys, but represent nearly 15% of LI conflicts and aberrant caused conflicts are reconciled at lower rates than conflicts not caused by aberrance. Displayed reconciliatory behaviours were accepted by opponents at similar rates in both groups and the distribution of reconciliatory behavioural 'categories' was similar between the groups. However, boys with LI attempt reconciliation in relatively fewer conflicts. In addition, the individual boys with LI attain reconciliation with strictly verbal reconciliatory behaviours in a smaller proportion of conflicts. The findings suggest that in addition to traditional psycholinguistic remediation, intervention programmes for children with LI should address that learned language and communication skills are applied effectively in initiating and maintaining naturalistic peer interactions.


Active testing of groups at increased risk of acquiring SARS-CoV-2 in Canada: costs and human resource needs.
Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely passive, which impedes epidemic control. We defined active testing strategies for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) for groups at increased risk of acquiring SARS-CoV-2 in all Canadian provinces. We identified 5 groups who should be prioritized for active RT-PCR testing: contacts of people who are positive for SARS-CoV-2, and 4 at-risk populations - hospital employees, community health care workers and people in long-term care facilities, essential business employees, and schoolchildren and staff. We estimated costs, human resources and laboratory capacity required to test people in each group or to perform surveillance testing in random samples. During July 8-17, 2020, across all provinces in Canada, an average of 41 751 RT-PCR tests were performed daily; we estimated this required 5122 personnel and cost $2.4 million per day ($67.8 million per month). Systematic contact tracing and testing would increase personnel needs 1.2-fold and monthly costs to $78.9 million. Conducted over a month, testing all hospital employees would require 1823 additional personnel, costing $29.0 million; testing all community health care workers and persons in long-term care facilities would require 11 074 additional personnel and cost $124.8 million; and testing all essential employees would cost $321.7 million, requiring 25 965 added personnel. Testing the larger population within schools over 6 weeks would require 46 368 added personnel and cost $816.0 million. Interventions addressing inefficiencies, including saliva-based sampling and pooling samples, could reduce costs by 40% and personnel by 20%. Surveillance testing in population samples other than contacts would cost 5% of the cost of a universal approach to testing at-risk populations. Active testing of groups at increased risk of acquiring SARS-CoV-2 appears feasible and would support the safe reopening of the economy and schools more broadly. This strategy also appears affordable compared with the $169.2 billion committed by the federal government as a response to the pandemic as of June 2020.


Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.
The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.


Research Note: Disturbance of intracellular calcium signal in salpingitis simulation of laying hens.
This study investigated whether there is disturbance of calcium signal in the simulated salpingitis of laying hens. A total of 90 Roman Pink layers (81 wk; 1.916 ± 0.17 kg) were divided into 3 groups (Control treated with PBS, 1.85 mg lipopolysaccharide (LPS)/layer as LPS group, 1.85 mg LPS/layer as LPS+organic chemical reagent (OCR) group) with 6 replicates of 5 layers. Compared with the Control, the mRNA expression of calcium/calmodulin dependent protein kinase IV (CaMK IV), sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), and plasma membrane calcium-transporting ATPase (PMCA) were not only decreased (P < 0.05) in magnum of laying hens from LPS and LPS+OCR groups, but also in isthmus and uterus of hens from LPS+OCR group. Moreover, the mRNA expression of calcium sensing receptor (CaSR) and Orai1 in uterus from LPS+OCR group were higher (P < 0.05) than that from Control. The relative fluorescence intensity of Ca2+ in uterus from LPS and LPS+OCR groups were significantly higher than that from Control (P < 0.05). In conclusion, it existed that the linkage of simulated salpingitis treated with LPS+OCR and altered intracellular calcium signals in layers, which provided a new insight for alleviating salpingitis and uterine dysfunction of laying hens.


Sensorimotor learning in children and adults: Exposure to frequency-altered auditory feedback during speech production.
Auditory feedback plays an important role in the acquisition of fluent speech; however, this role may change once speech is acquired and individuals no longer experience persistent developmental changes to the brain and vocal tract. For this reason, we investigated whether the role of auditory feedback in sensorimotor learning differs across children and adult speakers. Participants produced vocalizations while they heard their vocal pitch predictably or unpredictably shifted downward one semitone. The participants' vocal pitches were measured at the beginning of each vocalization, before auditory feedback was available, to assess the extent to which the deviant auditory feedback modified subsequent speech motor commands. Sensorimotor learning was observed in both children and adults, with participants' initial vocal pitch increasing following trials where they were exposed to predictable, but not unpredictable, frequency-altered feedback. Participants' vocal pitch was also measured across each vocalization, to index the extent to which the deviant auditory feedback was used to modify ongoing vocalizations. While both children and adults were found to increase their vocal pitch following predictable and unpredictable changes to their auditory feedback, adults produced larger compensatory responses. The results of the current study demonstrate that both children and adults rapidly integrate information derived from their auditory feedback to modify subsequent speech motor commands. However, these results also demonstrate that children and adults differ in their ability to use auditory feedback to generate compensatory vocal responses during ongoing vocalization. Since vocal variability also differed across the children and adult groups, these results also suggest that compensatory vocal responses to frequency-altered feedback manipulations initiated at vocalization onset may be modulated by vocal variability.


A fixed interval momentary sampling method for assessing on-going behaviours induced by dopamine receptor agonists.
1. An observational recording procedure for the objective measurement of unconditioned behaviour is described. 2. During an observation period an auditory cue (e.g. the click of a metronome) spaced at regular intervals (e.g. every 10 seconds) signals the observer to rate the presence or absence of target behaviours at the precise instant of the cue. 3. Practical and methodological considerations of the use of this technique are discussed. 4. This method has been used to compare behaviours elicited by the dopamine agonists apomorphine, LY-171555 and SK&F-38393. 5. These behaviours were also assessed using a stereotypy rating scale and these results are contrasted with those obtained using the time-sample method.